{"text": "Effects of docosahexaenoic acid and methylmercury on child ' s brain development due to consumption of fish by Finnish mother during pregnancy : a probabilistic modeling approach .", "entity": [{"entity": "docosahexaenoic acid", "entity_type": "Chemical", "pos": [11, 31]}, {"entity": "methylmercury", "entity_type": "Chemical", "pos": [36, 49]}], "task": "NER"}
{"text": "Fish contains both beneficial substances e . g . docosahexaenoic acids but also harmful compounds e . g . methylmercury .", "entity": [{"entity": "docosahexaenoic acids", "entity_type": "Chemical", "pos": [49, 70]}, {"entity": "methylmercury", "entity_type": "Chemical", "pos": [106, 119]}], "task": "NER"}
{"text": "Importantly , the health effects caused by these two substances can be evaluated in one common end point , intelligence quotient ( IQ ) , providing a more transparent analysis .", "entity": [], "task": "NER"}
{"text": "We estimated health effects of maternal fish consumption on child ' s central nervous system by creating a model with three alternative maternal fish consumption scenarios ( lean fish , fatty fish , and current fish consumption ) .", "entity": [], "task": "NER"}
{"text": "Additionally , we analyzed impacts of both regular fish consumption and extreme fish consumption habits .", "entity": [], "task": "NER"}
{"text": "At the individual level , the simulated net effects were small , encompassing a range of one IQ point in all scenarios .", "entity": [], "task": "NER"}
{"text": "Fatty fish consumption , however , clearly generated a beneficial net IQ effect , and lean fish consumption evoked an adverse net IQ effect .", "entity": [], "task": "NER"}
{"text": "In view of the current fish consumption pattern of Finnish mothers the benefits and risks seem to more or less compensate each other .", "entity": [], "task": "NER"}
{"text": "This study clearly shows the significance of which fish species are consumed during pregnancy and lactation , and the results can be generalized to apply to typical western population fish consumption habits .", "entity": [], "task": "NER"}
{"text": "The mechanisms responsible for garlic - drug interactions and their in vivo relevance .", "entity": [], "task": "NER"}
{"text": "Garlic phytochemicals and garlic supplements influence the pharmacokinetic and pharmacodynamic behavior of concomitantly ingested drugs .", "entity": [], "task": "NER"}
{"text": "In this paper we have summarized the mechanisms responsible for first - pass intestinal pharmacokinetic interactions by investigating the intestinal permeability of some cardiovascular , antiviral drugs , their transport with hepatic transporters and CYP3A4 metabolism .", "entity": [], "task": "NER"}
{"text": "Transporter - enzyme interplay was studied with several in vitro models of varying complexity : rat small intestine and Caco - 2 cell monolayers were used in studies of intestinal processes , and hepatic pharmacokinetics was monitored in HepG2 cells , isolated rat hepatocytes and rat liver slices .", "entity": [], "task": "NER"}
{"text": "Garlic phytochemicals from aged garlic extract modified the activities of secretory and absorptive transporters in both intestine and liver and competitively inhibited CYP3A4 enzyme .", "entity": [], "task": "NER"}
{"text": "The increased activities of the most important intestinal efflux ( P - glycoprotein - Pgp , Multidrug Resistance Associated Protein 2 - MRP - 2 , Breast Cancer Resistance Protein - BCRP ) and uptake ( MonoCarboxylate Transporter 1 - MCT1 , Organic Anion Transporting Polypeptide - OATP , Peptide transporter 1 - PepT1 ) transporters were caused by changes in electrophysiological membrane properties and by allosteric modifications .", "entity": [{"entity": "MonoCarboxylate", "entity_type": "Chemical", "pos": [201, 216]}], "task": "NER"}
{"text": "Because clinical studies investigating interactions between garlic and human immunodeficiency virus protease inhibitors saquinavir and ritonavir have already been performed , we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first - pass intestinal metabolism changes .", "entity": [{"entity": "saquinavir", "entity_type": "Chemical", "pos": [120, 130]}, {"entity": "ritonavir", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "We also assessed the probability of pharmacokinetic interactions with garlic of the novel drug darunavir and other cardiovascular drugs .", "entity": [{"entity": "darunavir", "entity_type": "Chemical", "pos": [95, 104]}], "task": "NER"}
{"text": "Finally , selected garlic phytochemicals were tested for their ability to influence P - glycoprotein and CYP3A4 activities .", "entity": [], "task": "NER"}
{"text": "Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [12, 24]}, {"entity": "sildenafil", "entity_type": "Chemical", "pos": [83, 93]}], "task": "NER"}
{"text": "Erectile dysfunction ( ED ) is usually treated with sildenafil .", "entity": [{"entity": "sildenafil", "entity_type": "Chemical", "pos": [52, 62]}], "task": "NER"}
{"text": "Although genetic polymorphisms in the endothelial nitric oxide synthase ( eNOS ) gene may impair endogenous NO formation , there is little information about how eNOS polymorphisms and haplotypes affect the responses to sildenafil .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [50, 62]}, {"entity": "NO", "entity_type": "Chemical", "pos": [75, 77]}, {"entity": "sildenafil", "entity_type": "Chemical", "pos": [219, 229]}], "task": "NER"}
{"text": "We studied 118 patients ; 63 patients had ED secondary to radical prostatectomy ( PED ) and 55 had organic , clinical ED .", "entity": [], "task": "NER"}
{"text": "eNOS genotypes for three eNOS polymorphisms ( T ( - 786 ) C , rs2070744 ; a variable number of tandem repeats ( VNTR ) in intron 4 ; and Glu298Asp , rs1799983 ) were determined , and eNOS haplotypes were estimated using PHASE 2 . 1 .", "entity": [], "task": "NER"}
{"text": "The clinical responses to sildenafil were evaluated and the patients were classified as good responders ( GR ) or poor responders ( PR ) when their changes in five - item version of International Index for Erectile Function questionnaire were above or below the median value .", "entity": [{"entity": "sildenafil", "entity_type": "Chemical", "pos": [26, 36]}], "task": "NER"}
{"text": "The TC / CC genotypes and the C allele for the T ( - 786 ) C polymorphism were more common in GR , compared with PR patients with PED .", "entity": [], "task": "NER"}
{"text": "However , the 4b4a / 4a4a genotypes and the 4a allele for the VNTR polymorphism in intron 4 were more common in GR , compared with PR patients with clinical ED .", "entity": [], "task": "NER"}
{"text": "The C - 4a - Glu haplotype was more common in GR than in PR patients with PED .", "entity": [], "task": "NER"}
{"text": "Conversely , the T - 4b - Asp haplotype was less common in GR than in PR patients with PED .", "entity": [], "task": "NER"}
{"text": "No other significant differences were found .", "entity": [], "task": "NER"}
{"text": "Our findings show evidence that eNOS polymorphisms affect the responses of PED and clinical ED patients to sildenafil .", "entity": [{"entity": "sildenafil", "entity_type": "Chemical", "pos": [107, 117]}], "task": "NER"}
{"text": "On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide .", "entity": [{"entity": "magnesium", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "aluminum phosphide", "entity_type": "Chemical", "pos": [79, 97]}], "task": "NER"}
{"text": "The present study was designed to determine the effect of a new ( 25 ) Mg ( 2 + ) - carrying nanoparticle ( ( 25 ) MgPMC16 ) on energy depletion , oxidative stress , and electrocardiographic ( ECG ) parameters on heart tissue of the rats poisoned by aluminum phosphide ( AlP ) .", "entity": [{"entity": "( 25 ) Mg ( 2 + )", "entity_type": "Chemical", "pos": [64, 81]}, {"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [108, 122]}, {"entity": "aluminum phosphide", "entity_type": "Chemical", "pos": [250, 268]}, {"entity": "AlP", "entity_type": "Chemical", "pos": [271, 274]}], "task": "NER"}
{"text": "( 25 ) MgPMC16 at doses of 0 . 025 , 0 . 05 , and 0 . 1 median lethal dose ( LD50 = 896 mg / kg ) was administered intravenously ( iv ) 30 min after a single intragastric administration of AlP ( 0 . 25 LD50 ) .", "entity": [{"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "AlP", "entity_type": "Chemical", "pos": [189, 192]}], "task": "NER"}
{"text": "Sodium bicarbonate ( Bicarb ; 2 mEq / kg , iv ) was used as the standard therapy .", "entity": [{"entity": "Sodium bicarbonate", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "Bicarb", "entity_type": "Chemical", "pos": [21, 27]}], "task": "NER"}
{"text": "After anesthesia , the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG , blood pressure ( BP ) , and heart rate ( HR ) .", "entity": [], "task": "NER"}
{"text": "Later lipid peroxidation , antioxidant power , ATP / ADP ratio , and Mg concentration in the heart were evaluated .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "ADP", "entity_type": "Chemical", "pos": [53, 56]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [69, 71]}], "task": "NER"}
{"text": "Results indicated that after AlP administration , BP and HR decreased while R - R duration increased .", "entity": [{"entity": "AlP", "entity_type": "Chemical", "pos": [29, 32]}], "task": "NER"}
{"text": "( 25 ) MgPMC16 significantly increased the BP and HR at all doses used .", "entity": [{"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "We found a considerable increase in antioxidant power , Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP / ATP ratio at various doses of ( 25 ) MgPMC16 , but ( 25 ) MgPMC16 - 0 . 025 + Bicarb was the most effective combination therapy .", "entity": [{"entity": "Mg", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "ADP", "entity_type": "Chemical", "pos": [135, 138]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [141, 144]}, {"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [171, 185]}, {"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [192, 206]}, {"entity": "Bicarb", "entity_type": "Chemical", "pos": [219, 225]}], "task": "NER"}
{"text": "The results of this study support that ( 25 ) MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells . ( 25 ) MgPMC16 seems ameliorating AlP - induced toxicity and cardiac failure necessitating further studies .", "entity": [{"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [39, 53]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [103, 105]}, {"entity": "( 25 ) MgPMC16", "entity_type": "Chemical", "pos": [133, 147]}, {"entity": "AlP", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "Ventilatory functions in cotton textile workers and the role of some inflammatory cytokines .", "entity": [], "task": "NER"}
{"text": "Exposure to cotton dust in industrial environments causes inflammation in the airways of the exposed workers .", "entity": [], "task": "NER"}
{"text": "This may manifest as respiratory complaints and changes in the respiratory functions after work shift and in the baseline of their ventilatory functions .", "entity": [], "task": "NER"}
{"text": "The study aimed to investigate the effect of occupational exposure to cotton dust on respiratory symptoms , ventilatory functions and pro - inflammatory cytokine levels ( tumor necrosis factor alpha , interleukin 6 and interleukin 1 beta ) .", "entity": [], "task": "NER"}
{"text": "The study was conducted on 63 textile workers and 65 nonexposed subjects .", "entity": [], "task": "NER"}
{"text": "Both groups were matched for age , socioeconomic status and smoking habit .", "entity": [], "task": "NER"}
{"text": "The respirable dust measured in the workplace did not exceed the permissible values of the Egyptian law 1994 .", "entity": [], "task": "NER"}
{"text": "The bacterial counts detected were within the occupational exposure limits of the industrial settings .", "entity": [], "task": "NER"}
{"text": "The results revealed that the percentage of respiratory symptoms was higher in textile workers .", "entity": [], "task": "NER"}
{"text": "Respiratory complaints were chronic cough ( 33 . 2 % ) , chronic bronchitis ( 39 . 7 % ) and dyspnea ( 23 . 8 % ) in textile workers compared to ( 6 . 2 % , 6 . 2 % and 1 . 5 % ) , respectively , in controls .", "entity": [], "task": "NER"}
{"text": "There was a marked reduction in the ventilatory functions ( forced vital capacity and forced expiratory volume in 1 s ) in the textile workers compared to the controls .", "entity": [], "task": "NER"}
{"text": "The additive effect of smoking on the ventilatory functions was not apparent .", "entity": [], "task": "NER"}
{"text": "The ventilatory functions of the workers were significantly positively correlated with the duration of exposure .", "entity": [], "task": "NER"}
{"text": "The cytokines were insignificantly higher in the textile workers compared to their controls .", "entity": [], "task": "NER"}
{"text": "The textile workers with respiratory complaints showed significant decline in ventilatory functions and elevation in the cytokine levels compared to the nonsymtomatizing workers with significant difference in interleukin 1 beta and interleukin 6 .", "entity": [], "task": "NER"}
{"text": "In conclusion , the results supported the fact that exposure to cotton dust deteriorates ventilatory functions and elevates proinflammatory cytokine levels .", "entity": [], "task": "NER"}
{"text": "Analysis of the release of cytokines can be used to evaluate the immune responses to organic dust - induced airway inflammation .", "entity": [], "task": "NER"}
{"text": "Heat stress decreases testicular germ cell proliferation and increases apoptosis in short term : an immunohistochemical and ultrastructural study .", "entity": [], "task": "NER"}
{"text": "Scrotal hyperthermia has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown .", "entity": [], "task": "NER"}
{"text": "This work was aimed to investigate the role of scrotal hyperthermia on cell proliferation and apoptosis in testes .", "entity": [], "task": "NER"}
{"text": "The rats were randomly allotted into one of the four experimental groups : A ( control ) , B ( 1 day after scrotal hyperthermia ) , C ( 14 days after scrotal hyperthermia ) , and D ( 35 days after scrotal hyperthermia ) ; each group comprised 7 animals .", "entity": [], "task": "NER"}
{"text": "Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43 degrees C for 30 min once daily for 6 consecutive days .", "entity": [], "task": "NER"}
{"text": "Control rats were treated in the same way , except the testes were immersed in a water bath maintained at 22 degrees C .", "entity": [], "task": "NER"}
{"text": "Hyperthermia - exposed rats were killed under 50 mg / kg ketamine anaesthesia and tissue samples were obtained for biochemical and histopathological investigations .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [57, 65]}], "task": "NER"}
{"text": "Hyperthermia treatment significantly decreased the testicular antioxidant system , including decreases in the glutathione level , superoxide dismutase , and glutathione peroxidase activities .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [110, 121]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [130, 140]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [157, 168]}], "task": "NER"}
{"text": "Moreover , exposure to hyperthermia resulted in lipid peroxidation increase in testes .", "entity": [], "task": "NER"}
{"text": "Our data indicate a significant reduction in the expression of proliferating cell nuclear antigen and an enhancement in the activity of terminal deoxynucleotidyl transferase dUTP nick end labelling after scrotal hyperthermia .", "entity": [{"entity": "dUTP", "entity_type": "Chemical", "pos": [174, 178]}], "task": "NER"}
{"text": "In scrotal hyperthermia , the mitochondrial degeneration , dilatation of smooth endoplasmic reticulum , and enlarged intercellular spaces were observed in both Sertoli and spermatid cells .", "entity": [], "task": "NER"}
{"text": "Scrotal hyperthermia is one of the major factors that impair spermatogenesis in testis .", "entity": [], "task": "NER"}
{"text": "This heat stress is shown to be closely associated with oxidative stress , followed by apoptosis of germ cells .", "entity": [], "task": "NER"}
{"text": "A genomic approach to predict synergistic combinations for breast cancer treatment .", "entity": [], "task": "NER"}
{"text": "We leverage genomic and biochemical data to identify synergistic drug regimens for breast cancer .", "entity": [], "task": "NER"}
{"text": "In order to study the mechanism of the histone deacetylase ( HDAC ) inhibitors valproic acid ( VPA ) and suberoylanilide hydroxamic acid ( SAHA ) in breast cancer , we generated and validated genomic profiles of drug response using a series of breast cancer cell lines sensitive to each drug .", "entity": [{"entity": "valproic acid", "entity_type": "Chemical", "pos": [79, 92]}, {"entity": "VPA", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "suberoylanilide hydroxamic acid", "entity_type": "Chemical", "pos": [105, 136]}, {"entity": "SAHA", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "These genomic profiles were then used to model drug response in human breast tumors and show significant correlation between VPA and SAHA response profiles in multiple breast tumor data sets , highlighting their similar mechanism of action .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [125, 128]}, {"entity": "SAHA", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "The genes deregulated by VPA and SAHA converge on the cell cycle pathway ( Bayes factor 5 . 21 and 5 . 94 , respectively ; P - value 10 ( - 8 . 6 ) and 10 ( - 9 ) , respectively ) .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "SAHA", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "In particular , VPA and SAHA upregulate key cyclin - dependent kinase ( CDK ) inhibitors .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "SAHA", "entity_type": "Chemical", "pos": [24, 28]}], "task": "NER"}
{"text": "In two independent datasets , cancer cells treated with CDK inhibitors have similar gene expression profile changes to the cellular response to HDAC inhibitors .", "entity": [], "task": "NER"}
{"text": "Together , these results led us to hypothesize that VPA and SAHA may interact synergistically with CDK inhibitors such as PD - 033299 .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [52, 55]}, {"entity": "SAHA", "entity_type": "Chemical", "pos": [60, 64]}, {"entity": "PD - 033299", "entity_type": "Chemical", "pos": [122, 133]}], "task": "NER"}
{"text": "Experiments show that HDAC and CDK inhibitors have statistically significant synergy in both breast cancer cell lines and primary 3 - dimensional cultures of cells from pleural effusions of patients .", "entity": [], "task": "NER"}
{"text": "Therefore , synergistic relationships between HDAC and CDK inhibitors may provide an effective combinatorial regimen for breast cancer .", "entity": [], "task": "NER"}
{"text": "Importantly , these studies provide an example of how genomic analysis of drug - response profiles can be used to design rational drug combinations for cancer treatment .", "entity": [], "task": "NER"}
{"text": "Chemical constituents and allelopathic and antioxidant activities of Alchorneopsis floribunda M u ll .", "entity": [], "task": "NER"}
{"text": "Arg .", "entity": [], "task": "NER"}
{"text": "( Euphorbiaceae ) .", "entity": [], "task": "NER"}
{"text": "Chemical investigation of extracts from the stems and leaves of Alchorneopsis floribunda M u ll .", "entity": [], "task": "NER"}
{"text": "Arg . , collected in the Amazon region , was performed .", "entity": [], "task": "NER"}
{"text": "The main isolated compounds were triterpenes ( alpha - amyrin , beta - amyrin , lupeol , betulin , betulinic acid , uvaol , erythrodiol and oleanolic acid ) and phenolic acid derivatives from 4 - hydroxybenzoic acid ( gallic and protocatechuic acids and isocorilagin ) .", "entity": [{"entity": "triterpenes", "entity_type": "Chemical", "pos": [33, 44]}, {"entity": "alpha - amyrin", "entity_type": "Chemical", "pos": [47, 61]}, {"entity": "beta - amyrin", "entity_type": "Chemical", "pos": [64, 77]}, {"entity": "lupeol", "entity_type": "Chemical", "pos": [80, 86]}, {"entity": "betulin", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "betulinic acid", "entity_type": "Chemical", "pos": [99, 113]}, {"entity": "uvaol", "entity_type": "Chemical", "pos": [116, 121]}, {"entity": "erythrodiol", "entity_type": "Chemical", "pos": [124, 135]}, {"entity": "oleanolic acid", "entity_type": "Chemical", "pos": [140, 154]}, {"entity": "phenolic acid", "entity_type": "Chemical", "pos": [161, 174]}, {"entity": "4 - hydroxybenzoic acid", "entity_type": "Chemical", "pos": [192, 215]}, {"entity": "gallic and protocatechuic acids", "entity_type": "Chemical", "pos": [218, 249]}, {"entity": "isocorilagin", "entity_type": "Chemical", "pos": [254, 266]}], "task": "NER"}
{"text": "In the germination assays , high inhibitory allelopathic effects of the extracts and isocorilagin were observed and 2 , 2 - diphenyl - 1 - picrylhydrazyl radical scavenging activity of isocorilagin was higher than those of the standards used ( Trolox and butylated hydroxyanisole ) .", "entity": [{"entity": "isocorilagin", "entity_type": "Chemical", "pos": [85, 97]}, {"entity": "2 , 2 - diphenyl - 1 - picrylhydrazyl", "entity_type": "Chemical", "pos": [116, 153]}, {"entity": "isocorilagin", "entity_type": "Chemical", "pos": [185, 197]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [244, 250]}, {"entity": "butylated hydroxyanisole", "entity_type": "Chemical", "pos": [255, 279]}], "task": "NER"}
{"text": "This is the first chemical study of the genus Alchorneopsis ( Euphorbiaceae ) .", "entity": [], "task": "NER"}
{"text": "Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis .", "entity": [], "task": "NER"}
{"text": "The objective of the present study was to determine the plasma total oxidative status ( TOS ) and total antioxidant capacity ( TAC ) in patients with endemic fluorosis .", "entity": [], "task": "NER"}
{"text": "A total of 79 ( 35 males and 44 females ; mean age 44 . 0 +/- 11 . 9 years ) patients with endemic fluorosis and 55 ( 23 males and 32 females ; mean age 48 . 3 +/- 8 . 5 years ) age - , sex - and body mass index - matched healthy controls were included in this study .", "entity": [], "task": "NER"}
{"text": "The urine fluoride levels and plasma TOS and TAC levels were measured .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected ( 1 . 91 +/- 0 . 15 vs . 0 . 49 +/- 0 . 13 mg / L , respectively ; p < 0 . 001 ) .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "TOS was significantly higher in fluorosis group than in control group ( 17 . 55 +/- 3 . 82 vs . 15 . 06 +/- 4 . 31 mu mol H ( 2 ) O ( 2 ) Eq / L , respectively ; p = 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "TAC was significantly lower in fluorosis group than in control group ( 1 . 60 +/- 0 . 36 vs . 1 . 82 +/- 0 . 51 mmol Trolox Eq / L , respectively ; p = 0 . 004 ) .", "entity": [{"entity": "Trolox", "entity_type": "Chemical", "pos": [117, 123]}], "task": "NER"}
{"text": "Oxidative stress index ( OSI ) was significantly higher in fluorosis group than in control group ( 11 . 5 +/- 3 . 8 vs . 8 . 8 +/- 3 . 7 , respectively ; p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "Correlation analysis in all the groups indicated that TAC was negatively correlated with urine fluoride ( r = - 0 . 25 , p = 0 . 003 ) , TOS was positively correlated with urine fluoride ( r = 0 . 34 , p < 0 . 001 ) and OSI was positively correlated with urine fluoride ( r = 0 . 36 , p < 0 . 001 ) .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [178, 186]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [261, 269]}], "task": "NER"}
{"text": "The results of our study demonstrate that oxidative stress plays an important role in the pathogenesis of the endemic fluorosis .", "entity": [], "task": "NER"}
{"text": "Impact of aqueous doash extract on urinary mutagenicity in rats exposed to heterocyclic amines .", "entity": [{"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [75, 94]}], "task": "NER"}
{"text": "Doash ( Origanum majorana ) is an herbaceous plant found commonly in Saudi Arabia .", "entity": [], "task": "NER"}
{"text": "It is used as a food flavor and a folk remedy to treat a number of diseases .", "entity": [], "task": "NER"}
{"text": "The 2 - amino - 3 - methylimidazo [ 4 , 5 - f ] quinoline ( IQ ) and 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine ( PhIP ) are the most abundant of the heterocyclic amine carcinogens present in cooked food .", "entity": [{"entity": "2 - amino - 3 - methylimidazo [ 4 , 5 - f ] quinoline", "entity_type": "Chemical", "pos": [4, 57]}, {"entity": "2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine", "entity_type": "Chemical", "pos": [69, 134]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [137, 141]}, {"entity": "heterocyclic amine", "entity_type": "Chemical", "pos": [173, 191]}], "task": "NER"}
{"text": "In the present study , the potential of doash tea to influence carcinogen metabolism was investigated indirectly using heterocyclic amines as model mutagens , IQ and PhIP .", "entity": [{"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [119, 138]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [166, 170]}], "task": "NER"}
{"text": "Results obtained showed that doash tea had no influence on body weight in both the studies .", "entity": [], "task": "NER"}
{"text": "Rats were treated with different doses of IQ ( 1 , 3 , 5 and 10 mg / kg ) or PhIP ( 1 , 5 , 10 and 20 mg / kg ) .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "The selected dosage was 5 mg / kg for both heterocyclic amines .", "entity": [{"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [43, 62]}], "task": "NER"}
{"text": "Results obtained revealed that rats treated with doash tea and given a single dose of the heterocyclic amines , whether for 1 day ( short - term ) or for 1 month ( long term ) , showed a statistically significant decrease in their excretion of indirect mutagens ( IQ or PhIP ) .", "entity": [{"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [90, 109]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [270, 274]}], "task": "NER"}
{"text": "Following treatment of the rats with a single oral dose of IQ or PhIP , the highest mutagenic activity determined in the presence of an activation system was excreted in the urine after 24 h , with much lower levels of mutagencity being excreted during subsequent elimination from the body .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "No mutagenicity was observed in the absence of an activation system that is direct - acting mutagenicity using ( IQ and PhIP ) .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [120, 124]}], "task": "NER"}
{"text": "Statistical analysis revealed that , in comparison with the control group , the aqueous doash extract significantly reduced the mutagenic response after 24 h .", "entity": [], "task": "NER"}
{"text": "It was concluded that doash extract significantly decreased the excretion of mutagens in comparison with the control group ( water only ) .", "entity": [], "task": "NER"}
{"text": "Genetic and epigenetic regulation of the organic cation transporter 3 , SLC22A3 .", "entity": [], "task": "NER"}
{"text": "Human organic cation transporter 3 ( OCT3 and SLC22A3 ) mediates the uptake of many important endogenous amines and basic drugs in a variety of tissues .", "entity": [{"entity": "amines", "entity_type": "Chemical", "pos": [105, 111]}], "task": "NER"}
{"text": "OCT3 is identified as one of the important risk loci for prostate cancer , and is markedly underexpressed in aggressive prostate cancers .", "entity": [], "task": "NER"}
{"text": "The goal of this study was to identify genetic and epigenetic factors in the promoter region that influence the expression level of OCT3 .", "entity": [], "task": "NER"}
{"text": "Haplotypes that contained the common variants , g . - 81G > delGA ( rs60515630 ) ( minor allele frequency 11 . 5 % in African American ) and g . - 2G > A ( rs555754 ) ( minor allele frequency > 30 % in all ethnic groups ) showed significant increases in luciferase reporter activities and exhibited stronger transcription factor - binding affinity than the haplotypes that contained the major alleles .", "entity": [], "task": "NER"}
{"text": "Consistent with the reporter assays , OCT3 messenger RNA expression levels were significantly higher in Asian ( P < 0 . 001 ) and Caucasian ( P < 0 . 05 ) liver samples from individuals who were homozygous for g . - 2A / A in comparison with those homozygous for the g . - 2G / G allele .", "entity": [], "task": "NER"}
{"text": "Studies revealed that the methylation level in the basal promoter region of OCT3 was associated with OCT3 expression level and tumorigenesis capability in various prostate cancer cell lines .", "entity": [], "task": "NER"}
{"text": "The methylation level of the OCT3 promoter was higher in 62 % of prostate tumor samples compared with matched normal samples .", "entity": [], "task": "NER"}
{"text": "Our studies demonstrate that genetic polymorphisms in the proximal promoter region of OCT3 alter the transcription rate of the gene and may be associated with altered expression levels of OCT3 in human liver .", "entity": [], "task": "NER"}
{"text": "Aberrant methylation contributes to the reduced expression of OCT3 in prostate cancer .", "entity": [], "task": "NER"}
{"text": "Accumulation patterns of some seed oil components from wild sources of Turkey .", "entity": [], "task": "NER"}
{"text": "Accumulation profiles of fatty acids and alpha - tocopherol were analysed at three ripening stages in the seed oils of Primula and Echium species .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [41, 59]}], "task": "NER"}
{"text": "Total seed oils were increased considerably with maturation , while alpha - tocopherol contents decreased in both species .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [68, 86]}], "task": "NER"}
{"text": "Increased levels of ALA and oleic acid , and decrease in linoleic and palmitic acids at late ripening stages of Primula sibthorpii , and slightly fluctuations of all examined fatty acids in Echium italicum were observed .", "entity": [{"entity": "ALA", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "linoleic and palmitic acids", "entity_type": "Chemical", "pos": [57, 84]}, {"entity": "fatty acids", "entity_type": "Chemical", "pos": [175, 186]}], "task": "NER"}
{"text": "Considerable amounts of alpha - tocopherol ( 27 . 4 mg / 100 g ) , linoleic acid ( 42 . 76 % ) and ALA ( 25 . 46 % ) and GLA ( 4 . 11 % ) were detected in Ribes alpinum .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [24, 42]}, {"entity": "linoleic acid", "entity_type": "Chemical", "pos": [67, 80]}, {"entity": "ALA", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "GLA", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "Typical accumulation patterns of the examined parameters may be useful for species characterisation and biochemical monitoring of seed development in natural conditions .", "entity": [], "task": "NER"}
{"text": "Mucopolysaccharidosis : cardiologic features and effects of enzyme - replacement therapy in 24 children with MPS I , II and VI .", "entity": [], "task": "NER"}
{"text": "We determined the cardiologic features of children with MPS I , II and VI , and evaluated the effect of enzyme - replacement therapy ( ERT ) on cardiac disease .", "entity": [], "task": "NER"}
{"text": "Twenty - four children aged 1 - 18 years with MPS I , II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme - replacement therapy up to 6 years of treatment .", "entity": [], "task": "NER"}
{"text": "At start of therapy , 66 % had abnormal cardiac geometric features .", "entity": [], "task": "NER"}
{"text": "Left - ventricular mass index ( LVMI ) was increased in half of the patients , due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI .", "entity": [], "task": "NER"}
{"text": "Regurgitation was most severe in a subgroup of young MPS VI patients ( < 5 years ) at the mitral valve .", "entity": [], "task": "NER"}
{"text": "At baseline , all patients had abnormal valves .", "entity": [], "task": "NER"}
{"text": "The ECG showed no clear rhythm or conduction abnormalities ; neither , in most patients , did it reflect the hypertrophy .", "entity": [], "task": "NER"}
{"text": "After ERT , the LVMI Z - score normalized in 70 % of the patients who had a Z - score > 2 .", "entity": [], "task": "NER"}
{"text": "LVMI Z - scores decreased significantly in patients with MPS I and MPS II ( p = 0 . 04 and p = 0 . 032 ) .", "entity": [], "task": "NER"}
{"text": "Despite ERT , valve regurgitation increased in 60 % of the patients .", "entity": [], "task": "NER"}
{"text": "We conclude that all our MPS patients have cardiac abnormalities .", "entity": [], "task": "NER"}
{"text": "The most severe cardiac disease was observed in a subgroup of young MPS VI patients .", "entity": [], "task": "NER"}
{"text": "While ERT had an effect on LVMI and IVSd , it apparently had little or none on valve regurgitation .", "entity": [], "task": "NER"}
{"text": "Structural basis for protein phosphatase 1 regulation and specificity .", "entity": [], "task": "NER"}
{"text": "The ubiquitous serine / threonine protein phosphatase 1 ( PP1 ) regulates diverse , essential cellular processes such as cell cycle progression , protein synthesis , muscle contraction , carbohydrate metabolism , transcription and neuronal signaling .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [15, 21]}, {"entity": "threonine", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [187, 199]}], "task": "NER"}
{"text": "However , the free catalytic subunit of PP1 , while an effective enzyme , lacks substrate specificity .", "entity": [], "task": "NER"}
{"text": "Instead , it depends on a diverse set of regulatory proteins ( >= 200 ) to confer specificity towards distinct substrates .", "entity": [], "task": "NER"}
{"text": "Here , we discuss recent advances in structural studies of PP1 holoenzyme complexes and summarize the new insights these studies have provided into the molecular basis of PP1 regulation and specificity .", "entity": [], "task": "NER"}
{"text": "Protective effect of vitamin E and epicatechin against nicotine - induced oxidative stress in rats .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [21, 30]}, {"entity": "epicatechin", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "Nicotine is a major pharmacologically active and addictive component of tobacco smoke , which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Epicatechin is one of the most potent antioxidants present in the human diet .", "entity": [{"entity": "Epicatechin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Particularly high levels of this compound are found in tea , apples and chocolate .", "entity": [], "task": "NER"}
{"text": "It has been reported that tea extracts and / or its constituents have antibacterial , antiviral , antioxidative , antitumor and antimutagenic activities .", "entity": [], "task": "NER"}
{"text": "Vitamin E is a major lipid - soluble antioxidant vitamin and free radical scavenger , presents as an integral component of cellular membranes and has important biological functions .", "entity": [{"entity": "Vitamin E", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "The goal of this study is to evaluate the effect of epicatechin alone or combined with vitamin E in inhibiting the oxidative stress induced by nicotine in rats .", "entity": [{"entity": "epicatechin", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [87, 96]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [143, 151]}], "task": "NER"}
{"text": "Results obtained indicated that there was a significant elevation in the levels of malondialdhyde ( MDA ) in nicotine injected rats .", "entity": [{"entity": "malondialdhyde", "entity_type": "Chemical", "pos": [83, 97]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [100, 103]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "The combined treatment ( epicatechin + Vit E ) group showed a potential reduction of these parameters more than individual treatment .", "entity": [{"entity": "epicatechin", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "Vit E", "entity_type": "Chemical", "pos": [39, 44]}], "task": "NER"}
{"text": "The activities of superoxide dismutase , catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [54, 65]}], "task": "NER"}
{"text": "In nicotine group , a negative significant correlation between reduced glutathione and MDA ( r = - 0 . 92 ) was observed .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [3, 11]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [71, 82]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "In conclusion , these results suggested that the supplementation of diet with epicatechin and vitamin E provided antioxidant defense with strong chemopreventive activity against nicotine - induced carcinogenesis .", "entity": [{"entity": "epicatechin", "entity_type": "Chemical", "pos": [78, 89]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [94, 103]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [178, 186]}], "task": "NER"}
{"text": "Prevention of cytotoxicity of nickel by quercetin : the role of reactive oxygen species and histone acetylation .", "entity": [{"entity": "nickel", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "Excessive exposure to nickel may cause health effects on the blood , lung , nose , kidney , reproductive system , skin and the unborn child .", "entity": [{"entity": "nickel", "entity_type": "Chemical", "pos": [22, 28]}], "task": "NER"}
{"text": "In the present study , we found that Ni ( 2 + ) exposure led to a time - and dose - dependent proliferation arrest and death in human leukemia HL - 60 cells .", "entity": [{"entity": "Ni ( 2 + )", "entity_type": "Chemical", "pos": [37, 47]}], "task": "NER"}
{"text": "In the presence of 1 mM Ni ( 2 + ) , reactive oxygen species ( ROS ) generation ( indicated by the level of malondialdehyde ) increased to 323 % and histone acetylation decreased to 32 % .", "entity": [{"entity": "Ni ( 2 + )", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [108, 123]}], "task": "NER"}
{"text": "Interestingly , quercetin ( QU ) dose dependently prevented Ni ( 2 + ) - induced cell proliferation arrest and death from 0 to 80 mu M but showed similar activity of scavenging ROS at the concentrations of 20 , 40 and 80 micro M .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "Ni ( 2 + )", "entity_type": "Chemical", "pos": [60, 70]}], "task": "NER"}
{"text": "When the effect of QU on histone acetylation was studied , QU significantly prevented Ni ( 2 + ) - induced histone hypoacetylation at 40 or 80 micro M .", "entity": [{"entity": "Ni ( 2 + )", "entity_type": "Chemical", "pos": [86, 96]}], "task": "NER"}
{"text": "Moreover , increase in histone acetylation by trichostatin A could also significantly enhance the protection effect of QU at 10 or 20 micro M but not at higher concentrations .", "entity": [{"entity": "trichostatin A", "entity_type": "Chemical", "pos": [46, 60]}], "task": "NER"}
{"text": "Thus , our results further confirmed the critical role of ROS and histone hypoacetylation in the cytotoxicity of Ni ( 2 + ) exposure and proved that QU is a potentially useful native dietary compound to efficiently prevent Ni ( 2 + ) - caused cytotoxicity through both diminishing ROS generation and increasing histone acetylation .", "entity": [{"entity": "Ni ( 2 + )", "entity_type": "Chemical", "pos": [113, 123]}, {"entity": "Ni ( 2 + )", "entity_type": "Chemical", "pos": [223, 233]}], "task": "NER"}
{"text": "Cadmium concentrations in shrimp ( Penaeus semisulcatus and Penaeus monodon ) caught from the coastal areas in Southern Iran .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "This study was undertaken to determine the concentration of cadmium in two shrimp species , namely , Penaeus semisulcatus and Penaeus monodon caught from the coastal areas in southern Iran .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "Cadmium concentration was determined by graphite furnace atomic absorption spectrophotometry in 91 shrimp samples after nitric acid / perchloric acid digestion .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [40, 48]}, {"entity": "nitric acid", "entity_type": "Chemical", "pos": [120, 131]}, {"entity": "perchloric acid", "entity_type": "Chemical", "pos": [134, 149]}], "task": "NER"}
{"text": "Accuracy of the analysis was checked by various methods including the use of reference material .", "entity": [], "task": "NER"}
{"text": "The mean +/- SD of cadmium concentrations in shrimp samples were 0 . 128 +/- 0 . 144 ( mu g / g ) .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "The cadmium concentrations ranged from 0 . 010 to 0 . 96 mu g / g of the muscle tissues of shrimp .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [4, 11]}], "task": "NER"}
{"text": "Higher cadmium concentration in shrimp samples was found in summer ( significant p < 0 . 05 ) .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [7, 14]}], "task": "NER"}
{"text": "The results show that the mean concentration of cadmium in shrimp is lower than the maximum allowed levels according to International standards , although the concentration of cadmium in only one sample was more than the amount recommended by Food and Agriculture Organization .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [176, 183]}], "task": "NER"}
{"text": "Therefore , no risk to the consumer arises from the cadmium contents of the shrimp caught in these areas .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [52, 59]}], "task": "NER"}
{"text": "Selective separation of patchouli alcohol from the essential oil of Cablin potchouli by inclusion crystalline method .", "entity": [{"entity": "patchouli alcohol", "entity_type": "Chemical", "pos": [24, 41]}], "task": "NER"}
{"text": "In this article , we have focused on the application of non - traditional separation approach , the host - guest inclusion method , into the separation of the active component patchouli alcohol from the essential oil of Cablin potchouli Herb .", "entity": [{"entity": "patchouli alcohol", "entity_type": "Chemical", "pos": [176, 193]}], "task": "NER"}
{"text": "The host molecule 1 , 1 , 6 , 6 - tetraphenylhexa - 2 , 4 - diyne - 1 , 6 - diol ( A ) was used to selectively recognise the guest molecule patchouli alcohol ( B ) in the essential oil of Pogostemon cablin ( Blanco ) Benth through two strong hydrogen bonding .", "entity": [{"entity": "1 , 1 , 6 , 6 - tetraphenylhexa - 2 , 4 - diyne - 1 , 6 - diol", "entity_type": "Chemical", "pos": [18, 80]}, {"entity": "patchouli alcohol", "entity_type": "Chemical", "pos": [140, 157]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [242, 250]}], "task": "NER"}
{"text": "The inclusion compound was structurally determined by the single crystal X - ray diffraction .", "entity": [], "task": "NER"}
{"text": "The separation effect was examined by gas chromatography for the whole essential oil and the inclusion compound , showing that the inclusion crystalline method is simple , rapid and effective for the separation of patchouli alcohol from the essential oil of C . potchouli Herb .", "entity": [{"entity": "patchouli alcohol", "entity_type": "Chemical", "pos": [214, 231]}], "task": "NER"}
{"text": "Toxic effects of some synthetic food colorants and / or flavor additives on male rats .", "entity": [], "task": "NER"}
{"text": "The objective of the present work was to evaluate the broadest toxic effect of some synthetic additives of colorants and / or flavors on different body organs and metabolic aspects in rats .", "entity": [], "task": "NER"}
{"text": "A number of chemical food color and flavor additives are routinely added during processing to improve the aesthetic appearance of the dietary items .", "entity": [], "task": "NER"}
{"text": "However , many of them are toxic after prolonged use .", "entity": [], "task": "NER"}
{"text": "In this experiment , a total of 100 male albino rats of Spargue Dawley strain were divided into 10 groups : G ( 1 ) was fed basal diet and served as control , G ( 2 ) : basal diet + Brilliant blue ( blue dye , No . 2 , 124 mg / kg diet ) , G ( 3 ) : basal diet + carmoisine ( red dye , No . 3 , 70 mg / kg diet ) , G ( 4 ) : basal diet + tartrazine ( yellow dye , FD & C yellow No . 5 , 75 mg / kg diet ) , G ( 5 ) : basal diet + trans - anethole ( 4 . 5 g / kg diet ) G ( 6 ) : basal diet + propylene glycol ( 0 . 25 g / kg diet ) , G ( 7 ) : basal diet + vanillin ( 1 . 25 g / kg diet ) , G ( 8 ) : basal diet + Brilliant blue + propylene glycol , G ( 9 ) : basal diet + carmoisine + trans - anethole , G ( 10 ) : basal diet + tartrazine + vanillin for 42 successive days .", "entity": [{"entity": "Brilliant blue", "entity_type": "Chemical", "pos": [182, 196]}, {"entity": "carmoisine", "entity_type": "Chemical", "pos": [263, 273]}, {"entity": "tartrazine", "entity_type": "Chemical", "pos": [338, 348]}, {"entity": "trans - anethole", "entity_type": "Chemical", "pos": [430, 446]}, {"entity": "propylene glycol", "entity_type": "Chemical", "pos": [492, 508]}, {"entity": "vanillin", "entity_type": "Chemical", "pos": [557, 565]}, {"entity": "Brilliant blue", "entity_type": "Chemical", "pos": [614, 628]}, {"entity": "propylene glycol", "entity_type": "Chemical", "pos": [631, 647]}, {"entity": "carmoisine", "entity_type": "Chemical", "pos": [673, 683]}, {"entity": "trans - anethole", "entity_type": "Chemical", "pos": [686, 702]}, {"entity": "tartrazine", "entity_type": "Chemical", "pos": [729, 739]}, {"entity": "vanillin", "entity_type": "Chemical", "pos": [742, 750]}], "task": "NER"}
{"text": "All food colorants mixed with or without flavor additives induced a significant decrease in body weight , hemoglobin concentration and red blood cell count .", "entity": [], "task": "NER"}
{"text": "Also there was a significant decrease in reduced glutathione content ; glutathione - S - transferase and superoxide dismutase activities in both blood and liver compared to control group .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [71, 82]}, {"entity": "S", "entity_type": "Chemical", "pos": [85, 86]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "On the other hand , a significant increase in serum alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase activities , bilirubin , urea , creatinine , total protein and albumin were observed in all test groups when compared to control group .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [142, 151]}, {"entity": "urea", "entity_type": "Chemical", "pos": [154, 158]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [161, 171]}], "task": "NER"}
{"text": "Finally , it is advisable to limit the uses of these food colorants and / or food flavor additives especially those used by children .", "entity": [], "task": "NER"}
{"text": "Steroids and phenolic constituents from the fruiting bodies of the basidiomycete Sarcodon joedes .", "entity": [{"entity": "Steroids", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [13, 21]}], "task": "NER"}
{"text": "Nine secondary metabolites , including four steroids , four phenolics and one cerebroside , were isolated from the methanol extract of the fruiting bodies of the basidiomycete Sarcodon joedes .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "phenolics", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "cerebroside", "entity_type": "Chemical", "pos": [78, 89]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "The isolated compounds were identified by spectroscopic analyses as ( 22E , 24R ) - 6 beta - methoxyergosta - 7 , 22 - diene - 3 beta , 5 alpha - diol ( 1 ) , 2 ' , 3 ' - diacetoxy - 3 , 4 , 5 ' , 6 ' , 4 '' - pentahydroxy - p - terphenyl ( 2 ) , cerebroside B ( 3 ) , ergosta - 7 , 22 - dien - 3 beta - ol ( 4 ) , ergosterol peroxide ( 5 ) , ( 22E , 24R ) - 3 beta - hydroxy - ergosta - 5 , 22 - dien - 7 - one ( 6 ) , benzoic acid ( 7 ) , methyl p - hydroxybenzoate ( 8 ) and 3 , 4 - dihydroxybenzoic acid ( 9 ) .", "entity": [{"entity": "( 22E , 24R ) - 6 beta - methoxyergosta - 7 , 22 - diene - 3 beta , 5 alpha - diol", "entity_type": "Chemical", "pos": [68, 150]}, {"entity": "2 ' , 3 ' - diacetoxy - 3 , 4 , 5 ' , 6 ' , 4 '' - pentahydroxy - p - terphenyl", "entity_type": "Chemical", "pos": [159, 238]}, {"entity": "cerebroside B", "entity_type": "Chemical", "pos": [247, 260]}, {"entity": "ergosta - 7 , 22 - dien - 3 beta - ol", "entity_type": "Chemical", "pos": [269, 306]}, {"entity": "ergosterol peroxide", "entity_type": "Chemical", "pos": [315, 334]}, {"entity": "( 22E , 24R ) - 3 beta - hydroxy - ergosta - 5 , 22 - dien - 7 - one", "entity_type": "Chemical", "pos": [343, 411]}, {"entity": "benzoic acid", "entity_type": "Chemical", "pos": [420, 432]}, {"entity": "methyl p - hydroxybenzoate", "entity_type": "Chemical", "pos": [441, 467]}, {"entity": "3 , 4 - dihydroxybenzoic acid", "entity_type": "Chemical", "pos": [478, 507]}], "task": "NER"}
{"text": "The cytotoxic activities of these compounds were evaluated .", "entity": [], "task": "NER"}
{"text": "All these compounds were isolated from this fungus for the first time .", "entity": [], "task": "NER"}
{"text": "In vitro evaluation of the protective effects of 4 - thujanol against mitomycin - C and cyclophosphamide - induced genotoxic damage in human peripheral lymphocytes .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [49, 61]}, {"entity": "mitomycin - C", "entity_type": "Chemical", "pos": [70, 83]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [88, 104]}], "task": "NER"}
{"text": "4 - Thujanol ( sabinene hydrate ) , a bicyclic monoterpene alcohol , is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products .", "entity": [{"entity": "4 - Thujanol", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "sabinene hydrate", "entity_type": "Chemical", "pos": [15, 31]}, {"entity": "bicyclic monoterpene alcohol", "entity_type": "Chemical", "pos": [38, 66]}], "task": "NER"}
{"text": "The aim of this study was to evaluate the protective effects of 4 - thujanol against the genotoxic effects induced by mitomycin C ( MMC ) and cyclophosphamide ( CP ) in human lymphocytes , using the chromosome aberrations , sister chromatid exchanges , and micronucleus tests , in the absence and in the presence of S9 mix , respectively .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [64, 76]}, {"entity": "mitomycin C", "entity_type": "Chemical", "pos": [118, 129]}, {"entity": "MMC", "entity_type": "Chemical", "pos": [132, 135]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [142, 158]}], "task": "NER"}
{"text": "The cells were treated with 0 . 25 micro g / mL MMC and 28 micro g / mL CP as alone and cotreated with 13 + 0 . 25 , 26 + 0 . 25 , and 52 + 0 . 25 micro g / mL 4 - thujanol + MMC and with 13 + 28 , 26 + 28 , and 52 + 28 micro g / mL 4 - thujanol + CP as a mixture .", "entity": [{"entity": "MMC", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [160, 172]}, {"entity": "MMC", "entity_type": "Chemical", "pos": [175, 178]}, {"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [233, 245]}], "task": "NER"}
{"text": "The present study showed that 4 - thujanol was unable to reduce the genetic damage induced by MMC , in the absence of S9 mix .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "MMC", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "On the other hand , probably the metabolites of 4 - thujanol act as an antagonist and markedly antagonize CP - induced genotoxicity , in the presence of S9 mix .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [48, 60]}], "task": "NER"}
{"text": "In general , 4 - thujanol + MMC and 4 - thujanol + CP decreased the mitotic index , proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [13, 25]}, {"entity": "MMC", "entity_type": "Chemical", "pos": [28, 31]}, {"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [36, 48]}, {"entity": "MMC", "entity_type": "Chemical", "pos": [195, 198]}], "task": "NER"}
{"text": "In conclusion , 4 - thujanol significantly reduced ( p < 0 . 001 ) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [16, 28]}, {"entity": "MMC", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "We can suggest that 4 - thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP , which is widely used in chemotherapy against cancer , without reducing its antiproliferative activities .", "entity": [{"entity": "4 - thujanol", "entity_type": "Chemical", "pos": [20, 32]}], "task": "NER"}
{"text": "Chlorogenic acid , rutin and hyperoside content in Fragaria vesca , F . viridis and F . moschata in Lithuania .", "entity": [{"entity": "Chlorogenic acid", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [19, 24]}, {"entity": "hyperoside", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "In Lithuania , two species of the genus Fragaria L .", "entity": [], "task": "NER"}
{"text": "( Rosaceae ) , F . vesca L . and F . viridis Weston , occur naturally in the wild and two others , F . moschata Weston and F .", "entity": [], "task": "NER"}
{"text": "x ananassa Duchesne ex Rozier are found escaped from cultivation .", "entity": [], "task": "NER"}
{"text": "The main objective of this study was to establish the variation pattern in the content of chlorogenic acid , rutin and hyperoside in leaves and fruits of the native Lithuanian species .", "entity": [{"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [90, 106]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [109, 114]}, {"entity": "hyperoside", "entity_type": "Chemical", "pos": [119, 129]}], "task": "NER"}
{"text": "In this work , the chemical polymorphisms of different Fragaria species were studied by growing plants side by side under the same cultivated field conditions .", "entity": [], "task": "NER"}
{"text": "F . vesca fruits had the highest rutin ( 1 . 38 +/- 0 . 19 mg g ( - 1 ) DM ) , hyperoside ( 0 . 69 +/- 0 . 10 mg g ( - 1 ) DM ) and chlorogenic acid ( 2 . 25 +/- 0 . 34 mg g ( - 1 ) DM ) content , followed by F . viridis and F . moschata .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [33, 38]}, {"entity": "hyperoside", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [132, 148]}], "task": "NER"}
{"text": "Our results showed that the leaves should be taken into account as important rutin and hyperoside contributors for strawberries .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [77, 82]}, {"entity": "hyperoside", "entity_type": "Chemical", "pos": [87, 97]}], "task": "NER"}
{"text": "Bromotheoynic acid , a brominated acetylenic acid from the marine sponge Theonella swinhoei .", "entity": [{"entity": "Bromotheoynic acid", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "brominated acetylenic acid", "entity_type": "Chemical", "pos": [23, 49]}], "task": "NER"}
{"text": "A new brominated C ( 17 ) acetylenic acid ( 1 ) designated as bromotheoynic acid has been isolated from the marine sponge Theonella swinhoei , collected off the coast of Tanegashima , Kagoshima Prefecture , Japan .", "entity": [{"entity": "brominated C ( 17 ) acetylenic acid", "entity_type": "Chemical", "pos": [6, 41]}, {"entity": "bromotheoynic acid", "entity_type": "Chemical", "pos": [62, 80]}], "task": "NER"}
{"text": "The structure was determined on the basis of the analysis of its extensive 2D NMR spectroscopic data as well as HRMS .", "entity": [], "task": "NER"}
{"text": "Bromotheoynic acid ( 1 ) inhibited maturation of starfish oocytes and cell division of fertilised starfish eggs .", "entity": [{"entity": "Bromotheoynic acid", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "Bromotheoynic acid ( 1 ) also inhibited proliferation of human leukaemia U937 and HL60 cells , human lung cancer A549 and H1299 cells , and human embryonic kidney 293 ( HEK293 ) cells .", "entity": [{"entity": "Bromotheoynic acid", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "Aromatic profiling of wild and rare species growing in Turkey : hypericum aviculariifolium Jaub . and Spach subsp . depilatum ( Freyn and Bornm . ) Robson var . depilatum and Hypericum pruinatum Boiss . and Bal .", "entity": [], "task": "NER"}
{"text": "The volatile constituents of the rare species of Hypericum , namely Hypericum pruinatum ( as one population ) and Hypericum aviculariifolium subp . depilatum var . depilatum ( endemic , as two populations namely ' G u m u s ' and ' Yenik o y ' ) growing wild in the mountainous parts of Northern Turkey were studied for the first time .", "entity": [], "task": "NER"}
{"text": "The essential oils ( EOs ) were extracted by hydrodistillation of the air - dried aerial parts and analysed by GC - FID and GC - MS .", "entity": [], "task": "NER"}
{"text": "A total of 56 , 49 and 50 EO components representing 98 . 2 % , 96 . 9 % and 99 . 4 % of the total composition were identified respectively from one population for H . pruinatum and two populations for Hypericum aviculariifolium subp . depilatum var . depilatum .", "entity": [], "task": "NER"}
{"text": "GC - MS profiles showed significant compositional variations not only between the two Turkish species , but also between the two populations of the same species highlighting the importance of genetic factors affecting secondary metabolite profile .", "entity": [], "task": "NER"}
{"text": "Cyclo - ( His , Leu ) : a new microbial diketopiperazine from a terrestrial Bacillus subtilis strain B38 .", "entity": [{"entity": "Cyclo - ( His , Leu )", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "diketopiperazine", "entity_type": "Chemical", "pos": [40, 56]}], "task": "NER"}
{"text": "In continuation of our search for bioactive secondary metabolites from terrestrial Bacillus spp . , a new microbial diketopiperazine , cis - cyclo - ( His , Leu ) ( 1 ) was isolated from the ethyl acetate extract of a strain B . subtilis B38 , together with cis - cyclo - ( Phe , Phe ) ( 2 ) , tryptophane ( 3 ) , cis - cyclo - ( Leu , Tyr ) ( 4 ) , cis - cyclo - ( Trp , Tyr ) ( 5 ) and macrolactin A ( 6 ) .", "entity": [{"entity": "diketopiperazine", "entity_type": "Chemical", "pos": [116, 132]}, {"entity": "cis - cyclo - ( His , Leu )", "entity_type": "Chemical", "pos": [135, 162]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [191, 204]}, {"entity": "cis - cyclo - ( Phe , Phe )", "entity_type": "Chemical", "pos": [258, 285]}, {"entity": "tryptophane", "entity_type": "Chemical", "pos": [294, 305]}, {"entity": "cis - cyclo - ( Leu , Tyr )", "entity_type": "Chemical", "pos": [314, 341]}, {"entity": "cis - cyclo - ( Trp , Tyr )", "entity_type": "Chemical", "pos": [350, 377]}, {"entity": "macrolactin A", "entity_type": "Chemical", "pos": [388, 401]}], "task": "NER"}
{"text": "The chemical structures of the isolated compounds were identified by comparison of their 1D , 2D NMR and HRESIMS data with authentic spectra and literatures .", "entity": [], "task": "NER"}
{"text": "To the best of our knowledge , this is the first time that cyclo - ( His , Leu ) has been isolated from natural products .", "entity": [{"entity": "cyclo - ( His , Leu )", "entity_type": "Chemical", "pos": [59, 80]}], "task": "NER"}
{"text": "Suppression of survival signalling pathways by the phosphatase PHLPP .", "entity": [], "task": "NER"}
{"text": "The recently discovered pleckstrin homology ( PH ) domain leucine - rich repeat protein phosphatase ( PHLPP ) family is emerging as a central component in suppressing cell survival pathways .", "entity": [{"entity": "leucine", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "Originally discovered in a rational search for a phosphatase that directly dephosphorylates and inactivates Akt , PHLPP is now known to potently suppress cell survival both by inhibiting proliferative pathways and by promoting apoptotic pathways .", "entity": [], "task": "NER"}
{"text": "In the first instance , PHLPP directly dephosphorylates a conserved regulatory site ( termed the hydrophobic motif ) on Akt , protein kinase C and S6 kinase , thereby terminating signalling by these pro - survival kinases .", "entity": [], "task": "NER"}
{"text": "In the second instance , PHLPP dephosphorylates and thus activates the pro - apoptotic kinase Mst1 , thereby promoting apoptosis .", "entity": [], "task": "NER"}
{"text": "PHLPP is deleted in a large number of cancers and the genetic deletion of one isozyme in a PTEN ( phosphatase and tensin homologue located on chromosome 1 ) + / - ( or heterozygous ) prostate cancer model results in increased tumourigenesis , underscoring the role of PHLPP as a tumour suppressor .", "entity": [], "task": "NER"}
{"text": "This review summarizes the targets and cellular actions of PHLPP , with emphasis on its role as a tumour suppressor in the oncogenic phosphoinositide 3 - kinase ( PI3K ) / Akt signalling cascade .", "entity": [{"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [133, 149]}], "task": "NER"}
{"text": "Chemical composition and antifungal activity of Artemisia nilagirica essential oil growing in northern hilly areas of India .", "entity": [], "task": "NER"}
{"text": "Essential oil extracted from aerial parts of Artemisia nilagirica was analysed by gas chromatography - mass spectroscopy .", "entity": [], "task": "NER"}
{"text": "Forty - three constituents amounting to 98 . 16 % of the total essential oil contents were identified .", "entity": [], "task": "NER"}
{"text": "The essential oil contained approximately 79 . 91 % monoterpenoids and 18 . 25 % sesquiterpenoids .", "entity": [{"entity": "monoterpenoids", "entity_type": "Chemical", "pos": [52, 66]}, {"entity": "sesquiterpenoids", "entity_type": "Chemical", "pos": [81, 97]}], "task": "NER"}
{"text": "alpha - Thujone ( 36 . 35 % ) , beta - thujone ( 9 . 37 % ) , germacrene D ( 6 . 32 % ) , 4 - terpineol ( 6 . 31 % ) , beta - caryophyllene ( 5 . 43 % ) , camphene ( 5 . 47 % ) and borneol ( 4 . 12 % ) were identified as the major constituents .", "entity": [{"entity": "alpha - Thujone", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "beta - thujone", "entity_type": "Chemical", "pos": [32, 46]}, {"entity": "germacrene D", "entity_type": "Chemical", "pos": [62, 74]}, {"entity": "4 - terpineol", "entity_type": "Chemical", "pos": [90, 103]}, {"entity": "beta - caryophyllene", "entity_type": "Chemical", "pos": [119, 139]}, {"entity": "camphene", "entity_type": "Chemical", "pos": [155, 163]}, {"entity": "borneol", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "The essential oil exhibited significant antifungal activity against Rhizoctonia solani ( ED ( 50 ) , 85 . 75 mg L ( - 1 ) ) , Sclerotium rolfsii ( ED ( 50 ) , 87 . 63 mg L ( - 1 ) ) and Macrophomina phaseolina ( ED ( 50 ) , 93 . 23 mg L ( - 1 ) ) .", "entity": [], "task": "NER"}
{"text": "This study indicated that A . nilagirica essential oil can be used to control phytopathogenic fungi infesting agricultural crops and commodities .", "entity": [], "task": "NER"}
{"text": "Structural basis for the altered drug sensitivities of non - small cell lung cancer - associated mutants of human epidermal growth factor receptor .", "entity": [], "task": "NER"}
{"text": "The epidermal growth factor receptor ( EGFR ) has an essential role in multiple signaling pathways , including cell proliferation and migration , through extracellular ligand binding and subsequent activation of its intracellular tyrosine kinase ( TK ) domain .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [230, 238]}], "task": "NER"}
{"text": "The non - small cell lung cancer ( NSCLC ) - associated EGFR mutants , L858R and G719S , are constitutively active and oncogenic .", "entity": [], "task": "NER"}
{"text": "They display sensitivity to TK inhibitors , including gefitinib and erlotinib .", "entity": [{"entity": "gefitinib", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "In contrast , the secondary mutation of the gatekeeper residue , T790M , reportedly confers inhibitor resistance on the oncogenic EGFR mutants .", "entity": [], "task": "NER"}
{"text": "In this study , our biochemical analyses revealed that the introduction of the T790M mutation confers gefitinib resistance on the G719S mutant .", "entity": [{"entity": "gefitinib", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "The G719S / T790M double mutant has enhanced activity and retains high gefitinib - binding affinity .", "entity": [{"entity": "gefitinib", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "The T790M mutation increases the ATP affinity of the G719S mutant , explaining the acquired drug resistance of the double mutant .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "Structural analyses of the G719S / T790M double mutant , as well as the wild type and the G719S and L858R mutants , revealed that the T790M mutation stabilizes the hydrophobic spine of the active EGFR - TK conformation .", "entity": [], "task": "NER"}
{"text": "The Met790 side chain of the G719S / T790M double mutant , in the apo form and gefitinib - and AMPPNP - bound forms , adopts different conformations that explain the accommodation of these ligands .", "entity": [{"entity": "Met790", "entity_type": "Chemical", "pos": [4, 10]}, {"entity": "gefitinib", "entity_type": "Chemical", "pos": [79, 88]}], "task": "NER"}
{"text": "In the L858R mutant structure , the active - site cleft is expanded by the repositioning of Phe723 within the P - loop .", "entity": [{"entity": "Phe723", "entity_type": "Chemical", "pos": [92, 98]}], "task": "NER"}
{"text": "Notably , the introduction of the F723A mutation greatly enhanced the gefitinib sensitivity of the wild - type EGFR in vivo , supporting our hypothesis that the expansion of the active - site cleft results in enhanced gefitinib sensitivity .", "entity": [{"entity": "gefitinib", "entity_type": "Chemical", "pos": [70, 79]}, {"entity": "gefitinib", "entity_type": "Chemical", "pos": [218, 227]}], "task": "NER"}
{"text": "Taken together , our results provide a structural basis for the altered drug sensitivities caused by distinct NSCLC - associated EGFR mutations .", "entity": [], "task": "NER"}
{"text": "TGF - beta 1 - dependent L1CAM expression has an essential role in macrophage - induced apoptosis resistance and cell migration of human intestinal epithelial cells .", "entity": [], "task": "NER"}
{"text": "Patients with chronic inflammatory bowel disease ( IBD ) have an increased risk to develop colorectal cancer ( CRC ) particularly after long duration of the disease .", "entity": [], "task": "NER"}
{"text": "Chronic inflammation of the intestinal mucosa is characterized by a marked enrichment of immune cells such as macrophages as well as by high expression of cytokines and growth factors including transforming growth factor - beta 1 ( TGF - beta 1 ) .", "entity": [], "task": "NER"}
{"text": "The adhesion molecule L1CAM mediates chemoresistance and migration of tumor cells and is elevated in CRC tissues being associated with metastatic spread and poor prognosis for the patients .", "entity": [], "task": "NER"}
{"text": "In this study , we examine the role of TGF - beta 1 - induced L1CAM expression and macrophages in malignant transformation of intestinal epithelial cells .", "entity": [], "task": "NER"}
{"text": "We demonstrate that TGF - beta 1 stimulation leads to a Slug - dependent upregulation of L1CAM expression already in the colonic intestinal epithelial cell line NCM460 thereby enhancing cell motility and apoptosis resistance .", "entity": [], "task": "NER"}
{"text": "Accordingly , NCM460 cells acquired a migratory and apoptosis - resistant phenotype if transfected with L1CAM .", "entity": [], "task": "NER"}
{"text": "Immunohistochemistry of colonic biopsies revealed considerable L1CAM expression in intestinal epithelial cells in tissues from IBD patients but not in normal colonic tissues .", "entity": [], "task": "NER"}
{"text": "Moreover , L1CAM expression increased with duration of disease being associated with the presence of CD33 + macrophages .", "entity": [], "task": "NER"}
{"text": "Coculture with macrophages generated from monocyte colony - stimulating factor ( MCSF ) - treated monocytes led to the upregulation of Slug and L1CAM in NCM460 cells thereby elevating cell motility and apoptosis resistance .", "entity": [], "task": "NER"}
{"text": "Pharmacological inhibition of TGF - beta 1 signalling abolished expression of Slug and L1CAM in cocultured NCM460 cells resulting in decreased cell migration and apoptosis resistance .", "entity": [], "task": "NER"}
{"text": "In conclusion , these data provide new insights into the mechanisms by which IBD promotes malignant transformation of intestinal epithelial cells and underscore the role of L1CAM and macrophages in this scenario .", "entity": [], "task": "NER"}
{"text": "Modulated release of 5 - fluorouracil from pH - sensitive and colon targeted pellets : an industrially feasible approach .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [21, 37]}], "task": "NER"}
{"text": "Pellets , reliant on pH - sensitivity and time - dependency for drug delivery , provide one of the most versatile opportunities for targeting colon .", "entity": [], "task": "NER"}
{"text": "5 - Fluorouracil ( 5 - FU ) loaded pellets were prepared by extrusion - spheronization using Avicel ( (R) ) PH101 as a spheronization aid and hydroxypropylmethylcellulose K4M ( HPMC K4M ) solution as a binder .", "entity": [{"entity": "5 - Fluorouracil", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [19, 25]}], "task": "NER"}
{"text": "A 3 ( 2 ) full factorial design was employed to optimize spheronization speed and time .", "entity": [], "task": "NER"}
{"text": "Obtained pellets were evaluated for flow properties , pellet size , roundness and aspect ratio .", "entity": [], "task": "NER"}
{"text": "Optimized batch was coated in a bottom - spray fluidized bed processor ( FBP ) with an inner coat of sustained release polymer Eudragit NE30D and an outer coat of pH - sensitive polymer Eudragit FS30D .", "entity": [{"entity": "Eudragit NE30D", "entity_type": "Chemical", "pos": [127, 141]}, {"entity": "Eudragit FS30D", "entity_type": "Chemical", "pos": [186, 200]}], "task": "NER"}
{"text": "The coating levels were statistically optimized and in vitro drug release was monitored by changing pH media method .", "entity": [], "task": "NER"}
{"text": "Optimized system with 15 % inner and outer coating levels revealed t ( 50 % ) ( time required for 50 % drug release ) to be about 9 h while almost complete drug was released in 24 h ( 98 . 71 +/- 1 . 33 % ) with highest dissolution efficiency ( DE ( 24h ) ) of 58 . 71 % .", "entity": [], "task": "NER"}
{"text": "The optimization model was validated ; the predicted and experimental / actual values for validation batch ( M1 ) were in close tolerance and the standard error ( SE ) was also small .", "entity": [], "task": "NER"}
{"text": "Drug release was also studied at pH 7 . 4 .", "entity": [], "task": "NER"}
{"text": "Scanning electron microscopy ( SEM ) demonstrated average coating thickness to be 32 . 50 +/- 3 . 0 micro m .", "entity": [], "task": "NER"}
{"text": "Hence , the present study provides constructive results for colon targeting of 5 - FU pellets with industrially feasible processes .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "Conditional activation of Pik3ca ( H1047R ) in a knock - in mouse model promotes mammary tumorigenesis and emergence of mutations .", "entity": [], "task": "NER"}
{"text": "Oncogenic mutations in PIK3CA , which encodes the phosphoinositide - 3 - kinase ( PI3K ) catalytic subunit p110 alpha , occur in ~ 25 % of human breast cancers .", "entity": [{"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [50, 66]}], "task": "NER"}
{"text": "In this study , we report the development of a knock - in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue - specific conditional expression of a frequently found Pik3ca ( H1047R ) ( Pik3ca ( e20H1047R ) ) mutant allele .", "entity": [], "task": "NER"}
{"text": "We found that activation of the latent Pik3ca ( H1047R ) allele resulted in breast tumors with multiple histological types .", "entity": [], "task": "NER"}
{"text": "Whole - exome analysis of the Pik3ca ( H1047R ) - driven mammary tumors identified multiple mutations , including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors .", "entity": [{"entity": "Trp53", "entity_type": "Chemical", "pos": [114, 119]}], "task": "NER"}
{"text": "Further , we used this model to test the efficacy of GDC - 0941 , a PI3K inhibitor , in clinical development , and showed that the tumors respond to PI3K inhibition .", "entity": [{"entity": "GDC - 0941", "entity_type": "Chemical", "pos": [53, 63]}], "task": "NER"}
{"text": "WNT6 is a novel target gene of caveolin - 1 promoting chemoresistance to epirubicin in human gastric cancer cells .", "entity": [{"entity": "epirubicin", "entity_type": "Chemical", "pos": [73, 83]}], "task": "NER"}
{"text": "Resistance to chemotherapy is a major obstacle for curative treatment of human gastric cancer ( GC ) .", "entity": [], "task": "NER"}
{"text": "However , the underlying molecular mechanisms are largely unknown .", "entity": [], "task": "NER"}
{"text": "Wingless - type MMTV integration site family members ( WNTs ) are secreted glycoproteins involved in embryogenesis and , on inappropriate expression in the adult , in cancer .", "entity": [], "task": "NER"}
{"text": "Here , we show expression of WNT6 in GC patient specimens , human GC cell lines and in a mouse model of GC .", "entity": [], "task": "NER"}
{"text": "In human GC cells , WNT6 expression was enhanced by caveolin - 1 ( Cav1 ) , a scaffold protein of plasma membrane caveolae .", "entity": [], "task": "NER"}
{"text": "WNT6 knock - down and overexpression experiments demonstrated that WNT6 increased the resistance to apoptotic cell death induced by the anthracycline chemotherapeutics epirubicin ( Epi ) and doxorubicin ( Dox ) .", "entity": [{"entity": "anthracycline", "entity_type": "Chemical", "pos": [136, 149]}, {"entity": "epirubicin", "entity_type": "Chemical", "pos": [168, 178]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [181, 184]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [191, 202]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [205, 208]}], "task": "NER"}
{"text": "Epi increased the activity of the human WNT6 promoter through Cav1 - dependent binding of beta - catenin to the proximal WNT6 promoter .", "entity": [{"entity": "Epi", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Epi increased both WNT6 / Wnt6 and Cav1 expression in human GC cells and within the tumor area of a murine model of GC ( CEA424 - SV40 TAg ) .", "entity": [{"entity": "Epi", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "In GC patients , WNT6 expression was positively associated with the tumor stage and the nodal status , and inversely correlated with the response to ECF ( Epi , cisplatin , 5 - fluorouracil ) chemotherapy .", "entity": [{"entity": "Epi", "entity_type": "Chemical", "pos": [155, 158]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [161, 170]}, {"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [173, 189]}], "task": "NER"}
{"text": "These results showed that WNT6 and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to anthracycline drugs .", "entity": [{"entity": "anthracycline", "entity_type": "Chemical", "pos": [119, 132]}], "task": "NER"}
{"text": "Understanding the molecular mechanisms driving WNT6 / Cav1 - induced drug resistance will provide benefits in developing new therapies for GC .", "entity": [], "task": "NER"}
{"text": "Three new alpha - glucosidase inhibitors from guggul , the oleogum resin of Commiphora wightii .", "entity": [], "task": "NER"}
{"text": "Three new compounds ; epi - mukulin , ( Z ) - Delta ( 1 , 2 ) dehydroguggulsterone and Delta ( 6 , 7 ) dehydro - 20 - hydroxygugglsterone were isolated from the n - hexane - soluble fraction ( HSF ) of the methanol extract of guggul , the oleogum resin of Commiphora wightii together with six known compounds : diasesartemin , ( + ) - epi - magnolin , ( + ) - diayangambin , gugglsterol I , ( E ) - guggulsterone and ( Z ) - guggulsterone .", "entity": [{"entity": "epi - mukulin", "entity_type": "Chemical", "pos": [22, 35]}, {"entity": "( Z ) - Delta ( 1 , 2 ) dehydroguggulsterone", "entity_type": "Chemical", "pos": [38, 82]}, {"entity": "Delta ( 6 , 7 ) dehydro - 20 - hydroxygugglsterone", "entity_type": "Chemical", "pos": [87, 137]}, {"entity": "n - hexane", "entity_type": "Chemical", "pos": [161, 171]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [206, 214]}, {"entity": "diasesartemin", "entity_type": "Chemical", "pos": [311, 324]}, {"entity": "( + ) - epi - magnolin", "entity_type": "Chemical", "pos": [327, 349]}, {"entity": "( + ) - diayangambin", "entity_type": "Chemical", "pos": [352, 372]}, {"entity": "gugglsterol I", "entity_type": "Chemical", "pos": [375, 388]}, {"entity": "( E ) - guggulsterone", "entity_type": "Chemical", "pos": [391, 412]}, {"entity": "( Z ) - guggulsterone", "entity_type": "Chemical", "pos": [417, 438]}], "task": "NER"}
{"text": "Their structures were elucidated on the basis of different spectroscopic data .", "entity": [], "task": "NER"}
{"text": "alpha - Glucosidase inhibitory effects of HSF and the isolated compounds were evaluated calorimetrically .", "entity": [], "task": "NER"}
{"text": "The HSF showed significant alpha - glucosidase inhibitory effect [ IC ( 50 ) value of 140 micro g mL ( - 1 ) ( p < 0 . 05 ) ] .", "entity": [], "task": "NER"}
{"text": "Under the assay conditions , diasesartemin ( IC ( 50 ) = 60 . 6 +/- 0 . 01 micro M ) was found to be more potent than the positive control , acarbose ( IC ( 50 ) = 92 . 94 +/- 0 . 01 micro M ) ; a known alpha - glucosidase inhibitor ( p < 0 . 05 ) .", "entity": [{"entity": "diasesartemin", "entity_type": "Chemical", "pos": [29, 42]}, {"entity": "acarbose", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "The IC ( 50 ) values of epi - mukulin and ( Z ) - guggulsterone were found to be 159 . 33 and 132 . 14 micro M , respectively .", "entity": [{"entity": "epi - mukulin", "entity_type": "Chemical", "pos": [24, 37]}, {"entity": "( Z ) - guggulsterone", "entity_type": "Chemical", "pos": [42, 63]}], "task": "NER"}
{"text": "Other compounds showed weak alpha - glucosidase inhibitory effects , < 30 % inhibition of the enzyme activity at 0 . 1 mg mL ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "Chemical constituents of Indonesian plant Protium javanicum Burm .", "entity": [], "task": "NER"}
{"text": "f . and their antifeedant activities against Coptotermes formosanus Shiraki .", "entity": [], "task": "NER"}
{"text": "In the continuing study of antifeedant compounds in Protium javanicum Burm .", "entity": [], "task": "NER"}
{"text": "f . against Coptotermes formosanus Shiraki , 6 - desacetylnimbin ( 1 ) , quercitrin ( 2 ) and myricitrin ( 3 ) were isolated from P . javanicum extract .", "entity": [{"entity": "6 - desacetylnimbin", "entity_type": "Chemical", "pos": [45, 64]}, {"entity": "quercitrin", "entity_type": "Chemical", "pos": [73, 83]}, {"entity": "myricitrin", "entity_type": "Chemical", "pos": [94, 104]}], "task": "NER"}
{"text": "All compounds were characterised by NMR and MS .", "entity": [], "task": "NER"}
{"text": "Furthermore , the structure of 6 - desacetylnimbin was confirmed by X - ray crystallography .", "entity": [{"entity": "6 - desacetylnimbin", "entity_type": "Chemical", "pos": [31, 50]}], "task": "NER"}
{"text": "The antifeedant activity was evaluated with no - choice feeding tests .", "entity": [], "task": "NER"}
{"text": "At a dose of 0 . 5 mg , 6 - desacetylnimbin exhibited the highest antifeedant activity among the isolates .", "entity": [{"entity": "6 - desacetylnimbin", "entity_type": "Chemical", "pos": [24, 43]}], "task": "NER"}
{"text": "Tumor angiogenesis is enforced by autocrine regulation of high - mobility group box 1 .", "entity": [], "task": "NER"}
{"text": "The endothelium plays a pivotal role in the progression of solid tumors and is considered a highly relevant target for therapy .", "entity": [], "task": "NER"}
{"text": "However , it emerges that current clinical angiogenesis inhibitors that act through inhibition of tumor - derived growth factors are prone to inducing drug resistance .", "entity": [], "task": "NER"}
{"text": "Therefore , markers of tumor endothelial cells ( ECs ) themselves provide attractive novel therapeutic targets .", "entity": [], "task": "NER"}
{"text": "In a screen for markers of tumor angiogenesis , we recently identified high - mobility group box 1 ( HMGB1 ) , known to act as proinflammatory cytokine and chromatin - binding molecule .", "entity": [], "task": "NER"}
{"text": "Here we report on the role of HMGB1 in angiogenesis by showing that its overexpression is associated with an increased angiogenic potential of ECs .", "entity": [], "task": "NER"}
{"text": "HMGB1 stimulates the expression of players in vascular endothelial growth factor and platelet - derived growth factor signaling , both in vitro and in vivo .", "entity": [], "task": "NER"}
{"text": "Importantly , we show that HMGB1 triggers and helps to sustain this proangiogenic gene expression program in ECs , additionally characterized by increased activity of matrix metalloproteinases , integrins and nuclear factor - kappa B .", "entity": [], "task": "NER"}
{"text": "Moreover , we found that HMGB1 is involved in several autocrine and / or paracrine feedback mechanisms resulting in positive enforcement of HMGB1 expression , and that of its receptors , RAGE ( receptor for advanced glycation end products ) and Toll - like receptor 4 ( TLR4 ) .", "entity": [], "task": "NER"}
{"text": "Interference in HMGB1 expression and / or function using knockdown approaches and antibody - mediated targeting to break this vicious circle resulted in inhibited migration and sprouting of ECs .", "entity": [], "task": "NER"}
{"text": "Using different in vivo models , therapeutic efficacy of HMGB1 targeting was confirmed .", "entity": [], "task": "NER"}
{"text": "First , we demonstrated induction of HMGB1 expression in the chicken embryo chorioallantoic membrane ( CAM ) neovasculature following both photodynamic therapy and tumor challenge .", "entity": [], "task": "NER"}
{"text": "We subsequently showed that anti - HMGB1 antibodies inhibited vessel density in both models , accompanied by a reduced vascular expression of angiogenic growth factor receptors .", "entity": [], "task": "NER"}
{"text": "Collectively , these data identify HMGB1 as an important modulator of tumor angiogenesis and suggest the feasibility of targeting HMGB1 for multi - level cancer treatment .", "entity": [], "task": "NER"}
{"text": "Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8 .", "entity": [], "task": "NER"}
{"text": "Mutation of the p53 gene is the most common genetic alteration in human cancer and contributes to malignant process by enhancing transformed properties of cells and resistance to anticancer therapy .", "entity": [], "task": "NER"}
{"text": "Mutant p53 is often highly expressed in tumor cells at least , in part , due to its increased half - life .", "entity": [], "task": "NER"}
{"text": "However , whether mutant p53 expression is regulated by other mechanisms in tumors is unclear .", "entity": [], "task": "NER"}
{"text": "Here we found that histone deacetylase ( HDAC ) inhibitors suppress both wild - type and mutant p53 transcription in time - and dose - dependent manners .", "entity": [], "task": "NER"}
{"text": "Consistent with this , the levels of wild - type and mutant p53 proteins are decreased upon treatment with HDAC inhibitors .", "entity": [], "task": "NER"}
{"text": "Importantly , we found that upon knockdown of each class I HDAC , only HDAC8 knockdown leads to decreased expression of wild - type and mutant p53 proteins and transcripts .", "entity": [], "task": "NER"}
{"text": "Conversely , we found that ectopic expression of wild - type , but not mutant HDAC8 , leads to increased transcription of p53 .", "entity": [], "task": "NER"}
{"text": "Furthermore , we found that knockdown of HDAC8 results in reduced expression of HoxA5 and consequently , attenuated ability of HoxA5 to activate p53 transcription , which can be rescued by ectopic expression of HoxA5 .", "entity": [], "task": "NER"}
{"text": "Because of the fact that HDAC8 is required for expression of both wild - type and mutant p53 , we found that targeted disruption of HDAC8 expression remarkably triggers proliferative defect in cells with a mutant , but not wild - type , p53 .", "entity": [], "task": "NER"}
{"text": "Together , our data uncover a regulatory mechanism of mutant p53 transcription via HDAC8 and suggest that HDAC inhibitors and especially HDAC8 - targeting agents might be explored as an adjuvant for tumors carrying a mutant p53 .", "entity": [], "task": "NER"}
{"text": "microRNA - 125b inhibits tube formation of blood vessels through translational suppression of VE - cadherin .", "entity": [], "task": "NER"}
{"text": "Angiogenesis is controlled positively or negatively by extrinsic and intrinsic molecular cues in endothelial cells ( ECs ) ; in the tumor microenvironment , the action of positive regulators exceeds that of negative regulators .", "entity": [], "task": "NER"}
{"text": "Thus , overinduction of negative regulators may inhibit tumor angiogenesis .", "entity": [], "task": "NER"}
{"text": "MicroRNAs ( miRNAs or miRs ) are endogenous short noncoding RNAs regulating gene expression either through translational inhibition or destabilization of target mRNA .", "entity": [], "task": "NER"}
{"text": "Here , we show that miR - 125b expression is transiently induced in ECs on stimulation with vascular endothelial growth factor or by ischemia .", "entity": [], "task": "NER"}
{"text": "miR - 125b inhibits translation of vascular endothelial ( VE ) - cadherin mRNA and in vitro tube formation by ECs .", "entity": [], "task": "NER"}
{"text": "Injection of miR - 125b into the tumor inhibited VE - cadherin expression by ECs and induced nonfunctional blood vessel formation , resulting in inhibition of tumor growth .", "entity": [], "task": "NER"}
{"text": "It has been suggested that pro - angiogenic signals in ECs also upregulate anti - angiogenic molecules simultaneously via negative feedback .", "entity": [], "task": "NER"}
{"text": "Because miR - 125b induction in ECs is transient after pro - angiogenic stimulation , prolonged overexpression of miR - 125b could result in blood vessel regression .", "entity": [], "task": "NER"}
{"text": "Thus , miR - 125b may be useful in cancer therapy by causing the collapse of the lumen of ECs .", "entity": [], "task": "NER"}
{"text": "Chemical constituents comparison between Rhizoma Smilacis Glabrae and Rhizoma Smilacis Chinae by HPLC - DAD - MS / MS .", "entity": [], "task": "NER"}
{"text": "Rhizoma Smilacis Glabrae ( RSG ) and Rhizoma Smilacis Chinae ( RSC ) are two herbal materials that belong to the same genera and are both listed in the Chinese Pharmacopoeia .", "entity": [], "task": "NER"}
{"text": "Chemical constituents in the two species were compared by HPLC - DAD - MS / MS .", "entity": [], "task": "NER"}
{"text": "Many common constituents were found in both species , including shikimic acid , 5 - O - caffeoylshikimic acid , trans - resveratrol , taxifolin , astilbin and its three stereoisomers , engeletin and isoengeletin .", "entity": [{"entity": "shikimic acid", "entity_type": "Chemical", "pos": [64, 77]}, {"entity": "5 - O - caffeoylshikimic acid", "entity_type": "Chemical", "pos": [80, 109]}, {"entity": "trans - resveratrol", "entity_type": "Chemical", "pos": [112, 131]}, {"entity": "taxifolin", "entity_type": "Chemical", "pos": [134, 143]}, {"entity": "astilbin", "entity_type": "Chemical", "pos": [146, 154]}, {"entity": "engeletin", "entity_type": "Chemical", "pos": [185, 194]}, {"entity": "isoengeletin", "entity_type": "Chemical", "pos": [199, 211]}], "task": "NER"}
{"text": "However , syringic acid was found only in RSG , while chlorogenic acid was found only in RSC .", "entity": [{"entity": "syringic acid", "entity_type": "Chemical", "pos": [10, 23]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [54, 70]}], "task": "NER"}
{"text": "Gonadal hormones and the control of reactive gliosis .", "entity": [], "task": "NER"}
{"text": "Astrocytes and microglia respond to central nervous system ( CNS ) injury with changes in morphology , proliferation , migration and expression of inflammatory regulators .", "entity": [], "task": "NER"}
{"text": "This phenomenon is known as reactive gliosis .", "entity": [], "task": "NER"}
{"text": "Activation of astrocytes and microglia after acute neural insults , such as stroke or traumatic CNS injury , is considered to be an adaptive response that contributes to minimize neuronal damage .", "entity": [], "task": "NER"}
{"text": "However , reactive gliosis may amplify CNS damage under chronic neurodegenerative conditions .", "entity": [], "task": "NER"}
{"text": "Progesterone , estradiol and testosterone have been shown to control reactive gliosis in different models of CNS injury , modifying the number of reactive astrocytes and reactive microglia and the expression of anti - inflammatory and proinflammatory mediators .", "entity": [{"entity": "Progesterone", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [29, 41]}], "task": "NER"}
{"text": "The actions of gonadal hormones on reactive gliosis involve different mechanisms , including the modulation of the activity of steroid receptors , such as estrogen receptors alpha and beta , the regulation of nuclear factor - kappa B mediated transcription of inflammatory molecules and the recruitment of the transcriptional corepressor c - terminal binding protein to proinflammatory promoters .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [155, 163]}], "task": "NER"}
{"text": "In addition , the Parkinson ' s disease related gene parkin and the endocannabinoid system also participate in the regulation of reactive gliosis by estradiol .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [149, 158]}], "task": "NER"}
{"text": "The control exerted by gonadal hormones on reactive gliosis may affect the response of neural tissue to trauma and neurodegeneration and may contribute to sex differences in the manifestation of neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "However , the precise functional consequences of the regulation of reactive gliosis by gonadal hormones under acute and chronic neurodegenerative conditions are still not fully clarified .", "entity": [], "task": "NER"}
{"text": "A 90 - day oral ( dietary ) toxicity study of arruva , an R , R - monatin salt isomer , in Crl : CD - 1 ( ICR ) mice .", "entity": [{"entity": "arruva", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "R , R - monatin", "entity_type": "Chemical", "pos": [58, 73]}], "task": "NER"}
{"text": "R , R - Monatin [ 2R , 4R - isomer of 2 - hydroxy - 2 - ( indol - 3 - ylmethyl ) - 4 - aminoglutaric acid ] is one of four natural constituent isomers in the root bark of Sclerochitin ilicifolius ; and \" arruva \" is the common / usual name that is proposed to represent R , R - monatin salt forms , which have potential use as high potency sweetener food ingredients .", "entity": [{"entity": "R , R - Monatin", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "2R , 4R - isomer of 2 - hydroxy - 2 - ( indol - 3 - ylmethyl ) - 4 - aminoglutaric acid", "entity_type": "Chemical", "pos": [18, 105]}, {"entity": "arruva", "entity_type": "Chemical", "pos": [204, 210]}, {"entity": "R , R - monatin", "entity_type": "Chemical", "pos": [270, 285]}], "task": "NER"}
{"text": "In the present study , groups of male and female Crl : CD - 1 ( ICR ) mice were exposed to 0 ( control ) , 5000 , 10 , 000 , 20 , 000 , or 35 , 000ppm of arruva in the diet for 90days .", "entity": [{"entity": "arruva", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "There were no toxicologically relevant clinical or histopathological findings in any of the test article - treated groups .", "entity": [], "task": "NER"}
{"text": "Significantly lower mean body weights and cumulative body weight gains were noted in the 35 , 000ppm group when compared to the control group .", "entity": [], "task": "NER"}
{"text": "Mean body weights in the 35 , 000ppm group males and females were 9 % and 7 % less than the control group , respectively , at week 13 .", "entity": [], "task": "NER"}
{"text": "In the absence of observations associated with systemic toxicity and in consideration of the magnitude of body weight difference , these effects were not considered toxicologically significant .", "entity": [], "task": "NER"}
{"text": "Based on the results of this study , the dietary no - observed - adverse - effect level ( NOAEL ) of arruva for 90days in male and female mice was 35 , 000ppm ( equivalent to an exposure level of 5764 and 8013mg / kg bw / day , respectively ) .", "entity": [{"entity": "arruva", "entity_type": "Chemical", "pos": [101, 107]}], "task": "NER"}
{"text": "Grewialin and optivanin new constituents from the stem bark of Grewia optiva Drummond ex Burret ( Tiliaceae ) .", "entity": [{"entity": "Grewialin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "optivanin", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Studies on the chemical constituents from the stem bark of Grewia optiva have led to the isolation of two new compounds , grewialin ( 1 ) and optivanin ( 2 ) , along with three known constituents which were hitherto unreported from this species .", "entity": [{"entity": "grewialin", "entity_type": "Chemical", "pos": [122, 131]}, {"entity": "optivanin", "entity_type": "Chemical", "pos": [142, 151]}], "task": "NER"}
{"text": "The structures of the new constituents have been elucidated by spectral studies including 1D and 2D NMR experiments ( HSQC , HMBC , COSY , NOESY and J - resolved ) as well as HR EI - MS spectroscopic data analysis , as 2S * - ( 3 - hydroxy - 4 - methoxyphenyl ) - 3R * - methyl - 2H - [ 1 , 4 ] - dioxin [ 2 , 3 ] - chromen - 7 ( 3H ) - one ( 1 ) ; a coumarinolignan and 3 - hydroxy - 1 - ( 3 - hydroxy - 4 - methoxyphenyl ) propan - 1 - one ( 2 ) .", "entity": [{"entity": "2S * - ( 3 - hydroxy - 4 - methoxyphenyl ) - 3R * - methyl - 2H - [ 1 , 4 ] - dioxin [ 2 , 3 ] - chromen - 7 ( 3H ) - one", "entity_type": "Chemical", "pos": [219, 340]}, {"entity": "coumarinolignan", "entity_type": "Chemical", "pos": [351, 366]}, {"entity": "3 - hydroxy - 1 - ( 3 - hydroxy - 4 - methoxyphenyl ) propan - 1 - one", "entity_type": "Chemical", "pos": [371, 441]}], "task": "NER"}
{"text": "The known compounds were identified as beta - sitosterol , stigmasterol and lupeol by comparing their spectral data with those reported in the literature .", "entity": [{"entity": "beta - sitosterol", "entity_type": "Chemical", "pos": [39, 56]}, {"entity": "stigmasterol", "entity_type": "Chemical", "pos": [59, 71]}, {"entity": "lupeol", "entity_type": "Chemical", "pos": [76, 82]}], "task": "NER"}
{"text": "Berberine inhibits myofibroblast differentiation in nasal polyp - derived fibroblasts via the p38 pathway .", "entity": [{"entity": "Berberine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The purposes of this study were to determine whether berberine has any effect on phenotype changes and extracellular matrix ( ECM ) production in nasal polyp - derived fibroblasts ( NPDFs ) and to investigate the underlying molecular mechanism .", "entity": [{"entity": "berberine", "entity_type": "Chemical", "pos": [53, 62]}], "task": "NER"}
{"text": "NPDFs were pre - treated with berberine prior to induction by transforming growth factor ( TGF ) - beta 1 .", "entity": [{"entity": "berberine", "entity_type": "Chemical", "pos": [30, 39]}], "task": "NER"}
{"text": "The expression of alpha - smooth muscle actin ( SMA ) and collagen type I mRNA was determined by a reverse transcription - polymerase chain reaction , and the expression of alpha - SMA protein and collagen type I was determined by western blotting and / or immunofluorescent staining .", "entity": [], "task": "NER"}
{"text": "The total soluble collagen production was analysed by the SirCol collagen assay .", "entity": [], "task": "NER"}
{"text": "The expression of several signaling molecules of the TGF - beta 1 pathway was evaluated by western blot analysis .", "entity": [], "task": "NER"}
{"text": "In TGF - beta 1 - induced NPDFs , berberine significantly inhibited the expression of alpha - SMA and collagen type I mRNA and reduced alpha - SMA and collagen protein levels .", "entity": [{"entity": "berberine", "entity_type": "Chemical", "pos": [34, 43]}], "task": "NER"}
{"text": "Berberine only suppressed the expression of pp38 among the evaluated signaling molecules .", "entity": [{"entity": "Berberine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "SB203580 ( a specific inhibitor of p38 kinase ) markedly suppressed the increased expression of collagen type I and alpha - SMA in TGF - beta 1 - induced NPDFs .", "entity": [{"entity": "SB203580", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Berberine exerts suppressive effects on phenotype changes and ECM production in NPDFs via p38 signaling pathway interference .", "entity": [{"entity": "Berberine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The findings provide new therapeutic options for ECM production in nasal polyps .", "entity": [], "task": "NER"}
{"text": "The nonhematopoietic effects of erythropoietin in skin regeneration and repair : from basic research to clinical use .", "entity": [], "task": "NER"}
{"text": "Erythropoietin ( EPO ) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties .", "entity": [], "task": "NER"}
{"text": "More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems , in particular the skin .", "entity": [], "task": "NER"}
{"text": "This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications .", "entity": [], "task": "NER"}
{"text": "There is clear evidence that EPO effectively influences all wound - healing phases in a dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "This includes inflammation , tissue , and blood vessel formation as well as the remodeling of the wound .", "entity": [], "task": "NER"}
{"text": "The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide ( NO ) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor ( VEGF ) in the wound .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [107, 119]}, {"entity": "NO", "entity_type": "Chemical", "pos": [122, 124]}, {"entity": "NO", "entity_type": "Chemical", "pos": [171, 173]}], "task": "NER"}
{"text": "The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound - healing problems and ischemia / reperfusion injury , especially during flap surgery , may lead to new considerations of this growth hormone for its regular clinical application in patients .", "entity": [], "task": "NER"}
{"text": "Essential oils composition of Periploca laevigata Aiton subsp . angustifolia ( Labill . ) Markgraf ( Apocynaceae - Periplocoideae ) .", "entity": [], "task": "NER"}
{"text": "The essential oil of roots , branches , leaves , flowers and fruits of Periploca laevigata Aiton subsp . angustifolia ( Apocynaceae ) from Lampedusa Island has been obtained by hydrodistillation and its composition analysed .", "entity": [], "task": "NER"}
{"text": "The analyses allowed the identification and quantification of 86 volatile compounds .", "entity": [], "task": "NER"}
{"text": "Branches showed the higher diversity with 57 compounds followed by fruits with 33 , roots with 23 , flowers with 16 and leaves with six compounds , respectively .", "entity": [], "task": "NER"}
{"text": "In the matrices examined three constituents , heneicosane , docosane and tricosane are in common , although with different percentages .", "entity": [{"entity": "heneicosane", "entity_type": "Chemical", "pos": [46, 57]}, {"entity": "docosane", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "tricosane", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "At least the most abundant compounds found in the matrices have been reported to have several biological activities .", "entity": [], "task": "NER"}
{"text": "2 - Hydroxy - 4 - methoxybenzaldehyde identified in the roots as the most abundant component ( 70 . 7 % ) and present with 8 . 3 % in the branches is a potent tyrosinase inhibitor present in several African medicinal plants , and thus being used as an ingredient in cosmetic and other medicinal products , primarily in relation to hyperpigmentation .", "entity": [{"entity": "2 - Hydroxy - 4 - methoxybenzaldehyde", "entity_type": "Chemical", "pos": [0, 37]}], "task": "NER"}
{"text": "Among the compounds identified , several play a role as semiochemicals for many animals , and 28 allomones , 43 pheromones , 21 kairomones have been identified .", "entity": [], "task": "NER"}
{"text": "P . laevigata subsp . angustifolia in Lampedusa Island is host to a community of visitors , and the possible ecological role of the volatiles found is briefly discussed .", "entity": [], "task": "NER"}
{"text": "P21 - activated kinase 4 ( PAK4 ) is required for metaphase spindle positioning and anchoring .", "entity": [], "task": "NER"}
{"text": "The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2 / M transition of the cell cycle .", "entity": [], "task": "NER"}
{"text": "We have also identified that PAK4 regulates Ran GTPase activity during mitosis .", "entity": [], "task": "NER"}
{"text": "Here , we show that after entering mitosis , PAK4 - depleted cells maintain a prolonged metaphase - like state .", "entity": [], "task": "NER"}
{"text": "In these cells , chromosome congression to the metaphase plate occurs with normal kinetics but is followed by an extended period during which membrane blebbing and spindle rotation are observed .", "entity": [], "task": "NER"}
{"text": "These bipolar PAK4 - depleted metaphase - like spindles have a defective astral microtubule ( MT ) network and are not centered in the cell but are in close contact with the cell cortex .", "entity": [], "task": "NER"}
{"text": "As the metaphase - like state persists , centrosome fragmentation occurs , chromosomes scatter from the metaphase plate and move toward the spindle poles with an active spindle assembly checkpoint , a phenotype that is reminiscent of cohesion fatigue .", "entity": [], "task": "NER"}
{"text": "PAK4 also regulates the acto - myosin cytoskeleton and we report that PAK4 depletion results in the induction of cortical membrane blebbing during prometaphase arrest .", "entity": [], "task": "NER"}
{"text": "However , we show that membrane blebs , which are strongly enriched in phospho - cofilin , are not responsible for the poor anchoring of the spindle .", "entity": [{"entity": "phospho", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "As PAK4 depletion interferes with the localization of components of the dynein / dynactin complexes at the kinetochores and on the astral MTs , we propose that loss of PAK4 could induce a change in the activities of motor proteins .", "entity": [], "task": "NER"}
{"text": "The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers .", "entity": [], "task": "NER"}
{"text": "We investigated the toxicity , psychotropic side effects and anxiolytic potential of an Echinacea angustifolia extract that produced promising effects in laboratory tests performed earlier .", "entity": [], "task": "NER"}
{"text": "Rats were studied in the elevated plus - maze , conditioned fear , open - field , object recognition and conditioned place preference tests .", "entity": [], "task": "NER"}
{"text": "Toxicity was studied in rats after intragastric administration .", "entity": [], "task": "NER"}
{"text": "The preparation decreased anxiety in the elevated plus - maze and ameliorated contextual conditioned fear .", "entity": [], "task": "NER"}
{"text": "No lethality or behavioural signs of discomfort were noticed in rats treated with 1000 and 3000 mg / kg Echinacea angustifolia .", "entity": [], "task": "NER"}
{"text": "The extract was without effect in tests of locomotion ( open - field ) , memory ( object recognition ) and rewarding potential ( conditioned place preference ) within a wide dose range .", "entity": [], "task": "NER"}
{"text": "A pharmacological formulation based on the same E . angustifolia extract was tested in human subjects .", "entity": [], "task": "NER"}
{"text": "One or two tablets per day were administered for 1 week to healthy volunteers scoring high on the State - Trait Anxiety Inventory ( STAI ) .", "entity": [], "task": "NER"}
{"text": "The tablets contained 20 mg of the plant extract .", "entity": [], "task": "NER"}
{"text": "Data were collected using a structured self - assessment diary technique .", "entity": [], "task": "NER"}
{"text": "The high dose ( 2 tablets per day ) decreased STAI scores within 3 days in human subjects , an effect that remained stable for the duration of the treatment ( 7 days ) and for the 2 weeks that followed treatment .", "entity": [], "task": "NER"}
{"text": "The lower dose ( 1 tablet per day ) did not affect anxiety significantly .", "entity": [], "task": "NER"}
{"text": "Antitrypanosomal properties of Panax ginseng C .", "entity": [], "task": "NER"}
{"text": "A .", "entity": [], "task": "NER"}
{"text": "Meyer : new possibilities for a remarkable traditional drug .", "entity": [], "task": "NER"}
{"text": "African trypanosomiasis is still a major health problem in many sub - Saharan countries in Africa .", "entity": [], "task": "NER"}
{"text": "We investigated the effects of three preparations of Panax ginseng , Panax notoginseng , isolated ginsenosides , and the polyacetylene panaxynol on Trypanosoma brucei brucei and the human cancer cell line HeLa .", "entity": [{"entity": "ginsenosides", "entity_type": "Chemical", "pos": [98, 110]}, {"entity": "polyacetylene", "entity_type": "Chemical", "pos": [121, 134]}, {"entity": "panaxynol", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "Hexane extracts and the pure panaxynol were toxic and at the same time highly selective against T .", "entity": [{"entity": "Hexane", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "panaxynol", "entity_type": "Chemical", "pos": [29, 38]}], "task": "NER"}
{"text": "b . brucei , whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic and showed only weak selectivity .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "ginsenosides", "entity_type": "Chemical", "pos": [55, 67]}], "task": "NER"}
{"text": "Panaxynol was cytotoxic against T .", "entity": [{"entity": "Panaxynol", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "b . brucei at the concentration of 0 . 01 micro g / mL with a selectivity index of 858 , superior even to established antitrypanosomal drugs .", "entity": [], "task": "NER"}
{"text": "We suggest that the inhibition of trypanothione reductase , which is only found in trypanosomes , might explain the observed selectivity .", "entity": [{"entity": "trypanothione", "entity_type": "Chemical", "pos": [34, 47]}], "task": "NER"}
{"text": "The high selectivity together with a cytotoxic concentration in the range of the bioavailability makes panaxynol and other polyacetylenes in general very promising lead compounds for the treatment of African trypanosomiasis .", "entity": [{"entity": "panaxynol", "entity_type": "Chemical", "pos": [103, 112]}, {"entity": "polyacetylenes", "entity_type": "Chemical", "pos": [123, 137]}], "task": "NER"}
{"text": "Androgenic and spermatogenic activity of alkylamide - rich ethanol solution extract of Anacyclus pyrethrum DC .", "entity": [{"entity": "alkylamide", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "Anacyclus pyrethrum ( A . pyrethrum ) has been used as Vajikaran Rasayana ( aphrodisiac ) in traditional Indian ayurvedic medicine to treat male sexual dysfunction , including infertility .", "entity": [], "task": "NER"}
{"text": "Aphrodisiac activity may be due to an increase in the production or effect of androgens , so this study sought to evaluate the androgenic and spermatogenic potential of the alkylamide - rich ethanol solution extract .", "entity": [{"entity": "androgens", "entity_type": "Chemical", "pos": [78, 87]}, {"entity": "alkylamide", "entity_type": "Chemical", "pos": [173, 183]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [191, 198]}], "task": "NER"}
{"text": "Male Wistar strain rats weighing between 150 and 180 g were completely randomized divided into five groups .", "entity": [], "task": "NER"}
{"text": "The ethanol solution extract of A . pyrethrum was administered to groups of rats in 50 , 100 , and 150 mg / kg doses for a period of 28 days , and the action was compared with control and testosterone - treated rats .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [4, 11]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [188, 200]}], "task": "NER"}
{"text": "Thirteen N - alkylamides were detected in the extract by using HPLC / UV / electrospray ionization mass spectrometry method .", "entity": [{"entity": "N - alkylamides", "entity_type": "Chemical", "pos": [9, 24]}], "task": "NER"}
{"text": "Extract administration at all the doses produced significant increase in body weight , sperm count , motility , and viability along with serum testosterone , luteinizing hormone , and follicle - stimulating hormone concentrations .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [143, 155]}], "task": "NER"}
{"text": "Histoarchitecture of testis revealed increased spermatogenic activities .", "entity": [], "task": "NER"}
{"text": "Seminal fructose content was also significantly increased after 28 days of treatment .", "entity": [{"entity": "fructose", "entity_type": "Chemical", "pos": [8, 16]}], "task": "NER"}
{"text": "Our results suggest that the ethanol solution extract of the roots of A . pyrethrum has androgenic potential and may improve male fertility by enhancing spermatogenesis .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "eIF4F suppression in breast cancer affects maintenance and progression .", "entity": [], "task": "NER"}
{"text": "Levels of eukaryotic initiation factor 4E ( eIF4E ) are frequently elevated in human cancers and in some instances have been associated with poor prognosis and outcome .", "entity": [], "task": "NER"}
{"text": "Here we utilize transgenic and allograft breast cancer models to demonstrate that increased mammalian target of rapamycin ( mTOR ) signalling can be a significant contributor to breast cancer progression in vivo .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [112, 121]}], "task": "NER"}
{"text": "Suppressing mTOR activity , as well as levels and activity of the downstream translation regulators , eIF4E and eIF4A , delayed breast cancer progression , onset of associated pulmonary metastasis in vivo and breast cancer cell invasion and migration in vitro .", "entity": [], "task": "NER"}
{"text": "Translation of vascular endothelial growth factor ( VEGF ) , matrix metallopeptidase 9 ( MMP9 ) and cyclin D1 mRNAs , which encode products associated with the metastatic phenotype , is inhibited upon eIF4E suppression .", "entity": [], "task": "NER"}
{"text": "Our results indicate that the mTOR / eIF4F axis is an important contributor to tumor maintenance and progression programs in breast cancer .", "entity": [], "task": "NER"}
{"text": "Targeting this pathway may be of therapeutic benefit .", "entity": [], "task": "NER"}
{"text": "Actions of Xanthurenic acid , a putative endogenous Group II metabotropic glutamate receptor agonist , on sensory transmission in the thalamus .", "entity": [{"entity": "Xanthurenic acid", "entity_type": "Chemical", "pos": [11, 27]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "Xanthurenic acid ( XA ) , a molecule arising from tryptophan metabolism by transamination of 3 - hydroxykynurenine , has recently been identified as an endogenous Group II ( mGlu2 and mGlu3 ) metabotropic glutamate ( mGlu ) receptor ligand in vitro .", "entity": [{"entity": "Xanthurenic acid", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "3 - hydroxykynurenine", "entity_type": "Chemical", "pos": [93, 114]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [205, 214]}], "task": "NER"}
{"text": "Impairments in Group II mGlu receptor expression and function have been implicated in the pathophysiology of schizophrenia , as have multiple steps in the kynurenine metabolism pathway .", "entity": [{"entity": "kynurenine", "entity_type": "Chemical", "pos": [155, 165]}], "task": "NER"}
{"text": "Therefore , we examined XA in vivo to further investigate its potential as a Group II mGlu receptor ligand using a preparation that has been previously demonstrated to efficiently reveal the action of other Group II mGlu receptor ligands in vivo .", "entity": [], "task": "NER"}
{"text": "Extracellular single - neurone recordings were made in the rat ventrobasal thalamus ( VB ) in conjunction with iontophoresis of agonists , an antagonist and a positive allosteric modulator and / or intravenous ( i . v . ) injection of XA .", "entity": [], "task": "NER"}
{"text": "We found the XA effect on sensory inhibition , when applied iontophoretically and i . v . , was similar to that of other Group II mGlu receptor agonists in reducing inhibition evoked in the VB from the thalamic reticular nucleus upon physiological sensory stimulation .", "entity": [], "task": "NER"}
{"text": "Furthermore , we postulate that XA may be the first potential endogenous allosteric agonist ( termed ' endocoid ' ) for the mGlu receptors .", "entity": [], "task": "NER"}
{"text": "As the Group II receptors and kynurenine metabolism pathway have both been heavily implicated in the pathophysiology of schizophrenia , XA could play a pivotal role in antipsychotic research as this potential endocoid represents both a convergence within these two biological parameters and a novel class of Group II mGlu receptor ligand .", "entity": [{"entity": "kynurenine", "entity_type": "Chemical", "pos": [30, 40]}], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors ' .", "entity": [{"entity": "Glutamate", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "Sol - flame synthesis : a general strategy to decorate nanowires with metal oxide / noble metal nanoparticles .", "entity": [{"entity": "metal oxide", "entity_type": "Chemical", "pos": [70, 81]}], "task": "NER"}
{"text": "The hybrid structure of nanoparticle - decorated nanowires ( NP @ NW ) combines the merits of large specific surface areas for NPs and anisotropic properties for NWs and is a desirable structure for applications including batteries , dye - sensitized solar cells , photoelectrochemical water splitting , and catalysis .", "entity": [], "task": "NER"}
{"text": "Here , we report a novel sol - flame method to synthesize the NP @ NW hybrid structure with two unique characteristics : ( 1 ) large loading of NPs per NW with the morphology of NP chains fanning radially from the NW core and ( 2 ) intimate contact between NPs and NWs .", "entity": [], "task": "NER"}
{"text": "Both features are advantageous for the above applications that involve both surface reactions and charge transport processes .", "entity": [], "task": "NER"}
{"text": "Moreover , the sol - flame method is simple and general , with which we have successfully decorated various NWs with binary / ternary metal oxide and even noble metal NPs .", "entity": [{"entity": "metal oxide", "entity_type": "Chemical", "pos": [134, 145]}], "task": "NER"}
{"text": "The unique aspects of the sol - flame method arise from the ultrafast heating rate and the high temperature of flame , which enables rapid solvent evaporation and combustion , and the combustion gaseous products blow out NPs as they nucleate , forming the NP chains around NWs .", "entity": [], "task": "NER"}
{"text": "Improving oral absorption via drug - loaded nanocarriers : absorption mechanisms , intestinal models and rational fabrication .", "entity": [], "task": "NER"}
{"text": "Although it is acknowledged that the main impediment of orally administered therapeutic agents is their extensive and changeable pre - systemic metabolism , low absorption and instability in harsh environment of the gastrointestinal ( GI ) tract are also main influential factors , resulting into inadequate and erratic drug bioavailability .", "entity": [], "task": "NER"}
{"text": "To overcome these shortcomings , nanotechnology has offered new promising strategies to prevent and treat a wide variety of diseases by employing different oral drug - carrier structures capable to enhance therapeutic effects and minimize the toxicity of healthy organs or cells .", "entity": [], "task": "NER"}
{"text": "This review , in general , elucidates some considerable features of in vitro oral drug delivery in three different parts .", "entity": [], "task": "NER"}
{"text": "The first one summarizes the main challenges for oral drug delivery and available absorption mechanisms .", "entity": [], "task": "NER"}
{"text": "The second part embodies an in - depth discussion on the role of the intestinal absorption models used to predict permeability , cellular uptake or even toxicity of nanoparticles , resulting into the design of nanocarriers with optimum efficacy for oral delivery .", "entity": [], "task": "NER"}
{"text": "The third section of the literature is devoted , more particularly , to nanocarriers developed for oral absorption in the past few years , including the behavior of nanovehicles upon oral administration with respect to membrane permeability , retention properties and stability , as well as methods which may lengthen residence time in the GI environment or improve drug absorption .", "entity": [], "task": "NER"}
{"text": "Precision - cut intestinal slices as in vitro tool for studies on drug metabolism .", "entity": [], "task": "NER"}
{"text": "The role of the intestine in drug metabolism has long been underestimated as a consequence of the technical difficulty to discern the role of the intestine from that of the liver in in vivo experiments and of the lack of in vitro models that are sufficiently viable and fully representing the physiology and anatomy of the intestine .", "entity": [], "task": "NER"}
{"text": "Recently the precision - cut slice model , which is widely used for liver and kidney , was also adapted for the small and large intestine .", "entity": [], "task": "NER"}
{"text": "In this review the application of precision - cut intestinal slices ( PCIS ) for research in drug metabolism and transport is discussed .", "entity": [], "task": "NER"}
{"text": "PCIS can be prepared from animal and human tissues from all regions of the intestine allowing investigation of species differences and regional gradients of activities of metabolizing enzymes .", "entity": [], "task": "NER"}
{"text": "They are viable for 8 - 24 h of incubation and show high activity of drug metabolizing enzymes , representative for the in vivo activity .", "entity": [], "task": "NER"}
{"text": "They have been successfully used to study drug - drug interactions such as induction , inhibition and regulation of drug metabolizing enzymes , transporters and nuclear factors .", "entity": [], "task": "NER"}
{"text": "Moreover they appear to be a suitable model for studies on cold preservation of donor organs for transplantation , and allow exploring inter - organ interactions by co - incubation with precision - cut slices of other organs .", "entity": [], "task": "NER"}
{"text": "Their application as model for drug - induced intestinal toxicity is still in its infancy but appears to be promising .", "entity": [], "task": "NER"}
{"text": "PCIS , prepared from human and animal tissues , represent a powerful translational model for drug metabolism , transport and toxicity studies and as such contributes to the reduction and replacement of animal experiments .", "entity": [], "task": "NER"}
{"text": "Topical antiinflammatory activity of essential oil of Lippia sidoides cham : possible mechanism of action .", "entity": [], "task": "NER"}
{"text": "This work reports the chemical composition of the essential oil of Lippia sidoides ( EOLS ) and evaluation of the topical effect of EOLS and thymol against different irritant agents in vivo .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [141, 147]}], "task": "NER"}
{"text": "The essential oil was obtained by hydrodistillation , and gas chromatography / mass spectrometry analysis identified the main constituents : thymol ( 84 . 9 % ) and p - cymene ( 5 . 33 % ) .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [141, 147]}, {"entity": "p - cymene", "entity_type": "Chemical", "pos": [165, 175]}], "task": "NER"}
{"text": "The antiinflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil , arachidonic acid , phenol or histamine , and chronic inflammation induced by croton oil .", "entity": [{"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [117, 133]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [136, 142]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [146, 155]}], "task": "NER"}
{"text": "The topical application of EOLS or thymol at a dose of 2 mg / ear significantly reduced ( p < 0 . 001 ) ear edema induced with arachidonic acid by 45 . 1 % and 47 . 4 % and reduced ear edema induced with phenol by 33 . 2 % ( p < 0 . 05 ) and 54 . 7 % ( p < 0 . 01 ) in acute ear edema .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [35, 41]}, {"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [127, 143]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [204, 210]}], "task": "NER"}
{"text": "However , a proinflammatory effect of EOLS and thymol was evidenced when it was applied for more than 1 day .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "There were no statistical differences in antiedematogenic activity between EOLS and thymol .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [84, 90]}], "task": "NER"}
{"text": "In conclusion , the results indicate that thymol is the constituent responsible for the topical antiinflammatory activity of EOLS .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [42, 48]}], "task": "NER"}
{"text": "Thus , these findings could justify the popular use of L . sidoides by alternative medicine , but chronic use has an inflammatory effect .", "entity": [], "task": "NER"}
{"text": "Effects of synthetic peptides on the inflammatory response and their therapeutic potential .", "entity": [], "task": "NER"}
{"text": "Recently , interest in small peptide molecules as potential drug candidates has revived .", "entity": [], "task": "NER"}
{"text": "In this review , two series of synthetic peptides and their selective effects on the inflammatory response have been described , focusing on the intracellular pathways involved and on their therapeutic potential .", "entity": [], "task": "NER"}
{"text": "A series of F ( D ) LF ( D ) LF analogs has been synthesized , including either N - t - Boc or different N - ureido substituents .", "entity": [{"entity": "N - t - Boc", "entity_type": "Chemical", "pos": [80, 91]}, {"entity": "N - ureido", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "The free acid derivatives as they are good candidates as antiinflammatory drugs are able to antagonize the multiple neutrophil functions evoked by N - formyl - L - methionyl - L - leucyl - Lphenylalanine ( fMLF ) , i . e . chemotaxis , superoxide anion production and lysozyme release .", "entity": [{"entity": "N - formyl - L - methionyl - L - leucyl - Lphenylalanine", "entity_type": "Chemical", "pos": [147, 203]}, {"entity": "fMLF", "entity_type": "Chemical", "pos": [206, 210]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [236, 246]}], "task": "NER"}
{"text": "Their methyl - ester derivatives are ineffective .", "entity": [{"entity": "methyl - ester", "entity_type": "Chemical", "pos": [6, 20]}], "task": "NER"}
{"text": "The second series of peptides derives from the endogenous protein kinase C ( PKC ) inhibitor PKI55 , a 55 - amino acid protein , whose synthesis is induced by PKC activation , so that a feedback loop of inhibition is established .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [108, 118]}], "task": "NER"}
{"text": "In vitro experiments showed that PKI55 inhibits recombinant PKC isoforms alpha , beta 1 , beta 2 , gamma , delta , zeta , ; to identify the minimal amino acid sequence of PKI55 protein maintaining the inhibitory effects on PKC , peptides derived from both C - and N - terminal sequences have been synthesized .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [148, 158]}, {"entity": "C", "entity_type": "Chemical", "pos": [225, 226]}, {"entity": "N", "entity_type": "Chemical", "pos": [264, 265]}], "task": "NER"}
{"text": "The N - terminal peptides 5 ( MLYKLHDVCRQLWFSC ) , 8 ( CRQLWFSC ) and 9 ( CRQLW ) , that in human neutrophils retain the inhibitory activity on PKC , decrease the chemotaxis , and , in mice , display anti - inflammatory and analgesic action , after both central and peripheral administration of very low doses .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [4, 5]}], "task": "NER"}
{"text": "Furthermore , the peptide 5 shows neuroprotective activity in a model of cerebral ischemia in vitro , favouring the recovery of synaptic function .", "entity": [], "task": "NER"}
{"text": "These findings suggest interesting possible therapeutic applications for these peptides .", "entity": [], "task": "NER"}
{"text": "A review on the development in the field of NIDDM based thiazolidinedione PPAR gamma agonists .", "entity": [{"entity": "thiazolidinedione", "entity_type": "Chemical", "pos": [56, 73]}], "task": "NER"}
{"text": "Peroxisome Proliferator Activated Receptors gamma ( PPAR gamma ) are a class of ligand activated transcription factors with a prominent role in the regulation of metabolic processes .", "entity": [], "task": "NER"}
{"text": "The present work aims towards examining the functional and structural features that facilitate the binding of small molecules based on Thiazolidinedione pharmacophore to PPARs .", "entity": [{"entity": "Thiazolidinedione", "entity_type": "Chemical", "pos": [135, 152]}], "task": "NER"}
{"text": "The intent of this article is to review all the reported thiazolidinediones and associated groups of PPAR gamma ligands .", "entity": [{"entity": "thiazolidinediones", "entity_type": "Chemical", "pos": [57, 75]}], "task": "NER"}
{"text": "A new triterpenoid from the rhizomes of Nelumbo nucifera .", "entity": [{"entity": "triterpenoid", "entity_type": "Chemical", "pos": [6, 18]}], "task": "NER"}
{"text": "A new triterpenoid , 2 alpha , 24 - diacetoxy - 3 beta - hydroxyolean - 12 - en - 28 - oic acid ( 1 ) , was characterised from the rhizomes of Nelumbo nucifera Gaertn by spectroscopic and chemical methods along with four known compounds , hyptatic acid - A ( 2 alpha , 3 beta , 24 - trihydroxyolean - 12 - en - 28 - oic acid ) ( 2 ) , maslinic acid ( 2 alpha , 3 beta - dihydroxyoleane - 12 - ene - 28 - oic acid ) , betulin and lupeol .", "entity": [{"entity": "triterpenoid", "entity_type": "Chemical", "pos": [6, 18]}, {"entity": "2 alpha , 24 - diacetoxy - 3 beta - hydroxyolean - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [21, 95]}, {"entity": "hyptatic acid - A", "entity_type": "Chemical", "pos": [239, 256]}, {"entity": "2 alpha , 3 beta , 24 - trihydroxyolean - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [259, 324]}, {"entity": "maslinic acid", "entity_type": "Chemical", "pos": [335, 348]}, {"entity": "2 alpha , 3 beta - dihydroxyoleane - 12 - ene - 28 - oic acid", "entity_type": "Chemical", "pos": [351, 412]}, {"entity": "betulin", "entity_type": "Chemical", "pos": [417, 424]}, {"entity": "lupeol", "entity_type": "Chemical", "pos": [429, 435]}], "task": "NER"}
{"text": "Vasodilatory effects of cinnamic acid via the nitric oxide - cGMP - PKG pathway in rat thoracic aorta .", "entity": [{"entity": "cinnamic acid", "entity_type": "Chemical", "pos": [24, 37]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [46, 58]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [61, 65]}], "task": "NER"}
{"text": "Cinnamic acid ( CA ) and its derivatives have a broad therapeutic spectrum that includes antimicrobial , antifungal , and antitumoral activities .", "entity": [{"entity": "Cinnamic acid", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "However , the vasodilative effect of CA has not been demonstrated .", "entity": [], "task": "NER"}
{"text": "The present study characterizes the vasodilative activity and the mechanism of CA in rat thoracic aorta .", "entity": [], "task": "NER"}
{"text": "The vasomotion of aortic strips following CA treatment was measured in an organ bath system .", "entity": [], "task": "NER"}
{"text": "In addition , vascular strips and human umbilical vein endothelial cells ( HUVECs ) were used in organ bath , Western blot , nitrite , and cyclic guanosine monophosphate ( cGMP ) measurements .", "entity": [{"entity": "nitrite", "entity_type": "Chemical", "pos": [125, 132]}, {"entity": "cyclic guanosine monophosphate", "entity_type": "Chemical", "pos": [139, 169]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [172, 176]}], "task": "NER"}
{"text": "CA relaxed phenylephrine - precontracted aortic strips in an endothelium - dependent manner .", "entity": [{"entity": "phenylephrine", "entity_type": "Chemical", "pos": [11, 24]}], "task": "NER"}
{"text": "Pretreatment of the endothelium - intact aortic strips with N ( G ) - nitro - l - arginine methyl ester ( 10 ( - 4 ) M ) , 1 H - [ 1 , 2 , 4 ] - oxadiazolole - [ 4 , 3 - a ] quinoxalin - 10 - one , ( 10 ( - 6 ) M ) and methylene blue ( 10 ( - 5 ) M ) inhibited CA - induced vasorelaxation .", "entity": [{"entity": "N ( G ) - nitro - l - arginine methyl ester", "entity_type": "Chemical", "pos": [60, 103]}, {"entity": "1 H - [ 1 , 2 , 4 ] - oxadiazolole - [ 4 , 3 - a ] quinoxalin - 10 - one", "entity_type": "Chemical", "pos": [123, 195]}, {"entity": "methylene blue", "entity_type": "Chemical", "pos": [219, 233]}], "task": "NER"}
{"text": "CA also increased the phosphorylation of endothelial nitric oxide synthase and nitric oxide generation in a concentration - dependent manner in HUVECs .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [53, 65]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [79, 91]}], "task": "NER"}
{"text": "In addition , cGMP generation and cGMP - dependent protein kinase G ( PKG ) expression in aortic strips were increased by CA treatment .", "entity": [{"entity": "cGMP", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "Furthermore , CA - induced vasorelaxation was inhibited by the PKG inhibitor KT5823 ( 0 . 3 mu M ) and the Ca ( 2 + ) - activated K ( + ) channel inhibitor tetraethylammonium ( 10 ( - 3 ) M ) .", "entity": [{"entity": "KT5823", "entity_type": "Chemical", "pos": [77, 83]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "tetraethylammonium", "entity_type": "Chemical", "pos": [156, 174]}], "task": "NER"}
{"text": "These findings suggest that CA exerts an endothelium - dependent vasodilation effect via the nitric oxide - cGMP - PKG - mediated pathway in rat thoracic aorta .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [93, 105]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [108, 112]}], "task": "NER"}
{"text": "The role of inflammation in epileptogenesis .", "entity": [], "task": "NER"}
{"text": "One compelling challenge in the therapy of epilepsy is to develop anti - epileptogenic drugs with an impact on the disease progression .", "entity": [], "task": "NER"}
{"text": "The search for novel targets has focused recently on brain inflammation since this phenomenon appears to be an integral part of the diseased hyperexcitable brain tissue from which spontaneous and recurrent seizures originate .", "entity": [], "task": "NER"}
{"text": "Although the contribution of specific proinflammatory pathways to the mechanism of ictogenesis in epileptic tissue has been demonstrated in experimental models , the role of these pathways in epileptogenesis is still under evaluation .", "entity": [], "task": "NER"}
{"text": "We review the evidence conceptually supporting the involvement of brain inflammation and the associated blood - brain barrier damage in epileptogenesis , and describe the available pharmacological evidence where post - injury intervention with anti - inflammatory drugs has been attempted .", "entity": [], "task": "NER"}
{"text": "Our review will focus on three main inflammatory pathways , namely the IL - 1 receptor / Toll - like receptor signaling , COX - 2 and the TGF - beta signaling .", "entity": [], "task": "NER"}
{"text": "The mechanisms underlying neuronal - glia network dysfunctions induced by brain inflammation are also discussed , highlighting novel neuromodulatory effects of classical inflammatory mediators such as cytokines and prostaglandins .", "entity": [{"entity": "prostaglandins", "entity_type": "Chemical", "pos": [215, 229]}], "task": "NER"}
{"text": "The increase in knowledge about a role of inflammation in disease progression , may prompt the use of specific anti - inflammatory drugs for developing disease - modifying treatments .", "entity": [], "task": "NER"}
{"text": "This article is part of the Special Issue entitled ' New Targets and Approaches to the Treatment of Epilepsy ' .", "entity": [], "task": "NER"}
{"text": "Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1 .", "entity": [], "task": "NER"}
{"text": "The medial prefrontal cortex ( mPFC ) serves executive cognitive functions such as decision - making that are impaired in neuropsychiatric disorders and pain .", "entity": [], "task": "NER"}
{"text": "We showed previously that amygdala - driven abnormal inhibition and decreased output of mPFC pyramidal cells contribute to pain - related impaired decision - making ( Ji et al . , 2010 ) .", "entity": [], "task": "NER"}
{"text": "Therefore , modulating pyramidal output is desirable therapeutic goal .", "entity": [], "task": "NER"}
{"text": "Targeting metabotropic glutamate receptor subtype mGluR5 has emerged as a cognitive - enhancing strategy in neuropsychiatric disorders , but synaptic and cellular actions of mGluR5 in the mPFC remain to be determined .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "The present study determined synaptic and cellular actions of mGluR5 to test the hypothesis that increasing mGluR5 function can enhance pyramidal cell output .", "entity": [], "task": "NER"}
{"text": "Whole - cell voltage - and current - clamp recordings were made from visually identified pyramidal neurons in layer V of the mPFC in rat brain slices .", "entity": [], "task": "NER"}
{"text": "Both the prototypical mGluR5 agonist CHPG and a positive allosteric modulator ( PAM ) for mGluR5 ( VU0360172 ) increased synaptically evoked spiking ( E - S coupling ) in mPFC pyramidal cells .", "entity": [{"entity": "CHPG", "entity_type": "Chemical", "pos": [37, 41]}, {"entity": "VU0360172", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "The facilitatory effects of CHPG and VU0360172 were inhibited by an mGluR5 antagonist ( MTEP ) .", "entity": [{"entity": "CHPG", "entity_type": "Chemical", "pos": [28, 32]}, {"entity": "VU0360172", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "MTEP", "entity_type": "Chemical", "pos": [88, 92]}], "task": "NER"}
{"text": "CHPG , but not VU0360172 , increased neuronal excitability ( frequency - current [ F - I ] function ) .", "entity": [{"entity": "CHPG", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "VU0360172", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "VU0360172 , but not CHPG , increased evoked excitatory synaptic currents ( EPSCs ) and amplitude , but not frequency , of miniature EPSCs , indicating a postsynaptic action .", "entity": [{"entity": "VU0360172", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "CHPG", "entity_type": "Chemical", "pos": [20, 24]}], "task": "NER"}
{"text": "VU0360172 , but not CHPG , decreased evoked inhibitory synaptic currents ( IPSCs ) through an action that involved cannabinoid receptor CB1 , because a CB1 receptor antagonist ( AM281 ) blocked the inhibitory effect of VU0360172 on synaptic inhibition .", "entity": [{"entity": "VU0360172", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "CHPG", "entity_type": "Chemical", "pos": [20, 24]}, {"entity": "AM281", "entity_type": "Chemical", "pos": [178, 183]}, {"entity": "VU0360172", "entity_type": "Chemical", "pos": [219, 228]}], "task": "NER"}
{"text": "VU0360172 also increased and prolonged CB1 - mediated depolarization - induced suppression of synaptic inhibition ( DSI ) .", "entity": [{"entity": "VU0360172", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Activation of CB1 with ACEA decreased inhibitory transmission through a presynaptic mechanism .", "entity": [{"entity": "ACEA", "entity_type": "Chemical", "pos": [23, 27]}], "task": "NER"}
{"text": "The results show that increasing mGluR5 function enhances mPFC output .", "entity": [], "task": "NER"}
{"text": "This effect can be accomplished by increasing excitability with an orthosteric agonist ( CHPG ) or by increasing excitatory synaptic drive and CB1 - mediated presynaptic suppression of synaptic inhibition ( \" dis - inhibition \" ) with a PAM ( VU0360172 ) .", "entity": [{"entity": "CHPG", "entity_type": "Chemical", "pos": [89, 93]}, {"entity": "VU0360172", "entity_type": "Chemical", "pos": [243, 252]}], "task": "NER"}
{"text": "Therefore , mGluR5 may be a useful target in conditions of impaired mPFC output .", "entity": [], "task": "NER"}
{"text": "Stratified medicine in psychiatry : a worrying example or new opportunity in the treatment of anxiety ?", "entity": [], "task": "NER"}
{"text": "Stratified medicine is a new term that figures highly in current MRC and NHS strategy .", "entity": [], "task": "NER"}
{"text": "It has developed from the earlier terms individualised or personalised medicine and refers to the use of genetic and / or endophenotypic measures to allow better targeting of treatments .", "entity": [], "task": "NER"}
{"text": "The best exemplar is HER2 positivity in breast cancer to determine the efficacy of Herceptin .", "entity": [], "task": "NER"}
{"text": "Clinical trials of this anti - cancer drug were initially unpromising , but once the HER2 positive subgroup was identified it was found , in this subgroup only , to be highly effective .", "entity": [], "task": "NER"}
{"text": "It is presumed that similar subgroups will be found for many common disorders not just cancers , and that these will lead to much better targeted treatments .", "entity": [], "task": "NER"}
{"text": "Such an advance may be necessary to develop new treatments in certain fields where the development of broad - spectrum / blockbuster treatments appears to have reached the end of the road ; a particular example of this is in psychiatry .", "entity": [], "task": "NER"}
{"text": "In this paper we discuss this issue in relation to psychiatry using a new and interesting example of how genotyping might help rescue an apparently failed novel treatment in anxiety disorders .", "entity": [], "task": "NER"}
{"text": "Extracts of Scutellaria baicalensis reduced body weight and blood triglyceride in db / db Mice .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [66, 78]}], "task": "NER"}
{"text": "Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia , atherosclerosis , hypertension , dysentery , inflammatory diseases , and the common cold .", "entity": [], "task": "NER"}
{"text": "The present study was performed to investigate the anti - obesity and anti - dyslipidemia effect of Scutellaria baicalensis extracts ( SBE ) in type 2 diabetic db / db mice .", "entity": [], "task": "NER"}
{"text": "Male db / db mice were divided into three groups ( n = 5 ) and orally administrated vehicle ( control ) , SBE 10 , and 100 mg / kg body weight / day for 4 weeks everyday .", "entity": [], "task": "NER"}
{"text": "Administration of SBE improves weight gain , hypertriglyceridemia , and hyperinsulinemia in db / db mice .", "entity": [], "task": "NER"}
{"text": "In obese db / db mice , SBE treatment also reduced plasma alanine aminotransferase levels .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "In the livers of db / db mice , SBE promoted 5 ' AMP - activated protein kinase activity and restored metabolic process and insulin signaling pathways .", "entity": [{"entity": "5 ' AMP", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "Our data demonstrate that SBE exerts potent anti - obesity and anti - hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia .", "entity": [], "task": "NER"}
{"text": "A new lignan with anti - tumour activity from Polygonum perfoliatum L .", "entity": [], "task": "NER"}
{"text": "The methanol extract of the tubers of Polygonum perfoliatum L . afforded a new lignan : 8 - oxo - pinoresinol ( 1 ) , and five known compounds 3 ' , 5 - dihydroxy - 3 , 4 ' , 5 ' , 7 - tetramethoxy - flavone ( 2 ) , catechin ( 3 ) , quercetin ( 4 ) , quercetin - 3 - O - beta - D - glucuronide ( 5 ) and rutin ( 6 ) .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "lignan", "entity_type": "Chemical", "pos": [79, 85]}, {"entity": "8 - oxo - pinoresinol", "entity_type": "Chemical", "pos": [88, 109]}, {"entity": "3 ' , 5 - dihydroxy - 3 , 4 ' , 5 ' , 7 - tetramethoxy - flavone", "entity_type": "Chemical", "pos": [143, 207]}, {"entity": "catechin", "entity_type": "Chemical", "pos": [216, 224]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [233, 242]}, {"entity": "quercetin - 3 - O - beta - D - glucuronide", "entity_type": "Chemical", "pos": [251, 293]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [304, 309]}], "task": "NER"}
{"text": "Their structures were established by MS , one - and two - dimensional NMR experiments .", "entity": [], "task": "NER"}
{"text": "Compound 1 showed cytotoxicity against human mammary carcinoma ( Bcap - 37 ) , human colon carcinoma ( RKO ) , human hepatocellular carcinoma ( SMMC - 7721 ) , human prostate carcinoma ( PC3 ) and human erythroleukaemia ( K562 ) cells .", "entity": [], "task": "NER"}
{"text": "Tonic GABA ( A ) receptor - mediated signalling in temporal lobe epilepsy .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [6, 10]}], "task": "NER"}
{"text": "The tonic activation of extrasynaptic GABAA receptors by extracellular GABA provides a powerful means of regulating neuronal excitability .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [38, 42]}], "task": "NER"}
{"text": "A consistent finding from studies that have used various models of temporal lobe epilepsy is that tonic GABAA receptor - mediated conductances are largely preserved in epileptic brain ( in contrast to synaptic inhibition which is often reduced ) .", "entity": [], "task": "NER"}
{"text": "Tonic inhibition is therefore an attractive target for antiepileptic drugs .", "entity": [], "task": "NER"}
{"text": "However , the network consequences of a commonly used approach to augment tonic GABAA receptor - mediated conductances by global manipulation of extracellular GABA are difficult to predict without understanding how epileptogenesis alters the pharmacology and GABA sensitivity of tonic inhibition , and how manipulation of tonic conductances modulates the output of individual neurons .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [80, 84]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [159, 163]}], "task": "NER"}
{"text": "Here we review the current literature on epilepsy - associated changes in tonic GABAA receptor - mediated signalling , and speculate about possible effects they have at the network level .", "entity": [], "task": "NER"}
{"text": "Metabotropic glutamate 7 ( mGlu7 ) receptor : a target for medication development for the treatment of cocaine dependence .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "Brain glutamate has been shown to play an important role in reinstatement to drug seeking , a behavior considered to be of relevance to relapse to drug taking in humans .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "Therefore , glutamate receptors , in particular metabotropic glutamate ( mGlu ) receptors , have become important targets for medication development for the treatment of drug dependence .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [12, 21]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [61, 70]}], "task": "NER"}
{"text": "In this review article , we focus on the mGlu7 receptor subtype , and discuss recent findings with AMN082 , a selective mGlu7 receptor allosteric agonist , in animal models with relevance to drug dependence .", "entity": [{"entity": "AMN082", "entity_type": "Chemical", "pos": [99, 105]}], "task": "NER"}
{"text": "Systemic or local administration of AMN082 into the nucleus accumbens ( NAc ) , a critical brain region involved in reward and drug dependence processes , inhibited the reinforcing and motivational effects of cocaine , heroin and ethanol , as assessed by the intravenous drug self - administration procedure .", "entity": [{"entity": "AMN082", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [209, 216]}, {"entity": "heroin", "entity_type": "Chemical", "pos": [219, 225]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [230, 237]}], "task": "NER"}
{"text": "In addition , AMN082 inhibited the reward - enhancing effects induced by cocaine , as assessed in the intracranial self - stimulation procedure , and cocaine - or cue - induced reinstatement of drug - seeking behavior .", "entity": [{"entity": "AMN082", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [150, 157]}], "task": "NER"}
{"text": "In vivo microdialysis studies indicated that systemic or intra - NAc administration of AMN082 significantly decreased extracellular gamma - aminobutyric acid ( GABA ) and elevated extracellular glutamate , but had no effect on extracellular dopamine in the NAc , suggesting that a non - dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine .", "entity": [{"entity": "AMN082", "entity_type": "Chemical", "pos": [87, 93]}, {"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [132, 157]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [160, 164]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [194, 203]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [241, 249]}, {"entity": "AMN082", "entity_type": "Chemical", "pos": [335, 341]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [360, 367]}], "task": "NER"}
{"text": "Further , data indicated that AMN082 - induced changes in glutamate were the net effect of two actions : one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons ; another is the indirect increases of glutamate release mediated by decreases in GABA transmission .", "entity": [{"entity": "AMN082", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [137, 146]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [191, 200]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [295, 299]}], "task": "NER"}
{"text": "These increases in extracellular glutamate functionally antagonized cocaine - induced inhibition of NAc - ventral pallidum GABAergic neurotransmission , and therefore , the rewarding effects of cocaine .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "pallidum", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [194, 201]}], "task": "NER"}
{"text": "In addition , elevated extracellular glutamate activated presynaptic mGlu2 / 3 autoreceptors which in turn inhibited cocaine priming - or cue - induced enhancement of glutamate release and reinstatement of drug - seeking behavior .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [117, 124]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [167, 176]}], "task": "NER"}
{"text": "Taken together , these findings suggest that the mGlu7 receptor is an important target for medication development for the treatment of drug dependence .", "entity": [], "task": "NER"}
{"text": "AMN082 or other mGlu7 receptor allosteric agonists may have potential as novel pharmacotherapies for cocaine addiction .", "entity": [{"entity": "AMN082", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "The synergistic apoptotic interaction of panaxadiol and epigallocatechin gallate in human colorectal cancer cells .", "entity": [{"entity": "panaxadiol", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "epigallocatechin gallate", "entity_type": "Chemical", "pos": [56, 80]}], "task": "NER"}
{"text": "Panaxadiol ( PD ) is a purified sapogenin of ginseng saponins , which exhibits anticancer activity .", "entity": [{"entity": "Panaxadiol", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "sapogenin", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [53, 61]}], "task": "NER"}
{"text": "Epigallocatechin gallate ( EGCG ) , a major catechin in green tea , is a strong botanical antioxidant .", "entity": [{"entity": "Epigallocatechin gallate", "entity_type": "Chemical", "pos": [0, 24]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "catechin", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "In this study , we investigated the possible synergistic anticancer effects of PD and EGCG on human colorectal cancer cells and explored the potential role of apoptosis in the synergistic activities .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [86, 90]}], "task": "NER"}
{"text": "Effects of selected compounds on HCT - 116 and SW - 480 human colorectal cancer cells were evaluated by a modified trichrome stain cell proliferation analysis .", "entity": [], "task": "NER"}
{"text": "Cell cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with PI / RNase or annexin V / PI .", "entity": [], "task": "NER"}
{"text": "Cell growth was suppressed after treatment with PD ( 10 and 20 micro m ) for 48 h .", "entity": [], "task": "NER"}
{"text": "When PD ( 10 and 20 micro m ) was combined with EGCG ( 10 , 20 , and 30 micro m ) , significantly enhanced antiproliferative effects were observed in both cell lines .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "Combining 20 micro m of PD with 20 and 30 micro m of EGCG significantly decreased S - phase fractions of cells .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [53, 57]}], "task": "NER"}
{"text": "In the apoptotic assay , the combination of PD and EGCG significantly increased the percentage of apoptotic cells compared with PD alone ( p < 0 . 01 ) .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "The synergistic apoptotic effects were also supported by docking analysis , which demonstrated that PD and EGCG bound in two different sites of the annexin V protein .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "Data from this study suggested that apoptosis might play an important role in the EGCG - enhanced antiproliferative effects of PD on human colorectal cancer cells .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [82, 86]}], "task": "NER"}
{"text": "HPLC analysis of Stephania rotunda extracts and correlation with antiplasmodial activity .", "entity": [], "task": "NER"}
{"text": "Stephania rotunda ( Menispermaceae ) , a creeper commonly found in the mountainous areas of Cambodia , has been mainly used for the treatment of fever and malaria .", "entity": [], "task": "NER"}
{"text": "Thus , the aim of this study is to investigate the chemical composition and antiplasmodial activity of different samples of S . rotunda and compare their antiplasmodial activity with their alkaloid content .", "entity": [], "task": "NER"}
{"text": "Sixteen samples from different parts ( roots , stem , and tuber ) of S . rotunda were collected from four regions of Cambodia ( Battambang , Pailin , Siem Reap , and Kampot ) .", "entity": [], "task": "NER"}
{"text": "Reversed - phase HPLC was used to determine the content of three bioactive alkaloids ( cepharanthine , tetrahydropalmatine , and xylopinine ) .", "entity": [{"entity": "cepharanthine", "entity_type": "Chemical", "pos": [87, 100]}, {"entity": "tetrahydropalmatine", "entity_type": "Chemical", "pos": [103, 122]}, {"entity": "xylopinine", "entity_type": "Chemical", "pos": [129, 139]}], "task": "NER"}
{"text": "These three alkaloids have been found in all samples from Battambang and Pailin ( samples I - IX ) , whereas only tetrahydropalmatine was present in samples from Siem Reap and Kampot ( samples X - XVI ) .", "entity": [{"entity": "tetrahydropalmatine", "entity_type": "Chemical", "pos": [114, 133]}], "task": "NER"}
{"text": "The analyzed extracts were evaluated for their antiplasmodial activity on W2 strain of Plasmodium falciparum .", "entity": [], "task": "NER"}
{"text": "Among them , 13 extracts were significantly active with inhibitory concentration 50 ( IC ( 50 ) ) from 1 . 2 to 3 . 7 micro g / mL and 2 extracts were moderately active ( IC ( 50 ) = 6 . 1 and 10 micro g / mL , respectively ) , whereas sample XI was not active ( IC ( 50 ) = 19 . 6 micro g / mL ) .", "entity": [], "task": "NER"}
{"text": "A comparison between antiplasmodial activity and concentration of the three bioactive alkaloids in S . rotunda extracts has been realized .", "entity": [], "task": "NER"}
{"text": "Preventive effects of North American ginseng ( Panax quinquefolius ) on diabetic retinopathy and cardiomyopathy .", "entity": [], "task": "NER"}
{"text": "Ginseng ( Araliaceae ) has multiple pharmacological actions because of its diverse phytochemical constituents .", "entity": [], "task": "NER"}
{"text": "The aims of the present study are to evaluate the preventive effects of North American ginseng on diabetic retinopathy and cardiomyopathy and to delineate the underlying mechanisms of such effects .", "entity": [], "task": "NER"}
{"text": "Models of both type 1 ( C57BL / 6 mice with streptozotocin - induced diabetes ) and type 2 diabetes ( db / db mice ) and age - matched and sex - matched controls were examined .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [44, 58]}], "task": "NER"}
{"text": "Alcoholic ginseng root ( 200 mg / kg body weight , daily oral gavage ) extract was administered to groups of both type 1 and type 2 diabetic mice for 2 or 4 months .", "entity": [], "task": "NER"}
{"text": "Dysmetabolic state in the diabetic mice was significantly improved by ginseng treatment .", "entity": [], "task": "NER"}
{"text": "In both the heart and retina of diabetic animals , ginseng treatment significantly prevented oxidative stress and diabetes - induced upregulations of extracellular matrix proteins and vasoactive factors .", "entity": [], "task": "NER"}
{"text": "Ginseng treatment in the diabetic animals resulted in enhancement of stroke volume , ejection fraction , cardiac output , and left ventricle pressure during systole and diastole and diminution of stroke work .", "entity": [], "task": "NER"}
{"text": "In addition , mRNA expressions of atrial natriuretic factor and brain natriuretic factor ( molecular markers for cardiac hypertrophy ) were significantly diminished in ginseng - treated diabetic mice .", "entity": [], "task": "NER"}
{"text": "These data indicate that North American ginseng prevents the diabetes - induced retinal and cardiac biochemical and functional changes probably through inhibition of oxidative stress .", "entity": [], "task": "NER"}
{"text": "Evaluation of food - drug interaction of guava leaf tea .", "entity": [], "task": "NER"}
{"text": "Guava leaf tea ( GLT ) contains guava leaf polyphenol ( Gvpp ) , which regulates the absorption of dietary carbohydrate from the intestines .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [43, 53]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [107, 119]}], "task": "NER"}
{"text": "Borderline diabetics , who are at high risk of development of diabetes , take GLT to suppress a rapid increase of blood sugar level after meals .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [120, 125]}], "task": "NER"}
{"text": "However , patients with diabetes in whom diabetic drugs or warfarin as a blood thinner are prescribed also take GLT with the expectation of glycemic control .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "Therefore , we studied whether GLT had potential for inhibition or induction of cytochrome P450 ( CYP ) and an influence on the action of warfarin .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [138, 146]}], "task": "NER"}
{"text": "Extract of guava leaf ( GvEx ) consists of carbohydrate and polyphenols , which are Gvpp , quercetin , and ellagic acid .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [43, 55]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [60, 71]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "ellagic acid", "entity_type": "Chemical", "pos": [107, 119]}], "task": "NER"}
{"text": "These polyphenols , but not GvEx , showed a certain level of inhibition of human - cDNA - expressed CYPs .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [6, 17]}], "task": "NER"}
{"text": "In a comparison of GLT and grapefruit juice , GLT showed weaker inhibition of CYP activities and of midazolam 1 ' - hydroxylation than grapefruit juice .", "entity": [{"entity": "midazolam", "entity_type": "Chemical", "pos": [100, 109]}], "task": "NER"}
{"text": "Furthermore , neither liver weight nor CYP3A expression in the liver was changed in rats that received GvEx for 90 days compared with the control group .", "entity": [], "task": "NER"}
{"text": "When rats were concomitantly treated with GLT and warfarin , the prolongation of clotting time of blood by warfarin was not influenced .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [107, 115]}], "task": "NER"}
{"text": "These data suggest that GLT is unlikely to interact with drugs .", "entity": [], "task": "NER"}
{"text": "A new phenylethanoid glucoside from Plantago depressa Willd .", "entity": [{"entity": "phenylethanoid glucoside", "entity_type": "Chemical", "pos": [6, 30]}], "task": "NER"}
{"text": "Chemical research of Plantago depressa Willd . led to one new phenylethanoid glucoside with alpha - L - rhamnosyl ( 1 --> 2 ) - beta - D - glucose structure , together with four known compounds .", "entity": [{"entity": "phenylethanoid glucoside", "entity_type": "Chemical", "pos": [62, 86]}, {"entity": "alpha - L - rhamnosyl ( 1 --> 2 ) - beta - D - glucose", "entity_type": "Chemical", "pos": [92, 146]}], "task": "NER"}
{"text": "These five compounds ( 1 - 5 ) were isolated from the family Plantaginaceae for the first time ; the chemotaxonomic significance of cerebrosides was also discussed .", "entity": [{"entity": "cerebrosides", "entity_type": "Chemical", "pos": [132, 144]}], "task": "NER"}
{"text": "Chemical composition of essential oil from Calligonum polygonoides Linn .", "entity": [], "task": "NER"}
{"text": "The essential oil from air dried buds and roots of Calligonum polygonoides Linn . , has been extracted from dry steam distillation and analysed for chemical composition by gas chromatography - mass spectrometry .", "entity": [], "task": "NER"}
{"text": "In total , 27 and 10 compounds were analysed qualitatively and quantitatively , accounting for 68 . 42 % and 82 . 12 % total contents of the essential oils of buds and roots , respectively .", "entity": [], "task": "NER"}
{"text": "It contains a complex mixture of terpenoids , hydrocarbons , phenolic compounds , acid derivatives and ketones .", "entity": [{"entity": "terpenoids", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "hydrocarbons", "entity_type": "Chemical", "pos": [46, 58]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "ketones", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "The main component of essential oil was ethyl homovanillate ( 11 . 79 % ) in buds and drimenol ( 29 . 42 % ) in roots .", "entity": [{"entity": "ethyl homovanillate", "entity_type": "Chemical", "pos": [40, 59]}, {"entity": "drimenol", "entity_type": "Chemical", "pos": [86, 94]}], "task": "NER"}
{"text": "The effects of temperature and salinity on 17 - alpha - ethynylestradiol uptake and its relationship to oxygen consumption in the model euryhaline teleost ( Fundulus heteroclitus ) .", "entity": [{"entity": "17 - alpha - ethynylestradiol", "entity_type": "Chemical", "pos": [43, 72]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [104, 110]}], "task": "NER"}
{"text": "The synthetic estrogen 17 - alpha - ethynylestradiol ( EE2 ) , a component of birth control and hormone replacement therapy , is discharged into the environment via wastewater treatment plant ( WWTP ) effluents .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "17 - alpha - ethynylestradiol", "entity_type": "Chemical", "pos": [23, 52]}, {"entity": "EE2", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "The present study employed radiolabeled EE2 to examine impacts of temperature and salinity on EE2 uptake in male killifish ( Fundulus heteroclitus ) .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "EE2", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "Fish were exposed to a nominal concentration of 100ng / L EE2 for 2h .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "The rate of EE2 uptake was constant over the 2h period .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "Oxygen consumption rates ( MO ( 2 ) ) , whole body uptake rates , and tissue - specific EE2 distribution were determined .", "entity": [{"entity": "Oxygen", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "EE2", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "In killifish acclimated to 18 degrees C at 16ppt ( 50 % sea water ) , MO ( 2 ) and EE2 uptake were both lower after 24h exposure to 10 degrees C and 4 degrees C , and increased after 24h exposure to 26 degrees C .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Transfer to fresh water ( FW ) for 24h lowered EE2 uptake rate , and long - term acclimation to fresh water reduced it by 70 % .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [47, 50]}], "task": "NER"}
{"text": "Both long - term acclimation to 100 % sea water ( 32ppt ) and a 24h transfer to 100 % sea water also reduced EE2 uptake rate by 50 % relative to 16ppt .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [109, 112]}], "task": "NER"}
{"text": "Tissue - specific accumulation of EE2 was highest ( 40 - 60 % of the total ) in the liver plus gall bladder across all exposures , and the vast majority of this was in the bile at 2h , regardless of temperature or salinity .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "The carcass was the next highest accumulator ( 30 - 40 % ) , followed by the gut ( 10 - 20 % ) with only small amounts in gill and spleen .", "entity": [], "task": "NER"}
{"text": "Killifish chronically exposed ( 15 days ) to 100ng / L EE2 displayed no difference in EE2 uptake rate or tissue - specific distribution .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "EE2", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "Drinking rate , measured with radiolabeled polyethylene glycol - 4000 , was about 25 times greater in 16ppt - acclimated killifish relative to FW - acclimated animals .", "entity": [{"entity": "polyethylene glycol - 4000", "entity_type": "Chemical", "pos": [43, 69]}], "task": "NER"}
{"text": "However , drinking accounted for less than 30 % of gut accumulation , and therefore a negligible percentage of whole body EE2 uptake rates .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "In general , there were strong positive relationships between EE2 uptake rates and MO ( 2 ) , suggesting similar uptake pathways of these lipophilic molecules across the gills .", "entity": [{"entity": "EE2", "entity_type": "Chemical", "pos": [62, 65]}], "task": "NER"}
{"text": "These data will be useful in developing a predictive model of how key environmental parameter variations ( salinity , temperature , dissolved oxygen ) affect EE2 uptake in estuarine fish , to determine optimal timing and location of WWTP discharges .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [142, 148]}, {"entity": "EE2", "entity_type": "Chemical", "pos": [158, 161]}], "task": "NER"}
{"text": "One new antitumour cassane - type diterpene from Caesalpinia crista .", "entity": [{"entity": "cassane", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "diterpene", "entity_type": "Chemical", "pos": [34, 43]}], "task": "NER"}
{"text": "1 alpha - acetoxy - 5 alpha , 7 beta - dihydroxycassa - 11 , 13 ( 15 ) - diene - 16 , 12 - lactone , a new cassane - type diterpene was isolated from Caesalpinia crista .", "entity": [{"entity": "1 alpha - acetoxy - 5 alpha , 7 beta - dihydroxycassa - 11 , 13 ( 15 ) - diene - 16 , 12 - lactone", "entity_type": "Chemical", "pos": [0, 98]}, {"entity": "cassane", "entity_type": "Chemical", "pos": [107, 114]}, {"entity": "diterpene", "entity_type": "Chemical", "pos": [122, 131]}], "task": "NER"}
{"text": "The structure of this compound was elucidated by analysis of NMR spectra , and the relative configuration was established by NOE experiment .", "entity": [], "task": "NER"}
{"text": "The new compound was evaluated for antitumour activity against T47D , DU145 and showed significant inhibitory activities .", "entity": [], "task": "NER"}
{"text": "MUC1 - C oncoprotein as a target in breast cancer : activation of signaling pathways and therapeutic approaches .", "entity": [], "task": "NER"}
{"text": "Mucin 1 ( MUC1 ) is a heterodimeric protein formed by two subunits that is aberrantly overexpressed in human breast cancer and other cancers .", "entity": [], "task": "NER"}
{"text": "Historically , much of the early work on MUC1 focused on the shed mucin subunit .", "entity": [], "task": "NER"}
{"text": "However , more recent studies have been directed at the transmembrane MUC1 - C - terminal subunit ( MUC1 - C ) that functions as an oncoprotein .", "entity": [], "task": "NER"}
{"text": "MUC1 - C interacts with EGFR ( epidermal growth factor receptor ) , ErbB2 and other receptor tyrosine kinases at the cell membrane and contributes to activation of the PI3K <E232> AKT and mitogen - activated protein kinase kinase ( MEK ) <E232> extracellular signal - regulated kinase ( ERK ) pathways .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "MUC1 - C also localizes to the nucleus where it activates the Wnt / beta - catenin , signal transducer and activator of transcription ( STAT ) and NF ( nuclear factor ) - kappa B RelA pathways .", "entity": [], "task": "NER"}
{"text": "These findings and the demonstration that MUC1 - C is a druggable target have provided the experimental basis for designing agents that block MUC1 - C function .", "entity": [], "task": "NER"}
{"text": "Notably , inhibitors of the MUC1 - C subunit have been developed that directly block its oncogenic function and induce death of breast cancer cells in vitro and in xenograft models .", "entity": [], "task": "NER"}
{"text": "On the basis of these findings , a first - in - class MUC1 - C inhibitor has entered phase I evaluation as a potential agent for the treatment of patients with breast cancers who express this oncoprotein .", "entity": [], "task": "NER"}
{"text": "beta - Eudesmol induces JNK - dependent apoptosis through the mitochondrial pathway in HL60 cells .", "entity": [{"entity": "beta - Eudesmol", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "beta - eudesmol , a natural sesquiterpenol present in a variety of Chinese herbs , is known to inhibit the proliferation of human tumor cells .", "entity": [{"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "sesquiterpenol", "entity_type": "Chemical", "pos": [28, 42]}], "task": "NER"}
{"text": "However , the molecular mechanisms of the effect of beta - eudesmol on human tumor cells are unknown .", "entity": [{"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [52, 67]}], "task": "NER"}
{"text": "In the present study , we report the cytotoxic effect of beta - eudesmol on the human leukemia HL60 cells and its molecular mechanisms .", "entity": [{"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [57, 72]}], "task": "NER"}
{"text": "The cytotoxic effect of beta - eudesmol on HL60 cells was associated with apoptosis , which was characterized by the presence of DNA fragmentation .", "entity": [{"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [24, 39]}], "task": "NER"}
{"text": "beta - eudesmol - induced apoptosis was accompanied by cleavage of caspase - 3 , caspase - 9 , and poly ( ADP - ribose ) polymerase ; downregulation of Bcl - 2 expression ; release of cytochrome c from mitochondria ; and decrease in mitochondrial membrane potential ( MMP ) .", "entity": [{"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [99, 120]}], "task": "NER"}
{"text": "Activation of c - Jun N - terminal kinases ( JNK ) mitogen - activated protein kinases was observed in beta - eudesmol - treated HL60 cells , and the inhibitor of JNK blocked the beta - eudesmol - induced apoptosis , downregulation of Bcl - 2 , and the loss of MMP .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [22, 23]}, {"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [103, 118]}, {"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [179, 194]}], "task": "NER"}
{"text": "These data suggest that beta - eudesmol induces apoptosis in HL60 cells via the mitochondrial apoptotic pathway , which is controlled through JNK signaling .", "entity": [{"entity": "beta - eudesmol", "entity_type": "Chemical", "pos": [24, 39]}], "task": "NER"}
{"text": "Copyright (c) 2012 John Wiley & Sons , Ltd .", "entity": [], "task": "NER"}
{"text": "A new triterpenoid saponin from Glinus oppositifolius with alpha - glucosidase inhibitory activity .", "entity": [{"entity": "triterpenoid saponin", "entity_type": "Chemical", "pos": [6, 26]}], "task": "NER"}
{"text": "Evaluation of alpha - glucosidase inhibitory activity led to the isolation of six triterpene saponins from the aerial parts of Glinus oppositifolius including one new and five known constituents .", "entity": [{"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [82, 101]}], "task": "NER"}
{"text": "The structure of the new saponin , glinoside C ( 1 ) , was established as 16 - O - ( beta - D - glucopyranosyl ) - 3 beta , 12 beta , 16 beta , 21 alpha , 22 - pentahydroxy hopane by extensive use of 1 - D , 2 - D NMR and mass spectral techniques .", "entity": [{"entity": "saponin", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "glinoside C", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "16 - O - ( beta - D - glucopyranosyl ) - 3 beta , 12 beta , 16 beta , 21 alpha , 22 - pentahydroxy hopane", "entity_type": "Chemical", "pos": [74, 179]}], "task": "NER"}
{"text": "The other constituents identified were 3 - O - ( beta - D - xylopyranosyl ) - spergulagenin A ( 2 ) , spergulacin ( 3 ) , spergulin A ( 4 ) , spergulacin A ( 5 ) and spergulin B ( 6 ) .", "entity": [{"entity": "3 - O - ( beta - D - xylopyranosyl ) - spergulagenin A", "entity_type": "Chemical", "pos": [39, 93]}, {"entity": "spergulacin", "entity_type": "Chemical", "pos": [102, 113]}, {"entity": "spergulin A", "entity_type": "Chemical", "pos": [122, 133]}, {"entity": "spergulacin A", "entity_type": "Chemical", "pos": [142, 155]}, {"entity": "spergulin B", "entity_type": "Chemical", "pos": [166, 177]}], "task": "NER"}
{"text": "Compound 1 exhibited the greatest inhibition of the enzyme with IC50 of 127 +/- 30 micro M .", "entity": [], "task": "NER"}
{"text": "Kinetics study for the compound 1 demonstrated mixed type of inhibition ( Ki = 157 . 9 micro M ) .", "entity": [], "task": "NER"}
{"text": "Optimization of PLGA nanoparticles formulation containing L - DOPA by applying the central composite design .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [16, 20]}, {"entity": "L - DOPA", "entity_type": "Chemical", "pos": [58, 66]}], "task": "NER"}
{"text": "The aim of this work was to prepare L - DOPA loaded poly ( D , L - lactide - co - glycolide ) ( PLGA ) nanoparticles by a modified water - in - oil - in - water ( W ( 1 ) / O / W ( 2 ) ) emulsification solvent evaporation method .", "entity": [{"entity": "L - DOPA", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "poly ( D , L - lactide - co - glycolide )", "entity_type": "Chemical", "pos": [52, 93]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [96, 100]}], "task": "NER"}
{"text": "A central composite design was applied for optimization of the formulation parameters and for studying the effects of three independent variables : PLGA concentration , polyvinyl alcohol ( PVA ) concentration and organic solvent removal rate on the particle size and the entrapment efficiency ( response variables ) .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [148, 152]}, {"entity": "polyvinyl alcohol", "entity_type": "Chemical", "pos": [169, 186]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [189, 192]}], "task": "NER"}
{"text": "Second - order models were obtained to adequately describe the influence of the independent variables on the selected responses .", "entity": [], "task": "NER"}
{"text": "The analysis of variance showed that the three independent variables had significant effects ( p < 0 . 05 ) on the responses .", "entity": [], "task": "NER"}
{"text": "The experimental results were in perfect accordance with the predictions estimated by the models .", "entity": [], "task": "NER"}
{"text": "Using the desirability approach and overlay contour plots , the optimal preparation area can be highlighted .", "entity": [], "task": "NER"}
{"text": "It was found that the optimum values of the responses could be obtained at higher concentration of PLGA ( 5 % , w / v ) and PVA ( 6 % , w / v ) ; and faster organic solvent removal rate ( 700 rpm ) .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [99, 103]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "The corresponding particle size was 256 . 2 nm and the entrapment efficiency was 62 . 19 % .", "entity": [], "task": "NER"}
{"text": "FTIR investigation confirmed that the L - DOPA and PLGA polymer maintained its backbone structure in the fabrication of nanoparticles .", "entity": [{"entity": "L - DOPA", "entity_type": "Chemical", "pos": [38, 46]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "The scanning electron microscopic images of nanoparticles showed that all particles had spherical shape with porous outer skin .", "entity": [], "task": "NER"}
{"text": "The results suggested that PLGA nanoparticles might represent a promising formulation for brain delivery of L - DOPA .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "L - DOPA", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "The preparation of L - DOPA loaded PLGA nanoparticles can be optimized by the central composite design .", "entity": [{"entity": "L - DOPA", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [35, 39]}], "task": "NER"}
{"text": "Impact of early - life stress , on group III mGlu receptor levels in the rat hippocampus : effects of ketamine , electroconvulsive shock therapy and fluoxetine treatment .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "fluoxetine", "entity_type": "Chemical", "pos": [149, 159]}], "task": "NER"}
{"text": "The glutamatergic system is increasingly being viewed as a promising target for the development of novel treatments for depression .", "entity": [], "task": "NER"}
{"text": "The group III metabotropic glutamate ( mGlu ) receptors ( mGlu ( 4 , 7 ) and ( 8 ) receptors ) in particular are beginning to show promise in this respect .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "It remains unclear how antidepressant medications modulate mGlu receptors .", "entity": [], "task": "NER"}
{"text": "In this study we investigated the effects of three antidepressant treatments ( fluoxetine , ketamine and electroconvulsive shock therapy ( ECT ) ) .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "Ketamine is an NMDA receptor antagonist which possess a rapid antidepressant therapeutic profile and moreover is effective in cases of treatment - resistant depression .", "entity": [{"entity": "Ketamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [15, 19]}], "task": "NER"}
{"text": "Furthermore , ECT is also a therapeutic strategy possessing increased efficacy compared to conventional monoamine based therapies .", "entity": [{"entity": "monoamine", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "The effect these two highly efficacious treatments have on hippocampal group III mGlu receptors remains completely unexplored .", "entity": [], "task": "NER"}
{"text": "To redress this deficit we investigated the effects these treatments and the prototypical selective serotonin reuptake inhibitor ( SSRI ) fluoxetine would have on hippocampal group III mGlu receptor mRNA levels in na i ve Sprague - Dawley rats and rats which had undergone early - life stress in the form of the maternal separation ( MS ) procedure .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [100, 109]}, {"entity": "fluoxetine", "entity_type": "Chemical", "pos": [138, 148]}], "task": "NER"}
{"text": "We found MS significantly reduced mGlu ( 4 ) receptor expression and fluoxetine reversed this MS induced change .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "ECT and ketamine treatment significantly reduced mGlu ( 4 ) receptor expression in non - separated ( NS ) animals while having no effect in MS animals .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [8, 16]}], "task": "NER"}
{"text": "Fluoxetine and ECT significantly increased mGlu ( 7 ) receptor expression in NS animals .", "entity": [{"entity": "Fluoxetine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "This work demonstrates changes to mGlu ( 4 ) receptor expression may be a lasting molecular change which occurs due to early - life stress .", "entity": [], "task": "NER"}
{"text": "Taken together our data shows there are selective changes to group III mGlu receptors under basal and early - life stress conditions .", "entity": [], "task": "NER"}
{"text": "In vitro biomonitoring of the genotoxic and oxidative potentials of two commonly eaten insects in southwestern Nigeria .", "entity": [], "task": "NER"}
{"text": "In this study , the cytogenetic and oxidative effects of water soluble extracts of two commonly eaten insects , Zonocerus variegatus ( Orthoptera : Pyrgomorphidae ) and Oryctes boas ( Solanales : Solanaceae ) , in southwestern Nigeria were evaluated on cultured human blood cells .", "entity": [], "task": "NER"}
{"text": "The extracts were added to the cultures at various concentrations ( 0 - 2000 ppm ) .", "entity": [], "task": "NER"}
{"text": "The chromosome aberration and micronucleus tests were used to find out the DNA and chromosomal damage potentials in vitro by aqueous insect extracts .", "entity": [], "task": "NER"}
{"text": "To assess the oxidative effects of these insect extracts , total antioxidant capacity ( TAC ) and total oxidant status ( TOS ) levels were also measured .", "entity": [], "task": "NER"}
{"text": "Our results indicated that these extracts did not show genotoxic effects at the tested concentrations .", "entity": [], "task": "NER"}
{"text": "However , the extracts caused dose - dependent alterations in both TAC and TOS levels .", "entity": [], "task": "NER"}
{"text": "Based on the findings , it was concluded that the studied insects can be consumed safely , but it is necessary to consider the cellular damages that are likely to appear depending on the oxidative stress .", "entity": [], "task": "NER"}
{"text": "We also suggest that this in vitro approach for oxidative and genotoxicity assessments may be useful to compare the potential health risks of edible insects .", "entity": [], "task": "NER"}
{"text": "The role of diallyl sulfides and dipropyl sulfides in the in vitro antimicrobial activity of the essential oil of garlic , Allium sativum L . , and Leek , Allium porrum L .", "entity": [{"entity": "diallyl sulfides", "entity_type": "Chemical", "pos": [12, 28]}, {"entity": "dipropyl sulfides", "entity_type": "Chemical", "pos": [33, 50]}], "task": "NER"}
{"text": "The in vitro antibacterial activity of essential oils ( EOs ) obtained from fresh bulbs of garlic , Allium sativum L . , and leek , Allium porrum L .", "entity": [], "task": "NER"}
{"text": "( Alliaceae ) , was studied .", "entity": [], "task": "NER"}
{"text": "A . sativum ( garlic ) EO showed a good antimicrobial activity against Staphylococcus aureus ( inhibition zone 14 . 8 mm ) , Pseudomonas aeruginosa ( inhibition zone 21 . 1 mm ) , and Escherichia coli ( inhibition zone 11 . 0 mm ) , whereas the EO of A . porrum ( leek ) had no antimicrobial activity .", "entity": [], "task": "NER"}
{"text": "The main constituents of the garlic EO were diallyl monosulfide , diallyl disulfide ( DADS ) , diallyl trisulfide , and diallyl tetrasulfide .", "entity": [{"entity": "diallyl monosulfide", "entity_type": "Chemical", "pos": [44, 63]}, {"entity": "diallyl disulfide", "entity_type": "Chemical", "pos": [66, 83]}, {"entity": "DADS", "entity_type": "Chemical", "pos": [86, 90]}, {"entity": "diallyl trisulfide", "entity_type": "Chemical", "pos": [95, 113]}, {"entity": "diallyl tetrasulfide", "entity_type": "Chemical", "pos": [120, 140]}], "task": "NER"}
{"text": "The EO of A . porrum was characterized by the presence of dipropyl disulfide ( DPDS ) , dipropyl trisulfide , and dipropyl tetrasulfide .", "entity": [{"entity": "dipropyl disulfide", "entity_type": "Chemical", "pos": [58, 76]}, {"entity": "DPDS", "entity_type": "Chemical", "pos": [79, 83]}, {"entity": "dipropyl trisulfide", "entity_type": "Chemical", "pos": [88, 107]}, {"entity": "dipropyl tetrasulfide", "entity_type": "Chemical", "pos": [114, 135]}], "task": "NER"}
{"text": "The antimicrobial activities of the DADS and DPDS were also studied .", "entity": [{"entity": "DADS", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "DPDS", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "The results obtained suggest that the presence of the allyl group is fundamental for the antimicrobial activity of these sulfide derivatives when they are present in Allium or in other species ( DADS inhibition zone on S . aureus 15 . 9 mm , P . aeruginosa 21 . 9 mm , E . coli 11 . 4 mm ) .", "entity": [{"entity": "allyl", "entity_type": "Chemical", "pos": [54, 59]}, {"entity": "sulfide", "entity_type": "Chemical", "pos": [121, 128]}, {"entity": "DADS", "entity_type": "Chemical", "pos": [195, 199]}], "task": "NER"}
{"text": "MicroRNA - 7 functions as an anti - metastatic microRNA in gastric cancer by targeting insulin - like growth factor - 1 receptor .", "entity": [], "task": "NER"}
{"text": "Metastasis is a major clinical obstacle in the treatment of gastric cancer ( GC ) and it accounts for the majority of cancer - related mortality .", "entity": [], "task": "NER"}
{"text": "MicroRNAs have recently emerged as regulators of metastasis by acting on multiple signaling pathways .", "entity": [], "task": "NER"}
{"text": "In this study , we found that miR - 7 is significantly downregulated in highly metastatic GC cell lines and metastatic tissues .", "entity": [], "task": "NER"}
{"text": "Both gain - of - function and loss - of - function experiments showed that increased miR - 7 expression significantly reduced GC cell migration and invasion , whereas decreased miR - 7 expression dramatically enhanced cell migration and invasion .", "entity": [], "task": "NER"}
{"text": "In vivo metastasis assays also demonstrated that overexpression of miR - 7 markedly inhibited GC metastasis .", "entity": [], "task": "NER"}
{"text": "Moreover , the insulin - like growth factor - 1 receptor ( IGF1R ) oncogene , which is often mutated or amplified in human cancers and functions as an important regulator of cell growth and tumor invasion , was identified as a direct target of miR - 7 .", "entity": [], "task": "NER"}
{"text": "Silencing of IGF1R using small interefering RNA ( siRNA ) recapitulated the anti - metastatic function of miR - 7 , whereas restoring the IGF1R expression attenuated the function of miR - 7 in GC cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , we found that suppression of Snail by miR - 7 , through targeting IGF1R , increased E - cadherin expression and partially reversed the epithelial - mesenchymal transition ( EMT ) .", "entity": [], "task": "NER"}
{"text": "Finally , analyses of miR - 7 and IGF1R levels in human primary GC with matched lymph node metastasis tissue arrays revealed that miR - 7 is inversely correlated with IGF1R expression .", "entity": [], "task": "NER"}
{"text": "The present study provides insight into the specific biological behavior of miR - 7 in EMT and tumor metastasis .", "entity": [], "task": "NER"}
{"text": "Targeting this novel miR - 7 / IGF1R / Snail axis would be helpful as a therapeutic approach to block GC metastasis .", "entity": [], "task": "NER"}
{"text": "Flavonoids and saponins from Zizyphus incurva .", "entity": [{"entity": "Flavonoids", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "A new flavonol triglycoside , myricetin - 3 - O - [ beta - xylopyranosyl - ( 1 - 2 ) - alpha - rhamnopyranoside ] - 4 ' - O - alpha - rhamnopyranoside , named as bayarin ( 1 ) , was isolated from the aerial parts of Zizyphus incurva Roxb .", "entity": [{"entity": "flavonol triglycoside", "entity_type": "Chemical", "pos": [6, 27]}, {"entity": "myricetin - 3 - O - [ beta - xylopyranosyl - ( 1 - 2 ) - alpha - rhamnopyranoside ] - 4 ' - O - alpha - rhamnopyranoside", "entity_type": "Chemical", "pos": [30, 150]}, {"entity": "bayarin", "entity_type": "Chemical", "pos": [162, 169]}], "task": "NER"}
{"text": "( Rhamnaceae ) along with eight known compounds : six flavonoids and two saponins .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [54, 64]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "All of these compounds were isolated for the first time from this plant .", "entity": [], "task": "NER"}
{"text": "Structures of these compounds were elucidated on the basis of spectroscopic data .", "entity": [], "task": "NER"}
{"text": "Rapid characterisation of flavonoids from Sophora alopecuroides L . by HPLC / DAD / ESI - MSn .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [26, 36]}], "task": "NER"}
{"text": "An HPLC / DAD / ESI - MSn method was established to characterise flavonoids in the seeds of Sophora alopecuroides L .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [65, 75]}], "task": "NER"}
{"text": "All the flavonoids exhibited abundant [ M - H ] - ions , which triggered data - dependent multistage mass spectrometry fragmentations .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [8, 18]}, {"entity": "H", "entity_type": "Chemical", "pos": [44, 45]}], "task": "NER"}
{"text": "Characteristic UV spectra were used to confirm flavonoid subtypes .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "In total , 22 flavonoids and two phenolic compounds were detected and identified .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "Five of them were identified by comparing with reference standards , and the others were characterised based on the retention behaviour , multistage fragmentation feature and UV absorption .", "entity": [], "task": "NER"}
{"text": "A total of 19 compounds were reported from S . alopecuroides for the first time .", "entity": [], "task": "NER"}
{"text": "This method accomplished rapid profiling of flavonoid constituents in S . alopecuroides L .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "cAMP regulation of airway smooth muscle function .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Agonists activating beta ( 2 ) - adrenoceptors ( beta ( 2 ) ARs ) on airway smooth muscle ( ASM ) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease ( COPD ) .", "entity": [], "task": "NER"}
{"text": "Moreover , the use of long - acting beta - agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases .", "entity": [{"entity": "corticosteroids", "entity_type": "Chemical", "pos": [74, 89]}], "task": "NER"}
{"text": "beta - Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction .", "entity": [], "task": "NER"}
{"text": "The presumed cellular mechanism of action involves the generation of intracellular cAMP , which in turn can activate the effector molecules cAMP - dependent protein kinase ( PKA ) and Epac .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "Other agents such as prostaglandin E ( 2 ) and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM , can also antagonize ASM contraction , and inhibit other ASM functions including proliferation and migration .", "entity": [{"entity": "prostaglandin E ( 2 )", "entity_type": "Chemical", "pos": [21, 42]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [109, 113]}], "task": "NER"}
{"text": "Therefore , beta ( 2 ) ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "However , limitations of beta - agonist therapy due to drug tachyphylaxis related to beta ( 2 ) AR desensitization , and recent findings regarding the manner in which beta ( 2 ) ARs and cAMP signal , have raised new and interesting questions about these well - studied molecules .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [186, 190]}], "task": "NER"}
{"text": "In this review we discuss current concepts regarding beta ( 2 ) ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [72, 76]}], "task": "NER"}
{"text": "Anxiolytic - but not antidepressant - like activity of Lu AF21934 , a novel , selective positive allosteric modulator of the mGlu 4 receptor .", "entity": [{"entity": "Lu AF21934", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "Previous studies demonstrated that the Group III mGlu receptor - selective orthosteric agonist , LSP1 - 2111 produced anxiolytic - but not antidepressant - like effects upon peripheral administration .", "entity": [{"entity": "LSP1 - 2111", "entity_type": "Chemical", "pos": [97, 108]}], "task": "NER"}
{"text": "Herein , we report the pharmacological actions of Lu AF21934 , a novel , selective , and brain - penetrant positive allosteric modulator ( PAM ) of the mGlu ( 4 ) receptor in the stress - induced hyperthermia ( SIH ) , four - plate , marble - burying and Vogel ' s conflict tests .", "entity": [{"entity": "Lu AF21934", "entity_type": "Chemical", "pos": [50, 60]}], "task": "NER"}
{"text": "In all models , except Vogel ' s conflict test , a dose - dependent anxiolytic - like effect was seen .", "entity": [], "task": "NER"}
{"text": "The anti - hyperthermic effect of Lu AF21934 ( 5 mg / kg ) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil ( 10 mg / kg ) and was not serotonin - dependent , as it persisted in serotonin - deficient mice and upon blockade of either 5 - HT ( 1A ) receptors by WAY100635 , or 5 - HT ( 2A / 2C ) receptors by ritanserin .", "entity": [{"entity": "Lu AF21934", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "benzodiazepine", "entity_type": "Chemical", "pos": [96, 110]}, {"entity": "flumazenil", "entity_type": "Chemical", "pos": [131, 141]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [169, 178]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [212, 221]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [267, 273]}, {"entity": "WAY100635", "entity_type": "Chemical", "pos": [294, 303]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [309, 315]}, {"entity": "ritanserin", "entity_type": "Chemical", "pos": [341, 351]}], "task": "NER"}
{"text": "These results suggest that the GABAergic system , but not the serotonergic system , is involved in the mechanism of the anxiolytic - like phenotype of Lu AF21934 in rodents .", "entity": [{"entity": "Lu AF21934", "entity_type": "Chemical", "pos": [151, 161]}], "task": "NER"}
{"text": "Lu AF21934 did not produce antidepressant - like effects in the tail suspension test ( TST ) in mice ; however , it decreased the basal locomotor activity of mice that were not habituated to activity cages .", "entity": [{"entity": "Lu AF21934", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Intraspecific variability of the essential oil of Calamintha nepeta subsp . nepeta from Southern Italy ( Apulia ) .", "entity": [], "task": "NER"}
{"text": "The essential oil of 46 spontaneous plants of Calamintha nepeta ( L . ) Savi subsp . nepeta growing wild in Sud , Italy ( Salento , Apulia ) , were investigated by GC / MS .", "entity": [], "task": "NER"}
{"text": "Fifty - seven components were identified in the oil representing over the 98 % of the total oil composition .", "entity": [], "task": "NER"}
{"text": "Four chemotypes were identified : piperitone oxide , piperitenone oxide , piperitone - menthone and pulegone .", "entity": [{"entity": "piperitone oxide", "entity_type": "Chemical", "pos": [34, 50]}, {"entity": "piperitenone oxide", "entity_type": "Chemical", "pos": [53, 71]}, {"entity": "piperitone", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "menthone", "entity_type": "Chemical", "pos": [87, 95]}, {"entity": "pulegone", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "Screening of venezuelan medicinal plant extracts for cytostatic and cytotoxic activity against tumor cell lines .", "entity": [], "task": "NER"}
{"text": "There are estimated to be more than 20 , 000 species of plants in Venezuela , of which more than 1500 are used for medicinal purposes by indigenous and local communities .", "entity": [], "task": "NER"}
{"text": "Only a relatively small proportion of these have been evaluated in terms of their potential as antitumor agents .", "entity": [], "task": "NER"}
{"text": "In this study , we screened 308 extracts from 102 species for cytostatic and cytotoxic activity against a panel of six tumor cell lines using a 24 - h sulphorhodamine B assay .", "entity": [{"entity": "sulphorhodamine B", "entity_type": "Chemical", "pos": [151, 168]}], "task": "NER"}
{"text": "Extracts from Clavija lancifolia , Hamelia patens , Piper san - vicentense , Physalis cordata , Jacaranda copaia , Heliotropium indicum , and Annona squamosa were the most cytotoxic , whereas other extracts from Calotropis gigantea , Hyptis dilatata , Chromolaena odorata , Siparuna guianensis , Jacaranda obtusifolia , Tapirira guianensis , Xylopia aromatica , Protium heptaphyllum , and Piper arboreum showed the greatest cytostatic activity .", "entity": [], "task": "NER"}
{"text": "These results confirm previous reports on the cytotoxic activities of the abovementioned plants as well as prompting further studies on others such as C . lancifolia and H . dilatata that have not been so extensively studied .", "entity": [], "task": "NER"}
{"text": "The interaction between mGluR1 and the calcium channel Cav 2 . 1 preserves coupling in the presence of long Homer proteins .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "Group I metabotropic glutamate receptors ( mGluR1 and 5 ) are G protein coupled receptors that regulate neuronal activity in a number of ways .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Some of the most well studied functions of group I mGluRs , such as initiation of multiple forms of mGluR - dependent long - term depression , require receptor localization near the post - synaptic density ( PSD ) .", "entity": [], "task": "NER"}
{"text": "This localization is in turn dependent on the Homer family of scaffolding proteins which bind to a small motif on the distal C - termini of mGluR1 and 5 , localize the receptors near the PSD , strengthen coupling to post - synaptic effectors and simultaneously uncouple the mGluRs from extra - synaptic effectors such as voltage dependent ion channels .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [125, 126]}], "task": "NER"}
{"text": "Here the selectivity of this uncoupling process was examined by testing the ability of Homer - 2b to uncouple mGluR1 from multiple voltage dependent calcium channels including Ca ( V2 . 2 ) ( N - type ) , Ca ( V3 . 2 ) ( T - type ) , and Ca ( V2 . 1 ) ( P / Q - type ) expressed in rat sympathetic neurons from the superior cervical ganglion ( SCG ) .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [149, 156]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [176, 178]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [205, 207]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [238, 240]}], "task": "NER"}
{"text": "Of these , only the mGluR1 - Ca ( V2 . 1 ) modulatory pathway was insensitive to Homer - 2b expression .", "entity": [], "task": "NER"}
{"text": "Uncoupling from this channel was achieved by co - expression of an mGluR1 C - terminal protein designed to disrupt a previously described direct interaction between these two proteins , suggesting that this interaction allows incorporation of Ca ( V2 . 1 ) into the mGluR1 / Homer signaling complex , thereby preserving modulation in the presence of scaffolding Homer proteins .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [74, 75]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [243, 245]}], "task": "NER"}
{"text": "Pharmacological profiling of native group II metabotropic glutamate receptors in primary cortical neuronal cultures using a FLIPR .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "The group II metabotropic glutamate ( mGlu ) receptors comprised of the mGlu2 and mGlu3 receptor subtypes have gained recognition in recent years as potential targets for psychiatric disorders , including anxiety and schizophrenia .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [26, 35]}], "task": "NER"}
{"text": "In addition to studies already indicating which subtype mediates the anxiolytic and anti - psychotic effects observed in disease models , studies to help further define the preferred properties of selective group II mGlu receptor ligands will be essential .", "entity": [], "task": "NER"}
{"text": "Comparison of the in vitro properties of these ligands to their in vivo efficacy and tolerance profiles may help provide these additional insights .", "entity": [], "task": "NER"}
{"text": "We have developed a relatively high - throughput native group II mGlu receptor functional assay to aid this characterisation .", "entity": [], "task": "NER"}
{"text": "We have utilised dissociated primary cortical neuronal cultures , which after 7 days in vitro have formed functional synaptic connections and display periodic and spontaneous synchronised calcium ( Ca ( 2 + ) ) oscillations in response to intrinsic action potential bursts .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [188, 195]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [198, 208]}], "task": "NER"}
{"text": "We herein demonstrate that in addition to non - selective group II mGlu receptor agonists , ( 2R , 4R ) - APDC , LY379268 and DCG - IV , a selective mGlu2 agonist , LY541850 , and mGlu2 positive allosteric modulators , BINA and CBiPES , inhibit the frequency of synchronised Ca ( 2 + ) oscillations in primary cultures of rat and mouse cortical neurons .", "entity": [{"entity": "( 2R , 4R ) - APDC", "entity_type": "Chemical", "pos": [92, 110]}, {"entity": "LY379268", "entity_type": "Chemical", "pos": [113, 121]}, {"entity": "DCG - IV", "entity_type": "Chemical", "pos": [126, 134]}, {"entity": "LY541850", "entity_type": "Chemical", "pos": [165, 173]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [275, 285]}], "task": "NER"}
{"text": "Use of cultures from wild - type , mGlu2 ( - / - ) , mGlu3 ( - / - ) and mGlu2 / 3 ( - / - ) mice allowed us to further probe the contribution of mGlu2 and mGlu3 , and revealed LY541850 to be a partial mGlu2 agonist and a full mGlu3 antagonist .", "entity": [{"entity": "LY541850", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "Overnight pre - treatment of cultures with these ligands revealed a preferred desensitisation profile after treatment with a positive allosteric modulator .", "entity": [], "task": "NER"}
{"text": "Glycine release is regulated by metabotropic glutamate receptors sensitive to mGluR2 / 3 ligands and activated by N - acetylaspartylglutamate ( NAAG ) .", "entity": [{"entity": "Glycine", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "N - acetylaspartylglutamate", "entity_type": "Chemical", "pos": [114, 141]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [144, 148]}], "task": "NER"}
{"text": "The presence of metabotropic glutamate receptors ( mGluRs ) of group II modulating glycine exocytosis from glycinergic nerve endings of mouse spinal cord was investigated .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "Purified synaptosomes were selectively prelabeled with [ ( 3 ) H ] glycine through the neuronal transporter GlyT2 and subsequently depolarized by superfusion with 12 mM KCl .", "entity": [{"entity": "[ ( 3 ) H ] glycine", "entity_type": "Chemical", "pos": [55, 74]}, {"entity": "KCl", "entity_type": "Chemical", "pos": [169, 172]}], "task": "NER"}
{"text": "The selective mGluR2 / 3 agonist LY379268 inhibited the K ( + ) - evoked overflow of [ ( 3 ) H ] glycine in a concentration - dependent manner ( EC ( 50 ) about 0 . 2 nM ) .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "[ ( 3 ) H ] glycine", "entity_type": "Chemical", "pos": [85, 104]}], "task": "NER"}
{"text": "The effect of LY379268 was prevented by the selective mGluR2 / 3 antagonist LY341495 ( IC ( 50 ) about 1 nM ) .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "LY341495", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "N - acetylaspartylglutamate ( NAAG ) inhibited [ ( 3 ) H ] glycine overflow with extraordinary potency ( EC ( 50 ) about 50 fmol ) .", "entity": [{"entity": "N - acetylaspartylglutamate", "entity_type": "Chemical", "pos": [0, 27]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [30, 34]}, {"entity": "[ ( 3 ) H ] glycine", "entity_type": "Chemical", "pos": [47, 66]}], "task": "NER"}
{"text": "In contrast , glutamate was ineffective up to 0 . 1 nM , excluding that glutamate contamination of commercial NAAG samples is responsible for the reported activity of NAAG at mGluR3 .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [110, 114]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [167, 171]}], "task": "NER"}
{"text": "LY341495 antagonized the NAAG inhibition of [ ( 3 ) H ] glycine release .", "entity": [{"entity": "LY341495", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [25, 29]}, {"entity": "[ ( 3 ) H ] glycine", "entity_type": "Chemical", "pos": [44, 63]}], "task": "NER"}
{"text": "The effect of a combination of maximally effective concentrations of LY379268 and NAAG exhibited no additivity .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [69, 77]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [82, 86]}], "task": "NER"}
{"text": "The non - hydrolysable NAAG analogue N - acetylaspartyl - beta - linked glutamate ( beta - NAAG ) antagonized NAAG and LY379268 .", "entity": [{"entity": "NAAG", "entity_type": "Chemical", "pos": [23, 27]}, {"entity": "N - acetylaspartyl - beta - linked glutamate", "entity_type": "Chemical", "pos": [37, 81]}, {"entity": "beta - NAAG", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "NAAG", "entity_type": "Chemical", "pos": [110, 114]}, {"entity": "LY379268", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "In conclusion , our results show that glycinergic nerve endings in spinal cord are endowed with group II mGluRs mediating inhibition of glycine exocytosis .", "entity": [{"entity": "glycine", "entity_type": "Chemical", "pos": [38, 45]}], "task": "NER"}
{"text": "NAAG can activate these presynaptic receptors with extremely high affinity and with characteristics compatible with the reported mGluR3 pharmacology .", "entity": [{"entity": "NAAG", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Attenuation of methamphetamine seeking by the mGluR2 / 3 agonist LY379268 in rats with histories of restricted and escalated self - administration .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [15, 30]}, {"entity": "LY379268", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "Recent findings implicate group II metabotropic glutamate receptors ( mGluR ( 2 / 3 ) ) in the reinforcing effects of psychostimulants and have identified these receptors as potential treatment targets for drug addiction .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "Here , we investigated the effects of mGluR ( 2 / 3 ) stimulation on cue - and drug - primed reinstatement in rats with different histories of methamphetamine ( METH ) self - administration training , under two conditions : 16 daily sessions of short access ( 90 min / day , ShA ) , or 8 daily sessions of short access followed by 8 sessions of long access ( 6 h / day , LgA ) .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [143, 158]}, {"entity": "METH", "entity_type": "Chemical", "pos": [161, 165]}], "task": "NER"}
{"text": "Following self - administration and subsequent extinction training , rats were pretreated with the selective mGluR ( 2 / 3 ) agonist LY379268 ( variable dose , 0 - 3 mg / kg ) , exposed to METH - paired cues or a priming injection of METH ( 1 mg / kg ) , and tested for reinstatement of METH - seeking behavior .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [133, 141]}, {"entity": "METH", "entity_type": "Chemical", "pos": [189, 193]}, {"entity": "METH", "entity_type": "Chemical", "pos": [234, 238]}, {"entity": "METH", "entity_type": "Chemical", "pos": [287, 291]}], "task": "NER"}
{"text": "LgA rats self - administered greater amounts of METH during the second half of training , but when pretreated with vehicle , ShA and LgA rats showed cue - and drug - primed reinstatement at equivalent response rates .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "However , LgA rats demonstrated greater sensitivity to mGluR ( 2 / 3 ) stimulation with attenuated responding during cue - induced reinstatement after 0 . 3 mg / kg and higher doses of LY379268 , whereas ShA rats decreased cue - induced reinstatement behavior following 1 . 0 mg / kg and 3 . 0 mg / kg LY379268 .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [185, 193]}, {"entity": "LY379268", "entity_type": "Chemical", "pos": [302, 310]}], "task": "NER"}
{"text": "Additionally , both LgA and ShA rats exhibited decreased METH - primed reinstatement behavior following 0 . 3 mg / kg and higher doses of LY379268 .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [57, 61]}, {"entity": "LY379268", "entity_type": "Chemical", "pos": [138, 146]}], "task": "NER"}
{"text": "A separate group of control rats was trained to self - administer sucrose pellets , and demonstrated attenuated cue - induced sucrose - seeking behavior following 1 . 0 and 3 . 0 mg / kg LY379268 .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [187, 195]}], "task": "NER"}
{"text": "Together , the results indicate that LY379268 has differential attenuating effects on cue - induced reinstatement behavior in rats with different histories of METH intake .", "entity": [{"entity": "LY379268", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "METH", "entity_type": "Chemical", "pos": [159, 163]}], "task": "NER"}
{"text": "Stathmin 1 is a potential novel oncogene in melanoma .", "entity": [], "task": "NER"}
{"text": "In previous studies , we demonstrated that miR - 193b expression is reduced in melanoma relative to benign nevi , and also that miR - 193b represses cyclin D1 and Mcl - 1 expression .", "entity": [], "task": "NER"}
{"text": "We suggested that stathmin 1 ( STMN1 ) might be a target of miR - 193b .", "entity": [], "task": "NER"}
{"text": "STMN1 normally regulates microtubule dynamics either by sequestering free tubulin heterodimers or by promoting microtubule catastrophe .", "entity": [], "task": "NER"}
{"text": "Increased expression of STMN1 has been observed in a variety of human malignancies , but its association with melanoma is unknown .", "entity": [], "task": "NER"}
{"text": "We now report that STMN1 is upregulated during the progression of melanoma relative to benign nevi , and that STMN1 is directly regulated by miR - 193b .", "entity": [], "task": "NER"}
{"text": "Using an experimental cell culture approach , overexpression of miR - 193b using synthetic microRNAs repressed STMN1 expression , whereas inhibition of miR - 193b with anti - miR oligos increased STMN1 expression in melanoma cells .", "entity": [], "task": "NER"}
{"text": "The use of a luciferase reporter assay confirmed that miR - 193b directly regulates STMN1 by targeting the 3 ' - untranslated region of STMN1 mRNA .", "entity": [], "task": "NER"}
{"text": "We further demonstrated that STMN1 is overexpressed in malignant melanoma compared with nevi in two independent melanoma cohorts , and that its level is inversely correlated with miR - 193b expression .", "entity": [], "task": "NER"}
{"text": "However , STMN1 expression was not significantly associated with patient survival , Breslow depth , mitotic count or patient age .", "entity": [], "task": "NER"}
{"text": "STMN1 knockdown by small - interfering RNA in melanoma cells drastically repressed cell proliferation and migration potential , whereas ectopic expression of STMN1 using lentivirus increased cell proliferation and migration rates .", "entity": [], "task": "NER"}
{"text": "Subsequent gene expression analysis indicated that interconnected cytoskeletal networks are directly affected following STMN1 knockdown .", "entity": [], "task": "NER"}
{"text": "In addition , we identified deregulated genes associated with proliferation and migration , and revealed that p21 ( Cip1 / Waf1 ) and p27 ( Kip ) could be downstream effectors of STMN1 signaling .", "entity": [], "task": "NER"}
{"text": "Taken together , our study suggests that downregulation of miR - 193b may contribute to increased STMN1 expression in melanoma , which consequently promotes migration and proliferation of tumor cells .", "entity": [], "task": "NER"}
{"text": "The p44 / wdr77 - dependent cellular proliferation process during lung development is reactivated in lung cancer .", "entity": [], "task": "NER"}
{"text": "During lung development , cells proliferate for a defined length of time before they begin to differentiate .", "entity": [], "task": "NER"}
{"text": "Factors that control this proliferative process and how this growth process is related to lung cancer are currently unknown .", "entity": [], "task": "NER"}
{"text": "Here , we found that the WD40 - containing protein ( p44 / wdr77 ) was expressed in growing epithelial cells at the early stages of lung development .", "entity": [], "task": "NER"}
{"text": "In contrast , p44 / wdr77 expression was diminished in fully differentiated epithelial cells in the adult lung .", "entity": [], "task": "NER"}
{"text": "Loss of p44 / wdr77 gene expression led to cell growth arrest and differentiation .", "entity": [], "task": "NER"}
{"text": "Re - expression of p44 / wdr77 caused terminally differentiated cells to re - enter the cell cycle .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that p44 / wdr77 is essential and sufficient for proliferation of lung epithelial cells .", "entity": [], "task": "NER"}
{"text": "P44 / Wdr77 was re - expressed in lung cancer , and silencing p44 / wdr77 expression strongly inhibited growth of lung adenocarcinoma cells in tissue culture and abolished growth of lung adenocarcinoma tumor xenografts in mice .", "entity": [], "task": "NER"}
{"text": "The growth arrest induced by loss of p44 / wdr77 expression was partially through the p21 - Rb signaling .", "entity": [], "task": "NER"}
{"text": "Our results suggest that p44 / wdr77 controls cellular proliferation during lung development , and this growth process is reactivated during lung tumorigenesis .", "entity": [], "task": "NER"}
{"text": "Two new phenolic glycosides from Inula cappa DC .", "entity": [{"entity": "phenolic glycosides", "entity_type": "Chemical", "pos": [8, 27]}], "task": "NER"}
{"text": "Two new phenolic glycosides were isolated from the ethanol extract of the roots of Inula cappa DC .", "entity": [{"entity": "phenolic glycosides", "entity_type": "Chemical", "pos": [8, 27]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "Their structures were defined as 4 - [ ( 6 - O - ( E ) - caffeoyl ) - beta - D - glucopyranosyl ] vanillic acid ( 1 ) and 3 - O - [ beta - D - apiofurarnosyl - ( 1 - 6 ) - beta - D - glucopyranoxy ] - 6 - hydroxy - p - cymene ( 2 ) on the basis of spectral analysis .", "entity": [{"entity": "4 - [ ( 6 - O - ( E ) - caffeoyl ) - beta - D - glucopyranosyl ] vanillic acid", "entity_type": "Chemical", "pos": [33, 111]}, {"entity": "3 - O - [ beta - D - apiofurarnosyl - ( 1 - 6 ) - beta - D - glucopyranoxy ] - 6 - hydroxy - p - cymene", "entity_type": "Chemical", "pos": [122, 225]}], "task": "NER"}
{"text": "In vitro characterization of organophosphorus compound hydrolysis by native and recombinant human prolidase .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [29, 45]}], "task": "NER"}
{"text": "Human prolidase is a binuclear metalloenzyme , which can potentially function as a catalytic bioscavenger for organophosphorus ( OP ) nerve agents .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [110, 126]}], "task": "NER"}
{"text": "Although the biochemical properties of native prolidase purified from human erythrocytes , liver , kidney , and fibroblast cells are well known , it is very poorly characterized with regard to its OP hydrolyzing activity .", "entity": [], "task": "NER"}
{"text": "Also , the high cost of purification of large quantities of native enzyme limits its use as a bioscavenger .", "entity": [], "task": "NER"}
{"text": "Thus , recombinant human prolidase with similar biochemical properties to those of native enzyme would be more suitable as a catalytic bioscavenger .", "entity": [], "task": "NER"}
{"text": "In this study , we established an Escherichia coli expression system , which produced a large amount of tagged human liver prolidase that was purified to over 95 % purity from the soluble fraction of cell lysate by affinity chromatography on Streptavidin - agarose resin .", "entity": [], "task": "NER"}
{"text": "The catalytic properties of the recombinant enzyme were compared in vitro with those of highly purified prolidase I isolated from human erythrocytes .", "entity": [], "task": "NER"}
{"text": "The catalytic properties of recombinant prolidase overlap with those of the erythrocyte - derived native enzyme .", "entity": [], "task": "NER"}
{"text": "Both enzymes efficiently hydrolyzed diisopropylfluorophosphate , sarin , soman , tabun and cyclosarin , but were much less efficient at hydrolyzing paraoxon and methyl paraoxon .", "entity": [{"entity": "diisopropylfluorophosphate", "entity_type": "Chemical", "pos": [36, 62]}, {"entity": "sarin", "entity_type": "Chemical", "pos": [65, 70]}, {"entity": "soman", "entity_type": "Chemical", "pos": [73, 78]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [81, 86]}, {"entity": "cyclosarin", "entity_type": "Chemical", "pos": [91, 101]}, {"entity": "paraoxon", "entity_type": "Chemical", "pos": [148, 156]}, {"entity": "methyl paraoxon", "entity_type": "Chemical", "pos": [161, 176]}], "task": "NER"}
{"text": "These results suggest that human prolidase expressed in E . coli is suitable for further development as a catalytic bioscavenger for OP nerve agents .", "entity": [], "task": "NER"}
{"text": "Theoretical study of the pH - dependent antioxidant properties of vitamin C .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "Molecules acting as antioxidants capable of scavenging reactive oxygen species ( ROS ) are of utmost importance in the living cell .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [64, 70]}], "task": "NER"}
{"text": "Vitamin C is known to be one of these molecules .", "entity": [{"entity": "Vitamin C", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "In this study we have analyzed the reactivity of vitamin C toward the [ Formula : see text ] and [ Formula : see text ] ROS species , in all acidic , neutral and basic media .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "In order to do so , density functional theory ( DFT ) have been used .", "entity": [], "task": "NER"}
{"text": "More concretely , the meta - GGA functional MPW1B95 have been used .", "entity": [], "task": "NER"}
{"text": "Two reaction types have been studied in each case : addition to the ring atoms , and hydrogen / proton abstraction .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [85, 93]}], "task": "NER"}
{"text": "Our results show that [ Formula : see text ] is the most reactive species , while [ Formula : see text ] displays low reactivity .", "entity": [], "task": "NER"}
{"text": "In all three media , vitamin C reactions with two hydroxyl radicals show a wide variety of possible products .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [21, 30]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Cooperation between p53 and the telomere - protecting shelterin component Pot1a in endometrial carcinogenesis .", "entity": [], "task": "NER"}
{"text": "Type II endometrial cancer ( EMCA ) represents only 10 % of all EMCAs , but accounts for 40 % of EMCA - related mortality .", "entity": [], "task": "NER"}
{"text": "Previous studies of human tumors have shown an association between Type II tumors and damaged telomeres .", "entity": [], "task": "NER"}
{"text": "We hypothesized that the lack of murine Type II EMCA models is due to the extremely long telomeres in laboratory mouse strains .", "entity": [], "task": "NER"}
{"text": "We previously showed that telomerase - null mice with critically short telomeres developed endometrial lesions histologically resembling endometrial intraepithelial carcinoma ( EIC ) , the accepted precursor for Type II EMCA .", "entity": [], "task": "NER"}
{"text": "However , these mice did not develop invasive endometrial adenocarcinoma , and instead succumbed prematurely to multi - organ failure .", "entity": [], "task": "NER"}
{"text": "Here , we modeled critical telomere attrition by conditionally inactivating Pot1a , a component of the shelterin complex that stabilizes telomeres , within endometrial epithelium .", "entity": [], "task": "NER"}
{"text": "Inactivation of Pot1a by itself did not stimulate endometrial carcinogenesis , and did not result in detectable DNA damage or apoptosis in endometrium .", "entity": [], "task": "NER"}
{"text": "However , simultaneous inactivation of Pot1a and p53 resulted in EIC - like lesions by 9 months indistinguishable from those seen in late generation telomerase - null mice .", "entity": [], "task": "NER"}
{"text": "These lesions progressed to invasive endometrial adenocarcinomas as early as 9 months of age with metastatic disease in 100 % of the animals by 15 months .", "entity": [], "task": "NER"}
{"text": "These tumors were poorly differentiated endometrial adenocarcinomas with prominent nuclear atypia , resembling human Type II cancers .", "entity": [], "task": "NER"}
{"text": "Furthermore , these tumors were aneuploid with double - stranded DNA breaks and end - to - end telomere fusions and most were tetraploid or near - tetraploid .", "entity": [], "task": "NER"}
{"text": "These studies lend further support to the hypothesis that telomeric instability has a critical role in Type II endometrial carcinogenesis and provides an intriguing in - vivo correlate to recent studies implicating telomere - dependent tetraploidization as an important mechanism in carcinogenesis .", "entity": [], "task": "NER"}
{"text": "Hyperinakin , a new anti - inflammatory phloroglucinol derivative from Hypericum nakamurai .", "entity": [{"entity": "Hyperinakin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "phloroglucinol", "entity_type": "Chemical", "pos": [40, 54]}], "task": "NER"}
{"text": "Phytochemical investigation of Hypericum nakamurai ( Masamune ) Robson has led to the isolation of three phloroglucinol derivatives 1 - 3 .", "entity": [{"entity": "phloroglucinol", "entity_type": "Chemical", "pos": [105, 119]}], "task": "NER"}
{"text": "The structures of these compounds were determined by the analysis of their spectroscopic data ( IR , mass and UV ) , and by the application of 1 - D and 2 - D - NMR techniques .", "entity": [], "task": "NER"}
{"text": "Hyperinakin ( 1 ) is a new compound .", "entity": [{"entity": "Hyperinakin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The anti - inflammatory activities of compounds 1 - 3 were also tested and evaluated .", "entity": [], "task": "NER"}
{"text": "A biogenetic pathway for compounds 1 - 3 was also proposed .", "entity": [], "task": "NER"}
{"text": "Recurrent gene deletions and the evolution of adaptive cyanogenesis polymorphisms in white clover ( Trifolium repens L . ) .", "entity": [], "task": "NER"}
{"text": "Understanding the molecular evolution of genes that underlie intraspecific polymorphisms can provide insights into the process of adaptive evolution .", "entity": [], "task": "NER"}
{"text": "For adaptive polymorphisms characterized by gene presence / absence ( P / A ) variation , underlying loci commonly show signatures of long - term balancing selection , with gene - presence and gene - absence alleles maintained as two divergent lineages .", "entity": [], "task": "NER"}
{"text": "We examined the molecular evolution of two unlinked P / A polymorphisms that underlie a well - documented adaptive polymorphism for cyanogenesis ( hydrogen cyanide release with tissue damage ) in white clover .", "entity": [{"entity": "hydrogen cyanide", "entity_type": "Chemical", "pos": [147, 163]}], "task": "NER"}
{"text": "Both cyanogenic and acyanogenic plants occur in this species , and the ecological forces that maintain this chemical defence polymorphism have been studied for several decades .", "entity": [], "task": "NER"}
{"text": "Using a sample of 65 plants , we investigated the molecular evolution of sequences flanking the two underlying cyanogenesis genes : Ac / ac ( controlling the presence / absence of cyanogenic glucosides ) and Li / li ( controlling the presence / absence of their hydrolysing enzyme , linamarase ) .", "entity": [{"entity": "cyanogenic glucosides", "entity_type": "Chemical", "pos": [180, 201]}], "task": "NER"}
{"text": "A combination of genome walking , PCR assays , DNA sequence analysis and Southern blotting was used to test whether these adaptive P / A polymorphisms show evidence of long - term balancing selection , or whether gene - absence alleles have evolved repeatedly through independent deletion events .", "entity": [], "task": "NER"}
{"text": "For both loci , we detect no signatures of balancing selection in the closest flanking genomic sequences .", "entity": [], "task": "NER"}
{"text": "Instead , we find evidence for variation in the size of the deletions characterizing gene - absence alleles .", "entity": [], "task": "NER"}
{"text": "These observations strongly suggest that both of these polymorphisms have been evolving through recurrent gene deletions over time .", "entity": [], "task": "NER"}
{"text": "We discuss the genetic mechanisms that could account for this surprising pattern and the implications of these findings for mechanisms of rapid adaptive evolution in white clover .", "entity": [], "task": "NER"}
{"text": "Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation .", "entity": [], "task": "NER"}
{"text": "We chose promoters responsive to sonication in LNCap cells , a prostate cancer cell line , out of a library composed of DNA fragments constructed by linking the TATA box sequence to randomly combined cis - acting elements of transcription factors activated in response to radiation in prostate cancer cells .", "entity": [], "task": "NER"}
{"text": "When a plasmid containing the luciferase gene under control of a promoter was transfected into LNCap cells and sonicated with 1 MHz ultrasound at 0 . 5 W / cm ( 2 ) , 10 % DF for 60s , 13 promoters showed more than 10 - fold enhancement compared with their counterparts without sonication 12h after sonication .", "entity": [], "task": "NER"}
{"text": "As to their responsiveness to sonication , the best two promoters were then compared to clone 880 - 8 , a derivative from clone 880 that was created by random introduction of point mutations and was shown to have an improved response to X - ray irradiation .", "entity": [], "task": "NER"}
{"text": "We then took clone 880 - 8 for further analyses since it showed the highest enhancement to sonication , though not statistically significant from the others .", "entity": [], "task": "NER"}
{"text": "Next , we employed a retrovirus vector and stably introduced the luciferase gene under control of clone 880 - 8 into LNCap cells to establish a cell line .", "entity": [], "task": "NER"}
{"text": "When the cell line was sonicated with 1 MHz ultrasound at 0 . 5 W / cm ( 2 ) , 10 % DF for 60s , luciferase expression was enhanced up to 14 . 8 - fold 12h after sonication .", "entity": [], "task": "NER"}
{"text": "We then established another cell line by replacing the luciferase gene with the fcy : : fur gene , a suicide gene , and when the cell line was sonicated with 1 MHz ultrasound at 0 . 5 W / cm ( 2 ) , 10 % DF for 60s , expression of the gene was enhanced , showing the maximum expression 12 - 24h after sonication .", "entity": [], "task": "NER"}
{"text": "When the cells were incubated in medium containing 5 - fluorocytosine , cell survival ratio decreased dose dependently with 5 - fluorocytosine only after sonication treatment , suggesting this promoter could be utilized for gene expression control with ultrasound .", "entity": [{"entity": "5 - fluorocytosine", "entity_type": "Chemical", "pos": [51, 69]}, {"entity": "5 - fluorocytosine", "entity_type": "Chemical", "pos": [124, 142]}], "task": "NER"}
{"text": "Genetic determinants of neuronal vulnerability to apoptosis .", "entity": [], "task": "NER"}
{"text": "Apoptosis is a common mode of cell death that contributes to neuronal loss associated with neurodegeneration .", "entity": [], "task": "NER"}
{"text": "Single - nucleotide polymorphisms ( SNPs ) in chromosomal DNA are contributing factors dictating natural susceptibility of humans to disease .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [9, 19]}], "task": "NER"}
{"text": "Here , the most common SNPs affecting neuronal vulnerability to apoptosis are reviewed in the context of neurological disorders .", "entity": [], "task": "NER"}
{"text": "Polymorphic variants in genes encoding apoptotic proteins , either from the extrinsic ( FAS , TNF - alpha , CASP8 ) or the intrinsic ( BAX , BCL2 , CASP3 , CASP9 ) pathways could be highly valuable in the diagnosis of neurodegenerative diseases and stroke .", "entity": [], "task": "NER"}
{"text": "Interestingly , the Arg72Pro SNP in TP53 , the gene encoding tumor suppressor p53 , was recently revealed a biomarker of poor prognosis in stroke due to its ability to modulate neuronal apoptotic death .", "entity": [], "task": "NER"}
{"text": "Search for new SNPs responsible for genetic variability to apoptosis will ensure the implementation of novel diagnostic and prognostic tools , as well as therapeutic strategies against neurological diseases .", "entity": [], "task": "NER"}
{"text": "Dissolved gas and ultrasonic cavitation - - a review .", "entity": [], "task": "NER"}
{"text": "The physics and chemistry of nonlinearly oscillating acoustic cavitation bubbles are strongly influenced by the dissolved gas in the surrounding liquid .", "entity": [], "task": "NER"}
{"text": "Changing the gas alters among others the luminescence spectrum , and the radical production of the collapsing bubbles .", "entity": [], "task": "NER"}
{"text": "An overview of experiments with various gas types and concentration described in literature is given and is compared to mechanisms that lead to the observed changes in luminescence spectra and radical production .", "entity": [], "task": "NER"}
{"text": "The dissolved gas type changes the bubble adiabatic ratio , thermal conductivity , and the liquid surface tension , and consequently the hot spot temperature .", "entity": [], "task": "NER"}
{"text": "The gas can also participate in chemical reactions , which can enhance radical production or luminescence of a cavitation bubble .", "entity": [], "task": "NER"}
{"text": "With this knowledge , the gas content in cavitation can be tailored to obtain the desired output .", "entity": [], "task": "NER"}
{"text": "Towards an understanding and control of cavitation activity in 1 MHz ultrasound fields .", "entity": [], "task": "NER"}
{"text": "Various industrial processes such as sonochemical processing and ultrasonic cleaning strongly rely on the phenomenon of acoustic cavitation .", "entity": [], "task": "NER"}
{"text": "As the occurrence of acoustic cavitation is incorporating a multitude of interdependent effects , the amount of cavitation activity in a vessel is strongly depending on the ultrasonic process conditions .", "entity": [], "task": "NER"}
{"text": "It is therefore crucial to quantify cavitation activity as a function of the process parameters .", "entity": [], "task": "NER"}
{"text": "At 1 MHz , the active cavitation bubbles are so small that it is becoming difficult to observe them in a direct way .", "entity": [], "task": "NER"}
{"text": "Hence , another metrology based on secondary effects of acoustic cavitation is more suitable to study cavitation activity .", "entity": [], "task": "NER"}
{"text": "In this paper we present a detailed analysis of acoustic cavitation phenomena at 1 MHz ultrasound by means of time - resolved measurements of sonoluminescence , cavitation noise , and synchronized high - speed stroboscopic Schlieren imaging .", "entity": [], "task": "NER"}
{"text": "It is shown that a correlation exists between sonoluminescence , and the ultraharmonic and broadband signals extracted from the cavitation noise spectra .", "entity": [], "task": "NER"}
{"text": "The signals can be utilized to characterize different regimes of cavitation activity at different acoustic power densities .", "entity": [], "task": "NER"}
{"text": "When cavitation activity sets on , the aforementioned signals correlate to fluctuations in the Schlieren contrast as well as the number of nucleated bubbles extracted from the Schlieren Images .", "entity": [], "task": "NER"}
{"text": "This additionally proves that signals extracted from cavitation noise spectra truly represent a measure for cavitation activity .", "entity": [], "task": "NER"}
{"text": "The cyclic behavior of cavitation activity is investigated and related to the evolution of the bubble populations in the ultrasonic tank .", "entity": [], "task": "NER"}
{"text": "It is shown that cavitation activity is strongly linked to the occurrence of fast - moving bubbles .", "entity": [], "task": "NER"}
{"text": "The origin of this \" bubble streamers \" is investigated and their role in the initialization and propagation of cavitation activity throughout the sonicated liquid is discussed .", "entity": [], "task": "NER"}
{"text": "Finally , it is shown that bubble activity can be stabilized and enhanced by the use of pulsed ultrasound by conserving and recycling active bubbles between subsequent pulsing cycles .", "entity": [], "task": "NER"}
{"text": "The potential of nicotinic enhancement of cognitive remediation training in schizophrenia .", "entity": [], "task": "NER"}
{"text": "Cognitive deficits in schizophrenia are critically important predictors of long - term psychosocial outcome and are not significantly ameliorated by currently available medications .", "entity": [], "task": "NER"}
{"text": "Cognitive remediation training has shown promise for alleviating cognitive symptoms of schizophrenia , but the clinical significance has often been limited by small effect sizes .", "entity": [], "task": "NER"}
{"text": "Approaches that achieve larger improvement involve time requirements that can be cost - prohibitive within the current clinical care system .", "entity": [], "task": "NER"}
{"text": "This mini - review evaluates the theoretical potential of a pharmacological enhancement strategy of cognitive remediation training with nicotinic acetylcholine receptor ( nAChR ) agonists .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [146, 159]}], "task": "NER"}
{"text": "nAChR agonists can facilitate sensory processing , alertness , attention , learning and memory .", "entity": [], "task": "NER"}
{"text": "While these effects may be too subtle and short - lasting to be of clinical relevance as a primary treatment of cognitive deficits , they constitute an ideal effects profile for enhancing training benefits .", "entity": [], "task": "NER"}
{"text": "Several mechanisms are described through which repeated coupling of cognitive training challenges with nAChR stimulation may enhance and accelerate cognitive remediation training effects , advancing such interventions into more effective and practicable treatments of some of the most debilitating symptoms of schizophrenia .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' Cognitive Enhancers ' .", "entity": [], "task": "NER"}
{"text": "Enhanced mGlu5 - receptor dependent long - term depression at the Schaffer collateral - CA1 synapse of congenitally learned helpless rats .", "entity": [], "task": "NER"}
{"text": "Alterations of the glutamatergic system have been implicated in the pathophysiology and treatment of major depression .", "entity": [], "task": "NER"}
{"text": "In order to investigate the expression and function of mGlu5 receptors in an animal model for treatment - resistant depression we used rats bred for congenital learned helplessness ( cLH ) and the control strain , bred for resistance against inescapable stress , congenitally . not learned helpless rats ( cNLH ) .", "entity": [], "task": "NER"}
{"text": "Western blot analysis showed an increased expression of mGlu5 ( but not mGlu1a ) receptors in the hippocampus of cLH rats , as compared with control cNLH rats .", "entity": [], "task": "NER"}
{"text": "We also examined mGlu1 / 5 receptor signaling by in vivo measurement of DHPG - stimulated polyphosphoinositides hydrolysis .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [72, 76]}, {"entity": "polyphosphoinositides", "entity_type": "Chemical", "pos": [90, 111]}], "task": "NER"}
{"text": "Stimulation of ( 3 ) H - inositolmonophosphate formation induced by i . c . v . injection of DHPG was enhanced by about 50 % in the hippocampus of cLH rats .", "entity": [{"entity": "( 3 ) H - inositolmonophosphate", "entity_type": "Chemical", "pos": [15, 46]}, {"entity": "DHPG", "entity_type": "Chemical", "pos": [93, 97]}], "task": "NER"}
{"text": "Correspondingly , DHPG - induced long - term depression ( LTD ) at Schaffer collateral / CA1 pyramidal cell synapses was amplified in hippocampal slices of cLH rats , whereas LTD induced by low frequency stimulation of the Schaffer collaterals did not change .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [18, 22]}], "task": "NER"}
{"text": "Moreover , these effects were associated with decreased basal dendritic spine density of CA1 pyramidal cell in cLH rats .", "entity": [], "task": "NER"}
{"text": "These data raise the attractive possibility that changes in the expression and function of mGlu5 receptors in the hippocampus might underlie the changes in synaptic plasticity associated with the depressive - like phenotype of cLH rats .", "entity": [], "task": "NER"}
{"text": "However , chronic treatment of cLH rats with MPEP did not reverse learned helplessness , indicating that the enhanced mGlu5 receptor function is not the only player in the behavioral phenotype of this genetic model of depression .", "entity": [{"entity": "MPEP", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "A variant in the carboxyl - terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot .", "entity": [{"entity": "carboxyl", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "GJA5 gene ( MIM no . 121013 ) , localized at 1q21 . 1 , encodes for the cardiac gap junction protein connexin 40 .", "entity": [], "task": "NER"}
{"text": "In humans , copy number variants of chromosome 1q21 . 1 have been associated with variable phenotypes comprising congenital heart disease ( CHD ) , including isolated TOF .", "entity": [], "task": "NER"}
{"text": "In mice , the deletion of Gja5 can cause a variety of complex CHDs , in particular of the cardiac outflow tract , corresponding to TOF in many cases .", "entity": [], "task": "NER"}
{"text": "In the present study , we screened for mutations in the GJA5 gene 178 unrelated probands with isolated TOF .", "entity": [], "task": "NER"}
{"text": "A heterozygous nucleotide change ( c . 793C > T ) in exon 2 of the gene leading to the p . Pro265Ser variant at the carboxyl - terminus of the protein was found in two unrelated sporadic patients , one with classic anatomy and one with pulmonary atresia .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "This GJA5 missense substitution was not observed in 1568 ethnically - matched control chromosomes .", "entity": [], "task": "NER"}
{"text": "Immunofluorescent staining and confocal microscopy revealed that cells expressing the mutant protein form sparse or no visible gap - junction plaques in the region of cell - cell contact .", "entity": [], "task": "NER"}
{"text": "Moreover , analysis of the transfer of the gap junction permanent tracer lucifer yellow showed that cells expressing the mutant protein have a reduced rate of dye transfer compared with wild - type cells .", "entity": [], "task": "NER"}
{"text": "Finally , use of a zebrafish model revealed that microinjection of the GJA5 - p . Pro265Ser mutant disrupts overall morphology of the heart tube in the 37 % ( 22 / 60 ) of embryos , compared with the 6 % ( 4 / 66 ) of the GJA5 wild - type - injected embryos .", "entity": [], "task": "NER"}
{"text": "These findings implicate GJA5 gene as a novel susceptibility gene for TOF .", "entity": [], "task": "NER"}
{"text": "A newly identified locus for benign adult familial myoclonic epilepsy on chromosome 3q26 . 32 - 3q28 .", "entity": [], "task": "NER"}
{"text": "Benign Adult Familial Myoclonic Epilepsy ( BAFME ) is an autosomal dominant disorder characterized by adult - onset cortical tremor or action myoclonus predominantly in the upper limbs , and generalized seizures .", "entity": [], "task": "NER"}
{"text": "We investigated a Thai BAFME family .", "entity": [], "task": "NER"}
{"text": "Clinical and electrophysiological studies revealed that 13 were affected with BAFME .", "entity": [], "task": "NER"}
{"text": "There were a total of 24 individuals studied .", "entity": [], "task": "NER"}
{"text": "Genetic analysis by genome - wide linkage study ( GWLS ) was performed using 400 microsatellite markers and excluded linkage of the previous BAFME loci , 8q23 . 3 - q24 . 1 , and 2p11 . 1 - q12 . 2 .", "entity": [], "task": "NER"}
{"text": "GWLS showed that the disease - associated region in our Thai family was linked to a newly identified locus on chromosome 3q26 . 32 - 3q28 .", "entity": [], "task": "NER"}
{"text": "This locus represents the fourth chromosomal region for BAFME .", "entity": [], "task": "NER"}
{"text": "Sonoluminescence quenching and cavitation bubble temperature measurements in an ionic liquid .", "entity": [], "task": "NER"}
{"text": "A comparison between the temperatures within imploding acoustic cavitation bubbles and the extent of sonoluminescence ( SL ) quenching by C ( 1 ) - C ( 5 ) aliphatic alcohols in 1 - ethyl - 3 - methylimidazolium ethylsulfate ( [ EMIM ] [ EtSO ( 4 ) ] , a well known imidazolium based room temperature ionic liquid ( RTIL ) ) , has been made at an ultrasound frequency of 213 kHz .", "entity": [{"entity": "aliphatic alcohols", "entity_type": "Chemical", "pos": [156, 174]}, {"entity": "1 - ethyl - 3 - methylimidazolium ethylsulfate", "entity_type": "Chemical", "pos": [178, 224]}, {"entity": "[ EMIM ] [ EtSO ( 4 ) ]", "entity_type": "Chemical", "pos": [227, 250]}, {"entity": "imidazolium", "entity_type": "Chemical", "pos": [266, 277]}], "task": "NER"}
{"text": "The temperatures obtained ranged from 3500 +/- 200K , in neat [ EMIM ] [ EtSO ( 4 ) ] , to about 3200 +/- 200K in RTIL - alcohol containing solutions .", "entity": [{"entity": "[ EMIM ] [ EtSO ( 4 ) ]", "entity_type": "Chemical", "pos": [62, 85]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [121, 128]}], "task": "NER"}
{"text": "It was also found that the SL intensity decreased with increasing concentration ( up to 1M ) of the alcohols to a greater extent compared with the relative changes to the bubble temperatures .", "entity": [{"entity": "alcohols", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "Both the extent of the reduction in the bubble temperatures and the SL quenching were much smaller than those obtained in comparable aqueous solutions containing aliphatic alcohols .", "entity": [{"entity": "aliphatic alcohols", "entity_type": "Chemical", "pos": [162, 180]}], "task": "NER"}
{"text": "Possible reasons for the differences in the observed trends between water / alcohol and [ EMIM ] [ EtSO ( 4 ) ] / alcohol systems under sonication at 213 kHz are discussed .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [76, 83]}, {"entity": "[ EMIM ] [ EtSO ( 4 ) ]", "entity_type": "Chemical", "pos": [88, 111]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "GABAergic activity in autism spectrum disorders : an investigation of cortical inhibition via transcranial magnetic stimulation .", "entity": [], "task": "NER"}
{"text": "Mounting evidence suggests a possible role for gamma - aminobutyric acid ( GABA ) in the neuropathophysiology of autism spectrum disorders ( ASD ) , but the extent of this impairment is unclear .", "entity": [{"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [47, 72]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [75, 79]}], "task": "NER"}
{"text": "A non - invasive , in vivo measure of GABA involves transcranial magnetic stimulation ( TMS ) of the primary motor cortex to probe cortical inhibition .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [38, 42]}], "task": "NER"}
{"text": "Individuals diagnosed with ASD ( high - functioning autism or Asperger ' s disorder ) ( n = 36 [ 28 male ] ; mean age : 26 . 00 years ) and a group of healthy individuals ( n = 34 [ 23 male ] ; mean age : 26 . 21 years ) ( matched for age , gender , and cognitive function ) were administered motor cortical TMS paradigms putatively measuring activity at GABAA and GABAB receptors ( i . e . , short and long interval paired pulse TMS , cortical silent period ) .", "entity": [], "task": "NER"}
{"text": "All cortical inhibition paradigms yielded no difference between ASD and control groups .", "entity": [], "task": "NER"}
{"text": "There was , however , evidence for short interval cortical inhibition ( SICI ) deficits among those ASD participants who had experienced early language delay , suggesting that GABA may be implicated in an ASD subtype .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [176, 180]}], "task": "NER"}
{"text": "The current findings do not support a broad role for GABA in the neuropathophysiology of ASD , but provide further indication that GABAA could be involved in ASD where there is a delay in language acquisition .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [53, 57]}], "task": "NER"}
{"text": "This article is part of the Special Issue entitled ' Neurodevelopmental Disorders ' .", "entity": [], "task": "NER"}
{"text": "Pharmacological treatment of tic disorders and Tourette Syndrome .", "entity": [], "task": "NER"}
{"text": "The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome ( TS ) .", "entity": [], "task": "NER"}
{"text": "After a short summary on phenomenology , clinical course and comorbid conditions we review indications for pharmacological treatment in detail .", "entity": [], "task": "NER"}
{"text": "Unfortunately , standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce .", "entity": [], "task": "NER"}
{"text": "Treatment decisions are often guided by individual needs and personal experience of treating clinicians .", "entity": [], "task": "NER"}
{"text": "The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion .", "entity": [], "task": "NER"}
{"text": "As first - line treatment of tics risperidone ( best evidence level for atypical antipsychotics ) or tiapride ( largest clinical experience in Europe and low rate of adverse reactions ) are recommended .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [34, 45]}, {"entity": "tiapride", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "Aripiprazole ( still limited but promising data with low risk for adverse reactions ) and pimozide ( best evidence of the typical antipsychotics ) are agents of second choice .", "entity": [{"entity": "Aripiprazole", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "pimozide", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "In TS patients with comorbid attention deficit hyperactivity disorder ( ADHD ) atomoxetine , stimulants or clonidine should be considered , or , if tics are severe , a combination of stimulants and risperidone .", "entity": [{"entity": "atomoxetine", "entity_type": "Chemical", "pos": [79, 90]}, {"entity": "clonidine", "entity_type": "Chemical", "pos": [107, 116]}, {"entity": "risperidone", "entity_type": "Chemical", "pos": [198, 209]}], "task": "NER"}
{"text": "When mild to moderate tics are associated with obsessive - compulsive symptoms , depression or anxiety sulpiride monotherapy can be helpful .", "entity": [{"entity": "sulpiride", "entity_type": "Chemical", "pos": [103, 112]}], "task": "NER"}
{"text": "In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [40, 51]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "In summary , further studies , particularly randomized , double - blind , placebo - controlled trials including larger and / or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders .", "entity": [], "task": "NER"}
{"text": "Cognitive enhancement as a treatment for drug addictions .", "entity": [], "task": "NER"}
{"text": "Drug addiction continues to be an important public health problem , with an estimated 22 . 6 million current illicit drug users in the United States alone .", "entity": [], "task": "NER"}
{"text": "For many addictions , including cocaine , methamphetamine , and marijuana addiction , there are no approved pharmacological treatments .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [42, 57]}], "task": "NER"}
{"text": "Behavioral treatments are effective but effects vary widely across individuals .", "entity": [], "task": "NER"}
{"text": "Treatments that are effective across multiple addictions are greatly needed , and accumulating evidence suggests that one such approach may be pharmacological or behavioral interventions that enhance executive inhibitory control in addicts .", "entity": [], "task": "NER"}
{"text": "Current evidence indicates that most forms of chronic drug use may be associated with significant cognitive impairments , especially in attention , working memory , and response inhibition functions .", "entity": [], "task": "NER"}
{"text": "In some studies , these impairments predict poor treatment retention and outcome .", "entity": [], "task": "NER"}
{"text": "A number of cognitive enhancing agents , including galantamine , modafinil , atomoxetine , methylphenidate , and guanfacine , have shown promising findings in human studies .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "modafinil", "entity_type": "Chemical", "pos": [65, 74]}, {"entity": "atomoxetine", "entity_type": "Chemical", "pos": [77, 88]}, {"entity": "methylphenidate", "entity_type": "Chemical", "pos": [91, 106]}, {"entity": "guanfacine", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "Specific behavioral interventions , including cognitive remediation , also show promise .", "entity": [], "task": "NER"}
{"text": "However , whether improvement of selective cognitive functions reduces drug use behavior remains to be determined .", "entity": [], "task": "NER"}
{"text": "Cognitive enhancement to improve treatment outcomes is a novel strategy worthy of future research , as are related questions such as whether these approaches may be broadly beneficial to most addicts or best reserved for substance users with specific demonstrated cognitive impairments .", "entity": [], "task": "NER"}
{"text": "Pinosylvin Induces Cell Survival , Migration and Anti - Adhesiveness of Endothelial Cells via Nitric Oxide Production .", "entity": [{"entity": "Pinosylvin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "Nitric Oxide", "entity_type": "Chemical", "pos": [94, 106]}], "task": "NER"}
{"text": "Pinosylvin is a phenolic compound mainly found in the Pinus species .", "entity": [{"entity": "Pinosylvin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [16, 24]}], "task": "NER"}
{"text": "To determine the vascular functions of pinosylvin , we first examined both proliferation and apoptosis of bovine aortic endothelial cells ( BAECs ) in the presence of pinosylvin .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "pinosylvin", "entity_type": "Chemical", "pos": [167, 177]}], "task": "NER"}
{"text": "When BAECs were treated with pinosylvin , etoposide - or starvation - induced apoptosis was shown to be significantly reduced .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [29, 39]}, {"entity": "etoposide", "entity_type": "Chemical", "pos": [42, 51]}], "task": "NER"}
{"text": "The anti - apoptotic effect of pinosylvin was mediated by inhibition of caspase - 3 .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [31, 41]}], "task": "NER"}
{"text": "Moreover , pinosylvin was shown to activate endothelial nitric oxide synthetase ( eNOS ) .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [11, 21]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [56, 68]}], "task": "NER"}
{"text": "At 1 pM , pinosylvin appeared to have a cell - proliferative effect in the endothelial cell .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [10, 20]}], "task": "NER"}
{"text": "The pinosylvin - induced cell proliferation was declined by treatment with L - NAME , an eNOS inhibitor .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "L - NAME", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "Then , we found that pinosylvin had a stimulatory effect on cell migration and tube formation .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "These stimulatory effects suggest that pinosylvin is likely to act as a pro - angiogenic factor .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "Yet another effect of pinosylvin was inhibition of lipopolysaccharide - induced THP - 1 cell adhesion to endothelial cells .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [22, 32]}], "task": "NER"}
{"text": "Altogether , we propose that pinosylvin may be utilized as a phytotherapic agent for the prevention of cardiovascular inflammatory diseases .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "Dihydroxy - Isosteviol Methyl Ester from Pulsatilla nigricans Induces Apoptosis in HeLa Cells : Its Cytoxicity and Interaction with Calf Thymus DNA .", "entity": [{"entity": "Dihydroxy - Isosteviol Methyl Ester", "entity_type": "Chemical", "pos": [0, 35]}], "task": "NER"}
{"text": "Dihydroxy - isosteviol methyl ester ( DIME ) , the principal biological compound isolated from the medicinal plant Pulsatilla nigricans ( Fam : Ranunculaceae ) having the molecular formula of C21 H34 O3 ( molecular weight 334 . 25 ) , was administered to cervical cancer cells ( HeLa ) in vitro to evaluate its possible apoptotic ( anti - cancer ) potentials .", "entity": [{"entity": "Dihydroxy - isosteviol methyl ester", "entity_type": "Chemical", "pos": [0, 35]}, {"entity": "DIME", "entity_type": "Chemical", "pos": [38, 42]}, {"entity": "C21 H34 O3", "entity_type": "Chemical", "pos": [192, 202]}], "task": "NER"}
{"text": "We analyzed the expression of p53 , Bax , Bcl2 , Apaf and caspase 3 signal proteins and analyzed the early apoptotic events in HeLa cells induced by DIME using protocols like Annexin V - FITC and PI staining .", "entity": [{"entity": "DIME", "entity_type": "Chemical", "pos": [149, 153]}], "task": "NER"}
{"text": "DIME caused a significant decrease in cell viability , induced nuclear condensation and inter - nucleosomal DNA fragmentation .", "entity": [{"entity": "DIME", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "We further studied the interaction of DIME with calf thymus DNA as target through circular - dichroism spectra .", "entity": [{"entity": "DIME", "entity_type": "Chemical", "pos": [38, 42]}], "task": "NER"}
{"text": "Results showed that DIME interacted with DNA , bringing indiscernible changes in structure and conformation .", "entity": [{"entity": "DIME", "entity_type": "Chemical", "pos": [20, 24]}], "task": "NER"}
{"text": "Thus , DIME showed its capability to induce apoptosis in cancer cells , signifying its utility in drug design as a possible candidate for chemoprevention .", "entity": [{"entity": "DIME", "entity_type": "Chemical", "pos": [7, 11]}], "task": "NER"}
{"text": "Genome - wide patterns of standing genetic variation in a marine population of three - spined sticklebacks .", "entity": [], "task": "NER"}
{"text": "Since the end of the Pleistocene , the three - spined stickleback ( Gasterosteus aculeatus ) has repeatedly colonized and adapted to various freshwater habitats probably originating from ancestral marine populations .", "entity": [], "task": "NER"}
{"text": "Standing genetic variation and the underlying genomic architecture both have been speculated to contribute to recent adaptive radiations of sticklebacks .", "entity": [], "task": "NER"}
{"text": "Here , we expand on the current genomic resources of this fish by providing extensive genome - wide variation data from six individuals from a marine ( North Sea ) stickleback population .", "entity": [], "task": "NER"}
{"text": "Using next - generation sequencing and a combination of paired - end and mate - pair libraries , we detected a wide size range of genetic variation .", "entity": [], "task": "NER"}
{"text": "Among the six individuals , we found more than 7 % of the genome is polymorphic , consisting of 2599111 SNPs , 233464 indels and structural variation ( SV ) ( > 50 bp ) such as 1054 copy - number variable regions ( deletions and duplications ) and 48 inversions .", "entity": [], "task": "NER"}
{"text": "Many of these polymorphisms affect gene and coding sequences .", "entity": [], "task": "NER"}
{"text": "Based on SNP diversity , we determined outlier regions concordant with signatures expected under adaptive evolution .", "entity": [], "task": "NER"}
{"text": "As some of these outliers overlap with pronounced regions of copy - number variation , we propose the consideration of such SV when analysing SNP data from re - sequencing approaches .", "entity": [], "task": "NER"}
{"text": "We further discuss the value of this resource on genome - wide variation for further investigation upon the relative contribution of standing variation on the parallel evolution of sticklebacks and the importance of the genomic architecture in adaptive radiation .", "entity": [], "task": "NER"}
{"text": "Structure - based optimization of oxadiazole - based GSK - 3 inhibitors .", "entity": [{"entity": "oxadiazole", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "Inhibition of glycogen synthase kinase - 3 ( GSK - 3 ) induces neuroprotective effects , e . g . decreases beta - amyloid production and reduces tau hyperphosphorylation , which are both associated with Alzheimer ' s disease ( AD ) .", "entity": [], "task": "NER"}
{"text": "The two isoforms of GSK - 3 in mammalians are GSK - 3 alpha and beta , which share 98 % homology in their catalytic domains .", "entity": [], "task": "NER"}
{"text": "We investigated GSK - 3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP - binding pocket [ 1 ] .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "Particularly , the oxadiazole scaffold provided potent and selective GSK - 3 inhibitors .", "entity": [{"entity": "oxadiazole", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "For example , the most potent inhibitor of the present series , the acetamide 26d , is characterized by an IC50 of 2 nM for GSK - 3 alpha and 17 nM for GSK - 3 beta .", "entity": [{"entity": "acetamide", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "In addition , the benzodioxane 8g showed up to 27 - fold selectivity for GSK - 3 alpha over GSK - 3 beta , with an IC50 of 35 nM for GSK - 3 alpha .", "entity": [{"entity": "benzodioxane", "entity_type": "Chemical", "pos": [18, 30]}], "task": "NER"}
{"text": "Two GSK - 3 inhibitors were further profiled for efficacy and toxicity in the wild - type ( wt ) zebrafish embryo assay to evaluate simultaneously permeability and safety .", "entity": [], "task": "NER"}
{"text": "Dual inhibitor of PDE7 and GSK - 3 - VP1 . 15 acts as antipsychotic and cognitive enhancer in C57BL / 6J mice .", "entity": [], "task": "NER"}
{"text": "Cognitive deficit is a core of schizophrenia and it is not effectively treated by the available antipsychotic drugs , hence new and more effective therapy is needed .", "entity": [], "task": "NER"}
{"text": "Schizophrenia is considered as a pathway disorder where Disrupted - In - Schizophrenia - 1 ( DISC1 ) is important molecular player that regulates multiple cellular cascades .", "entity": [], "task": "NER"}
{"text": "We recently reported synergistic action between phosphodiesterase - 4 ( PDE4 ) and glycogen synthase kinase - 3 ( GSK - 3 ) as DISC1 interacting proteins .", "entity": [], "task": "NER"}
{"text": "In the current study we characterized behavioural effects of a newly developed compound , VP1 . 15 that inhibits both PDE7 and GSK - 3 with main focus on its antipsychotic and cognitive capacities .", "entity": [], "task": "NER"}
{"text": "VP1 . 15 reduced ambulation in C57BL / 6J mice in a dose - dependent manner ( 7 . 5 mg / kg and 3 mg / kg , respectively ) and , hence , lower dose was chosen for the further analysis .", "entity": [], "task": "NER"}
{"text": "VP1 . 1 . 5 facilitated pre - pulse inhibition ( PPI ) , reversed amphetamine - but not MK - 801 - induced PPI deficit .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [66, 77]}, {"entity": "MK - 801", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "The drug was able to ameliorate the disrupted latent inhibition ( LI ) induced by the increased number of conditioning trials and reversed amphetamine - induced LI deficit , supporting further its antipsychotic effects .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [139, 150]}], "task": "NER"}
{"text": "The drug also significantly improved episodic memory in the spatial object recognition test , facilitated working memory in Y - maze and enhanced cued fear memory , but had no effect on executive function in the Puzzle box and contextual fear conditioning .", "entity": [], "task": "NER"}
{"text": "Taken together , VP1 . 15 elicited antipsychotic effects and also facilitated cognitive domains in mice , suggesting that multitarget drugs , affecting molecular substrates from the same pathway , perhaps could be antipsychotics of new - generation that open a new possibilities in drug discoveries .", "entity": [], "task": "NER"}
{"text": "The novel phosphodiesterase 10A inhibitor THPP - 1 has antipsychotic - like effects in rat and improves cognition in rat and rhesus monkey .", "entity": [{"entity": "THPP - 1", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "Phosphodiesterase 10A ( PDE10A ) is a novel target for the treatment of schizophrenia that may address multiple symptomatic domains associated with this disorder .", "entity": [], "task": "NER"}
{"text": "PDE10A is highly expressed in the brain and functions to metabolically inactivate the important second messengers cAMP and cGMP .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [114, 118]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [123, 127]}], "task": "NER"}
{"text": "Here we describe effects of a potent and orally bioavailable PDE10A inhibitor [ 2 - ( 6 - chloropyridin - 3 - yl ) - 4 - ( 2 - methoxyethoxy ) - 7 , 8 - dihydropyrido [ 4 , 3 - d ] pyrimidin - 6 ( 5H ) - yl ] ( imidazo [ 1 , 5 - a ] pyridin - 1 - yl ) methanone ] ( THPP - 1 ) on striatal signaling pathways , in behavioral tests that predict antipsychotic potential , and assays that measure episodic - like memory in rat and executive function in rhesus monkey .", "entity": [{"entity": "2 - ( 6 - chloropyridin - 3 - yl ) - 4 - ( 2 - methoxyethoxy ) - 7 , 8 - dihydropyrido [ 4 , 3 - d ] pyrimidin - 6 ( 5H ) - yl ] ( imidazo [ 1 , 5 - a ] pyridin - 1 - yl ) methanone", "entity_type": "Chemical", "pos": [80, 261]}, {"entity": "THPP - 1", "entity_type": "Chemical", "pos": [266, 274]}], "task": "NER"}
{"text": "THPP - 1 exhibits nanomolar potency on the PDE10A enzyme , demonstrates excellent pharmacokinetic properties in multiple preclinical animal species , and is selective for PDE10A over other PDE families of enzymes .", "entity": [{"entity": "THPP - 1", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "THPP - 1 significantly increased phosphorylation of proteins in the striatum involved in synaptic plasticity , including the a - amino - 3 - hydroxy - 5 - methylisoxazole - 4 - proprionic acid receptor ( AMPA ) GluR1 subunit , extracellular receptor kinase ( ERK ) , and cAMP - response element binding protein ( CREB ) .", "entity": [{"entity": "THPP - 1", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "a - amino - 3 - hydroxy - 5 - methylisoxazole - 4 - proprionic acid", "entity_type": "Chemical", "pos": [125, 192]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [204, 208]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [271, 275]}], "task": "NER"}
{"text": "THPP - 1 produced dose - dependent effects in preclinical assays predictive of antipsychotic activity including attenuation of MK - 801 - induced psychomotor activation and condition avoidance responding in rats .", "entity": [{"entity": "THPP - 1", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "MK - 801", "entity_type": "Chemical", "pos": [127, 135]}], "task": "NER"}
{"text": "At similar plasma exposures , THPP - 1 significantly increased object recognition memory in rat and attenuated a ketamine - induced deficit in the object retrieval detour task in rhesus monkey .", "entity": [{"entity": "THPP - 1", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [113, 121]}], "task": "NER"}
{"text": "These findings suggest that PDE10A inhibitors have the potential to impact multiple symptomatic domains of schizophrenia including positive symptoms and cognitive impairment .", "entity": [], "task": "NER"}
{"text": "Quetiapine ameliorates stress - induced cognitive inflexibility in rats .", "entity": [{"entity": "Quetiapine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The antidepressant action of quetiapine has been demonstrated in clinical and preclinical studies .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "Nevertheless , little is known about its effectiveness in the treatment of frontal - like cognitive disturbances that may be associated with stress - related disorder .", "entity": [], "task": "NER"}
{"text": "Therefore , the aim of the present study was to investigate whether quetiapine would prevent and / or reverse stress - induced cognitive impairments in a rat model of prefrontal cortex ( PFC ) - dependent attentional set - shifting task ( ASST ) .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [68, 78]}], "task": "NER"}
{"text": "Because quetiapine augmentation to selective serotonin reuptake inhibitors ( SSRIs ) has recently been proven to be beneficial in neuropsychiatric disorders , a separate experiment was designed to assess the impact of combined administration of inactive doses of quetiapine and escitalopram on ASST performance in rats .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [8, 18]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "quetiapine", "entity_type": "Chemical", "pos": [263, 273]}, {"entity": "escitalopram", "entity_type": "Chemical", "pos": [278, 290]}], "task": "NER"}
{"text": "According to our previous studies , 1 h daily exposure to restraint stress for 7 days significantly and specifically impaired extra - dimensional ( ED ) set - shifting ability of rats .", "entity": [], "task": "NER"}
{"text": "Quetiapine ( 2 . 5 mg / kg , PO ) given to rats prior to the restraint sessions completely prevented this stress - induced cognitive inflexibility .", "entity": [{"entity": "Quetiapine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Similar effect was demonstrated after pretreatment with the alpha 1 - adrenoceptor antagonist , prazosin ( 1 mg / kg , IP ) .", "entity": [{"entity": "prazosin", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "Moreover , acute administration of quetiapine before the test reversed set - shifting deficits in stressed rats ( 0 . 63 , 1 . 25 and 2 . 5 mg / kg , PO ) and improved ED performance of cognitively unimpaired control animals ( 1 . 25 and 2 . 5 mg / kg , PO ) .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [35, 45]}], "task": "NER"}
{"text": "Finally , the combined administration of inactive doses of quetiapine ( 0 . 63 and 0 . 3 mg / kg in control and stressed rats , respectively ) and escitalopram ( 0 . 3 mg / kg , IP ) facilitated set - shifting performance in either control or stressed rats .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "escitalopram", "entity_type": "Chemical", "pos": [147, 159]}], "task": "NER"}
{"text": "In conclusion , quetiapine administration either prevented or reversed stress - induced cognitive inflexibility in rats .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [16, 26]}], "task": "NER"}
{"text": "In addition to promoting of set - shifting by itself , quetiapine also enhanced the procognitive efficacy of escitalopram .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "escitalopram", "entity_type": "Chemical", "pos": [109, 121]}], "task": "NER"}
{"text": "The potential contribution of the antagonism at alpha 1 - adrenoceptors to the mechanisms underlying the protective action of quetiapine requires further evaluation .", "entity": [{"entity": "quetiapine", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "These findings may have therapeutic implications for the treatment of frontal - like disturbances , particularly cognitive inflexibility , in stress - related psychiatric disorders .", "entity": [], "task": "NER"}
{"text": "Modified - release prednisone decreases complaints and fatigue compared to standard prednisolone in patients with adrenal insufficiency .", "entity": [{"entity": "prednisone", "entity_type": "Chemical", "pos": [19, 29]}, {"entity": "prednisolone", "entity_type": "Chemical", "pos": [84, 96]}], "task": "NER"}
{"text": "Patients with adrenal insufficiency ( AI ) receive first glucocorticoid replacement dose after waking , resulting in a 3 - 5 h delay compared to physiological secretion .", "entity": [], "task": "NER"}
{"text": "Impaired quality of life ( QoL ) and fatigue might be due to this delayed dose scheme .", "entity": [], "task": "NER"}
{"text": "Modified - release glucocorticoid preparations might have therapeutic advantages .", "entity": [], "task": "NER"}
{"text": "Exploratory pilot study including 14 patients with AI was conducted in a single university center .", "entity": [], "task": "NER"}
{"text": "Patients on morning dose prednisolone ( 5 mg ) were included , switched to modified - release prednisone ( 5 mg ) at 10 PM for 3 months , and then switched back on standard prednisolone .", "entity": [{"entity": "prednisolone", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "prednisone", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "prednisolone", "entity_type": "Chemical", "pos": [173, 185]}], "task": "NER"}
{"text": "3 standardized questionnaires ( GBB - 24 , MFI , and AddiQoL ) investigating complaints and fatigue were completed at baseline , after 3 , and 6 months .", "entity": [], "task": "NER"}
{"text": "Data regarding clinical and hormonal parameters were assessed .", "entity": [], "task": "NER"}
{"text": "Modified - release prednisone showed significant improvement in one of 4 scales of GBB - 24 and positive trends to better scores in 3 of 4 scales .", "entity": [{"entity": "prednisone", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "The global score of discomfort improved significantly .", "entity": [], "task": "NER"}
{"text": "The MFI showed also significant improvement in 3 of 5 scales and positive trend to better scores in 2 scales .", "entity": [], "task": "NER"}
{"text": "Significant changes to better scores were seen in 4 out of 30 items of the AddiQoL .", "entity": [], "task": "NER"}
{"text": "Modified - release prednisone showed decreased complaints and fatigue compared to standard prednisolone indicating importance of glucocorticoid increase in early morning hours before waking .", "entity": [{"entity": "prednisone", "entity_type": "Chemical", "pos": [19, 29]}, {"entity": "prednisolone", "entity_type": "Chemical", "pos": [91, 103]}], "task": "NER"}
{"text": "Bioactivity of Diosmetin Glycosides Isolated from the Epicarp of Date Fruits , Phoenix dactylifera , on the Biochemical Profile of Alloxan Diabetic Male Rats .", "entity": [{"entity": "Diosmetin Glycosides", "entity_type": "Chemical", "pos": [15, 35]}, {"entity": "Alloxan", "entity_type": "Chemical", "pos": [131, 138]}], "task": "NER"}
{"text": "The new natural flavonoid compounds - diosmetin 7 - O - beta - L - arabinofuranosyl ( 1 --> 2 ) beta - D - apiofuranoside ( 1 ) and diosmetin 7 - O - beta - D - apiofuranoside ( 2 ) - were isolated from the acetone extract of date fruits epicarp belonging to family Arecaceae ( Palmae ) .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "diosmetin 7 - O - beta - L - arabinofuranosyl ( 1 --> 2 ) beta - D - apiofuranoside", "entity_type": "Chemical", "pos": [38, 121]}, {"entity": "diosmetin 7 - O - beta - D - apiofuranoside", "entity_type": "Chemical", "pos": [132, 175]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [207, 214]}], "task": "NER"}
{"text": "Elucidation of their chemical structures was determined by different spectroscopic methods in addition to the chemical and physical methods of analysis .", "entity": [], "task": "NER"}
{"text": "These compounds were assessed for their biological activity on alloxan diabetic rats .", "entity": [{"entity": "alloxan", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "A dose of 1 . 5 ml of ( 1 ) and ( 2 ) suspensions / 100 gm b .", "entity": [], "task": "NER"}
{"text": "wt were orally administrated to alloxan diabetic rats for 30 days .", "entity": [{"entity": "alloxan", "entity_type": "Chemical", "pos": [32, 39]}], "task": "NER"}
{"text": "The treatment of diabetic rats with these compounds resulted in marked improvement of the different biochemical results , i . e . the serum glucose level ( highly significant , from 330 + 5 . 5 mg / dL to 140 + 1 . 2 mg / dL ) treated with ( 1 ) ; liver functions markedly developed both by AST and ALT levels , ( reduced significantly from 68 . 3 + 4 . 8 mu / L to 54 + 5 . 5 mu / L and from 61 . 0 + 3 . 6 mu / L to 40 . 1 + 3 . 6 mu / L , respectively ) treated with ( 2 ) , accompanying with mild decrease in both cholesterol and triglycerides levels with ( 1 ) or ( 2 ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [140, 147]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [518, 529]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [534, 547]}], "task": "NER"}
{"text": "Decrease of TBARS level was observed in whole blood when treated with ( 1 ) or ( 2 ) , while levels of glutathione peroxidase and superoxide dismutase were increased in liver .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [103, 114]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [130, 140]}], "task": "NER"}
{"text": "Serum testosterone level was highly significantly increased ( from 705 . 1 + 3 . 6 mg / 100 ml to 720 + 4 . 7 mg / 100 ml ) , total acid phosphatase and prostate acid phosphatase activities were highly significantly decreased ( from 16 . 9 + 0 . 28 mu / L to 10 . 7 + 1 . 2 mu / L and from 9 . 7 + 0 . 7 mu / L to 6 . 5 + 1 mu / L , respectively ) for compound ( 1 ) .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [6, 18]}], "task": "NER"}
{"text": "Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations .", "entity": [], "task": "NER"}
{"text": "The 185delAG * BRCA1 mutation is encountered primarily in Jewish Ashkenazi and Iraqi individuals , and sporadically in non - Jews .", "entity": [], "task": "NER"}
{"text": "Previous studies estimated that this is a founder mutation in Jewish mutation carriers that arose before the dispersion of Jews in the Diaspora ~ 2500 years ago .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to assess the haplotype in ethnically diverse 185delAG * BRCA1 mutation carriers , and to estimate the age at which the mutation arose .", "entity": [], "task": "NER"}
{"text": "Ethnically diverse Jewish and non - Jewish 185delAG * BRCA1 mutation carriers and their relatives were genotyped using 15 microsatellite markers and three SNPs spanning 12 . 5 MB , encompassing the BRCA1 gene locus .", "entity": [], "task": "NER"}
{"text": "Estimation of mutation age was based on a subset of 11 markers spanning a region of ~ 5 MB , using a previously developed algorithm applying the maximum likelihood method .", "entity": [], "task": "NER"}
{"text": "Overall , 188 participants ( 154 carriers and 34 noncarriers ) from 115 families were included : Ashkenazi , Iraq , Kuchin - Indians , Syria , Turkey , Iran , Tunisia , Bulgaria , non - Jewish English , non - Jewish Malaysian , and Hispanics .", "entity": [], "task": "NER"}
{"text": "Haplotype analysis indicated that the 185delAG mutation arose 750 - 1500 years ago .", "entity": [], "task": "NER"}
{"text": "In Ashkenazim , it is a founder mutation that arose 61 generations ago , and with a small group of founder mutations was introduced into the Hispanic population ( conversos ) ~ 650 years ago , and into the Iraqi - Jewish community ~ 450 years ago .", "entity": [], "task": "NER"}
{"text": "The 185delAG mutation in the non - Jewish populations in Malaysia and the UK arose at least twice independently .", "entity": [], "task": "NER"}
{"text": "We conclude that the 185delAG * BRCA1 mutation resides on a common haplotype among Ashkenazi Jews , and arose about 61 generations ago and arose independently at least twice in non - Jews .", "entity": [], "task": "NER"}
{"text": "Role of AMPK in pancreatic beta cell function .", "entity": [], "task": "NER"}
{"text": "Pharmacological activation of AMP activated kinase ( AMPK ) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes .", "entity": [{"entity": "metformin", "entity_type": "Chemical", "pos": [63, 72]}], "task": "NER"}
{"text": "Despite improved glucose regulation achieved by administration of small molecule activators of AMPK , the potential negative impact of enhanced AMPK activity on insulin secretion by the pancreatic beta cell is an important consideration .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [17, 24]}], "task": "NER"}
{"text": "In this review , we discuss our current understanding of the role of AMPK in central functions of the pancreatic beta cell , including glucose - stimulated insulin secretion ( GSIS ) , proliferation , and survival .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [135, 142]}], "task": "NER"}
{"text": "In addition we discuss the controversy surrounding the role of AMPK in insulin secretion , underscoring the merits and caveats of methods used to date .", "entity": [], "task": "NER"}
{"text": "Enhancement of cognitive function in models of brain disease through environmental enrichment and physical activity .", "entity": [], "task": "NER"}
{"text": "This review will provide an overview of the non - drug based approaches that have been demonstrated to enhance cognitive function of the compromised brain , primarily focussed on the two most widely adopted paradigms of environmental enrichment and enhanced physical exercise .", "entity": [], "task": "NER"}
{"text": "Environmental enrichment involves the generation of novelty and complexity in animal housing conditions which facilitates enhanced sensory and cognitive stimulation as well as physical activity .", "entity": [], "task": "NER"}
{"text": "In a wide variety of animal models of brain disorders , environmental enrichment and exercise have been found to have beneficial effects , including cognitive enhancement , delayed disease onset , enhanced cellular plasticity and associated molecular processes .", "entity": [], "task": "NER"}
{"text": "Potential cellular and molecular mechanisms will also be discussed , which have relevance for the future development of ' enviromimetics ' , drugs which could mimic or enhance the beneficial effects of environmental stimulation .", "entity": [], "task": "NER"}
{"text": "Human neuronal coenzyme Q10 deficiency results in global loss of mitochondrial respiratory chain activity , increased mitochondrial oxidative stress and reversal of ATP synthase activity : implications for pathogenesis and treatment .", "entity": [{"entity": "coenzyme Q10", "entity_type": "Chemical", "pos": [15, 27]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [165, 168]}], "task": "NER"}
{"text": "Disorders of coenzyme Q ( 10 ) ( CoQ ( 10 ) ) biosynthesis represent the most treatable subgroup of mitochondrial diseases .", "entity": [{"entity": "coenzyme Q ( 10 )", "entity_type": "Chemical", "pos": [13, 30]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "Neurological involvement is frequently observed in CoQ ( 10 ) deficiency , typically presenting as cerebellar ataxia and / or seizures .", "entity": [{"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [51, 61]}], "task": "NER"}
{"text": "The aetiology of the neurological presentation of CoQ ( 10 ) deficiency has yet to be fully elucidated and therefore in order to investigate these phenomena we have established a neuronal cell model of CoQ ( 10 ) deficiency by treatment of neuronal SH - SY5Y cell line with para - aminobenzoic acid ( PABA ) .", "entity": [{"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [202, 212]}, {"entity": "para - aminobenzoic acid", "entity_type": "Chemical", "pos": [274, 298]}, {"entity": "PABA", "entity_type": "Chemical", "pos": [301, 305]}], "task": "NER"}
{"text": "PABA is a competitive inhibitor of the CoQ ( 10 ) biosynthetic pathway enzyme , COQ2 .", "entity": [{"entity": "PABA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "PABA treatment ( 1 mM ) resulted in a 54 % decrease ( 46 % residual CoQ ( 10 ) ) decrease in neuronal CoQ ( 10 ) status ( p < 0 . 01 ) .", "entity": [{"entity": "PABA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [68, 78]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "Reduction of neuronal CoQ ( 10 ) status was accompanied by a progressive decrease in mitochondrial respiratory chain enzyme activities , with a 67 . 5 % decrease in cellular ATP production at 46 % residual CoQ ( 10 ) .", "entity": [{"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [174, 177]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [206, 216]}], "task": "NER"}
{"text": "Mitochondrial oxidative stress increased four - fold at 77 % and 46 % residual CoQ ( 10 ) .", "entity": [{"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [79, 89]}], "task": "NER"}
{"text": "A 40 % increase in mitochondrial membrane potential was detected at 46 % residual CoQ ( 10 ) with depolarisation following oligomycin treatment suggesting a reversal of complex V activity .", "entity": [{"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [82, 92]}], "task": "NER"}
{"text": "This neuronal cell model provides insights into the effects of CoQ ( 10 ) deficiency on neuronal mitochondrial function and oxidative stress , and will be an important tool to evaluate candidate therapies for neurological conditions associated with CoQ ( 10 ) deficiency .", "entity": [{"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "CoQ ( 10 )", "entity_type": "Chemical", "pos": [249, 259]}], "task": "NER"}
{"text": "Evaluation of potential Myt1 kinase inhibitors by TR - FRET based binding assay .", "entity": [], "task": "NER"}
{"text": "In the human cell cycle , the Myt1 kinase is a crucial regulator of the G2 / M transition .", "entity": [], "task": "NER"}
{"text": "Because this membrane - associated kinase is hard to obtain and assay , there is a distinct lack of data so far .", "entity": [], "task": "NER"}
{"text": "Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay .", "entity": [], "task": "NER"}
{"text": "These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full - length Myt1 expressed in a human cell line .", "entity": [], "task": "NER"}
{"text": "Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect .", "entity": [{"entity": "Dasatinib", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "sunitinib", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "staurosporine", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase .", "entity": [], "task": "NER"}
{"text": "The glycoglycerolipids showed no significant effects in the binding assay , endorsing the idea of a mechanism of action distant from the active site .", "entity": [], "task": "NER"}
{"text": "Nicotine improves performance in an attentional set shifting task in rats .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "A large number of studies in both humans and experimental animals have demonstrated nicotine - induced improvements in various aspects of cognitive function , including attention and memory .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "The prefrontal cortex ( PFC ) is thought to be critically involved in the modulation of executive function and these attentional processes are enhanced by nicotine acting at nicotinic acetylcholine receptors .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [155, 163]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [184, 197]}], "task": "NER"}
{"text": "The involvement of nicotinic processes on cognitive flexibility in particular has not been specifically investigated .", "entity": [], "task": "NER"}
{"text": "The effects of nicotine on attentional flexibility were therefore evaluated using the rodent attentional set shifting task in rats .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "Nicotine injected both acutely and following repeated pre - exposure significantly improved both intradimensional and extradimensional set shifting performance in the task .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Further investigation of the acute effects of nicotine demonstrated this improvement in attentional flexibility to be dose - dependent .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [46, 54]}], "task": "NER"}
{"text": "These results implicate the nicotinic receptor system in the mediation of processes underlying cognitive flexibility and suggest that nicotine improves attentional flexibility in rats , both within and between perceptual dimensions of a compound stimulus .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "Nicotine - induced alterations in prefrontal circuitry may underlie these effects on cognitive flexibility .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Co - learning facilitates memory in mice : a new avenue in social neuroscience .", "entity": [], "task": "NER"}
{"text": "Social context affects brain function but our understanding of its neurobiology is at an early stage .", "entity": [], "task": "NER"}
{"text": "The mere presence of one individual can alter the cognitive capacities of another and social learning has been demonstrated in many species , including the mouse .", "entity": [], "task": "NER"}
{"text": "We asked several questions : 1 .", "entity": [], "task": "NER"}
{"text": "How can active engagement of two familiar mice in the same learning activity ( co - learning ) alter their memory ?", "entity": [], "task": "NER"}
{"text": "2 .", "entity": [], "task": "NER"}
{"text": "Under which environmental conditions ( aversive vs non - aversive ) can we expect the memory to be enhanced , impaired , or not affected ?", "entity": [], "task": "NER"}
{"text": "3 .", "entity": [], "task": "NER"}
{"text": "Can a genetic factor modify the co - learning effect on memory ?", "entity": [], "task": "NER"}
{"text": "More specifically , can co - learning correct memory deficits in autistic - like BTBR inbred mice with deficient sociability ?", "entity": [], "task": "NER"}
{"text": "We demonstrated that pairs of familiar inbred mice of the same or different genotypes ( C57BL / 6J and BTBR ) that were habituated to new objects and their spatial location , had enhanced episodic memory in the spatial object recognition test , whereas individually - trained animals failed to solve this task .", "entity": [], "task": "NER"}
{"text": "Notably , the co - learning effect was genotype - dependent .", "entity": [], "task": "NER"}
{"text": "BTBR mice paired with BTBR cage - mates in the habituation session modestly ameliorated their performance in the object recognition test but co - learning with a familiar C57BL / 6J mouse completely normalized episodic memory deficit .", "entity": [], "task": "NER"}
{"text": "Next , we explored the co - learning effect on fear memory in these inbred strains .", "entity": [], "task": "NER"}
{"text": "Interestingly , mice of both genotypes displayed significantly enhanced contextual fear memory once they had been conditioned together with BTBR animals .", "entity": [], "task": "NER"}
{"text": "The same influence of BTBR presence was observed on cued fear memory in C57BL / 6J mice , whereas a modest co - learning effect was found on cued fear conditioning in the BTBR strain .", "entity": [], "task": "NER"}
{"text": "Taken together , we demonstrated for the first time the co - learning effect on cognitive capacities in mice , which can be modified by genetic background and environmental conditions .", "entity": [], "task": "NER"}
{"text": "The possible implications of this methodological approach in social neuroscience are discussed .", "entity": [], "task": "NER"}
{"text": "Passive stiffness of airway smooth muscle : the next target for improving airway distensibility and treatment for asthma ?", "entity": [], "task": "NER"}
{"text": "Reduced airway distensibility due to increased airway stiffness is a characteristic of asthma .", "entity": [], "task": "NER"}
{"text": "Airway stiffness is determined by the property and structural organization of the various elements of the airway wall , and is often divided into active and passive components .", "entity": [], "task": "NER"}
{"text": "Active stiffness is thought to be associated with activation of muscle cells in the airway wall .", "entity": [], "task": "NER"}
{"text": "This component of stiffness can be inhibited when active force produced by the muscle is abolished .", "entity": [], "task": "NER"}
{"text": "Passive stiffness , on the other hand , is thought to stem from non - muscle component of the airway wall , especially the collagen / elastin fibrous network of the extracellular matrix within which the muscle cells are embedded .", "entity": [], "task": "NER"}
{"text": "In this brief review , the notion that passive stiffness is exclusively extracellular in origin is challenged .", "entity": [], "task": "NER"}
{"text": "Recent evidence suggests that a substantial portion of the passive stiffness of an in vitro preparation of tracheal smooth muscle is calcium sensitive and is regulated by Rho - kinase , although the underlying mechanism and the details of regulation for the development of this intracellular passive stiffness are still largely unknown .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [133, 140]}], "task": "NER"}
{"text": "To reduce airway stiffness different lines of attack must be tailored to different components of the stiffness .", "entity": [], "task": "NER"}
{"text": "The regulatable passive stiffness is distinct from the relatively permanent stiffness of the extracellular matrix and the stiffness associated with active muscle contraction .", "entity": [], "task": "NER"}
{"text": "To improve airway distensibility during asthma exacerbation , a comprehensive approach to reduce overall airway stiffness should therefore include a strategy for targeting the regulatable passive stiffness .", "entity": [], "task": "NER"}
{"text": "Harmonization of description and classification of fetal observations : achievements and problems still unresolved : report of the 7th Workshop on the Terminology in Developmental Toxicology Berlin , 4 - 6 May 2011 .", "entity": [], "task": "NER"}
{"text": "This article summarizes the 7th Workshop on the Terminology in Developmental Toxicology held in Berlin , May 4 - 6 , 2011 .", "entity": [], "task": "NER"}
{"text": "The series of Berlin Workshops has been mainly concerned with the harmonization of terminology and classification of fetal anomalies in developmental toxicity studies .", "entity": [], "task": "NER"}
{"text": "The main topics of the 7th Workshop were knowledge on the fate of anomalies after birth , use of Version 2 terminology for maternal - fetal observations and non - routinely used species , reclassification of \" grey zone \" anomalies and categorization of fetal observations for human health risk assessment .", "entity": [], "task": "NER"}
{"text": "The paucity of data on health consequences of the postnatal permanence of fetal anomalies is relevant and further studies are needed .", "entity": [], "task": "NER"}
{"text": "The Version 2 terminology is an important step forward and the terms listed in this glossary are considered also to be appropriate for most observations in non - routinely used species .", "entity": [], "task": "NER"}
{"text": "Continuation of the Berlin Workshops was recommended .", "entity": [], "task": "NER"}
{"text": "Topics suggested for the next Workshop were grouping of fetal observations for reporting and statistical analysis .", "entity": [], "task": "NER"}
{"text": "Natural anthocyanins from phytoresources and their chemical researches .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [8, 20]}], "task": "NER"}
{"text": "Anthocyanins are a class of naturally occurring polyphenols which have been most widely studied in recent decades for the rapid development of relative techniques .", "entity": [{"entity": "Anthocyanins", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [48, 59]}], "task": "NER"}
{"text": "This article first reviews the various anthocyanin resources including fruits , flowers , vegetables and beverages .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [39, 50]}], "task": "NER"}
{"text": "Besides the direct extraction from natural resources , anthocyanins can also be obtained by semi - or total synthesis .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [55, 67]}], "task": "NER"}
{"text": "After the introduction of new representative anthocyanins found in the past few years and the major relationships between structures and stability , modern separation and analysis technologies in related studies were summarised , which play an important role in chemical researches of anthocyanins .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [45, 57]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [285, 297]}], "task": "NER"}
{"text": "Classification of Aurora kinase inhibitors by self - organizing map ( SOM ) and support vector machine ( SVM ) .", "entity": [], "task": "NER"}
{"text": "The Aurora kinase family ( consisting of Aurora - A , - B and - C ) is an important group of enzymes that controls several aspects of cell division in mammalian cells .", "entity": [], "task": "NER"}
{"text": "In this study , 512 compounds of Aurora - A and - B inhibitors were collected .", "entity": [], "task": "NER"}
{"text": "They were classified into three classes : dual Aurora - A and Aurora - B inhibitors , selective inhibitors of Aurora - A and selective inhibitors of Aurora - B by Self - Organizing Map ( SOM ) and Support Vector Machine ( SVM ) .", "entity": [], "task": "NER"}
{"text": "The prediction accuracies of the models ( based on the training / test set splitting using SOM method ) for the test set were 92 . 2 % for SOM1 and 93 . 8 % for SVM1 , respectively .", "entity": [], "task": "NER"}
{"text": "In addition , the extended connectivity fingerprints ( ECFP _ 4 ) for all the molecules were calculated and structure - activity relationship of Aurora kinase inhibitors was summarized , which may be helpful to find the important structural features of inhibitors relating to the selectivity to Aurora kinases .", "entity": [], "task": "NER"}
{"text": "Role of metabotropic glutamate receptor 1 in the basolateral amygdala - driven prefrontal cortical deactivation in inflammatory pain in the rat .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Plastic changes in the amygdala and limbic cortex networks have been widely shown in chronic pain .", "entity": [], "task": "NER"}
{"text": "We have here investigated the role of group I metabotropic glutamate receptors ( mGluRs ) in the basolateral amygdala ( BLA ) pre - infra - limbic ( PL - IL ) divisions of the medial prefrontal cortex ( mPFC ) neuron connections after carrageenan - induced inflammatory pain in the rat .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [59, 68]}], "task": "NER"}
{"text": "Intra - plantar injection of carrageenan decreased either spontaneous or mechanically / electrically evoked activity of PL cortex pyramidal neurons which responded with excitation in a way prevented by CPCOOEt , a selective mGluR1 antagonist , though not by MPEP , a selective mGluR5 antagonist .", "entity": [{"entity": "CPCOOEt", "entity_type": "Chemical", "pos": [202, 209]}, {"entity": "MPEP", "entity_type": "Chemical", "pos": [258, 262]}], "task": "NER"}
{"text": "Accordingly , intra - BLA microinjection of DHPG , a group I mGluR agonist , caused PL cortex neuron activity depression , antagonized by CPCCOEt .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "CPCCOEt", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "CPCOOEt , but not MPEP , reduced also carrageenan - induced mechanical allodynia .", "entity": [{"entity": "CPCOOEt", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "MPEP", "entity_type": "Chemical", "pos": [18, 22]}], "task": "NER"}
{"text": "The PL cortex cell deactivation in inflammatory pain condition was associated with increased GABA ( conversely glutamate was decreased ) in the PL / IL cortex .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [93, 97]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [111, 120]}], "task": "NER"}
{"text": "The local application of bicuculline , a GABA ( A ) receptor selective antagonist , reduced mechanical allodynia .", "entity": [{"entity": "bicuculline", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "An over - expression of mGluR1 , but not mGluR5 , have been observed in the PL - IL cortex after inflammatory pain suggesting an increased mGluR1 - dependent cross - talk among BLA and IL - PL cortex neurons in inflammatory pain conditions .", "entity": [], "task": "NER"}
{"text": "Emerging role of AMP - activated protein kinase in endocrine control of metabolism in the liver .", "entity": [{"entity": "AMP", "entity_type": "Chemical", "pos": [17, 20]}], "task": "NER"}
{"text": "This review summarizes the emerging role of AMP - activated protein kinase ( AMPK ) in mediating endocrine regulation of metabolic fluxes in the liver .", "entity": [{"entity": "AMP", "entity_type": "Chemical", "pos": [44, 47]}], "task": "NER"}
{"text": "There are a number of hormones which , when acting on the liver , alter AMPK activation .", "entity": [], "task": "NER"}
{"text": "Here we describe those hormones associated with activation and de - activation of AMPK and the potential mechanisms for changes in AMPK activation state .", "entity": [], "task": "NER"}
{"text": "The actions of these hormones , in many cases , are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK - mediated hormone action .", "entity": [], "task": "NER"}
{"text": "In recent years , genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone - stimulated metabolism in the liver .", "entity": [], "task": "NER"}
{"text": "Few experiments have , however , firmly established a causal relationship between hormone action at the liver and AMPK signaling .", "entity": [], "task": "NER"}
{"text": "Rectifying behavior of charge transfer complexes of tetrakis ( dimethylamino ) ethene with acceptor molecules : a theoretical study .", "entity": [{"entity": "tetrakis ( dimethylamino ) ethene", "entity_type": "Chemical", "pos": [52, 85]}], "task": "NER"}
{"text": "The effect of electric field induced electron transfer on the rectification properties of molecular rectifiers based on charge transfer complexes of tetrakis ( dimethylamino ) ethane ( TDAE ) with acceptor molecules was explored .", "entity": [{"entity": "tetrakis ( dimethylamino ) ethane", "entity_type": "Chemical", "pos": [149, 182]}, {"entity": "TDAE", "entity_type": "Chemical", "pos": [185, 189]}], "task": "NER"}
{"text": "The current - voltage curves and the rectification ratios ( RR ) for two different molecular rectifiers were obtained using a direct ab initio method at M06 / LACVP ( d ) level of theory in the range from - 2 to + 2 V .", "entity": [], "task": "NER"}
{"text": "The highest RR of 25 . 7 was determined for the complex of TDAE with 2 - nitropyrene - 4 , 5 , 9 , 10 - tetraone at 0 . 5 V ( D1 ) , while another rectifier [ complex of TDAE with 2 , 7 - dimethyl nitropyrene - 4 , 5 , 9 , 10 - tetraone ( D2 ) ] showed a maximum RR of only 2 . 9 at 0 . 3 V .", "entity": [{"entity": "TDAE", "entity_type": "Chemical", "pos": [59, 63]}, {"entity": "2 - nitropyrene - 4 , 5 , 9 , 10 - tetraone", "entity_type": "Chemical", "pos": [69, 112]}, {"entity": "TDAE", "entity_type": "Chemical", "pos": [170, 174]}, {"entity": "2 , 7 - dimethyl nitropyrene - 4 , 5 , 9 , 10 - tetraone", "entity_type": "Chemical", "pos": [180, 236]}], "task": "NER"}
{"text": "The electric field induced electron transfer occurring in D1 creates a one - way conducting channel consisting of two SOMOs involving the entire D1 complex .", "entity": [], "task": "NER"}
{"text": "In the case of D2 , no electron transfer occurs at the applied bias voltages due to the relatively high energy difference between HOMO and LUMO .", "entity": [], "task": "NER"}
{"text": "Increased expression of P450scc and CYP17 in development of endogenous hyperandrogenism in a rat model of PCOS .", "entity": [], "task": "NER"}
{"text": "The objective of the present study was to characterize the effect of insulin plus hCG on the expression of steroidogenic enzymes ( P450scc and CYP17 ) in polycystic ovaries of rats .", "entity": [], "task": "NER"}
{"text": "Changes in estrous cycle , ovarian morphology , hormonal levels , and protein levels by immunohistochemistry and western - blot were determined .", "entity": [], "task": "NER"}
{"text": "Rats treated with insulin plus hCG displayed abnormal estrous cycles with increasing androgen biosynthesis .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [85, 93]}], "task": "NER"}
{"text": "Meanwhile , insulin plus hCG resulted in multiple large cysts with diminished granulosa layers and increased thecal layers and stromal - interstitial tissue .", "entity": [], "task": "NER"}
{"text": "Moreover , there was an increase in the expression of P450scc and CYP17 in thecal and stromal cells in our PCOS rat model compared with control rats .", "entity": [], "task": "NER"}
{"text": "These results indicate that administration of insulin with hCG can synergistically result in endogenous hyperandrogenism which may partially upregulate the expression of steroidogenic enzymes in ovarian tissue .", "entity": [], "task": "NER"}
{"text": "beta - Orcinol - type depsides from the lichen Thamnolia vermicularis .", "entity": [{"entity": "beta - Orcinol", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "A phytochemical investigation of a herb tea made from Thamnolia vermicularis led to the isolation of three new beta - orcinol - type depsides ( 1 , 2 and 3 ) , along with seven known compounds hypothamnolic acid ( 4 ) , 3 ' - methylevenic acid ( 5 ) , baeomycesic acid ( 6 ) , squamatic acid ( 7 ) , methyl 3 ' - methyllecanorate ( 8 ) , barbatinic acid ( 9 ) and atranorin ( 10 ) .", "entity": [{"entity": "beta - orcinol", "entity_type": "Chemical", "pos": [111, 125]}, {"entity": "depsides", "entity_type": "Chemical", "pos": [133, 141]}, {"entity": "hypothamnolic acid", "entity_type": "Chemical", "pos": [193, 211]}, {"entity": "3 ' - methylevenic acid", "entity_type": "Chemical", "pos": [220, 243]}, {"entity": "baeomycesic acid", "entity_type": "Chemical", "pos": [252, 268]}, {"entity": "squamatic acid", "entity_type": "Chemical", "pos": [277, 291]}, {"entity": "methyl 3 ' - methyllecanorate", "entity_type": "Chemical", "pos": [300, 329]}, {"entity": "barbatinic acid", "entity_type": "Chemical", "pos": [338, 353]}, {"entity": "atranorin", "entity_type": "Chemical", "pos": [364, 373]}], "task": "NER"}
{"text": "The structures of the new compounds were determined on the basis of spectroscopic evidence , including 1 - D and 2 - D NMR and ESI - MS techniques .", "entity": [], "task": "NER"}
{"text": "AMPAKINE enhancement of social interaction in the BTBR mouse model of autism .", "entity": [{"entity": "AMPAKINE", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Autism is a neurodevelopmental disorder in which the first diagnostic symptom is unusual reciprocal social interactions .", "entity": [], "task": "NER"}
{"text": "Approximately half of the children diagnosed with an autism spectrum disorder also have intellectual impairments .", "entity": [], "task": "NER"}
{"text": "General cognitive abilities may be fundamental to many aspects of social cognition .", "entity": [], "task": "NER"}
{"text": "Cognitive enhancers could conceivably be of significant benefit to children and adults with autism .", "entity": [], "task": "NER"}
{"text": "AMPAKINE compounds are a novel class of pharmacological agents that act as positive modulators of AMPA receptors to enhance excitatory glutamatergic neurotransmission .", "entity": [{"entity": "AMPAKINE", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [98, 102]}], "task": "NER"}
{"text": "This class of compounds was reported to improve learning and memory in several rodent and non - human primate tasks , and to normalize respiratory abnormalities in a mouse model of Rett syndrome .", "entity": [], "task": "NER"}
{"text": "Here we evaluate the actions of AMPA compounds in adult male and female BTBR mice , a well characterized mouse model of autism .", "entity": [{"entity": "AMPA", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "Acute treatment with CX1837 and CX1739 reversed the deficit in sociability in BTBR mice on the most sensitive parameter , time spent sniffing a novel mouse as compared to time spent sniffing a novel object .", "entity": [{"entity": "CX1837", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "CX1739", "entity_type": "Chemical", "pos": [32, 38]}], "task": "NER"}
{"text": "The less sensitive parameter , time in the chamber containing the novel mouse versus time in the chamber containing the novel object , was not rescued by CX1837 or CX1739 treatment .", "entity": [{"entity": "CX1837", "entity_type": "Chemical", "pos": [154, 160]}, {"entity": "CX1739", "entity_type": "Chemical", "pos": [164, 170]}], "task": "NER"}
{"text": "Preliminary data with CX546 , in which beta - cyclodextrin was the vehicle , revealed behavioral effects of the acute intraperitoneal and oral administration of vehicle alone .", "entity": [{"entity": "CX546", "entity_type": "Chemical", "pos": [22, 27]}, {"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [39, 58]}], "task": "NER"}
{"text": "To circumvent the artifacts introduced by the vehicle administration , we employed a novel treatment regimen using pellets of peanut butter for drug delivery .", "entity": [], "task": "NER"}
{"text": "Absence of vehicle treatment effects when CX1837 and CX1739 were given in the peanut butter pellets , to multiple cohorts of BTBR and B6 control mice , confirmed that the pharmacologically - induced improvements in sociability in BTBR were not confounded by the administration procedures .", "entity": [{"entity": "CX1837", "entity_type": "Chemical", "pos": [42, 48]}, {"entity": "CX1739", "entity_type": "Chemical", "pos": [53, 59]}], "task": "NER"}
{"text": "The highest dose of CX1837 improved the cognitive deficit in novel object recognition in BTBR .", "entity": [{"entity": "CX1837", "entity_type": "Chemical", "pos": [20, 26]}], "task": "NER"}
{"text": "No drug effects were detected on the high levels of repetitive self - grooming in BTBR .", "entity": [], "task": "NER"}
{"text": "In open field tests , CX1837 and CX1739 did not induce hyperactivity or sedation in either strain .", "entity": [{"entity": "CX1837", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "CX1739", "entity_type": "Chemical", "pos": [33, 39]}], "task": "NER"}
{"text": "It is interesting to speculate that the ability of CX1837 and CX1739 to restore aspects of sociability in BTBR mice could utilize synaptic mechanisms regulating social cognition , suggesting a potential pharmacological target for interventions to treat symptoms of autism .", "entity": [{"entity": "CX1837", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "CX1739", "entity_type": "Chemical", "pos": [62, 68]}], "task": "NER"}
{"text": "Androgen insensitivity syndrome .", "entity": [{"entity": "Androgen", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Androgen insensitivity syndrome ( AIS ) is a disorder caused by a mutation of the gene encoding the androgen receptor ( AR ; Xq11 - q12 ) .", "entity": [{"entity": "Androgen", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "The prevalence of AIS has been estimated to be one case in every 20 , 000 to 64 , 000 newborn males for the complete syndrome ( CAIS ) , and the prevalence is unknown for the partial syndrome ( PAIS ) .", "entity": [], "task": "NER"}
{"text": "The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea .", "entity": [], "task": "NER"}
{"text": "Various forms of ambiguous genitalia have been observed at birth .", "entity": [], "task": "NER"}
{"text": "The diagnosis is confirmed by determining the exact mutation in the AR gene .", "entity": [], "task": "NER"}
{"text": "PAIS individuals require precise diagnosis as early as possible so that the sex can be assigned , treatment can be recommended , and they can receive proper genetic counseling .", "entity": [], "task": "NER"}
{"text": "After birth , differential diagnosis should be performed using other forms of abnormal sexual differentiation of primary amenorrhea .", "entity": [], "task": "NER"}
{"text": "The treatment of AIS is based on reinforcement sexual identity , gonadectomy planning , and hormone replacement therapy .", "entity": [], "task": "NER"}
{"text": "The prognosis for CAIS is good if the testicular tissue is removed at the appropriate time .", "entity": [], "task": "NER"}
{"text": "For PAIS , the prognosis depends on the ambiguity of the genitalia and physical and psychosocial adjustment to the assigned sex .", "entity": [], "task": "NER"}
{"text": "Deep understanding of the interaction between thienorphine and UDP - glucuronosyltransferase ( UGT ) isoforms .", "entity": [{"entity": "thienorphine", "entity_type": "Chemical", "pos": [46, 58]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "Thienorphine has been demonstrated to be a potent , long - acting partial opioid agonist .", "entity": [{"entity": "Thienorphine", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "It is being developed as a good candidate to treat opioid dependence .", "entity": [], "task": "NER"}
{"text": "The thienorphine ' s glucuronide was detected after thienorphine was incubated with human liver microsomes ( HLMs ) .", "entity": [{"entity": "thienorphine", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "thienorphine", "entity_type": "Chemical", "pos": [52, 64]}], "task": "NER"}
{"text": "Recombinant UGT isoforms screening experiment and enzyme kinetic study showed that UGT1A1 completely contributed to the glucuronidation of thienorphine .", "entity": [{"entity": "thienorphine", "entity_type": "Chemical", "pos": [139, 151]}], "task": "NER"}
{"text": "Among the tested UGT isoforms , UGT1A3 and UGT2B7 were inhibited by thienorphine , with other UGT isoforms negligibly influenced .", "entity": [{"entity": "thienorphine", "entity_type": "Chemical", "pos": [68, 80]}], "task": "NER"}
{"text": "The inhibition type is competitive , and inhibition kinetic parameters ( K ( i ) ) were 1 . 65 and 5 . 27 mu M for UGT1A3 and UGT2B7 , respectively .", "entity": [], "task": "NER"}
{"text": "However , due to low plasma concentration of thienorphine , in vivo drug - drug interaction might not occur .", "entity": [{"entity": "thienorphine", "entity_type": "Chemical", "pos": [45, 57]}], "task": "NER"}
{"text": "Adnexal torsion in children and adolescents : new trends to conservative surgical approach - - our experience and review of literature .", "entity": [], "task": "NER"}
{"text": "The purpose of this study is to discuss the surgical treatment for ovarian torsion in children and adolescents with a focus on the procedures of adnexal conservation surgery and its frequency in the literature of the last 10 years .", "entity": [], "task": "NER"}
{"text": "We retrospectively reviewed the medical charts of 127 operative ovarian lesions including 30 ovarian torsions ( 23 . 6 % ) treated in two pediatric centers over a 10 - year period .", "entity": [], "task": "NER"}
{"text": "Age at presentation , presenting symptoms , diagnostic studies , surgical procedure and pathological findings were analyzed .", "entity": [], "task": "NER"}
{"text": "Mean age was 13 . 7 years .", "entity": [], "task": "NER"}
{"text": "Conservative surgery has been performed in 46 . 7 % of the cases and laparoscopic approach in 40 % .", "entity": [], "task": "NER"}
{"text": "Ovarian torsion occurred in 56 . 7 % on ovaries with functional lesion , in 23 . 3 % on normal adnexa and in 20 % on ovaries with benign neoplasm .", "entity": [], "task": "NER"}
{"text": "The article includes a literature review ( 2000 - 2010 ) and a statistical analysis which shows a slow increase in conservative surgery from 28 to 45 % .", "entity": [], "task": "NER"}
{"text": "Laparoscopic surgery accounts for 23 . 5 % .", "entity": [], "task": "NER"}
{"text": "Literature review shows 40 . 5 % normal adnexa , 33 . 2 % non - neoplastic lesions , 25 . 3 % benign neoplasms and 1 % malignant neoplasms .", "entity": [], "task": "NER"}
{"text": "The surgical treatment of children and adolescents presenting adnexal torsion should be practiced as an emergency and it should be more conservative as possible in order to maximize the future reproductive potential .", "entity": [], "task": "NER"}
{"text": "Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine - induced hypertrophy : potential mechanisms .", "entity": [{"entity": "Silibinin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [73, 86]}], "task": "NER"}
{"text": "Cardiac hypertrophy is the main response of the heart to various extrinsic and intrinsic stimuli , and it is characterized by specific molecular and phenotypic changes .", "entity": [], "task": "NER"}
{"text": "Recent in vitro and in vivo studies indicate the involvement of reactive oxygen species in the hypertrophic response .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "In this study , silibinin , a plant flavonolignan extracted from milk thistle with potent antioxidant activity , was evaluated for its effects in ( a ) preventing hydrogen peroxide ( H2O2 ) - induced cellular damage and ( b ) blocking the phenylephrine - induced hypertrophic response .", "entity": [{"entity": "silibinin", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "flavonolignan", "entity_type": "Chemical", "pos": [36, 49]}, {"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [163, 180]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [183, 187]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [239, 252]}], "task": "NER"}
{"text": "Using the in vitro model of embryonic rat heart - derived H9c2 cells , we showed that silibinin has a rather safe profile as concentrations up to 200 mu M did not affect cell viability .", "entity": [{"entity": "silibinin", "entity_type": "Chemical", "pos": [86, 95]}], "task": "NER"}
{"text": "Pretreatment of H9c2 cells with silibinin resulted in better protection of H9c2 cells under conditions of H2O2 - induced cellular stress compared to untreated cells as indicated by cell viability and DNA fragmentation assays .", "entity": [{"entity": "silibinin", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [106, 110]}], "task": "NER"}
{"text": "Furthermore , silibinin attenuated the phenylephrine - induced hypertrophic response as evidenced by the measurement of cell surface , up - regulation of atrial natriuretic peptide and increase of cellular protein levels .", "entity": [{"entity": "silibinin", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [39, 52]}], "task": "NER"}
{"text": "Moreover , silibinin repressed the phenylephrine - induced phosphorylation of ERK1 / 2 kinases , while it appeared to inhibit the weakly activated by phenylephrine phosphorylation of Akt .", "entity": [{"entity": "silibinin", "entity_type": "Chemical", "pos": [11, 20]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [35, 48]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [150, 163]}], "task": "NER"}
{"text": "Based on our results , silibinin may attenuate the phenylephrine - induced hypertrophic response of H9c2 cells via antioxidant mechanisms involving mainly the inhibition of the intracellular signaling pathways mediated by ERK1 / 2 MAPKs and Akt .", "entity": [{"entity": "silibinin", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [51, 64]}], "task": "NER"}
{"text": "Modafinil effects on cognition and emotion in schizophrenia and its neurochemical modulation in the brain .", "entity": [{"entity": "Modafinil", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping .", "entity": [{"entity": "Modafinil", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer , before its neural functions were understood .", "entity": [], "task": "NER"}
{"text": "Here , we review the effects of modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [32, 41]}], "task": "NER"}
{"text": "We also performed a systematic review on the effects of modafinil on neurotransmitter signalling in different areas of the brain in order to better understand the neuromechanisms of its cognitive and emotional enhancing properties .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [56, 65]}], "task": "NER"}
{"text": "A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions , with pro - mnemonic effects and problem solving improvements .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "Emotional processing also appears to be enhanced by the drug , although to date there are only a limited number of studies .", "entity": [], "task": "NER"}
{"text": "The systematic review on the neurochemical modulation of the modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [61, 70]}], "task": "NER"}
{"text": "Other neurotransmitters were also activated by modafinil in various limbic brain areas , suggesting that the drug acts on these brain regions to influence emotional responses .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "These reviews seek to delineate the neuronal mechanisms by which modafinil affects cognitive and emotional function .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [65, 74]}], "task": "NER"}
{"text": "Current understanding of TRPM7 pharmacology and drug development for stroke .", "entity": [], "task": "NER"}
{"text": "The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials .", "entity": [], "task": "NER"}
{"text": "Currently , a thrombolytic agent called recombinant tissue plasminogen activator ( rt - PA ) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries .", "entity": [], "task": "NER"}
{"text": "Even though its efficacy has been confirmed repeatedly , rt - PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use .", "entity": [], "task": "NER"}
{"text": "A search for alternative mechanisms that may operate dependently or independently with the well - established excitotoxic mechanism has led researchers to the discovery of newly described non - glutamate mechanisms .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [194, 203]}], "task": "NER"}
{"text": "Among the latter , transient receptor potential melastatin 7 ( TRPM7 ) is one of the important nonglutamate mechanisms in stroke , which has been evaluated in both in - vitro and in - vivo .", "entity": [], "task": "NER"}
{"text": "In this review , we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke .", "entity": [], "task": "NER"}
{"text": "Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model .", "entity": [], "task": "NER"}
{"text": "It is well established that both estrogen loss and type II diabetes mellitus ( DMII ) can impair bone metabolism , but whether estrogen loss exacerbates the effects of DMII is unclear .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [127, 135]}], "task": "NER"}
{"text": "Therefore , we determined if ovariectomy ( OVX ) of rats on a long - term high - fat / sugar diet and injection of a low dose of streptozotocin ( DMII ) decreased bone mineral density ( BMD ) more than OVX or DMII alone .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [87, 92]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [129, 143]}], "task": "NER"}
{"text": "Bone insulin signaling is known to support bone metabolism ; therefore , we also tested the hypothesis that OVX DMII rats ( DOVX ) would exhibit greater reductions in the expression of proteins important in insulin signaling , including IRS - 1 , IRS - 2 , and IGF - 1 .", "entity": [], "task": "NER"}
{"text": "As hypothesized , BMD and plasma estrogen levels were decreased more in DOVX rats than in rats following OVX ( NOVX ) or DMII ( DS ) alone .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "IGF - 1 expression was decreased in the liver , kidney , skeletal muscle , and bone of DOVX , DS , and NOVX rats ; however , the decrease was larger and occurred sooner in DOVX rats .", "entity": [], "task": "NER"}
{"text": "While IRS - 1 and IRS - 2 decreased in most groups in all tissues examined , the expression patterns differed in both a group - and tissue - dependent fashion .", "entity": [], "task": "NER"}
{"text": "In conclusion , these data demonstrate that estrogen loss and DMII induced by a high - fat / sugar diet interact to produce osteoporosis and support the hypothesis that the bone loss may be mediated at least in part by concurrent decreases in the insulin signaling proteins in bone .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [93, 98]}], "task": "NER"}
{"text": "Egis - 11150 : a candidate antipsychotic compound with procognitive efficacy in rodents .", "entity": [{"entity": "Egis - 11150", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Classical antipsychotics , e . g . haloperidol , chlorpromazine , are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side - effects .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "chlorpromazine", "entity_type": "Chemical", "pos": [49, 63]}], "task": "NER"}
{"text": "The introduction of atypical antipsychotics such as risperidone , olanzapine and clozapine has obviated this problem , but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "olanzapine", "entity_type": "Chemical", "pos": [66, 76]}, {"entity": "clozapine", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition .", "entity": [], "task": "NER"}
{"text": "Here , we report the preclinical properties of a candidate antipsychotic , Egis - 11150 , that shows marked pro - cognitive efficacy .", "entity": [{"entity": "Egis - 11150", "entity_type": "Chemical", "pos": [75, 87]}], "task": "NER"}
{"text": "Egis - 11150 displayed high affinity for adrenergic alpha ( 1 ) , alpha ( 2c ) , 5 - HT ( 2A ) 5 - HT 7 , moderate affinity for adrenergic alpha ( 2a ) and D 2 receptors .", "entity": [{"entity": "Egis - 11150", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "It was a functional antagonist on all of the above receptors , with the exception of 5 - HT 7 receptors , where it was an inverse agonist .", "entity": [], "task": "NER"}
{"text": "Phencyclidine - induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia .", "entity": [{"entity": "Phencyclidine", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Passive - avoidance learning , novel object recognition and radial maze tests in rats were used to assess pro - cognitive activity , while phencyclidine - induced disruption of prepulse inhibition in mice was examined to test for effects on attention .", "entity": [{"entity": "phencyclidine", "entity_type": "Chemical", "pos": [139, 152]}], "task": "NER"}
{"text": "Egis - 11150 ( 0 . 01 - 0 . 3 mg / kg , ip . ) was effective in all of the preclinical models of schizophrenia examined .", "entity": [{"entity": "Egis - 11150", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Moreover , a robust pro - cognitive profile was apparent .", "entity": [], "task": "NER"}
{"text": "In summary , work in preclinical models indicates that Egis - 11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia .", "entity": [{"entity": "Egis - 11150", "entity_type": "Chemical", "pos": [55, 67]}], "task": "NER"}
{"text": "Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence - accelerated mouse model .", "entity": [{"entity": "Propranolol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Ageing is associated with a deterioration of cognitive performance and with increased risk of neurodegenerative disorders .", "entity": [], "task": "NER"}
{"text": "Hypertension is the most - prevalent modifiable risk factor for cardiovascular morbidity and mortality worldwide , and clinical data suggest that hypertension is a risk factor for Alzheimer ' s disease ( AD ) .", "entity": [], "task": "NER"}
{"text": "In the present study we tested whether propranolol , a beta - receptor antagonist commonly used as antihypertensive drug , could ameliorate the cognitive impairments and increases in AD - related markers shown by the senescence - accelerated mouse prone - 8 ( SAMP8 ) .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [39, 50]}], "task": "NER"}
{"text": "Propranolol administration ( 5 mg / kg for 3 weeks ) to 6 - month - old SAMP8 mice attenuated cognitive memory impairments shown by these mice in the novel object recognition test .", "entity": [{"entity": "Propranolol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In the hippocampus of SAMP8 mice it has been found increases in A beta ( 42 ) levels , the principal constituent of amyloid plaques observed in AD , accompanied by both an increased expression of the cleaving enzyme BACE1 and a decreased expression of the degrading enzyme IDE .", "entity": [], "task": "NER"}
{"text": "All these effects were reversed by propranolol treatment .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [35, 46]}], "task": "NER"}
{"text": "Tau hyperphosphorylation ( PHF - 1 epitope ) shown by SAMP8 mice at this age was also decreased in the hippocampus of propranolol - treated mice , an effect probably related to a decrease in JNK1 expression .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [118, 129]}], "task": "NER"}
{"text": "Interestingly , propranolol also phosphorylated Akt in SAMP8 mice , which was associated with an increase of glycogen synthase kinase - 3 beta phosphorylation , contributing therefore to the reductions in Tau hyperphosphorylation .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [16, 27]}], "task": "NER"}
{"text": "Synaptic pathology in SAMP8 mice , as shown by decreases in synaptophysin and BDNF , was also counteracted by propranolol treatment .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [110, 121]}], "task": "NER"}
{"text": "Overall , propranolol might be beneficial in age - related brain dysfunction and could be an emerging candidate for the treatment of other neurodegenerative diseases .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [10, 21]}], "task": "NER"}
{"text": "Metabolism and disposition of [ 14C ] n - butyl - p - hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application .", "entity": [{"entity": "[ 14C ] n - butyl - p - hydroxybenzoate", "entity_type": "Chemical", "pos": [30, 69]}], "task": "NER"}
{"text": "n - Butyl - p - hydroxybenzoate ( n - butylparaben , BPB ) is an antioxidant used in foods , pharmaceuticals and cosmetics .", "entity": [{"entity": "n - Butyl - p - hydroxybenzoate", "entity_type": "Chemical", "pos": [0, 31]}, {"entity": "n - butylparaben", "entity_type": "Chemical", "pos": [34, 50]}, {"entity": "BPB", "entity_type": "Chemical", "pos": [53, 56]}], "task": "NER"}
{"text": "This study investigated the disposition of ring - labelled [ ( 14 ) C ] BPB in Harlan Sprague Dawley rats , and in rat and human hepatocytes .", "entity": [{"entity": "[ ( 14 ) C ] BPB", "entity_type": "Chemical", "pos": [59, 75]}], "task": "NER"}
{"text": "BPB was rapidly cleared in hepatocytes from rat ( t ( 1 / 2 ) = 3 - 4 min ) and human ( t ( 1 / 2 ) = 20 - 30 min ) .", "entity": [{"entity": "BPB", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The major metabolites detected in rat hepatocytes were hydroxybenzoic acid and in human hepatocytes were hydroxybenzoic acid and hydroxyhippuric acid .", "entity": [{"entity": "hydroxybenzoic acid", "entity_type": "Chemical", "pos": [55, 74]}, {"entity": "hydroxybenzoic acid", "entity_type": "Chemical", "pos": [105, 124]}, {"entity": "hydroxyhippuric acid", "entity_type": "Chemical", "pos": [129, 149]}], "task": "NER"}
{"text": "[ ( 14 ) C ] BPB was administered to male rats orally at 10 , 100 or 1000 mg / kg , intravenously at 10 mg / kg and dermally at 10 and 100 mg / kg ; female rats were administered oral doses at 10 mg / kg .", "entity": [{"entity": "[ ( 14 ) C ] BPB", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Oral doses of BPB were well - absorbed ( > 83 % ) and eliminated chiefly in urine ( 83 - 84 % ) ; <= 1 % of the radioactivity remained in tissues at 24 h or 72 h after dosing .", "entity": [{"entity": "BPB", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "About 4 % and 8 % , respectively , of 100 mg / kg dermal doses were absorbed in 24 h and 72 h , and about 50 % of a 10 mg / kg dose was absorbed in 72 h .", "entity": [], "task": "NER"}
{"text": "Metabolites detected in urine included those previously reported , BPB - glucuronide , BPB - sulfate , hydroxybenzoic acid and hydroxyhippuric acid , but also novel metabolites arising from ring hydroxylation followed by glucuronidation and sulfation .", "entity": [{"entity": "BPB - glucuronide", "entity_type": "Chemical", "pos": [67, 84]}, {"entity": "BPB - sulfate", "entity_type": "Chemical", "pos": [87, 100]}, {"entity": "hydroxybenzoic acid", "entity_type": "Chemical", "pos": [103, 122]}, {"entity": "hydroxyhippuric acid", "entity_type": "Chemical", "pos": [127, 147]}], "task": "NER"}
{"text": "Fertility and endocrine outcome after robot - assisted laparoscopic myomectomy ( RALM ) .", "entity": [], "task": "NER"}
{"text": "Introduction : Laparoscopic myomectomy has recently gained wide acceptance but this procedure remains technically highly demanding and concerns have been raised about the increased blood loss and an higher risk of postoperative uterine rupture of the pregnant uterus .", "entity": [], "task": "NER"}
{"text": "Objective : The aim of the present study is to evaluate the fertility and endocrine outcome in women underwent robot - assisted laparoscopic myomectomy ( RALM ) .", "entity": [], "task": "NER"}
{"text": "Methods : Data from 48 RALM performed in our department between the years 2007 and 2011 have been collected .", "entity": [], "task": "NER"}
{"text": "Conception rate , abortion rate , incidence of feto - maternal morbidity or severe pregnancy and labor - related complications were reported ; FSH and AMH levels and ultrasound valuation of AFC has been made before and 6 months after operation .", "entity": [], "task": "NER"}
{"text": "Number of cesarean sections and vaginal deliveries were described .", "entity": [], "task": "NER"}
{"text": "Results : The average age of the patients was 35 years and median Body Mass Index was 23 kg / m ( 2 ) ( range 18 - 35 kg / m ( 2 ) ) .", "entity": [], "task": "NER"}
{"text": "Seven women ( 13 % ) became pregnant after RALM with eight pregnancies .", "entity": [], "task": "NER"}
{"text": "One pregnancy is actually on going ; there were six deliveries with caesarian section and one spontaneous delivery .", "entity": [], "task": "NER"}
{"text": "No spontaneous abortions .", "entity": [], "task": "NER"}
{"text": "No uterine ruptures occurred .", "entity": [], "task": "NER"}
{"text": "No significant modification of ovarian function was found after myomectomy .", "entity": [], "task": "NER"}
{"text": "Conclusion : RALM seems to have a favorable impact on the reproductive outcome of young patients with no impact on the ovarian function .", "entity": [], "task": "NER"}
{"text": "Sour Cherry Seed Kernel Extract Increases Heme Oxygenase - 1 Expression and Decreases Representation of CD3 + TNF - alpha + and CD3 + IL - 8 + Subpopulations in Peripheral Blood Leukocyte Cultures from Type 2 Diabetes Patients .", "entity": [{"entity": "Heme", "entity_type": "Chemical", "pos": [42, 46]}], "task": "NER"}
{"text": "The present study evaluates a hypothesis that sour cherry ( Prunus cerasus ) seed extracts ( SCE ) modulate CD3 + T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases .", "entity": [], "task": "NER"}
{"text": "Peripheral blood mononuclear cells ( PBMC ) from 12 type 2 diabetes ( T2DM ) patients and eight healthy control subjects were cultured 24 h with 100 ng / ml lipopolysaccharide ( LPS ) to increase inflammatory signaling and co - incubated with 0 . 5 - 100 micro g / ml SCE .", "entity": [], "task": "NER"}
{"text": "Cultures were evaluated by two - color flow cytometry for percent representation of CD3 + IL8 + and CD3 + TNF - alpha + cells which express interleukin - 8 ( IL - 8 ) , and tumor necrosis factor - alpha , ( TNF - alpha + ) respectively , and by enzyme - linked immunoassay for lymphocyte - associated heme oxygenase - 1 ( HO - 1 , known to be induced by SCE ) .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [301, 305]}], "task": "NER"}
{"text": "SCE dosage ranges of 0 . 5 - 100 micro g / ml in cell cultures significantly suppressed LPS - increased CD3 + TNF - alpha + and CD3 + IL8 + representation from all participants ( p < 0 . 05 ) , with greater pharmacological effect noted in suppression of CD3 + TNF - alpha + noted in cells from T2DM patients versus healthy control subjects .", "entity": [], "task": "NER"}
{"text": "These effects correlated with increased HO - 1 expression in SCE - treated PBMC from all subjects ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Since TNF - alpha and IL - 8 are diagnostic / prognostic biomarkers for many inflammatory syndromes , the capacity of SCE to down - regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases .", "entity": [], "task": "NER"}
{"text": "Combined effects of treatment with vitamin C , vitamin E and selenium on the skin of diabetic rats .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [47, 56]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "The aim of this study was to investigate the effects of vitamin C , vitamin E and selenium ( Se ) on the skin tissue of streptozotocin - induced diabetic rats .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "Se", "entity_type": "Chemical", "pos": [93, 95]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [120, 134]}], "task": "NER"}
{"text": "Swiss albino rats were divided into four groups : control , control + antioxidants , diabetic , diabetic + antioxidants groups .", "entity": [], "task": "NER"}
{"text": "Diabetes was induced by intraperitoneal injection of 65 mg / kg streptozotocin .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [64, 78]}], "task": "NER"}
{"text": "Vitamin C ( 250 mg / kg ) , vitamin E ( 250 mg / kg ) and Se ( 0 . 2 mg / kg ) were given by gavage technique to rats of one diabetic and one control group for 30 days .", "entity": [{"entity": "Vitamin C", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "Se", "entity_type": "Chemical", "pos": [58, 60]}], "task": "NER"}
{"text": "In the diabetic group , the levels of serum urea and creatinine , skin lipid peroxidation and nonenzymatic glycosylation levels increased , but skin glutathione levels decreased .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [149, 160]}], "task": "NER"}
{"text": "Treatment with vitamin C , vitamin E and Se reversed these effects .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "Se", "entity_type": "Chemical", "pos": [41, 43]}], "task": "NER"}
{"text": "The present study showed that vitamin C , vitamin E and Se exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin - induced diabetes .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [30, 39]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "Se", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [138, 152]}], "task": "NER"}
{"text": "Dopamine D 2 - agonist rotigotine effects on cortical excitability and central cholinergic transmission in Alzheimer ' s disease patients .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "rotigotine", "entity_type": "Chemical", "pos": [23, 33]}], "task": "NER"}
{"text": "Dopamine is a neurotransmitter involved in several brain functions ranging from emotions control , movement organization to memory formation .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "It is also involved in the regulation of mechanisms of synaptic plasticity .", "entity": [], "task": "NER"}
{"text": "However , its role in Alzheimer ' s disease ( AD ) pathogenesis is still puzzling .", "entity": [], "task": "NER"}
{"text": "Several recent line of research instead indicates a clear role for dopamine in both amyloid beta formation as well as in cognitive decline progression .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "In particular it has been shown that dopamine D 2 - like receptors ( namely D 3 and D 2 ) could be mostly responsible for dopamine dysfunction in AD .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [122, 130]}], "task": "NER"}
{"text": "Here we aimed to study the effects of the dopamine agonist Rotigotine on cortical excitability and on central cholinergic transmission in cases of AD .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "Rotigotine", "entity_type": "Chemical", "pos": [59, 69]}], "task": "NER"}
{"text": "Rotigotine is a dopamine agonist with a pharmacological profile with high affinity for D 3 and D 2 receptors .", "entity": [{"entity": "Rotigotine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [16, 24]}], "task": "NER"}
{"text": "We used paired pulse protocols assessing short intracortical inhibition ( SICI ) and intracortical facilitation ( ICF ) to asses cortical excitability over the primary motor cortex and Short Latency Afferent Inhibition ( SLAI ) protocols , to verify the effects of the drug on central cholinergic transmission in a group of AD patients compared to age - matched controls .", "entity": [], "task": "NER"}
{"text": "We observed that rotigotine induces unexpected changes in both cortical excitability ( increased ) and central cholinergic transmission ( restored ) of AD patients .", "entity": [{"entity": "rotigotine", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "These unexpected effects might depend on the dopamine D 2 - like receptors dysfunction previously described in AD brains .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "The current findings could indicate that future strategies aimed to ameliorate symptoms of the related AD cognitive decline could also involve some dopaminergic drugs .", "entity": [], "task": "NER"}
{"text": "Absorption of TAK - 491 , a new angiotensin II receptor antagonist , in animals .", "entity": [{"entity": "TAK - 491", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "angiotensin II", "entity_type": "Chemical", "pos": [32, 46]}], "task": "NER"}
{"text": "The absorption process in animals of TAK - 491 , designed as ester - based prodrug with medoxomil moiety , was evaluated .", "entity": [{"entity": "TAK - 491", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "ester", "entity_type": "Chemical", "pos": [61, 66]}, {"entity": "medoxomil", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "In the plasma of rats and dogs , TAK - 536 , the pharmacologically active metabolite , was present as the main component with hardly detectable concentrations of TAK - 491 after oral administration of TAK - 491 .", "entity": [{"entity": "TAK - 536", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [162, 171]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [201, 210]}], "task": "NER"}
{"text": "In the rat portal plasma , TAK - 536 was also present as the main component with hardly detectable concentrations of TAK - 491 after jejunal loop injection of TAK - 491 , suggesting TAK - 491 was absorbed from small intestine and hydrolyzed almost completely during absorption .", "entity": [{"entity": "TAK - 536", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [117, 126]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [159, 168]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [182, 191]}], "task": "NER"}
{"text": "Caco - 2 study indicated the permeability of TAK - 491 was improved by prodrug modification and the compound could be mainly transferred as TAK - 491 .", "entity": [{"entity": "TAK - 491", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [140, 149]}], "task": "NER"}
{"text": "This is well consistent with the facts that the AUC and T ( max ) of TAK - 536 after oral administration of TAK - 491 were higher and shorter than those after oral administration of TAK - 536 in dogs Hydrolysis of TAK - 491 is observed not only by the intestinal and hepatic S9 fraction , but also by plasma and human serum albumin .", "entity": [{"entity": "TAK - 536", "entity_type": "Chemical", "pos": [69, 78]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "TAK - 536", "entity_type": "Chemical", "pos": [182, 191]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [214, 223]}], "task": "NER"}
{"text": "However , medoxomil alcohol wasn ' t detected during the hydrolysis of TAK - 491 .", "entity": [{"entity": "medoxomil alcohol", "entity_type": "Chemical", "pos": [10, 27]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "These metabolic features of TAK - 491 were similar to olmesartan medoxomil , suggesting the hydrolytic pathway and enzymes for TAK - 491 when catalyzing to TAK - 536 would be the same as olmesartan medoxomil .", "entity": [{"entity": "TAK - 491", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "olmesartan medoxomil", "entity_type": "Chemical", "pos": [54, 74]}, {"entity": "TAK - 491", "entity_type": "Chemical", "pos": [127, 136]}, {"entity": "TAK - 536", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "olmesartan medoxomil", "entity_type": "Chemical", "pos": [187, 207]}], "task": "NER"}
{"text": "Synthesis , characterization , screening and docking analysis of 4 - anilinoquinazoline derivatives as tyrosine kinase inhibitors .", "entity": [{"entity": "4 - anilinoquinazoline", "entity_type": "Chemical", "pos": [65, 87]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "We report here the design and synthesis of a series of 4 - anilinoquinazoline derivatives , of which 7 compounds were crystallographically characterized , as epidermal growth factor receptor ( EGFR ) inhibitors by modifications on the aniline ring or at the 6 - alkoxy site of the 6 , 7 - dimethoxy - 4 - anilinoquinazoline pharmacophore .", "entity": [{"entity": "4 - anilinoquinazoline", "entity_type": "Chemical", "pos": [55, 77]}, {"entity": "aniline", "entity_type": "Chemical", "pos": [235, 242]}, {"entity": "6 - alkoxy", "entity_type": "Chemical", "pos": [258, 268]}, {"entity": "6 , 7 - dimethoxy - 4 - anilinoquinazoline", "entity_type": "Chemical", "pos": [281, 323]}], "task": "NER"}
{"text": "The relative inhibition efficiency on EGFR of all as - prepared compounds were measured and ordered , and the IC50 values of nine highly active compounds were determined by ELISA .", "entity": [], "task": "NER"}
{"text": "Docking studies indicated that all 4 - anilinoquinazoline derivatives could be inserted into the ATP - binding pocket of the EGFR via indirect docking , and that the modifications at the 3 ' - position of the anilino group and 6 - alkoxy site of the quinazoline ring have little interference with the formation of the two essential H - bonds between the N3 of the quinazoline ring and Thr766 through a water molecule , and the N1 of the quinazoline ring and N - H of Met769 .", "entity": [{"entity": "4 - anilinoquinazoline", "entity_type": "Chemical", "pos": [35, 57]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [97, 100]}, {"entity": "anilino", "entity_type": "Chemical", "pos": [209, 216]}, {"entity": "6 - alkoxy", "entity_type": "Chemical", "pos": [227, 237]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [250, 261]}, {"entity": "H", "entity_type": "Chemical", "pos": [332, 333]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [364, 375]}, {"entity": "Thr766", "entity_type": "Chemical", "pos": [385, 391]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [437, 448]}, {"entity": "N - H", "entity_type": "Chemical", "pos": [458, 463]}, {"entity": "Met769", "entity_type": "Chemical", "pos": [467, 473]}], "task": "NER"}
{"text": "The displacing of the phenyl at 4 - position with pyridinyl dramatically reduces the activity of the quinazoline pharmacophore , the resulting derivative ( 10 ) being the least active compound .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "pyridinyl", "entity_type": "Chemical", "pos": [50, 59]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [101, 112]}], "task": "NER"}
{"text": "The docking results also showed that the formation of new H - bonds between the N - H of the ethylenediamine group linked to the 6 - alkoxy site and Asp776 / Cys773 in the binding pocket of EGFR makes compounds 19 ( IC50 = 12 . 1 +/- 1 . 6 nM ) and 20 ( IC50 = 13 . 6 +/- 0 . 8 nM ) the most potent EGFR inhibitors in this class and worthy of further modification to obtain more potent anticancer compounds .", "entity": [{"entity": "H", "entity_type": "Chemical", "pos": [58, 59]}, {"entity": "N - H", "entity_type": "Chemical", "pos": [80, 85]}, {"entity": "ethylenediamine", "entity_type": "Chemical", "pos": [93, 108]}, {"entity": "6 - alkoxy", "entity_type": "Chemical", "pos": [129, 139]}, {"entity": "Asp776", "entity_type": "Chemical", "pos": [149, 155]}, {"entity": "Cys773", "entity_type": "Chemical", "pos": [158, 164]}], "task": "NER"}
{"text": "Small molecule modulation of nuclear receptor conformational dynamics : implications for function and drug discovery .", "entity": [], "task": "NER"}
{"text": "Nuclear receptors are targets for a wide range of ligands , both natural and synthetic , that regulate their activity and provide a means to pharmacologically modulate the receptor .", "entity": [], "task": "NER"}
{"text": "Recent emphasis in the nuclear receptor field has focused on selective nuclear receptor modulators , which can display graded transcriptional responses and tissue selective pharmacological responses that deviate from the prototypical agonist or antagonist .", "entity": [], "task": "NER"}
{"text": "Understanding the molecular mechanism of action of these selective modulators will provide significant insight toward the development of the next generation of modulators .", "entity": [], "task": "NER"}
{"text": "Although most nuclear receptor structural studies have primarily focused on obtaining ligand - receptor cocrystal structures , recent studies implicate an important role for protein dynamics in the mechanism of action of nuclear receptor ligands .", "entity": [], "task": "NER"}
{"text": "Here we review nuclear receptor studies reporting how ligands modulate the conformational dynamics of the nuclear receptor ligand - binding domain ( LBD ) .", "entity": [], "task": "NER"}
{"text": "A particular emphasis is placed on protein NMR and hydrogen / deuterium exchange ( HDX ) techniques and how they provide complementary information that , when combined with crystallography , provide detailed insight into the function of nuclear receptors .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "deuterium", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "Gelucire 44 / 14 based immediate release formulations for poorly water - soluble drugs .", "entity": [], "task": "NER"}
{"text": "Here , we aim to evaluate Gelucire 44 / 14 as non - ionic surface - active excipient to produce immediate - release solid dosage forms for poorly water - soluble drugs .", "entity": [], "task": "NER"}
{"text": "Gelucires are polyethylene glycol ( PEG ) glycerides composed of mono - , di - and triglycerides and mono - and diesters of PEG .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [14, 33]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "mono - , di - and triglycerides", "entity_type": "Chemical", "pos": [65, 96]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "They are inert semi - solid waxy amphiphilic excipients with surface - active properties that spontaneously form a fine dispersion or emulsion upon contact with water .", "entity": [], "task": "NER"}
{"text": "Monolithic Gelucire 44 / 14 structures are prone to prolonged erosion times , thereby slowing down drug dissolution .", "entity": [], "task": "NER"}
{"text": "To overcome this issue , we combine either granulation or spray - drying , followed by compression into tablets , with an optimized composition of disintegration promoting agents .", "entity": [], "task": "NER"}
{"text": "This formulation strategy allows obtaining nearly 100 % drug release within 10 min dissolution time .", "entity": [], "task": "NER"}
{"text": "Modeling the structure and proton transfer pathways of the mutant His - 107 - Tyr of human carbonic anhydrase II .", "entity": [{"entity": "His", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "We present molecular modeling of the structure and possible proton transfer pathways from the surface of the protein to the zinc - bound water molecule in the active site of the mutant His - 107 - Tyr of human carbonic anhydrase II ( HCAII ) .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [124, 128]}, {"entity": "His", "entity_type": "Chemical", "pos": [185, 188]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [197, 200]}], "task": "NER"}
{"text": "No high - resolution structure or crystal structure is available till now for this particular mutant due to its lack of stability at physiological temperature .", "entity": [], "task": "NER"}
{"text": "Our analysis utilizes as starting point a series of structures derived from high - resolution crystal structure of the wild type protein .", "entity": [], "task": "NER"}
{"text": "While many of the structures investigated do not reveal a complete path between the zinc bound water and His - 64 , several others do indicate the presence of a transient connection even when His - 64 is present in its outward conformation .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [84, 88]}, {"entity": "His", "entity_type": "Chemical", "pos": [105, 108]}, {"entity": "His", "entity_type": "Chemical", "pos": [192, 195]}], "task": "NER"}
{"text": "Mutation at the residue 107 also reveals the formation of a new path into the active site .", "entity": [], "task": "NER"}
{"text": "Competing contributions from His - 64 sidechain rotation from its outward conformation are also evaluated in terms of optimal path analysis .", "entity": [{"entity": "His", "entity_type": "Chemical", "pos": [29, 32]}], "task": "NER"}
{"text": "No indication of a lower catalytic efficiency of the mutant is evident from our results under the condition of thermal stability of the mutant .", "entity": [], "task": "NER"}
{"text": "Oxysterol generation and liver X receptor - dependent reverse cholesterol transport : not all roads lead to Rome .", "entity": [{"entity": "Oxysterol", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [62, 73]}], "task": "NER"}
{"text": "Cell cholesterol metabolism is a tightly regulated process , dependent in part on activation of nuclear liver X receptors ( LXRs ) to increase expression of genes mediating removal of excess cholesterol from cells in the reverse cholesterol transport pathway .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [5, 16]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [191, 202]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [229, 240]}], "task": "NER"}
{"text": "LXRs are thought to be activated predominantly by oxysterols generated enzymatically from cholesterol in different cell organelles .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [90, 101]}], "task": "NER"}
{"text": "Defects resulting in slowed release of cholesterol from late endosomes and lysosomes or reduction in sterol - 27 - hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR - dependent gene activation .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [101, 107]}, {"entity": "oxysterol", "entity_type": "Chemical", "pos": [163, 172]}], "task": "NER"}
{"text": "This block does not appear to be compensated by oxysterol production in other cell compartments .", "entity": [{"entity": "oxysterol", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "The purpose of this review is to summarize current knowledge about oxysterol - dependent activation by LXR of genes involved in reverse cholesterol transport , and what these defects of cell cholesterol homeostasis can teach us about the critical pathways of oxysterol generation for expression of LXR - dependent genes .", "entity": [{"entity": "oxysterol", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [136, 147]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [191, 202]}, {"entity": "oxysterol", "entity_type": "Chemical", "pos": [259, 268]}], "task": "NER"}
{"text": "The mGlu 5 positive allosteric modulator LSN2463359 differentially modulates motor , instrumental and cognitive effects of NMDA receptor antagonists in the rat .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [123, 127]}], "task": "NER"}
{"text": "Metabotropic glutamate 5 ( mGlu 5 ) receptors are known to functionally interact with N - methyl - d - aspartate ( NMDA ) receptors at both neuronal and behavioural levels , in a manner that may be of relevance to the treatment of schizophrenia .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "N - methyl - d - aspartate", "entity_type": "Chemical", "pos": [86, 112]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [115, 119]}], "task": "NER"}
{"text": "We have previously described a novel mGlu 5 positive allosteric modulator ( PAM ) , LSN2463359 and provided evidence of its ability to attenuate aspects of the behavioural response to administration of the competitive NMDA receptor antagonist , SDZ 220 , 581 .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [218, 222]}, {"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [245, 258]}], "task": "NER"}
{"text": "In addition , LSN2463359 was found to selectively attenuate reversal learning deficits observed in the neurodevelopmental MAM E17 model but not in the acute phencyclidine ( PCP ) model .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "phencyclidine", "entity_type": "Chemical", "pos": [157, 170]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [173, 176]}], "task": "NER"}
{"text": "In the present study , the interactions between this mGlu 5 PAM and the NMDA receptor were explored further by assessing the effects of LSN2463359 against some of the motor , instrumental and cognitive effects induced by the non - competitive NMDA receptor antagonists PCP and MK - 801 , the competitive NMDA receptor antagonist SDZ 220 , 581 and the GluN2B selective NMDA receptor antagonist , Ro 63 - 1908 .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [72, 76]}, {"entity": "LSN2463359", "entity_type": "Chemical", "pos": [136, 146]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [243, 247]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [269, 272]}, {"entity": "MK - 801", "entity_type": "Chemical", "pos": [277, 285]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [304, 308]}, {"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [329, 342]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [368, 372]}, {"entity": "Ro 63 - 1908", "entity_type": "Chemical", "pos": [395, 407]}], "task": "NER"}
{"text": "LSN2463359 had either no or minor impact on locomotor hyperactivity induced by either PCP or SDZ 220 , 581 .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [93, 106]}], "task": "NER"}
{"text": "However , in rats lever pressing for food rewards under a variable interval 30s schedule of instrumental responding , the drug clearly attenuated not only the suppression of response rate induced by SDZ 220 , 581 but also the stimulation of response rate induced by Ro 63 - 1908 .", "entity": [{"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [199, 212]}, {"entity": "Ro 63 - 1908", "entity_type": "Chemical", "pos": [266, 278]}], "task": "NER"}
{"text": "In contrast , LSN2463359 failed to alter both of the instrumental effects induced by the open channel blockers PCP and MK - 801 .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [111, 114]}, {"entity": "MK - 801", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "In addition , although PCP and SDZ 220 , 581 induced similar deficits in a discrimination and reversal learning task , LSN2463359 was again only able to reverse the deficit induced by SDZ 220 , 581 .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [31, 44]}, {"entity": "LSN2463359", "entity_type": "Chemical", "pos": [119, 129]}, {"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [184, 197]}], "task": "NER"}
{"text": "The results indicate that the interactions between mGlu 5 and NMDA receptors are dependent on both the mechanism of the blockade of the receptor and the behavioural domain under investigation .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "Our work has implications for the preclinical use of NMDA receptor antagonists in the prediction of potential therapeutic efficacy in the search for novel treatments for schizophrenia .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [53, 57]}], "task": "NER"}
{"text": "Positive allosteric modulators of the mGlu 5 receptor certainly question the predictive validity of such approaches .", "entity": [], "task": "NER"}
{"text": "In vitro characterisation of the novel positive allosteric modulators of the mGlu 5 receptor , LSN2463359 and LSN2814617 , and their effects on sleep architecture and operant responding in the rat .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [95, 105]}, {"entity": "LSN2814617", "entity_type": "Chemical", "pos": [110, 120]}], "task": "NER"}
{"text": "The demonstrated functional interaction of metabotropic glutamate 5 ( mGlu 5 ) receptors with N - methyl - d - aspartate ( NMDA ) receptors has prompted speculation that their activation may offer a potential treatment for aspects of schizophrenia .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "N - methyl - d - aspartate", "entity_type": "Chemical", "pos": [94, 120]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [123, 127]}], "task": "NER"}
{"text": "Development of selective mGlu 5 agonists has been difficult , but several different positive allosteric modulator ( PAM ) molecules have now been identified .", "entity": [], "task": "NER"}
{"text": "This study describes two novel mGlu 5 PAMs , LSN2463359 ( N - ( 1 - methylethyl ) - 5 - ( pyridin - 4 - ylethynyl ) pyridine - 2 - carboxamide ) and LSN2814617 [ ( 7S ) - 3 - tert - butyl - 7 - [ 3 - ( 4 - fluorophenyl ) - 1 , 2 , 4 - oxadiazol - 5 - yl ] - 5 , 6 , 7 , 8 - tetrahydro [ 1 , 2 , 4 ] triazolo [ 4 , 3 - A ] pyridine ] , which are useful tools for this field of research .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "N - ( 1 - methylethyl ) - 5 - ( pyridin - 4 - ylethynyl ) pyridine - 2 - carboxamide", "entity_type": "Chemical", "pos": [58, 142]}, {"entity": "LSN2814617", "entity_type": "Chemical", "pos": [149, 159]}, {"entity": "( 7S ) - 3 - tert - butyl - 7 - [ 3 - ( 4 - fluorophenyl ) - 1 , 2 , 4 - oxadiazol - 5 - yl ] - 5 , 6 , 7 , 8 - tetrahydro [ 1 , 2 , 4 ] triazolo [ 4 , 3 - A ] pyridine", "entity_type": "Chemical", "pos": [162, 330]}], "task": "NER"}
{"text": "Both compounds are potent and selective potentiators of human and rat mGlu 5 receptors in vitro , displaying curve shift ratios of two to three fold in the concentration - response relationship to glutamate or the glutamate receptor agonist , DHPG , with no detectable intrinsic agonist properties .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [197, 206]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [214, 223]}, {"entity": "DHPG", "entity_type": "Chemical", "pos": [243, 247]}], "task": "NER"}
{"text": "Both compounds displaced the mGlu 5 receptor antagonist radioligand , [ (3) H ] MPEP in vitro and , following oral administration reached brain concentrations sufficient to occupy hippocampal mGlu 5 receptors as measured in vivo by dose - dependent displacement from the hippocampus of intravenously administered MPEPy .", "entity": [{"entity": "[ (3) H ] MPEP", "entity_type": "Chemical", "pos": [70, 84]}, {"entity": "MPEPy", "entity_type": "Chemical", "pos": [313, 318]}], "task": "NER"}
{"text": "In vivo EEG studies demonstrated that these mGlu 5 PAMs have marked wake - promoting properties but little in the way of rebound hypersomnolence .", "entity": [], "task": "NER"}
{"text": "In contrast , the previously described mGlu 5 PAMs CDPPB and ADX47273 showed relatively poor evidence of in vivo target engagement in either receptor occupancy assays or EEG disturbance .", "entity": [{"entity": "CDPPB", "entity_type": "Chemical", "pos": [51, 56]}, {"entity": "ADX47273", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "Wake - promoting doses of LSN2463359 and LSN2814617 attenuated deficits in performance induced by the competitive NMDA receptor antagonist SDZ 220 , 581 in two tests of operant behaviour : the variable interval 30 s task and the DMTP task .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [26, 36]}, {"entity": "LSN2814617", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [114, 118]}, {"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [139, 152]}], "task": "NER"}
{"text": "These effects were lost if the dose of either compound extended into the range which disrupted performance in the baseline DMTP task .", "entity": [], "task": "NER"}
{"text": "However , the improvements in response accuracy induced by the mGlu 5 potentiators in SDZ 220 , 581 - treated rats were not delay - dependent and , therefore , perhaps more likely reflected optimization of general arousal than specific beneficial effects on discrete cognitive processes .", "entity": [{"entity": "SDZ 220 , 581", "entity_type": "Chemical", "pos": [86, 99]}], "task": "NER"}
{"text": "The systematic profiling of LSN2463359 and LSN2814617 alongside other previously described molecules will help determine more precisely how mGlu 5 potentiator pharmacology might provide therapeutic benefit .", "entity": [{"entity": "LSN2463359", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "LSN2814617", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "The development and application of small molecule modulators of SF3b as therapeutic agents for cancer .", "entity": [], "task": "NER"}
{"text": "The identification of potent spliceosome modulators that demonstrate antitumor activity indicates that this complex may be a target for drug development .", "entity": [], "task": "NER"}
{"text": "Several natural products have been demonstrated to bind to the SF3b1 subunit of this macromolecule and these agents modulate alternative RNA splicing .", "entity": [], "task": "NER"}
{"text": "In this article we describe their biological properties , discuss the validity of the spliceosome as a therapeutic target , and propose that alteration of alternative splicing represents a viable approach for inducing tumor - selective cytotoxicity .", "entity": [], "task": "NER"}
{"text": "Size of TiO ( 2 ) nanoparticles influences their phototoxicity : an in vitro investigation .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [8, 17]}], "task": "NER"}
{"text": "To uncover the size influence of TiO ( 2 ) nanoparticles on their potential toxicity , the cytotoxicity of different - sized TiO ( 2 ) nanoparticles with and without photoactivation was tested .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [125, 134]}], "task": "NER"}
{"text": "It was demonstrated that without photoactivation , TiO ( 2 ) nanoparticles were inert up to 100 mu g / ml .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "On the contrary , with photoactivation , the toxicity of TiO ( 2 ) nanoparticles significantly increased , which correlated well with the specific surface area of the particles .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "Our results also suggest that the generation of hydroxyl radicals and reactive oxygen species ( ROS ) - mediated damage to the surface - adsorbed biomolecules could be the two major reasons for the cytotoxicity of TiO ( 2 ) nanoparticles after photoactivation .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [79, 85]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [214, 223]}], "task": "NER"}
{"text": "Higher ROS generation from smaller particles was detected under both biotic and abiotic conditions .", "entity": [], "task": "NER"}
{"text": "Smaller particles could adsorb more proteins , which was confirmed by thermogravimetric analysis .", "entity": [], "task": "NER"}
{"text": "To further investigate the influence of the generation of hydroxyl radicals and adsorption of protein , poly ( ethylene - alt - maleic anhydride ) ( PEMA ) and chitosan were used to coat TiO ( 2 ) nanoparticles .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [58, 66]}, {"entity": "poly ( ethylene - alt - maleic anhydride )", "entity_type": "Chemical", "pos": [104, 146]}, {"entity": "PEMA", "entity_type": "Chemical", "pos": [149, 153]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [187, 196]}], "task": "NER"}
{"text": "The results confirmed that surface coating of TiO ( 2 ) nanoparticles could reduce such toxicity after photoactivation , by hindering adsorption of biomolecules and generation of hydroxyl radical ( . OH ) during photoactivation .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [46, 55]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [179, 187]}, {"entity": ". OH", "entity_type": "Chemical", "pos": [198, 202]}], "task": "NER"}
{"text": "Fibroblast growth factor 23 inhibits extrarenal synthesis of 1 , 25 - dihydroxyvitamin D in human monocytes .", "entity": [{"entity": "1 , 25 - dihydroxyvitamin D", "entity_type": "Chemical", "pos": [61, 88]}], "task": "NER"}
{"text": "Vitamin D is a potent stimulator of monocyte innate immunity , and this effect is mediated via intracrine conversion of 25 - hydroxyvitamin D ( 25OHD ) to 1 , 25 - dihydroxyvitamin D ( 1 , 25 ( OH ) ( 2 ) D ) .", "entity": [{"entity": "Vitamin D", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [120, 141]}, {"entity": "25OHD", "entity_type": "Chemical", "pos": [144, 149]}, {"entity": "1 , 25 - dihydroxyvitamin D", "entity_type": "Chemical", "pos": [155, 182]}, {"entity": "1 , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [185, 206]}], "task": "NER"}
{"text": "In the kidney , synthesis of 1 , 25 ( OH ) ( 2 ) D is suppressed by fibroblast growth factor 23 ( FGF23 ) , via transcriptional suppression of the vitamin D - activating enzyme 1 alpha - hydroxylase ( CYP27B1 ) .", "entity": [{"entity": "1 , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [29, 50]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [147, 156]}], "task": "NER"}
{"text": "We hypothesized that FGF23 also suppresses CYP27B1 in monocytes , with concomitant effects on intracrine responses to 1 , 25 ( OH ) ( 2 ) D .", "entity": [{"entity": "1 , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [118, 139]}], "task": "NER"}
{"text": "Healthy donor peripheral blood mononuclear cell monocytes ( PBMCm ) and peritoneal dialysate monocyte ( PDm ) effluent from kidney disease patients were assessed at baseline to confirm the presence of mRNA for FGF23 receptors ( FGFRs ) , with Klotho and FGFR1 being more strongly expressed than FGFR2 / 3 / 4 in both cell types .", "entity": [], "task": "NER"}
{"text": "Immunohistochemistry showed coexpression of Klotho and FGFR1 in PBMCm and PDm , with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm .", "entity": [], "task": "NER"}
{"text": "Treatment with FGF23 activated mitogen - activated protein kinase ( MAPK ) and protein kinase B ( Akt ) pathways in PBMCm , demonstrating functional FGFR signaling in these cells .", "entity": [], "task": "NER"}
{"text": "FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1 .", "entity": [], "task": "NER"}
{"text": "In PBMCm this was associated with downregulation of 25OHD to 1 , 25 ( OH ) ( 2 ) D metabolism , and concomitant suppression of intracrine induced 24 - hydroxylase ( CYP24A1 ) and antibacterial cathelicidin ( LL37 ) .", "entity": [{"entity": "25OHD", "entity_type": "Chemical", "pos": [52, 57]}, {"entity": "1 , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [61, 82]}], "task": "NER"}
{"text": "FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin - 15 to stimulate synthesis of 1 , 25 ( OH ) ( 2 ) D .", "entity": [{"entity": "1 , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [122, 143]}], "task": "NER"}
{"text": "These data indicate that FGF23 can inhibit extra - renal expression of CYP27B1 and subsequent intracrine responses to 1 , 25 ( OH ) ( 2 ) D in two different human monocyte models .", "entity": [{"entity": "1 , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [118, 139]}], "task": "NER"}
{"text": "Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this , in turn , may be a key determinant of infection in patients with chronic kidney disease ( CKD ) .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [95, 104]}], "task": "NER"}
{"text": "A crown - ether loop - derivatized oligothiophene doubly attached on gold surface as cation - binding switchable molecular junction .", "entity": [{"entity": "crown - ether", "entity_type": "Chemical", "pos": [2, 15]}, {"entity": "oligothiophene", "entity_type": "Chemical", "pos": [35, 49]}], "task": "NER"}
{"text": "A crown - ether dithiol quaterthiophene is synthesized and immobilized on gold surface by double covalent fixation .", "entity": [{"entity": "crown - ether dithiol quaterthiophene", "entity_type": "Chemical", "pos": [2, 39]}], "task": "NER"}
{"text": "UV - vis spectroscopy and cyclic voltammetry show that the corresponding dithioester precursor can complex Pb ( 2 + ) in solution and that this property is maintained for monolayers of the dithiol on gold .", "entity": [{"entity": "dithioester", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "dithiol", "entity_type": "Chemical", "pos": [189, 196]}], "task": "NER"}
{"text": "Current - voltage measurements by eutectic GaIn drop contact on the monolayer show a significant increase ( up to 1 . 6 x 10 ( 3 ) times ) of the current at low bias after Pb ( 2 + ) complexation .", "entity": [{"entity": "GaIn", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [172, 182]}], "task": "NER"}
{"text": "Microindentation for in vivo measurement of bone tissue material properties in atypical femoral fracture patients and controls .", "entity": [], "task": "NER"}
{"text": "Atypical femoral fractures ( AFF ) associated with long - term bisphosphonates ( LTB ) are a growing concern .", "entity": [{"entity": "bisphosphonates", "entity_type": "Chemical", "pos": [63, 78]}], "task": "NER"}
{"text": "Their etiology is unknown , but bone material properties might be deteriorated .", "entity": [], "task": "NER"}
{"text": "In an AFF series , we analyzed the bone material properties by microindentation .", "entity": [], "task": "NER"}
{"text": "Four groups of patients were included : 6 AFF , 38 typical osteoporotic fractures , 6 LTB , and 20 controls without fracture .", "entity": [], "task": "NER"}
{"text": "Neither typical osteoporotic fractures nor controls have received any antiosteoporotic medication .", "entity": [], "task": "NER"}
{"text": "A general laboratory workup , bone densitometry by dual - energy X - ray absorptiometry ( DXA ) , and microindentation testing at the tibia were done in all patients .", "entity": [], "task": "NER"}
{"text": "Total indentation distance ( Total ID ) , indentation distance increase ( IDI ) , and creep indentation distance ( Creep ID ) were measured ( microns ) .", "entity": [], "task": "NER"}
{"text": "Age - adjusted analysis of covariance ( ANCOVA ) was used for comparisons .", "entity": [], "task": "NER"}
{"text": "Controls were significantly younger than fracture groups .", "entity": [], "task": "NER"}
{"text": "Bisphosphonate exposure was on average 5 . 5 years ( range 5 to 12 years ) for the AFF and 5 . 4 years ( range 5 to 8 years ) for the LTB groups .", "entity": [{"entity": "Bisphosphonate", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Total ID ( microns ) showed better material properties ( lower Total ID ) for controls 36 ( +/- 6 ; mean +/- SD ) than for AFF 46 ( +/- 4 ) and for typical femoral fractures 47 ( +/- 13 ) , respectively .", "entity": [], "task": "NER"}
{"text": "Patients on LTB showed values between controls and fractures , 38 ( +/- 4 ) , although not significantly different from any of the other three groups .", "entity": [], "task": "NER"}
{"text": "IDI values showed a similar pattern 13 ( +/- 2 ) , 16 ( +/- 6 ) , 19 ( +/- 3 ) , and 18 ( +/- 5 ) .", "entity": [], "task": "NER"}
{"text": "After adjusting by age , significant differences were seen between controls and typical ( p < 0 . 001 ) and atypical fractures ( p = 0 . 03 ) for Total ID and for IDI ( p < 0 . 001 and p < 0 . 05 , respectively ) .", "entity": [], "task": "NER"}
{"text": "There were no differences in Creep ID between groups .", "entity": [], "task": "NER"}
{"text": "Our data suggest that patients with AFF have a deep deterioration in bone material properties at a tissue level similar to that for the osteoporotic fracture group .", "entity": [], "task": "NER"}
{"text": "The LTB group shows levels that are in between controls and both type of fractures , although not statistically different .", "entity": [], "task": "NER"}
{"text": "These results suggest that bisphosphonate therapy probably does not put the majority of patients at risk for AFF .", "entity": [{"entity": "bisphosphonate", "entity_type": "Chemical", "pos": [27, 41]}], "task": "NER"}
{"text": "Biotransformation of serotonin derivatives by the larvae of common cutworm ( Spodoptera litura ) .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Seven serotonin derivatives ( 1 - 7 ) were biotransformed using larvae of Spodoptera litura .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "N - p - methoxy cinnamoyl serotonin ( 3 ) was converted into its O - demethylated compound , N - p - coumaroyl serotonin ( 2 ) .", "entity": [{"entity": "N - p - methoxy cinnamoyl serotonin", "entity_type": "Chemical", "pos": [0, 35]}, {"entity": "O", "entity_type": "Chemical", "pos": [65, 66]}, {"entity": "N - p - coumaroyl serotonin", "entity_type": "Chemical", "pos": [93, 120]}], "task": "NER"}
{"text": "Furthermore , N - feruloyl serotonin ( 5 ) and N - isoferuloyl serotonin ( 6 ) were converted into , two new compounds , N - feruloyl serotonin - 4 ' - O - beta - D - glucopyranoside ( 8 ) and N - isoferuloyl serotonin - 3 ' - O - beta - D - glucopyranoside ( 9 ) , respectively .", "entity": [{"entity": "N - feruloyl serotonin", "entity_type": "Chemical", "pos": [14, 36]}, {"entity": "N - isoferuloyl serotonin", "entity_type": "Chemical", "pos": [47, 72]}, {"entity": "N - feruloyl serotonin - 4 ' - O - beta - D - glucopyranoside", "entity_type": "Chemical", "pos": [121, 182]}, {"entity": "N - isoferuloyl serotonin - 3 ' - O - beta - D - glucopyranoside", "entity_type": "Chemical", "pos": [193, 257]}], "task": "NER"}
{"text": "These structures were established by IR , 1D - NMR and 2D - NMR spectral studies .", "entity": [], "task": "NER"}
{"text": "New precursor of tetraterpenoids from the soft coral Sarcophyton glaucum .", "entity": [{"entity": "tetraterpenoids", "entity_type": "Chemical", "pos": [17, 32]}], "task": "NER"}
{"text": "One new precursor of tetraterpenoids , Sarglaucol ( 1 ) , along with eight known compounds have been isolated from the soft coral Sarcophyton glaucum collected from the Sanya Bay , Hainan Island , China .", "entity": [{"entity": "tetraterpenoids", "entity_type": "Chemical", "pos": [21, 36]}, {"entity": "Sarglaucol", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "Their structures were elucidated through spectroscopic techniques including 1D - and 2D - NMR , and their relative configurations were also assigned by NMR and NOESY analysis .", "entity": [], "task": "NER"}
{"text": "Compounds 1 showed weak antitumour activities .", "entity": [], "task": "NER"}
{"text": "Theoretical study of the decomposition of ethyl and ethyl 3 - phenyl glycidate .", "entity": [{"entity": "ethyl and ethyl 3 - phenyl glycidate", "entity_type": "Chemical", "pos": [42, 78]}], "task": "NER"}
{"text": "The mechanism of the decomposition of ethyl and ethyl 3 - phenyl glycidate in gas phase was studied by density functional theory ( DFT ) and MP2 methods .", "entity": [{"entity": "ethyl and ethyl 3 - phenyl glycidate", "entity_type": "Chemical", "pos": [38, 74]}], "task": "NER"}
{"text": "A proposed mechanism for the reaction indicates that the ethyl side of the ester is eliminated as ethylene through a concerted six - membered cyclic transition state , and the unstable intermediate glycidic acid decarboxylates rapidly to give the corresponding aldehyde .", "entity": [{"entity": "ethyl", "entity_type": "Chemical", "pos": [57, 62]}, {"entity": "ethylene", "entity_type": "Chemical", "pos": [98, 106]}, {"entity": "glycidic acid", "entity_type": "Chemical", "pos": [198, 211]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [261, 269]}], "task": "NER"}
{"text": "Two possible pathways for glycidic acid decarboxylation were studied : one via a five - membered cyclic transition state , and the other via a four - membered cyclic transition state .", "entity": [{"entity": "glycidic acid", "entity_type": "Chemical", "pos": [26, 39]}], "task": "NER"}
{"text": "The results of the calculations indicate that the decarboxylation reaction occurs via a mechanism with five - membered cyclic transition state .", "entity": [], "task": "NER"}
{"text": "Coordination and bond activation in complexes of regioisomeric phenylpyridines with the nickel ( II ) chloride cation in the gas phase .", "entity": [{"entity": "phenylpyridines", "entity_type": "Chemical", "pos": [63, 78]}, {"entity": "nickel ( II ) chloride", "entity_type": "Chemical", "pos": [88, 110]}], "task": "NER"}
{"text": "Electrospray ionization of dilute solutions of phenylpyridines ( phpy ) in the presence of nickel ( II ) chloride leads to gaseous ions of the type [ Ni ( phpy ) ( m ) ] ( 2 + ) with m = 3 - 5 and [ NiCl ( phpy ) ( n ) ] ( + ) with n = 1 - 3 , which are characterized by various gas - phase experiments in combination with calculations using density functional theory .", "entity": [{"entity": "phenylpyridines", "entity_type": "Chemical", "pos": [47, 62]}, {"entity": "phpy", "entity_type": "Chemical", "pos": [65, 69]}, {"entity": "nickel ( II ) chloride", "entity_type": "Chemical", "pos": [91, 113]}, {"entity": "[ Ni ( phpy ) ( m ) ] ( 2 + )", "entity_type": "Chemical", "pos": [148, 177]}, {"entity": "[ NiCl ( phpy ) ( n ) ] ( + )", "entity_type": "Chemical", "pos": [197, 226]}], "task": "NER"}
{"text": "Of the regioisomeric phpy ' s , 2 - phpy behaves drastically different compared to 3 - and 4 - phpy .", "entity": [{"entity": "phpy", "entity_type": "Chemical", "pos": [21, 25]}, {"entity": "2 - phpy", "entity_type": "Chemical", "pos": [32, 40]}, {"entity": "3 - and 4 - phpy", "entity_type": "Chemical", "pos": [83, 99]}], "task": "NER"}
{"text": "Ion mobility mass spectrometry allows a differentiation of the gaseous ions and an elucidation of characteristic properties of the metal complexes .", "entity": [], "task": "NER"}
{"text": "For 2 - phpy , C - H bond activation in the [ NiCl ( phpy ) ( 2 ) ] ( + ) complex is significant , whereas this route is almost suppressed for the corresponding complexes of 3 - and 4 - phpy and only occurs at elevated energies .", "entity": [{"entity": "2 - phpy", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "C - H", "entity_type": "Chemical", "pos": [15, 20]}, {"entity": "[ NiCl ( phpy ) ( 2 ) ] ( + )", "entity_type": "Chemical", "pos": [44, 73]}, {"entity": "3 - and 4 - phpy", "entity_type": "Chemical", "pos": [174, 190]}], "task": "NER"}
{"text": "Show me your license , please : deregulation of centriole duplication mechanisms that promote amplification .", "entity": [], "task": "NER"}
{"text": "Centrosomes are organelles involved in generating and organizing the interphase microtubule cytoskeleton , mitotic spindles and cilia .", "entity": [], "task": "NER"}
{"text": "At the centrosome core are a pair of centrioles , structures that act as the duplicating elements of this organelle .", "entity": [], "task": "NER"}
{"text": "Centrioles function to recruit and organize pericentriolar material which nucleates microtubules .", "entity": [], "task": "NER"}
{"text": "While centrioles are relatively simple in construction , the mechanics of centriole biogenesis remain an important yet poorly understood process .", "entity": [], "task": "NER"}
{"text": "More mysterious still are the regulatory mechanisms that oversee centriole assembly .", "entity": [], "task": "NER"}
{"text": "The fidelity of centriole duplication is critical as defects in either the assembly or number of centrioles promote aneuploidy , primary microcephaly , birth defects , ciliopathies and tumorigenesis .", "entity": [], "task": "NER"}
{"text": "In addition , some pathogens employ mechanisms to promote centriole overduplication to the detriment of the host cell .", "entity": [], "task": "NER"}
{"text": "This review summarizes our current understanding of this important topic , highlighting the need for further study if new therapeutics are to be developed to treat diseases arising from defects of centrosome duplication .", "entity": [], "task": "NER"}
{"text": "A significant dose - dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers : A further assessment of the Casa Pia children ' s dental amalgam trial .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [52, 59]}], "task": "NER"}
{"text": "Dental amalgams are a commonly used dental restorative material .", "entity": [], "task": "NER"}
{"text": "Amalgams are about 50 % mercury ( Hg ) , and Hg is known to significantly accumulate in the kidney .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [24, 31]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [34, 36]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [45, 47]}], "task": "NER"}
{"text": "It was hypothesized that because Hg accumulates in the proximal tubules ( PTs ) , glutathione - S - transferases ( GST ) - alpha ( suggestive of kidney damage at the level of PT ) would be expected to be more related to Hg exposure than GST - pi ( suggestive of kidney damage at the level of the distal tubules ) .", "entity": [{"entity": "Hg", "entity_type": "Chemical", "pos": [33, 35]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [82, 93]}, {"entity": "S", "entity_type": "Chemical", "pos": [96, 97]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [220, 222]}], "task": "NER"}
{"text": "Urinary biomarkers of kidney integrity were examined in children of 8 - 18 years old , with and without dental amalgam fillings , from a completed clinical trial ( parent study ) .", "entity": [], "task": "NER"}
{"text": "Our study determined whether there was a significant dose - dependent correlation between increasing Hg exposure from dental amalgams and GST - alpha and GST - pi as biomarkers of kidney integrity .", "entity": [{"entity": "Hg", "entity_type": "Chemical", "pos": [101, 103]}], "task": "NER"}
{"text": "Overall , the present study , using a different and more sensitive statistical model than the parent study , revealed a statistically significant dose - dependent correlation between cumulative exposure to Hg from dental amalgams and urinary levels of GST - alpha , after covariate adjustment ; where as , a nonsignificant relationship was observed with urinary levels of GST - pi .", "entity": [{"entity": "Hg", "entity_type": "Chemical", "pos": [206, 208]}], "task": "NER"}
{"text": "Furthermore , it was observed that urinary GST - alpha levels increased by about 10 % over the 8 - year course of the study among individuals with an average exposure to amalgams among the study subjects from the amalgam group , in comparison with study subjects with no exposure to dental amalgams .", "entity": [], "task": "NER"}
{"text": "The results of our study suggest that dental amalgams contribute to ongoing kidney damage at the level of the PTs in a dose - dependent fashion .", "entity": [], "task": "NER"}
{"text": "Emergency Do Not Consume / do Not Use concentrations for potassium permanganate in drinking water .", "entity": [{"entity": "potassium permanganate", "entity_type": "Chemical", "pos": [57, 79]}], "task": "NER"}
{"text": "Over the past decade , regulatory authorities and water purveyors have become increasingly concerned with accidental or intentional adulteration of municipal drinking water .", "entity": [], "task": "NER"}
{"text": "Emergency response guidelines , such as the ' Do Not Consume ' or use concentration limits derived herein , can be used to notify the public in such cases .", "entity": [], "task": "NER"}
{"text": "Potassium permanganate ( KMnO ( 4 ) ) is used to control iron concentrations and to reduce the levels of nuisance materials that affect odor or taste of finished drinking water .", "entity": [{"entity": "Potassium permanganate", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [25, 35]}], "task": "NER"}
{"text": "Manganese ( Mn ) is recognized an essential nutrient , permanganate ( MnO4 ( - ) ) and manganous ( Mn ( + 2 ) ) ions are caustic , and the acute toxicity of KMnO ( 4 ) is defined by its oxidant / irritant properties and by the toxicity of Mn .", "entity": [{"entity": "Manganese", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [12, 14]}, {"entity": "permanganate", "entity_type": "Chemical", "pos": [55, 67]}, {"entity": "MnO4 ( - )", "entity_type": "Chemical", "pos": [70, 80]}, {"entity": "manganous", "entity_type": "Chemical", "pos": [87, 96]}, {"entity": "Mn ( + 2 )", "entity_type": "Chemical", "pos": [99, 109]}, {"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [157, 167]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [239, 241]}], "task": "NER"}
{"text": "Ingestion of small amounts ( 4 - 20 mg / kg ) of aqueous KMnO ( 4 ) solutions that are above 200 mg / L causes gastrointestinal distress , while bolus ingestion has caused respiratory arrest following coagulative necrosis and hemorrhage in the esophagus , stomach , or liver .", "entity": [{"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "Dilute KMnO ( 4 ) solutions ( 1 - 100 mg / L ) are used as a topical antiseptics and astringents , but > 1 : 5000 ( 200 mg / L ) dilutions can irritate or discolor sensitive mucous membranes and direct skin or ocular contact with concentrated KMnO ( 4 ) can perforate tissues .", "entity": [{"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [7, 17]}, {"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [243, 253]}], "task": "NER"}
{"text": "Based on clinical experience with 200 mg / L KMnO ( 4 ) , a Do Not Consume concentration of 7 mg / L KMnO ( 4 ) ( equivalent to 2 mg Mn / L ) is recommended .", "entity": [{"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "KMnO ( 4 )", "entity_type": "Chemical", "pos": [101, 111]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [133, 135]}], "task": "NER"}
{"text": "Recognizing limited empirical data from which to calculate an ocular reference value , a skin contact ' Do Not Use ' concentration of 30 mg Mn / L is recommended based on the skin irritation in some patients after a 10 - min contact with 100 mg KMnO4 / L .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [140, 142]}, {"entity": "KMnO4", "entity_type": "Chemical", "pos": [245, 250]}], "task": "NER"}
{"text": "Cresyl saligenin phosphate makes multiple adducts on free histidine , but does not form an adduct on histidine 438 of human butyrylcholinesterase .", "entity": [{"entity": "Cresyl saligenin phosphate", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "Cresyl saligenin phosphate ( CBDP ) is a suspected causative agent of \" aerotoxic syndrome \" , affecting pilots , crew members and passengers .", "entity": [{"entity": "Cresyl saligenin phosphate", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "CBDP", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "CBDP is produced in vivo from ortho - containing isomers of tricresyl phosphate ( TCP ) , a component of jet engine lubricants and hydraulic fluids .", "entity": [{"entity": "CBDP", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "tricresyl phosphate", "entity_type": "Chemical", "pos": [60, 79]}, {"entity": "TCP", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "CBDP irreversibly inhibits butyrylcholinesterase ( BChE ) in human plasma by forming adducts on the active site serine ( Ser - 198 ) .", "entity": [{"entity": "CBDP", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "serine", "entity_type": "Chemical", "pos": [112, 118]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "Inhibited BChE undergoes aging to release saligenin and o - cresol .", "entity": [{"entity": "saligenin", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "o - cresol", "entity_type": "Chemical", "pos": [56, 66]}], "task": "NER"}
{"text": "The active site histidine ( His - 438 ) was hypothesized to abstract o - hydroxybenzyl moiety from the initial adduct on Ser - 198 .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "His", "entity_type": "Chemical", "pos": [28, 31]}, {"entity": "o - hydroxybenzyl", "entity_type": "Chemical", "pos": [69, 86]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "Our goal was to test this hypothesis .", "entity": [], "task": "NER"}
{"text": "Mass spectral analysis of CBDP - inhibited BChE digested with Glu - C showed an o - hydroxybenzyl adduct ( + 106amu ) on lysine 499 , a residue far from the active site , but not on His - 438 .", "entity": [{"entity": "CBDP", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "Glu", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "o - hydroxybenzyl", "entity_type": "Chemical", "pos": [80, 97]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [121, 127]}, {"entity": "His", "entity_type": "Chemical", "pos": [182, 185]}], "task": "NER"}
{"text": "Nevertheless , the nitrogen of the imidazole ring of free l - histidine formed a variety of adducts upon reaction with CBDP , including the o - hydroxybenzyl adduct , suggesting that histidine - CBDP adducts may form on other proteins .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "imidazole", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "l - histidine", "entity_type": "Chemical", "pos": [58, 71]}, {"entity": "CBDP", "entity_type": "Chemical", "pos": [119, 123]}, {"entity": "o - hydroxybenzyl", "entity_type": "Chemical", "pos": [140, 157]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [183, 192]}, {"entity": "CBDP", "entity_type": "Chemical", "pos": [195, 199]}], "task": "NER"}
{"text": "Training your brain : Do mental and physical ( MAP ) training enhance cognition through the process of neurogenesis in the hippocampus ?", "entity": [], "task": "NER"}
{"text": "New neurons are produced each day in the hippocampus through the process of neurogenesis .", "entity": [], "task": "NER"}
{"text": "Both mental and physical training can modify this process by increasing the number of new cells that mature into functional neurons in the adult brain .", "entity": [], "task": "NER"}
{"text": "However , the mechanisms whereby these increases occur are not necessarily the same .", "entity": [], "task": "NER"}
{"text": "Physical activity , especially aerobic exercise greatly increases the number of new neurons that are produced in the hippocampal formation .", "entity": [], "task": "NER"}
{"text": "In contrast , mental training via skill learning increases the numbers that survive , particularly when the training goals are challenging .", "entity": [], "task": "NER"}
{"text": "Both manipulations can increase cognitive performance in the future , some of which are reportedly mediated by the presence of new neurons in the adult hippocampus .", "entity": [], "task": "NER"}
{"text": "Based on these data , we suggest that a combination of mental and physical training , referred to here as MAP training , is more beneficial for neuronal recruitment and overall mental health than either activity alone .", "entity": [], "task": "NER"}
{"text": "Organochlorine pesticide levels and risk of Alzheimer ' s disease in north Indian population .", "entity": [{"entity": "Organochlorine", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Alzheimer ' s disease ( AD ) could result from a multifactorial process involving both genetic predisposition and exposure to environmental factors like pesticides .", "entity": [], "task": "NER"}
{"text": "A case control study of 70 patients of AD and 75 controls was done to examine the association between organochlorine pesticides ( OCPs ) and risk of AD .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [102, 116]}], "task": "NER"}
{"text": "OCPs ( hexachlorocyclohexane ( HCH ) , aldrin , dieldrin , endosulfan , pp ' - dichlorodiphenyldichloroethylene ( pp ' - DDE ) , op ' - DDE , pp ' - dichlorodiphenyltrichloroethane ( pp ' - DDT ) , op ' - DDT , pp ' - dichlorodiphenyldichloroethane ( pp ' - DDD ) and op ' - DDD ) were extracted from blood and quantitatively estimated using gas chromatography .", "entity": [{"entity": "hexachlorocyclohexane", "entity_type": "Chemical", "pos": [7, 28]}, {"entity": "HCH", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "aldrin", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "endosulfan", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "pp ' - dichlorodiphenyldichloroethylene", "entity_type": "Chemical", "pos": [72, 111]}, {"entity": "pp ' - DDE", "entity_type": "Chemical", "pos": [114, 124]}, {"entity": "op ' - DDE", "entity_type": "Chemical", "pos": [129, 139]}, {"entity": "pp ' - dichlorodiphenyltrichloroethane", "entity_type": "Chemical", "pos": [142, 180]}, {"entity": "pp ' - DDT", "entity_type": "Chemical", "pos": [183, 193]}, {"entity": "op ' - DDT", "entity_type": "Chemical", "pos": [198, 208]}, {"entity": "pp ' - dichlorodiphenyldichloroethane", "entity_type": "Chemical", "pos": [211, 248]}, {"entity": "pp ' - DDD", "entity_type": "Chemical", "pos": [251, 261]}, {"entity": "op ' - DDD", "entity_type": "Chemical", "pos": [268, 278]}], "task": "NER"}
{"text": "A Mann - Whitney U test revealed significant difference in beta - HCH levels ( U = 1237 . 00 , W = 4087 . 00 , z = - 6 . 296 , p = 0 . 000 , r = - 0 . 71 ) , dieldrin levels ( U = 1449 . 00 , W = 4299 . 00 , z = - 5 . 809 , p = 0 . 000 , r = - 0 . 68 ) and pp ' - DDE levels ( U = 2062 . 00 , W = 4912 . 00 , z = - 2 . 698 , p = 0 . 007 , r = - 0 . 59 ) between AD patients and controls .", "entity": [{"entity": "beta - HCH", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [158, 166]}, {"entity": "pp ' - DDE", "entity_type": "Chemical", "pos": [257, 267]}], "task": "NER"}
{"text": "In conclusion , this study supports epidemiological studies that associate exposure to pesticides with increased risk of AD , and we identified the specific pesticides beta - HCH , dieldrin and pp ' - DDE that are associated with the risk of AD in the north Indian population .", "entity": [{"entity": "beta - HCH", "entity_type": "Chemical", "pos": [168, 178]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [181, 189]}, {"entity": "pp ' - DDE", "entity_type": "Chemical", "pos": [194, 204]}], "task": "NER"}
{"text": "However , further research is needed to establish the potential role of these OCPs as an etiologic agent for AD case .", "entity": [], "task": "NER"}
{"text": "Therapeutic efficacy of silymarin from milk thistle in reducing manganese - induced hepatic damage and apoptosis in rats .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "Oxidative stress has been proposed as a possible mechanism involved in manganese ( Mn ) toxicity .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [71, 80]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [83, 85]}], "task": "NER"}
{"text": "Using natural antioxidants against metal - induced hepatotoxicity is a modern approach .", "entity": [], "task": "NER"}
{"text": "The present study investigated the beneficial role of silymarin , a natural flavonoid , in Mn - induced hepatotoxicity focusing on histopathology and biochemical approaches .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [76, 85]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [91, 93]}], "task": "NER"}
{"text": "Male Wistar rats were exposed orally to manganese chloride ( 20 mg / mL ) for 30 days followed by intraperitoneal cotreatment with silymarin ( 100 mg / kg ) .", "entity": [{"entity": "manganese chloride", "entity_type": "Chemical", "pos": [40, 58]}], "task": "NER"}
{"text": "Exposure to Mn resulted in a significant elevation of the plasma marker enzyme activities and bilirubin level related to liver dysfunction of reactive oxygen species ( ROS ) production and hepatic oxidative stress indices .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [12, 14]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [94, 103]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [151, 157]}], "task": "NER"}
{"text": "This metal reduced the activities of superoxide dismutase , catalase and glutathione peroxidase and nonenzymatic antioxidant levels such as reduced glutathione , total sulfhydryl groups and vitamin C .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [148, 159]}, {"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [168, 178]}, {"entity": "vitamin C", "entity_type": "Chemical", "pos": [190, 199]}], "task": "NER"}
{"text": "In addition , it caused hepatic hemorrhage , cellular degeneration and necrosis of hepatocytes as indicated by liver histopathology and DNA fragmentation studies .", "entity": [], "task": "NER"}
{"text": "Coadministration of silymarin alleviated Mn oxidative damage effects by inhibiting ROS generation .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [41, 43]}], "task": "NER"}
{"text": "Histological studies also supported the beneficial role of silymarin against Mn - induced hepatic damages .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [77, 79]}], "task": "NER"}
{"text": "Combining all , results suggested that silymarin could protect hepatic tissues against Mn - induced oxidative stress probably through its antioxidant activity .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [87, 89]}], "task": "NER"}
{"text": "Therefore , its supplementation could provide a new approach for the reduction in hepatic complication due to Mn poisoning .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [110, 112]}], "task": "NER"}
{"text": "Effect of copper overload on the survival of HepG2 and A - 549 human - derived cells .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [10, 16]}], "task": "NER"}
{"text": "We investigated the effect of copper ( Cu ) overload ( 20 - 160 micro M / 24 h ) in two cell lines of human hepatic ( HepG2 ) and pulmonary ( A - 549 ) origin by determining lipid and protein damage and the response of the antioxidant defence system .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [39, 41]}], "task": "NER"}
{"text": "A - 549 cells were more sensitive to Cu overload than HepG2 cells .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [37, 39]}], "task": "NER"}
{"text": "A marked increase was observed in both the cell lines in the nitrate plus nitrite concentration , protein carbonyls and thiobarbituric acid reactive substances ( TBARS ) .", "entity": [{"entity": "nitrate", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "nitrite", "entity_type": "Chemical", "pos": [74, 81]}, {"entity": "carbonyls", "entity_type": "Chemical", "pos": [106, 115]}, {"entity": "thiobarbituric acid", "entity_type": "Chemical", "pos": [120, 139]}], "task": "NER"}
{"text": "The TBARS increase was consistent with an increment in saturated fatty acids at the expense of polyunsaturated acids in a Cu concentration - dependent fashion .", "entity": [{"entity": "saturated fatty acids", "entity_type": "Chemical", "pos": [55, 76]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [122, 124]}], "task": "NER"}
{"text": "Antioxidant enzymes were stimulated by Cu overload .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [39, 41]}], "task": "NER"}
{"text": "Superoxide dismutase activity increased significantly in both the cell lines , with greater increases in HepG2 than in A - 549 cells .", "entity": [{"entity": "Superoxide", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "A marked increase in ceruloplasmin and metallothionein content in both the cell types was also observed .", "entity": [], "task": "NER"}
{"text": "Dose - dependent decreases in alpha - tocopherol and ferric reducing ability were observed .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [30, 48]}, {"entity": "ferric", "entity_type": "Chemical", "pos": [53, 59]}], "task": "NER"}
{"text": "Total glutathione content was lower in A - 549 cells and higher in HepG2 .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [6, 17]}], "task": "NER"}
{"text": "Calpain and caspase - 3 were differentially activated in a dose - dependent manner under copper - induced reactive oxygen species production .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [89, 95]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [115, 121]}], "task": "NER"}
{"text": "We conclude that Cu exposure of human lung - and liver - derived cells should be considered a reliable experimental system for detailed study of mechanism / mechanisms by which Cu overload exerts its deleterious effects .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [17, 19]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [177, 179]}], "task": "NER"}
{"text": "A human hemi - cornea model for eye irritation testing : quality control of production , reliability and predictive capacity .", "entity": [], "task": "NER"}
{"text": "We have developed a 3 - dimensional human hemi - cornea which comprises an immortalized epithelial cell line and keratocytes embedded in a collagen stroma .", "entity": [], "task": "NER"}
{"text": "In the present study , we have used MTT reduction of the whole tissue to clarify whether the production of this complex 3 - D - model is transferable into other laboratories and whether these tissues can be constructed reproducibly .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "Our results demonstrate the reproducible production of the hemi - cornea model according to standard operation procedures using 15 independent batches of reconstructed hemi - cornea models in two independent laboratories each .", "entity": [], "task": "NER"}
{"text": "Furthermore , the hemi - cornea tissues have been treated with 20 chemicals of different eye - irritating potential under blind conditions to assess the performance and limitations of our test system comparing three different prediction models .", "entity": [], "task": "NER"}
{"text": "The most suitable prediction model revealed an overall in vitro - in vivo concordance of 80 % and 70 % in the participating laboratories , respectively , and an inter - laboratory concordance of 80 % .", "entity": [], "task": "NER"}
{"text": "Sensitivity of the test was 77 % and specificity was between 57 % and 86 % to discriminate classified from non - classified chemicals .", "entity": [], "task": "NER"}
{"text": "We conclude that additional physiologically relevant endpoints in both epithelium and stroma have to be developed for the reliable prediction of all GHS classes of eye irritation in one stand alone test system .", "entity": [], "task": "NER"}
{"text": "High levels of arachidonic acid and peroxisome proliferator - activated receptor - alpha in breast cancer tissues are associated with promoting cancer cell proliferation .", "entity": [{"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [15, 31]}], "task": "NER"}
{"text": "Fatty acids are endogenous ligands of peroxisome proliferator - activated receptor - alpha ( PPAR alpha ) , which is linked to the regulation of fatty acid uptake , lipid metabolism and breast cancer cell growth .", "entity": [{"entity": "Fatty acids", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [145, 155]}], "task": "NER"}
{"text": "This study was designed to screen candidate fatty acids from breast cancer tissue and to investigate the effects of these candidate fatty acids on PPAR alpha expression , cell growth and cell cycle progression in breast cancer cell lines .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [44, 55]}, {"entity": "fatty acids", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "One breast cancer tissue and one reference tissue were each taken from 30 individual breasts to examine for fatty acid composition and PPAR alpha expression .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [108, 118]}], "task": "NER"}
{"text": "The cancer cell lines MDA - MB - 231 ( ER - ) , MCF - 7 ( ER + + + + ) and BT - 474 ( ER + + ) were used to explore the mechanisms regulating cell proliferation .", "entity": [], "task": "NER"}
{"text": "We found that arachidonic acid ( AA ) and PPAR alpha were highly expressed in the breast cancer tissues .", "entity": [{"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [14, 30]}], "task": "NER"}
{"text": "AA stimulated the growth of all three breast cancer cells in a time - and dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "The growth stimulatory effect of AA was associated with PPAR alpha activation , and the most potent effect was found in MCF - 7 cells .", "entity": [], "task": "NER"}
{"text": "The stimulation of cell proliferation by AA was accompanied by the increased expression of cyclin E , a reduced population of G1 phase cells , and a faster G1 / S phase transition .", "entity": [], "task": "NER"}
{"text": "In contrast , AA had no effects on the levels of CDK2 , CDK4 , cyclin D1 , p27 , Bcl - 2 and Bax .", "entity": [], "task": "NER"}
{"text": "Our results demonstrate that high levels of AA and PPAR alpha expression in human breast cancer tissues are associated with ER - overexpressed breast cancer cell proliferation , which is involved in activating PPAR alpha , stimulating cyclin E expression , and promoting faster G1 / S transition .", "entity": [], "task": "NER"}
{"text": "Vitamin E deficiency impairs the somatostatinergic receptor - effector system and leads to phosphotyrosine phosphatase overactivation and cell death in the rat hippocampus .", "entity": [{"entity": "Vitamin E", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "phosphotyrosine", "entity_type": "Chemical", "pos": [91, 106]}], "task": "NER"}
{"text": "Vitamin E plays an essential role in maintaining the structure and function of the nervous system , and its deficiency , commonly associated with fat malabsorption diseases , may reduce neuronal survival .", "entity": [{"entity": "Vitamin E", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "We previously demonstrated that the somatostatinergic system , implicated in neuronal survival control , can be modulated by alpha - tocopherol in the rat dentate gyrus , increasing cyclic adenosine monophosphate response element binding protein phosphorylation .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [125, 143]}, {"entity": "cyclic adenosine monophosphate", "entity_type": "Chemical", "pos": [182, 212]}], "task": "NER"}
{"text": "To gain a better understanding of the molecular actions of tocopherols and examine the link among vitamin E , somatostatin and neuronal survival , we have investigated the effects of a deficiency and subsequent administration of tocopherol on the somatostatin signaling pathway and neuronal survival in the rat hippocampus .", "entity": [{"entity": "tocopherols", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [110, 122]}, {"entity": "tocopherol", "entity_type": "Chemical", "pos": [229, 239]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [247, 259]}], "task": "NER"}
{"text": "No changes in somatostatin expression were detected in vitamin - E - deficient rats .", "entity": [{"entity": "somatostatin", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "vitamin - E", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "These rats , however , showed a significant increase in the somatostatin receptor density and dissociation constant , which correlated with a significant increase in the protein levels of somatostatin receptors .", "entity": [{"entity": "somatostatin", "entity_type": "Chemical", "pos": [60, 72]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [188, 200]}], "task": "NER"}
{"text": "Nevertheless , vitamin E deficiency impaired the ability of the somatostatin receptors to couple to the effectors adenylyl cyclase and phosphotyrosine phosphatase by diminishing Gi protein functionality .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [64, 76]}, {"entity": "adenylyl", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "phosphotyrosine", "entity_type": "Chemical", "pos": [135, 150]}], "task": "NER"}
{"text": "Furthermore , vitamin E deficiency significantly increased phosphotyrosine phosphatase activity and PTP eta expression , as well as PKC delta activation , and decreased extracellular - signal - regulated kinase phosphorylation .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "phosphotyrosine", "entity_type": "Chemical", "pos": [59, 74]}], "task": "NER"}
{"text": "All these changes were accompanied by an increase in neuronal cell death .", "entity": [], "task": "NER"}
{"text": "Subsequent alpha - tocopherol administration partially or completely reversed all these values to control levels .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [11, 29]}], "task": "NER"}
{"text": "Altogether , our results prove the importance of vitamin E homeostasis in the somatostatin receptor - effector system and suggest a possible mechanism by which this vitamin may regulate the neuronal cell survival in the adult hippocampus .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [49, 58]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [78, 90]}], "task": "NER"}
{"text": "Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials .", "entity": [], "task": "NER"}
{"text": "The in vivo zebrafish models have recently attracted great attention in molecular oncology to investigate multiple genetic alterations associated with the development of human cancers and validate novel anticancer drug targets .", "entity": [], "task": "NER"}
{"text": "Particularly , the transparent zebrafish models can be used as a xenotransplantation system to rapidly assess the tumorigenicity and metastatic behavior of cancer stem and / or progenitor cells and their progenies .", "entity": [], "task": "NER"}
{"text": "Moreover , the zebrafish models have emerged as powerful tools for an in vivo testing of novel anticancer agents and nanomaterials for counteracting tumor formation and metastases and improving the efficacy of current radiation and chemotherapeutic treatments against aggressive , metastatic and lethal cancers .", "entity": [], "task": "NER"}
{"text": "Skin phototoxicity of cosmetic formulations containing photounstable and photostable UV - filters and vitamin A palmitate .", "entity": [{"entity": "vitamin A palmitate", "entity_type": "Chemical", "pos": [102, 121]}], "task": "NER"}
{"text": "The aim of this study was to evaluate the in vitro skin phototoxicity of cosmetic formulations containing photounstable and photostable UV - filters and vitamin A palmitate , assessed by two in vitro techniques : 3T3 Neutral Red Uptake Phototoxicity Test and Human 3 - D Skin Model In Vitro Phototoxicity Test .", "entity": [{"entity": "vitamin A palmitate", "entity_type": "Chemical", "pos": [153, 172]}], "task": "NER"}
{"text": "For this , four different formulations containing vitamin A palmitate and different UV - filters combinations , two of them considered photostable and two of them considered photounstable , were prepared .", "entity": [{"entity": "vitamin A palmitate", "entity_type": "Chemical", "pos": [50, 69]}], "task": "NER"}
{"text": "Solutions of each UV - filter and vitamin under study and solutions of four different combinations under study were also prepared .", "entity": [], "task": "NER"}
{"text": "The phototoxicity was assessed in vitro by the 3T3 NRU phototoxicity test ( 3T3 - NRU - PT ) and subsequently in a phototoxicity test on reconstructed human skin model ( H3D - PT ) .", "entity": [], "task": "NER"}
{"text": "Avobenzone presented a pronounced phototoxicity and vitamin A presented a tendency to a weak phototoxic potential .", "entity": [{"entity": "Avobenzone", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "vitamin A", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "A synergistic effect of vitamin A palmitate on the phototoxicity of combinations containing avobenzone was observed .", "entity": [{"entity": "vitamin A palmitate", "entity_type": "Chemical", "pos": [24, 43]}, {"entity": "avobenzone", "entity_type": "Chemical", "pos": [92, 102]}], "task": "NER"}
{"text": "H3D - PT results did not confirm the positive 3T3 - NRU - PT results .", "entity": [], "task": "NER"}
{"text": "However , despite the four formulations studied did not present any acute phototoxicity potential , the combination 2 containing octyl methoxycinnamate ( OMC ) , avobenzone ( AVB ) and 4 - methylbenzilidene camphor ( MBC ) presented an indication of phototoxicity that should be better investigated in terms of the frequency of photoallergic or chronic phototoxicity in humans , once these tests are scientifically validated only to detect phototoxic potential with the aim of preventing phototoxic reactions in the general population , and positive results cannot predict the exact incidence of phototoxic reactions in humans .", "entity": [{"entity": "octyl methoxycinnamate", "entity_type": "Chemical", "pos": [129, 151]}, {"entity": "OMC", "entity_type": "Chemical", "pos": [154, 157]}, {"entity": "avobenzone", "entity_type": "Chemical", "pos": [162, 172]}, {"entity": "AVB", "entity_type": "Chemical", "pos": [175, 178]}, {"entity": "4 - methylbenzilidene camphor", "entity_type": "Chemical", "pos": [185, 214]}, {"entity": "MBC", "entity_type": "Chemical", "pos": [217, 220]}], "task": "NER"}
{"text": "Improved procedures for in vitro skin irritation testing of sticky and greasy natural botanicals .", "entity": [], "task": "NER"}
{"text": "Skin irritation evaluation is an important endpoint for the safety assessment of cosmetic ingredients required by various regulatory authorities for notification and / or import of test substances .", "entity": [], "task": "NER"}
{"text": "The present study was undertaken to investigate possible protocol adaptations of the currently validated in vitro skin irritation test methods based on reconstructed human epidermis ( RhE ) for the testing of plant extracts and natural botanicals .", "entity": [], "task": "NER"}
{"text": "Due to their specific physico - chemical properties , such as lipophilicity , sticky / buttery - like texture , waxy / creamy foam characteristics , normal washing procedures can lead to an incomplete removal of these materials and / or to mechanical damage to the tissues , resulting in an impaired prediction of the true skin irritation potential of the materials .", "entity": [], "task": "NER"}
{"text": "For this reason different refined washing procedures were evaluated for their ability to ensure appropriate removal of greasy and sticky substances while not altering the normal responses of the validated RhE test method .", "entity": [], "task": "NER"}
{"text": "Amongst the different procedures evaluated , the use of a SDS 0 . 1 % PBS solution to remove the sticky and greasy test material prior to the normal washing procedures was found to be the most suitable adaptation to ensure efficient removal of greasy and sticky in - house controls without affecting the results of the negative control .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "The predictive capacity of the refined SDS 0 . 1 % washing procedure , was investigated by using twelve oily and viscous compounds having known skin irritation effects supported by raw and / or peer reviewed in vivo data .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "The normal washing procedure resulted in 8 out of 10 correctly predicted compounds as compared to 9 out of 10 with the refined washing procedures , showing an increase in the predictive ability of the assay .", "entity": [], "task": "NER"}
{"text": "The refined washing procedure allowed to correctly identify all in vivo skin irritant materials showing the same sensitivity as the normal washing procedures , and further increased the specificity of the assay from 5 to 6 correct predictions out of 7 non irritants as compared to the normal washing procedures .", "entity": [], "task": "NER"}
{"text": "In addition , when exposed to non - irritant oily and viscous materials , tissues rinsed with 0 . 1 % SDS generally showed increased viabilities accompanied by decreased variabilities as compared to the normal washing procedures .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Similar results were obtained when testing typical in - house natural botanical ingredients .", "entity": [], "task": "NER"}
{"text": "In conclusion , the use of a refined washing procedure making use of SDS 0 . 1 % in PBS was found a suitable procedure to ensure efficient removal of greasy and sticky materials , leading to an increased predictive capacity and decreased variability of the tissue responses while maintaining its sensitivity and not affecting untreated tissues morphology and viability .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "Photochromic materials : more than meets the eye .", "entity": [], "task": "NER"}
{"text": "Photochromic materials are a family of compounds which can undergo reversible photo - switches between two different states or isomers with remarkably different properties .", "entity": [], "task": "NER"}
{"text": "Inspired by their smart photo - switchable characteristics , a variety of light - driven functional materials have been exploited , such as ultrahigh - density optical data storage , molecular switches , logic gates , molecular wires , optic / electronic devices , sensors , bio - imaging and so on .", "entity": [], "task": "NER"}
{"text": "This review commences with a brief description of exciting progress in this field , from systems in solution to modified functional surfaces .", "entity": [], "task": "NER"}
{"text": "Further development of these photo - switchable systems into practical applications as well as existing challenges are also discussed and put in prospect .", "entity": [], "task": "NER"}
{"text": "Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate - induced panic - like response in panic - vulnerable rats .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "sodium lactate", "entity_type": "Chemical", "pos": [80, 94]}], "task": "NER"}
{"text": "Rats with chronic inhibition of GABA synthesis by infusion of l - allyglycine , a glutamic acid decarboxylase inhibitor , into their dorsomedial / perifornical hypothalamus are anxious and exhibit panic - like cardio - respiratory responses to treatment with intravenous ( i . v . ) sodium lactate ( NaLac ) infusions , in a manner similar to what occurs in patients with panic disorder .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [32, 36]}, {"entity": "l - allyglycine", "entity_type": "Chemical", "pos": [62, 77]}, {"entity": "glutamic acid", "entity_type": "Chemical", "pos": [82, 95]}, {"entity": "sodium lactate", "entity_type": "Chemical", "pos": [283, 297]}, {"entity": "NaLac", "entity_type": "Chemical", "pos": [300, 305]}], "task": "NER"}
{"text": "We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2 / 3 receptor agonists can block such a NaLac response , suggesting that a glutamate mechanism is contributing to this panic - like state .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [33, 37]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [75, 84]}, {"entity": "NaLac", "entity_type": "Chemical", "pos": [140, 145]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [175, 184]}], "task": "NER"}
{"text": "Using this animal model of panic , we tested the efficacy of CBiPES and THIIC , which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators ( at 10 - 30 mg / kg i . p . ) , in preventing NaLac - induced panic - like behavioral and cardiovascular responses .", "entity": [{"entity": "CBiPES", "entity_type": "Chemical", "pos": [61, 67]}, {"entity": "THIIC", "entity_type": "Chemical", "pos": [72, 77]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [122, 131]}, {"entity": "NaLac", "entity_type": "Chemical", "pos": [219, 224]}], "task": "NER"}
{"text": "The positive control was alprazolam ( 3mg / kg i . p . ) , a clinically effective anti - panic benzodiazepine .", "entity": [{"entity": "alprazolam", "entity_type": "Chemical", "pos": [25, 35]}, {"entity": "benzodiazepine", "entity_type": "Chemical", "pos": [95, 109]}], "task": "NER"}
{"text": "As predicted , panic - prone rats given a NaLac challenge displayed NaLac - induced panic - like cardiovascular ( i . e . tachycardia and hypertensive ) responses and \" anxiety \" ( i . e . decreased social interaction time ) and \" flight \" ( i . e . increased locomotion ) - associated behaviors ; however , systemic injection of the panic - prone rats with CBiPES , THIIC or alprazolam prior to the NaLac dose blocked all NaLac - induced panic - like behaviors and cardiovascular responses .", "entity": [{"entity": "NaLac", "entity_type": "Chemical", "pos": [42, 47]}, {"entity": "NaLac", "entity_type": "Chemical", "pos": [68, 73]}, {"entity": "CBiPES", "entity_type": "Chemical", "pos": [358, 364]}, {"entity": "THIIC", "entity_type": "Chemical", "pos": [367, 372]}, {"entity": "alprazolam", "entity_type": "Chemical", "pos": [376, 386]}, {"entity": "NaLac", "entity_type": "Chemical", "pos": [400, 405]}, {"entity": "NaLac", "entity_type": "Chemical", "pos": [423, 428]}], "task": "NER"}
{"text": "These data suggested that in a rat animal model , selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti - panic efficacy similar to alprazolam .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "alprazolam", "entity_type": "Chemical", "pos": [173, 183]}], "task": "NER"}
{"text": "High multivitamin intakes during pregnancy and postweaning obesogenic diets interact to affect the relationship between expression of PPAR genes and glucose regulation in the offspring .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [149, 156]}], "task": "NER"}
{"text": "High multivitamin intake ( HV ) during pregnancy increases body fat and weight and alters glucose and fatty acid metabolism in Wistar rat offspring .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [90, 97]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "This study investigated the expression of peroxisome - proliferator activated receptors ( PPARs ) genes involved in regulation of glucose and fatty acid metabolism in their tissues .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [142, 152]}], "task": "NER"}
{"text": "Dams received the AIN - 93G diet with either the regular ( RV ) or 10 - fold multivitamins ( HV ) during pregnancy .", "entity": [], "task": "NER"}
{"text": "Male offspring were weaned to either the RV diet ( RV - RV and HV - RV ) or an obesogenic diet ( RV - Ob and HV - Ob ) .", "entity": [], "task": "NER"}
{"text": "Gene expression of PPARs in tissues was analyzed by real - time reverse transcriptase polymerase chain reaction .", "entity": [], "task": "NER"}
{"text": "Gestational diet ( GD ) did not affect PPARs gene expression in offspring at either birth or weaning .", "entity": [], "task": "NER"}
{"text": "In liver , at 14 weeks postweaning , PPAR - gamma was 30 % lower in the HV - RV and 30 % higher in HV - Ob than in the RV - RV group [ GD P = . 76 , postweaning diet ( PD ) P = . 19 , interaction P = . 02 , by two - way analysis of variance ] .", "entity": [], "task": "NER"}
{"text": "In muscle , PPAR - alpha expression was affected by GD and PD ( GD P = . 05 , PD P < . 01 , interaction P = . 07 ) .", "entity": [], "task": "NER"}
{"text": "In adipose tissue , PPAR - alpha expression was higher in all groups compared to RV - RV ( GD P = . 25 , PD P = . 85 , interaction P = . 03 ) .", "entity": [], "task": "NER"}
{"text": "PPAR - gamma mRNA levels correlated with abdominal fat ( r = 0 . 45 , P < . 05 ) and insulin resistance index ( r = 0 . 39 , P < . 05 ) .", "entity": [], "task": "NER"}
{"text": "In liver , PPAR - gamma expression correlated with insulin resistance index in offspring from RV ( r = - 0 . 62 , P < . 05 ) , but not in those from HV dams ( r = 0 . 13 , P > . 05 ) .", "entity": [], "task": "NER"}
{"text": "In conclusion , the HV diet during pregnancy interacts with postweaning diets in determining the expression of PPARs genes in a tissue - and age - dependent manner and uncouples the relationship between these genes and glucose regulation and fat mass in the rat offspring .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [219, 226]}], "task": "NER"}
{"text": "CCAAT / Enhancer - binding protein - homologous protein sensitizes to SU5416 by modulating p21 and PI3K / Akt signal pathway in FRO anaplastic thyroid carcinoma cells .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "SU5416 , vascular endothelial cell growth factor receptor inhibitor , suppresses hypoxia - induced angiogenesis , growth , proliferation , and metastasis in cancer cells .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "CCAAT / enhancer - binding protein - homologous protein ( CHOP ) has pivotal roles in regulation of growth and survival .", "entity": [], "task": "NER"}
{"text": "In the present study , we evaluated the effects of SU5416 on cell survival , p21 , and PI3K / Akt signal pathway in FRO anaplastic thyroid carcinoma ( ATC ) cells .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [51, 57]}], "task": "NER"}
{"text": "Moreover , we investigated the roles of CHOP in cell survival under condition of SU5416 treatment in FRO ATC cells .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "After SU5416 treatment , cell viability , PARP - 1 , and caspase - 3 protein levels were not changed .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [6, 12]}], "task": "NER"}
{"text": "p53 and p27 protein levels decreased while p21 protein levels increased .", "entity": [], "task": "NER"}
{"text": "Phospho - Akt protein levels were not altered .", "entity": [{"entity": "Phospho", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In SU5416 - treated situation , cell viability was not different before and after administration of either p21 siRNA or LY294002 whereas it was lessened after co - administration of p21 siRNA and LY294002 .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [3, 9]}, {"entity": "LY294002", "entity_type": "Chemical", "pos": [120, 128]}, {"entity": "LY294002", "entity_type": "Chemical", "pos": [196, 204]}], "task": "NER"}
{"text": "Compared to SU5416 treatment alone , cell viability was reduced with CHOP plasmid but it was unchanged with CHOP siRNA .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [12, 18]}], "task": "NER"}
{"text": "PARP - 1 and caspase - 3 protein levels with CHOP plasmid were elevated whereas the protein levels with CHOP siRNA were similar .", "entity": [], "task": "NER"}
{"text": "While CHOP plasmid transfection diminished p21 and phospho - Akt protein levels , CHOP siRNA transfection did not alter the protein levels .", "entity": [{"entity": "phospho", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "In conclusion , these results suggest that CHOP may sensitize FRO ATC cells to SU5416 thereby inhibiting cell survival by modulating p21 and PI3K / Akt signal pathway .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "Furthermore , these findings imply that CHOP may be a possible candidate as the chemosensitizing factor for induction of cytotoxicity in ATC cells exposed to SU5416 .", "entity": [{"entity": "SU5416", "entity_type": "Chemical", "pos": [158, 164]}], "task": "NER"}
{"text": "Functional phenotype of airway myocytes from asthmatic airways .", "entity": [], "task": "NER"}
{"text": "In asthma , the airway smooth muscle ( ASM ) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function .", "entity": [], "task": "NER"}
{"text": "The answer to the long debated question of what makes a ' healthy ' ASM cell become ' asthmatic ' still remains speculative .", "entity": [], "task": "NER"}
{"text": "What is known of an ' asthmatic ' ASM cell , is its ability to contribute to the hallmarks of asthma such as bronchoconstriction ( contractile phenotype ) , inflammation ( synthetic phenotype ) and ASM hyperplasia ( proliferative phenotype ) .", "entity": [], "task": "NER"}
{"text": "The phenotype of healthy or diseased ASM cells or tissue for the most part is determined by expression of key phenotypic markers .", "entity": [], "task": "NER"}
{"text": "ASM is commonly accepted to have different phenotypes : the contractile ( differentiated ) state versus the synthetic ( dedifferentiated ) state ( with the capacity to synthesize mediators , proliferate and migrate ) .", "entity": [], "task": "NER"}
{"text": "There is now accumulating evidence that the synthetic functions of ASM in culture derived from asthmatic and non - asthmatic donors differ .", "entity": [], "task": "NER"}
{"text": "Some of these differences include an altered profile and increased production of extracellular matrix proteins , pro - inflammatory mediators and adhesion receptors , collectively suggesting that ASM cells from asthmatic subjects have the capacity to alter their environment , actively participate in repair processes and functionally respond to changes in their microenvironment .", "entity": [], "task": "NER"}
{"text": "Lead - induced ER calcium release and inhibitory effects of methionine choline in cultured rat hippocampal neurons .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [18, 25]}, {"entity": "methionine choline", "entity_type": "Chemical", "pos": [60, 78]}], "task": "NER"}
{"text": "Lead , a ubiquitous neurotoxicant , can result in learning and memory dysfunction .", "entity": [], "task": "NER"}
{"text": "Long term potentiation in the hippocampus , a potential neural substrate for learning and memory , is thought to be linked to calcium - triggered intracellular events .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "In this study , laser scanning confocal microscopy was used to examine the effects of Pb ( 2 + ) on intracellular and endoplasmic reticulum free calcium concentration ( [ Ca ( 2 + ) ] ( i ) and [ Ca ( 2 + ) ] ( ER ) ) in cultured neonatal rat hippocampal neurons and their possible antagonism by methionine choline ; understanding these effects would help explain the lead - induced cognitive and learning dysfunction and explore efficient safety and relief strategies .", "entity": [{"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [86, 96]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [145, 152]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [171, 181]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [196, 206]}, {"entity": "methionine choline", "entity_type": "Chemical", "pos": [296, 314]}], "task": "NER"}
{"text": "The results showed that Pb ( 2 + ) increased [ Ca ( 2 + ) ] ( i ) and decreased [ Ca ( 2 + ) ] ( ER ) linearly in a time - and concentration - dependant manner , and Pb ( 2 + ) addition after the applying of a ryanodine receptor ( RyR ) antagonist and an inositol - 1 , 4 , 5 - triphosphate receptor ( IP ( 3 ) R ) antagonist did not increase [ Ca ( 2 + ) ] ( i ) .", "entity": [{"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [82, 92]}, {"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [166, 176]}, {"entity": "ryanodine", "entity_type": "Chemical", "pos": [210, 219]}, {"entity": "inositol - 1 , 4 , 5 - triphosphate", "entity_type": "Chemical", "pos": [255, 290]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [345, 355]}], "task": "NER"}
{"text": "The addition of 10 , 20 , or 40 mmol / L methionine choline simultaneously with addition of 10 mu mol / L Pb ( 2 + ) decreased [ Ca ( 2 + ) ] ( i ) in Ca ( 2 + ) - free culture medium by 39 . 0 % , 66 . 0 % , and 61 . 6 % , respectively , in a concentration - dependant manner in a certain dose range .", "entity": [{"entity": "methionine choline", "entity_type": "Chemical", "pos": [41, 59]}, {"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [106, 116]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [129, 139]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [151, 161]}], "task": "NER"}
{"text": "Our results suggest that Pb ( 2 + ) induces ER calcium release to increase the resting [ Ca ( 2 + ) ] ( i ) ; and methionine choline inhibit this increase in [ Ca ( 2 + ) ] ( i ) .", "entity": [{"entity": "Pb ( 2 + )", "entity_type": "Chemical", "pos": [25, 35]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "methionine choline", "entity_type": "Chemical", "pos": [114, 132]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [160, 170]}], "task": "NER"}
{"text": "Interactions between bufadienolides derived from toad venom and verapamil in langendorff - perfused guinea - pig hearts .", "entity": [{"entity": "bufadienolides", "entity_type": "Chemical", "pos": [21, 35]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "Drug toxicity may occur due to dangerous drug combination .", "entity": [], "task": "NER"}
{"text": "We aimed to investigate the influence of verapamil ( a P - gp inhibitor ) - - bufadienolides interaction on cardiotoxicity and bufadienolide uptake by the isolated heart .", "entity": [{"entity": "verapamil", "entity_type": "Chemical", "pos": [41, 50]}, {"entity": "bufadienolides", "entity_type": "Chemical", "pos": [78, 92]}, {"entity": "bufadienolide", "entity_type": "Chemical", "pos": [127, 140]}], "task": "NER"}
{"text": "The study was performed in Langendorff isolated perfused guinea - pig hearts by bufadienolides infusion in the absence and presence of verapamil ( 250 , 500ng / ml ) .", "entity": [{"entity": "bufadienolides", "entity_type": "Chemical", "pos": [80, 94]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "Arrhythmia parameters were evaluated by ECG and the content of bufadienolides in heart were measured by ultra - performance liquid chromatography tandem mass spectrometry ( UPLC - MS ) .", "entity": [{"entity": "bufadienolides", "entity_type": "Chemical", "pos": [63, 77]}], "task": "NER"}
{"text": "In the present of verapamil , the wide QRS duration and lightly rapid heart rate ( HR ) were markedly reduced in the early stage of bufadienolide intoxication .", "entity": [{"entity": "verapamil", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "bufadienolide", "entity_type": "Chemical", "pos": [132, 145]}], "task": "NER"}
{"text": "However , the ECG changes characterized by prolonged P - R interval , and slow heart rate and low QRS amplitude in the late stage of bufadienolide intoxication were significantly enhanced .", "entity": [{"entity": "bufadienolide", "entity_type": "Chemical", "pos": [133, 146]}], "task": "NER"}
{"text": "Furthermore , the contents of a variety of bufadienolide compounds in the verapamil + bufadienolide group were significantly higher when cardiac arrest occurred .", "entity": [{"entity": "bufadienolide", "entity_type": "Chemical", "pos": [43, 56]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [74, 83]}, {"entity": "bufadienolide", "entity_type": "Chemical", "pos": [86, 99]}], "task": "NER"}
{"text": "Although verapamil reduced the bufadienolide - induced ventricular arrhythmias , verapamil worsened heart block and lethal bradycardia of bufadienolides partly via increasing the uptake of bufadienolides in heart tissue , which could compromise the protective effects of verapamil against bufadienolide intoxication .", "entity": [{"entity": "verapamil", "entity_type": "Chemical", "pos": [9, 18]}, {"entity": "bufadienolide", "entity_type": "Chemical", "pos": [31, 44]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "bufadienolides", "entity_type": "Chemical", "pos": [138, 152]}, {"entity": "bufadienolides", "entity_type": "Chemical", "pos": [189, 203]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [271, 280]}, {"entity": "bufadienolide", "entity_type": "Chemical", "pos": [289, 302]}], "task": "NER"}
{"text": "These results suggested that the verapamil may produce dangerous interactions with drugs containing bufadienolides .", "entity": [{"entity": "verapamil", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "bufadienolides", "entity_type": "Chemical", "pos": [100, 114]}], "task": "NER"}
{"text": "Synthesis of NaP zeolite at room temperature and short crystallization time by sonochemical method .", "entity": [{"entity": "NaP zeolite", "entity_type": "Chemical", "pos": [13, 24]}], "task": "NER"}
{"text": "NaP zeolite nano crystals were synthesized by sonochemical method at room temperature with crystallization time of 3h .", "entity": [{"entity": "NaP zeolite", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "For comparison , to insure the effect of sonochemical method , the hydrothermal method at conventional synthesis condition , with same initial sol composition was studied .", "entity": [], "task": "NER"}
{"text": "NaP zeolites are directly formed by ultrasonic treatment without the application of autogenous pressure and also hydrothermal treatment .", "entity": [{"entity": "NaP zeolites", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "The effect of ultrasonic energy and irradiation time showed that with increasing sonication energy , the crystallinity of the powders decreased but phase purity remain unchanged .", "entity": [], "task": "NER"}
{"text": "The synthesized powders were characterized by XRD , IR , DTA TGA , FESEM , and TEM analysis .", "entity": [], "task": "NER"}
{"text": "FESEM images revealed that 50 nm zeolite crystals were formed at room temperature by using sonochemical method .", "entity": [], "task": "NER"}
{"text": "However , agglomerated particles having cactus / cabbage like structure was obtained by sonochemical method followed by hydrothermal treatment .", "entity": [], "task": "NER"}
{"text": "In sonochemical process , formation of cavitation and the collapsing of bubbles produced huge energy which is sufficient for crystallization of zeolite compared to that supplied by hydrothermal process for conventional synthesis .", "entity": [], "task": "NER"}
{"text": "With increasing irradiation energy and time , the crystallinity of the synthesized zeolite samples increased slightly .", "entity": [], "task": "NER"}
{"text": "The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context : Results from the European Project ACuteTox .", "entity": [], "task": "NER"}
{"text": "ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop , optimise and prevalidate a non - animal testing strategy for predicting human acute oral toxicity .", "entity": [], "task": "NER"}
{"text": "In its last 6months , a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones .", "entity": [], "task": "NER"}
{"text": "Thirty - two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project .", "entity": [], "task": "NER"}
{"text": "This paper describes the classification approaches studied : single step procedures and two step tiered testing strategies .", "entity": [], "task": "NER"}
{"text": "In summary , four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification .", "entity": [], "task": "NER"}
{"text": "In addition , a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells , with information on neurotoxicity alerts identified by the primary rat brain aggregates test method .", "entity": [], "task": "NER"}
{"text": "Octanol - water partition coefficients and in silico prediction of intestinal absorption and blood - brain barrier passage are also considered .", "entity": [{"entity": "Octanol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "This approach allows to reduce the number of chemicals wrongly predicted as not classified ( LD50 > 2000mg / kg b . w . ) .", "entity": [], "task": "NER"}
{"text": "Amino acid sequence of the ligand - binding domain of the aryl hydrocarbon receptor 1 predicts sensitivity of wild birds to effects of dioxin - like compounds .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [58, 74]}, {"entity": "dioxin", "entity_type": "Chemical", "pos": [135, 141]}], "task": "NER"}
{"text": "The sensitivity of avian species to the toxic effects of dioxin - like compounds ( DLCs ) varies up to 1000 - fold among species , and this variability has been associated with interspecies differences in aryl hydrocarbon receptor 1 ligand - binding domain ( AHR1 LBD ) sequence .", "entity": [{"entity": "dioxin", "entity_type": "Chemical", "pos": [57, 63]}, {"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [205, 221]}], "task": "NER"}
{"text": "We previously showed that LD ( 50 ) values , based on in ovo exposures to DLCs , were significantly correlated with in vitro EC ( 50 ) values obtained with a luciferase reporter gene ( LRG ) assay that measures AHR1 - mediated induction of cytochrome P4501A in COS - 7 cells transfected with avian AHR1 constructs .", "entity": [], "task": "NER"}
{"text": "Those findings suggest that the AHR1 LBD sequence and the LRG assay can be used to predict avian species sensitivity to DLCs .", "entity": [], "task": "NER"}
{"text": "In the present study , the AHR1 LBD sequences of 86 avian species were studied , and differences at amino acid sites 256 , 257 , 297 , 324 , 337 , and 380 were identified .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [100, 110]}], "task": "NER"}
{"text": "Site - directed mutagenesis , the LRG assay , and homology modeling highlighted the importance of each amino acid site in AHR1 sensitivity to 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin and other DLCs .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [103, 113]}, {"entity": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [142, 189]}], "task": "NER"}
{"text": "The results of the study revealed that ( 1 ) only amino acids at sites 324 and 380 affect the sensitivity of AHR1 expression constructs of the 86 avian species to DLCs and ( 2 ) in vitro luciferase activity of AHR1 constructs containing only the LBD of the species of interest is significantly correlated ( r ( 2 ) = 0 . 93 , p < 0 . 0001 ) with in ovo toxicity data for those species .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "These results indicate promise for the use of AHR1 LBD amino acid sequences independently , or combined with the LRG assay , to predict avian species sensitivity to DLCs .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "Acid - induced gelation behavior of soybean protein isolate with high intensity ultrasonic pre - treatments .", "entity": [], "task": "NER"}
{"text": "High intensity ultrasonic ( HUS , 20 kHz , 400 W ) pre - treatments of soybean protein isolate ( SPI ) improved the water holding capacity ( WHC ) , gel strength and gel firmness ( final elastic moduli ) of glucono - delta - lactone induced SPI gels ( GISG ) .", "entity": [{"entity": "glucono - delta - lactone", "entity_type": "Chemical", "pos": [207, 232]}], "task": "NER"}
{"text": "Sonication time ( 0 , 5 , 20 , and 40 min ) had a significant effect on the above three properties .", "entity": [], "task": "NER"}
{"text": "20 min HUS - GISG had the highest WHC ( 95 . 53 +/- 0 . 25 % ) , gel strength ( 60 . 90 +/- 2 . 87 g ) and gel firmness ( 96340Pa ) , compared with other samples .", "entity": [], "task": "NER"}
{"text": "Moreover , SH groups and non - covalent interactions of GISG also changed after HUS pre - treatments .", "entity": [{"entity": "SH", "entity_type": "Chemical", "pos": [11, 13]}], "task": "NER"}
{"text": "The HUS GISG had denser and more uniform microstructures than the untreated GISG .", "entity": [], "task": "NER"}
{"text": "Rheological investments showed that the cooling step ( reduce the temperature from 95 to 25 degrees C at a speed of 2 degrees C / min ) was more important for the HUS GISG network formation while the heat preservation step ( keep temperature at 95 for 20 min ) was more important for the untreated GISG .", "entity": [], "task": "NER"}
{"text": "HUS reduced the particle size of SPI and Pearson correlation test showed that the particle size of SPI dispersions was negatively correlated with WHC , gel strength and gel firmness .", "entity": [], "task": "NER"}
{"text": "Proteomic allergen - peptide / protein interaction assay for the identification of human skin sensitizers .", "entity": [], "task": "NER"}
{"text": "Modification of proteins by skin sensitizers is a pivotal step in T cell mediated allergic contact dermatitis ( ACD ) .", "entity": [], "task": "NER"}
{"text": "In this process small reactive chemicals interact covalently or non - covalently with cellular or extracellular skin self - proteins or self - peptides to become recognized by the human immune system .", "entity": [], "task": "NER"}
{"text": "Aiming to develop a novel non - animal in vitro test system for predicting sensitization potential of small reactive chemicals in human skin the allergen - peptide / protein interaction assay ( APIA ) has been developed .", "entity": [], "task": "NER"}
{"text": "By applying modern proteomic technologies together with a target peptide containing all amino acids , the assay permits the profiling of all amino acid specific allergen - peptide interactions .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [141, 151]}], "task": "NER"}
{"text": "Moreover , potentially crucial allergen - specific Cys - modifications are qualitatively monitored by mass spectrometry and confirmed by a dual peptide approach .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "Assay conditions chosen mimic the distinct human epidermal reactivity compartments of the skin surface ( pH 5 . 5 ) , stratum basale ( pH 6 . 8 ) , and typical physiological conditions ( pH 7 . 4 ) .", "entity": [], "task": "NER"}
{"text": "An extreme as well as a moderate human contact sensitizer produced Cys - specific mass shifts , whereas a skin irritant did not .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [67, 70]}], "task": "NER"}
{"text": "Our data indicate that MALDI - MS based and skin - related in vitro technology platforms - like the APIA - are promising tools in developing alternative non - animal allergen assays .", "entity": [], "task": "NER"}
{"text": "This will assist in chemical classification and next generation risk assessment strategies , including REACH and experimental immunotoxicology .", "entity": [], "task": "NER"}
{"text": "An overview of transcriptional regulation in response to toxicological insult .", "entity": [], "task": "NER"}
{"text": "The completion of the human genome project and the subsequent advent of DNA microarray and high - throughput sequencing technologies have led to a renaissance in molecular toxicology .", "entity": [], "task": "NER"}
{"text": "Toxicogenomic data sets , from both in vivo and in vitro studies , are growing exponentially , providing a wealth of information on regulation of stress pathways at the transcriptome level .", "entity": [], "task": "NER"}
{"text": "Through such studies , we are now beginning to appreciate the diversity and complexity of biological responses to xenobiotics .", "entity": [], "task": "NER"}
{"text": "In this review , we aim to consolidate and summarise the major toxicologically relevant transcription factor - governed molecular pathways .", "entity": [], "task": "NER"}
{"text": "It is becoming clear that different chemical entities can cause oxidative , genotoxic and proteotoxic stress , which induce cellular responses in an effort to restore homoeostasis .", "entity": [], "task": "NER"}
{"text": "Primary among the response pathways involved are NFE2L2 ( Nrf2 ) , NFE2L1 ( Nrf1 ) , p53 , heat shock factor and the unfolded protein response .", "entity": [], "task": "NER"}
{"text": "Additionally , more specific mechanisms exist where xenobiotics act as ligands , including the aryl hydrocarbon receptor , metal - responsive transcription factor - 1 and the nuclear receptor family of transcription factors .", "entity": [{"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [95, 111]}], "task": "NER"}
{"text": "Other pathways including the immunomodulatory transcription factors NF - kappa B and STAT together with the hypoxia - inducible transcription factor HIF are also implicated in cellular responses to xenobiotic exposure .", "entity": [], "task": "NER"}
{"text": "A less specific but equally important aspect to cellular injury controlled by transcriptional activity is loss of tissue - specific gene expression , resulting in dedifferentiation of target cells and compromise of tissue function .", "entity": [], "task": "NER"}
{"text": "Here , we review these pathways and the genes they regulate in order to provide an overview of this growing field of molecular toxicology .", "entity": [], "task": "NER"}
{"text": "Creaming enhancement in a liter scale ultrasonic reactor at selected transducer configurations and frequencies .", "entity": [], "task": "NER"}
{"text": "Recent research has shown that high frequency ultrasound ( 0 . 4 - 3 MHz ) , can enhance milkfat separation in small scale systems able to treat only a few milliliters of sample .", "entity": [], "task": "NER"}
{"text": "In this work , the effect of ultrasonic standing waves on milkfat creaming was studied in a 6L reactor and the influence of different frequencies and transducer configurations in direct contact with the fluid was investigated .", "entity": [], "task": "NER"}
{"text": "A recombined coarse milk emulsion with fat globules stained with oil - red - O dye was selected for the separation trials .", "entity": [{"entity": "oil - red - O", "entity_type": "Chemical", "pos": [65, 78]}], "task": "NER"}
{"text": "Runs were performed with one or two transducers placed in vertical ( parallel or perpendicular ) and horizontal positions ( at the reactor base ) at 0 . 4 , 1 and / or 2 MHz ( specific energy 8 . 5 +/- 0 . 6 kJ / kg per transducer ) .", "entity": [], "task": "NER"}
{"text": "Creaming behavior was assessed by measuring the thickness of the separated cream layer .", "entity": [], "task": "NER"}
{"text": "Other methods supporting this assessment included the measurement of fat content , backscattering , particle size distribution , and microscopy of samples taken at the bottom and top of the reactor .", "entity": [], "task": "NER"}
{"text": "Most efficient creaming was found after treatment at 0 . 4 MHz in single and double vertical transducer configurations .", "entity": [], "task": "NER"}
{"text": "Among these configurations , a higher separation rate was obtained when sonicating at 0 . 4 MHz in a vertical perpendicular double transducer setup .", "entity": [], "task": "NER"}
{"text": "The horizontal transducer configuration promoted creaming at 2 MHz only .", "entity": [], "task": "NER"}
{"text": "Fat globule size increase was observed when creaming occurred .", "entity": [], "task": "NER"}
{"text": "This research highlights the potential for enhanced separation of milkfat in larger scale systems from selected transducer configurations in contact with a dairy emulsion , or emulsion splitting in general .", "entity": [], "task": "NER"}
{"text": "Variations in the nature of behavioral experience can differentially alter the consequences of developmental exposures to lead , prenatal stress , and the combination .", "entity": [], "task": "NER"}
{"text": "Behavioral experience ( BE ) can critically influence later behavior and brain function , but the central nervous system ( CNS ) consequences of most developmental neurotoxicants are examined in the absence of any such context .", "entity": [], "task": "NER"}
{"text": "We previously demonstrated marked differences in neurotransmitter changes produced by developmental lead ( Pb ) exposure +/- prenatal stress ( PS ) depending upon whether or not rats had been given BE ( Cory - Slechta , D .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [107, 109]}], "task": "NER"}
{"text": "A . , Virgolini , M .", "entity": [], "task": "NER"}
{"text": "B . , Rossi - George , A . , Weston , D . , and Thiruchelvam , M .", "entity": [], "task": "NER"}
{"text": "( 2009 ) .", "entity": [], "task": "NER"}
{"text": "The current study examined the hypothesis that the nature of the BE itself would be a critical determinant of outcome in mice that had been continually exposed to 0 or 100 ppm Pb acetate in drinking water alone or in combination with prenatal restraint stress .", "entity": [{"entity": "Pb acetate", "entity_type": "Chemical", "pos": [176, 186]}], "task": "NER"}
{"text": "Half of the offspring in each of the four resulting groups / gender were exposed to positively reinforced ( food - rewarded Fixed Interval schedule - controlled behavior ) or negatively reinforced ( inescapable forced swim ) BE .", "entity": [], "task": "NER"}
{"text": "Brain monoamines and amino acids differed significantly in relation to BE , even in control animals , as did the trajectory of effects of Pb +/- PS , particularly in frontal cortex , hippocampus ( both genders ) , and midbrain ( males ) .", "entity": [{"entity": "monoamines", "entity_type": "Chemical", "pos": [6, 16]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [21, 32]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [138, 140]}], "task": "NER"}
{"text": "In males , Pb +/- PS - related changes in neurotransmitters correlated with behavioral performance .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [11, 13]}], "task": "NER"}
{"text": "These findings suggest that CNS consequences of developmental toxicants studied in the absence of a broader spectrum of BEs may not necessarily be predictive of human outcomes .", "entity": [], "task": "NER"}
{"text": "Evaluating the role of specific BEs as a modulator of neurodevelopmental insults offers the opportunity to determine what specific BEs may ameliorate the associated impacts and can assist in establishing underlying neurobiological mechanisms .", "entity": [], "task": "NER"}
{"text": "alpha - Amino - alpha ' - Halomethylketones : Synthetic Methodologies and Pharmaceutical Applications as Serine and Cysteine Protease Inhibitors .", "entity": [{"entity": "alpha - Amino - alpha ' - Halomethylketones", "entity_type": "Chemical", "pos": [0, 43]}, {"entity": "Serine", "entity_type": "Chemical", "pos": [105, 111]}, {"entity": "Cysteine", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "alpha - Amino - alpha ' - halomethylketones are interesting scaffolds bearing ( at least ) two sequential electrophilic carbons that by interacting with the nucleophilic moieties of several enzymes , represent the ideal candidates for in vivo and in vitro inhibition studies .", "entity": [{"entity": "alpha - Amino - alpha ' - halomethylketones", "entity_type": "Chemical", "pos": [0, 43]}, {"entity": "carbons", "entity_type": "Chemical", "pos": [120, 127]}], "task": "NER"}
{"text": "In this work a summary of their use as optimal inhibitors of physiologically relevant serine and cysteine proteases is given with a particular emphasis on recently established SAR studies .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [86, 92]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "A brief survey of the most relevant synthetic processes for their obtainment and the importance they possess in synthetic medicinal chemistry is reported .", "entity": [], "task": "NER"}
{"text": "Cholinergic modulation by opioid receptor ligands : potential application to Alzheimer ' s disease .", "entity": [], "task": "NER"}
{"text": "Morphinans have a storied history in medicinal chemistry as pain management drugs but have received attention as modulators of cholinergic signaling for the treatment of Alzheimer ' s Disease ( AD ) .", "entity": [{"entity": "Morphinans", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Galantamine is a reversible , competitive acetylcholinesterase ( AChE ) inhibitor and allosteric potentiating ligand of nicotinic acetylcholine receptors ( nAChR - APL ) that shares many common structural elements with morphinan - based opioids .", "entity": [{"entity": "Galantamine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "morphinan", "entity_type": "Chemical", "pos": [219, 228]}], "task": "NER"}
{"text": "The structurally diverse opioids codeine and eseroline , like galantamine , are also nAChR - APL that have greatly diminished affinity for AChE , representing potential lead compounds for selective nAChR - APL development .", "entity": [{"entity": "codeine", "entity_type": "Chemical", "pos": [33, 40]}, {"entity": "eseroline", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "galantamine", "entity_type": "Chemical", "pos": [62, 73]}], "task": "NER"}
{"text": "In accordance with the emerging repurposing trend of evaluating known compounds for novel pharmacological activity , ongoing research on augmentation of cholinergic signaling that has been aided by the use of opioids will be reviewed .", "entity": [], "task": "NER"}
{"text": "Adhesion of osteoblasts to a vertically aligned TiO2 nanotube surface .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "The adhesion of cells to vertically aligned TiO2 nanotubes is reviewed .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "The attraction between a negatively charged nanotube surface and a negatively charged osteoblast is facilitated by charged protein - mediators like proteins with a quadrupolar internal charge distribution , fibronectin and vitronectin .", "entity": [], "task": "NER"}
{"text": "It is shown that adhesion and spreading of osteoblasts on vertically aligned TiO2 nanotube surfaces depend on the diameter of the nanotubes .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "Apparently , a small diameter nanotube surface has on average more sharp convex edges per unit area than a large one , leading to stronger binding affinity on its surface .", "entity": [], "task": "NER"}
{"text": "Manganese - enhanced magnetic resonance imaging detects declining pancreatic beta - cell mass in a cyclophosphamide - accelerated mouse model of type 1 diabetes .", "entity": [{"entity": "Manganese", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [99, 115]}], "task": "NER"}
{"text": "Currently , there is no ideal noninvasive method to quantify the progressive loss of pancreatic beta - cell mass ( BCM ) that occurs in type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "Magnetic resonance imaging has detected gross differences in BCM between healthy and diabetic mice using the contrast agent manganese , which labels functional beta - cells and increases the water proton relaxation rate ( R1 ) , but its ability to measure gradations in BCM during disease progression is unknown .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [124, 133]}], "task": "NER"}
{"text": "Our objective was to test the hypothesis that measurements of the manganese - enhanced pancreatic R1 could detect decreasing BCM in a mouse model of type 1 diabetes .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "We used cyclophosphamide - accelerated BDC2 . 5 T - cell receptor transgenic nonobese diabetic mice , which experience development of type 1 diabetes during a 7 - day time period after cyclophosphamide injection , whereas transgene - negative mice do not .", "entity": [{"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [8, 24]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [185, 201]}], "task": "NER"}
{"text": "We measured the manganese - enhanced pancreatic R1 before cyclophosphamide injection ( day 0 ) and on days 3 , 4 , 5 , and 7 afterward .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [58, 74]}], "task": "NER"}
{"text": "Pancreatic R1 remained constant in transgene - negative mice and decreased stepwise day - to - day in transgene - positive mice , mirroring their loss of BCM , confirmed by pancreatic insulin measurements and histology .", "entity": [], "task": "NER"}
{"text": "Changes in R1 in transgene - positive mice occurred before elevations in blood glucose , a clinical indicator of diabetes , suggesting potential for early noninvasive detection of changes in functional BCM .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "Bcl - 2 and Bcl - xL suppress glucose signaling in pancreatic beta - cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "B - cell lymphoma 2 ( Bcl - 2 ) family proteins are established regulators of cell survival , but their involvement in the normal function of primary cells has only recently begun to receive attention .", "entity": [], "task": "NER"}
{"text": "In this study , we demonstrate that chemical and genetic loss - of - function of antiapoptotic Bcl - 2 and Bcl - x ( L ) significantly augments glucose - dependent metabolic and Ca ( 2 + ) signals in primary pancreatic beta - cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [144, 151]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [178, 188]}], "task": "NER"}
{"text": "Antagonism of Bcl - 2 / Bcl - x ( L ) by two distinct small - molecule compounds rapidly hyperpolarized beta - cell mitochondria , increased cytosolic Ca ( 2 + ) , and stimulated insulin release via the ATP - dependent pathway in beta - cell under substimulatory glucose conditions .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [151, 161]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [203, 206]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [263, 270]}], "task": "NER"}
{"text": "Experiments with single and double Bax - Bak knockout beta - cells established that this occurred independently of these proapoptotic binding partners .", "entity": [], "task": "NER"}
{"text": "Pancreatic beta - cells from Bcl - 2 ( - / - ) mice responded to glucose with significantly increased NAD ( P ) H levels and cytosolic Ca ( 2 + ) signals , as well as significantly augmented insulin secretion .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [65, 72]}, {"entity": "NAD ( P ) H", "entity_type": "Chemical", "pos": [102, 113]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [135, 145]}], "task": "NER"}
{"text": "Inducible deletion of Bcl - x ( L ) in adult mouse beta - cells also increased glucose - stimulated NAD ( P ) H and Ca ( 2 + ) responses and resulted in an improvement of in vivo glucose tolerance in the conditional Bcl - x ( L ) knockout animals .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "NAD ( P ) H", "entity_type": "Chemical", "pos": [100, 111]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [116, 126]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "Our work suggests that prosurvival Bcl proteins normally dampen the beta - cell response to glucose and thus reveals these core apoptosis proteins as integrators of cell death and physiology in pancreatic beta - cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "Dual - responsive nanoparticles and their self - assembly .", "entity": [], "task": "NER"}
{"text": "Dual - responsive nanoparticles are designed by functionalizing magnetic cores with light - responsive ligands .", "entity": [], "task": "NER"}
{"text": "These materials respond to both light and magnetic fields and can be assembled into various higher - order structures , depending on the relative contributions of these two stimuli .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetics , pharmacodynamics and clinical use of valganciclovir in newborns with symptomatic congenital cytomegalovirus infection .", "entity": [{"entity": "valganciclovir", "entity_type": "Chemical", "pos": [56, 70]}], "task": "NER"}
{"text": "Congenital cytomegalovirus infection is the most common cause of nonhereditary sensorineural hearing loss and an important cause of psychomotor retardation .", "entity": [], "task": "NER"}
{"text": "Newborns suffering from symptomatic congenital cytomegalovirus infection have been typically treated with i . v . ganciclovir ( GCV ) .", "entity": [{"entity": "ganciclovir", "entity_type": "Chemical", "pos": [114, 125]}, {"entity": "GCV", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "Nowadays valganciclovir ( V - GCV ) , a mono - valyl ester pro - drug of GCV , is available as an oral syrup .", "entity": [{"entity": "valganciclovir", "entity_type": "Chemical", "pos": [9, 23]}, {"entity": "V - GCV", "entity_type": "Chemical", "pos": [26, 33]}, {"entity": "mono - valyl ester", "entity_type": "Chemical", "pos": [40, 58]}, {"entity": "GCV", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "The existing literature demonstrated that V - GCV is well absorbed from the gastrointestinal tract and is rapidly converted into GCV in the intestinal wall and liver .", "entity": [{"entity": "V - GCV", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "GCV", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "The mechanism of antiviral action is the same that has been described for GCV .", "entity": [{"entity": "GCV", "entity_type": "Chemical", "pos": [74, 77]}], "task": "NER"}
{"text": "All these characteristics make this formulation particularly suitable for the symptomatic congenitally infected newborns .", "entity": [], "task": "NER"}
{"text": "In neonates , V - GCV oral formulation proved stable and constant GVC plasma concentrations , in the suggested therapeutic range .", "entity": [{"entity": "V - GCV", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "The syrup demonstrated to be clinically effective and well tolerated and to be appropriate for a prolonged post - discharge therapy avoiding the discomfort of hospitalization , reducing the risk for nosocomial infections and decreasing the cost for the National Health Service .", "entity": [], "task": "NER"}
{"text": "This article reviews all the available literature about V - GCV syrup in the treatment of newborns and infants with congenital CMV infection with the regard to pharmacokinetics , pharmacodynamic properties and clinical use , focussing on new data and on our experience .", "entity": [{"entity": "V - GCV", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "Noncanonical control of C . elegans germline apoptosis by the insulin / IGF - 1 and Ras / MAPK signaling pathways .", "entity": [], "task": "NER"}
{"text": "The insulin / IGF - 1 pathway controls a number of physiological processes in the nematode worm Caenorhabditis elegans , including development , aging and stress response .", "entity": [], "task": "NER"}
{"text": "We previously found that the Akt / PKB ortholog AKT - 1 dampens the apoptotic response to genotoxic stress in the germline by negatively regulating the p53 - like transcription factor CEP - 1 .", "entity": [], "task": "NER"}
{"text": "Here , we report unexpected rearrangements to the insulin / IGF - 1 pathway , whereby the insulin - like receptor DAF - 2 and 3 - phosphoinositide - dependent protein kinase PDK - 1 oppose AKT - 1 to promote DNA damage - induced apoptosis .", "entity": [{"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [130, 146]}], "task": "NER"}
{"text": "While DNA damage does not affect phosphorylation at the PDK - 1 site Thr350 / Thr308 of AKT - 1 , it increased phosphorylation at Ser517 / Ser473 .", "entity": [{"entity": "Ser517", "entity_type": "Chemical", "pos": [130, 136]}, {"entity": "Ser473", "entity_type": "Chemical", "pos": [139, 145]}], "task": "NER"}
{"text": "Although ablation of daf - 2 or pdk - 1 completely suppressed akt - 1 - dependent apoptosis , the transcriptional activation of CEP - 1 was unaffected , suggesting that daf - 2 and pdk - 1 act independently or downstream of cep - 1 and akt - 1 .", "entity": [], "task": "NER"}
{"text": "Ablation of the akt - 1 paralog akt - 2 or the downstream target of the insulin / IGF - 1 pathway daf - 16 ( a FOXO transcription factor ) restored sensitivity to damage - induced apoptosis in daf - 2 and pdk - 1 mutants .", "entity": [], "task": "NER"}
{"text": "In addition , daf - 2 and pdk - 1 mutants have reduced levels of phospho - MPK - 1 / ERK in their germ cells , indicating that the insulin / IGF - 1 pathway promotes Ras signaling in the germline .", "entity": [{"entity": "phospho", "entity_type": "Chemical", "pos": [65, 72]}], "task": "NER"}
{"text": "Ablation of the Ras effector gla - 3 , a negative regulator of mpk - 1 , restored sensitivity to apoptosis in daf - 2 mutants , suggesting that gla - 3 acts downstream of daf - 2 .", "entity": [], "task": "NER"}
{"text": "In addition , the hypersensitivity of let - 60 / Ras gain - of - function mutants to damage - induced apoptosis was suppressed to wild - type levels by ablation of daf - 2 .", "entity": [], "task": "NER"}
{"text": "Thus , insulin / IGF - 1 signaling selectively engages AKT - 2 / DAF - 16 to promote DNA damage - induced germ cell apoptosis downstream of CEP - 1 through the Ras pathway .", "entity": [], "task": "NER"}
{"text": "Inactivation of anoctamin - 6 / Tmem16f , a regulator of phosphatidylserine scrambling in osteoblasts , leads to decreased mineral deposition in skeletal tissues .", "entity": [{"entity": "phosphatidylserine", "entity_type": "Chemical", "pos": [57, 75]}], "task": "NER"}
{"text": "During vertebrate skeletal development , osteoblasts produce a mineralized bone matrix by deposition of hydroxyapatite crystals in the extracellular matrix .", "entity": [{"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [104, 118]}], "task": "NER"}
{"text": "Anoctamin6 / Tmem16F ( Ano6 ) belongs to a conserved family of transmembrane proteins with chloride channel properties .", "entity": [{"entity": "chloride", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "In addition , Ano6 has been linked to phosphatidylserine ( PS ) scrambling in the plasma membrane .", "entity": [{"entity": "phosphatidylserine", "entity_type": "Chemical", "pos": [38, 56]}], "task": "NER"}
{"text": "During skeletogenesis , Ano6 mRNA is expressed in differentiating and mature osteoblasts .", "entity": [], "task": "NER"}
{"text": "Deletion of Ano6 in mice results in reduced skeleton size and skeletal deformities .", "entity": [], "task": "NER"}
{"text": "Molecular analysis revealed that chondrocyte and osteoblast differentiation are not disturbed .", "entity": [], "task": "NER"}
{"text": "However , mutant mice display increased regions of nonmineralized , Ibsp - expressing osteoblasts in the periosteum during embryonic development and increased areas of uncalcified osteoid postnatally .", "entity": [], "task": "NER"}
{"text": "In primary Ano6 ( - / - ) osteoblasts , mineralization is delayed , indicating a cell autonomous function of Ano6 .", "entity": [], "task": "NER"}
{"text": "Furthermore , we demonstrate that calcium - dependent PS scrambling is impaired in osteoblasts .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [34, 41]}], "task": "NER"}
{"text": "Our study is the first to our knowledge to reveal the requirement of Ano6 in PS scrambling in osteoblasts , supporting a function of PS exposure in the deposition of hydroxyapatite .", "entity": [{"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [166, 180]}], "task": "NER"}
{"text": "Fragrance chemicals lyral and lilial decrease viability of HaCat cells ' by increasing free radical production and lowering intracellular ATP level : protection by antioxidants .", "entity": [{"entity": "lyral", "entity_type": "Chemical", "pos": [20, 25]}, {"entity": "lilial", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [138, 141]}], "task": "NER"}
{"text": "We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals : lyral and lilial .", "entity": [{"entity": "lyral", "entity_type": "Chemical", "pos": [116, 121]}, {"entity": "lilial", "entity_type": "Chemical", "pos": [126, 132]}], "task": "NER"}
{"text": "Whereas both chemicals exerted a significant effect on primary keratinocyte ( s ) , HaCat cells , no effect was obtained with any of HepG2 , Hek293 , Caco2 , NIH3T3 , and MCF7 cells .", "entity": [], "task": "NER"}
{"text": "Lyral and lilial : ( a ) decreased the viability of HaCat cells with a 50 % cell death at 100 and 60 nM respectively ; ( b ) decreased significantly in a dose dependant manner the intracellular ATP level following 12 - h of treatment ; ( c ) inhibited complexes I and II of electron transport chain in liver sub - mitochondrial particles ; and ( d ) increased reactive oxygen species generation that was reversed by N - acetyl cysteine and trolox and the natural antioxidant lipoic acid , without influencing the level of free and / or oxidized glutathione .", "entity": [{"entity": "Lyral", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "lilial", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [194, 197]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [369, 375]}, {"entity": "N - acetyl cysteine", "entity_type": "Chemical", "pos": [416, 435]}, {"entity": "trolox", "entity_type": "Chemical", "pos": [440, 446]}, {"entity": "lipoic acid", "entity_type": "Chemical", "pos": [475, 486]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [545, 556]}], "task": "NER"}
{"text": "Lipoic acid protected HaCat cells against the decrease in viability induced by either compound .", "entity": [{"entity": "Lipoic acid", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Dehydrogenation of lyral and lilial produce alpha , beta - unsaturated aldehydes , that reacts with lipoic acid requiring proteins resulting in their inhibition .", "entity": [{"entity": "lyral", "entity_type": "Chemical", "pos": [19, 24]}, {"entity": "lilial", "entity_type": "Chemical", "pos": [29, 35]}, {"entity": "alpha , beta - unsaturated aldehydes", "entity_type": "Chemical", "pos": [44, 80]}, {"entity": "lipoic acid", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain , increase ROS production , derange mitochondrial membrane potential , and decrease cellular ATP level , leading thus to cell death .", "entity": [{"entity": "lyral", "entity_type": "Chemical", "pos": [11, 16]}, {"entity": "lilial", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [200, 203]}], "task": "NER"}
{"text": "Silver nanoparticles induce toxicity in A549 cells via ROS - dependent and ROS - independent pathways .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Silver nanoparticles ( AgNPs ) are incorporated into a large number of consumer and medical products .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Several experiments have demonstrated that AgNPs can be toxic to the vital organs of humans and especially to the lung .", "entity": [], "task": "NER"}
{"text": "The present study evaluated the in vitro mechanisms of AgNP ( < 100 nm ) toxicity in relationship to the generation of reactive oxygen species ( ROS ) in A549 cells .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [128, 134]}], "task": "NER"}
{"text": "AgNPs caused ROS formation in the cells , a reduction in their cell viability and mitochondrial membrane potential ( MMP ) , an increase in the proportion of cells in the sub - G1 ( apoptosis ) population , S phase arrest and down - regulation of the cell cycle associated proliferating cell nuclear antigen ( PCNA ) protein , in a concentration - and time - dependent manner .", "entity": [], "task": "NER"}
{"text": "Pretreatment of the A549 cells with N - acetyl - cysteine ( NAC ) , an antioxidant , decreased the effects of AgNPs on the reduced cell viability , change in the MMP and proportion of cells in the sub - G1population , but had no effect on the AgNP - mediated S phase arrest or down - regulation of PCNA .", "entity": [{"entity": "N - acetyl - cysteine", "entity_type": "Chemical", "pos": [36, 57]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "These observations allow us to propose that the in vitro toxic effects of AgNPs on A549 cells are mediated via both ROS - dependent ( cytotoxicity ) and ROS - independent ( cell cycle arrest ) pathways .", "entity": [], "task": "NER"}
{"text": "In silico structural and functional analysis of the human TOPK protein by structure modeling and molecular dynamics studies .", "entity": [], "task": "NER"}
{"text": "Over expression of T - lymphokine - activated killer cell - originated protein kinase ( TOPK ) has been associated with leukemia , myeloma tumors and various other cancers .", "entity": [], "task": "NER"}
{"text": "The function and regulatory mechanism of TOPK in tumor cells remains unclear .", "entity": [], "task": "NER"}
{"text": "Structural studies that could reveal the regulatory mechanism have been a challenge because of the unavailabity of TOPK ' s crystal structure .", "entity": [], "task": "NER"}
{"text": "Hence , in this study , the 3D structure of TOPK protein has been constructed by using multiple templates .", "entity": [], "task": "NER"}
{"text": "The quality and reliability of the generated model was checked and the molecular dynamics method was utilized to refine the model .", "entity": [], "task": "NER"}
{"text": "APBS method was employed to know the electrostatic potential surface of the modeled protein and it was found that the optimum pH for protein stability is 3 . 4 which will further help in mechanistic hypothesis of TOPK protein .", "entity": [], "task": "NER"}
{"text": "Active site of TOPK was identified from available literature and HTVS was employed to identify the lead molecules .", "entity": [], "task": "NER"}
{"text": "The expected binding modes of protein - ligand complexes were reproduced in the MD simulation which indicates that the complex is relatively stable .", "entity": [], "task": "NER"}
{"text": "The pharmacokinetic properties of the lead molecules are also under acceptable range .", "entity": [], "task": "NER"}
{"text": "TOPK act as a substrate for CDK1 and the protein - protein docking and dynamics studies were carried out to analyze the effect of Thr9Ala mutation of TOPK in the two protein complex formation .", "entity": [], "task": "NER"}
{"text": "It shows that the wild type complex is more stable when compared with the mutant type .", "entity": [], "task": "NER"}
{"text": "Such structural information at atomic level not only exhibits the action modes of TOPK inhibitors but also furnishes a novel starting point for structure based drug design of TOPK inhibitors .", "entity": [], "task": "NER"}
{"text": "Low calorie and carbohydrate diet : to improve the cardiovascular risk indicators in overweight or obese adults with prediabetes .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [16, 28]}], "task": "NER"}
{"text": "Our objective was to evaluate the effects of a moderate calorie and carbohydrate - restricted diet on cardiovascular risk indicators in overweight or obese patients with prediabetes .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [68, 80]}], "task": "NER"}
{"text": "A clinical trial was conducted in which 86 subjects presenting with overweight or obesity and prediabetes received a personalized diet of 1 , 200 to 1 , 700 calories with a distribution of 50 % carbohydrates , 20 % proteins , and 30 % fat .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [194, 207]}], "task": "NER"}
{"text": "Body weight , fat mass , and lean mass were measured through bioimpedance .", "entity": [], "task": "NER"}
{"text": "Glucose , total cholesterol , high density lipoprotein cholesterol and low density cholesterol , and triglycerides were measured .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [55, 66]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [83, 94]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [101, 114]}], "task": "NER"}
{"text": "The measurements were taken at the beginning of , and at , 6 and 12 months during the intervention , and the differences were compared by paired Student ' s t and chi ( 2 ) tests .", "entity": [], "task": "NER"}
{"text": "At 12 months , a significant reduction was noticed in body weight in patients with overweight and obesity ( 72 . 4 +/- 7 . 8 - 69 . 6 +/- 7 . 5 kg ) ( 85 . 7 +/- 14 . 8 - 80 . 2 +/- 12 . 7 kg ) with body mass index ( 28 . 2 +/- 0 . 8 - 27 . 2 +/- 2 . 1 kg / m ( 2 ) ) ( 34 . 3 +/- 3 . 5 - 32 . 1 +/- 3 . 2 kg / m ( 2 ) ) , systolic ( 120 . 9 +/- 14 . 2 - 112 . 4 +/- 11 . 5 mmHg ) ( 124 . 1 +/- 11 . 9 - 115 . 7 +/- 14 . 0 mmHg ) , diastolic blood pressures ( 79 . 0 +/- 9 . 3 - 71 . 8 +/- 8 . 3 mmHg ) ( 80 . 4 +/- 9 . 0 - 73 . 7 +/- 13 . 1 mmHg ) , glucose ( 106 . 0 +/- 8 . 9 - 95 . 9 +/- 7 . 5 mg / dL ) ( 107 . 3 +/- 7 . 0 - 97 . 0 +/- 8 . 2 mg / dL ) , and significant improvement on lipid profile ( p < 0 . 05 ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [551, 558]}], "task": "NER"}
{"text": "The restrictions in the calorie and carbohydrate diet decrease the cardiovascular risk indicators in overweight or obese adults with prediabetes .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [36, 48]}], "task": "NER"}
{"text": "Quantitation of UGT1A1 in human liver microsomes using stable isotope - labelled peptides and mass spectrometry based proteomic approaches .", "entity": [], "task": "NER"}
{"text": "1 . UDP - glucuronosyltransferases ( UGTs ) are a group of drug - metabolizing enzymes that catalyse the conjugation of endogeonous compounds and xenobiotics to yield hydrophilic glucuronides which subsequently undergo excretion .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "This report describes an approach for the identification and accurate quantitation of human UGT1A1 in complex biological matrices using liquid chromatography / mass spectrometry / mass spectrometry ( LC - MS / MS ) analysis of protein digests .", "entity": [], "task": "NER"}
{"text": "2 . A stable isotope - labelled ( SIL ) peptide of a unique peptide spanning residues 54 - 69 in exon 1 of the human UGT1A1 protein with the sequence RIYLSADPALVVIEHG was synthesized .", "entity": [], "task": "NER"}
{"text": "The peptide sequence synthesized was in the reverse order of the human peptide with the stable isotope - labels in the amino acid arginine ( ( 13 ) C6 ( 15 ) N4 ) resulting in an increase in the mass of the SIL peptide of 10 amu , from 1753 to 1763 .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [119, 129]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "( 13 ) C6 ( 15 ) N4", "entity_type": "Chemical", "pos": [141, 160]}], "task": "NER"}
{"text": "The SIL peptide was quantitated by injecting increasing concentrations of the peptide into the LC - MS to obtain a standard curve .", "entity": [], "task": "NER"}
{"text": "3 . The labelled peptide along with precursor ion monitoring was used to quantify the levels of UGT1A1 in commercial recombinant preparations ( supersomes ) and individual human liver microsomal samples and pooled human liver micrsomes obtained from BD Biosciences .", "entity": [], "task": "NER"}
{"text": "4 . Glucuronidation activity studies were performed , which demonstrated a positive correlation between enzyme activity levels and the UGT1A1 content in the liver microsomes obtained from individual human donors .", "entity": [], "task": "NER"}
{"text": "A dose response study to assess effects after dietary administration of diisononyl phthalate ( DINP ) in gestation and lactation on male rat sexual development .", "entity": [{"entity": "diisononyl phthalate", "entity_type": "Chemical", "pos": [72, 92]}, {"entity": "DINP", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Male rat sexual development was evaluated after dietary administration of 0 , 760 , 3800 , 11 , 400 ppm diisononyl phthalate ( DiNP ) and 7600 ppm dibutyl phthalate ( DBP ) from gestation day ( GD ) 12 to postnatal day ( PND ) 14 .", "entity": [{"entity": "diisononyl phthalate", "entity_type": "Chemical", "pos": [104, 124]}, {"entity": "DiNP", "entity_type": "Chemical", "pos": [127, 131]}, {"entity": "dibutyl phthalate", "entity_type": "Chemical", "pos": [147, 164]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "Maternal weight was reduced on GD 20 , PND 2 and 14 at 11 , 400 ppm DiNP .", "entity": [{"entity": "DiNP", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "Pup weight was reduced on PND 2 and 14 at 11 , 400 and 3800 ppm DiNP .", "entity": [{"entity": "DiNP", "entity_type": "Chemical", "pos": [64, 68]}], "task": "NER"}
{"text": "DBP induced multinucleated germ cells ( MNGs ) and Leydig cell aggregates ( LCAs ) in PND 2 testes .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "7600 ppm DBP reduced anogenital distance ( AGD ) on PND 2 and 14 , and increased nipple retention and reproductive tract malformations on PND 49 .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "DiNP induced MNGs ( 3800 ppm ) and LCAs ( 11 , 400 ppm ) on PND 2 , and reduced AGD ( 11 , 400 ppm ) on PND 14 .", "entity": [{"entity": "DiNP", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "DiNP did not alter AGD , nipple retention or reproductive tract malformations on PND 49 .", "entity": [{"entity": "DiNP", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Global endpoint analysis showed no evidence of a rat \" phthalate syndrome \" on PND 49 with DiNP administration .", "entity": [{"entity": "phthalate", "entity_type": "Chemical", "pos": [55, 64]}, {"entity": "DiNP", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "Suppression of collagen Q expression in the extrajunctional regions of rat fast muscles is encoded in their stem cells ( satellite cells ) .", "entity": [], "task": "NER"}
{"text": "In rat fast muscles , collagen Q ( ColQ ) expression is restricted to the neuromuscular junctions .", "entity": [], "task": "NER"}
{"text": "In contrast , it is high also extrajunctionally in the slow soleus muscles .", "entity": [], "task": "NER"}
{"text": "Fast muscles activated by chronic low - frequency electrical stimulation , similar to neural activation of the soleus muscles , did not increase their extrajunctional expression of ColQ .", "entity": [], "task": "NER"}
{"text": "We assumed that the myogenic stem cells ( satellite cells ) in fast and slow muscles were intrinsically different in regard to the capacity that they convey to their respective muscle fibers to increase the extrajunctional ColQ expression upon innervation .", "entity": [], "task": "NER"}
{"text": "ColQ mRNA levels were determined by quantitative real - time PCR .", "entity": [], "task": "NER"}
{"text": "Extensive neural suppression of the extrajunctional ColQ expression in regenerating fast muscles during maturation is a very slow process requiring 30 - 60days .", "entity": [], "task": "NER"}
{"text": "If the immature regenerating fast EDL muscles were indirectly or directly electrically stimulated immediately after innervation by chronic low - frequency impulse pattern for 8days , no significant increase of the extrajunctional ColQ mRNA levels was observed in stimulated regenerates in comparison to non - stimulated ones .", "entity": [], "task": "NER"}
{"text": "In contrast , the extrajunctional ColQ mRNA levels in the regenerates of the soleus muscles , trans - innervated by the EDL nerve at the time of muscle injury , increased 4 - to 5 - fold after 8days of the same chronic low - frequency electrical stimulation in comparison to those in the stimulated EDL regenerates .", "entity": [], "task": "NER"}
{"text": "Since both fast and slow muscles completely regenerated only from their own myogenic stem cells and were innervated by the same nerve and later activated by the same tonic pattern of impulses , these results demonstrated that the mechanism causing incapacity of regenerating fast muscles to increase their extrajunctional ColQ expression upon tonic activation is encoded in their satellite cells , which in this respect differ from those in the slow muscles .", "entity": [], "task": "NER"}
{"text": "Lithium treatment induces proteasomal degradation of over - expressed acetylcholinesterase ( AChE - S ) and inhibit GSK3 beta .", "entity": [{"entity": "Lithium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Lithium is one of the most widely used mood - stabilizing agents for the treatment of bipolar disorder .", "entity": [{"entity": "Lithium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Lithium is also a potent inhibitor of glycogen synthase kinase - 3 beta ( GSK3 beta ) activity , which is linked to Alzheimer ' s disease ( AD ) .", "entity": [{"entity": "Lithium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In experiments with cultured HEK293T cells , we show here that GSK3 beta stabilizes synaptic acetylcholinesterase ( AChE - S ) , a critical component of AD development .", "entity": [], "task": "NER"}
{"text": "Cells treated with lithium exhibited rapid proteasomal degradation of AChE - S .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "Furthermore treatment of the cells with MG132 , an inhibitor of the 26S proteasome , prevented the destabilizing effect of lithium on AChE - S .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [40, 45]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "Taken together , these findings suggest that regulation of AChE - S protein stability may be an important biological target of lithium therapy .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity .", "entity": [{"entity": "terpenes", "entity_type": "Chemical", "pos": [12, 20]}], "task": "NER"}
{"text": "Terpenes are considered potent skin permeation enhancers with low toxicity .", "entity": [{"entity": "Terpenes", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Electron paramagnetic resonance ( EPR ) spectroscopy of the spin label 5 - doxyl stearic acid ( 5 - DSA ) was used to monitor the effect of sesquiterpene nerolidol and various monoterpenes on membrane fluidity in erythrocyte and fibroblast cells .", "entity": [{"entity": "5 - doxyl stearic acid", "entity_type": "Chemical", "pos": [71, 93]}, {"entity": "5 - DSA", "entity_type": "Chemical", "pos": [96, 103]}, {"entity": "sesquiterpene", "entity_type": "Chemical", "pos": [140, 153]}, {"entity": "nerolidol", "entity_type": "Chemical", "pos": [154, 163]}, {"entity": "monoterpenes", "entity_type": "Chemical", "pos": [176, 188]}], "task": "NER"}
{"text": "In addition , the hemolytic levels and cytotoxic effects on cultured fibroblast cells were also measured to investigate possible relationships between the cellular irritation potentials of terpenes and the ability to modify membrane fluidity .", "entity": [{"entity": "terpenes", "entity_type": "Chemical", "pos": [189, 197]}], "task": "NER"}
{"text": "All terpenes increased cell membrane fluidity with no significant differences between the monoterpenes , but the effect of sesquiterpene was significantly greater than that of the monoterpenes .", "entity": [{"entity": "terpenes", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "monoterpenes", "entity_type": "Chemical", "pos": [90, 102]}, {"entity": "sesquiterpene", "entity_type": "Chemical", "pos": [123, 136]}, {"entity": "monoterpenes", "entity_type": "Chemical", "pos": [180, 192]}], "task": "NER"}
{"text": "The IC ( 50 ) values for the terpenes in the cytotoxicity assay indicated that 1 , 8 - cineole showed lower cytotoxicity and alpha - terpineol and nerolidol showed higher cytotoxicity .", "entity": [{"entity": "terpenes", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "1 , 8 - cineole", "entity_type": "Chemical", "pos": [79, 94]}, {"entity": "alpha - terpineol", "entity_type": "Chemical", "pos": [125, 142]}, {"entity": "nerolidol", "entity_type": "Chemical", "pos": [147, 156]}], "task": "NER"}
{"text": "The correlation between the hemolytic effect and the IC ( 50 ) values for fibroblast viability was low ( R = 0 . 61 ) ; however , in both tests , nerolidol was among the most aggressive of terpenes and 1 , 8 - cineole was among the least aggressive .", "entity": [{"entity": "nerolidol", "entity_type": "Chemical", "pos": [146, 155]}, {"entity": "terpenes", "entity_type": "Chemical", "pos": [189, 197]}, {"entity": "1 , 8 - cineole", "entity_type": "Chemical", "pos": [202, 217]}], "task": "NER"}
{"text": "Obtaining information concerning the toxicity and potency of terpenes could aid in the design of topical formulations optimized to facilitate drug absorption for the treatment of many skin diseases .", "entity": [{"entity": "terpenes", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "A probable clinically significant interaction between warfarin and cloxacillin : three case reports .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "cloxacillin", "entity_type": "Chemical", "pos": [67, 78]}], "task": "NER"}
{"text": "CASES : Three patients were admitted to the Imam Hospital , Tehran , Iran with a diagnosis of bacterial endocarditis .", "entity": [], "task": "NER"}
{"text": "The patients had indications for valve replacement surgery and anticoagulant therapy .", "entity": [], "task": "NER"}
{"text": "The administration of cloxacillin reduced the effect of warfarin , and subsequent increases in warfarin doses were unable to overcome this effect .", "entity": [{"entity": "cloxacillin", "entity_type": "Chemical", "pos": [22, 33]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "CONCLUSION : A decrease in warfarin anticoagulation effects was detected in our three patients following cloxacillin therapy for infective endocarditis .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "cloxacillin", "entity_type": "Chemical", "pos": [105, 116]}], "task": "NER"}
{"text": "Penicillinase - resistant penicillins remain essential antibiotics in the treatment of severe infections caused by Staphylococcus aureus due to their bactericidal activity , safety , and cost .", "entity": [{"entity": "penicillins", "entity_type": "Chemical", "pos": [26, 37]}], "task": "NER"}
{"text": "Thus , in situations where anticoagulants are indicated in patients with infective endocarditis , it would be better to replace warfarin with low - molecular - weight or unfractionated heparin .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "Abnormal uterine bleeding and dysfunctional uterine bleeding in pediatric and adolescent gynecology .", "entity": [], "task": "NER"}
{"text": "Abnormal uterine bleeding ( AUB ) , which is defined as excessively heavy , prolonged and / or frequent bleeding of uterine origin , is a frequent cause of visits to the Emergency Department and / or health care provider .", "entity": [], "task": "NER"}
{"text": "While there are many etiologies of AUB , the one most likely among otherwise healthy adolescents is dysfunctional uterine bleeding ( DUB ) , which is characterizing any AUB when all possible underlying pathologic causes have been previously excluded .", "entity": [], "task": "NER"}
{"text": "The most common cause of DUB in adolescence is anovulation , which is very frequent in the first 2 - 3 post - menarchal years and is associated with immaturity of the hypothalamic - pituitary - ovarian axis .", "entity": [], "task": "NER"}
{"text": "Management of AUB is based on the underlying etiology and the severity of the bleeding and primary goals are prevention of complications , such as anemia and reestablishment of regular cyclical bleeding , while the management of DUB can in part be directed by the amount of flow , the degree of associated anemia , as well as patient and family comfort with different treatment modalities .", "entity": [], "task": "NER"}
{"text": "Treatment options for DUB are : combined oral contraceptives ( COCs ) , progestogens , non steroidal anti inflammatory drugs ( NSAIDs ) , tranexamic acid ( anti - fibrinolytic ) , GnRH analogues , Danazol and Levonorgestrel releasing intra uterine system ( LNG IUS ) .", "entity": [{"entity": "progestogens", "entity_type": "Chemical", "pos": [72, 84]}, {"entity": "tranexamic acid", "entity_type": "Chemical", "pos": [138, 153]}, {"entity": "GnRH", "entity_type": "Chemical", "pos": [180, 184]}, {"entity": "Danazol", "entity_type": "Chemical", "pos": [197, 204]}, {"entity": "Levonorgestrel", "entity_type": "Chemical", "pos": [209, 223]}], "task": "NER"}
{"text": "An assessment of pure , hybrid , meta , and hybrid - meta GGA density functional theory methods for open - shell systems : the case of the nonheme iron enzyme 8R - LOX .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "The performance of a range density functional theory functionals combined in a quantum mechanical ( QM ) / molecular mechanical ( MM ) approach was investigated in their ability to reliably provide geometries , electronic distributions , and relative energies of a multicentered open - shell mechanistic intermediate in the mechanism 8R - Lipoxygenase .", "entity": [], "task": "NER"}
{"text": "With the use of large QM / MM active site chemical models , the smallest average differences in geometries between the catalytically relevant quartet and sextet complexes were obtained with the B3LYP ( * ) functional .", "entity": [], "task": "NER"}
{"text": "Moreover , in the case of the relative energies between ( 4 ) II and ( 6 ) II , the use of the B3LYP ( * ) functional provided a difference of 0 . 0 kcal mol ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "However , B3LYP ( +/- ) and B3LYP also predicted differences in energies of less than 1 kcal mol ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "In the case of describing the electronic distribution ( i . e . , spin density ) , the B3LYP ( * ) , B3LYP , or M06 - L functionals appeared to be the most suitable .", "entity": [], "task": "NER"}
{"text": "Overall , the results obtained suggest that for systems with multiple centers having unpaired electrons , the B3LYP ( * ) appears most well rounded to provide reliable geometries , electronic structures , and relative energies .", "entity": [], "task": "NER"}
{"text": "Design of a testing strategy using non - animal based test methods : Lessons learnt from the ACuteTox project .", "entity": [], "task": "NER"}
{"text": "In the framework of toxicology , a testing strategy can be viewed as a series of steps which are taken to come to a final prediction about a characteristic of a compound under study .", "entity": [], "task": "NER"}
{"text": "The testing strategy is performed as a single - step procedure , usually called a test battery , using simultaneously all information collected on different endpoints , or as tiered approach in which a decision tree is followed .", "entity": [], "task": "NER"}
{"text": "Design of a testing strategy involves statistical considerations , such as the development of a statistical prediction model .", "entity": [], "task": "NER"}
{"text": "During the EU FP6 ACuteTox project , several prediction models were proposed on the basis of statistical classification algorithms which we illustrate here .", "entity": [], "task": "NER"}
{"text": "The final choice of testing strategies was not based on statistical considerations alone .", "entity": [], "task": "NER"}
{"text": "However , without thorough statistical evaluations a testing strategy cannot be identified .", "entity": [], "task": "NER"}
{"text": "We present here a number of observations made from the statistical viewpoint which relate to the development of testing strategies .", "entity": [], "task": "NER"}
{"text": "The points we make were derived from problems we had to deal with during the evaluation of this large research project .", "entity": [], "task": "NER"}
{"text": "A central issue during the development of a prediction model is the danger of overfitting .", "entity": [], "task": "NER"}
{"text": "Procedures are presented to deal with this challenge .", "entity": [], "task": "NER"}
{"text": "Role of TNF - alpha in renal damage in mice showing hepatic steatosis induced by high fat diet .", "entity": [], "task": "NER"}
{"text": "The present study was designed to investigate the role of TNF - alpha in renal damage observed in mice with hepatic steatosis .", "entity": [], "task": "NER"}
{"text": "We induced hepatic steatosis in mice using high fat diet and treated mice with ectanercept at the dose sufficient to block TNF - alpha receptors or vehicle for 1 month .", "entity": [], "task": "NER"}
{"text": "Plasma TNF - alpha , total cholesterol ( TC ) , triglyceride ( TG ) , LDL - cholesterol ( LDL - C ) , and HDL - cholesterol ( HDL - C ) were determined at the end of this treatment .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [48, 60]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [76, 87]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [112, 123]}], "task": "NER"}
{"text": "Renal damage was identified by histologic observation and the higher of serum blood urea nitrogen ( BUN ) and creatinine .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [84, 88]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [89, 97]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [110, 120]}], "task": "NER"}
{"text": "Also , changes of PPAR - delta in kidney and renal mesangial cell ( RMC ) were analyzed using Western blot .", "entity": [], "task": "NER"}
{"text": "Plasma TNF - alpha was markedly raised in mice showing hepatic steatosis .", "entity": [], "task": "NER"}
{"text": "However , the levels of blood lipids ( TC , TG , HDL - C , and LDL - C ) and TNF - alpha were not modified by the treatment of etanercept although the hepatic steatosis has been improved .", "entity": [], "task": "NER"}
{"text": "Etanercept shows renal protection from histological identification and recovery of serum BUN and creatinine levels .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [97, 107]}], "task": "NER"}
{"text": "Moreover , restoration of PPAR - delta expression by etanercept was observed in mice kidney .", "entity": [], "task": "NER"}
{"text": "Direct effect of TNF - alpha on PPAR - delta expression was also characterized in RMC cell .", "entity": [], "task": "NER"}
{"text": "We suggest that renal damage in mice with hepatic steatosis is mainly induced by increase of TNF - alpha through the decrease of renal PPAR - delta .", "entity": [], "task": "NER"}
{"text": "Etanercept could block TNF - alpha receptors to restore PPAR - delta and improve renal function in mice with hepatic steatosis .", "entity": [], "task": "NER"}
{"text": "Loss of A ( 1 ) adenosine receptor attenuates alpha - naphthylisothiocyanate - induced cholestatic liver injury in mice .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "alpha - naphthylisothiocyanate", "entity_type": "Chemical", "pos": [46, 76]}], "task": "NER"}
{"text": "Cholestasis has limited therapeutic options and is associated with high morbidity and mortality .", "entity": [], "task": "NER"}
{"text": "The A ( 1 ) adenosine receptor ( A ( 1 ) AR ) was postulated to participate in the pathogenesis of hepatic fibrosis induced by experimental extrahepatic cholestasis ; however , the contribution of A ( 1 ) AR to intrahepatic cholestatic liver injury remains unknown .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [12, 21]}], "task": "NER"}
{"text": "Here , we found that mice lacking A ( 1 ) AR were resistant to alpha - naphthyl isothiocyanate ( ANIT ) - induced liver injury , as evidenced by lower serum liver enzyme levels and reduced extent of histological necrosis .", "entity": [{"entity": "alpha - naphthyl isothiocyanate", "entity_type": "Chemical", "pos": [63, 94]}, {"entity": "ANIT", "entity_type": "Chemical", "pos": [97, 101]}], "task": "NER"}
{"text": "Bile acid accumulation in liver and serum was markedly diminished in A ( 1 ) AR ( - / - ) mice compared with wild - type ( WT ) mice .", "entity": [{"entity": "Bile acid", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "However , biliary and urinary outputs of bile acids were significantly enhanced in A ( 1 ) AR ( - / - ) mice .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "In the liver , mRNA expression of genes related to bile acid transport ( Bsep and Mdr2 ) and hydroxylation ( Cyp3a11 ) was increased in A ( 1 ) AR ( - / - ) mice .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "In the kidney , A ( 1 ) AR deficiency prevented the decrease of glomerular filtration rate caused by ANIT .", "entity": [{"entity": "ANIT", "entity_type": "Chemical", "pos": [101, 105]}], "task": "NER"}
{"text": "Treatment of WT mice with A ( 1 ) AR antagonist DPCPX also protected against ANIT hepatotoxicity .", "entity": [{"entity": "DPCPX", "entity_type": "Chemical", "pos": [48, 53]}, {"entity": "ANIT", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "Our results indicated that lack of A ( 1 ) AR gene protects mice from ANIT - induced cholestasis by enhancing toxic biliary constituents efflux through biliary excretory route and renal elimination system and suggested a potential role of A ( 1 ) AR as therapeutic target for the treatment of intrahepatic cholestasis .", "entity": [{"entity": "ANIT", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "Methamphetamine - induced nitric oxide promotes vesicular transport in blood - brain barrier endothelial cells .", "entity": [{"entity": "Methamphetamine", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [26, 38]}], "task": "NER"}
{"text": "Methamphetamine ' s ( METH ) neurotoxicity is thought to be in part due to its ability to induce blood - brain barrier ( BBB ) dysfunction .", "entity": [{"entity": "Methamphetamine", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "METH", "entity_type": "Chemical", "pos": [22, 26]}], "task": "NER"}
{"text": "Here , we investigated the effect of METH on barrier properties of cultured rat primary brain microvascular endothelial cells ( BMVECs ) .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "Transendothelial flux doubled in response to METH , irrespective of the size of tracer used .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "At the same time , transendothelial electrical resistance was unchanged as was the ultrastructural appearance of inter - endothelial junctions and the distribution of key junction proteins , suggesting that METH promoted vesicular but not junctional transport .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [207, 211]}], "task": "NER"}
{"text": "Indeed , METH significantly increased uptake of horseradish peroxidase into vesicular structures .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [9, 13]}], "task": "NER"}
{"text": "METH also enhanced transendothelial migration of lymphocytes indicating that the endothelial barrier against both molecules and cells was compromised .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Barrier breakdown was only observed in response to METH at low micromolar concentrations , with enhanced vesicular uptake peaking at 1 mu M METH .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "METH", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "The BMVEC response to METH also involved rapid activation of endothelial nitric oxide synthase and its inhibition abrogated METH - induced permeability and lymphocyte migration , indicating that nitric oxide was a key mediator of BBB disruption in response to METH .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [22, 26]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [73, 85]}, {"entity": "METH", "entity_type": "Chemical", "pos": [124, 128]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [195, 207]}, {"entity": "METH", "entity_type": "Chemical", "pos": [260, 264]}], "task": "NER"}
{"text": "This study underlines the key role of nitric oxide in BBB function and describes a novel mechanism of drug - induced fluid - phase transcytosis at the BBB .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [38, 50]}], "task": "NER"}
{"text": "Centrally acting oximes in reactivation of tabun - phosphoramidated AChE .", "entity": [{"entity": "oximes", "entity_type": "Chemical", "pos": [17, 23]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [43, 48]}], "task": "NER"}
{"text": "Organophosphates ( OP ) inhibit acetylcholinesterase ( AChE , EC 3 . 1 . 1 . 7 ) , both in peripheral tissues and central nervous system ( CNS ) , causing adverse and sometimes fatal effects due to the accumulation of neurotransmitter acetylcholine ( ACh ) .", "entity": [{"entity": "Organophosphates", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [32, 45]}, {"entity": "ACh", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "The currently used therapy , focusing on the reactivation of inhibited AChE , is limited to peripheral tissues because commonly used quaternary pyridinium oxime reactivators do not cross the blood brain barrier ( BBB ) at therapeutically relevant levels .", "entity": [{"entity": "quaternary pyridinium oxime", "entity_type": "Chemical", "pos": [133, 160]}], "task": "NER"}
{"text": "A directed library of thirty uncharged oximes that contain tertiary amine or imidazole protonable functional groups that should cross the BBB as unionized species was tested as tabun - hAChE conjugate reactivators along with three reference oximes : DAM ( diacetylmonoxime ) , MINA ( monoisonitrosoacetone ) , and 2 - PAM .", "entity": [{"entity": "oximes", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "tertiary amine", "entity_type": "Chemical", "pos": [59, 73]}, {"entity": "imidazole", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [177, 182]}, {"entity": "oximes", "entity_type": "Chemical", "pos": [241, 247]}, {"entity": "DAM", "entity_type": "Chemical", "pos": [250, 253]}, {"entity": "diacetylmonoxime", "entity_type": "Chemical", "pos": [256, 272]}, {"entity": "MINA", "entity_type": "Chemical", "pos": [277, 281]}, {"entity": "monoisonitrosoacetone", "entity_type": "Chemical", "pos": [284, 305]}, {"entity": "2 - PAM", "entity_type": "Chemical", "pos": [314, 321]}], "task": "NER"}
{"text": "The oxime RS150D [ N - ( ( 1 - ( 3 - ( 2 - ( ( hydroxyimino ) methyl ) - 1H - imidazol - 1 - yl ) propyl ) - 1H - 1 , 2 , 3 - triazol - 4 - yl ) methyl ) benzamide ] was highlighted as the most promising reactivator of the tabun - hAChE conjugate .", "entity": [{"entity": "oxime", "entity_type": "Chemical", "pos": [4, 9]}, {"entity": "RS150D", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "N - ( ( 1 - ( 3 - ( 2 - ( ( hydroxyimino ) methyl ) - 1H - imidazol - 1 - yl ) propyl ) - 1H - 1 , 2 , 3 - triazol - 4 - yl ) methyl ) benzamide", "entity_type": "Chemical", "pos": [19, 163]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [223, 228]}], "task": "NER"}
{"text": "We also observed that oximes RS194B [ N - ( 2 - ( azepan - 1 - yl ) ethyl ) - 2 - ( hydroxyimino ) acetamide ] and RS41A [ 2 - ( hydroxyimino ) - N - ( 2 - ( pyrrolidin - 1 - yl ) ethyl ) acetamide ] , which emerged as lead uncharged reactivators of phosphylated hAChE with other OPs ( sarin , cyclosarin and VX ) , exhibited only moderate reactivation potency for tabun inhibited hAChE .", "entity": [{"entity": "oximes", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "RS194B", "entity_type": "Chemical", "pos": [29, 35]}, {"entity": "N - ( 2 - ( azepan - 1 - yl ) ethyl ) - 2 - ( hydroxyimino ) acetamide", "entity_type": "Chemical", "pos": [38, 108]}, {"entity": "RS41A", "entity_type": "Chemical", "pos": [115, 120]}, {"entity": "2 - ( hydroxyimino ) - N - ( 2 - ( pyrrolidin - 1 - yl ) ethyl ) acetamide", "entity_type": "Chemical", "pos": [123, 197]}, {"entity": "sarin", "entity_type": "Chemical", "pos": [286, 291]}, {"entity": "cyclosarin", "entity_type": "Chemical", "pos": [294, 304]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [365, 370]}], "task": "NER"}
{"text": "This implies that geometry of oxime access to the phosphorus atom conjugated to the active serine is an important criterion for efficient reactivation , along with the chemical nature of the conjugated moiety : phosphorate , phosphonate , or phosphoramidate .", "entity": [{"entity": "oxime", "entity_type": "Chemical", "pos": [30, 35]}, {"entity": "phosphorus", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "serine", "entity_type": "Chemical", "pos": [91, 97]}, {"entity": "phosphorate", "entity_type": "Chemical", "pos": [211, 222]}, {"entity": "phosphonate", "entity_type": "Chemical", "pos": [225, 236]}, {"entity": "phosphoramidate", "entity_type": "Chemical", "pos": [242, 257]}], "task": "NER"}
{"text": "Moreover , modification of the active center through mutagenesis enhances the rates of reactivation .", "entity": [], "task": "NER"}
{"text": "The phosphoramidated - hAChE choline - binding site mutant Y337A showed three - times enhanced reactivation capacity with non - triazole imidazole containing aldoximes ( RS113B , RS113A and RS115A ) and acetamide derivative ( RS194B ) than with 2PAM .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [29, 36]}, {"entity": "triazole", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "imidazole", "entity_type": "Chemical", "pos": [137, 146]}, {"entity": "aldoximes", "entity_type": "Chemical", "pos": [158, 167]}, {"entity": "RS113B", "entity_type": "Chemical", "pos": [170, 176]}, {"entity": "RS113A", "entity_type": "Chemical", "pos": [179, 185]}, {"entity": "RS115A", "entity_type": "Chemical", "pos": [190, 196]}, {"entity": "acetamide", "entity_type": "Chemical", "pos": [203, 212]}, {"entity": "RS194B", "entity_type": "Chemical", "pos": [226, 232]}, {"entity": "2PAM", "entity_type": "Chemical", "pos": [245, 249]}], "task": "NER"}
{"text": "Increased nuclear thioredoxin - 1 potentiates cadmium - induced cytotoxicity .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Cadmium ( Cd ) is a widely dispersed environmental agent that causes oxidative toxicity through mechanisms that are sensitive to thioredoxin - 1 ( Trx1 ) .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [10, 12]}], "task": "NER"}
{"text": "Trx1 is a cytoplasmic protein that translocates to nuclei during oxidative stress .", "entity": [], "task": "NER"}
{"text": "Recent research shows that interaction of Trx1 with actin plays a critical role in cell survival and that increased nuclear Trx - 1 potentiates proinflammatory signaling and death in cell and mouse models .", "entity": [], "task": "NER"}
{"text": "These observations indicate that oxidative toxicity caused by low - dose Cd could involve disruption of actin - Trx1 interaction , nuclear Trx1 translocation , and potentiation of proinflammatory cell death mechanisms .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [73, 75]}], "task": "NER"}
{"text": "In this study , we investigated the role of nuclei - localized Trx1 in Cd - induced inflammation and cytotoxicity using in vitro and in vivo models .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [71, 73]}], "task": "NER"}
{"text": "The results show that Cd stimulated nuclear translocation of Trx1 and p65 of NF - kappa B .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [22, 24]}], "task": "NER"}
{"text": "Elevation of Trx1 in nuclei in in vitro cells and kidney of transgenic mice potentiated Cd - stimulated NF - kappa B activation and cell death .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [88, 90]}], "task": "NER"}
{"text": "Cd - stimulated Trx1 nuclear translocation and NF - kappa B activation were inhibited by cytochalasin D , an inhibitor of actin polymerization , suggesting that actin regulates Trx1 nuclear translocation and NF - kappa B activation by Cd .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "cytochalasin D", "entity_type": "Chemical", "pos": [89, 103]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [235, 237]}], "task": "NER"}
{"text": "A nuclear - targeted dominant negative form of Trx1 blocked Cd - stimulated NF - kappa B activation and decreased cell death .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [60, 62]}], "task": "NER"}
{"text": "Addition of zinc , known to antagonize Cd toxicity by increasing metallothionein , had no effect on Cd - stimulated nuclear translocation of Trx1 and NF - kappa B activation .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [100, 102]}], "task": "NER"}
{"text": "Taken together , the results show that nuclear translocation and accumulation of redox - active Trx1 in nuclei play an important role in Cd - induced inflammation and cell death .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [137, 139]}], "task": "NER"}
{"text": "The influence of pH on phosphatidylethanolamine monolayer at the air / aqueous solution interface .", "entity": [{"entity": "phosphatidylethanolamine", "entity_type": "Chemical", "pos": [23, 47]}], "task": "NER"}
{"text": "The dependence of the interfacial tension of a phosphatidylethanolamine ( PE ) monolayer on the pH of the aqueous solution has been studied .", "entity": [{"entity": "phosphatidylethanolamine", "entity_type": "Chemical", "pos": [47, 71]}], "task": "NER"}
{"text": "A theoretical equation is derived to describe this dependence .", "entity": [], "task": "NER"}
{"text": "A simple model of the influence of pH on the phosphatidylethanolamine monolayer at the air / hydrophobic chains of PE is presented .", "entity": [{"entity": "phosphatidylethanolamine", "entity_type": "Chemical", "pos": [45, 69]}], "task": "NER"}
{"text": "The contributions of additive phosphatidylethanolamine forms ( both interfacial tension values and molecular area values ) depend on pH .", "entity": [{"entity": "phosphatidylethanolamine", "entity_type": "Chemical", "pos": [30, 54]}], "task": "NER"}
{"text": "The interfacial tension values and the molecular area values for PEH ( + ) and PEOH ( - ) forms of phosphatidylethanolamine were calculated .", "entity": [{"entity": "PEH ( + )", "entity_type": "Chemical", "pos": [65, 74]}, {"entity": "PEOH ( - )", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "phosphatidylethanolamine", "entity_type": "Chemical", "pos": [99, 123]}], "task": "NER"}
{"text": "The assumed model was verified experimentally .", "entity": [], "task": "NER"}
{"text": "The experimental results agreed with those derived from the theoretical equation in a whole range of pH values .", "entity": [], "task": "NER"}
{"text": "A new flavonoid and other polar compounds from Galeopsis angustifolia Ehrh .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "ex Hoffm .", "entity": [], "task": "NER"}
{"text": "The analysis of the polar fraction of Galeopsis angustifolia Ehrh .", "entity": [], "task": "NER"}
{"text": "ex Hoffm . indicates that the main components are iridoids and flavonoids .", "entity": [{"entity": "iridoids", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [63, 73]}], "task": "NER"}
{"text": "Six compounds were identified : a new flavonoid , 3 ' - hydroxy - isoscutellarein 7 - O - [ 6 ' '' acetyl - beta - D - glucopyranosyl - ( 1 --> 2 ) - beta - D - glucopyranoside ] ; three iridoid glucosides : harpagide , acetyl harpagide and for the first time in this species , 8 - epi - loganin ; two known acetylated flavonoid glycosides : 3 ' - hydroxy - 4 ' - O - methylisoscutellarein 7 - O - [ 6 ' '' acetyl - beta - D - allopyranosyl - ( 1 --> 2 ) - 6 '' - acetyl - beta - D - glucopyranoside ] , 3 ' - hydroxy - 4 ' - O - methylisoscutellarein 7 - O - [ 6 ' '' acetyl - beta - D - allopyranosyl - ( 1 --> 2 ) - beta - D - glucopyranoside ] .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "3 ' - hydroxy - isoscutellarein 7 - O - [ 6 ' '' acetyl - beta - D - glucopyranosyl - ( 1 --> 2 ) - beta - D - glucopyranoside ]", "entity_type": "Chemical", "pos": [50, 178]}, {"entity": "iridoid glucosides", "entity_type": "Chemical", "pos": [187, 205]}, {"entity": "harpagide", "entity_type": "Chemical", "pos": [208, 217]}, {"entity": "acetyl harpagide", "entity_type": "Chemical", "pos": [220, 236]}, {"entity": "8 - epi - loganin", "entity_type": "Chemical", "pos": [278, 295]}, {"entity": "acetylated flavonoid glycosides", "entity_type": "Chemical", "pos": [308, 339]}, {"entity": "3 ' - hydroxy - 4 ' - O - methylisoscutellarein 7 - O - [ 6 ' '' acetyl - beta - D - allopyranosyl - ( 1 --> 2 ) - 6 '' - acetyl - beta - D - glucopyranoside ]", "entity_type": "Chemical", "pos": [342, 501]}, {"entity": "3 ' - hydroxy - 4 ' - O - methylisoscutellarein 7 - O - [ 6 ' '' acetyl - beta - D - allopyranosyl - ( 1 --> 2 ) - beta - D - glucopyranoside ]", "entity_type": "Chemical", "pos": [504, 647]}], "task": "NER"}
{"text": "Both flavonoids and iridoids are present in high amount ; respectively , 16 . 7 % and 4 . 5 % of the crude extract .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [5, 15]}, {"entity": "iridoids", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "Pharmacological and dietary antioxidant therapies for chronic obstructive pulmonary disease .", "entity": [], "task": "NER"}
{"text": "The progression and exacerbations of chronic obstructive pulmonary disease ( COPD ) are intimately associated with tobacco smoke / biomass fuel - induced oxidative and aldehyde / carbonyl stress .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [168, 176]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [179, 187]}], "task": "NER"}
{"text": "Alterations in redox signaling proinflammatory kinases and transcription factors , steroid resistance , unfolded protein response , mucus hypersecretion , extracellular matrix remodeling , autophagy / apoptosis , epigenetic changes , cellular senescence / aging , endothelial dysfunction , autoimmunity , and skeletal muscle dysfunction are some of the pathological hallmarks of COPD .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "In light of the above it would be prudent to target systemic and local oxidative stress with agents that can modulate the antioxidants / redox system or by boosting the endogenous levels of antioxidants for the treatment and management of COPD .", "entity": [], "task": "NER"}
{"text": "Identification of various antioxidant agents , such as thiol molecules ( glutathione and mucolytic drugs , such as N - acetyl - Lcysteine , N - acystelyn , erdosteine , fudosteine , ergothioneine , and carbocysteine lysine salt ) , dietary natural productderived polyphenols and other compounds ( curcumin , resveratrol , green tea catechins , quercetin sulforaphane , lycopene , acai , alpha - lipoic acid , tocotrienols , and apocynin ) have made it possible to modulate various biochemical aspects of COPD .", "entity": [{"entity": "thiol", "entity_type": "Chemical", "pos": [55, 60]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "N - acetyl - Lcysteine", "entity_type": "Chemical", "pos": [115, 137]}, {"entity": "N - acystelyn", "entity_type": "Chemical", "pos": [140, 153]}, {"entity": "erdosteine", "entity_type": "Chemical", "pos": [156, 166]}, {"entity": "fudosteine", "entity_type": "Chemical", "pos": [169, 179]}, {"entity": "ergothioneine", "entity_type": "Chemical", "pos": [182, 195]}, {"entity": "carbocysteine lysine", "entity_type": "Chemical", "pos": [202, 222]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [263, 274]}, {"entity": "curcumin", "entity_type": "Chemical", "pos": [297, 305]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [308, 319]}, {"entity": "catechins", "entity_type": "Chemical", "pos": [332, 341]}, {"entity": "quercetin sulforaphane", "entity_type": "Chemical", "pos": [344, 366]}, {"entity": "lycopene", "entity_type": "Chemical", "pos": [369, 377]}, {"entity": "alpha - lipoic acid", "entity_type": "Chemical", "pos": [387, 406]}, {"entity": "tocotrienols", "entity_type": "Chemical", "pos": [409, 421]}, {"entity": "apocynin", "entity_type": "Chemical", "pos": [428, 436]}], "task": "NER"}
{"text": "Various researches and clinical trials have revealed that these antioxidants can detoxify free radicals and oxidants , control expression of redox and glutathione biosynthesis genes , chromatin remodeling , and ultimately inflammatory gene expression .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [151, 162]}], "task": "NER"}
{"text": "In addition , modulation of cigarette smoke - induced oxidative stress and related cellular changes have also been reported to be effected by synthetic molecules .", "entity": [], "task": "NER"}
{"text": "This includes specific spin traps like alpha - phenyl - N - tert - butyl nitrone , a catalytic antioxidant ( ECSOD mimetic ) , porphyrins ( AEOL 10150 and AEOL 10113 ) , and a superoxide dismutase mimetic M40419 , lipid peroxidation and protein carbonylation blockers / inhibitors , such as edaravone and lazaroids / tirilazad , myeloperoxidase inhibitors , as well as specialized pro - resolving mediators / inflammatory resolving lipid mediators , omega - 3 fatty acids , vitamin D , and hydrogen sulfide .", "entity": [{"entity": "alpha - phenyl - N - tert - butyl nitrone", "entity_type": "Chemical", "pos": [39, 80]}, {"entity": "porphyrins", "entity_type": "Chemical", "pos": [127, 137]}, {"entity": "AEOL 10150", "entity_type": "Chemical", "pos": [140, 150]}, {"entity": "AEOL 10113", "entity_type": "Chemical", "pos": [155, 165]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [176, 186]}, {"entity": "M40419", "entity_type": "Chemical", "pos": [205, 211]}, {"entity": "edaravone", "entity_type": "Chemical", "pos": [291, 300]}, {"entity": "lazaroids", "entity_type": "Chemical", "pos": [305, 314]}, {"entity": "tirilazad", "entity_type": "Chemical", "pos": [317, 326]}, {"entity": "omega - 3 fatty acids", "entity_type": "Chemical", "pos": [450, 471]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [474, 483]}, {"entity": "hydrogen sulfide", "entity_type": "Chemical", "pos": [490, 506]}], "task": "NER"}
{"text": "According to various studies it appears that the administration of multiple antioxidants could be a more effective mode used in the treatment of COPD .", "entity": [], "task": "NER"}
{"text": "In this review , various pharmacological and dietary approaches to enhance lung antioxidant levels and beneficial effects of antioxidant therapeutics in treating or intervening the progression of COPD have been discussed .", "entity": [], "task": "NER"}
{"text": "A photochemical mechanism for homochirogenesis .", "entity": [], "task": "NER"}
{"text": "Part 2 .", "entity": [], "task": "NER"}
{"text": "A theoretical investigation of the photochemistry of racemic compounds with circularly polarized light was undertaken .", "entity": [], "task": "NER"}
{"text": "The exact solutions of the differential equations by numerical integration to the approximate solutions used in an earlier article were compared .", "entity": [], "task": "NER"}
{"text": "The exact solutions showed that sequential reactions yield enhanced optical activities in the products .", "entity": [], "task": "NER"}
{"text": "For irreversible reactions , all enantiomeric excesses are lost if the reactions are carried to completion , but appreciable resolution occurs in many cases for partial conversion .", "entity": [], "task": "NER"}
{"text": "For reversible reactions , significant enantiomeric excesses are found at the photostationary state .", "entity": [], "task": "NER"}
{"text": "Clear evidence of carcinogenic activity by a whole - leaf extract of Aloe barbadensis miller ( aloe vera ) in F344 / N rats .", "entity": [], "task": "NER"}
{"text": "Aloe barbadensis Miller ( Aloe vera ) is an herbal remedy promoted to treat a variety of illnesses ; however , only limited data are available on the safety of this dietary supplement .", "entity": [], "task": "NER"}
{"text": "Drinking water exposure of F344 / N rats and B6C3F1 mice to an Aloe vera whole - leaf extract ( 1 , 2 , and 3 % ) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species .", "entity": [], "task": "NER"}
{"text": "Based upon this observation , 2 - year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole - leaf extract when administered to F344 / N rats ( 48 per sex per group ) at 0 . 5 , 1 , and 1 . 5 % , and B6C3F1 mice ( 48 per sex per group ) at 1 , 2 , and 3 % .", "entity": [], "task": "NER"}
{"text": "Compared with controls , survival was decreased in the 1 . 5 % dose group of female rats .", "entity": [], "task": "NER"}
{"text": "Treatment - related neoplasms and nonneoplastic lesions in both species were confined primarily to the large intestine .", "entity": [], "task": "NER"}
{"text": "Incidences of adenomas and / or carcinomas of the ileo - cecal and cecal - colic junction , cecum , and ascending and transverse colon were significantly higher than controls in male and female rats in the 1 and 1 . 5 % dose groups .", "entity": [], "task": "NER"}
{"text": "There were no neoplasms of the large intestine in mice or in the 0 or 0 . 5 % dose groups of rats .", "entity": [], "task": "NER"}
{"text": "Increased incidences of mucosa hyperplasia of the large intestine were observed in F344 / N rats , and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice .", "entity": [], "task": "NER"}
{"text": "These results indicate that Aloe vera whole - leaf extract is an intestinal irritant in F344 / N rats and B6C3F1 mice and a carcinogen of the large intestine in F344 / N rats .", "entity": [], "task": "NER"}
{"text": "Advances in supramolecular electronics - from randomly self - assembled nanostructures to addressable self - organized interconnects .", "entity": [], "task": "NER"}
{"text": "Supramolecular organic electronics rests on the use of bottom - up chemical self - assembly processes in order to design conducting components on the 5 - 100 nm scale .", "entity": [], "task": "NER"}
{"text": "The challenges in this field are both the construction of 1D - nanostructures displaying optimized transport properties and their precise connections to electrodes .", "entity": [], "task": "NER"}
{"text": "The present Research News highlights important advances in such materials regarding their electrical performances , from semiconductors to organic metals , but also regarding their processability .", "entity": [], "task": "NER"}
{"text": "In particular , by externally controlling light - responsive supramolecular polymerization processes , and by using appropriate methods of casting with an applied electric field , it becomes possible to pre - determine the accurate positioning of organic interconnects within patterned nano - circuitry .", "entity": [], "task": "NER"}
{"text": "These strategies using external stimuli to obtain addressability , thus hold promising alternatives to other conducting materials such as carbon nanotubes for further technological applications in nanosciences .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [138, 144]}], "task": "NER"}
{"text": "Recent developments in antimalarial natural products isolated from medicinal plants .", "entity": [], "task": "NER"}
{"text": "Malaria is an infectious disease causing almost one million deaths each year .", "entity": [], "task": "NER"}
{"text": "There is an urgent need for discovery of new antimalarial compounds .", "entity": [], "task": "NER"}
{"text": "Natural products have been the single most productive source of leads for the development of drugs , because of their great variety of chemical structures .", "entity": [], "task": "NER"}
{"text": "This review covers studies on antimalarial natural products isolated from plants , published from January 2010 until April 2012 .", "entity": [], "task": "NER"}
{"text": "A total of 171 structures comprising alkaloids , terpenoids , phenolics and other metabolites are listed in this review , including information on their antiplasmodial and cytotoxic activity .", "entity": [{"entity": "terpenoids", "entity_type": "Chemical", "pos": [49, 59]}, {"entity": "phenolics", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "Four new coumarinolignoids from seeds of Solanum indicum .", "entity": [{"entity": "coumarinolignoids", "entity_type": "Chemical", "pos": [9, 26]}], "task": "NER"}
{"text": "Activity - guided fractionation of seeds of Solanum indicum for anti - HBV activity led to the isolation of two novel coumarinolignoid alkaloids ( indicumines A - B , 1 - 2 ) and two new coumarinolignoids ( indicumines C - D , 3 - 4 ) , together with four known coumarins ( 5 - 8 ) .", "entity": [{"entity": "coumarinolignoid alkaloids", "entity_type": "Chemical", "pos": [118, 144]}, {"entity": "indicumines A - B", "entity_type": "Chemical", "pos": [147, 164]}, {"entity": "coumarinolignoids", "entity_type": "Chemical", "pos": [187, 204]}, {"entity": "indicumines C - D", "entity_type": "Chemical", "pos": [207, 224]}, {"entity": "coumarins", "entity_type": "Chemical", "pos": [262, 271]}], "task": "NER"}
{"text": "Their structures were established on the basis of spectroscopic data .", "entity": [], "task": "NER"}
{"text": "The two novel coumarinolignoid alkaloids shows anti - HBV activities through specifically inhibiting the secretion of HBsAg in HepG2 . 2 . 15 .", "entity": [{"entity": "coumarinolignoid alkaloids", "entity_type": "Chemical", "pos": [14, 40]}], "task": "NER"}
{"text": "Relevance of non - guideline studies for risk assessment : the coverage model based on most frequent targets in repeated dose toxicity studies .", "entity": [], "task": "NER"}
{"text": "A common challenge for human risk assessment is the quality of the available animal studies .", "entity": [], "task": "NER"}
{"text": "Non - guideline studies are often limited for different aspects of study design and documentation .", "entity": [], "task": "NER"}
{"text": "Within this publication the relevance of a limited scope of examination is discussed .", "entity": [], "task": "NER"}
{"text": "Preliminary analyses of the RepDose database have shown that liver , body weight , kidney and clinical symptoms are frequently affected in oral repeated dose toxicity in rats and mice ( Bitsch et al . , 2006 ) , while many other targets are seldom affected .", "entity": [], "task": "NER"}
{"text": "As most of these targets are investigated frequently also in non - guideline studies , it is likely that they provide a reliable NOEL , although the full spectrum of endpoints has not been covered .", "entity": [], "task": "NER"}
{"text": "Based on RepDose data we investigate the relevance of individual targets for determining the LOEL and the consequences for risk assessment .", "entity": [], "task": "NER"}
{"text": "The resulting coverage model for subchronic oral rat studies includes up to six targets and an additional assessment factor for LOEL extrapolation .", "entity": [], "task": "NER"}
{"text": "It can be applied to assess the reliability of non - guideline studies with respect to the scope of examination .", "entity": [], "task": "NER"}
{"text": "Furthermore the application of the coverage model to other databases will increase and / or specify the chemical domain and reveal respective targets as well as effects .", "entity": [], "task": "NER"}
{"text": "Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations .", "entity": [], "task": "NER"}
{"text": "Mucopolysaccharidosis ( MPS ) disorders are heterogeneous and caused by deficient lysosomal degradation of glycosaminoglycans , resulting in distinct but sometimes overlapping phenotypes .", "entity": [], "task": "NER"}
{"text": "Molecular analysis was performed for a total of 355 MPS patients with MPSI ( n = 15 ) , MPSII ( n = 218 ) , MPSIIIA ( n = 86 ) , MPSIIIB ( n = 20 ) , MPSIVA ( n = 6 ) or MPSVI ( n = 10 ) .", "entity": [], "task": "NER"}
{"text": "This analysis revealed 104 previously unreported mutations : seven in IDUA ( MPSI ) , 61 in IDS ( MPSII ) , 19 in SGSH ( MPSIIIA ) , 11 in NAGLU ( MPSIIIB ) , two in GALNS ( MPSIVA ) and four in ARSB ( MPSVI ) .", "entity": [], "task": "NER"}
{"text": "The intergenic comparison of the mutation data for these disorders has revealed interesting differences .", "entity": [], "task": "NER"}
{"text": "Whereas IDUA , IDS , NAGLU and ARSB demonstrate similar levels of mutation heterogeneity ( 0 . 6 - 0 . 675 different mutations per total alleles ) , SGSH and GALNS have lower levels of mutation heterogeneity ( 0 . 282 and 0 . 455 , respectively ) , due to more recurrent mutations .", "entity": [], "task": "NER"}
{"text": "The type of mutation also varies significantly by gene .", "entity": [], "task": "NER"}
{"text": "SGSH , GALNS and ARSB mutations are usually missense ( 76 . 5 % , 81 . 8 % and 85 % ) , while IDUA has many more nonsense mutations ( 56 % ) than the other genes ( <= 20 % ) .", "entity": [], "task": "NER"}
{"text": "The mutation spectrum is most diverse for IDS , including intergenic inversions and multi - exon deletions .", "entity": [], "task": "NER"}
{"text": "By testing 102 mothers of MPSII patients , we determined that 22 . 5 % of IDS mutations are de novo .", "entity": [], "task": "NER"}
{"text": "We report the allele frequency of common mutations for each gene in our patient cohort and the exonic distribution of coding sequence alterations in the IDS , SGSH and NAGLU genes , which reveals several potential \" hot - spots \" .", "entity": [], "task": "NER"}
{"text": "This further molecular characterization of these MPS disorders is expected to assist in the diagnosis and counseling of future patients .", "entity": [], "task": "NER"}
{"text": "The role of residues T248 , Y249 and T422 in the function of human pregnane X receptor .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "The pregnane X receptor ( PXR ) is a key xenobiotic receptor that regulates the expression of numerous drug - metabolizing enzymes .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "Some posttranslational mechanisms modulate its transcriptional activity .", "entity": [], "task": "NER"}
{"text": "Although several kinases have been shown to directly phosphorylate this receptor , little is known about phosphorylation sites of PXR .", "entity": [], "task": "NER"}
{"text": "In the present work , we examined T248 , Y249 and T422 putative phosphorylation sites determined based on in silico consensus kinase site prediction analysis .", "entity": [], "task": "NER"}
{"text": "T248 and T422 residues are critical for the interaction of the PXR ligand - binding domain and the activation function - 2 ( AF2 ) domain .", "entity": [], "task": "NER"}
{"text": "Site - directed mutagenesis analysis was performed to generate phospho - deficient and phospho - mimetic mutants .", "entity": [{"entity": "phospho", "entity_type": "Chemical", "pos": [63, 70]}, {"entity": "phospho", "entity_type": "Chemical", "pos": [87, 94]}], "task": "NER"}
{"text": "We examined transactivation activity of the PXR mutants in gene reporter assays , formation of PXRmutant / RXR alpha heterodimer , binding of PXR mutants to the CYP3A4 gene response element DR3 and CYP3A4 expression in HepG2 cells after expression of the mutants .", "entity": [], "task": "NER"}
{"text": "We found that T248D mutant activated CYP3A4 transactivation constitutively regardless of the presence or absence of a ligand .", "entity": [], "task": "NER"}
{"text": "Contrary , T248V mutant exhibited low basal and ligand - inducible transactivation capacity as compared to wild - type PXR .", "entity": [], "task": "NER"}
{"text": "Dose - response analysis revealed reduced ligand - dependent transactivation potency of PXR Y249D mutant .", "entity": [], "task": "NER"}
{"text": "Transactivation of the CYP3A4 promoter was abolished with T422A / D mutants .", "entity": [], "task": "NER"}
{"text": "All PXR mutants formed heterodimer with RXR alpha at a similar level to that observed with wild - type PXR .", "entity": [], "task": "NER"}
{"text": "The ability to bind to DNA in vitro was substantially decreased in case of T248D , T422D and T248V mutants .", "entity": [], "task": "NER"}
{"text": "Our data thus indicate that phosphorylation of T248 , Y249 and T422 residues may be critical for the both basal and ligand - activated function of PXR .", "entity": [], "task": "NER"}
{"text": "Circadian rhythm of salivary cortisol in infants with congenital heart disease .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Children with congenital heart disease ( CHD ) have associated extracardiac co - morbidities at the time of surgery and during ongoing growth and development .", "entity": [], "task": "NER"}
{"text": "Perioperative events include disrupted glucose homeostasis , capillary leak , and fluid retention .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "The hypothalamic - pituitary - adrenal ( HPA ) axis has an important role in homeostasis in that the secretion of cortisol contributes to the response to stress , glucose regulation , blood volume control , and immune regulation .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "We investigated the diurnal rhythm of the HPA axis in infants with CHD by measuring salivary cortisol in the morning ( 0600 - 0900 h - circadian peak ) and evening ( 2100 - 2400 h - circadian nadir ) .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "Twenty - nine infants aged 12 weeks to 1 year were included : 16 with acyanotic disease ( SpO ( 2 ) >= 90 % ) and 13 with cyanotic disease ( SpO2 < 90 % ) .", "entity": [], "task": "NER"}
{"text": "Morning salivary cortisol was similar between the two groups [ acyanotic 7 . 0 nmol / L ( 1 . 8 - 23 . 1 ) ; cyanotic 9 . 7 nmol / L ( 0 . 9 - 15 . 6 ) ; p = 0 . 68 ] .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "Evening salivary cortisol was similar between the two groups [ acyanotic 0 . 9 nmol / L ( 0 . 2 - 8 . 5 ) ; cyanotic 1 . 4 nmol / L ( 0 . 5 - 14 . 9 ) ; p = 0 . 32 ] .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "Both cyanotic and acyanotic groups demonstrated an intact diurnal rhythm .", "entity": [], "task": "NER"}
{"text": "In conclusion , chronic hypoxia secondary to cyanotic CHD does not affect the circadian rhythm of the HPA axis .", "entity": [], "task": "NER"}
{"text": "By 12 weeks of age , infants with hypoxia secondary to cyanotic CHD have a normal cortisol diurnal rhythm .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "Brain involvement in glaucoma : advanced neuroimaging for understanding and monitoring a new target for therapy .", "entity": [], "task": "NER"}
{"text": "On the basis of a large body of experimental data the notion that glaucoma damages retinal ganglion cells and central areas of the visual system has been put forward .", "entity": [], "task": "NER"}
{"text": "The mechanisms underlying glaucomatous involvement of the central areas are not known : the most likely hypothesis is that this event is the result of an anterograde transynaptic neurodegeneration triggered by ganglion cells ' death .", "entity": [], "task": "NER"}
{"text": "However , it is possible that in some cases it may be the consequence of a neurodegenerative disease of the central nervous system .", "entity": [], "task": "NER"}
{"text": "In any event , novel mechanisms leading to cell demise might be implicated .", "entity": [], "task": "NER"}
{"text": "The development of powerful neuroimaging techniques in conjunction with sophisticated analysis has recently provided compelling support to the involvement of central stations of the visual pathway in patients suffering of glaucoma .", "entity": [], "task": "NER"}
{"text": "Diffusion Tensor - MRI allows the central damage associated with glaucoma to be assessed and therapeutic efficacy of novel neuroprotective interventions to be quantified .", "entity": [], "task": "NER"}
{"text": "Peptide reactivity assay using spectrophotometric method for high - throughput screening of skin sensitization potential of chemical haptens .", "entity": [], "task": "NER"}
{"text": "Haptens must react with cellular proteins to be recognized by antigen presenting cells .", "entity": [], "task": "NER"}
{"text": "Therefore , monitoring reactivity of chemicals with peptide / protein has been considered an in vitro skin sensitization testing method .", "entity": [], "task": "NER"}
{"text": "The reactivity of peptides with chemicals ( peptide reactivity ) has usually been monitored by chromatographic methods like HPLC or LC / MS , which are robust tools for monitoring common chemical reactions but are rather expensive and time consuming .", "entity": [], "task": "NER"}
{"text": "Here , we examined the possibility of using spectrophotometric methods to monitor peptide reactivity .", "entity": [], "task": "NER"}
{"text": "Two synthetic peptides , Ac - RWAACAA and Ac - RWAAKAA , were reacted with 48 chemicals ( 34 sensitizers and 14 non - sensitizers ) .", "entity": [], "task": "NER"}
{"text": "Peptide reactivity was measured by monitoring unreacted peptides with UV - Vis spectrophotometer using 5 , 5 ' - dithiobis - 2 - nitrobenzoic acid as a detection reagent for the free thiol group of cysteine - containing peptide or fluorometer using fluorescamine (TM) as a detection reagent for the free amine group of lysine - containing peptide .", "entity": [{"entity": "5 , 5 ' - dithiobis - 2 - nitrobenzoic acid", "entity_type": "Chemical", "pos": [103, 146]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [183, 188]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [198, 206]}, {"entity": "fluorescamine", "entity_type": "Chemical", "pos": [249, 262]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [319, 325]}], "task": "NER"}
{"text": "Chemicals were categorized as sensitizers when they induced more than 10 % depletion of cysteine - containing peptide or 20 % depletion of lysine - containing peptide .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [88, 96]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [139, 145]}], "task": "NER"}
{"text": "The sensitivity , specificity , and accuracy of this method were 82 . 4 % , 85 . 7 % , and 83 . 3 % , respectively .", "entity": [], "task": "NER"}
{"text": "These results demonstrate that spectrophotometric methods can be easy , fast , and high - throughput screening tools for the prediction of the skin sensitization potential of chemical haptens .", "entity": [], "task": "NER"}
{"text": "Biomarkers of Parkinson ' s disease : current status and future perspectives .", "entity": [], "task": "NER"}
{"text": "This review summarizes major advances in biomarker discovery for diagnosis , differential diagnosis and progression of Parkinson ' s disease ( PD ) , with emphasis on neuroimaging and biochemical markers .", "entity": [], "task": "NER"}
{"text": "Potential strategies to develop biomarkers capable of predicting PD in the prodromal stage before the appearance of motor symptoms or correlating with nonmotor symptoms , an active area of research , are also discussed .", "entity": [], "task": "NER"}
{"text": "Leukotriene D4 induces cognitive impairment through enhancement of CysLT 1 R - mediated amyloid - beta generation in mice .", "entity": [{"entity": "Leukotriene D4", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Amyloid plaques in the extracellular parenchyma mainly consist of amyloid - beta peptides ( A beta ) , one of the pathological hallmarks in Alzheimer ' s disease ( AD ) .", "entity": [], "task": "NER"}
{"text": "In the present study , we examined neuroinflammation , amyloidogenesis , and memory performance following intracerebral infusions of leukotriene D4 ( LTD4 ) in mice .", "entity": [{"entity": "leukotriene D4", "entity_type": "Chemical", "pos": [133, 147]}, {"entity": "LTD4", "entity_type": "Chemical", "pos": [150, 154]}], "task": "NER"}
{"text": "The results demonstrated that intracerebral infusions of LTD4 ( 1 ng / mouse ) produced memory impairment as determined by Morris water maze test and Y - maze test in mice , and caused the accumulation of A beta 1 - 40 and A beta 1 - 42 in the hippocampus and cortex through increased activity of beta - and gamma - secretases accompanied with increased expression of amyloid precursor protein ( APP ) .", "entity": [{"entity": "LTD4", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "LTD4 also induced expression of cysteinyl leukotriene receptor 1 ( CysLT ( 1 ) R ) and NF - kappa B p65 in the hippocampus and cortex .", "entity": [{"entity": "LTD4", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "cysteinyl leukotriene", "entity_type": "Chemical", "pos": [32, 53]}], "task": "NER"}
{"text": "Pretreatment with pranlukast ( 1 . 5 ng / mouse , intracerebroventricularly ) , a CysLT ( 1 ) R antagonist , blocked LTD4 - induced amyloidogenesis , memory deficits .", "entity": [{"entity": "pranlukast", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "LTD4", "entity_type": "Chemical", "pos": [117, 121]}], "task": "NER"}
{"text": "Pranlukast ( 0 . 6 mu M ) also prevented LTD4 ( 20 nM ) - induced amyloidogenesis in the cultured neurons in vitro .", "entity": [{"entity": "Pranlukast", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "LTD4", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Moreover , LTD4 - induced increases in CysLT ( 1 ) R and NF - kappa B p65 in the brain were also attenuated by pranlukast .", "entity": [{"entity": "LTD4", "entity_type": "Chemical", "pos": [11, 15]}, {"entity": "pranlukast", "entity_type": "Chemical", "pos": [111, 121]}], "task": "NER"}
{"text": "These results suggest that LTD4 increases A beta peptide burden via activation of CysLT ( 1 ) R , which further affects APP levels and activity of beta - and gamma - secretases via the NF - kappa B pathway .", "entity": [{"entity": "LTD4", "entity_type": "Chemical", "pos": [27, 31]}], "task": "NER"}
{"text": "Our findings identify CysLT ( 1 ) R signaling as a novel proinflammatory and proamyloidogenic pathway , and suggest a rationale for development of therapeutics targeting the CysLT ( 1 ) R in neuroinflammatory diseases such as AD .", "entity": [], "task": "NER"}
{"text": "Comparative gene expression profiling in human - induced pluripotent stem cell - - derived cardiocytes and human and cynomolgus heart tissue .", "entity": [], "task": "NER"}
{"text": "Cardiotoxicity is one of the leading causes of drug attrition .", "entity": [], "task": "NER"}
{"text": "Current in vitro models insufficiently predict cardiotoxicity , and there is a need for alternative physiologically relevant models .", "entity": [], "task": "NER"}
{"text": "Here we describe the gene expression profile of human - induced pluripotent stem cell - derived cardiocytes ( iCC ) postthaw over a period of 42 days in culture and compare this profile to human fetal and adult as well as adult cynomolgus nonhuman primate ( NHP , Macaca fascicularis ) heart tissue .", "entity": [], "task": "NER"}
{"text": "Our results indicate that iCC express relevant cardiac markers such as ion channels ( SCN5A , KCNJ2 , CACNA1C , KCNQ1 , and KCNH2 ) , tissue - specific structural markers ( MYH6 , MYLPF , MYBPC3 , DES , TNNT2 , and TNNI3 ) , and transcription factors ( NKX2 . 5 , GATA4 , and GATA6 ) and lack the expression of stem cell markers ( FOXD3 , GBX2 , NANOG , POU5F1 , SOX2 , and ZFP42 ) .", "entity": [], "task": "NER"}
{"text": "Furthermore , we performed a functional evaluation of contractility of the iCC and showed functional and pharmacological correlations with myocytes isolated from adult NHP hearts .", "entity": [], "task": "NER"}
{"text": "These results suggest that stem cell - derived cardiocytes may represent a novel in vitro model to study human cardiac toxicity with potential ex vivo and in vivo translation .", "entity": [], "task": "NER"}
{"text": "A modern in vivo pharmacokinetic paradigm : combining snapshot , rapid and full PK approaches to optimize and expedite early drug discovery .", "entity": [], "task": "NER"}
{"text": "Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic ( PK ) properties as well as appropriate preclinical efficacy and safety profiles .", "entity": [], "task": "NER"}
{"text": "In vivo PK profiling is often a bottleneck in the discovery process .", "entity": [], "task": "NER"}
{"text": "In this review , we focus on the tiered in vivo PK approaches implemented at the Genomics Institute of the Novartis Research Foundation ( GNF ) , which includes snapshot PK , rapid PK and full PK studies .", "entity": [], "task": "NER"}
{"text": "These in vivo PK approaches are well integrated within discovery research , allow tremendous flexibility and are highly efficient in supporting the diverse needs and increasing demand for in vivo profiling .", "entity": [], "task": "NER"}
{"text": "The tiered in vivo PK studies expedite compound profiling and help guide the selection of more desirable compounds into efficacy models and for progression into development .", "entity": [], "task": "NER"}
{"text": "Enhancement of social novelty discrimination by positive allosteric modulators at metabotropic glutamate 5 receptors : adolescent administration prevents adult - onset deficits induced by neonatal treatment with phencyclidine .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [95, 104]}, {"entity": "phencyclidine", "entity_type": "Chemical", "pos": [212, 225]}], "task": "NER"}
{"text": "Metabotropic glutamate - 5 receptors ( mGluR5 ) , which physically and functionally interact with N - methyl - D - Aspartate ( NMDA ) receptors , likewise control cognitive processes and have been proposed as targets for novel classes of antipsychotic agent .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "N - methyl - D - Aspartate", "entity_type": "Chemical", "pos": [98, 124]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [127, 131]}], "task": "NER"}
{"text": "Since social cognition is impaired in schizophrenia and disrupted by NMDA receptor antagonists like dizocilpine , we evaluated its potential modulation by mGluR5 .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [69, 73]}, {"entity": "dizocilpine", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "Acute administration ( 0 . 63 - 40 mg / kg ) of the mGluR5 positive allosteric modulators ( PAMs ) , 3 - cyano - N - ( 1 , 3 - diphenyl - 1H - pyrazol - 5 - yl ) benzamide ( CDPPB ) and ADX47273 , reversed a delay - induced impairment in social novelty discrimination ( SND ) in adult rats .", "entity": [{"entity": "3 - cyano - N - ( 1 , 3 - diphenyl - 1H - pyrazol - 5 - yl ) benzamide", "entity_type": "Chemical", "pos": [101, 171]}, {"entity": "CDPPB", "entity_type": "Chemical", "pos": [174, 179]}, {"entity": "ADX47273", "entity_type": "Chemical", "pos": [186, 194]}], "task": "NER"}
{"text": "The action of CDPPB was blocked by the mGluR5 antagonist , 2 - methyl - 6 - ( phenylethynyl ) - pyridine ( 2 . 5 - 10 mg / kg ) , and was also expressed upon microinjection into frontal cortex ( 0 . 63 - 10 mu g / side ) , but not striatum .", "entity": [{"entity": "CDPPB", "entity_type": "Chemical", "pos": [14, 19]}, {"entity": "2 - methyl - 6 - ( phenylethynyl ) - pyridine", "entity_type": "Chemical", "pos": [59, 104]}], "task": "NER"}
{"text": "Supporting an interrelationship between mGluR5 and NMDA receptors , enhancement of SND by CDPPB was blocked by dizocilpine ( 0 . 08 mg / kg ) while , reciprocally , dizocilpine - induced impairment in SND was attenuated by CDPPB ( 10 mg / kg ) .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "CDPPB", "entity_type": "Chemical", "pos": [90, 95]}, {"entity": "dizocilpine", "entity_type": "Chemical", "pos": [111, 122]}, {"entity": "dizocilpine", "entity_type": "Chemical", "pos": [165, 176]}, {"entity": "CDPPB", "entity_type": "Chemical", "pos": [223, 228]}], "task": "NER"}
{"text": "The SND deficit elicited by post - natal administration of phencyclidine ( 10 mg / kg , days 7 - 11 ) was reversed by CDPPB or ADX47273 in adults at week 8 .", "entity": [{"entity": "phencyclidine", "entity_type": "Chemical", "pos": [59, 72]}, {"entity": "CDPPB", "entity_type": "Chemical", "pos": [118, 123]}, {"entity": "ADX47273", "entity_type": "Chemical", "pos": [127, 135]}], "task": "NER"}
{"text": "This phencyclidine - induced impairment in cognition emerged in adult rats from week 7 on , and chronic , pre - symptomatic treatment of adolescent rats with CDPPB over weeks 5 - 6 ( 10 mg / kg per day ) prevented the appearance of SND deficits in adults until at least week 13 .", "entity": [{"entity": "phencyclidine", "entity_type": "Chemical", "pos": [5, 18]}, {"entity": "CDPPB", "entity_type": "Chemical", "pos": [158, 163]}], "task": "NER"}
{"text": "In conclusion , as evaluated by a SND procedure , mGluR5 PAMs promote social cognition via actions expressed in interaction with NMDA receptors and exerted in frontal cortex .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [129, 133]}], "task": "NER"}
{"text": "MGluR5 PAMs not only reverse but also ( when given during adolescence ) prevent the emergence of cognitive impairment associated with a developmental model of schizophrenia .", "entity": [], "task": "NER"}
{"text": "Swim training of monosodium L - glutamate - obese mice improves the impaired insulin receptor tyrosine phosphorylation in pancreatic islets .", "entity": [{"entity": "monosodium L - glutamate", "entity_type": "Chemical", "pos": [17, 41]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "The goal of the present study was to investigate changes on glucose homoeostasis and of the insulin receptor ( IR ) and insulin receptor substrate - 1 ( IRS - 1 ) signalling in pancreatic islets from MSG - obese mice submitted to or not submitted to swim training .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [200, 203]}], "task": "NER"}
{"text": "Swim training of 90 - day - old MSG mice was used to evaluate whether signalling pathways of the IR and IRS - 1 in islets are involved with the insulin resistance and glucose intolerance observed in this obese animal model .", "entity": [{"entity": "MSG", "entity_type": "Chemical", "pos": [32, 35]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [167, 174]}], "task": "NER"}
{"text": "The results showed that IR tyrosine phosphorylation ( pIR ) was reduced by 42 % in MSG - obese mice ( MSG , 6 . 7 +/- 0 . 2 arbitrary units ( a . u . ) ; control , 11 . 5 +/- 0 . 4 a . u . ) ; on the other hand , exercise training increased pIR by 76 % in MSG mice without affecting control mice ( MSG , 11 . 8 +/- 0 . 3 ; control , 12 . 8 +/- 0 . 2 a . u . ) .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [256, 259]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [298, 301]}], "task": "NER"}
{"text": "Although the treatment with MSG increased IRS - 1 tyrosine phosphorylation ( pIRS - 1 ) by 96 % ( MSG , 17 . 02 +/- 0 . 6 ; control , 8 . 7 +/- 0 . 2 a . u . ) , exercise training also increased it in both groups ( control , 13 . 6 +/- 0 . 1 ; MSG , 22 . 2 +/- 1 . 1 a . u . ) .", "entity": [{"entity": "MSG", "entity_type": "Chemical", "pos": [28, 31]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [98, 101]}, {"entity": "MSG", "entity_type": "Chemical", "pos": [244, 247]}], "task": "NER"}
{"text": "Current research shows that the practice of swim training increases the tyrosine phosphorylation of IRS - 1 which can modulate the effect caused by obesity in insulin receptors .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "Juvenile hormone levels reflect social opportunities in the facultatively eusocial sweat bee Megalopta genalis ( Hymenoptera : Halictidae ) .", "entity": [{"entity": "Juvenile hormone", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "The evolution of eusociality is hypothesized to have involved de - coupling parental care from reproduction mediated by changes in endocrine regulation .", "entity": [], "task": "NER"}
{"text": "While data for obligately eusocial insects are consistent with this hypothesis , we lack information from species representative of the transition from solitary reproduction to eusociality .", "entity": [], "task": "NER"}
{"text": "Here we report the first evidence for a link between endocrine processes and social behavior in a facultatively eusocial bee , Megalopta genalis ( Halictidae ) .", "entity": [], "task": "NER"}
{"text": "Using females that varied in social , reproductive , and ecological context , we measured juvenile hormone ( JH ) , a major regulator of colony caste dynamics in other eusocial species .", "entity": [{"entity": "juvenile hormone", "entity_type": "Chemical", "pos": [90, 106]}], "task": "NER"}
{"text": "JH was low at adult emergence , but elevated after 10 days in all nesting females .", "entity": [], "task": "NER"}
{"text": "Females reared in cages with ad lib nutrition , however , did not elevate JH levels after 10 days .", "entity": [], "task": "NER"}
{"text": "All reproductive females had significantly more JH than all age - matched non - reproductive females , suggesting a gonadotropic function .", "entity": [], "task": "NER"}
{"text": "Among females in established nests , JH was higher in queens than workers and solitary reproductives , suggesting a role for JH in social dominance .", "entity": [], "task": "NER"}
{"text": "A lack of significant differences in JH between solitary reproductives and non - reproductive workers suggests that JH content reflects more than reproductive status .", "entity": [], "task": "NER"}
{"text": "Our data support the hypothesis that endocrine modifications are involved in the evolutionary decoupling of reproductive and somatic effort in social insects .", "entity": [], "task": "NER"}
{"text": "These are the first measurements of JH in a solitary - nesting hymenopteran , and the first to compare eusocial and solitary nesting individuals of the same species .", "entity": [], "task": "NER"}
{"text": "Friedelin and lanosterol from Garcinia prainiana stimulated glucose uptake and adipocytes differentiation in 3T3 - L1 adipocytes .", "entity": [{"entity": "Friedelin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "lanosterol", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "Friedelin and lanosterol have been isolated from twigs of Garcinia prainiana .", "entity": [{"entity": "Friedelin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "lanosterol", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "Their structures were elucidated by spectroscopic methods .", "entity": [], "task": "NER"}
{"text": "The compounds were examined for their effects on 3T3 - L1 adipocytes .", "entity": [], "task": "NER"}
{"text": "In the MTT assay , it was found that the compounds had no cytotoxic effects up to 25 micro M .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [7, 10]}], "task": "NER"}
{"text": "Adipocyte differentiation analysis was carried out by Oil Red O staining method .", "entity": [{"entity": "Oil Red O", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "In the presence of adipogenic cocktail ( MDI ) , it was found that friedelin and lanosterol enhanced intracellular fat accumulation by 2 . 02 and 2 . 18 - fold , respectively , compared with the vehicle - treated cells .", "entity": [{"entity": "friedelin", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "lanosterol", "entity_type": "Chemical", "pos": [81, 91]}], "task": "NER"}
{"text": "Deoxyglucose uptake assay was used to examine the insulin sensitivity of adipocytes in the presence of the compounds .", "entity": [{"entity": "Deoxyglucose", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "It was found that friedelin was able to stimulate glucose uptake up to 1 . 8 - fold compared with insulin - treated cells .", "entity": [{"entity": "friedelin", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "It was suggested that friedelin and lanosterol may be beneficial to mimic insulin action that would be useful in the treatment of diabetes type 2 patients .", "entity": [{"entity": "friedelin", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "lanosterol", "entity_type": "Chemical", "pos": [36, 46]}], "task": "NER"}
{"text": "Airway contractility and remodeling : links to asthma symptoms .", "entity": [], "task": "NER"}
{"text": "Respiratory symptoms are largely caused by obstruction of the airways .", "entity": [], "task": "NER"}
{"text": "In asthma , airway narrowing mediated by airway smooth muscle ( ASM ) contraction contributes significantly to obstruction .", "entity": [], "task": "NER"}
{"text": "The spasmogens produced following exposure to environmental triggers , such as viruses or allergens , are initially responsible for ASM activation .", "entity": [], "task": "NER"}
{"text": "However , the extent of narrowing of the airway lumen due to ASM shortening can be influenced by many factors and it remains a real challenge to decipher the exact role of ASM in causing asthmatic symptoms .", "entity": [], "task": "NER"}
{"text": "Innovative tools , such as the forced oscillation technique , continue to develop and have been proven useful to assess some features of ASM function in vivo .", "entity": [], "task": "NER"}
{"text": "Despite these technologic advances , it is still not clear whether excessive narrowing in asthma is driven by ASM abnormalities , by other alterations in non - muscle factors or simply because of the overexpression of spasmogens .", "entity": [], "task": "NER"}
{"text": "This is because a multitude of forces are acting on the airway wall , and because not only are these forces constantly changing but they are also intricately interconnected .", "entity": [], "task": "NER"}
{"text": "To counteract these limitations , investigators have utilized in vitro and ex vivo systems to assess and compare asthmatic and non - asthmatic ASM contractility .", "entity": [], "task": "NER"}
{"text": "This review describes : 1 - some muscle and non - muscle factors that are altered in asthma that may lead to airway narrowing and asthma symptoms ; 2 - some technologies such as the forced oscillation technique that have the potential to unveil the role of ASM in airway narrowing in vivo ; and 3 - some data from ex vivo and in vitro methods that probe the possibility that airway hyperresponsiveness is due to the altered environment surrounding the ASM or , alternatively , to a hypercontractile ASM phenotype that can be either innate or acquired .", "entity": [], "task": "NER"}
{"text": "Cost - effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan .", "entity": [{"entity": "alendronate", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "Many postmenopausal women have osteopenia , a condition characterized by loss of bone mineral density ( BMD ) that is not as severe as in osteoporosis .", "entity": [], "task": "NER"}
{"text": "The objective of this study was to estimate the cost - effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan .", "entity": [{"entity": "alendronate", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "An individual simulation model was developed to predict lifetime costs and quality - adjusted life years ( QALYs ) of 5 years of preventive alendronate therapy versus no preventive therapy .", "entity": [{"entity": "alendronate", "entity_type": "Chemical", "pos": [140, 151]}], "task": "NER"}
{"text": "The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan .", "entity": [], "task": "NER"}
{"text": "We ran the model with different combinations of age ( 65 , 70 , and 75 years ) , BMD ( 70 % , 75 % , and 80 % of young adult mean [ YAM ] ) , and additional clinical risk factors .", "entity": [], "task": "NER"}
{"text": "For 70 - year - old women with a BMD of 70 % of the YAM having one of the following risk factors : a family history of hip fracture , high alcohol intake , or current smoking , the incremental cost - effectiveness ratio ( ICER ) of alendronate was $ 92 , 937 , $ 126 , 251 , and $ 129 , 067 per QALY , respectively .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [139, 146]}, {"entity": "alendronate", "entity_type": "Chemical", "pos": [232, 243]}], "task": "NER"}
{"text": "These results were sensitive to age , BMD , and number of clinical risk factors .", "entity": [], "task": "NER"}
{"text": "Probabilistic sensitivity analysis for the base case showed that in the presence of one , two , and three risk factors , alendronate was cost - effective in 0 . 2 % to 2 . 6 % , 13 . 1 % to 56 . 1 % , and 99 . 1 % of the simulations , respectively , if society is willing to pay $ 50 , 000 per QALY .", "entity": [{"entity": "alendronate", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10 - year probability for a osteoporotic hip or vertebral fracture is more than 26 . 2 % .", "entity": [{"entity": "alendronate", "entity_type": "Chemical", "pos": [35, 46]}], "task": "NER"}
{"text": "Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age , BMD , and number of clinical risk factors in terms of cost - effectiveness .", "entity": [{"entity": "alendronate", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "Targeted disruption of inducible nitric oxide synthase protects against aging , S - nitrosation , and insulin resistance in muscle of male mice .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [33, 45]}, {"entity": "S", "entity_type": "Chemical", "pos": [80, 81]}], "task": "NER"}
{"text": "Accumulating evidence has demonstrated that S - nitrosation of proteins plays a critical role in several human diseases .", "entity": [{"entity": "S", "entity_type": "Chemical", "pos": [44, 45]}], "task": "NER"}
{"text": "Here , we explored the role of inducible nitric oxide synthase ( iNOS ) in the S - nitrosation of proteins involved in the early steps of the insulin - signaling pathway and insulin resistance in the skeletal muscle of aged mice .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "S", "entity_type": "Chemical", "pos": [68, 69]}], "task": "NER"}
{"text": "Aging increased iNOS expression and S - nitrosation of major proteins involved in insulin signaling , thereby reducing insulin sensitivity in skeletal muscle .", "entity": [{"entity": "S", "entity_type": "Chemical", "pos": [19, 20]}], "task": "NER"}
{"text": "Conversely , aged iNOS - null mice were protected from S - nitrosation - induced insulin resistance .", "entity": [{"entity": "S", "entity_type": "Chemical", "pos": [21, 22]}], "task": "NER"}
{"text": "Moreover , pharmacological treatment with an iNOS inhibitor and acute exercise reduced iNOS - induced S - nitrosation and increased insulin sensitivity in the muscle of aged animals .", "entity": [{"entity": "S", "entity_type": "Chemical", "pos": [48, 49]}], "task": "NER"}
{"text": "These findings indicate that the insulin resistance observed in aged mice is mainly mediated through the S - nitrosation of the insulin - signaling pathway .", "entity": [{"entity": "S", "entity_type": "Chemical", "pos": [105, 106]}], "task": "NER"}
{"text": "Variation in osteocyte lacunar morphology and density in the human femur - - a synchrotron radiation micro - CT study .", "entity": [], "task": "NER"}
{"text": "In recent years there has been growing interest in the spatial properties of osteocytes ( including density and morphology ) and how these potentially relate to adaptation , disease and aging .", "entity": [], "task": "NER"}
{"text": "This interest has , in part , arisen from the availability of increasingly high - resolution 3D imaging modalities such as synchrotron radiation ( SR ) micro - CT .", "entity": [], "task": "NER"}
{"text": "As resolution increases , field of view generally decreases .", "entity": [], "task": "NER"}
{"text": "Thus , while increasingly detailed spatial information is obtained , it is unclear how representative this information is of the skeleton or even the isolated bone .", "entity": [], "task": "NER"}
{"text": "The purpose of this research was to describe the variation in osteocyte lacunar density , morphology and orientation within the femur from a healthy young male human .", "entity": [], "task": "NER"}
{"text": "Multiple anterior , posterior , medial and lateral blocks ( 2 mm x 2 mm ) were prepared from the proximal femoral shaft and SR micro - CT imaged at the Advanced Photon Source .", "entity": [], "task": "NER"}
{"text": "Average lacunar densities ( +/- standard deviation ) from the anterior , posterior , medial and lateral regions were 27 , 169 +/- 1935 , 26 , 3643 +/- 1262 , 37 , 521 +/- 6416 and 33 , 972 +/- 2513 lacunae per mm ( 3 ) of bone tissue , respectively .", "entity": [], "task": "NER"}
{"text": "These values were significantly different between the medial and both the anterior and posterior regions ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "The density of the combined anterior and posterior regions was also significantly lower ( p = 0 . 001 ) than the density of the combined medial and lateral regions .", "entity": [], "task": "NER"}
{"text": "Although no difference was found in predominant orientation , shape differences were found ; with the combined anterior and posterior regions having more elongated ( p = 0 . 004 ) and flattened ( p = 0 . 045 ) lacunae , than those of the medial and lateral regions .", "entity": [], "task": "NER"}
{"text": "This study reveals variation in osteocyte lacunar density and morphology within the cross - section of a single bone and that this variation can be considerable ( up to 30 % difference in density between regions ) .", "entity": [], "task": "NER"}
{"text": "The underlying functional significance of the observed variation in lacunar density likely relates to localized variations in loading conditions as the pattern corresponds well with mechanical axes .", "entity": [], "task": "NER"}
{"text": "Lower density and more elongate shapes being associated with the antero - posterior oriented neutral axis .", "entity": [], "task": "NER"}
{"text": "Our findings demonstrate that the functional and pathological interpretations that are increasingly being drawn from high resolution imaging of osteocyte lacunae need to be better situated within the broader context of normal variation , including that which occurs even within a single skeletal element .", "entity": [], "task": "NER"}
{"text": "In vivo imaging of retinal ganglion cell apoptosis .", "entity": [], "task": "NER"}
{"text": "Apoptosis , or programmed cell death , plays a vital role in normal development and ageing .", "entity": [], "task": "NER"}
{"text": "However , dysregulation of this process is responsible for many disease states including ; cancer , autoimmune and neurodegeneration .", "entity": [], "task": "NER"}
{"text": "For this reason , in vivo visualisation of apoptosis may prove a useful tool for both laboratory research and clinical diagnostics .", "entity": [], "task": "NER"}
{"text": "Glaucoma comprises a distinctive group of chronic optic neuropathies , characterised by the progressive loss of retinal ganglion cells ( RGCs ) .", "entity": [], "task": "NER"}
{"text": "Early diagnosis of glaucoma remains a clear and unmet need .", "entity": [], "task": "NER"}
{"text": "Recently , there have been significant advances in the detection of apoptosis in vivo using fluorescent probes to visualise single RGCs undergoing apoptosis , specifically DARC ( Detection of Apoptotic Retinal Cells ) [ 1 ] and capQ technology [ 2 ( * * ) ] .", "entity": [], "task": "NER"}
{"text": "Microtubule network is required for insulin - induced signal transduction and actin remodeling .", "entity": [], "task": "NER"}
{"text": "Both microtubule and actin are required for insulin - induced glucose uptake .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [62, 69]}], "task": "NER"}
{"text": "However , the roles of these two cytoskeletons and their relationship in insulin action still remain unclear .", "entity": [], "task": "NER"}
{"text": "In this work , we examined the morphological change of microtubule / actin and their involvement in insulin signal transduction using rat skeletal muscle cells .", "entity": [], "task": "NER"}
{"text": "Insulin rapidly led to microtubule clustering from ventral to dorsal surface of the cell .", "entity": [], "task": "NER"}
{"text": "Microtubule filaments were rearranged to create space where new actin structures formed .", "entity": [], "task": "NER"}
{"text": "Disruption of microtubule prevented insulin - induced actin remodeling and distal insulin signal transduction , with reduction in surface glucose transporter isoform 4 ( GLUT4 ) and glucose uptake .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [138, 145]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [182, 189]}], "task": "NER"}
{"text": "Though microtubule mediated actin remodeling through PKC zeta , reorganization of microtubule depended on tyrosine phosphorylation of insulin receptor , the mechanism is different from insulin - induced actin remodeling , which relied on the activity of PI3 - kinase and PKC zeta .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "We propose that microtubule network is required for insulin - induced signal transduction and actin remodeling in skeletal muscle cells .", "entity": [], "task": "NER"}
{"text": "Selective regulation of nicotine and polyamines biosynthesis in tobacco cells by enantiomers of ornithine .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "polyamines", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "ornithine", "entity_type": "Chemical", "pos": [96, 105]}], "task": "NER"}
{"text": "L - and D - amino acids have diverse functions and effects on the metabolism , growth , and development of plants .", "entity": [{"entity": "L - and D - amino acids", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "Ornithine ( Orn ) plays a main role in the biosynthesis of many amino acids , nicotinic alkaloids , and polyamines in tobacco .", "entity": [{"entity": "Ornithine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Orn", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [64, 75]}, {"entity": "nicotinic alkaloids", "entity_type": "Chemical", "pos": [78, 97]}, {"entity": "polyamines", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "This investigation describes the impact of Orn enantiomers on the production and distribution of free , conjugated , and bound polyamines , as well as nicotine in tobacco cells .", "entity": [{"entity": "Orn", "entity_type": "Chemical", "pos": [43, 46]}, {"entity": "polyamines", "entity_type": "Chemical", "pos": [127, 137]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "It was recognized that the biosynthesis of metabolites was differently upregulated by each enantiomer .", "entity": [], "task": "NER"}
{"text": "Putrescine was abundantly produced by exogenous L - ornithine ( L - Orn ) , and both spermidine and spermine were significantly accumulated in D - ornithine ( D - Orn ) - supplied tobacco cells .", "entity": [{"entity": "Putrescine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "L - ornithine", "entity_type": "Chemical", "pos": [48, 61]}, {"entity": "L - Orn", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "spermidine", "entity_type": "Chemical", "pos": [85, 95]}, {"entity": "spermine", "entity_type": "Chemical", "pos": [100, 108]}, {"entity": "D - ornithine", "entity_type": "Chemical", "pos": [143, 156]}, {"entity": "D - Orn", "entity_type": "Chemical", "pos": [159, 166]}], "task": "NER"}
{"text": "Furthermore , nicotine production was highly upregulated by L - Orn , while the addition of D - Orn had no effect on the nicotine content of tobacco cells .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "L - Orn", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "D - Orn", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [121, 129]}], "task": "NER"}
{"text": "It was observed that transcript expression of S - adenosylmethionine decarboxylase , as the key enzyme of spermidine / spermine biosynthesis , is coincident with their metabolic levels and is highly upregulated by D - Orn , as opposed to L - Orn .", "entity": [{"entity": "S - adenosylmethionine", "entity_type": "Chemical", "pos": [46, 68]}, {"entity": "spermidine", "entity_type": "Chemical", "pos": [106, 116]}, {"entity": "spermine", "entity_type": "Chemical", "pos": [119, 127]}, {"entity": "D - Orn", "entity_type": "Chemical", "pos": [214, 221]}, {"entity": "L - Orn", "entity_type": "Chemical", "pos": [238, 245]}], "task": "NER"}
{"text": "These results indicate that both enantiomers of Orn can trigger selected biosynthetic pathways in the cells , at the transcript level .", "entity": [{"entity": "Orn", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "Regarding these observations , it is proposed that L - and D - Orn function differently in the same biological pathways in which the latter , D - Orn specifically regulates important polyamines in the plant cells .", "entity": [{"entity": "L - and D - Orn", "entity_type": "Chemical", "pos": [51, 66]}, {"entity": "D - Orn", "entity_type": "Chemical", "pos": [142, 149]}, {"entity": "polyamines", "entity_type": "Chemical", "pos": [183, 193]}], "task": "NER"}
{"text": "Human gastric TFF2 peptide contains an N - linked fucosylated N , N ' - diacetyllactosediamine ( LacdiNAc ) oligosaccharide .", "entity": [{"entity": "N - linked fucosylated N , N ' - diacetyllactosediamine", "entity_type": "Chemical", "pos": [39, 94]}, {"entity": "LacdiNAc", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "In the human stomach , the peptide trefoil factor family 2 ( TFF2 ) is secreted together with the mucin MUC6 by mucous neck cells ( MNCs ) and antral gland cells .", "entity": [], "task": "NER"}
{"text": "TFF2 is strongly associated with the gastric mucus and promotes gastric restitution .", "entity": [], "task": "NER"}
{"text": "Here , TFF2 was purified from the human corpus and antrum , respectively , by size - exclusion chromatography , and the N - linked glycan structure at N - 15 of the mature peptide was determined .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [120, 121]}], "task": "NER"}
{"text": "As a hallmark , the unusual monofucosylated N , N ' - diacetylhexosediamine ( tentatively assigned as GalNAc beta 1 --> 4GlcNAc , LacdiNAc ) modification was detected as the terminal structure of a bi - antennary complex type N - glycan exhibiting also core fucosylation .", "entity": [{"entity": "monofucosylated N , N ' - diacetylhexosediamine", "entity_type": "Chemical", "pos": [28, 75]}, {"entity": "GalNAc beta 1 --> 4GlcNAc", "entity_type": "Chemical", "pos": [102, 127]}, {"entity": "LacdiNAc", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "N", "entity_type": "Chemical", "pos": [226, 227]}], "task": "NER"}
{"text": "Replicate analyses did not show microheterogeneities in the fraction of peptide - N - glycosidase F cleaved and permethylated N - glycans when analyzed by matrix - assisted laser desorption ionization ( MALDI ) mass spectrometry ( MS ) .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [82, 83]}, {"entity": "N", "entity_type": "Chemical", "pos": [126, 127]}], "task": "NER"}
{"text": "On the glycopeptide level , a minor glycan microheterogeneity was evident in liquid chromatography - electrospray ionization ( ESI ) - MS , demonstrating the presence of underfucosylated species .", "entity": [], "task": "NER"}
{"text": "The tryptic TFF2 N - glycopeptide p34 - 39 ( LSPHNR N - glycosylated with Fuc3Hex3HexNAc6 ) was identified by both ESI - tandem mass spectrometry and MALDI - post - source decay analysis .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [17, 18]}, {"entity": "N", "entity_type": "Chemical", "pos": [49, 50]}, {"entity": "Fuc3Hex3HexNAc6", "entity_type": "Chemical", "pos": [74, 89]}], "task": "NER"}
{"text": "Lectin analyses with the Wisteria floribunda agglutinin indicated the potential presence of LacdiNAc terminating glycans and revealed minor differences between TFF2 from fundic units , i . e . MNCs , and antral units , i . e . antral gland cells .", "entity": [{"entity": "LacdiNAc", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "Strikingly , on the level of the primary structure , there was no indication that the formation of the proposed LacdiNAc structure is cis - controlled by a peptidic determinant related to the published sequences .", "entity": [{"entity": "LacdiNAc", "entity_type": "Chemical", "pos": [112, 120]}], "task": "NER"}
{"text": "Altering the way the optic nerve head responds to intraocular pressure - a potential approach to glaucoma therapy .", "entity": [], "task": "NER"}
{"text": "Over the past decade , engineering principles have been used to explain why a mechanical load , intraocular pressure , can lead to the development of glaucomatous optic neuropathy .", "entity": [], "task": "NER"}
{"text": "This has led to the ' biomechanical theory ' of glaucoma , which posits that the behavior of optic nerve head connective tissues ( specifically within the peripapillary sclera and lamina cribrosa ) in response to intraocular pressure ( regardless of its magnitude ) can directly and indirectly influence the physiology and pathophysiology of the optic nerve head .", "entity": [], "task": "NER"}
{"text": "Given that the biomechanics of the sclera and lamina cribrosa probably influence retinal ganglion cell loss in glaucoma , the idea that altering biomechanical behavior might be protective against glaucoma is an appealing notion .", "entity": [], "task": "NER"}
{"text": "There is some evidence to suggest that stiffening the peripapillary sclera may be protective against the development of glaucoma in an animal model .", "entity": [], "task": "NER"}
{"text": "It is technically possible to stiffen the sclera in vivo using collagen cross - linking techniques already applied in vivo to the cornea in the treatment of keratoconus .", "entity": [], "task": "NER"}
{"text": "It has yet to be established whether scleral cross - linking is safe in humans and that it confers anything more than a theoretical advantage in terms of reducing the risk of glaucomatous damage .", "entity": [], "task": "NER"}
{"text": "Maintenance of retinal ganglion cell mitochondrial functions as a neuroprotective strategy in glaucoma .", "entity": [], "task": "NER"}
{"text": "Loss of vision in glaucoma occurs because retinal ganglion cells ( RGCs ) die .", "entity": [], "task": "NER"}
{"text": "RGCs have probably more mitochondria than any other neurone in the CNS .", "entity": [], "task": "NER"}
{"text": "It is proposed that stress to mitochondria of individual RGCs is a major trigger of the disease and also provides an explanation why different RGCs die at different times .", "entity": [], "task": "NER"}
{"text": "Pharmacological agents that can maintain mitochondrial functions , in particular to attenuate oxidative stress and to sustain energy production , might therefore provide a novel way of slowing down RGC death and help in the treatment of glaucoma .", "entity": [], "task": "NER"}
{"text": "Cannabinoid CB 1 receptor in the modulation of stress coping behavior in mice : the role of serotonin and different forebrain neuronal subpopulations .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [92, 101]}], "task": "NER"}
{"text": "The endocannabinoid system ( ECS ) may either enhance or inhibit responses to aversive stimuli , possibly caused by its modulatory activity on diverse neurotransmitters .", "entity": [], "task": "NER"}
{"text": "The aim of this work was to investigate the involvement of serotonin ( 5 - HT ) and catecholamines , as well as the role of glutamatergic and GABAergic cannabinoid type 1 ( CB ( 1 ) ) receptor , in responses to the antidepressant - like doses of the CB ( 1 ) receptor agonist Delta ( 9 ) - tetrahydrocannabinol ( THC ) and the antagonist rimonabant in the forced swim test ( FST ) .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [59, 68]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [71, 77]}, {"entity": "catecholamines", "entity_type": "Chemical", "pos": [84, 98]}, {"entity": "Delta ( 9 ) - tetrahydrocannabinol", "entity_type": "Chemical", "pos": [276, 310]}, {"entity": "THC", "entity_type": "Chemical", "pos": [313, 316]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [338, 348]}], "task": "NER"}
{"text": "Mice received acute injections of low doses of THC ( 0 . 1 or 0 . 5 mg / kg ) or high dose of rimonabant ( 3 or 10 mg / kg ) after treatment with the 5 - HT synthesis inhibitor pCPA ( 100 mg / kg , 4 days ) , the 5 - HT ( 1A ) receptor antagonist WAY100635 ( 1 mg / kg , acute ) or the non - selective blocker of catecholamine synthesis , AMPT ( 20 mg / kg , acute ) .", "entity": [{"entity": "THC", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [150, 156]}, {"entity": "pCPA", "entity_type": "Chemical", "pos": [177, 181]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [213, 219]}, {"entity": "WAY100635", "entity_type": "Chemical", "pos": [247, 256]}, {"entity": "catecholamine", "entity_type": "Chemical", "pos": [313, 326]}, {"entity": "AMPT", "entity_type": "Chemical", "pos": [339, 343]}], "task": "NER"}
{"text": "THC and rimonabant were also tested in mutant mice lacking CB ( 1 ) receptor in specific forebrain neuronal subpopulations .", "entity": [{"entity": "THC", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [8, 18]}], "task": "NER"}
{"text": "Both THC and rimonabant induced antidepressant - like effects , quantified as immobility in the FST .", "entity": [{"entity": "THC", "entity_type": "Chemical", "pos": [5, 8]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [13, 23]}], "task": "NER"}
{"text": "However , only THC effects were reversed by pCPA or WAY100635 .", "entity": [{"entity": "THC", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "pCPA", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "WAY100635", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "In contrast , only AMPT could attenuate the rimonabant effect .", "entity": [{"entity": "AMPT", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [44, 54]}], "task": "NER"}
{"text": "We also found decreased immobility in mice lacking the CB ( 1 ) receptor in glutamatergic cortical neurons , but not in forebrain GABAergic neurons , as compared with wild - type controls .", "entity": [], "task": "NER"}
{"text": "The effect of THC persisted in mutant mice with CB ( 1 ) receptor inactivation in GABAergic neurons , whereas rimonabant effects were alleviated in these mutants .", "entity": [{"entity": "THC", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [110, 120]}], "task": "NER"}
{"text": "Thus , employing both pharmacological and genetic tools , we could show that the ECS regulates stress responses by influencing GABAergic , glutamatergic and monoaminergic transmission .", "entity": [], "task": "NER"}
{"text": "The antidepressant - like action of THC depends on serotonergic neurotransmission , whereas rimonabant effects are mediated by CB ( 1 ) receptor on GABAergic neurons and by catecholamine signaling .", "entity": [{"entity": "THC", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "rimonabant", "entity_type": "Chemical", "pos": [92, 102]}, {"entity": "catecholamine", "entity_type": "Chemical", "pos": [173, 186]}], "task": "NER"}
{"text": "Pharmacological targeting of endoplasmic reticulum stress signaling in cancer .", "entity": [], "task": "NER"}
{"text": "The endoplasmic reticulum ( ER ) stress response constitutes a cellular process that can be triggered by a great variety of conditions that cause imbalances in intracellular homeostasis and threaten proper cell functioning .", "entity": [], "task": "NER"}
{"text": "In response , the ER stress response activates an adaptive effort aimed at neutralizing these threats and reestablishing homeostasis .", "entity": [], "task": "NER"}
{"text": "However , if these countermeasures are unsuccessful and severe imbalances persist , the ER stress response may abandon its pro - survival efforts and instead may initiate a pro - apoptotic program to eliminate the faulty cell for the benefit of the organism as a whole .", "entity": [], "task": "NER"}
{"text": "Because vigorous growth of malignant tumors may create stressful conditions , such as hypoglycemia , hypoxia , or accumulation of misfolded proteins during revved up protein synthesis , the adaptive , pro - survival components of the ER stress response system ( e . g . , GRP78 / BiP ) are frequently found chronically activated in tumor cells .", "entity": [], "task": "NER"}
{"text": "This differential to non - stressed normal cells has been proposed to represent an Achilles ' heel of tumor cells that may be exploitable by therapeutic intervention .", "entity": [], "task": "NER"}
{"text": "In this model , the goal would be to further aggravate the pre - existing stress conditions in tumor cells with appropriate pharmacological agents , so that the already engaged pro - survival mechanism would be overwhelmed and the ER stress response forced to switch to its pro - apoptotic mode ( e . g . , CHOP / GADD153 ) .", "entity": [], "task": "NER"}
{"text": "This review will discuss the principle of pharmacological ER stress aggravation , and will present preclinical models with promise for cancer therapeutic applications .", "entity": [], "task": "NER"}
{"text": "The risky cocktail : what combination effects can we expect between ecstasy and other amphetamines ?", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "amphetamines", "entity_type": "Chemical", "pos": [86, 98]}], "task": "NER"}
{"text": "The recreational and illicit use of amphetaminic designer compounds , specially 3 , 4 - methylenedioxymethamphetamine ( MDMA ; Ecstasy ) , is of concern worldwide .", "entity": [{"entity": "3 , 4 - methylenedioxymethamphetamine", "entity_type": "Chemical", "pos": [80, 117]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [120, 124]}, {"entity": "Ecstasy", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "Such psychostimulating drugs are frequently present as complex mixtures in ' rave ' pills , making concomitant polysubstance use a common trend .", "entity": [], "task": "NER"}
{"text": "However , the understanding of possible combination effects with these substances is still scarce .", "entity": [], "task": "NER"}
{"text": "The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives : MDMA , methamphetamine , 4 - methylthioamphetamine and d - amphetamine in a human hepatoma cell line .", "entity": [{"entity": "MDMA", "entity_type": "Chemical", "pos": [111, 115]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [118, 133]}, {"entity": "4 - methylthioamphetamine", "entity_type": "Chemical", "pos": [136, 161]}, {"entity": "d - amphetamine", "entity_type": "Chemical", "pos": [166, 181]}], "task": "NER"}
{"text": "Concentration - response curves for all single - mixture components were recorded by the MTT assay .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition , using the pharmacological models of concentration addition ( CA ) and independent action .", "entity": [], "task": "NER"}
{"text": "By comparing the predicted calculations with the experimentally observed effects , we concluded that CA accurately predicts the combination of amphetamines , which act together to generate additive effects over a large range of concentrations .", "entity": [{"entity": "amphetamines", "entity_type": "Chemical", "pos": [143, 155]}], "task": "NER"}
{"text": "Notably , we observed substantial mixture effects even when each drug was present at low concentrations , which individually produced unnoticeable effects .", "entity": [], "task": "NER"}
{"text": "Nonetheless , for all tested mixtures , a small deviation from additivity was observed towards higher concentrations , particularly at high effect levels .", "entity": [], "task": "NER"}
{"text": "A possible metabolic interaction , which could explain such deviation , was investigated , and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity .", "entity": [{"entity": "MDMA", "entity_type": "Chemical", "pos": [159, 163]}], "task": "NER"}
{"text": "In conclusion , the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly .", "entity": [], "task": "NER"}
{"text": "Resistin knockout mice exhibit impaired adipocyte glucose - dependent insulinotropic polypeptide receptor ( GIPR ) expression .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "Glucose - dependent insulinotropic polypeptide ( GIP ) is an incretin hormone that also plays a regulatory role in fat metabolism .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In 3T3 - L1 cells , resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase ( LPL ) activity , involving activation of protein kinase B ( PKB ) and reduced phosphorylation of liver kinase B1 ( LKB1 ) and AMP - activated protein kinase ( AMPK ) .", "entity": [{"entity": "AMP", "entity_type": "Chemical", "pos": [236, 239]}], "task": "NER"}
{"text": "The current study was initiated to determine whether resistin has additional roles in GIP - regulated adipocyte functions .", "entity": [], "task": "NER"}
{"text": "Analysis of primary adipocytes isolated from Retn ( - / - ) , Retn ( + / - ) , and Retn ( + / + ) mice found that GIP stimulated the PKB / LKB1 / AMPK / LPL pathway and fatty acid uptake only in Retn ( + / + ) adipocytes , suggesting that GIP signaling and / or GIP responsiveness were compromised in Retn ( + / - ) and Retn ( - / - ) adipocytes .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [169, 179]}], "task": "NER"}
{"text": "GIP receptor ( GIPR ) protein and mRNA were decreased in Retn ( + / - ) and Retn ( - / - ) adipocytes , but resistin treatment rescued LPL responsiveness to GIP .", "entity": [], "task": "NER"}
{"text": "In addition , genes encoding tumor necrosis factor ( TNF ) , TNF receptor 2 ( TNFR2 ) , and the signaling proteins stress - activated protein kinase ( SAPK ) / Jun NH ( 2 ) - terminal kinase ( JNK ) , were downregulated , and phosphorylated levels of SAPK / JNK / c - Jun were decreased in Retn ( - / - ) mice .", "entity": [{"entity": "NH ( 2 )", "entity_type": "Chemical", "pos": [164, 172]}], "task": "NER"}
{"text": "Chromatin immunoprecipitation assays were used to identify a 12 - O - tetradecanoylphorbol - 13 - acetate ( TPA ) - response element ( TRE - III ) responsible for c - Jun - mediated transcriptional activation of Gipr .", "entity": [{"entity": "12 - O - tetradecanoylphorbol - 13 - acetate", "entity_type": "Chemical", "pos": [61, 105]}, {"entity": "TPA", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Blunted GIP responsiveness in Retn ( + / - ) and Retn ( - / - ) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c - Jun - mediated transcriptional activation of Gipr .", "entity": [], "task": "NER"}
{"text": "When did decapods invade hydrothermal vents ?", "entity": [], "task": "NER"}
{"text": "Clues from the Western Pacific and Indian Oceans .", "entity": [], "task": "NER"}
{"text": "Hydrothermal vents are typically located in midocean ridges and back - arc basins and are usually generated by the movement of tectonic plates .", "entity": [], "task": "NER"}
{"text": "Life thrives in these environments despite the extreme conditions .", "entity": [], "task": "NER"}
{"text": "In addition to chemoautotrophic bacteria , decapod crustaceans are dominant in many of the hydrothermal vents discovered to date .", "entity": [], "task": "NER"}
{"text": "Contrary to the hypothesis that these species are remnants of relic fauna , increasing evidence supports the notion that hydrothermal vent decapods have diversified in more recent times with previous research attributing the origin of alvinocarid shrimps to the Miocene .", "entity": [], "task": "NER"}
{"text": "This study investigated seven representative decapod species from four hydrothermal vents throughout the Western Pacific and Indian Oceans .", "entity": [], "task": "NER"}
{"text": "A partitioned mix - model phylogenomic analysis of mitochondrial DNA produced a consistent phylogenetic topology of these vent - endemic species .", "entity": [], "task": "NER"}
{"text": "Additionally , molecular dating analysis calibrated using multiple fossils suggested that both bythograeid crabs and alvinocarid shrimps originated in the late Mesozoic and early Cenozoic .", "entity": [], "task": "NER"}
{"text": "Although of limited sampling , our estimates support the extinction / repopulation hypothesis , which postulates recent diversification times for most hydrothermal vent species due to their mass extinction by global deep - water anoxic / dysoxic events during the Late Cretaceous and Early Tertiary .", "entity": [], "task": "NER"}
{"text": "The continental - derived property of the West Pacific province is compatible with the possibility that vent decapods diversified from ancestors from shallow - water regions such as cold seeps .", "entity": [], "task": "NER"}
{"text": "Our results move us a step closer toward understanding the evolutionary origin of hydrothermal vent species and their distribution in the Western Pacific - Indian Ocean Region .", "entity": [], "task": "NER"}
{"text": "Cellular and molecular mechanisms of hepatocellular carcinoma : an update .", "entity": [], "task": "NER"}
{"text": "Hepatocellular carcinoma ( HCC ) is the most common primary malignant tumor that accounts for ~ 80 % of all liver cancer cases worldwide .", "entity": [], "task": "NER"}
{"text": "It is a multifactorial disease caused by a variety of risk factors and often develops in the background of underlying cirrhosis .", "entity": [], "task": "NER"}
{"text": "A number of cellular phenomena , such as tumor microenvironment , inflammation , oxidative stress , and hypoxia act in concert with various molecular events to facilitate tumor initiation , progression , and metastasis .", "entity": [], "task": "NER"}
{"text": "The emergence of microRNAs and molecular - targeted therapies adds a new dimension in our efforts to combat this deadly disease .", "entity": [], "task": "NER"}
{"text": "Intense research in this multitude of areas has led to significant progress in our understanding of cellular processes and molecular mechanisms that occur during multistage events that lead to hepatocarcinogenesis .", "entity": [], "task": "NER"}
{"text": "In this review , we discuss the current knowledge of HCC , focusing mainly on advances that have occurred during the past 5 years and on the development of novel therapeutics for liver cancer .", "entity": [], "task": "NER"}
{"text": "The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain .", "entity": [], "task": "NER"}
{"text": "The present study was designed to evaluate the effects of chronic fluorosis on the dynamics ( including fusion and fission proteins ) , fragmentation , and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with excess accumulation of fluoride .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [341, 349]}], "task": "NER"}
{"text": "Sixty Sprague - Dawley rats were divided randomly into three groups of 20 each , that is , the untreated control group ( drinking water naturally containing < 0 . 5 mg fluoride / l , NaF ) , the low - fluoride group ( whose drinking water was supplemented with 10 mg fluoride / l ) and the high - fluoride group ( 50 mg fluoride / l ) .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [168, 176]}, {"entity": "NaF", "entity_type": "Chemical", "pos": [183, 186]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [201, 209]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [267, 275]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [297, 305]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [320, 328]}], "task": "NER"}
{"text": "After 6 months of exposure , the expression of mitofusin - 1 ( Mfn1 ) , fission - 1 ( Fis1 ) , and dynamin - related protein - 1 ( Drp1 ) at both the protein and mRNA levels were detected by Western blotting , immunohistochemistry , and real - time PCR , respectively .", "entity": [], "task": "NER"}
{"text": "Moreover , mitochondrial morphology and distribution in neurons were observed by transmission electron or fluorescence microscopy .", "entity": [], "task": "NER"}
{"text": "In the cortices of the brains of rats with chronic fluorosis , the level of Mfn1 protein was clearly reduced , whereas the levels of Fis1 and Drp1 were elevated .", "entity": [], "task": "NER"}
{"text": "The alternations of expression of the mRNAs encoding all three of these proteins were almost the same as the corresponding changes at the protein levels .", "entity": [], "task": "NER"}
{"text": "The mitochondria were fragmented and the redistributed away from the axons of the cortical neurons .", "entity": [], "task": "NER"}
{"text": "These findings indicate that chronic fluorosis induces abnormal mitochondrial dynamics , which might in turn result in a high level of oxidative stress .", "entity": [], "task": "NER"}
{"text": "Cyclooxygenase ( COX ) - 1 and COX - 2 both play an important role in the protection of the duodenal mucosa in cats .", "entity": [], "task": "NER"}
{"text": "Although nonsteroidal anti - inflammatory drugs often cause ulcers in the duodenum in humans , the role of cyclooxygenase ( COX ) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated .", "entity": [], "task": "NER"}
{"text": "We examined in cats the 1 ) ulcerogenic effects of selective COX - 1 ( SC - 560 , ketorolac ) and COX - 2 ( celecoxib , meloxicam ) inhibitors on the gastrointestinal mucosa , 2 ) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E ( 2 ) ( PGE ( 2 ) ) level in the duodenum , and 3 ) localization of COX isoforms in the duodenum .", "entity": [{"entity": "SC - 560", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "ketorolac", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "meloxicam", "entity_type": "Chemical", "pos": [120, 129]}, {"entity": "cimetidine", "entity_type": "Chemical", "pos": [202, 212]}, {"entity": "prostaglandin E ( 2 )", "entity_type": "Chemical", "pos": [251, 272]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [275, 284]}], "task": "NER"}
{"text": "COX inhibitors were administered after the morning meal in cats once daily for 3 days .", "entity": [], "task": "NER"}
{"text": "Gastrointestinal lesions were examined on day 4 .", "entity": [], "task": "NER"}
{"text": "Localization and expression of COX isoforms ( by immunohistochemistry , Western blot ) and PGE ( 2 ) level ( by enzyme immunoassay ) were examined .", "entity": [{"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [91, 100]}], "task": "NER"}
{"text": "Results were as follows .", "entity": [], "task": "NER"}
{"text": "First , selective COX - 1 or COX - 2 inhibitors alone produced marked ulcers in the duodenum but did not cause obvious lesions in the small intestine .", "entity": [], "task": "NER"}
{"text": "Coadministration of SC - 560 and celecoxib produced marked lesions in the small intestine .", "entity": [{"entity": "SC - 560", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [33, 42]}], "task": "NER"}
{"text": "Second , feeding increased both the expression of COX isoforms and PGE ( 2 ) level in the duodenum , and the effects were markedly inhibited by pretreatment with cimetidine .", "entity": [{"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "cimetidine", "entity_type": "Chemical", "pos": [162, 172]}], "task": "NER"}
{"text": "Third , COX - 1 was localized in goblet and Brunner ' s gland cells , Meissner ' s and Auerbach ' s plexus , smooth muscle cells , and arterioles ; and COX - 2 was observed in capillaries , venules , and basal granulated cells .", "entity": [], "task": "NER"}
{"text": "The expression of COX isoforms in the duodenum is up - regulated by feeding , and inhibition of either COX - 1 or COX - 2 causes ulcers in the duodenum , suggesting that both isoforms play an important role in the protection of the duodenal mucosa .", "entity": [], "task": "NER"}
{"text": "Development of a live tissue microtome : reflections of an amateur machinist .", "entity": [], "task": "NER"}
{"text": "Live circular tissue slices of nearly identical diameter and thickness can be generated from most tissues by the use of two instruments ; a coring tool to cut cylindrical tissue cores which are subsequently sliced by a microtome into thin circular sections 5 - 8 mm in diameter and 50 - 300 microns thick .", "entity": [], "task": "NER"}
{"text": "The sections are of very similar geometry permitting direct comparisons without normalization .", "entity": [], "task": "NER"}
{"text": "Both instruments operate submerged in a cold isotonic medium that caries the cut slices outside the microtome .", "entity": [], "task": "NER"}
{"text": "The slices are cut by a rapidly oscillating disposable Gillette blade mounted at an angle of 20 degrees to the vertical main axis of the tissue core .", "entity": [], "task": "NER"}
{"text": "The latter is advanced against the oscillating blade by a weighted plunger pushing it against a screw adjustable limit plate that defines the desired slice thickness .", "entity": [], "task": "NER"}
{"text": "Both instruments can be sterilized and slices can be obtained at a rate of approximately one every ten seconds .", "entity": [], "task": "NER"}
{"text": "pH - and thermo - sensitive pluronic / poly ( acrylic acid ) in situ hydrogels for sustained release of an anticancer drug .", "entity": [{"entity": "pluronic", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "poly ( acrylic acid )", "entity_type": "Chemical", "pos": [39, 60]}], "task": "NER"}
{"text": "In this study , we developed oral in situ gelling formulations composed of pluronic ( Plu ) and polyacrylic acid ( PAA ) for the delivery of an anticancer drug , epirubicin ( Epi ) .", "entity": [{"entity": "pluronic", "entity_type": "Chemical", "pos": [75, 83]}, {"entity": "Plu", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "polyacrylic acid", "entity_type": "Chemical", "pos": [96, 112]}, {"entity": "PAA", "entity_type": "Chemical", "pos": [115, 118]}, {"entity": "epirubicin", "entity_type": "Chemical", "pos": [162, 172]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [175, 178]}], "task": "NER"}
{"text": "We investigated various Plu / PAA / Epi formulations for their physicochemical properties and in vitro permeation and accumulation , as well as for in vivo pharmacokinetic and antitumor efficacy .", "entity": [{"entity": "Plu", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "PAA", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "A scanning electron microscopic ( SEM ) image of Plu 14 % / PAA 0 . 75 % / Epi hydrogel showed a sponge - like structure .", "entity": [{"entity": "Plu", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "PAA", "entity_type": "Chemical", "pos": [60, 63]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [75, 78]}], "task": "NER"}
{"text": "This formulation has suitable gelation time , water content , bioadhesive force , structural stability , and a high permeation percentage of Epi , with sustained drug release characteristics for 96 h .", "entity": [{"entity": "Epi", "entity_type": "Chemical", "pos": [141, 144]}], "task": "NER"}
{"text": "This hydrogel was retained at the end of the ileum near the colon of Sprague - Dawley ( SD ) rats for at least 12 h .", "entity": [], "task": "NER"}
{"text": "An in vivo pharmacokinetic study using SD rats showed that after oral administration in this formulation , Epi had prolonged half - life , greater area under the curve , and higher relative bioavailability than in an oral Epi solution .", "entity": [{"entity": "Epi", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [222, 225]}], "task": "NER"}
{"text": "In vivo tumor growth inhibition of Epi in this formulation was more pronounced compared with oral Epi and intravenous Epi solutions in CT - 26 mouse colon adenocarcinoma bearing Balb / c mice .", "entity": [{"entity": "Epi", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [98, 101]}, {"entity": "Epi", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "This study highlights the advantages of using oral in situ temperature - and pH - sensitive hydrogels for future cancer therapy .", "entity": [], "task": "NER"}
{"text": "For whom the bell tolls : Distress signals from long - lived osteocytes and the pathogenesis of metabolic bone diseases .", "entity": [], "task": "NER"}
{"text": "Osteocytes are long - lived and far more numerous than the short - lived osteoblasts and osteoclasts .", "entity": [], "task": "NER"}
{"text": "Immured within the lacunar - canalicular system and mineralized matrix , osteocytes are ideally located throughout the bone to detect the need for , and accordingly choreograph , the bone regeneration process by independently controlling rate limiting steps of bone resorption and formation .", "entity": [], "task": "NER"}
{"text": "Consistent with this role , emerging evidence indicates that signals arising from apoptotic and old / or dysfunctional osteocytes are seminal culprits in the pathogenesis of involutional , post - menopausal , steroid - , and immobilization - induced osteoporosis .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [209, 216]}], "task": "NER"}
{"text": "Osteocyte - originated signals may also contribute to the increased bone fragility associated with bone matrix disorders like osteogenesis imperfecta , and perhaps the rapid reversal of bone turnover above baseline following discontinuation of anti - resorptive treatments , like denosumab .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled \" The Osteocyte \" .", "entity": [], "task": "NER"}
{"text": "The continuing saga of snake venom disintegrins .", "entity": [], "task": "NER"}
{"text": "Disintegrins , a family of polypeptides released in the venoms of viperid snakes ( vipers and rattlesnakes ) by the proteolytic processing of multidomain metalloproteinases , selectively block the function of beta ( 1 ) and beta ( 3 ) integrin receptors .", "entity": [], "task": "NER"}
{"text": "Few of the proteins isolated and characterized from snake venoms have proven to be more structural and functional versatile than the disintegrins .", "entity": [], "task": "NER"}
{"text": "Not surprisingly , 25 years after their discovery , our knowledge on the evolutionary history and the molecular determinants modulating the integrin inhibitory activity of disintegrins still remain fragmentary .", "entity": [], "task": "NER"}
{"text": "This paper highlights some seminal contributions , including personal accounts of pioneer authors , related to basic and applied research on disintegrins .", "entity": [], "task": "NER"}
{"text": "Investigators have evaluated disintegrin applications in therapies for a number of pathologies in which integrin receptors play relevant roles , particularly myocardial infarction and inappropriate tumor angiogenesis .", "entity": [], "task": "NER"}
{"text": "Completing the continuing story of the disintegrin family by applying novel research approaches may hold the key to learn how to use deadly toxins as therapeutic agents .", "entity": [], "task": "NER"}
{"text": "Development of histopathological indices in a commercial marine bivalve ( Ruditapes decussatus ) to determine environmental quality .", "entity": [], "task": "NER"}
{"text": "Bivalve histopathology is an acknowledged tool in environmental toxicology studies , however geographically restricted , limited to a few species and still lacking the degree of detail needed to develop effective ( semi ) quantitative approaches .", "entity": [], "task": "NER"}
{"text": "A first - time detailed histopathological screening was performed on grooved carpet shell clams collected from commercial shellfish beds in distinct coastal ecosystems of the Southern Portuguese coast : two parted sites within an impacted estuary ( S ( 1 ) and S ( 2 ) ) , an inlet channel of a fish farm at a considered pristine estuary ( site M ) and a site allocated in a clean coastal lagoon ( A ) .", "entity": [], "task": "NER"}
{"text": "A total of thirty histopathological lesions and alterations were analysed in the gills and digestive glands following a weighted condition indices approach , including inflammation - related responses , necrosis , neoplastic diseases and parasites .", "entity": [], "task": "NER"}
{"text": "Digestive glands were consistently more damaged than gills , except for animals collected from site M , where the most severe lesions were found in both organs , immediately followed by S ( 2 ) .", "entity": [], "task": "NER"}
{"text": "Clams from sites S ( 1 ) and A were overall the least damaged .", "entity": [], "task": "NER"}
{"text": "Neoplastic diseases were infrequent in all cases .", "entity": [], "task": "NER"}
{"text": "Inflammation - related traits were some of the most common alterations progressing in animals enduring severe lesions such as digestive tubule ( diverticula ) and intertubular tissue necrosis .", "entity": [], "task": "NER"}
{"text": "Some alterations , such as lipofuscin aggregates within digestive tubule cells , did not relate to histological lesions .", "entity": [], "task": "NER"}
{"text": "Granulocytomas only occurred in heavily infected tissues .", "entity": [], "task": "NER"}
{"text": "Animals from M and A presented the highest infections in the digestive gland , especially by protozoa .", "entity": [], "task": "NER"}
{"text": "Gill infections were more similar between sites .", "entity": [], "task": "NER"}
{"text": "Still , the level of infection does not account for all histopathological lesions in either organ .", "entity": [], "task": "NER"}
{"text": "Overall , the results are in accordance with environmental parameters , such as distance to pollution sources , sediment type and hydrodynamics , and show that the combination of multiple histopathological features in these clams provides good sensitivity for inter - site distinction even when low or moderate anthropogenic impacts are at stake .", "entity": [], "task": "NER"}
{"text": "Changes in trace elements during lactation in a marine top predator , the grey seal .", "entity": [], "task": "NER"}
{"text": "Lactation in pinnipeds represents the most significant cost to mothers during the reproductive cycle .", "entity": [], "task": "NER"}
{"text": "Dynamics of trace elements and their mobilization associated with energy reserves during such an intense physiological process remains poorly understood in marine mammals .", "entity": [], "task": "NER"}
{"text": "The changes in tissue concentrations of 11 elements ( Ca , Cd , Cr , Cu , Fe , Hg , Ni , Pb , Se , V , and Zn ) were investigated in a longitudinal study during the lactation period and during the post - weaning fast period .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [59, 61]}, {"entity": "Cr", "entity_type": "Chemical", "pos": [64, 66]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [69, 71]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [74, 76]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [79, 81]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [84, 86]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [89, 91]}, {"entity": "Se", "entity_type": "Chemical", "pos": [94, 96]}, {"entity": "V", "entity_type": "Chemical", "pos": [99, 100]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [107, 109]}], "task": "NER"}
{"text": "Blood , milk , blubber , and hair samples were collected sequentially from 21 mother - pup pairs of grey seals ( Halichoerus grypus ) from the Isle of May in Scotland .", "entity": [], "task": "NER"}
{"text": "Maternal transfer through the milk was observed for all trace elements , except for Cd .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [84, 86]}], "task": "NER"}
{"text": "As an indicator of the placental transfer , levels in pup lanugo ( natal coat ) revealed also the existence of maternal transfer and accumulation of all assayed trace elements during the foetal development .", "entity": [], "task": "NER"}
{"text": "The placental and mammary barriers against non - essential metal transfer to offspring appear to be absent or weak in grey seals .", "entity": [], "task": "NER"}
{"text": "Examining the contamination levels showed that this grey seal population seems more highly exposed to Pb than other phocid populations ( 2 . 2 mg / kg dw of grey seal hair ) .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [102, 104]}], "task": "NER"}
{"text": "In contrast , blood and hair levels reflected a lower Hg exposure in grey seals from the Isle of May than in harbour seals from the southeastern North Sea .", "entity": [{"entity": "Hg", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "This study also showed that trace element concentrations in blood and blubber could change rapidly over the lactation period .", "entity": [], "task": "NER"}
{"text": "Such physiological processes must be considered carefully during biomonitoring of trace elements , and potential impacts that rapid fluctuations in concentrations can exert on seal health should be further investigated .", "entity": [], "task": "NER"}
{"text": "Iodinated nano - emulsions as contrast agents for preclinical X - ray imaging : Impact of the free surfactants on the pharmacokinetics .", "entity": [], "task": "NER"}
{"text": "This study presents new important aspects in the design of contrast agents for X - ray preclinical imaging .", "entity": [], "task": "NER"}
{"text": "The first one is a new simple formulation of long circulating contrast agents , formulated from a commercial iodinated oil , and resulting in CT contrast agents containing more than twice the iodine concentration commercial contrast agents .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [192, 198]}], "task": "NER"}
{"text": "The second point is a methodological aspect , utilizing tangential filtration for reducing the residual surfactants in the bulk phase and serving as well for concentrating droplets ( and iodine ) in the suspension .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [187, 193]}], "task": "NER"}
{"text": "The last point is a more general aspect regarding the influence of the free surfactant on the pharmacokinetics and biodistribution of the nano - emulsion droplets on mice .", "entity": [], "task": "NER"}
{"text": "We showed that cross - flow filtration is efficient for concentrating the droplets and reducing the concentration of free surfactant from 10wt . % to 1wt . % , without any changes in the nano - emulsion droplet morphologies or surface properties .", "entity": [], "task": "NER"}
{"text": "We also showed that the presence of free surfactant has a significant impact on the elimination way of the nano - emulsion droplets , shared between liver and kidneys .", "entity": [], "task": "NER"}
{"text": "The purified nano - emulsions are preferentially eliminated by the kidneys in contrast to raw nano - emulsions , predominantly eliminated by the liver .", "entity": [], "task": "NER"}
{"text": "In practice , for two similar suspensions , half - life decreases from 4 . 1 +/- 1 . 10h to 2 . 5 +/- 0 . 77h before and after purification .", "entity": [], "task": "NER"}
{"text": "Since the design and development of long circulating systems are critical in numerous domains , and not for preclinical CT imaging , this study presents important results in that field , taken under a formulation and technical point of view .", "entity": [], "task": "NER"}
{"text": "Medium and high oxidation state metal / non - metal fluoride and oxide - fluoride complexes with neutral donor ligands .", "entity": [{"entity": "metal / non - metal fluoride", "entity_type": "Chemical", "pos": [32, 60]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [65, 70]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "While most high and medium oxidation state ( O . S . >= 3 ) metal and non - metal fluorides and oxide fluorides are strong Lewis acids , exploration of their coordination chemistry with neutral ligands has been limited and mostly non - systematic .", "entity": [{"entity": "metal and non - metal fluorides", "entity_type": "Chemical", "pos": [60, 91]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [96, 101]}, {"entity": "fluorides", "entity_type": "Chemical", "pos": [102, 111]}, {"entity": "Lewis acids", "entity_type": "Chemical", "pos": [123, 134]}], "task": "NER"}
{"text": "This is despite the very different properties conferred on the acceptor centre by the small electronegative fluoride ligands compared to the heavier halides .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [108, 116]}, {"entity": "halides", "entity_type": "Chemical", "pos": [149, 156]}], "task": "NER"}
{"text": "This article sets out these key differences , discusses possible synthetic routes , the key characterisation techniques , and appropriate bonding models .", "entity": [], "task": "NER"}
{"text": "Current knowledge of the coordination chemistry of d , f and p - block fluorides and oxide fluorides with neutral ligands ( with donor atoms drawn from Groups 15 and 16 and including N - heterocyclic carbenes ) is then presented and discussed , and the differences in properties compared to complexes containing the heavier halides are illustrated .", "entity": [{"entity": "fluorides", "entity_type": "Chemical", "pos": [71, 80]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [85, 90]}, {"entity": "fluorides", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "N - heterocyclic carbenes", "entity_type": "Chemical", "pos": [183, 208]}, {"entity": "halides", "entity_type": "Chemical", "pos": [324, 331]}], "task": "NER"}
{"text": "The emphasis is on work published post 1990 , but earlier work is also included as essential background and where no more recent information exists .", "entity": [], "task": "NER"}
{"text": "Attention is drawn to unexplored areas meriting investigation and to possible applications of these complexes .", "entity": [], "task": "NER"}
{"text": "Caffeine , extraversion and working memory .", "entity": [{"entity": "Caffeine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Research has shown that extraverts performing a working memory task benefit more from caffeine than do introverts .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [86, 94]}], "task": "NER"}
{"text": "The present study aimed to replicate this and extend our knowledge by using a lower dose of caffeine ( 65 mg ) and a range of tasks related to different components of working memory .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "In addition , tasks assessing psychomotor speed and the encoding of new information were included to determine whether caffeine - extraversion interactions were restricted to working memory tasks .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "A double - blind design was used , with 128 participants being randomly assigned to caffeinated or de - caffeinated coffee conditions .", "entity": [], "task": "NER"}
{"text": "The results showed that caffeine interacted with extraversion in the predicted direction for serial recall and running memory tasks .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [24, 32]}], "task": "NER"}
{"text": "Caffeine improved simple reaction time and the speed of encoding of new information , effects which were not modified by extraversion .", "entity": [{"entity": "Caffeine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "These results suggest possible biological mechanisms underlying effects of caffeine on cognitive performance .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "Quantitative analysis of the interaction of constitutive androstane receptor with chemicals and steroid receptor coactivator 1 using surface plasmon resonance biosensor systems : a case study of the Baikal seal ( Pusa sibirica ) and the mouse .", "entity": [{"entity": "androstane", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [96, 103]}], "task": "NER"}
{"text": "The constitutive androstane receptor ( CAR ) not only displays a high basal transcriptional activity but also acts as a ligand - dependent transcriptional factor .", "entity": [{"entity": "androstane", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "It is known that CAR exhibits different ligand profiles across species .", "entity": [], "task": "NER"}
{"text": "However , the mechanisms underlying CAR activation by chemicals and the species - specific responses are not fully understood .", "entity": [], "task": "NER"}
{"text": "The objectives of this study are to establish a high - throughput tool to screen CAR ligands and to clarify how CAR proteins from the Baikal seal ( bsCAR ) and the mouse ( mCAR ) interact with chemicals and steroid receptor coactivator 1 ( SRC1 ) .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [207, 214]}], "task": "NER"}
{"text": "We developed the surface plasmon resonance ( SPR ) system to assess quantitatively the interaction of CAR with potential ligands and SRC1 .", "entity": [], "task": "NER"}
{"text": "The ligand - binding domain ( LBD ) of bsCAR and mCAR was synthesized in a wheat germ cell - free system .", "entity": [], "task": "NER"}
{"text": "The purified CAR LBD was then immobilized on the sensor chip for the SPR assay , and the kinetics of direct interaction of CARs with ligand candidates was measured .", "entity": [], "task": "NER"}
{"text": "Androstanol and androstenol , estrone , 17 beta - estradiol , TCPOBOP , and CITCO showed compound - specific but similar affinities for both CARs .", "entity": [{"entity": "Androstanol", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "androstenol", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "estrone", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [40, 59]}, {"entity": "TCPOBOP", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "CITCO", "entity_type": "Chemical", "pos": [76, 81]}], "task": "NER"}
{"text": "The CAR - SRC1 interaction was ligand dependent but exhibited a different ligand profile between the seal and the mouse .", "entity": [], "task": "NER"}
{"text": "The results of SRC1 interaction assay accounted for those of our previous in vitro CAR - mediated transactivation assay .", "entity": [], "task": "NER"}
{"text": "In silico analyses also supported the results of CAR - SRC1 interaction ; there is little structural difference in the ligand - binding pocket of bsCAR and mCAR , but there is a distinct discrimination in the helix 11 and 12 of these receptors , suggesting that the interaction of ligand - bound CAR and SRC1 is critical for determining species - specific and ligand - dependent transactivation over the basal activity .", "entity": [], "task": "NER"}
{"text": "The SPR assays demonstrated a potential as a high - throughput screening tool of CAR ligands .", "entity": [], "task": "NER"}
{"text": "Obesity and addiction : neurobiological overlaps .", "entity": [], "task": "NER"}
{"text": "Drug addiction and obesity appear to share several properties .", "entity": [], "task": "NER"}
{"text": "Both can be defined as disorders in which the saliency of a specific type of reward ( food or drug ) becomes exaggerated relative to , and at the expense of others rewards .", "entity": [], "task": "NER"}
{"text": "Both drugs and food have powerful reinforcing effects , which are in part mediated by abrupt dopamine increases in the brain reward centres .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "The abrupt dopamine increases , in vulnerable individuals , can override the brain ' s homeostatic control mechanisms .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity .", "entity": [], "task": "NER"}
{"text": "Predictably , they also engendered a heated debate .", "entity": [], "task": "NER"}
{"text": "Specifically , brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits .", "entity": [], "task": "NER"}
{"text": "The combined results suggest that both obese and drug - addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation , but also with conditioning , self - control , stress reactivity and interoceptive awareness .", "entity": [], "task": "NER"}
{"text": "In parallel , studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake .", "entity": [], "task": "NER"}
{"text": "Here , we focus on the shared neurobiological substrates of obesity and addiction .", "entity": [], "task": "NER"}
{"text": "Cellular assessment of the extract of bambangan ( Mangifera pajang ) as a potential cytoprotective agent for the human hepatocellular HepG2 cell line .", "entity": [], "task": "NER"}
{"text": "This study was conducted to investigate the potential of bambangan ( Mangifera pajang ) fruit extracts in the protection against oxidative damage caused by tert - butyl hydroperoxide in the human hepatocellular HepG2 cell line .", "entity": [{"entity": "tert - butyl hydroperoxide", "entity_type": "Chemical", "pos": [156, 182]}], "task": "NER"}
{"text": "Proteins which might be involved in the cytoprotective mechanism were investigated using western blotting technique .", "entity": [], "task": "NER"}
{"text": "Quercetin was used as a positive control .", "entity": [{"entity": "Quercetin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The results showed that only the kernel extract of M . pajang and quercetin displayed cytoprotective activity in HepG2 cells , with EC ( 50 ) values of 1 . 2 and 5 . 3 mu g / ml , respectively .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "Expression of quinone reductase , glutathione reductase and methionine sulfoxide reductase A proteins were significantly up - regulated by quercetin , suggesting their involvement in the cytoprotective activity of quercetin .", "entity": [{"entity": "quinone", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [34, 45]}, {"entity": "methionine sulfoxide", "entity_type": "Chemical", "pos": [60, 80]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [139, 148]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [214, 223]}], "task": "NER"}
{"text": "However , expressions of only glutathione reductase and methionine sulfoxide reductase A proteins were significantly up - regulated by the kernel extract , again suggesting their involvement in the cytoprotective activity of bambangan kernel extract .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [30, 41]}, {"entity": "methionine sulfoxide", "entity_type": "Chemical", "pos": [56, 76]}], "task": "NER"}
{"text": "Future study is needed to investigate the involvement of other cytoprotective proteins in the cytoprotection mechanism .", "entity": [], "task": "NER"}
{"text": "Stability of bioactive polyphenols from honey during different extraction methods .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [23, 34]}], "task": "NER"}
{"text": "The LC - MS / MS technique was applied to the stability study of several flavonoids and phenolic acids in honey samples during the ultrasonic extraction ( USE ) and microwave - assisted extraction ( MAE ) .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [73, 83]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [88, 102]}], "task": "NER"}
{"text": "Phenolic compounds from the standard mixture were stable under ultrasounds action with the mean recovery of ( 90 . 4 % +/- 7 . 1 % ) , but during microwave - assisted extraction the benzoic acid derivatives and aglycones of flavonoids showed lower recovery ( 70 - 80 % ) .", "entity": [{"entity": "Phenolic", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "benzoic acid", "entity_type": "Chemical", "pos": [182, 194]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [224, 234]}], "task": "NER"}
{"text": "In honey matrix , the phenolic acids and the glycosides exhibited the high stability for MAE and USE treatments .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [22, 36]}], "task": "NER"}
{"text": "However , the recoveries of tested aglycones were below 10 % .", "entity": [], "task": "NER"}
{"text": "In the presence of an artificial sugar matrix , flavonols were almost completely degraded after successive treatment under MAE and USE conditions .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [33, 38]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "The obtained results indicated that standard addition method for flavonoids quantification in honey samples should not be recommended .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [65, 75]}], "task": "NER"}
{"text": "Application of the USE conditions provided higher and / or similar extraction yields for phenolic acids than usually applied shaking with solvent .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [89, 103]}], "task": "NER"}
{"text": "It also allowed shortening the time required for the whole sample preparation procedure .", "entity": [], "task": "NER"}
{"text": "Phenolic acids and glycosides such as quercetrin , rutin and hesperidin appeared to be stable under such conditions .", "entity": [{"entity": "Phenolic acids", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "quercetrin", "entity_type": "Chemical", "pos": [38, 48]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [51, 56]}, {"entity": "hesperidin", "entity_type": "Chemical", "pos": [61, 71]}], "task": "NER"}
{"text": "A novel one - step microbial transformation of betulin to betulinic acid catalysed by Cunninghamella blakesleeana .", "entity": [{"entity": "betulin", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "betulinic acid", "entity_type": "Chemical", "pos": [58, 72]}], "task": "NER"}
{"text": "Betulinic acid and its derivatives are potential bioactive compounds present in nature .", "entity": [{"entity": "Betulinic acid", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "This study investigated the biotransformation of betulin to betulinic acid by Cunninghamella blakesleeana cells .", "entity": [{"entity": "betulin", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "betulinic acid", "entity_type": "Chemical", "pos": [60, 74]}], "task": "NER"}
{"text": "LC - MS analysis demonstrated that betulin could be transformed into at least five products from cultured C . blakesleeana cells , among which betulinic acid was the most important .", "entity": [{"entity": "betulin", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "betulinic acid", "entity_type": "Chemical", "pos": [143, 157]}], "task": "NER"}
{"text": "The presented method provides an attractive alternative approach to chemical synthesis , because is less time - consuming and more environmentally friendly .", "entity": [], "task": "NER"}
{"text": "C . blakesleeana can transform betulin into potent derivatives with high pharmacological activities .", "entity": [{"entity": "betulin", "entity_type": "Chemical", "pos": [31, 38]}], "task": "NER"}
{"text": "Bioefficacy of EPA - DHA from lipids recovered from fish processing wastes through biotechnological approaches .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "The effect of fish oil recovered from fish visceral waste ( FVW - FO ) on serum and liver lipids , activity of HMG - CoA reductase in liver microsomes and EPA + DHA incorporation in liver , heart and brain were evaluated .", "entity": [{"entity": "HMG - CoA", "entity_type": "Chemical", "pos": [111, 120]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [155, 158]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [161, 164]}], "task": "NER"}
{"text": "Rats were fed different concentrations of FVW - FO providing 1 . 25 % , 2 . 50 % , 5 . 0 % EPA + DHA recovered by either fermentation or enzymatic hydrolysis for 8weeks .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "Feeding FVW - FO reduce triacylglycerols ( 5 . 96 - 20 . 3 % ) , total cholesterol ( 7 . 9 - 21 . 5 % ) and LDL ( 7 . 39 - 21 . 7 % ) cholesterol levels in serum compared to group fed on a control diet ( groundnut oil ) .", "entity": [{"entity": "triacylglycerols", "entity_type": "Chemical", "pos": [24, 40]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [71, 82]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [134, 145]}], "task": "NER"}
{"text": "The activity of HMG - CoA reductase was reduced ( p < 0 . 05 ) in the FVW - FO fed groups compared to the control .", "entity": [{"entity": "HMG - CoA", "entity_type": "Chemical", "pos": [16, 25]}], "task": "NER"}
{"text": "EPA + DHA level in serum , liver , brain and heart increased with increments in dietary EPA + DHA .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [6, 9]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [88, 91]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "Results show the hypolipidemic property of FVW - FO and reduced HMG - CoA reductase activity which is proportional to the incorporation of EPA + DHA .", "entity": [{"entity": "HMG - CoA", "entity_type": "Chemical", "pos": [64, 73]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [139, 142]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [145, 148]}], "task": "NER"}
{"text": "Recovery of FVW - FO will address the increasing demand for fish oil and reduce pollution problems .", "entity": [], "task": "NER"}
{"text": "C - dideoxyhexosyl flavones from the stems and leaves of Passiflora edulis Sims .", "entity": [{"entity": "C - dideoxyhexosyl flavones", "entity_type": "Chemical", "pos": [0, 27]}], "task": "NER"}
{"text": "The stems and leaves of Passiflora edulis Sims , are used as a folk medicine for treating both anxiety and nervousness in American countries .", "entity": [], "task": "NER"}
{"text": "Phytochemical investigation of the n - butanol ( n - BuOH ) fraction of this plant led to the isolation of four new 2 , 6 - dideoxyhexose - C - glycosyl flavones , including luteolin - 8 - C - beta - digitoxopyranosyl - 4 ' - O - beta - d - glucopyranoside ( 1 ) , apigenin - 8 - C - beta - digitoxopyranoside ( 2 ) , apigenin - 8 - C - beta - boivinopyranoside ( 3 ) and luteolin - 8 - C - beta - boivinopyranoside ( 4 ) , together with five known compounds ( 5 - 9 ) .", "entity": [{"entity": "n - butanol", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "n - BuOH", "entity_type": "Chemical", "pos": [49, 57]}, {"entity": "2 , 6 - dideoxyhexose - C - glycosyl flavones", "entity_type": "Chemical", "pos": [116, 161]}, {"entity": "luteolin - 8 - C - beta - digitoxopyranosyl - 4 ' - O - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [174, 256]}, {"entity": "apigenin - 8 - C - beta - digitoxopyranoside", "entity_type": "Chemical", "pos": [265, 309]}, {"entity": "apigenin - 8 - C - beta - boivinopyranoside", "entity_type": "Chemical", "pos": [318, 361]}, {"entity": "luteolin - 8 - C - beta - boivinopyranoside", "entity_type": "Chemical", "pos": [372, 415]}], "task": "NER"}
{"text": "The structures of these compounds were elucidated by extensive spectroscopic methods .", "entity": [], "task": "NER"}
{"text": "All compounds were evaluated for their neurite outgrowth enhancing activities and the results indicated that luteolin ( 7 ) enhanced NGF - induced neurite outgrowth in PC12 cells at 50 . 0 mu M .", "entity": [{"entity": "luteolin", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti - proliferative activity .", "entity": [], "task": "NER"}
{"text": "The goal of this study was to monitor the anti - proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography / diode array detection / electrospray ion trap tandem mass spectrometry ( LC / DAD / ESI - MS ( n ) ) .", "entity": [], "task": "NER"}
{"text": "For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements , both applied for the first time , for the case of betulinic acid .", "entity": [{"entity": "triterpenic acids", "entity_type": "Chemical", "pos": [35, 52]}, {"entity": "betulinic acid", "entity_type": "Chemical", "pos": [201, 215]}], "task": "NER"}
{"text": "Both extracts exerted cytotoxic activity through dose - dependent impairment of viability and mitochondrial activity of rat insulinoma m5F ( RINm5F ) cells .", "entity": [], "task": "NER"}
{"text": "Decrease of RINm5F viability was mediated by nitric oxide ( NO ) - induced apoptosis .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [45, 57]}, {"entity": "NO", "entity_type": "Chemical", "pos": [60, 62]}], "task": "NER"}
{"text": "Importantly , these extracts potentiated NO and TNF - alpha release from macrophages therefore enhancing their cytocidal action .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [41, 43]}], "task": "NER"}
{"text": "The rosemary extract developed more pronounced antioxidant , cytotoxic and immunomodifying activities , probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile .", "entity": [{"entity": "betulinic acid", "entity_type": "Chemical", "pos": [136, 150]}, {"entity": "carnosic acid", "entity_type": "Chemical", "pos": [181, 194]}], "task": "NER"}
{"text": "Phenylalanine ammonia lyase ( PAL ) enzyme activity and antioxidant properties of some cyanobacteria isolates .", "entity": [{"entity": "Phenylalanine ammonia", "entity_type": "Chemical", "pos": [0, 21]}], "task": "NER"}
{"text": "In the present study , six cyanobacteria isolates were evaluated for the PAL enzyme activity , and their methanol extracts were assessed for the total phenolic amount and other antioxidant parameters .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [105, 113]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "Synechocystis sp .", "entity": [], "task": "NER"}
{"text": "BASO444 and Synechocystis sp .", "entity": [], "task": "NER"}
{"text": "BASO673 isolates with high levels of total phenols ( 66 . 0 +/- 1 . 2 mu g / mg , 78 . 1 +/- 1 . 8 mu g / mg , respectively ) also showed high levels of PAL activities ( 20 . 5 +/- 3 . 1U / mg protein , 17 . 2 +/- 2 . 3U / mg protein , respectively ) and strong antioxidant activities .", "entity": [{"entity": "phenols", "entity_type": "Chemical", "pos": [43, 50]}], "task": "NER"}
{"text": "To understand the effect of l - phenylalanine ( l - phe ) on the PAL activity , total phenolic amount , and phenolic constituents , isolates were evaluated with 100mg / l l - phe .", "entity": [{"entity": "l - phenylalanine", "entity_type": "Chemical", "pos": [28, 45]}, {"entity": "l - phe", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [86, 94]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [108, 116]}, {"entity": "l - phe", "entity_type": "Chemical", "pos": [171, 178]}], "task": "NER"}
{"text": "While PAL activities exhibited no significant change with l - phe addition , total phenolic amount of the isolates significantly increased .", "entity": [{"entity": "l - phe", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "HPLC analysis revealed gallic acid , trans - cinnamic acid , p - coumaric acid , and ferulic acid as the main compounds .", "entity": [{"entity": "gallic acid", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "trans - cinnamic acid", "entity_type": "Chemical", "pos": [37, 58]}, {"entity": "p - coumaric acid", "entity_type": "Chemical", "pos": [61, 78]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [85, 97]}], "task": "NER"}
{"text": "Results suggested that the two isolate mights be an important source for the l - phe inducible phenolic compounds .", "entity": [{"entity": "l - phe", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "Ginger extract and zingerone ameliorated trinitrobenzene sulphonic acid - induced colitis in mice via modulation of nuclear factor - kappa B activity and interleukin - 1 beta signalling pathway .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [19, 28]}, {"entity": "trinitrobenzene sulphonic acid", "entity_type": "Chemical", "pos": [41, 71]}], "task": "NER"}
{"text": "Ginger is a commonly used spice with anti - inflammatory potential .", "entity": [], "task": "NER"}
{"text": "Colitis is the common pathological lesion of inflammatory bowel diseases .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated the therapeutic effects of ginger and its component zingerone in mice with 2 , 4 , 6 - trinitrobenzene sulphonic acid ( TNBS ) - induced colitis .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [84, 93]}, {"entity": "2 , 4 , 6 - trinitrobenzene sulphonic acid", "entity_type": "Chemical", "pos": [107, 149]}, {"entity": "TNBS", "entity_type": "Chemical", "pos": [152, 156]}], "task": "NER"}
{"text": "Ginger and zingerone ameliorated TNBS - induced colonic injury in a dose - dependent manner .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [11, 20]}, {"entity": "TNBS", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "Pathway analysis of ginger - and zingerone - regulated gene expression profiles showed that ginger and zingerone significantly regulated cytokine - related pathways .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "zingerone", "entity_type": "Chemical", "pos": [103, 112]}], "task": "NER"}
{"text": "Network analysis showed that nuclear factor - kappa B ( NF - kappa B ) and interleukin - 1 beta ( IL - 1 beta ) were key molecules involved in the expression of ginger - and zingerone - affected genes .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [174, 183]}], "task": "NER"}
{"text": "Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS - induced NF - kappa B activation and IL - 1 beta protein level in the colon .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "TNBS", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "In conclusion , ginger improved TNBS - induced colitis via modulation of NF - kappa B activity and IL - 1 beta signalling pathway .", "entity": [{"entity": "TNBS", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "Moreover , zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS .", "entity": [{"entity": "zingerone", "entity_type": "Chemical", "pos": [11, 20]}, {"entity": "TNBS", "entity_type": "Chemical", "pos": [116, 120]}], "task": "NER"}
{"text": "Metabolite profiling of phenolic and carotenoid contents in tomatoes after moderate - intensity pulsed electric field treatments .", "entity": [], "task": "NER"}
{"text": "A metabolite profiling approach was used to study the effect of moderate - intensity pulsed electric field ( MIPEF ) treatments on the individual polyphenol and carotenoid contents of tomato fruit after refrigeration at 4 degrees C for 24h .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [146, 156]}], "task": "NER"}
{"text": "The MIPEF processing variables studied were electric field strength ( from 0 . 4 to 2 . 0kV / cm ) and number of pulses ( from 5 to 30 ) .", "entity": [], "task": "NER"}
{"text": "Twenty four hours after MIPEF treatments , an increase was observed in hydroxycinnamic acids and flavanones , whereas flavonols , coumaric and ferulic acid - O - glucoside were not affected .", "entity": [{"entity": "hydroxycinnamic acids", "entity_type": "Chemical", "pos": [71, 92]}, {"entity": "flavanones", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [118, 127]}, {"entity": "coumaric and ferulic acid - O - glucoside", "entity_type": "Chemical", "pos": [130, 171]}], "task": "NER"}
{"text": "Major changes were also observed for carotenoids , except for the 5 - cis - lycopene isomer , which remain unchanged after 24h of MIPEF treatments .", "entity": [{"entity": "5 - cis - lycopene", "entity_type": "Chemical", "pos": [66, 84]}], "task": "NER"}
{"text": "MIPEF treatments , conducted at 1 . 2kV / cm and 30 pulses , led to the greatest increases in chlorogenic ( 152 % ) , caffeic acid - O - glucoside ( 170 % ) and caffeic ( 140 % ) acids .", "entity": [{"entity": "caffeic acid - O - glucoside", "entity_type": "Chemical", "pos": [118, 146]}, {"entity": "caffeic", "entity_type": "Chemical", "pos": [161, 168]}], "task": "NER"}
{"text": "On the other hand , treatments at 1 . 2kV / cm and 5 pulses led to maximum increases of alpha - carotene , 9 - and 13 - cis - lycopene , which increased by 93 % , 94 % and 140 % , respectively .", "entity": [{"entity": "alpha - carotene", "entity_type": "Chemical", "pos": [88, 104]}, {"entity": "9 - and 13 - cis - lycopene", "entity_type": "Chemical", "pos": [107, 134]}], "task": "NER"}
{"text": "Therefore , MIPEF could stimulate synthesis of secondary metabolites and contribute to production of tomatoes with high individual polyphenol and carotenoid contents .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [131, 141]}], "task": "NER"}
{"text": "Amino acid composition , antinutrients and allergens in the peanut protein fraction obtained by an aqueous enzymatic process .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Enzyme - assisted aqueous extraction ( EAE ) of peanut kernel was used to extract oil and protein .", "entity": [], "task": "NER"}
{"text": "The aqueous fraction ( AF ) obtained by EAE had a better essential amino acid profile than the residues obtained by solvent extraction ( Rs ) and cold pressing ( Rc ) .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "No major difference in the trypsin inhibitor activity among AF , Rs and Rc was observed ; however , the trypsin inhibitor activity was drastically reduced in the residue obtained after EAE .", "entity": [], "task": "NER"}
{"text": "AF was subjected to MALDI - TOF / MS , revealing it to be rich in peptides ( 107 ) with molecular masses from m / z 700 to 2369Da .", "entity": [], "task": "NER"}
{"text": "AF had an extremely low phytate content and was rich in peptides , which could be used as a food supplement .", "entity": [{"entity": "phytate", "entity_type": "Chemical", "pos": [24, 31]}], "task": "NER"}
{"text": "ESI - MS / MS data were used for the identification of major peanut allergens , viz . , Ara h1 , h3 , h6 - 8 .", "entity": [], "task": "NER"}
{"text": "Their allergenic potential needs to be established .", "entity": [], "task": "NER"}
{"text": "Determination of volatile compounds in New Zealand Greenshell (TM) mussels ( Perna canaliculus ) during chilled storage using solid phase microextraction gas chromatography - mass spectrometry .", "entity": [], "task": "NER"}
{"text": "Greenshell (TM) mussels ( Perna canaliculus ) were dry - stored at 6 . 44 +/- 0 . 54 degrees C for 8 days during which time volatile organic compounds ( VOCs ) were monitored using SPME GC - MS .", "entity": [], "task": "NER"}
{"text": "Thirty - four VOCs were identified in homogenised mussel meat and 29 in the mussel liquor ( i . e . the seawater enclosed in the mantle cavity ) .", "entity": [], "task": "NER"}
{"text": "Of the 34 VOCs identified 20 were reliably identified throughout the storage treatment and 9 were found to change in relative concentration in homogenised mussel meat .", "entity": [], "task": "NER"}
{"text": "Dimethyl sulphide , 1 - penten - 3 - ol , 1 - hexen - 3 - ol and 1 - octen - 3 - ol increased during storage , whereas pentanal , hexanal , heptanal , octanal and 3 - undecen - 2 - one decreased .", "entity": [{"entity": "Dimethyl sulphide", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "1 - penten - 3 - ol", "entity_type": "Chemical", "pos": [20, 39]}, {"entity": "1 - hexen - 3 - ol", "entity_type": "Chemical", "pos": [42, 60]}, {"entity": "1 - octen - 3 - ol", "entity_type": "Chemical", "pos": [65, 83]}, {"entity": "pentanal", "entity_type": "Chemical", "pos": [119, 127]}, {"entity": "hexanal", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "heptanal", "entity_type": "Chemical", "pos": [140, 148]}, {"entity": "octanal", "entity_type": "Chemical", "pos": [151, 158]}, {"entity": "3 - undecen - 2 - one", "entity_type": "Chemical", "pos": [163, 184]}], "task": "NER"}
{"text": "In the mussel liquor , dimethyl sulphide was undetectable pre - storage , becoming detectable after 2 days , and a large increase was noted after 6 days .", "entity": [{"entity": "dimethyl sulphide", "entity_type": "Chemical", "pos": [23, 40]}], "task": "NER"}
{"text": "SPME GC - MS was a useful tool for monitoring VOC profiles of Greenshell (TM) mussels and could aid in the development of technologies that monitor and improve product quality and consistency .", "entity": [], "task": "NER"}
{"text": "Phytochemical composition and in vitro antimicrobial and antioxidant activities of some medicinal plants .", "entity": [], "task": "NER"}
{"text": "Different parts of three plants ( Primula auriculata , Fumaria vaillantii and Falcaria vulgaris ) were extracted with three different solvents to yield 72 crude extracts .", "entity": [], "task": "NER"}
{"text": "The phytochemical analysis ( chemical screening , GC - MS ) of three plants was investigated for their antioxidant and antibacterial activity using nine Gram - positive and Gram - negative bacteria .", "entity": [], "task": "NER"}
{"text": "The principal antioxidant and antimicrobial components were determined using HPLC with UV detection .", "entity": [], "task": "NER"}
{"text": "All extracts possessed antibacterial activity especially methanolic extracts from flowers of P . auriculata .", "entity": [], "task": "NER"}
{"text": "The DPPH - radical scavenging assay exhibited high antioxidant activities in three plants ( more than 80 % at 50 mu g ) .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [4, 8]}], "task": "NER"}
{"text": "The F . vulgaris showed high content of carvacrol ( 29 . 8 % ) as main component .", "entity": [{"entity": "carvacrol", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "The contents of carvacrol and fumaric acid in the methanolic - water extracts were 1119 and 1966mg / l respectively .", "entity": [{"entity": "carvacrol", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "fumaric acid", "entity_type": "Chemical", "pos": [30, 42]}], "task": "NER"}
{"text": "Our results indicate that these plants would be able to promise sources of natural products with potential antibacterial and antioxidant activity .", "entity": [], "task": "NER"}
{"text": "Hypocholesterolemic effects of low calorie structured lipids on rats and rabbits fed on normal and atherogenic diet .", "entity": [], "task": "NER"}
{"text": "The hypocholesterolemic effects of two low calorie structured lipids ( SL1 and SL2 ) containing essential fatty acids , prepared by lipase catalysed interesterification of ethyl behenate respectively with sunflower and soybean oils were studied in rats and rabbits .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [106, 117]}, {"entity": "ethyl behenate", "entity_type": "Chemical", "pos": [172, 186]}], "task": "NER"}
{"text": "The feeding experiment conducted on rats as well as rabbits , fed on normal and atherogenic diet containing 10 % of SL1 and SL2 ( experimental ) and sunflower oil ( control ) indicated no adverse effects on growth and food intake .", "entity": [], "task": "NER"}
{"text": "However , the structured lipids beneficially lowered serum and liver lipids , particularly cholesterol , LDL cholesterol , triglycerides and also maintains the essential fatty acid status in serum and liver .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [91, 102]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [123, 136]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [170, 180]}], "task": "NER"}
{"text": "The lipid deposition observed in the arteries of rabbits fed on atherogenic diets was significantly reduced when structured lipids were included in the diet .", "entity": [], "task": "NER"}
{"text": "These observations coincided with reduced levels of serum cholesterol particularly LDL cholesterol observed in experimental groups .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Therefore the structured lipids , designed to have low calorific value also beneficially lower serum lipids and lipid deposition in animals fed on atherogenic diets .", "entity": [], "task": "NER"}
{"text": "Effects of solvent and alkaline earth metals on the heat - induced precipitation process of sodium caseinate .", "entity": [{"entity": "alkaline earth metals", "entity_type": "Chemical", "pos": [23, 44]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [92, 98]}], "task": "NER"}
{"text": "The precipitation temperatures of sodium caseinate in H ( 2 ) O and D ( 2 ) O in the presence of Mg ( 2 + ) , Ca ( 2 + ) , Sr ( 2 + ) and Ba ( 2 + ) were investigated through fluorescence , turbidity and conductivity experiments .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [34, 40]}, {"entity": "H ( 2 ) O", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "D ( 2 ) O", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [110, 120]}, {"entity": "Sr ( 2 + )", "entity_type": "Chemical", "pos": [123, 133]}, {"entity": "Ba ( 2 + )", "entity_type": "Chemical", "pos": [138, 148]}], "task": "NER"}
{"text": "As for the ability of the divalent cations ( 1 - 17 . 5mM ) to induce the precipitation process in H ( 2 ) O , the sequence Ba ( 2 + ) >= Ca ( 2 + ) > Mg ( 2 + ) > Sr ( 2 + ) was found .", "entity": [{"entity": "H ( 2 ) O", "entity_type": "Chemical", "pos": [99, 108]}, {"entity": "Ba ( 2 + )", "entity_type": "Chemical", "pos": [124, 134]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [138, 148]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [151, 161]}, {"entity": "Sr ( 2 + )", "entity_type": "Chemical", "pos": [164, 174]}], "task": "NER"}
{"text": "Remarkably , while at low salt concentrations ( < 10mM ) precipitation temperatures ( T ( Ps ) ) were found to change significantly depending on the specific cation , at higher concentrations ( > 10mM ) the differences among the different cations were greatly reduced .", "entity": [], "task": "NER"}
{"text": "By fitting these results with a modified Jones - Dole equation , we confirmed that the less hydrated ions possess a greater capacity to induce precipitation .", "entity": [], "task": "NER"}
{"text": "In D ( 2 ) O , the order of ion ability to induce caseinate precipitation was Ba ( 2 + ) > Ca ( 2 + ) > Sr ( 2 + ) > Mg ( 2 + ) .", "entity": [{"entity": "D ( 2 ) O", "entity_type": "Chemical", "pos": [3, 12]}, {"entity": "Ba ( 2 + )", "entity_type": "Chemical", "pos": [78, 88]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [91, 101]}, {"entity": "Sr ( 2 + )", "entity_type": "Chemical", "pos": [104, 114]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [117, 127]}], "task": "NER"}
{"text": "The different hydrophobicity between D ( 2 ) O and H ( 2 ) O was shown to affect significantly the T ( Ps ) of caseinate in the presence of calcium , strontium and barium .", "entity": [{"entity": "D ( 2 ) O", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "H ( 2 ) O", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [140, 147]}, {"entity": "strontium", "entity_type": "Chemical", "pos": [150, 159]}, {"entity": "barium", "entity_type": "Chemical", "pos": [164, 170]}], "task": "NER"}
{"text": "Purification and characterisation of antibacterial peptide - containing compound derived from palm kernel cake .", "entity": [], "task": "NER"}
{"text": "Palm kernel cake ( PKC ) , the most useful by - product resulted from palm kernel oil production .", "entity": [], "task": "NER"}
{"text": "In this study , PKC - derived protein product was found suitable for use as an antimicrobial agent with potent antibacterial activity , particularly against Bacillus species , after enzymatic hydrolysis with alcalase .", "entity": [], "task": "NER"}
{"text": "The hydrolysate was further purified by gel filtration chromatography .", "entity": [], "task": "NER"}
{"text": "The purified fraction was found to have 14 . 63 +/- 0 . 70 % ( w / w ) protein , a molecular mass of 2 . 4kDa and low hemolytic activity ( < 50 % hemolysis of human erythrocytes at concentration of 1000 mu g / ml ) .", "entity": [], "task": "NER"}
{"text": "The presence of lysine and the major component lauric acid derivative , as indicated by electrospray ionisation - mass spectrometry ( ESI - MS ) direct infusion and nuclear magnetic resonance ( NMR ) spectroscopy , may have contributed to the antibacterial effect of purified PKC fraction .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "lauric acid", "entity_type": "Chemical", "pos": [47, 58]}], "task": "NER"}
{"text": "This study suggests that the antibacterial PKC compound may be not a pure peptide but instead a peptide - containing compound high in lauric acid derivative .", "entity": [{"entity": "lauric acid", "entity_type": "Chemical", "pos": [134, 145]}], "task": "NER"}
{"text": "Therapeutic modulation of intestinal dysbiosis .", "entity": [], "task": "NER"}
{"text": "The human gastrointestinal tract is home to an extremely numerous and diverse collection of microbes , collectively termed the \" intestinal microbiota \" .", "entity": [], "task": "NER"}
{"text": "This microbiota is considered to play a number of key roles in the maintenance of host health , including aiding digestion of otherwise indigestible dietary compounds , synthesis of vitamins and other beneficial metabolites , immune system regulation and enhanced resistance against colonisation by pathogenic microorganisms .", "entity": [], "task": "NER"}
{"text": "Conversely , the intestinal microbiota is also a potent source of antigens and potentially harmful compounds .", "entity": [], "task": "NER"}
{"text": "In health , humans can therefore be considered to exist in a state of natural balance with their microbial inhabitants .", "entity": [], "task": "NER"}
{"text": "A shift in the balance of microbiota composition such that it may become deleterious to host health is termed \" dysbiosis \" .", "entity": [], "task": "NER"}
{"text": "Dysbiosis of the gut microbiota has been implicated in numerous disorders , ranging from intestinal maladies such as inflammatory bowel diseases and colorectal cancer to disorders with more systemic effects such as diabetes , metabolic syndrome and atopy .", "entity": [], "task": "NER"}
{"text": "Given the far reaching influence of the intestinal microbiota on human health a clear future goal must be to develop reliable means to alter the composition of the microbiota and restore a healthy balance of microbial species .", "entity": [], "task": "NER"}
{"text": "While it is clear that much fundamental research remains to be done , potentially important therapeutic options include narrow spectrum antibiotics , novel probiotics , dietary interventions and more radical techniques such as faecal transplantation , all of which aim to suppress clinical dysbiosis , restore intestinal microbiota diversity and improve host health .", "entity": [], "task": "NER"}
{"text": "A review on antioxidants , prooxidants and related controversy : natural and synthetic compounds , screening and analysis methodologies and future perspectives .", "entity": [], "task": "NER"}
{"text": "Many studies have been conducted with regard to free radicals , oxidative stress and antioxidant activity of food , giving antioxidants a prominent beneficial role , but , recently many authors have questioned their importance , whilst trying to understand the mechanisms behind oxidative stress .", "entity": [], "task": "NER"}
{"text": "Many scientists defend that regardless of the quantity of ingested antioxidants , the absorption is very limited , and that in some cases prooxidants are beneficial to human health .", "entity": [], "task": "NER"}
{"text": "The detection of antioxidant activity as well as specific antioxidant compounds can be carried out with a large number of different assays , all of them with advantages and disadvantages .", "entity": [], "task": "NER"}
{"text": "The controversy around antioxidant in vivo benefits has become intense in the past few decades and the present review tries to shed some light on research on antioxidants ( natural and synthetic ) and prooxidants , showing the potential benefits and adverse effects of these opposing events , as well as their mechanisms of action and detection methodologies .", "entity": [], "task": "NER"}
{"text": "It also identifies the limitations of antioxidants and provides a perspective on the likely future trends in this field .", "entity": [], "task": "NER"}
{"text": "Effects of vitamin D on antigen - specific and non - antigen - specific immune modulation : relevance for type 1 diabetes .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [11, 20]}], "task": "NER"}
{"text": "Vitamin D is a fat - soluble precursor of the circulating 25 - hydroxyvitamin D 3 ( 25 ( OH ) D 3 ) which can be converted by the 1 alpha - hydroxylase ( 1 alpha ( OH ) ase ) enzyme into the bioactive hormonal metabolite 1 , 25 - dihydroxyvitamin D 3 ( 1 , 25 ( OH ) 2 D 3 ) , generally known to promote bone mineralization through its ability to enhance calcium absorption from the gut .", "entity": [{"entity": "Vitamin D", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "25 - hydroxyvitamin D 3", "entity_type": "Chemical", "pos": [58, 81]}, {"entity": "25 ( OH ) D 3", "entity_type": "Chemical", "pos": [84, 97]}, {"entity": "1 , 25 - dihydroxyvitamin D 3", "entity_type": "Chemical", "pos": [221, 250]}, {"entity": "1 , 25 ( OH ) 2 D 3", "entity_type": "Chemical", "pos": [253, 272]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [355, 362]}], "task": "NER"}
{"text": "Importantly , in humans , vitamin D is mainly derived from endogenous production of vitamin D 3 from ultraviolet ( UV ) radiation exposure to the skin while a small part ( < 10 % ) is obtained via dietary intake of dairy products and fatty fish ( 1 ) .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "vitamin D 3", "entity_type": "Chemical", "pos": [84, 95]}], "task": "NER"}
{"text": "Taking these factors into account , geographic distribution and seasonality , skin pigmentation , age , and lifestyle may predispose certain populations to be at a higher risk of developing vitamin D insufficiency or deficiency ( 2 ) .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [190, 199]}], "task": "NER"}
{"text": "The first valid reports correlating the importance of an adequate vitamin D status to optimal human health originate from the early part of the 20th century , when vitamin D was described to prevent and treat the bone disease rickets .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [66, 75]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [164, 173]}], "task": "NER"}
{"text": "Since then , the findings that vitamin D receptors ( VDR ) are present in many body tissues and that vitamin D metabolizing enzymes can be found in various cells outside the kidney , including the intestine , prostate , immune cells , and within the skin itself ( reviewed in reference 3 ) , have revolutionized the vitamin D business .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [101, 110]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [316, 325]}], "task": "NER"}
{"text": "In this review , we will mainly focus on vitamin D as a component of immune regulation and on the role of vitamin D in antigen - specific and non - specific therapies with potential relevance for type 1 diabetes ( T1D ) .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [41, 50]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [106, 115]}], "task": "NER"}
{"text": "Developmental effects of prenatal di - n - hexyl phthalate and dicyclohexyl phthalate exposure on reproductive tract of male rats : Postnatal outcomes .", "entity": [{"entity": "di - n - hexyl phthalate", "entity_type": "Chemical", "pos": [34, 58]}, {"entity": "dicyclohexyl phthalate", "entity_type": "Chemical", "pos": [63, 85]}], "task": "NER"}
{"text": "The present study is to investigate the effects of in utero di - n - hexyl phthalate ( DHP ) and dicyclohexyl phthalate exposure ( DCHP ) on the development of male reproductive tract at prepubertal , pubertal and adult stages .", "entity": [{"entity": "di - n - hexyl phthalate", "entity_type": "Chemical", "pos": [60, 84]}, {"entity": "DHP", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "dicyclohexyl phthalate", "entity_type": "Chemical", "pos": [97, 119]}, {"entity": "DCHP", "entity_type": "Chemical", "pos": [131, 135]}], "task": "NER"}
{"text": "Pregnant rats were exposed to DHP and DCHP at doses of 0 , 20 , 100 and 500mg / kg / day , by gavage , on gestational days ( GD ) 6 - 19 .", "entity": [{"entity": "DHP", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "DCHP", "entity_type": "Chemical", "pos": [38, 42]}], "task": "NER"}
{"text": "Testosterone ( T ) levels of prepubertal rats diminished at high dose DHP and middle dose DCHP groups .", "entity": [{"entity": "Testosterone", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "DHP", "entity_type": "Chemical", "pos": [70, 73]}, {"entity": "DCHP", "entity_type": "Chemical", "pos": [90, 94]}], "task": "NER"}
{"text": "MIS / AMH levels elevated in DHP and DCHP groups .", "entity": [{"entity": "DHP", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "DCHP", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "T levels of pubertal rats decreased in low and high dose DHP and DCHP groups .", "entity": [{"entity": "DHP", "entity_type": "Chemical", "pos": [57, 60]}, {"entity": "DCHP", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "Inhibin B levels of adult rats diminished in DCHP groups .", "entity": [{"entity": "DCHP", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "Atrophic and amorphous tubules , spermatogenic cell debris , apoptotic cells , adherent tubules , Sertoli cell vacuolisation , prostatic atrophic tubules and prostatic intraepithelial neoplasia ( PIN ) were observed in the reproductive organs of treated animals at all developmental stages .", "entity": [], "task": "NER"}
{"text": "There was an increase in immunoexpression of MIS / AMH in testes of treated rats .", "entity": [], "task": "NER"}
{"text": "There were no changes in sperm head count but percentages of abnormal sperms increased .", "entity": [], "task": "NER"}
{"text": "The diameters of seminiferous and epididymal tubules in treatment groups were significantly lower .", "entity": [], "task": "NER"}
{"text": "This study shows that DHP and DCHP may have antiandrogenic effects on male reproductive development before and after birth .", "entity": [{"entity": "DHP", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "DCHP", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "Modeling the binding mechanism of Alzheimer ' s A beta 1 - 4 2 to nicotinic acetylcholine receptors based on similarity with snake alpha - neurotoxins .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [76, 89]}], "task": "NER"}
{"text": "For over a decade , it has been known that amyloid beta ( A beta ) peptides of Alzheimer ' s disease bind to the nicotinic alpha 7 acetylcholine receptor ( AChR ) with picomolar affinity , and that snake alpha - neurotoxins competitively inhibit this binding .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [131, 144]}], "task": "NER"}
{"text": "Here we propose a model of the binding mechanism of A beta peptides to alpha 7 - AChR at atomic level .", "entity": [], "task": "NER"}
{"text": "The binding mechanism is based on sequence and structure similarities of A beta residues with functional residues of snake alpha - neurotoxins ( ATX ) in complex with AChR .", "entity": [], "task": "NER"}
{"text": "The binding mechanism involves residue ( A beta ) K28 ( similar to ( ATX ) R32 ) which forms cation / pi interactions in the acetylcholine binding site , and residues ( A beta ) G29 - ( A beta ) I32 [ GAII ] ( similar to ( ATX ) G33 - ( ATX ) I36 [ GTII ] ) which form an intermolecular beta - sheet with residues ( alpha 7 ) F189 - ( alpha 7 ) E191 of AChR .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [125, 138]}], "task": "NER"}
{"text": "Through these interactions , we propose that the AChR serves as a chaperone for A beta conformational changes from alpha - to beta - hairpin .", "entity": [], "task": "NER"}
{"text": "The interactions which block channel opening provide fundamental insight into A beta neurotoxicity and cognition impairment , that could contribute to pathogenic processes in Alzheimer ' s disease , thus paving the way for structure based therapies .", "entity": [], "task": "NER"}
{"text": "Electrical detection of spin precession in freely suspended graphene spin valves on cross - linked poly ( methyl methacrylate ) .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "poly ( methyl methacrylate )", "entity_type": "Chemical", "pos": [99, 127]}], "task": "NER"}
{"text": "Spin injection and detection is achieved in freely suspended graphene using cobalt electrodes and a nonlocal spin - valve geometry .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "cobalt", "entity_type": "Chemical", "pos": [76, 82]}], "task": "NER"}
{"text": "The devices are fabricated with a single electron - beam - resist poly ( methyl methacrylate ) process that minimizes both the fabrication steps and the number of ( aggressive ) chemicals used , greatly reducing contamination and increasing the yield of high - quality , mechanically stable devices .", "entity": [{"entity": "poly ( methyl methacrylate )", "entity_type": "Chemical", "pos": [66, 94]}], "task": "NER"}
{"text": "As - grown devices can present mobilities exceeding 10 ( 4 ) cm ( 2 ) V ( - 1 ) s ( - 1 ) at room temperature and , because the contacts deposited on graphene are only exposed to acetone and isopropanol , the method is compatible with almost any contacting material .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [150, 158]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [179, 186]}, {"entity": "isopropanol", "entity_type": "Chemical", "pos": [191, 202]}], "task": "NER"}
{"text": "Spin accumulation and spin precession are studied in these nonlocal spin valves .", "entity": [], "task": "NER"}
{"text": "Fitting of Hanle spin precession data in bilayer and multilayer graphene yields a spin relaxation time of ~ 125 - 250 ps and a spin diffusion length of 1 . 7 - 1 . 9 mu m at room temperature .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "The organometallic chemistry of cycloheptatrienyl zirconium complexes .", "entity": [{"entity": "cycloheptatrienyl zirconium", "entity_type": "Chemical", "pos": [32, 59]}], "task": "NER"}
{"text": "This tutorial review summarizes the organometallic chemistry derived from the half - sandwich complex [ ( eta ( 7 ) - C ( 7 ) H ( 7 ) ) ZrCl ( tmeda ) ] , which was used as an efficient and versatile starting material for the incorporation of monoanionic ligands into the cycloheptatrienyl zirconium coordination sphere by conventional salt metathesis reactions .", "entity": [{"entity": "( eta ( 7 ) - C ( 7 ) H ( 7 ) ) ZrCl ( tmeda )", "entity_type": "Chemical", "pos": [104, 150]}, {"entity": "cycloheptatrienyl zirconium", "entity_type": "Chemical", "pos": [272, 299]}], "task": "NER"}
{"text": "A broad variety of ligands was employed , affording novel and previously inaccessible cycloheptatrienyl ( sandwich ) complexes of the type [ ( eta ( 7 ) - C ( 7 ) H ( 7 ) ) Zr ( Y ) ] ; Y comprises pentadienyl , cyclopentadienyl , allyl , phospholyl , boratabenzene , imidazolin - 2 - iminato and amido systems .", "entity": [{"entity": "cycloheptatrienyl", "entity_type": "Chemical", "pos": [86, 103]}, {"entity": "( eta ( 7 ) - C ( 7 ) H ( 7 ) ) Zr ( Y )", "entity_type": "Chemical", "pos": [141, 181]}, {"entity": "pentadienyl", "entity_type": "Chemical", "pos": [198, 209]}, {"entity": "cyclopentadienyl", "entity_type": "Chemical", "pos": [212, 228]}, {"entity": "allyl", "entity_type": "Chemical", "pos": [231, 236]}, {"entity": "phospholyl", "entity_type": "Chemical", "pos": [239, 249]}, {"entity": "boratabenzene", "entity_type": "Chemical", "pos": [252, 265]}, {"entity": "imidazolin - 2 - iminato", "entity_type": "Chemical", "pos": [268, 292]}, {"entity": "amido", "entity_type": "Chemical", "pos": [297, 302]}], "task": "NER"}
{"text": "The cycloheptatrienyl ring in these systems usually acts as an \" innocent spectator ligand \" , but reactivity can arise from the second ligand Y or the Lewis acidity of the , formally , Zr ( + iv ) center , which was probed in selected examples and put in perspective to related studies .", "entity": [{"entity": "cycloheptatrienyl", "entity_type": "Chemical", "pos": [4, 21]}, {"entity": "Zr ( + iv )", "entity_type": "Chemical", "pos": [186, 197]}], "task": "NER"}
{"text": "The corresponding results emphasize why the use of [ ( eta ( 7 ) - C ( 7 ) H ( 7 ) ) ZrCl ( tmeda ) ] is clearly an advancement in the chemistry of the still fairly unexplored area of cycloheptatrienyl transition metal complexes .", "entity": [{"entity": "( eta ( 7 ) - C ( 7 ) H ( 7 ) ) ZrCl ( tmeda )", "entity_type": "Chemical", "pos": [53, 99]}, {"entity": "cycloheptatrienyl transition metal complexes", "entity_type": "Chemical", "pos": [184, 228]}], "task": "NER"}
{"text": "Portal vein glucose entry triggers a coordinated cellular response that potentiates hepatic glucose uptake and storage in normal but not high - fat / high - fructose - fed dogs .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "The cellular events mediating the pleiotropic actions of portal vein glucose ( PoG ) delivery on hepatic glucose disposition have not been clearly defined .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [69, 76]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [105, 112]}], "task": "NER"}
{"text": "Likewise , the molecular defects associated with postprandial hyperglycemia and impaired hepatic glucose uptake ( HGU ) following consumption of a high - fat , high - fructose diet ( HFFD ) are unknown .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [167, 175]}], "task": "NER"}
{"text": "Our goal was to identify hepatocellular changes elicited by hyperinsulinemia , hyperglycemia , and PoG signaling in normal chow - fed ( CTR ) and HFFD - fed dogs .", "entity": [], "task": "NER"}
{"text": "In CTR dogs , we demonstrated that PoG infusion in the presence of hyperinsulinemia and hyperglycemia triggered an increase in the activity of hepatic glucokinase ( GK ) and glycogen synthase ( GS ) , which occurred in association with further augmentation in HGU and glycogen synthesis ( GSYN ) in vivo .", "entity": [], "task": "NER"}
{"text": "In contrast , 4 weeks of HFFD feeding markedly reduced GK protein content and impaired the activation of GS in association with diminished HGU and GSYN in vivo .", "entity": [], "task": "NER"}
{"text": "Furthermore , the enzymatic changes associated with PoG sensing in chow - fed animals were abolished in HFFD - fed animals , consistent with loss of the stimulatory effects of PoG delivery .", "entity": [], "task": "NER"}
{"text": "These data reveal new insight into the molecular physiology of the portal glucose signaling mechanism under normal conditions and to the pathophysiology of aberrant postprandial hepatic glucose disposition evident under a diet - induced glucose - intolerant condition .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [74, 81]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [186, 193]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [237, 244]}], "task": "NER"}
{"text": "Identification of the metabolites of lesogaberan using linear trap quadrupole orbitrap mass spectrometry and hydrophilic interaction liquid chromatography .", "entity": [{"entity": "lesogaberan", "entity_type": "Chemical", "pos": [37, 48]}], "task": "NER"}
{"text": "1 . In this study , hydrophilic interaction liquid chromatography ( HILIC ) , radiochemical activity monitoring and linear trap quadrupole orbitrap mass spectrometry ( MS ) and tandem mass spectrometry ( MS / MS ) were used to identify the metabolites of a highly polar novel gamma - aminobutyric acid type - B receptor agonist , lesogaberan , in rats .", "entity": [{"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [276, 301]}, {"entity": "lesogaberan", "entity_type": "Chemical", "pos": [330, 341]}], "task": "NER"}
{"text": "2 . Urine was collected from three male Wistar rats for 24 h after dosing with ( 14 ) C - labelled lesogaberan ( 170 mg / kg , 10 MBq / kg ) ; plasma samples were taken 2 and 24 h after dosing .", "entity": [{"entity": "( 14 ) C - labelled lesogaberan", "entity_type": "Chemical", "pos": [79, 110]}], "task": "NER"}
{"text": "Pooled samples were separated by HILIC and eluents were analysed by radiochemical activity monitoring , MS and MS / MS .", "entity": [], "task": "NER"}
{"text": "3 . Only the parent compound was detected in plasma , but six metabolites ( M1 - M6 ) were detected in urine .", "entity": [], "task": "NER"}
{"text": "Analysis of MS and MS / MS data and comparison with synthetic reference standards enabled the identification of the structure of each metabolite .", "entity": [], "task": "NER"}
{"text": "M1 was identified as the N - acetylated species [ ( 2R ) - 3 - acetamido - 2 - fluoropropyl ] - phosphinic acid , and M6 as [ ( 2R ) - 3 - amino - 2 - fluoropropyl ] - phosphonic acid .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [25, 26]}, {"entity": "[ ( 2R ) - 3 - acetamido - 2 - fluoropropyl ] - phosphinic acid", "entity_type": "Chemical", "pos": [48, 111]}, {"entity": "[ ( 2R ) - 3 - amino - 2 - fluoropropyl ] - phosphonic acid", "entity_type": "Chemical", "pos": [124, 183]}], "task": "NER"}
{"text": "Metabolites M2 and M5 were the alcohol and carboxylic acid species 3 - hydroxypropyl - phosphinic acid and 3 - hydroxyphosphonoyl - propanoic acid , respectively , both of which had lost the fluorine atom present in the parent compound .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [43, 58]}, {"entity": "3 - hydroxypropyl - phosphinic acid", "entity_type": "Chemical", "pos": [67, 102]}, {"entity": "3 - hydroxyphosphonoyl - propanoic acid", "entity_type": "Chemical", "pos": [107, 146]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [191, 199]}], "task": "NER"}
{"text": "M3 was the corresponding carboxylic acid species retaining the fluorine atom , ( 2R ) - 2 - fluoro - 3 - hydroxyphosphonoyl - propanoic acid .", "entity": [{"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [25, 40]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [63, 71]}, {"entity": "( 2R ) - 2 - fluoro - 3 - hydroxyphosphonoyl - propanoic acid", "entity_type": "Chemical", "pos": [79, 140]}], "task": "NER"}
{"text": "Finally M4 was identified as [ ( 2R ) - 2 - fluoro - 3 - guanidino - propyl ] - phosphinic acid .", "entity": [{"entity": "[ ( 2R ) - 2 - fluoro - 3 - guanidino - propyl ] - phosphinic acid", "entity_type": "Chemical", "pos": [29, 95]}], "task": "NER"}
{"text": "Preparation and culture of precision - cut organ slices from human and animal .", "entity": [], "task": "NER"}
{"text": "1 . Human and animal precision - cut organ slices are being widely used to obtain drug metabolism and toxicity profiles in vitro .", "entity": [], "task": "NER"}
{"text": "These data are then used to predict what might be seen in human patients .", "entity": [], "task": "NER"}
{"text": "The accuracy of this prediction and extrapolation of the findings based on human or animal in vitro systems to the findings that occur in vivo is dependent on both the quality of the tissue itself and the quality of the in vitro system .", "entity": [], "task": "NER"}
{"text": "2 . The quality of human organs used in research is dependent on procurement methods , warm ischaemia time , preservation solutions , cold ischaemia time , and donor - specific factors .", "entity": [], "task": "NER"}
{"text": "It is important to confirm that the organs being used are highly viable and fully functional before using them in scientific studies .", "entity": [], "task": "NER"}
{"text": "3 . The optimal preparation and incubation of organ slices is also essential in maintaining slice viability and function .", "entity": [], "task": "NER"}
{"text": "It is important to prepare the slices in a cold preservation solution , to prepare the slices at a correct thickness , and to incubate the slices in a system where the slice rotates in out of the oxygen atmosphere and medium .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [196, 202]}], "task": "NER"}
{"text": "4 . Meeting the criteria outlined here will lead to successful organ slice cultures for investigating drug - induced mechanisms and organ - specific toxicity .", "entity": [], "task": "NER"}
{"text": "Wnt / beta - catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts .", "entity": [], "task": "NER"}
{"text": "The BMP and Wnt / beta - catenin signaling pathways cooperatively regulate osteoblast differentiation and bone formation .", "entity": [], "task": "NER"}
{"text": "Although BMP signaling regulates gene expression of the Wnt pathway , much less is known about whether Wnt signaling modulates BMP expression in osteoblasts .", "entity": [], "task": "NER"}
{"text": "Given the presence of putative Tcf / Lef response elements that bind beta - catenin / TCF transcription complex in the BMP2 promoter , we hypothesized that the Wnt / beta - catenin pathway stimulates BMP2 expression in osteogenic cells .", "entity": [], "task": "NER"}
{"text": "In this study , we showed that Wnt / beta - catenin signaling is active in various osteoblast or osteoblast precursor cell lines , including MC3T3 - E1 , 2T3 , C2C12 , and C3H10T1 / 2 cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , crosstalk between the BMP and Wnt pathways affected BMP signaling activity , osteoblast differentiation , and bone formation , suggesting Wnt signaling is an upstream regulator of BMP signaling .", "entity": [], "task": "NER"}
{"text": "Activation of Wnt signaling by Wnt3a or overexpression of beta - catenin / TCF4 both stimulated BMP2 transcription at promoter and mRNA levels .", "entity": [], "task": "NER"}
{"text": "In contrast , transcription of BMP2 in osteogenic cells was decreased by either blocking the Wnt pathway with DKK1 and sFRP4 , or inhibiting beta - catenin / TCF4 activity with FWD1 / beta - TrCP , ICAT , or Delta TCF4 .", "entity": [], "task": "NER"}
{"text": "Using a site - directed mutagenesis approach , we confirmed that Wnt / beta - catenin transactivation of BMP2 transcription is directly mediated through the Tcf / Lef response elements in the BMP2 promoter .", "entity": [], "task": "NER"}
{"text": "These results , which demonstrate that the Wnt / beta - catenin signaling pathway is an upstream activator of BMP2 expression in osteoblasts , provide novel insights into the nature of functional cross talk integrating the BMP and Wnt / beta - catenin pathways in osteoblastic differentiation and maintenance of skeletal homeostasis .", "entity": [], "task": "NER"}
{"text": "Imaging in the cardiovascular and metabolic disease area .", "entity": [], "task": "NER"}
{"text": "There is a widely held belief that the use of non - invasive imaging can reduce the gap between basic science and clinical proof - of - concept , ultimately improving decision - making and therefore the efficiency of the drug development process .", "entity": [], "task": "NER"}
{"text": "Imaging techniques such as positron emission tomography ( PET ) and magnetic resonance imaging ( MRI ) are routinely used in oncology and neuroscience drug development .", "entity": [], "task": "NER"}
{"text": "However , less attention has been paid to the systematic use of imaging in the cardiovascular and metabolic disease area .", "entity": [], "task": "NER"}
{"text": "Here , with an emphasis on ' early clinical ' development , we discuss the application of imaging in those areas , highlighting opportunities and challenges .", "entity": [], "task": "NER"}
{"text": "Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist into early childhood .", "entity": [{"entity": "polychlorinated biphenyls", "entity_type": "Chemical", "pos": [21, 46]}, {"entity": "dioxins", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls ( PCBs ) and dioxins is associated with the development of immune - related diseases in childhood .", "entity": [{"entity": "polychlorinated biphenyls", "entity_type": "Chemical", "pos": [82, 107]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [110, 114]}, {"entity": "dioxins", "entity_type": "Chemical", "pos": [121, 128]}], "task": "NER"}
{"text": "Children participating in BraMat , a sub - cohort of the Norwegian Mother and Child Cohort Study ( MoBa ) , were followed in the three first years of life using annual questionnaires ( 0 - 3years ; n = 162 , 2 - 3years ; n = 180 ) , and blood parameters were examined at three years of age ( n = 114 ) .", "entity": [], "task": "NER"}
{"text": "The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa .", "entity": [], "task": "NER"}
{"text": "Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [21, 25]}, {"entity": "dioxins", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Furthermore , maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [35, 39]}, {"entity": "dioxins", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "No associations were found between prenatal exposure and immunophenotype data , allergic sensitization and vaccine - induced antibody responses other than measles .", "entity": [], "task": "NER"}
{"text": "Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "dioxins", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "A subchronic dietary toxicity study of rice hull fiber in rats .", "entity": [], "task": "NER"}
{"text": "We conducted a 90 - day feeding study to investigate subchronic toxicity of rice hull fiber .", "entity": [], "task": "NER"}
{"text": "Sprague Dawley rats were randomly divided into four groups ; each received a diet containing 0 % , 2 . 5 % , 3 . 75 % and 5 . 0 % ( w / w ) rice hull fiber for 90days .", "entity": [], "task": "NER"}
{"text": "Clinical observations were carried out daily , with weekly measurements of body weight and food consumption .", "entity": [], "task": "NER"}
{"text": "We performed ophthalmic and histological examinations at termination .", "entity": [], "task": "NER"}
{"text": "Blood and urine samples were collected to measure hematology and clinical chemistry parameters .", "entity": [], "task": "NER"}
{"text": "No mortality , ophthalmic abnormalities , or adverse treatment - related effects were seen during clinical observations , hematological tests , or analyses of urine .", "entity": [], "task": "NER"}
{"text": "Macroscopic or microscopic examinations of organs revealed no treatment related abnormalities .", "entity": [], "task": "NER"}
{"text": "The only treatment related significant changes were reduced concentrations of fasting blood glucose ( up to 17 . 6 % ) and cholesterol ( up to 22 . 0 % ) , typical benefits of dietary fiber , in males treated with 3 . 75 and 5 % rice hull fiber .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [123, 134]}], "task": "NER"}
{"text": "The no - observed - adverse - effect - level ( NOAEL ) for rice hull fiber was 5 . 0 % for both genders ( females , 3 . 80g / kg body weight / day ; males , 4 . 11g / kg body weight / day ) .", "entity": [], "task": "NER"}
{"text": "PUB - NChIP - - \" in vivo biotinylation \" approach to study chromatin in proximity to a protein of interest .", "entity": [], "task": "NER"}
{"text": "We have developed an approach termed PUB - NChIP ( proximity utilizing biotinylation with native ChIP ) to purify and study the protein composition of chromatin in proximity to a nuclear protein of interest .", "entity": [], "task": "NER"}
{"text": "It is based on coexpression of ( 1 ) a protein of interest , fused with the bacterial biotin ligase BirA , together with ( 2 ) a histone fused to a biotin acceptor peptide ( BAP ) , which is specifically biotinylated by BirA - fusion in the proximity of the protein of interest .", "entity": [{"entity": "biotin", "entity_type": "Chemical", "pos": [86, 92]}, {"entity": "biotin", "entity_type": "Chemical", "pos": [148, 154]}], "task": "NER"}
{"text": "Using the RAD18 protein as a model , we demonstrate that the RAD18 - proximal chromatin is enriched in some H4 acetylated species .", "entity": [], "task": "NER"}
{"text": "Moreover , the RAD18 - proximal chromatin containing a replacement histone H2AZ has a different pattern of H4 acetylation .", "entity": [], "task": "NER"}
{"text": "Finally , biotin pulse - chase experiments show that the H4 acetylation pattern starts to resemble the acetylation pattern of total H4 after the proximity of chromatin to RAD18 has been lost .", "entity": [{"entity": "biotin", "entity_type": "Chemical", "pos": [10, 16]}], "task": "NER"}
{"text": "Anatomical and functional damage in experimental glaucoma .", "entity": [], "task": "NER"}
{"text": "Glaucoma is a progressive neurodegenerative disease caused by retinal ganglion cell ( RGC ) loss .", "entity": [], "task": "NER"}
{"text": "One important risk factor for glaucoma is elevated intraocular pressure and thus many animal models are based on spontaneous or induced ocular hypertension ( OHT ) .", "entity": [], "task": "NER"}
{"text": "Using these models it has been shown that RGCs initially suffer an impairment of the active axonal transport that progresses to a lack of passive diffusion along the axon .", "entity": [], "task": "NER"}
{"text": "This axonal damage eventually causes the death of the parent RGCs in pie - shaped sectors of the retina , but there is also diffuse RGC loss , without involving displaced amacrine cells .", "entity": [], "task": "NER"}
{"text": "Recent data show that OHT results in a protracted insult to the inner and outer retina that causes functional alterations and ultimately , degeneration and death of cones .", "entity": [], "task": "NER"}
{"text": "Phlorotannin - rich Ecklonia cava reduces the production of beta - amyloid by modulating alpha - and gamma - secretase expression and activity .", "entity": [{"entity": "Phlorotannin", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Beta - amyloid ( A beta ) is a major pathogenic peptide in Alzheimer ' s disease ( AD ) and is generated by the processing of amyloid precursor protein ( APP ) .", "entity": [], "task": "NER"}
{"text": "We have previously reported that the brown algae Ecklonia cava , which has anti - oxidant and anti - inflammatory functions , decreased A beta production and further aggregation in HEK293 cells expressing the APP Swedish mutation .", "entity": [], "task": "NER"}
{"text": "Here , we show the reduction mechanism of A beta production using the butanol extract of Ecklonia cava through the examination of expression and activity of alpha - , beta - , and gamma - secretase .", "entity": [{"entity": "butanol", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "Treatment with the extract resulted in the activation of alpha - secretase with a contrasting decrease in its mRNA and protein expression .", "entity": [], "task": "NER"}
{"text": "This activation was consistent with the translocation of the extract into the plasma membrane of the secretase .", "entity": [], "task": "NER"}
{"text": "Gamma - secretase activity was lowered by E . cava , and this effect may be due to the decreased expression of PSEN1 mRNA and protein .", "entity": [], "task": "NER"}
{"text": "In addition , the basal nuclear location of PSEN1 , which may affect chromosome missegregation in neurodegenerative disease , was reduced by the extract , despite the significance of this finding remains unclear .", "entity": [], "task": "NER"}
{"text": "Taken together , these results led us to conclude that E . cava regulated the expression and activity of gamma - secretase and alpha - secretase , leading to a reduction in A beta production by the stable cells .", "entity": [], "task": "NER"}
{"text": "Our data indicate that E . cava is a novel natural - product candidate for AD treatment , although further in vivo studies are needed .", "entity": [], "task": "NER"}
{"text": "Apoptosis induced neurotoxicity of Di - n - butyl - di - ( 4 - chlorobenzohydroxamato ) Tin ( IV ) via mitochondria - mediated pathway in PC12 cells .", "entity": [{"entity": "Di - n - butyl - di - ( 4 - chlorobenzohydroxamato ) Tin ( IV )", "entity_type": "Chemical", "pos": [35, 98]}], "task": "NER"}
{"text": "The severe toxicity of antitumor organotin ( IV ) compounds limits their application in clinic , however , the toxic mechanism is still unclear .", "entity": [{"entity": "organotin ( IV )", "entity_type": "Chemical", "pos": [33, 49]}], "task": "NER"}
{"text": "Di - n - butyl - di - ( 4 - chlorobenzohydroxamato ) Tin ( IV ) ( DBDCT ) , an antitumor agent with high activity and obvious neurotoxicity was chosen as a typical diorganotin ( IV ) compound to investigate its neurotoxic mechanism using PC12 cells and comprehensive methods .", "entity": [{"entity": "Di - n - butyl - di - ( 4 - chlorobenzohydroxamato ) Tin ( IV )", "entity_type": "Chemical", "pos": [0, 63]}, {"entity": "DBDCT", "entity_type": "Chemical", "pos": [66, 71]}, {"entity": "diorganotin ( IV )", "entity_type": "Chemical", "pos": [164, 182]}], "task": "NER"}
{"text": "Treatment with DBDCT resulted in a dose - and time - dependent growth inhibition of PC12 cells .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [15, 20]}], "task": "NER"}
{"text": "The changes in cell morphology were observed using light microscopy , fluorescence microscopy and transmission electron microscopy .", "entity": [], "task": "NER"}
{"text": "PC12 cell apoptosis induced by DBDCT was confirmed by annexin V / propidium iodide staining , and characterized by cleavage of caspase - 9 and caspase - 3 proteins .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [31, 36]}, {"entity": "propidium iodide", "entity_type": "Chemical", "pos": [66, 82]}], "task": "NER"}
{"text": "DBDCT induced the release of cytochrome c from the mitochondria to the cytosol and the generation of reactive oxygen species .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "DBDCT up - regulated the expression of Bax , down - regulated the expression of Bcl - 2 , and significantly increased the ratio of Bax / Bcl - 2 .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "DBDCT also caused the phosphorylation of JNK and p38 ( MAPK ) .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "In rats exposed to DBDCT , apoptosis was also observed in brain , as shown by the detection of cleaved caspase - 9 and caspase - 3 proteins and increased TUNEL positive staining .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [19, 24]}], "task": "NER"}
{"text": "In conclusion , the results demonstrated that DBDCT caused the neurotoxicity by inducing apoptosis via mitochondria - mediated pathway .", "entity": [{"entity": "DBDCT", "entity_type": "Chemical", "pos": [46, 51]}], "task": "NER"}
{"text": "Inclusion compound based approach to forming arrays of artificial dipolar molecular rotors : a search for optimal rotor structures .", "entity": [], "task": "NER"}
{"text": "Hexagonal tris ( o - phenylenedioxy ) cyclotriphosphazene ( TPP ) is used as ahost for organizing dipolar molecular rotor guests into regular trigonal arrays .", "entity": [{"entity": "tris ( o - phenylenedioxy ) cyclotriphosphazene", "entity_type": "Chemical", "pos": [10, 57]}, {"entity": "TPP", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "Inclusion of molecular rotors with transversely dipolar rotators into TPP channels is followed by solid - state nuclear magnetic resonance , diifferential scanning calorimetry , X - ray diffraction , and dielectric spectroscopy .", "entity": [{"entity": "TPP", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "The more polar of the two rotors does not form an inclusion .", "entity": [], "task": "NER"}
{"text": "The second rotor forms two different inclusions differing in crystallite size and the rotational barriers .", "entity": [], "task": "NER"}
{"text": "Glycopolymers and glyco - nanoparticles in biomolecular recognition processes and vaccine development .", "entity": [], "task": "NER"}
{"text": "With advances in polymerization techniques as well as selective chemical modification of carbohydrates , glycopolymers and glyco - nanoparticles are emerging as an important class of materials with tailored properties or novel nanotechnology - based platforms for a number of applications .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [89, 102]}], "task": "NER"}
{"text": "The field of the so - called glyco - nanotechnology is starting to show some promises for future clinical applications .", "entity": [], "task": "NER"}
{"text": "Glyco - nanoparticles , due to their versatile nature , could offer a platform for the design of carbohydrate - based vaccines and possibly allow the development of new single - dose vaccines in disease areas of unmet need .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [97, 109]}], "task": "NER"}
{"text": "This paper surveys the emerging roles of carbohydrate - based polymeric and nanomaterials for biomolecular recognition processes and vaccine development .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [41, 53]}], "task": "NER"}
{"text": "Interactions between CYP2E1 and CYP2B4 : effects on affinity for NADPH - cytochrome P450 reductase and substrate metabolism .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [65, 70]}], "task": "NER"}
{"text": "Studies in microsomal and reconstituted systems have shown that the presence of one cytochrome P450 isoform can significantly influence the catalytic activity of another isoform .", "entity": [], "task": "NER"}
{"text": "In this study , we assessed whether CYP2E1 could influence the catalytic activity of CYP2B4 under steady - state turnover conditions .", "entity": [], "task": "NER"}
{"text": "The results show that CYP2E1 inhibits CYP2B4 - mediated metabolism of benzphetamine ( BNZ ) with a K ( i ) of 0 . 04 micro M .", "entity": [{"entity": "benzphetamine", "entity_type": "Chemical", "pos": [70, 83]}, {"entity": "BNZ", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "However , CYP2B4 is not an inhibitor of CYP2E1 - mediated p - nitrophenol hydroxylation .", "entity": [{"entity": "p - nitrophenol", "entity_type": "Chemical", "pos": [58, 73]}], "task": "NER"}
{"text": "When these inhibition studies were performed with the artificial oxidant tert - butyl hydroperoxide , CYP2E1 did not significantly inhibit CYP2B4 activity .", "entity": [{"entity": "tert - butyl hydroperoxide", "entity_type": "Chemical", "pos": [73, 99]}], "task": "NER"}
{"text": "Determinations of the apparent K ( M ) and k ( cat ) of CYP2B4 for CPR in the presence of increasing concentrations of CYP2E1 revealed a mixed inhibition of CYP2B4 by CYP2E1 .", "entity": [], "task": "NER"}
{"text": "At low concentrations of CYP2E1 , the apparent K ( M ) of CYP2B4 for CPR increased up to 23 - fold with virtually no change in the k ( cat ) for the reaction , however , at higher concentrations of CYP2E1 , the apparent K ( M ) of CYP2B4 for CPR decreased to levels similar to those observed in the absence of CYP2E1 and the k ( cat ) also decreased by 11 - fold .", "entity": [], "task": "NER"}
{"text": "Additionally , CYP2E1 increased the apparent K ( M ) of CYP2B4 for BNZ by 8 - fold and the apparent K ( M ) did not decrease to its original value when saturating concentrations of CPR were used .", "entity": [{"entity": "BNZ", "entity_type": "Chemical", "pos": [67, 70]}], "task": "NER"}
{"text": "While the individual apparent K ( M ) values of CYP2B4 and CYP2E1 for CPR are similar , the apparent K ( M ) of CYP2E1 for CPR in the presence of CYP2B4 decreased significantly , thus suggesting that CYP2B4 enhances the affinity of CYP2E1 for CPR and this may allow CYP2E1 to out - compete CYP2B4 for CPR .", "entity": [], "task": "NER"}
{"text": "Songaricalarins A - E , cytotoxic oplopane sesquiterpenes from Ligularia songarica .", "entity": [{"entity": "Songaricalarins A - E", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "oplopane sesquiterpenes", "entity_type": "Chemical", "pos": [34, 57]}], "task": "NER"}
{"text": "Five new highly oxygenated oplopane sesquiterpenes , songaricalarins A - E ( 1 - 5 ) , and two known analogues ( 6 and 7 ) were isolated from the roots and rhizomes of Ligularia songarica .", "entity": [{"entity": "oxygenated oplopane sesquiterpenes", "entity_type": "Chemical", "pos": [16, 50]}, {"entity": "songaricalarins A - E", "entity_type": "Chemical", "pos": [53, 74]}], "task": "NER"}
{"text": "Their structures and configurations were elucidated by spectroscopic methods , including 2D - NMR techniques , and the structure of 1 was confirmed by single - crystal X - ray diffraction .", "entity": [], "task": "NER"}
{"text": "All compounds were evaluated for in vitro cytotoxic activity against cultured A - 549 , MCF - 7 , KB , and KBVIN cells , and 4 exhibited cytotoxicity with EC50 values of 4 . 9 , 0 . 8 , 3 . 4 , and 3 . 2 mu g / mL , respectively .", "entity": [], "task": "NER"}
{"text": "Angiogenesis is required for stress fracture healing in rats .", "entity": [], "task": "NER"}
{"text": "Although angiogenesis and osteogenesis are critically linked , the importance of angiogenesis for stress fracture healing is unknown .", "entity": [], "task": "NER"}
{"text": "In this study , mechanical loading was used to create a non - displaced stress fracture in the adult rat forelimb .", "entity": [], "task": "NER"}
{"text": "Fumagillin , an anti - angiogenic agent , was used as the water soluble analogue TNP - 470 ( 25mg / kg ) as well as incorporated into lipid - encapsulated alpha ( v ) beta ( 3 ) integrin targeted nanoparticles ( 0 . 25mg / kg ) .", "entity": [{"entity": "Fumagillin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "TNP - 470", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "In the first experiment , TNP - 470 was administered daily for 5 days following mechanical loading , and changes in gene expression , vascularity , and woven bone formation were quantified .", "entity": [{"entity": "TNP - 470", "entity_type": "Chemical", "pos": [26, 35]}], "task": "NER"}
{"text": "Although no changes in vascularity were detected 3 days after loading , treatment - related downregulation of angiogenic ( Pecam1 ) and osteogenic ( Bsp , Osx ) genes was observed at this early time point .", "entity": [], "task": "NER"}
{"text": "On day 7 , microCT imaging of loaded limbs revealed diminished woven bone formation in treated limbs compared to vehicle treated limbs .", "entity": [], "task": "NER"}
{"text": "In the second experiment , alpha ( v ) beta ( 3 ) integrin targeted fumagillin nanoparticles were administered as before , albeit with a 100 - fold lower dose , and changes in vascularity and woven bone formation were determined .", "entity": [{"entity": "fumagillin", "entity_type": "Chemical", "pos": [68, 78]}], "task": "NER"}
{"text": "There were no treatment - related changes in vessel count or volume 3 days after loading , although fewer angiogenic ( CD105 positive ) blood vessels were present in treated limbs compared to vehicle treated limbs .", "entity": [], "task": "NER"}
{"text": "This result manifested on day 7 as a reduction in total vascularity , as measured by histology ( vessel count ) and microCT ( vessel volume ) .", "entity": [], "task": "NER"}
{"text": "Similar to the first experiment , treated limbs had diminished woven bone formation on day 7 compared to vehicle treated limbs .", "entity": [], "task": "NER"}
{"text": "These results indicate that angiogenesis is required for stress fracture healing , and may have implications for inducing rapid repair of stress fractures .", "entity": [], "task": "NER"}
{"text": "Amino acid residues at the N - and C - termini are essential for the folding of active human butyrylcholinesterase polypeptide .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Human serum butyrylcholinesterase ( HuBChE ) is currently the most suitable bioscavenger for the prophylaxis of highly toxic organophosphate ( OP ) nerve agents .", "entity": [{"entity": "organophosphate", "entity_type": "Chemical", "pos": [125, 140]}], "task": "NER"}
{"text": "A dose of 200mg of HuBChE is envisioned as a prophylactic treatment that can protect humans from an exposure of up to 2 x LD50 of soman .", "entity": [], "task": "NER"}
{"text": "The limited availability and administration of multiple doses of this stoichiometric bioscavenger make this pretreatment difficult .", "entity": [], "task": "NER"}
{"text": "Thus , the goal of this study was to produce a smaller enzymatically active HuBChE polypeptide ( HBP ) that could bind to nerve agents with high affinity thereby reducing the dose of enzyme .", "entity": [], "task": "NER"}
{"text": "Studies have indicated that the three - dimensional structure and the domains of HuBChE ( acyl pocket , lip of the active center gorge , and the anionic substrate - binding domain ) that are critical for the binding of substrate are also essential for the selectivity and binding of inhibitors including OPs .", "entity": [{"entity": "acyl", "entity_type": "Chemical", "pos": [90, 94]}], "task": "NER"}
{"text": "Therefore , we designed three HBPs by deleting some N - and C - terminal residues of HuBChE by maintaining the folds of the active site core that includes the three active site residues ( S198 , E325 , and H438 ) .", "entity": [], "task": "NER"}
{"text": "HBP - 4 that lacks 45 residues from C - terminus but known to have BChE activity was used as a control .", "entity": [], "task": "NER"}
{"text": "The cDNAs for the HBPs containing signal sequences were synthesized , cloned into different mammalian expression vectors , and recombinant polypeptides were transiently expressed in different cell lines .", "entity": [], "task": "NER"}
{"text": "No BChE activity was detected in the culture media of cells transfected with any of the newly designed HBPs , and the inactive polypeptides remained inside the cells .", "entity": [], "task": "NER"}
{"text": "Only enzymatically active HBP - 4 was secreted into the culture medium .", "entity": [], "task": "NER"}
{"text": "These results suggest that residues at the N - and C - termini are required for the folding and / or maintenance of HBP into an active stable , conformation .", "entity": [], "task": "NER"}
{"text": "Overexpression of H1 calponin in osteoblast lineage cells leads to a decrease in bone mass by disrupting osteoblast function and promoting osteoclast formation .", "entity": [], "task": "NER"}
{"text": "H1 calponin ( CNN1 ) is known as a smooth muscle - specific , actin - binding protein which regulates smooth muscle contractive activity .", "entity": [], "task": "NER"}
{"text": "Although previous studies have shown that CNN1 has effect on bone , the mechanism is not well defined .", "entity": [], "task": "NER"}
{"text": "To investigate the role of CNN1 in maintaining bone homeostasis , we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast - specific 3 . 6 - kb Col1a1 promoter .", "entity": [], "task": "NER"}
{"text": "Col1a1 - Cnn1 transgenic mice showed delayed bone formation at embryonic stage and decreased bone mass at adult stage .", "entity": [], "task": "NER"}
{"text": "Morphology analyses showed reduced trabecular number , thickness and defects in bone formation .", "entity": [], "task": "NER"}
{"text": "The proliferation and migration of osteoblasts were decreased in Col1a1 - Cnn1 mice due to alterations in cytoskeleton .", "entity": [], "task": "NER"}
{"text": "The early osteoblast differentiation of Col1a1 - Cnn1 mice was increased , but the late stage differentiation and mineralization of osteoblasts derived from Col1a1 - Cnn1 mice were significantly decreased .", "entity": [], "task": "NER"}
{"text": "In addition to impaired bone formation , the decreased bone mass was also associated with enhanced osteoclastogenesis .", "entity": [], "task": "NER"}
{"text": "Tartrate - resistant acid phosphatase ( TRAP ) staining revealed increased osteoclast numbers in tibias of 2 - month - old Col1a1 - Cnn1 mice , and increased numbers of osteoclasts co - cultured with Col1a1 - Cnn1 osteoblasts .", "entity": [{"entity": "Tartrate", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The ratio of RANKL to OPG was significantly increased in Col1a1 - Cnn1 osteoblasts .", "entity": [], "task": "NER"}
{"text": "These findings reveal a novel function of CNN1 in maintaining bone homeostasis by coupling bone formation to bone resorption .", "entity": [], "task": "NER"}
{"text": "Optical imaging techniques for point - of - care diagnostics .", "entity": [], "task": "NER"}
{"text": "Improving access to effective and affordable healthcare has long been a global endeavor .", "entity": [], "task": "NER"}
{"text": "In this quest , the development of cost - effective and easy - to - use medical testing equipment that enables rapid and accurate diagnosis is essential to reduce the time and costs associated with healthcare services .", "entity": [], "task": "NER"}
{"text": "To this end , point - of - care ( POC ) diagnostics plays a crucial role in healthcare delivery in both developed and developing countries by bringing medical testing to patients , or to sites near patients .", "entity": [], "task": "NER"}
{"text": "As the diagnosis of a wide range of diseases , including various types of cancers and many endemics , relies on optical techniques , numerous compact and cost - effective optical imaging platforms have been developed in recent years for use at the POC .", "entity": [], "task": "NER"}
{"text": "Here , we review the state - of - the - art optical imaging techniques that can have a significant impact on global health by facilitating effective and affordable POC diagnostics .", "entity": [], "task": "NER"}
{"text": "Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome .", "entity": [], "task": "NER"}
{"text": "The impact of glucocorticoids ( GC ) on skeletal development has not been established .", "entity": [], "task": "NER"}
{"text": "The objective of this study was to examine changes in volumetric bone mineral density ( vBMD ) and cortical structure over 1 year in childhood nephrotic syndrome ( NS ) and to identify associations with concurrent GC exposure and growth .", "entity": [], "task": "NER"}
{"text": "Fifty - six NS participants , aged 5 to 21 years , were enrolled a median of 4 . 3 ( 0 . 5 to 8 . 1 ) years after diagnosis .", "entity": [], "task": "NER"}
{"text": "Tibia peripheral quantitative computed tomography ( pQCT ) scans were obtained at enrollment and 6 and 12 months later .", "entity": [], "task": "NER"}
{"text": "Sex , race , and age - specific Z - scores were generated for trabecular vBMD ( TrabBMD - Z ) , cortical vBMD ( CortBMD - Z ) , and cortical area ( CortArea - Z ) based on > 650 reference participants .", "entity": [], "task": "NER"}
{"text": "CortArea - Z was further adjusted for tibia length - for - age Z - score .", "entity": [], "task": "NER"}
{"text": "Quasi - least squares regression was used to identify determinants of changes in pQCT Z - scores .", "entity": [], "task": "NER"}
{"text": "At enrollment , mean TrabBMD - Z ( - 0 . 54 +/- 1 . 32 ) was significantly lower ( p = 0 . 0001 ) and CortBMD - Z ( 0 . 73 +/- 1 . 16 , p < 0 . 0001 ) and CortArea - Z ( 0 . 27 +/- 0 . 91 , p = 0 . 03 ) significantly greater in NS versus reference participants , as previously described .", "entity": [], "task": "NER"}
{"text": "Forty - eight ( 86 % ) participants were treated with GC over the study interval ( median dose 0 . 29 mg / kg / day ) .", "entity": [], "task": "NER"}
{"text": "On average , TrabBMD - Z and CortBMD - Z did not change significantly over the study interval ; however , CortArea - Z decreased ( p = 0 . 003 ) .", "entity": [], "task": "NER"}
{"text": "Greater GC dose ( p < 0 . 001 ) , lesser increases in tibia length ( p < 0 . 001 ) , and lesser increases in CortArea - Z ( p = 0 . 003 ) were independently associated with greater increases in CortBMD - Z .", "entity": [], "task": "NER"}
{"text": "Greater increases in tibia length were associated with greater declines in CortArea - Z ( p < 0 . 01 ) ; this association was absent in reference participants ( interaction p < 0 . 02 ) .", "entity": [], "task": "NER"}
{"text": "In conclusion , GC therapy was associated with increases in CortBMD - Z , potentially related to suppressed bone formation and greater secondary mineralization .", "entity": [], "task": "NER"}
{"text": "Conversely , greater growth and expansion of CortArea - Z ( ie , new bone formation ) were associated with declines in CortBMD - Z .", "entity": [], "task": "NER"}
{"text": "Greater linear growth was associated with impaired expansion of cortical area in NS .", "entity": [], "task": "NER"}
{"text": "Studies are needed to determine the fracture implications of these findings .", "entity": [], "task": "NER"}
{"text": "Neuropeptide Y is a critical modulator of leptin ' s regulation of cortical bone .", "entity": [], "task": "NER"}
{"text": "Leptin signaling is required for normal bone homeostasis ; however , loss of leptin results in differing effects on cortical and cancellous bone , as well as altered responses between the axial and appendicular regions .", "entity": [], "task": "NER"}
{"text": "Local beta - adrenergic actions are responsible for the greater cancellous bone volume in leptin - deficient ( ob / ob ) mice ; however , the mechanism responsible for the opposing reduction in cortical bone in ob / ob mice is not known .", "entity": [], "task": "NER"}
{"text": "Here we show that blocking the leptin - deficient increase in neuropeptide Y ( NPY ) expression reverses the cortical bone loss in ob / ob mice .", "entity": [], "task": "NER"}
{"text": "Mice null for both NPY and leptin ( NPY ( - / - ) ob / ob ) , display greater cortical bone mass in both long - bones and vertebra , with NPY ( - / - ) ob / ob mice exhibiting thicker and denser cortical bone , associated with greater endocortical and periosteal mineral apposition rate ( MAR ) , compared to ob / ob animals .", "entity": [], "task": "NER"}
{"text": "Importantly , these cortical changes occurred without significant increases in body weight , with NPY ( - / - ) ob / ob mice showing significantly reduced adiposity compared to ob / ob controls , most likely due to the reduced respiratory exchange ratio seen in these animals .", "entity": [], "task": "NER"}
{"text": "Interestingly , cancellous bone volume was not different between NPY ( - / - ) ob / ob and ob / ob , suggesting that NPY is not influencing the adrenergic axis .", "entity": [], "task": "NER"}
{"text": "Taken together , this work demonstrates the critical role of NPY signaling in the regulation of bone and energy homeostasis , and more importantly , suggests that reduced leptin levels or leptin resistance , which occurs in obesity , could potentially inhibit cortical bone formation via increased central NPY signaling .", "entity": [], "task": "NER"}
{"text": "Characterisation of acetylcholinesterase release from neuronal cells .", "entity": [], "task": "NER"}
{"text": "Although acetylcholinesterase ( AChE ) is primarily a hydrolytic enzyme , metabolising the neurotransmitter acetylcholine in cholinergic synapses , it also has some non - catalytic functions in the brain which are far less well characterised .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [9, 22]}], "task": "NER"}
{"text": "AChE was shown to be secreted or shed from the neuronal cell surface like several other membrane proteins , such as the amyloid precursor protein ( APP ) .", "entity": [], "task": "NER"}
{"text": "Since AChE does not possess a transmembrane domain , its anchorage in the membrane is established via the Proline Rich Membrane Anchor ( PRiMA ) , a transmembrane protein .", "entity": [{"entity": "Proline", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "Both the subunit oligomerisation and membrane anchor of AChE are shared by a related enzyme , butyrylcholinesterase ( BChE ) , the physiological function of which in the brain is unclear .", "entity": [], "task": "NER"}
{"text": "In this work , we have assayed the relative activities of AChE and BChE in membrane fractions and culture medium of three different neuronal cell lines , namely the neuroblastoma cell lines SH - SY5Y and NB7 and the mouse basal forebrain cell line SN56 .", "entity": [], "task": "NER"}
{"text": "In an effort to understand the shedding process of AChE , we have used several pharmacological treatments , which showed that it is likely to be mediated in part by an EDTA - and batimastat - sensitive , but GM6001 - insensitive metalloprotease , with the possible additional involvement of a thiol isomerase .", "entity": [{"entity": "EDTA", "entity_type": "Chemical", "pos": [168, 172]}, {"entity": "batimastat", "entity_type": "Chemical", "pos": [179, 189]}, {"entity": "GM6001", "entity_type": "Chemical", "pos": [208, 214]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [293, 298]}], "task": "NER"}
{"text": "Cellular release of AChE by SH - SY5Y is significantly enhanced by the muscarinic acetylcholine receptor ( mAChR ) agonists carbachol or muscarine , with the effect of carbachol blocked by the mAChR antagonist atropine .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [82, 95]}, {"entity": "carbachol", "entity_type": "Chemical", "pos": [124, 133]}, {"entity": "muscarine", "entity_type": "Chemical", "pos": [137, 146]}, {"entity": "carbachol", "entity_type": "Chemical", "pos": [168, 177]}, {"entity": "atropine", "entity_type": "Chemical", "pos": [210, 218]}], "task": "NER"}
{"text": "AChE has been implicated in the pathogenesis of Alzheimer ' s disease and it has been shown that it accelerates formation and increases toxicity of amyloid fibrils , which have been closely linked to the pathology of AD .", "entity": [], "task": "NER"}
{"text": "In light of this , greater understanding of AChE and BChE physiology may also benefit AD research .", "entity": [], "task": "NER"}
{"text": "Cholinesterases in development : AChE as a firewall to inhibit cell proliferation and support differentiation .", "entity": [], "task": "NER"}
{"text": "Acetylcholinesterase ( AChE ) is a most remarkable protein , not only because it is one of the fastest enzymes in nature , but also since it appears in many molecular forms and is regulated by elaborate genetic networks .", "entity": [], "task": "NER"}
{"text": "AChE is expressed in many tissues during development and in mature organisms , as well as in healthy and diseased states .", "entity": [], "task": "NER"}
{"text": "In search for alternative , \" non - classical \" functions of cholinesterases ( ChEs ) , AChE could either work within the frame of classic cholinergic systems , but in non - neural tissues ( \" non - synaptic function \" ) , or act non - enzymatically .", "entity": [], "task": "NER"}
{"text": "Here , we review briefly some of the major ideas and advances of this field , and report on some recent progress from our own experimental work , e . g . that ( i ) non - neural ChEs have pronounced , predominantly enzymatic effects on early embryonic ( limb ) development in chick and mouse , that ( ii ) retinal R28 cells of the rat overexpressing synaptic AChE present a significantly decreased cell proliferation , and that ( iii ) in developing chick retina ACh - synthesizing and ACh - degrading cells originate from the same postmitotic precursor cells , which later form two locally opposing cell populations .", "entity": [{"entity": "ACh", "entity_type": "Chemical", "pos": [359, 362]}, {"entity": "ACh", "entity_type": "Chemical", "pos": [463, 466]}], "task": "NER"}
{"text": "We suggest that such distinct distributions of ChAT ( + ) vs . AChE ( + ) cells in the inner half retina provide graded distributions of ACh , which can direct cell differentiation and network formation .", "entity": [{"entity": "ACh", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "Thus , as corroborated by works from many labs , AChE can be considered a highly co - opting protein , which can combine enzymatic and non - enzymatic functions within one molecule .", "entity": [], "task": "NER"}
{"text": "Nanoengineered colloidal probes for Raman - based detection of biomolecules inside living cells .", "entity": [], "task": "NER"}
{"text": "Gold nanoparticle aggregate carbon nanotube functionalized colloidal particles serve as an efficient platform for probing the intracellular environment .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [28, 34]}], "task": "NER"}
{"text": "The probes provide the means of effective localization of signal and detection of molecular fingerprints of biomolecules in living cells .", "entity": [], "task": "NER"}
{"text": "The approach demonstrated in this work opens significant opportunities in molecular imaging as well as intracellular sensing and trafficking .", "entity": [], "task": "NER"}
{"text": "Sex and dose - dependent effects of developmental exposure to bisphenol A on anxiety and spatial learning in deer mice ( Peromyscus maniculatus bairdii ) offspring .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [62, 73]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is a widely produced , endocrine disrupting compound that is pervasive in the environment .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "Data suggest that developmental exposure to BPA during sexual differentiation of the brain leads to later behavioral consequences in offspring .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [44, 47]}], "task": "NER"}
{"text": "Outbred deer mice ( Peromyscus maniculatus bairdii ) are an excellent animal model for such studies as they exhibit well - defined sex - and steroid - dependent behaviors .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [141, 148]}], "task": "NER"}
{"text": "Here , dams during gestation and lactation were fed with a phytoestrogen - free control diet , the same diet supplemented with either ethinyl estradiol ( 0 . 1 ppb ) , or one of the three doses of BPA ( 50 mg , 5 mg , 50 mu g / kg feed weight ) .", "entity": [{"entity": "ethinyl estradiol", "entity_type": "Chemical", "pos": [134, 151]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [197, 200]}], "task": "NER"}
{"text": "After weaning , the pups were maintained on control diet until they reached sexual maturity and then assessed for both spatial learning capabilities and anxiety - like and exploratory behaviors .", "entity": [], "task": "NER"}
{"text": "Relative to controls , males exposed to the two upper but not the lowest dose of BPA demonstrated similar impairments in spatial learning , increased anxiety and reduced exploratory behaviors as ethinyl estradiol - exposed males , while females exposed to ethinyl estradiol , but not to BPA , consistently exhibited masculinized spatial abilities .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "ethinyl estradiol", "entity_type": "Chemical", "pos": [195, 212]}, {"entity": "ethinyl estradiol", "entity_type": "Chemical", "pos": [256, 273]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [287, 290]}], "task": "NER"}
{"text": "We also determined whether dams maintained chronically on the upper dose of BPA contained environmentally relevant concentrations of BPA in their blood .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [133, 136]}], "task": "NER"}
{"text": "While serum concentrations of unconjugated BPA in controls were below the minimum level of detection , those from dams on the BPA diet were comparable ( 5 . 48 +/- 2 . 07 ng / ml ) to concentrations that have been observed in humans .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [43, 46]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [126, 129]}], "task": "NER"}
{"text": "Together , these studies demonstrate that developmental exposure to environmentally relevant concentrations of BPA can disrupt adult behaviors in a dose - and sex - dependent manner .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [111, 114]}], "task": "NER"}
{"text": "Self - propelled nanojets via template electrodeposition .", "entity": [], "task": "NER"}
{"text": "In this paper , we present a rapid , high - yield , low - end and low - cost fabrication of nanojet motors using a template directed electrochemical deposition method .", "entity": [], "task": "NER"}
{"text": "Using an electrochemical deposition method , the bubble - ejecting nanojets were grown within the alumina template , which is commercially available .", "entity": [{"entity": "alumina", "entity_type": "Chemical", "pos": [98, 105]}], "task": "NER"}
{"text": "These fabricated nanosized devices have typical dimensions of 300 nm ( diameter ) by 4 . 5 mu m ( length ) , and they are able to move in a hydrogen peroxide fuel solution with velocities up to approximately 40 body lengths per second .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [140, 157]}], "task": "NER"}
{"text": "They are also capable of exhibiting various modes of movement such as straight , screw - like and circular motions , in a similar manner comparable to larger micro - sized jets .", "entity": [], "task": "NER"}
{"text": "In addition , due to their small dimensions , the movements of these nanojets can be strongly influenced by colliding them with microbubbles .", "entity": [], "task": "NER"}
{"text": "This highly parallel method which is of low - cost and requires the usage of low - end equipment that can be easily located in any laboratory opens up the doors for world - wide nanojet fabrication in the near future .", "entity": [], "task": "NER"}
{"text": "Endocrine disruptors fludioxonil and fenhexamid stimulate miR - 21 expression in breast cancer cells .", "entity": [{"entity": "fludioxonil", "entity_type": "Chemical", "pos": [21, 32]}, {"entity": "fenhexamid", "entity_type": "Chemical", "pos": [37, 47]}], "task": "NER"}
{"text": "Fenhexamid and fludioxonil are antifungal agents used in agricultural applications , which are present at measurable amounts in fruits and vegetables .", "entity": [{"entity": "Fenhexamid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [15, 26]}], "task": "NER"}
{"text": "Fenhexamid and fludioxonil showed endocrine disruptor activity as antiandrogens in an androgen receptor reporter assay in engineered human breast cancer cells .", "entity": [{"entity": "Fenhexamid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [15, 26]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [70, 78]}], "task": "NER"}
{"text": "Little is known about how environmental chemicals regulate microRNA ( miRNA ) expression .", "entity": [], "task": "NER"}
{"text": "This study examined the effect of fenhexamid and fludioxonil on the expression of the oncomiR miR - 21 in MCF - 7 , T47D , and MDA - MB - 231 human breast cancer cells and downstream targets of miR - 21 in MCF - 7 cells .", "entity": [{"entity": "fenhexamid", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Fenhexamid and fludioxonil stimulated miR - 21 expression in a concentration - dependent manner and reduced the expression of miR - 21 target Pdcd4 protein .", "entity": [{"entity": "Fenhexamid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [15, 26]}], "task": "NER"}
{"text": "Antisense to miR - 21 blocked the increase in Pdcd4 protein by fenhexamid and fludioxonil .", "entity": [{"entity": "fenhexamid", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [78, 89]}], "task": "NER"}
{"text": "Fenhexamid and fludioxonil reduced miR - 125b and miR - 181a , demonstrating specificity of miRNA regulation .", "entity": [{"entity": "Fenhexamid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [15, 26]}], "task": "NER"}
{"text": "Induction of miR - 21 was inhibited by the estrogen receptor antagonist fulvestrant , by androgen receptor antagonist bicalutamide , by actinomycin D and cycloheximide , and by inhibitors of the mitogen - activated protein kinases and phosphoinositide 3 - kinase pathways .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [43, 51]}, {"entity": "fulvestrant", "entity_type": "Chemical", "pos": [72, 83]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [89, 97]}, {"entity": "bicalutamide", "entity_type": "Chemical", "pos": [118, 130]}, {"entity": "actinomycin D", "entity_type": "Chemical", "pos": [136, 149]}, {"entity": "cycloheximide", "entity_type": "Chemical", "pos": [154, 167]}, {"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [235, 251]}], "task": "NER"}
{"text": "Fenhexamid activation was inhibited by the arylhydrocarbon receptor antagonist alpha - napthoflavone .", "entity": [{"entity": "Fenhexamid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "arylhydrocarbon", "entity_type": "Chemical", "pos": [43, 58]}, {"entity": "alpha - napthoflavone", "entity_type": "Chemical", "pos": [79, 100]}], "task": "NER"}
{"text": "Fenhexamid and fludioxonil did not affect dihydrotestosterone - induced miR - 21 expression .", "entity": [{"entity": "Fenhexamid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [15, 26]}, {"entity": "dihydrotestosterone", "entity_type": "Chemical", "pos": [42, 61]}], "task": "NER"}
{"text": "Fludioxonil , but not fenhexamid , inhibited MCF - 7 cell viability , and both inhibited estradiol - induced cell proliferation and reduced cell motility .", "entity": [{"entity": "Fludioxonil", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "fenhexamid", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [89, 98]}], "task": "NER"}
{"text": "Together these data indicate that fenhexamid and fludioxonil use similar and distinct mechanisms to increase miR - 21 expression with downstream antiestrogenic activity .", "entity": [{"entity": "fenhexamid", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "fludioxonil", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Benzo [ a ] pyrene - induced transcriptomic responses in primary hepatocytes and in vivo liver : toxicokinetics is essential for in vivo - in vitro comparisons .", "entity": [{"entity": "Benzo [ a ] pyrene", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "The traditional 2 - year cancer bioassay needs replacement by more cost - effective and predictive tests .", "entity": [], "task": "NER"}
{"text": "The use of toxicogenomics in an in vitro system may provide a more high - throughput method to investigate early alterations induced by carcinogens .", "entity": [], "task": "NER"}
{"text": "Recently , the differential gene expression response in wild - type and cancer - prone Xpa ( - / - ) p53 ( + / - ) primary mouse hepatocytes after exposure to benzo [ a ] pyrene ( B [ a ] P ) revealed downregulation of cancer - related pathways in Xpa ( - / - ) p53 ( + / - ) hepatocytes only .", "entity": [{"entity": "benzo [ a ] pyrene", "entity_type": "Chemical", "pos": [159, 177]}, {"entity": "B [ a ] P", "entity_type": "Chemical", "pos": [180, 189]}], "task": "NER"}
{"text": "Here , we investigated pathway regulation upon in vivo B [ a ] P exposure of wild - type and Xpa ( - / - ) p53 ( + / - ) mice .", "entity": [{"entity": "B [ a ] P", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "In vivo transcriptomics analysis revealed a limited gene expression response in mouse livers , but with a significant induction of DNA replication and apoptotic / anti - apoptotic cellular responses in Xpa ( - / - ) p53 ( + / - ) livers only .", "entity": [], "task": "NER"}
{"text": "In order to be able to make a meaningful in vivo - in vitro comparison we estimated internal in vivo B [ a ] P concentrations using DNA adduct levels and physiologically based kinetic modeling .", "entity": [{"entity": "B [ a ] P", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "Based on these results , the in vitro concentration that corresponded best with the internal in vivo dose was chosen .", "entity": [], "task": "NER"}
{"text": "Comparison of in vivo and in vitro data demonstrated similarities in transcriptomics response : xenobiotic metabolism , lipid metabolism and oxidative stress .", "entity": [], "task": "NER"}
{"text": "However , we were unable to detect cancer - related pathways in either wild - type or Xpa ( - / - ) p53 ( + / - ) exposed livers , which were previously found to be induced by B [ a ] P in Xpa ( - / - ) p53 ( + / - ) primary hepatocytes .", "entity": [{"entity": "B [ a ] P", "entity_type": "Chemical", "pos": [176, 185]}], "task": "NER"}
{"text": "In conclusion , we showed parallels in gene expression responses between livers and primary hepatocytes upon exposure to equivalent concentrations of B [ a ] P .", "entity": [{"entity": "B [ a ] P", "entity_type": "Chemical", "pos": [150, 159]}], "task": "NER"}
{"text": "Furthermore , we recommend considering toxicokinetics when modeling a complex in vivo endpoint with in vitro models .", "entity": [], "task": "NER"}
{"text": "Environmentally relevant concentrations of a common insecticide increase predation risk in a freshwater gastropod .", "entity": [], "task": "NER"}
{"text": "Ecological receptors are faced with a multitude of stressors that include abiotic and biotic factors creating a challenge for assessing risk of chemical exposure .", "entity": [], "task": "NER"}
{"text": "Of particular interest and importance are the effects of contaminants on inter - species interactions such as competition and predator - prey relationships .", "entity": [], "task": "NER"}
{"text": "The objective of this study was to determine whether environmentally relevant concentrations of the commonly used insecticide , malathion , would alter predator avoidance behavior in a freshwater gastropod that could translate to increased predation risk .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [128, 137]}], "task": "NER"}
{"text": "We exposed adult Physa pomilia snails to 0 , 0 . 25 , or 1 . 0 mg / L malathion for 2 , 24 , or 48 h and evaluated predator avoidance using a behavioral assay in which snails were exposed to cues from predatory crayfish .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "We found a significant reduction in predator avoidance in snails exposed to both concentrations of malathion after 48 h of exposure .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "To evaluate whether observed effects of malathion on predator avoidance actually increased susceptibility of snails to predators , we conducted a predator challenge experiment .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "Snails exposed to 0 . 25 mg / L malathion for 48 h were significantly more susceptible to predation .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [32, 41]}], "task": "NER"}
{"text": "That increased predation risk was evident 48 h after initial malathion exposures is a unique result because most studies have evaluated behavioral responses soon after ( < 12 h ) initiation of pesticide exposure .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [61, 70]}], "task": "NER"}
{"text": "The extent to which the observed interactions affect natural populations , and the mechanisms through which they are mediated are largely unexplored .", "entity": [], "task": "NER"}
{"text": "However , our study is the first to show that a commonly used insecticide decreases predator avoidance and may actually increase predation susceptibility in gastropods at concentrations several orders of magnitude below acute toxicity levels .", "entity": [], "task": "NER"}
{"text": "Contamination by metals and pharmaceuticals in northern Taihu Lake ( China ) and its relation to integrated biomarker response in fish .", "entity": [], "task": "NER"}
{"text": "Taihu Lake is the largest shallow freshwater lake in eastern China and is suffering not only from an increasingly serious threat of eutrophication but also potential ecological risk due to the input of emerging contaminants .", "entity": [], "task": "NER"}
{"text": "Active biomonitoring was conducted in Taihu Lake using transplanted goldfish ( Carassius auratus ) to determine the contamination by pharmaceuticals and metals and to assess the potential ecological risk .", "entity": [], "task": "NER"}
{"text": "A suite of biomarkers including acetylcholinesterase , ethoxyresorufin O - deethylase , glutathione S - transferase , glutathione peroxidase and superoxide dismutase activities in fish after 7 , 14 , 21 and 28 days of exposure in situ , as well as pharmaceuticals and metals in water , were determined during the field exposure period .", "entity": [{"entity": "ethoxyresorufin", "entity_type": "Chemical", "pos": [55, 70]}, {"entity": "O", "entity_type": "Chemical", "pos": [71, 72]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "S", "entity_type": "Chemical", "pos": [100, 101]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [118, 129]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [145, 155]}], "task": "NER"}
{"text": "The results indicate that pharmaceuticals exist mainly in Zhushan Bay and Meiliang Bay , while metals are present mainly in Gong Bay .", "entity": [], "task": "NER"}
{"text": "An integrated biomarker response ( IBR ) was calculated and used to evaluate the ecological risk of the polluted area of Taihu Lake .", "entity": [], "task": "NER"}
{"text": "It was found that Zhushan Bay might present higher risk to fish , followed by Meiliang Bay .", "entity": [], "task": "NER"}
{"text": "IBR values were in good agreement with copper and caffeine concentrations .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "New markers of apoptosis in children on chronic dialysis .", "entity": [], "task": "NER"}
{"text": "Enhanced apoptosis is characteristic for chronic kidney disease ( CKD ) .", "entity": [], "task": "NER"}
{"text": "A specific type of apoptosis , anoikis , is connected with the extracellular matrix turnover and cell detachment .", "entity": [], "task": "NER"}
{"text": "Although E - cadherin , extracellular matrix metalloproteinase inducer ( EMMPRIN ) and matrix metalloproteinase ( MMP ) - 8 may play an important role in this process , they have not been analyzed in any nephrological aspect , either in CKD .", "entity": [], "task": "NER"}
{"text": "The aim of study was to evaluate the serum concentrations of E - cadherin , EMMPRIN and their potential regulators ( MMP - 8 , MMP - 7 , TIMP - 1 , TIMP - 2 ) , with relevance to apoptosis / cell damage markers ( sFas , sFasL , Hsp27 ) , in children with CKD .", "entity": [], "task": "NER"}
{"text": "39 CKD children stages 3 - 4 , 26 CKD children stage 5 still on conservative treatment , 19 patients on hemodialysis ( HD ) , 22 children on automated peritoneal dialysis ( APD ) and 30 controls were examined .", "entity": [], "task": "NER"}
{"text": "Serum concentrations of those parameters were assessed by ELISA .", "entity": [], "task": "NER"}
{"text": "Median E - cadherin , EMMPRIN and MMP - 8 values were significantly increased in patients on dialysis versus those in pre - dialysis period and versus controls .", "entity": [], "task": "NER"}
{"text": "The highest values were noticed in the HD subjects .", "entity": [], "task": "NER"}
{"text": "Regression analysis revealed that EMMPRIN and MMP - 8 predicted various apoptosis markers , whereas E - cadherin turned out the best predictor of both apoptosis ( Hsp27 , sFas , sFasL ) and matrix turnover ( MMP - 7 , TIMP - 1 , TIMP - 2 ) indexes in dialyzed patients .", "entity": [], "task": "NER"}
{"text": "Children with CKD are prone to E - cadherin , EMMPRIN and MMP - 8 elevation , aggravated by the dialysis commencement and most evident on hemodialysis .", "entity": [], "task": "NER"}
{"text": "Correlations between parameters suggest their role as indexes of apoptosis in children on dialysis .", "entity": [], "task": "NER"}
{"text": "E - cadherin seems the most accurate marker of anoikis in this population .", "entity": [], "task": "NER"}
{"text": "Regulation of hepatic phase II metabolism in pregnant mice .", "entity": [], "task": "NER"}
{"text": "Phase II enzymes , including Ugts , Sults , and Gsts , are critical for the disposition and detoxification of endo - and xenobiotics .", "entity": [], "task": "NER"}
{"text": "In this study , the mRNA and protein expression of major phase II enzymes , as well as key regulatory transcription factors , were quantified in livers of time - matched pregnant and virgin control C57BL / 6 mice on gestation days ( GD ) 7 , 11 , 14 , 17 , and postnatal days ( PND ) 1 , 15 , and 30 .", "entity": [], "task": "NER"}
{"text": "Compared with virgin controls , the mRNA expression of Ugt1a1 , 1a6 , 1a9 , 2a3 , 2b1 , 2b34 , and 2b35 decreased 40 to 80 % in pregnant dams .", "entity": [], "task": "NER"}
{"text": "Protein expression of Ugt1a6 also decreased and corresponded with reduced in vitro glucuronidation of bisphenol A in S9 fractions from livers of pregnant mice .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [102, 113]}], "task": "NER"}
{"text": "Similar to Ugts levels , Gsta1 and a4 mRNAs were reduced in pregnant dams in mid to late gestation ; however no change in protein expression was observed .", "entity": [], "task": "NER"}
{"text": "Conversely , Sult1a1 , 2a1 / 2 , and 3a1 mRNAs increased 100 to 500 % at various time points in pregnant and lactating mice and corresponded with enhanced in vitro sulfation of acetaminophen in liver S9 fractions .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [177, 190]}], "task": "NER"}
{"text": "Coinciding with maximal decreases in Ugts as well as increases in Sults , the expression of transcription factors CAR , PPAR alpha , and PXR and their target genes were downregulated , whereas ER alpha mRNA was upregulated .", "entity": [], "task": "NER"}
{"text": "Collectively , these data demonstrate altered regulation of hepatic phase II metabolism in mice during pregnancy and suggest that CAR , PPAR alpha , PXR , and ER alpha signaling pathways may be candidate signaling pathways responsible for these changes .", "entity": [], "task": "NER"}
{"text": "Dendritic arbor of neurons in the hypothalamic ventromedial nucleus in female prairie voles ( Microtus ochrogaster ) .", "entity": [], "task": "NER"}
{"text": "Female mating behavior in rats is associated with hormone - induced changes in the dendritic arbor of neurons in the ventromedial nucleus of the hypothalamus ( VMH ) , particularly the ventrolateral portion .", "entity": [], "task": "NER"}
{"text": "Regulation of mating behavior in female prairie voles differs substantially from that in rats ; therefore , we examined the dendritic morphology of VMH neurons in this species .", "entity": [], "task": "NER"}
{"text": "Sexually na i ve adult female prairie voles were housed with a male to activate the females ' reproductive endocrine system .", "entity": [], "task": "NER"}
{"text": "Following 48 h of cohabitation , females were tested for evidence of reproductive activation by assessing the level of male sexual interest , after which their brains were processed using Golgi impregnation , which allowed ventrolateral VMH neurons to be visualized and analyzed .", "entity": [], "task": "NER"}
{"text": "Dendritic arborization in the female prairie vole VMH neurons was strikingly similar to that of female rats .", "entity": [], "task": "NER"}
{"text": "The key difference was that in the prairie voles the long primary dendrites extended considerably further than those observed in rats .", "entity": [], "task": "NER"}
{"text": "Although most female voles paired with males exhibited sexual activation , some females did not .", "entity": [], "task": "NER"}
{"text": "These two groups displayed specific differences in their VMH dendrites .", "entity": [], "task": "NER"}
{"text": "In particular , the long primary dendrites were longer in the reproductively active females compared with those in the non - activated females .", "entity": [], "task": "NER"}
{"text": "Overall , dendrite lengths were positively correlated with plasma estradiol levels in females exposed to males , but not in unpaired females .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "Although causal relationships between the neuroendocrine events , dendrite length , and the outward , behavioral manifestation of reproductive activation cannot be determined from this study , these results suggest an association between ventrolateral VMH dendrite morphology and female mating behavior in prairie voles , akin to what has been observed in female rats .", "entity": [], "task": "NER"}
{"text": "Hormesis : its impact on medicine and health .", "entity": [], "task": "NER"}
{"text": "This article offers a broad assessment of the hormetic dose response and its relevance to biomedical researchers , physicians , the pharmaceutical industry , and public health scientists .", "entity": [], "task": "NER"}
{"text": "This article contains a series of 61 questions followed by relatively brief but referenced responses that provides support for the conclusion that hormesis is a reproducible phenomenon , commonly observed , with a frequency far greater than other dose - response models such as the threshold and linear nonthreshold dose - response models .", "entity": [], "task": "NER"}
{"text": "The article provides a detailed background information on the historical foundations of hormesis , its quantitative features , mechanistic foundations , as well as how hormesis is currently being used within medicine and identifying how this concept could be further applied in the development of new therapeutic advances and in improved public health practices .", "entity": [], "task": "NER"}
{"text": "APP independent and dependent effects on neurite outgrowth are modulated by the receptor associated protein ( RAP ) .", "entity": [], "task": "NER"}
{"text": "Amyloid precursor protein ( APP ) and its secreted form , sAPP , contribute to the development of neurons in hippocampus , a brain region critical for learning and memory .", "entity": [], "task": "NER"}
{"text": "Full - length APP binds the low - density lipoprotein receptor - related protein ( LRP ) , which stimulates APP endocytosis .", "entity": [], "task": "NER"}
{"text": "LRP also contributes to neurite growth .", "entity": [], "task": "NER"}
{"text": "Furthermore , the receptor associated protein ( RAP ) binds LRP in a manner that blocks APP - LRP interactions .", "entity": [], "task": "NER"}
{"text": "To elucidate APP contributions to neurite growth for full - length APP and sAPP , we cultured wild type ( WT ) and APP knockout ( KO ) neurons in sAPP alpha and / or RAP and measured neurite outgrowth at 1 day in vitro .", "entity": [], "task": "NER"}
{"text": "Our data reveal that WT neurons had less axonal outgrowth including less axon branching .", "entity": [], "task": "NER"}
{"text": "RAP treatment potentiated the inhibitory effects of APP .", "entity": [], "task": "NER"}
{"text": "KO neurons had significantly more outgrowth and branching , especially in response to RAP , effects which were also associated with ERK2 activation .", "entity": [], "task": "NER"}
{"text": "Our results affirm a major inhibitory role by full - length APP on all aspects of axonal and dendritic outgrowth , and show that RAP - LRP binding stimulated axon growth independently of APP .", "entity": [], "task": "NER"}
{"text": "These findings support a major role for APP as an inhibitor of neurite growth and reveal novel signaling functions for LRP that may be disrupted by Alzheimer ' s pathology or therapies aimed at APP processing .", "entity": [], "task": "NER"}
{"text": "Human ether - a - go - go - related gene channel blockers and its structural analysis for drug design .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [6, 11]}], "task": "NER"}
{"text": "The human ether - a - go - go - related gene ( hERG ) is a K + channel protein mainly expressed in the heart and the nervous systems and its blockade by non - cardiovascular acting drugs resulted in tachycardia and sudden death .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [10, 15]}, {"entity": "K +", "entity_type": "Chemical", "pos": [59, 62]}], "task": "NER"}
{"text": "In this present review , we have focused the physicochemical properties responsible for the hERG blocking activity of structurally different compounds .", "entity": [], "task": "NER"}
{"text": "The reported research works showed that the hydrophobicity on the van der Waals ( vdW ) surface of the molecules ( aroused from the aromatic ring ) necessary for the hERG blocking activity along with topological and electronic properties .", "entity": [], "task": "NER"}
{"text": "The quinolizidine alkaloids ( natural products ) such as oxymatrine , sophoridine , sophocarpine and matrine carry the common molecular structure of O = C = N - C - C - C - N that possessed positive ionotropic effect and hERG blocking activity .", "entity": [{"entity": "quinolizidine alkaloids", "entity_type": "Chemical", "pos": [4, 27]}, {"entity": "oxymatrine", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "sophoridine", "entity_type": "Chemical", "pos": [70, 81]}, {"entity": "sophocarpine", "entity_type": "Chemical", "pos": [84, 96]}, {"entity": "matrine", "entity_type": "Chemical", "pos": [101, 108]}, {"entity": "O = C = N - C - C - C - N", "entity_type": "Chemical", "pos": [149, 174]}], "task": "NER"}
{"text": "Acehytisine hydrochloride ( previously named Guangfu base A ) was isolated from the root of Aconitum coreanum ( Levl . ) , is an anti - arrhythmic drug in phase IV clinical trial .", "entity": [{"entity": "Acehytisine hydrochloride", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "Guangfu base A", "entity_type": "Chemical", "pos": [45, 59]}], "task": "NER"}
{"text": "The isoquinoline alkaloid , neferine ( Nef ) induces a concentration - dependent decrease in current amplitude ( IC50 of 7 . 419 MM ) .", "entity": [{"entity": "isoquinoline alkaloid", "entity_type": "Chemical", "pos": [4, 25]}, {"entity": "neferine", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "Nef", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "Most of these natural product compounds contain non - flexible aromatic structures but have significant activity due to the presence of optimum hydrophobicity .", "entity": [], "task": "NER"}
{"text": "Recent research works revealed that Eag and hERG channels are expressed by a variety of cancer cell lines and tissues .", "entity": [], "task": "NER"}
{"text": "The Eag channel showed an oncogenic potential while hERG channels are associated with more aggressive tumors and have a role in mediating invasion .", "entity": [], "task": "NER"}
{"text": "This review concluded that the consideration of physicochemical properties necessary for the hERG blocking activity will guide to develop novel drugs with less cardiotoxicity .", "entity": [], "task": "NER"}
{"text": "In vitro synergistic interaction between amide piplartine and antimicrobial peptide dermaseptin against Schistosoma mansoni schistosomula and adult worms .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [41, 46]}, {"entity": "piplartine", "entity_type": "Chemical", "pos": [47, 57]}], "task": "NER"}
{"text": "Schistosomiasis is one of the world ' s major public health problems , and praziquantel is the only available drug to treat this notable neglected disease .", "entity": [{"entity": "praziquantel", "entity_type": "Chemical", "pos": [75, 87]}], "task": "NER"}
{"text": "Drug combinations have been considered an important strategy for treatment of infectious diseases , which might enhance therapeutic efficacy and delaying resistance .", "entity": [], "task": "NER"}
{"text": "In this study , we have examined the in vitro activities of the amide piplartine and the antimicrobial peptide dermaseptin 01 administered singly or in combination against Schistosoma mansoni of different ages including 3 - hour - old and 7 - day - old schistosomula and 49 - day - old adult schistosomes as well as on egg output by adult worms .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [64, 69]}, {"entity": "piplartine", "entity_type": "Chemical", "pos": [70, 80]}], "task": "NER"}
{"text": "We calculated the median lethal concentrations ( LC ( 50 ) ) of 7 . 87 and 17 . 99 mu M on 49 - day - old adults , 11 . 02 and 71 . 58 mu M on 7 - day - old schistosomula , and 70 . 87 and 98 . 42 mu M on 3 - hour - old schistosomula for piplartine and dermaseptin , respectively .", "entity": [{"entity": "piplartine", "entity_type": "Chemical", "pos": [238, 248]}], "task": "NER"}
{"text": "Most Piplartine / dermaseptin combinations showed synergistic effect , with combination index ( CI ) values less than 0 . 9 when S . mansoni adults or schistosomula were simultaneously incubated with both drugs in vitro ; synergy between these two compounds was also indicated using isobolograms .", "entity": [{"entity": "Piplartine", "entity_type": "Chemical", "pos": [5, 15]}], "task": "NER"}
{"text": "Additionally , we observed alterations on the tegumental surface of schistosomula and adult schistosomes by means of laser scanning confocal microscopy .", "entity": [], "task": "NER"}
{"text": "Furthermore , egg laying of surviving worms was considerably more reduced when exposed to the piplartine / dermaseptin combinations than each drug alone , and this inhibition was irreversible .", "entity": [{"entity": "piplartine", "entity_type": "Chemical", "pos": [94, 104]}], "task": "NER"}
{"text": "This is the first report on the synergistic effect between piplartine and dermaseptin against S . mansoni and opens the route to further studies ( e . g . in vivo ) to characterize this combination in greater detail .", "entity": [{"entity": "piplartine", "entity_type": "Chemical", "pos": [59, 69]}], "task": "NER"}
{"text": "Physiological effects of waterborne lead exposure in spiny dogfish ( Squalus acanthias ) .", "entity": [], "task": "NER"}
{"text": "To broaden our knowledge about the toxicity of metals in marine elasmobranchs , cannulated spiny dogfish ( Squalus acanthias ) were exposed to 20 mu M and 100 mu M lead ( Pb ) .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [171, 173]}], "task": "NER"}
{"text": "Since we wanted to focus on sub lethal ion - osmoregulatory and respiratory disturbances , arterial blood samples were analysed for pH ( a ) , PaO ( 2 ) , haematocrit and total CO ( 2 ) values at several time points .", "entity": [{"entity": "CO ( 2 )", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "Plasma was used to determine urea , TMAO , lactate and ion concentrations .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "TMAO", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [43, 50]}], "task": "NER"}
{"text": "After 96 h , Pb concentrations were determined in a number of tissues , such as gill , rectal gland , skin and liver .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [13, 15]}], "task": "NER"}
{"text": "To further investigate ion and osmoregulation , Na ( + ) / K ( + ) - ATPase activities in gill and rectal gland were analysed as well as rates of ammonia and urea excretion .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [146, 153]}, {"entity": "urea", "entity_type": "Chemical", "pos": [158, 162]}], "task": "NER"}
{"text": "Additionally , we studied the energy reserves in muscle and liver .", "entity": [], "task": "NER"}
{"text": "Pb strongly accumulated in gills and especially in skin .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Lower accumulation rates occurred in gut , kidney and rectal gland .", "entity": [], "task": "NER"}
{"text": "A clear disturbance in acid - base status was observed after one day of exposure indicating a transient period of hyperventilation .", "entity": [], "task": "NER"}
{"text": "The increase in pH ( a ) was temporary at 20 mu M , but persisted at 100 mu M .", "entity": [], "task": "NER"}
{"text": "After 2 days , plasma Na and Cl concentrations were reduced compared to controls at 100 mu M Pb and urea excretion rates were elevated .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [93, 95]}, {"entity": "urea", "entity_type": "Chemical", "pos": [100, 104]}], "task": "NER"}
{"text": "Pb caused impaired Na ( + ) / K ( + ) - ATPase activity in gills , but not in rectal gland .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "We conclude that spiny dogfish experienced relatively low ion - osmoregulatory and respiratory distress when exposed to lead , particularly when compared to effects of other metals such as silver .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [189, 195]}], "task": "NER"}
{"text": "These elasmobranchs appear to be able to minimize the disturbance and maintain physiological homeostasis during an acute Pb exposure .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [121, 123]}], "task": "NER"}
{"text": "An omics based assessment of cadmium toxicity in the green alga Chlamydomonas reinhardtii .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "The effects of cadmium were assessed in the freshwater alga Chlamydomonas reinhardtii .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [15, 22]}], "task": "NER"}
{"text": "Algae were exposed to concentrations of 0 , 8 . 1 or 114 . 8 mu M of cadmium and growth rates , gene transcription and metabolite profiles were examined after 48 and 72 h of exposure .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [69, 76]}], "task": "NER"}
{"text": "In algae exposed to 8 . 1 mu M Cd , several genes were differentially transcribed after 48 h but no adverse growth related effects were detected .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [31, 33]}], "task": "NER"}
{"text": "A transient effect on both gene transcription patterns and metabolite profiles could be discerned after 48 h of exposure but the majority of these changes disappeared after 72 h .", "entity": [], "task": "NER"}
{"text": "In contrast , all effects were more pronounced at the 114 . 8 mu M cadmium exposure .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [67, 74]}], "task": "NER"}
{"text": "Here growth was clearly reduced and transcription of a large number of genes involved in oxidative stress defense mechanisms was differentially increased .", "entity": [], "task": "NER"}
{"text": "Metabolites involved in the glutathione synthesis pathway ( an important antioxidant defense ) were also affected but the effects of cadmium were found to be more pronounced at the transcript level than in the metabolome , suggesting that the former exhibits greater sensitivity toward cadmium exposure .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [28, 39]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [133, 140]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [286, 293]}], "task": "NER"}
{"text": "Establishment of a robust hepatitis C virus replicon cell line over - expressing P - glycoprotein that facilitates analysis of P - gp drug transporter effects on inhibitor antiviral activity .", "entity": [], "task": "NER"}
{"text": "P - glycoprotein ( P - gp ) is an active efflux pump affecting the pharmacokinetic ( PK ) profiles of drugs that are P - gp substrates .", "entity": [], "task": "NER"}
{"text": "The Caco - 2 bi - directional assay is widely used to identify drug - P - gp interactions in vitro .", "entity": [], "task": "NER"}
{"text": "For molecules exhibiting non - classical drug properties however , ambiguous results limit its use in lead optimization .", "entity": [], "task": "NER"}
{"text": "The goal of this study was to develop a robust cell - based assay system to directly measure the role of P - gp - driven efflux in reducing the potency of hepatitis C virus ( HCV ) replication inhibitors .", "entity": [], "task": "NER"}
{"text": "Vinblastine ( Vin ) was employed to select for a Vin - resistant HCV replicon ( 313 - 11 ) from the parental cell line ( 377 - 2 ) .", "entity": [{"entity": "Vinblastine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "Vin", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "Vin", "entity_type": "Chemical", "pos": [49, 52]}], "task": "NER"}
{"text": "The 313 - 11 cell line was > 50 - fold resistant to Vin and over - expressed P - gp , as determined by Western immunoblots .", "entity": [{"entity": "Vin", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "Increased expression of P - gp was mediated by up - regulation of the MDR1 transcript .", "entity": [], "task": "NER"}
{"text": "The reduced potency of different classes of HCV replication inhibitors in the 313 - 11 P - gp cell line was restored in the presence of known P - gp inhibitors .", "entity": [], "task": "NER"}
{"text": "Addition of the P - gp inhibitor , tariquidar , increased the uptake of a radiolabeled HCV replication inhibitor by 14 - fold in the 313 - 11 replicon cell line .", "entity": [{"entity": "tariquidar", "entity_type": "Chemical", "pos": [35, 45]}], "task": "NER"}
{"text": "Finally , a positive correlation was demonstrated between potency in the 313 - 11 replicon and the bi - directional Caco - 2 efflux ratio for a panel of HCV protease inhibitors .", "entity": [], "task": "NER"}
{"text": "In conclusion , a robust P - gp HCV replicon cell - based assay has been developed to measure the effect of the P - gp efflux pump on the potency of different classes of HCV replication inhibitors .", "entity": [], "task": "NER"}
{"text": "This system establishes a direct correlation between antiviral activity and the effect of P - gp efflux in a single cell line .", "entity": [], "task": "NER"}
{"text": "Multifunctional targets of dietary polyphenols in disease : a case for the chemokine network and energy metabolism .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [35, 46]}], "task": "NER"}
{"text": "Chronic , non - acute inflammation is behind conditions that represent most of the disease burden in humans and is clearly linked to immune and metabolic mechanisms .", "entity": [], "task": "NER"}
{"text": "The convergence of pathways involving the immune response , oxidative stress , increased circulating lipids and aberrant insulin signaling results in CCL2 - associated macrophage recruitment and altered energy metabolism .", "entity": [], "task": "NER"}
{"text": "The CCL2 / CCR2 pathway and the energy sensor AMP - activated protein kinase ( AMPK ) are attractive therapeutic targets as a part of preventive management of disease .", "entity": [{"entity": "AMP", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "Several effects of polyphenols are useful in this scenario , including a reduction in the activities of cytokines and modulation of cellular metabolism through histone deacetylase inhibitors , AMPK activators , calorie - restriction mimetics or epigenetic regulators .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [19, 30]}], "task": "NER"}
{"text": "Research is currently underway to develop orally active drugs with these effects , but it is convenient to examine more closely what we are eating .", "entity": [], "task": "NER"}
{"text": "If a lack of relevance in terms of toxicity and substantial effectiveness are confirmed , plant - derived components may provide useful druggable components and dietary supplements .", "entity": [], "task": "NER"}
{"text": "We consider therapeutic actions as a combination of synergistic and / or antagonistic interactions in a multi - target strategy .", "entity": [], "task": "NER"}
{"text": "Hence , improvement in food through enrichment with polyphenols with demonstrated activity may represent a major advance in the design of diets with both industrial and sanitary value .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [52, 63]}], "task": "NER"}
{"text": "Emerging Fusarium mycotoxins in organic and conventional pasta collected in Spain .", "entity": [], "task": "NER"}
{"text": "One of the main sources of emerging Fusarium mycotoxins in human nutrition is the cereals and cereal products .", "entity": [], "task": "NER"}
{"text": "In this study , an analytical method to determine enniatins A , A1 , B and B1 ( ENs ) , beauvericin ( BEA ) and fusaproliferin ( FUS ) based on Ultra - Turrax extraction followed by liquid chromatography coupled to triple quadrupole mass spectrometer detector ( MS / MS QqQ ) , was applied for the analysis of pasta .", "entity": [{"entity": "enniatins A , A1 , B and B1", "entity_type": "Chemical", "pos": [50, 77]}, {"entity": "beauvericin", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "BEA", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "fusaproliferin", "entity_type": "Chemical", "pos": [112, 126]}, {"entity": "FUS", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "For this purpose , 114 commercial samples of pasta were acquired from supermarkets located in Valencia .", "entity": [], "task": "NER"}
{"text": "The results showed higher frequencies of contamination in organic pasta than in conventional pasta , while the concentration levels were variable for both types of pasta .", "entity": [], "task": "NER"}
{"text": "In positive samples , BEA levels varied from 0 . 10 to 20 . 96 mu g / kg and FUS levels varied from 0 . 05 to 8 . 02 mu g / kg .", "entity": [{"entity": "BEA", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "FUS", "entity_type": "Chemical", "pos": [77, 80]}], "task": "NER"}
{"text": "ENs levels ranged from 0 . 25 to 979 . 56 mu g / kg , though the majority of the values were below 25 mu g / kg .", "entity": [], "task": "NER"}
{"text": "Besides , it was observed the simultaneous presence of two or more mycotoxins in a high percentage of the samples .", "entity": [], "task": "NER"}
{"text": "Finally , an evaluation of the dietary exposure of the emerging Fusarium mycotoxins was performed in the Spanish population .", "entity": [], "task": "NER"}
{"text": "The prevalence of ENs , BEA and FUS in cereal products suggests that the toxins may pose a health risk to Spanish population .", "entity": [{"entity": "BEA", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "FUS", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Structure - based design and synthesis of novel pseudosaccharine derivatives as antiproliferative agents and kinase inhibitors .", "entity": [{"entity": "pseudosaccharine", "entity_type": "Chemical", "pos": [48, 64]}], "task": "NER"}
{"text": "This study is concerned with the implementation of structure - based techniques for the design of new heterocyclic compounds based on pseudosaccharine scaffold with protein kinase inhibition activity .", "entity": [{"entity": "pseudosaccharine", "entity_type": "Chemical", "pos": [134, 150]}], "task": "NER"}
{"text": "This nucleus was exploited based on the well - known quinazoline core and its interactions with several protein kinases .", "entity": [{"entity": "quinazoline", "entity_type": "Chemical", "pos": [53, 64]}], "task": "NER"}
{"text": "Two series of compounds employing this new scaffold were synthesized and evaluated at enzymatic and cellular levels .", "entity": [], "task": "NER"}
{"text": "Compound 9b displayed broad spectrum antiproliferative activity on NCI 60 - cell lines panel with mean GI50 of 5 . 4 mu M .", "entity": [], "task": "NER"}
{"text": "Investigation of the molecular mechanism showed probable inhibitory activity against Src kinase .", "entity": [], "task": "NER"}
{"text": "Giant cell tumor of bone : a basic science perspective .", "entity": [], "task": "NER"}
{"text": "Comprehending the pathogenesis of giant cell tumor of bone ( GCT ) is of critical importance for developing novel targeted treatments for this locally - aggressive primary bone tumor .", "entity": [], "task": "NER"}
{"text": "GCT is characterized by the presence of large multinucleated osteoclast - like giant cells distributed amongst mononuclear spindle - like stromal cells and other monocytes .", "entity": [], "task": "NER"}
{"text": "The giant cells are principally responsible for the extensive bone resorption by the tumor .", "entity": [], "task": "NER"}
{"text": "However , the spindle - like stromal cells chiefly direct the pathology of the tumor by recruiting monocytes and promoting their fusion into giant cells .", "entity": [], "task": "NER"}
{"text": "The stromal cells also enhance the resorptive ability of the giant cells .", "entity": [], "task": "NER"}
{"text": "This review encompasses many of the attributes of GCT , including the process of giant cell formation and the mechanisms of bone resorption .", "entity": [], "task": "NER"}
{"text": "The significance of the receptor activator of nuclear factor - kappa B ligand ( RANKL ) in the development of GCT and the importance of proteases , including numerous matrix metalloproteinases , are highlighted .", "entity": [], "task": "NER"}
{"text": "The mesenchymal lineage of the stromal cells and the origin of the hematopoietic monocytes are also discussed .", "entity": [], "task": "NER"}
{"text": "Several aspects of GCT that require further understanding , including the etiology of the tumor , the mechanisms of metastases , and the development of an appropriate animal model , are also considered .", "entity": [], "task": "NER"}
{"text": "By exploring the current status of GCT research , this review accentuates the significant progress made in understanding the biology of the tumor , and discusses important areas for future investigation .", "entity": [], "task": "NER"}
{"text": "NCTC 2544 and IL - 18 production : a tool for the identification of contact allergens .", "entity": [], "task": "NER"}
{"text": "Progress in understanding the mechanisms of skin sensitization , provides us with the opportunity to develop in vitro tests as an alternative to in vivo sensitization testing .", "entity": [], "task": "NER"}
{"text": "Keratinocytes play a key role in all phases of skin sensitization .", "entity": [], "task": "NER"}
{"text": "We have recently identified interleukin - 18 ( IL - 18 ) production in keratinocyte as a potentially useful endpoint for determination of contact sensitization potential of low molecular weight chemicals .", "entity": [], "task": "NER"}
{"text": "The aim of the present article is to further exploit the performance of the NCTC 2544 assay .", "entity": [], "task": "NER"}
{"text": "NCTC 2544 is a commercially available skin epithelial - like cell line originating from normal human skin , which posses a good expression of cytochrome P450 - dependent enzymatic activities .", "entity": [], "task": "NER"}
{"text": "Cells were exposed to contact allergens ( 2 - bromo - 2 - bromomethyl glutaronitrile , cinnamaldehyde , citral , diethylmaleate , dinitrochlorobenzene , glyoxal , 2 - mercaptobenzothiazole , nickel sulfate , 4 - nitrobenzylbromide , oxazolone , penicillin G , resorcinol , tetramethylthiuram disulfide ) , to pre - pro - haptens ( cinnamyl alcohol , eugenol , isoeugenol , p - phenylediamine ) , to respiratory allergens ( ammonium hexachloroplatinate , diphenylmethane diisocyanate , glutaraldehyde , hexamethylenediisocyanate , maleic anhydride , trimellitic anhydride ) and to irritants ( benzaldehyde , cholorobenzene , diethylphtalate , hydrobenzoic acid , lactic acid , octanoic acid , phenol , salicylic acid , sodium lauryl sulphate , sulfamic acid ) .", "entity": [{"entity": "2 - bromo - 2 - bromomethyl glutaronitrile", "entity_type": "Chemical", "pos": [42, 84]}, {"entity": "cinnamaldehyde", "entity_type": "Chemical", "pos": [87, 101]}, {"entity": "citral", "entity_type": "Chemical", "pos": [104, 110]}, {"entity": "diethylmaleate", "entity_type": "Chemical", "pos": [113, 127]}, {"entity": "dinitrochlorobenzene", "entity_type": "Chemical", "pos": [130, 150]}, {"entity": "glyoxal", "entity_type": "Chemical", "pos": [153, 160]}, {"entity": "2 - mercaptobenzothiazole", "entity_type": "Chemical", "pos": [163, 188]}, {"entity": "nickel sulfate", "entity_type": "Chemical", "pos": [191, 205]}, {"entity": "4 - nitrobenzylbromide", "entity_type": "Chemical", "pos": [208, 230]}, {"entity": "oxazolone", "entity_type": "Chemical", "pos": [233, 242]}, {"entity": "penicillin G", "entity_type": "Chemical", "pos": [245, 257]}, {"entity": "resorcinol", "entity_type": "Chemical", "pos": [260, 270]}, {"entity": "tetramethylthiuram disulfide", "entity_type": "Chemical", "pos": [273, 301]}, {"entity": "cinnamyl alcohol", "entity_type": "Chemical", "pos": [331, 347]}, {"entity": "eugenol", "entity_type": "Chemical", "pos": [350, 357]}, {"entity": "isoeugenol", "entity_type": "Chemical", "pos": [360, 370]}, {"entity": "p - phenylediamine", "entity_type": "Chemical", "pos": [373, 391]}, {"entity": "ammonium hexachloroplatinate", "entity_type": "Chemical", "pos": [423, 451]}, {"entity": "diphenylmethane diisocyanate", "entity_type": "Chemical", "pos": [454, 482]}, {"entity": "glutaraldehyde", "entity_type": "Chemical", "pos": [485, 499]}, {"entity": "hexamethylenediisocyanate", "entity_type": "Chemical", "pos": [502, 527]}, {"entity": "maleic anhydride", "entity_type": "Chemical", "pos": [530, 546]}, {"entity": "trimellitic anhydride", "entity_type": "Chemical", "pos": [549, 570]}, {"entity": "benzaldehyde", "entity_type": "Chemical", "pos": [592, 604]}, {"entity": "cholorobenzene", "entity_type": "Chemical", "pos": [607, 621]}, {"entity": "diethylphtalate", "entity_type": "Chemical", "pos": [624, 639]}, {"entity": "hydrobenzoic acid", "entity_type": "Chemical", "pos": [642, 659]}, {"entity": "lactic acid", "entity_type": "Chemical", "pos": [662, 673]}, {"entity": "octanoic acid", "entity_type": "Chemical", "pos": [676, 689]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [692, 698]}, {"entity": "salicylic acid", "entity_type": "Chemical", "pos": [701, 715]}, {"entity": "sodium lauryl sulphate", "entity_type": "Chemical", "pos": [718, 740]}, {"entity": "sulfamic acid", "entity_type": "Chemical", "pos": [743, 756]}], "task": "NER"}
{"text": "Cell associated IL - 18 was evaluated 24 later by ELISA .", "entity": [], "task": "NER"}
{"text": "At not - cytotoxic concentrations ( cell viability higher of 80 % , as assessed by MTT reduction assay ) , all contact sensitizers , including pre - pro - haptens , induced a dose - related increase in IL - 18 , whereas both irritants , with the exception of sulfamic acid , and respiratory allergens failed .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "sulfamic acid", "entity_type": "Chemical", "pos": [259, 272]}], "task": "NER"}
{"text": "A total of 33 chemicals were tested , with an overall accuracy of 97 % .", "entity": [], "task": "NER"}
{"text": "Overall , results obtained indicated that cell - associated IL - 18 might provide an in vitro tool for identification and discrimination of contact vs . respiratory allergens and / or irritants .", "entity": [], "task": "NER"}
{"text": "Application of the acquired knowledge and implementation of the Sens - it - iv toolbox for identification and classification of skin and respiratory sensitizers .", "entity": [], "task": "NER"}
{"text": "The contribution of the Sens - it - iv project to the reduction and replacement of animal experimentation is 3 - fold .", "entity": [], "task": "NER"}
{"text": "The funding of basic research has expanded the existing scientific knowledge thereby strengthening the understanding of the cellular and molecular mechanisms driving skin and respiratory sensitization .", "entity": [], "task": "NER"}
{"text": "Examples are given on how a better understanding was used to improve existing test concepts .", "entity": [], "task": "NER"}
{"text": "This knowledge was also applied to develop novel test systems .", "entity": [], "task": "NER"}
{"text": "While some of test systems did not reach sufficient maturity for being considered for pre - validation others did and entered into the Sens - it - iv toolbox .", "entity": [], "task": "NER"}
{"text": "In the process , developments outside the Sens - it - iv orbit were carefully followed and assessed in order to avoid duplication and to assure synergy between the ongoing activities ( e . g . Cosmetics Europe Task Force for Sensitization ) .", "entity": [], "task": "NER"}
{"text": "Tests from the Sens - it - iv toolbox were submitted to the European Reference Laboratory for Alternative Methods ( EuRL - ECVAM ) to initiate the rigid procedures for regulatory acceptance by national and international authorities .", "entity": [], "task": "NER"}
{"text": "In spite of not being validated yet , selected tests were already applied in a weight - of - evidence approach in the context of REACH .", "entity": [], "task": "NER"}
{"text": "Furthermore , several chemical , pharmaceutical , cosmetic and consumer product companies are currently assessing selected tests and testing strategies for their value as tools for screening and hazard identification using in house compounds and mixtures .", "entity": [], "task": "NER"}
{"text": "The main points of concern related to transfer to and implementation by industry were cost , through - put and applicability domain , rather than regulatory acceptance .", "entity": [], "task": "NER"}
{"text": "These issues are currently addressed in applied research projects which are financially supported by individual companies , or consortia of companies , representing the various industry sectors .", "entity": [], "task": "NER"}
{"text": "Assay of vtg , ERs and PPARs as endpoint for the rapid in vitro screening of the harmful effect of Di - ( 2 - ethylhexyl ) - phthalate ( DEHP ) and phthalic acid ( PA ) in zebrafish primary hepatocyte cultures .", "entity": [{"entity": "Di - ( 2 - ethylhexyl ) - phthalate", "entity_type": "Chemical", "pos": [99, 134]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [137, 141]}, {"entity": "phthalic acid", "entity_type": "Chemical", "pos": [148, 161]}], "task": "NER"}
{"text": "In the last years the concern about the negative effects of phthalates on reproduction significantly increased .", "entity": [{"entity": "phthalates", "entity_type": "Chemical", "pos": [60, 70]}], "task": "NER"}
{"text": "Considering that , at date data available dealing with the adverse outcome of Di - ( 2 - ethylhexyl ) - phthalate ( DEHP ) on the reproduction of several species are still contrasting , in this study , the effects induced by DEHP ( 0 . 05 , 0 . 1 , 1 , 10 and 100 nM ) and its active metabolite , phthalic acid ( PA ) ( 0 . 01 , 0 . 1 , 1 and 10 mu M ) , were analyzed in zebrafish , Danio rerio , primary hepatocyte cultures , using target molecules involved in fish reproduction ( vitellogenin - - vtg and estrogen receptors - - ER alpha , beta 1 and beta 2 ) and metabolism ( peroxisome proliferators activated receptors - - PPAR alpha , beta , gamma ) .", "entity": [{"entity": "Di - ( 2 - ethylhexyl ) - phthalate", "entity_type": "Chemical", "pos": [78, 113]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [116, 120]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [225, 229]}, {"entity": "phthalic acid", "entity_type": "Chemical", "pos": [297, 310]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [508, 516]}], "task": "NER"}
{"text": "The use of in vitro culture , in fact , has the potential to significantly reduce the number of animals sacrificed for research allowing a precise control of the physical and chemical parameters that is often not possible in vivo .", "entity": [], "task": "NER"}
{"text": "Moreover , since many toxicological studies revealed a sex specific response to toxicants , male and female primary hepatocyte cultures were set up to elucidate the possible gender specific effects of two common environmental phthalates .", "entity": [{"entity": "phthalates", "entity_type": "Chemical", "pos": [226, 236]}], "task": "NER"}
{"text": "The increase of vtg levels observed in the culture media of male or female hepatocytes strongly evidenced the phthalates E2 - like action .", "entity": [{"entity": "phthalates", "entity_type": "Chemical", "pos": [110, 120]}], "task": "NER"}
{"text": "Moreover , the data obtained suggested that the observed different ERs isoforms modulation is otherwise associated with the vtg increase , depending on fish gender .", "entity": [], "task": "NER"}
{"text": "Regarding PPARs , a similar trend of expression was found in both males and females .", "entity": [], "task": "NER"}
{"text": "In conclusion , this study enforces the role of vtg as biomarker for evaluate the presence of environmental doses of DEHP and PA .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [117, 121]}], "task": "NER"}
{"text": "Considering the similar gender modulation observed for vtg and PPARs , these molecules could be used for the rapid screening of the presence of DEHP and PA .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [144, 148]}], "task": "NER"}
{"text": "Noteworthy the gender specific modulation observed for ERs opens a debate on the estrogenic mechanism of action of DEHP and PA and their role on vtg induction .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [115, 119]}], "task": "NER"}
{"text": "Inhibition of EGF / EGFR activation with naphtho [ 1 , 2 - b ] furan - 4 , 5 - dione blocks migration and invasion of MDA - MB - 231 cells .", "entity": [{"entity": "naphtho [ 1 , 2 - b ] furan - 4 , 5 - dione", "entity_type": "Chemical", "pos": [41, 84]}], "task": "NER"}
{"text": "Naphtho [ 1 , 2 - b ] furan - 4 , 5 - dione ( NFD ) , a bioactive component of Avicennia marina , has been demonstrated to display anti - cancer activity .", "entity": [{"entity": "Naphtho [ 1 , 2 - b ] furan - 4 , 5 - dione", "entity_type": "Chemical", "pos": [0, 43]}, {"entity": "NFD", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "Activation of epidermal growth factor receptor ( EGFR ) - induced signaling pathway has been correlated with cancer metastasis in various tumors , including breast carcinoma .", "entity": [], "task": "NER"}
{"text": "We use EGF as a metastatic inducer of MDA - MB - 231 cells to investigate the effect of NFD on cell migration and invasion .", "entity": [{"entity": "NFD", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "NFD suppressed EGF - mediated protein levels of c - Jun and c - Fos , and reduced MMP - 9 expression and activity , concomitantly with a marked inhibition on cell migration and invasion without obvious cellular cytotoxicity .", "entity": [{"entity": "NFD", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "NFD abrogated EGF - induced phosphorylation of EGF receptor ( EGFR ) and phosphatidylinositol 3 - kinase ( PI3K ) / Akt .", "entity": [{"entity": "NFD", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [73, 93]}], "task": "NER"}
{"text": "The specific PI3K inhibitor , wortmannin , blocked significantly EGF - induced cell migration and invasion .", "entity": [{"entity": "wortmannin", "entity_type": "Chemical", "pos": [30, 40]}], "task": "NER"}
{"text": "Furthermore , the EGFR inhibitor AG1478 inhibited EGF - induced MMP - 9 expression , cell migration and invasion , as well as the activation of PI3K / Akt , suggesting that PI3K / Akt activation occur downstream of EGFR activation .", "entity": [{"entity": "AG1478", "entity_type": "Chemical", "pos": [33, 39]}], "task": "NER"}
{"text": "These findings suggest that NFD inhibited the EGF - induced invasion and migration of MDA - MB - 231 cells via EGFR - dependent PI3K / Akt signaling , leading to the down - regulation of MMP - 9 expression .", "entity": [{"entity": "NFD", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "These results provide a novel mechanism to explain the role of NFD as a potent anti - metastatic agent in MDA - MB - 231 cells .", "entity": [{"entity": "NFD", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "The association of serum 25 - hydroxyvitamin D and vertebral fractures in patients with type 2 diabetes .", "entity": [{"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [25, 46]}], "task": "NER"}
{"text": "Vitamin D is an important regulator of bone health .", "entity": [{"entity": "Vitamin D", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Previous studies examining the association between vitamin D deficiency and osteoporotic fractures have reported conflicting results .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "The relationship between vitamin D status and risk of vertebral fractures in diabetic patients is unknown .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [25, 34]}], "task": "NER"}
{"text": "The objective of this study was to examine whether low serum 25 - hydroxyvitamin D [ 25 ( OH ) D ] levels were associated with vertebral fractures in patients with type 2 diabetes .", "entity": [{"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [61, 82]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [85, 96]}], "task": "NER"}
{"text": "This cross - sectional study was conducted among 161 postmenopausal women and 180 men with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Serum concentrations of 25 ( OH ) D were measured and the presence of vertebral fracture was assessed using lateral plain radiographs of the thoracolumbar spine .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "Women had lower 25 ( OH ) D levels than men ( 31 . 3 +/- 17 . 7 vs . 41 . 3 +/- 26 . 5 ng / mL , p < 0 . 001 ) .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [16, 27]}], "task": "NER"}
{"text": "Vertebral fractures were found in 16 % of patients .", "entity": [], "task": "NER"}
{"text": "Men with a serum 25 ( OH ) D concentration greater than 30 ng / mL showed a lower prevalence of vertebral fractures compared to those with 20 - 29 . 9 ng / mL or those with less than 20 ng / mL ( 9 . 4 % vs . 17 . 9 % vs . 21 . 7 % , p for trend = 0 . 036 ) .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [17, 28]}], "task": "NER"}
{"text": "However , there was no significant association between vitamin D status and the prevalence of vertebral fractures in women ( 14 . 4 % vs . 19 . 2 % vs . 26 . 6 % , p for trend = 0 . 111 ) .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "After adjusting for multiple confounding factors , men with a serum 25 ( OH ) D concentration of less than 20 ng / mL were associated with an increased risk of vertebral fractures ( OR 7 . 87 ; 95 % CI 1 . 69 - 36 . 71 ) , but not women .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [68, 79]}], "task": "NER"}
{"text": "In conclusion , serum 25 ( OH ) D levels below 20 ng / mL were associated with an increased vertebral fracture risk in men with type 2 diabetes .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "Chiral and chemical oscillations in a simple dimerization model .", "entity": [], "task": "NER"}
{"text": "We consider the APED model ( activation - polymerization - epimerization - depolymerization ) for describing the emergence of chiral solutions within a non - catalytic framework for chiral polymerization .", "entity": [], "task": "NER"}
{"text": "The minimal APED model for dimerization can lead to the spontaneous appearance of chiral oscillations and we describe in detail the nature of these oscillations in the enantiomeric excess , which are the consequence of oscillations of the concentrations of the associated chemical species .", "entity": [], "task": "NER"}
{"text": "Ketamine - induced neuronal damage and altered N - methyl - D - aspartate receptor function in rat primary forebrain culture .", "entity": [{"entity": "Ketamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [47, 73]}], "task": "NER"}
{"text": "Ketamine , a noncompetitive N - methyl - D - aspartate ( NMDA ) receptor antagonist , is frequently used in pediatric general anesthesia .", "entity": [{"entity": "Ketamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [28, 54]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "Accumulating evidence from animal experiments has demonstrated that ketamine causes neuronal cell death during the brain growth spurt .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [68, 76]}], "task": "NER"}
{"text": "To elucidate the underlying mechanisms associated with ketamine - induced neuronal toxicity and search for approaches or agents to prevent ketamine ' s adverse effects on the developing brain , a primary nerve cell culture system was utilized .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "Neurons harvested from the forebrain of newborn rats were maintained under normal control conditions or exposed to either ketamine ( 10 micro M ) or ketamine plus L - carnitine ( an antioxidant ; 1 - 100 micro M ) for 24h , followed by a 24 - h withdrawal period .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [122, 130]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [149, 157]}, {"entity": "L - carnitine", "entity_type": "Chemical", "pos": [163, 176]}], "task": "NER"}
{"text": "Ketamine exposure resulted in elevated NMDA receptor ( NR1 ) expression , increased generation of reactive oxygen species ( ROS ) as indicated by higher levels of 8 - oxoguanine production , and enhanced neuronal damage .", "entity": [{"entity": "Ketamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [39, 43]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [107, 113]}, {"entity": "8 - oxoguanine", "entity_type": "Chemical", "pos": [163, 177]}], "task": "NER"}
{"text": "Coadministration of L - carnitine significantly diminished ROS generation and provided near complete protection of neurons from ketamine - induced cell death .", "entity": [{"entity": "L - carnitine", "entity_type": "Chemical", "pos": [20, 33]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "NMDA receptors regulate channels that are highly permeable to calcium , and calcium imaging data demonstrated that neurons exposed to ketamine had a significantly elevated amplitude of calcium influx and higher intracellular free calcium concentrations ( [ Ca ( 2 + ) ] i ) evoked by NMDA ( 50 micro M ) , compared with control neurons .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [76, 83]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [134, 142]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [185, 192]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [230, 237]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [257, 267]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [284, 288]}], "task": "NER"}
{"text": "These findings suggest that prolonged ketamine exposure produces an increase in NMDA receptor expression ( compensatory upregulation ) , which allows for a higher / toxic influx of calcium into neurons once ketamine is removed from the system , leading to elevated ROS generation and neuronal cell death .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [38, 46]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [80, 84]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [181, 188]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [207, 215]}], "task": "NER"}
{"text": "L - Carnitine appears to be a promising agent in preventing or reversing ketamine ' s toxic effects on neurons at an early developmental stage .", "entity": [{"entity": "L - Carnitine", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "Resonance Raman spectral imaging of intracellular uptake of beta - carotene loaded poly ( D , L - lactide - co - glycolide ) nanoparticles .", "entity": [{"entity": "beta - carotene", "entity_type": "Chemical", "pos": [60, 75]}, {"entity": "poly ( D , L - lactide - co - glycolide )", "entity_type": "Chemical", "pos": [83, 124]}], "task": "NER"}
{"text": "The use of nanoparticles for drug delivery has been drawing considerable attention in pharmaceutical research .", "entity": [], "task": "NER"}
{"text": "With increasing diversity and potential of various carrier systems , it is important to study the impact of nanocarriers on sub - cellular metabolic processes and organelles , since the delivery of a drug usually involves intra - cellular internalization .", "entity": [], "task": "NER"}
{"text": "Herein , we employ Raman microscopy as a non - invasive method for cellular and sub - cellular imaging , to monitor the uptake and translocation patterns of particles based on poly ( D , L - lactide - co - glycolide ) over time .", "entity": [{"entity": "poly ( D , L - lactide - co - glycolide )", "entity_type": "Chemical", "pos": [176, 217]}], "task": "NER"}
{"text": "As the technique detects inherent signals from the molecules of interest , it does not rely on external labels or dyes , which is an advantage over fluorescence labeling .", "entity": [], "task": "NER"}
{"text": "For this purpose , the particles were loaded with beta - carotene .", "entity": [{"entity": "beta - carotene", "entity_type": "Chemical", "pos": [50, 65]}], "task": "NER"}
{"text": "The conjugated pi - system of the molecule has a large Raman scattering cross - section and gives rise to resonance Raman effects , which can enhance the sensitivity by orders of magnitude .", "entity": [], "task": "NER"}
{"text": "beta - Carotene as a provitamin is not soluble in water and is thus usually of low bioavailability , which is enhanced by encapsulation into the nanoparticles .", "entity": [{"entity": "beta - Carotene", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Activation of group I metabotropic glutamate receptors potentiates heteromeric kainate receptors .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "kainate", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "Kainate receptors ( KARs ) , a family of ionotropic glutamate receptors , are widely expressed in the central nervous system and are critically involved in synaptic transmission .", "entity": [{"entity": "Kainate", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "KAR activation is influenced by metabotropic glutamate receptor ( mGlu ) signaling , but the underlying mechanisms are not understood .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "We undertook studies to examine how mGlu modulation affects activation of KARs .", "entity": [], "task": "NER"}
{"text": "Confocal immunohistochemistry of rat hippocampus and cultured rat cortex revealed colocalization of the high - affinity KAR subunits with group I mGlu receptors .", "entity": [], "task": "NER"}
{"text": "In hippocampal and cortical cultures , the calcium signal caused by activation of native KARs was potentiated by activation of group I mGlu receptors .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [43, 50]}], "task": "NER"}
{"text": "In Xenopus laevis oocytes , activation of group I mGlu receptors potentiated heteromeric but not homomeric KAR - mediated currents , with no change in agonist potency .", "entity": [], "task": "NER"}
{"text": "The potentiation of heteromeric KARs by mGlu1 activation was attenuated by GDP beta S , blocked by an inhibitor of phospholipase C or the calcium chelator 1 , 2 - bis ( o - aminophenoxy ) ethane - N , N , N ' , N ' - tetraacetic acid ( BAPTA ) , prolonged by the phosphatase inhibitor okadaic acid , but unaffected by the tyrosine kinase inhibitor lavendustin A .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [138, 145]}, {"entity": "1 , 2 - bis ( o - aminophenoxy ) ethane - N , N , N ' , N ' - tetraacetic acid", "entity_type": "Chemical", "pos": [155, 233]}, {"entity": "BAPTA", "entity_type": "Chemical", "pos": [236, 241]}, {"entity": "okadaic acid", "entity_type": "Chemical", "pos": [285, 297]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [322, 330]}, {"entity": "lavendustin A", "entity_type": "Chemical", "pos": [348, 361]}], "task": "NER"}
{"text": "Protein kinase C ( PKC ) inhibition reduced the potentiation by mGlu1 of GluK2 / GluK5 , and conversely , direct activation of PKC by phorbol 12 - myristate , 13 - acetate potentiated GluK2 / GluK5 .", "entity": [{"entity": "phorbol 12 - myristate , 13 - acetate", "entity_type": "Chemical", "pos": [134, 171]}], "task": "NER"}
{"text": "Using site - directed mutagenesis , we identified three serines ( Ser833 , Ser836 , and Ser840 ) within the membrane proximal region of the GluK5 C - terminal domain that , in combination , are required for mGlu1 - mediated potentiation of KARs .", "entity": [{"entity": "serines", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "Ser833", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "Ser836", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "Ser840", "entity_type": "Chemical", "pos": [88, 94]}, {"entity": "C", "entity_type": "Chemical", "pos": [146, 147]}], "task": "NER"}
{"text": "Together , these data suggest that phosphorylation of key residues in the C - terminal domain changes the overall charge of this domain , resulting in potentiated agonist responses .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [74, 75]}], "task": "NER"}
{"text": "beta - Adrenergic agonists mediate enhancement of beta 1 - adrenergic receptor N - terminal cleavage and stabilization in vivo and in vitro .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [79, 80]}], "task": "NER"}
{"text": "The beta ( 1 ) - adrenergic receptor ( beta ( 1 ) AR ) is the predominant beta AR in the heart and is the main target for beta - adrenergic antagonists , widely used in the treatment of cardiovascular diseases .", "entity": [], "task": "NER"}
{"text": "Previously , we have shown that the human ( h ) beta ( 1 ) AR is cleaved in its N terminus by a metalloproteinase , both constitutively and in a receptor activation - dependent manner .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [80, 81]}], "task": "NER"}
{"text": "In this study , we investigated the specific events involved in beta ( 1 ) AR regulation , focusing on the effects of long - term treatment with beta - adrenergic ligands on receptor processing in stably transfected human embryonic kidney 293 ( i ) cells .", "entity": [], "task": "NER"}
{"text": "The key findings were verified using the transiently transfected h beta ( 1 ) AR and the endogenously expressed receptor in neonatal rat cardiomyocytes .", "entity": [], "task": "NER"}
{"text": "By using flow cytometry and Western blotting , we demonstrated that isoproterenol , S - propranolol , CGP - 12177 [ 4 - [ 3 - [ ( 1 , 1 - dimethylethyl ) amino ] 2 - hydroxypropoxy ] - 1 , 3 - dihydro - 2H - benzimidazol - 2 - one ] , pindolol , and timolol , which displayed agonistic properties toward the beta ( 1 ) AR in either the adenylyl cyclase or the mitogen - activated protein kinase signaling pathways , induced cleavage of the mature cell - surface receptor .", "entity": [{"entity": "isoproterenol", "entity_type": "Chemical", "pos": [68, 81]}, {"entity": "S - propranolol", "entity_type": "Chemical", "pos": [84, 99]}, {"entity": "CGP - 12177", "entity_type": "Chemical", "pos": [102, 113]}, {"entity": "4 - [ 3 - [ ( 1 , 1 - dimethylethyl ) amino ] 2 - hydroxypropoxy ] - 1 , 3 - dihydro - 2H - benzimidazol - 2 - one", "entity_type": "Chemical", "pos": [116, 230]}, {"entity": "pindolol", "entity_type": "Chemical", "pos": [235, 243]}, {"entity": "timolol", "entity_type": "Chemical", "pos": [250, 257]}, {"entity": "adenylyl", "entity_type": "Chemical", "pos": [336, 344]}], "task": "NER"}
{"text": "In contrast , metoprolol , bisoprolol , and CGP - 20712 [ 1 - [ 2 - ( ( 3 - carbamoyl - 4 - hydroxy ) phenoxy ) ethylamino ] - 3 - [ 4 - ( 1 - methyl - 4 - trifluoromethyl - 2 - imidazolyl ) phenoxy ] - 2 - propanol ] , which showed no agonistic activity , had only a marginal or no effect .", "entity": [{"entity": "metoprolol", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "bisoprolol", "entity_type": "Chemical", "pos": [27, 37]}, {"entity": "CGP - 20712", "entity_type": "Chemical", "pos": [44, 55]}, {"entity": "1 - [ 2 - ( ( 3 - carbamoyl - 4 - hydroxy ) phenoxy ) ethylamino ] - 3 - [ 4 - ( 1 - methyl - 4 - trifluoromethyl - 2 - imidazolyl ) phenoxy ] - 2 - propanol", "entity_type": "Chemical", "pos": [58, 215]}], "task": "NER"}
{"text": "Importantly , the agonists also stabilized intracellular receptor precursors , possibly via their pharmacological chaperone action , and they stabilized the receptor in vitro .", "entity": [], "task": "NER"}
{"text": "The opposing effects on the two receptor forms thus led to an increase in the amount of cleaved receptor fragments at the plasma membrane .", "entity": [], "task": "NER"}
{"text": "The results underscore the pluridimensionality of beta - adrenergic ligands and extend this property from receptor activation and signaling to the regulation of beta ( 1 ) AR levels .", "entity": [], "task": "NER"}
{"text": "This phenomenon may contribute to the exceptional resistance of beta ( 1 ) ARs to downregulation and tendency toward upregulation following long - term ligand treatments .", "entity": [], "task": "NER"}
{"text": "The biarylpyrazole compound AM251 alters mitochondrial physiology via proteolytic degradation of ERR alpha .", "entity": [{"entity": "biarylpyrazole", "entity_type": "Chemical", "pos": [4, 18]}, {"entity": "AM251", "entity_type": "Chemical", "pos": [28, 33]}], "task": "NER"}
{"text": "The orphan nuclear receptor estrogen - related receptor alpha ( ERR alpha ) directs the transcription of nuclear genes involved in energy homeostasis control and the regulation of mitochondrial mass and function .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [28, 36]}], "task": "NER"}
{"text": "A crucial role for controlling ERR alpha - mediated target gene expression has been ascribed to the biarylpyrazole compound 1 - ( 2 , 4 - dichlorophenyl ) - 5 - ( 4 - iodophenyl ) - 4 - methyl - N - 1 - piperidinyl - 1H - pyrazole - 3 - carboxamide ( AM251 ) through direct binding to and destabilization of ERR alpha protein .", "entity": [{"entity": "biarylpyrazole", "entity_type": "Chemical", "pos": [100, 114]}, {"entity": "1 - ( 2 , 4 - dichlorophenyl ) - 5 - ( 4 - iodophenyl ) - 4 - methyl - N - 1 - piperidinyl - 1H - pyrazole - 3 - carboxamide", "entity_type": "Chemical", "pos": [124, 248]}, {"entity": "AM251", "entity_type": "Chemical", "pos": [251, 256]}], "task": "NER"}
{"text": "Here , we provide evidence that structurally related AM251 analogs also have negative impacts on ERR alpha protein levels in a cell - type - dependent manner while having no deleterious actions on ERR gamma .", "entity": [{"entity": "AM251", "entity_type": "Chemical", "pos": [53, 58]}], "task": "NER"}
{"text": "We show that these off - target cellular effects of AM251 are mediated by proteasomal degradation of nuclear ERR alpha .", "entity": [{"entity": "AM251", "entity_type": "Chemical", "pos": [52, 57]}], "task": "NER"}
{"text": "Cell treatment with the nuclear export inhibitor leptomycin B did not prevent AM251 - induced destabilization of ERR alpha protein , whereas proteasome inhibition with MG132 stabilized and maintained its DNA - binding function , indicative of ERR alpha being a target of nuclear proteasomal complexes .", "entity": [{"entity": "leptomycin B", "entity_type": "Chemical", "pos": [49, 61]}, {"entity": "AM251", "entity_type": "Chemical", "pos": [78, 83]}, {"entity": "MG132", "entity_type": "Chemical", "pos": [168, 173]}], "task": "NER"}
{"text": "NativePAGE analysis revealed that ERR alpha formed a ~ 220 - kDa multiprotein nuclear complex that was devoid of ERR gamma and the coregulator peroxisome proliferator - activated receptor gamma coactivator - 1 .", "entity": [], "task": "NER"}
{"text": "AM251 induced SUMO - 2 , 3 incorporation in ERR alpha in conjunction with increased protein kinase C activity , whose activation by phorbol ester also promoted ERR alpha protein loss .", "entity": [{"entity": "AM251", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "phorbol ester", "entity_type": "Chemical", "pos": [132, 145]}], "task": "NER"}
{"text": "Down - regulation of ERR alpha by AM251 or small interfering RNA led to increased mitochondria biogenesis while negatively impacting mitochondrial membrane potential .", "entity": [{"entity": "AM251", "entity_type": "Chemical", "pos": [34, 39]}], "task": "NER"}
{"text": "These results reveal a novel molecular mechanism by which AM251 and related compounds alter mitochondrial physiology through destabilization of ERR alpha .", "entity": [{"entity": "AM251", "entity_type": "Chemical", "pos": [58, 63]}], "task": "NER"}
{"text": "Metformin directly inhibits ghrelin secretion through AMP - activated protein kinase in rat primary gastric cells .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "AMP", "entity_type": "Chemical", "pos": [54, 57]}], "task": "NER"}
{"text": "The antidiabetic drug Metformin causes weight loss in both diabetic and non - diabetic individuals .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [22, 31]}], "task": "NER"}
{"text": "Metformin treatment is also associated with lower circulating levels of the orexigenic hormone ghrelin .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "To test whether Metformin directly affects ghrelin cells , rat primary stomach cells were treated with Metformin and the levels of ghrelin secretion , proghrelin gene expression and activation of adenosine monophosphate - activated protein kinase ( AMPK ) were examined .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "Metformin", "entity_type": "Chemical", "pos": [103, 112]}, {"entity": "adenosine monophosphate", "entity_type": "Chemical", "pos": [196, 219]}], "task": "NER"}
{"text": "Metformin significantly reduced ghrelin secretion and proghrelin mRNA production and both these effects were blocked by co - incubation with the AMPK inhibitor compound C .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "compound C", "entity_type": "Chemical", "pos": [160, 170]}], "task": "NER"}
{"text": "Furthermore , the AMPK activator 5 - amino - 1 - beta - D - ribofuranosyl - imidazole - 4 - carboxamide ( AICAR ) significantly inhibited ghrelin secretion .", "entity": [{"entity": "5 - amino - 1 - beta - D - ribofuranosyl - imidazole - 4 - carboxamide", "entity_type": "Chemical", "pos": [33, 103]}, {"entity": "AICAR", "entity_type": "Chemical", "pos": [106, 111]}], "task": "NER"}
{"text": "Additionally , ghrelin cells were shown to express AMPK .", "entity": [], "task": "NER"}
{"text": "Finally , Metformin treatment caused a significant increase in the level of phosphorylated ( active ) AMPK .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [10, 19]}], "task": "NER"}
{"text": "Our results show that Metformin directly inhibits stomach ghrelin production and secretion through AMPK .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [22, 31]}], "task": "NER"}
{"text": "This reduction in ghrelin secretion may be one of the key components in Metformin ' s mechanism of weight loss .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [72, 81]}], "task": "NER"}
{"text": "A hybrid method employing breakdown anodization and electrophoretic deposition for superhydrophilic surfaces .", "entity": [], "task": "NER"}
{"text": "A fabrication method is developed for superhydrophilic surfaces with high capillary pressure and fast spreading speed .", "entity": [], "task": "NER"}
{"text": "The fabrication method consists of electrophoretic deposition ( EPD ) and breakdown anodization ( BDA ) .", "entity": [], "task": "NER"}
{"text": "Nanopores and micropores were produced on titanium plates by EPD and BDA , respectively .", "entity": [{"entity": "titanium", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "In EPD , TiO ( 2 ) nanoparticles were used to enhance the surface energy and create nanoporous structures , while BDA was employed to produce microporous structures .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [9, 18]}], "task": "NER"}
{"text": "Capillary rise measurements ( CRM ) were utilized to characterize superhydrophilic surfaces in terms of capillary pressure and spreading speed .", "entity": [], "task": "NER"}
{"text": "From CRM , it was revealed that microporous structures play a dominant role in determining transport properties , and nanoporous structures affect local wettability without significantly reducing spreading speed .", "entity": [], "task": "NER"}
{"text": "By combining BDA and EPD into a hybrid method , dual - scale ( nano and micro ) porous structures were produced on titanium plates .", "entity": [{"entity": "titanium", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "The methods presented offer the potential to vary the transport characteristics of superhydrophilic surfaces by altering the nanoscale and microscale features independently .", "entity": [], "task": "NER"}
{"text": "As an example , surfaces with unconventional capillary flows were produced by the hybrid method .", "entity": [], "task": "NER"}
{"text": "This method provides additional opportunities to investigate wetting phenomena while offering a potentially low cost process for industrial applications .", "entity": [], "task": "NER"}
{"text": "Genetic approaches in Drosophila for the study neurodevelopmental disorders .", "entity": [], "task": "NER"}
{"text": "The fruit fly Drosophila melanogaster is one of the premier genetic model organisms used in biomedical research today owing to the extraordinary power of its genetic tool - kit .", "entity": [], "task": "NER"}
{"text": "Made famous by numerous seminal discoveries of basic developmental mechanisms and behavioral genetics , the power of fruit fly genetics is becoming increasingly applied to questions directly relevant to human health .", "entity": [], "task": "NER"}
{"text": "In this review we discuss how Drosophila research is applied to address major questions in neurodevelopmental disorders .", "entity": [], "task": "NER"}
{"text": "Voluntary exercise does not ameliorate spatial learning and memory deficits induced by chronic administration of nandrolone decanoate in rats .", "entity": [{"entity": "nandrolone decanoate", "entity_type": "Chemical", "pos": [113, 133]}], "task": "NER"}
{"text": "Chronic exposure to the anabolic androgenic steroids ( AAS ) nandrolone decanoate ( ND ) in supra - physiological doses is associated with learning and memory impairments .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "nandrolone decanoate", "entity_type": "Chemical", "pos": [61, 81]}], "task": "NER"}
{"text": "Given the well - known beneficial effects of voluntary exercise on cognitive functions , we examined whether voluntary exercise would improve the cognitive deficits induced by chronic administration of ND .", "entity": [], "task": "NER"}
{"text": "We also investigated the effects of ND and voluntary exercise on hippocampal BDNF levels .", "entity": [], "task": "NER"}
{"text": "The rats were randomly distributed into 4 experimental groups : the vehicle - sedentary group , the ND - sedentary group , the vehicle - exercise group , and the ND - exercise group .", "entity": [], "task": "NER"}
{"text": "The vehicle - exercise and the ND - exercise groups were allowed to freely exercise in a running wheel for 15 days .", "entity": [], "task": "NER"}
{"text": "The vehicle - sedentary and the ND - sedentary groups were kept sedentary for the same period .", "entity": [], "task": "NER"}
{"text": "Vehicle or ND injections were started 14 days prior to the voluntary exercise and continued throughout the 15 days of voluntary exercise .", "entity": [], "task": "NER"}
{"text": "After the 15 - day period , the rats were trained and tested on a water maze spatial task using four trials per day for 5 consecutive days followed by a probe trial two days later .", "entity": [], "task": "NER"}
{"text": "Exercise significantly improved performance during both the training and retention of the water maze task , and enhanced hippocampal BDNF .", "entity": [], "task": "NER"}
{"text": "ND impaired spatial learning and memory , and this effect was not rescued by exercise .", "entity": [], "task": "NER"}
{"text": "ND also potentiated the exercise - induced increase in hippocampal BDNF levels .", "entity": [], "task": "NER"}
{"text": "These results seem to indicate that voluntary exercise is unable to improve the disruption of cognitive functions by chronic ND .", "entity": [], "task": "NER"}
{"text": "Moreover , increased levels of BDNF may play a role in ND - induced impairments in learning and memory .", "entity": [], "task": "NER"}
{"text": "The harmful effects of ND and other AAS on learning and memory should be taken into account when athletes decide to use AAS for performance or body image improvement .", "entity": [], "task": "NER"}
{"text": "Rosiglitazone disrupts endosteal bone formation during distraction osteogenesis by local adipocytic infiltration .", "entity": [{"entity": "Rosiglitazone", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Rosiglitazone ( Rosi ) is a drug in the thiazolidinedione class for treatment of type 2 diabetes mellitus ( T2DM ) , which binds and activates PPAR gamma nuclear receptor in fat cells , sensitizing them to insulin .", "entity": [{"entity": "Rosiglitazone", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "Rosi", "entity_type": "Chemical", "pos": [16, 20]}, {"entity": "thiazolidinedione", "entity_type": "Chemical", "pos": [40, 57]}], "task": "NER"}
{"text": "Despite proven antidiabetic efficacy , Rosi therapy may be associated with trabecular bone loss and an increased risk of fractures .", "entity": [{"entity": "Rosi", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "To examine the potential side effects of Rosi treatment on bone formation , we delivered Rosi to mice using a combined model of distraction osteogenesis ( DO ) and type 2 diabetes mellitus ( T2DM ) .", "entity": [{"entity": "Rosi", "entity_type": "Chemical", "pos": [41, 45]}, {"entity": "Rosi", "entity_type": "Chemical", "pos": [89, 93]}], "task": "NER"}
{"text": "DO provides a unique method to isolate the sequence of intramembranous bone formation , an important component of both fracture healing and bone homeostasis .", "entity": [], "task": "NER"}
{"text": "Four groups of n = 6 mice were used to compare the effects of Rosi on bone formation and cellular composition in both diabetic ( Avy / a strain ) and non - diabetic mice ( a / a strain ) .", "entity": [{"entity": "Rosi", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "New bone formation was examined by high resolution radiographs , micro - computed tomography , and histology .", "entity": [], "task": "NER"}
{"text": "Precursor cells in the distraction gap were quantitated using immunohistochemical stains for proliferating cell nuclear antigen .", "entity": [], "task": "NER"}
{"text": "Committed osteoblasts and adipocytes in the gap were identified and quantitated by immunostaining for osteocalcin and FABP4 / aP2 , respectively .", "entity": [], "task": "NER"}
{"text": "The diabetic model developed obesity , hyperglycemia , hyperinsulinemia and insulin resistance , while the control littermates remained lean , normoglycemic and insulin sensitive .", "entity": [], "task": "NER"}
{"text": "Rosi treatment decreased levels of non - fasted glucose and insulin and improved insulin sensitivity in the A ( vy ) / a mice , but had no effect in a / a mice , indicating antidiabetic efficacy of Rosi at the tested dose .", "entity": [{"entity": "Rosi", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "Rosi", "entity_type": "Chemical", "pos": [198, 202]}], "task": "NER"}
{"text": "Despite the diabetic , obese mice having twice the number of fat cells in their marrow than the non - diabetic mice , bone formation using DO was not adversely affected by the diabetes itself .", "entity": [], "task": "NER"}
{"text": "However , Rosi treatment significantly diminished intramembranous endosteal bone formation , while increasing adipogenesis in and adjacent to the distraction gap up to 3 . 5 - to 3 . 8 - fold in both diabetic and non - diabetic models .", "entity": [{"entity": "Rosi", "entity_type": "Chemical", "pos": [10, 14]}], "task": "NER"}
{"text": "This effect was independent of the anti - diabetic therapeutic response .", "entity": [], "task": "NER"}
{"text": "These results raise the question of whether osteoblast precursors are inhibited in their development or actually converted to adipocytic phenotypes , possibly via marrow fat PPAR gamma nuclear receptor .", "entity": [], "task": "NER"}
{"text": "Pharmacological management of ocular hypertension : current approaches and future prospective .", "entity": [], "task": "NER"}
{"text": "Elevated eye pressure is the main risk factor for glaucoma , and intraocular pressure rises when the balance between aqueous humor formation and outflow resistance is compromised .", "entity": [], "task": "NER"}
{"text": "In a normal eye there is a precise tune of aqueous outflow under the fine control of ciliary body and trabecular meshwork .", "entity": [], "task": "NER"}
{"text": "Current pharmacological therapies for lowering the intraocular pressure in glaucoma include increasing aqueous humor outflow and suppression of aqueous humor production .", "entity": [], "task": "NER"}
{"text": "However , most of antiglaucoma drugs currently on the market do not target the trabecular meshwork that represents the site of the pathology .", "entity": [], "task": "NER"}
{"text": "This review focuses on pharmacological management of ocular hypertension with a particular attention to the future pharmacotherapy scenario .", "entity": [], "task": "NER"}
{"text": "Perfluorooctane sulfonate ( PFOS ) affects hormone receptor activity , steroidogenesis , and expression of endocrine - related genes in vitro and in vivo .", "entity": [{"entity": "Perfluorooctane sulfonate", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "PFOS", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "Perfluorooctane sulfonate ( PFOS ) is a widespread and persistent chemical in the environment .", "entity": [{"entity": "Perfluorooctane sulfonate", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "PFOS", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "We investigated the endocrine - disrupting effects of PFOS using a combination of in vitro and in vivo assays .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [54, 58]}], "task": "NER"}
{"text": "Reporter gene assays were used to detect receptor - mediated ( anti - ) estrogenic , ( anti - ) androgenic , and ( anti - ) thyroid hormone activities .", "entity": [{"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [124, 139]}], "task": "NER"}
{"text": "The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone - induced genes in the H295R cell .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "A zebrafish - based short - term screening method was developed to detect the effect of PFOS on endocrine function in vivo .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [88, 92]}], "task": "NER"}
{"text": "The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [45, 53]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [75, 90]}], "task": "NER"}
{"text": "Exposure to PFOS decreased supernatant testosterone ( T ) , increased estradiol ( E2 ) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [39, 51]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "In addition , PFOS increased early thyroid development gene ( hhex and pax8 ) expression in a concentration - dependent manner , decreased steroidogenic enzyme gene ( CYP17 , CYP19a , CYP19b ) expression , and changed the expression pattern of estrogen receptor production genes ( esr1 , esr2b ) after 500 micro g / L PFOS treatment in zebrafish embryos .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [244, 252]}, {"entity": "PFOS", "entity_type": "Chemical", "pos": [318, 322]}], "task": "NER"}
{"text": "These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors , interfering with steroidogenesis , and altering the expression of endocrine - related genes in zebrafish embryo .", "entity": [{"entity": "PFOS", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "Solid - state nanopore detection of protein complexes : applications in healthcare and protein kinetics .", "entity": [], "task": "NER"}
{"text": "Protein conjugation provides a unique look into many biological phenomena and has been used for decades for molecular recognition purposes .", "entity": [], "task": "NER"}
{"text": "In this study , the use of solid - state nanopores for the detection of gp120 - associated complexes are investigated .", "entity": [], "task": "NER"}
{"text": "They exhibit monovalent and multivalent binding to anti - gp120 antibody monomer and dimers .", "entity": [], "task": "NER"}
{"text": "In order to investigate the feasibility of many practical applications related to nanopores , detection of specific protein complexes is attempted within a heterogeneous protein sample , and the role of voltage on complexed proteins is researched .", "entity": [], "task": "NER"}
{"text": "It is found that the electric field within the pore can result in unbinding of a freely translocating protein complex within the transient event durations measured experimentally .", "entity": [], "task": "NER"}
{"text": "The strong dependence of the unbinding time with voltage can be used to improve the detection capability of the nanopore system by adding an additional level of specificity that can be probed .", "entity": [], "task": "NER"}
{"text": "These data provide a strong framework for future protein - specific detection schemes , which are shown to be feasible in the realm of a ' real - world ' sample and an automated multidimensional method of detecting events .", "entity": [], "task": "NER"}
{"text": "Multicenter precision of cortical and trabecular bone quality measures assessed by high - resolution peripheral quantitative computed tomography .", "entity": [], "task": "NER"}
{"text": "High - resolution peripheral quantitative computed tomography ( HR - pQCT ) has recently been introduced as a clinical research tool for in vivo assessment of bone quality .", "entity": [], "task": "NER"}
{"text": "The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools .", "entity": [], "task": "NER"}
{"text": "Our goal was to evaluate the feasibility of pooling data in multicenter HR - pQCT imaging trials .", "entity": [], "task": "NER"}
{"text": "Reproducibility imaging experiments were performed using structure and composition - realistic phantoms constructed from cadaveric radii .", "entity": [], "task": "NER"}
{"text": "Single - center precision was determined by repeat scanning over short - term ( < 72 hours ) , intermediate - term ( 3 - 5 months ) , and long - term intervals ( 28 months ) .", "entity": [], "task": "NER"}
{"text": "Multicenter precision was determined by imaging the phantoms at nine different HR - pQCT centers .", "entity": [], "task": "NER"}
{"text": "Least significant change ( LSC ) and root mean squared coefficient of variation ( RMSCV ) for each interval and across centers was calculated for bone density , geometry , microstructure , and biomechanical parameters .", "entity": [], "task": "NER"}
{"text": "Single - center short - term RMSCVs were < 1 % for all parameters except cortical thickness ( Ct . Th ) ( 1 . 1 % ) , spatial variability in cortical thickness ( Ct . Th . SD ) ( 2 . 6 % ) , standard deviation of trabecular separation ( Tb . Sp . SD ) ( 1 . 8 % ) , and porosity measures ( 6 % to 8 % ) .", "entity": [], "task": "NER"}
{"text": "Intermediate - term RMSCVs were generally not statistically different from short - term values .", "entity": [], "task": "NER"}
{"text": "Long - term variability was significantly greater for all density measures ( 0 . 7 % to 2 . 0 % ; p < 0 . 05 versus short - term ) and several structure measures : cortical thickness ( Ct . Th ) ( 3 . 4 % ; p < 0 . 01 versus short - term ) , cortical porosity ( Ct . Po ) ( 15 . 4 % ; p < 0 . 01 versus short - term ) , and trabecular thickness ( Tb . Th ) ( 2 . 2 % ; p < 0 . 01 versus short - term ) .", "entity": [], "task": "NER"}
{"text": "Multicenter RMSCVs were also significantly higher than short - term values : 2 % to 4 % for density and micro - finite element analysis ( micro FE ) measures ( p < 0 . 0001 ) , 2 . 6 % to 5 . 3 % for morphometric measures ( p < 0 . 001 ) , whereas Ct . Po was 16 . 2 % ( p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "In the absence of subject motion , multicenter precision errors for HR - pQCT parameters were generally less than 5 % .", "entity": [], "task": "NER"}
{"text": "Phantom - based multicenter precision was comparable to previously reported in in vivo single - center precision errors , although this was approximately two to five times worse than ex vivo short - term precision .", "entity": [], "task": "NER"}
{"text": "The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetics and metabolism of [ ( 14 ) C ] anagliptin , a novel dipeptidyl peptidase - 4 inhibitor , in humans .", "entity": [{"entity": "[ ( 14 ) C ] anagliptin", "entity_type": "Chemical", "pos": [35, 58]}], "task": "NER"}
{"text": "1 . The disposition of anagliptin , an orally active , highly selective dipeptidyl peptidase - 4 inhibitor , was investigated after a single oral dose of 100 mg / 1 . 92 MBq [ ( 14 ) C ] anagliptin to six healthy men .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "[ ( 14 ) C ] anagliptin", "entity_type": "Chemical", "pos": [174, 197]}], "task": "NER"}
{"text": "Almost all the dose ( 98 . 2 % ) was recovered within 168 h : 73 . 2 % in urine and 25 . 0 % in faeces .", "entity": [], "task": "NER"}
{"text": "2 . Anagliptin was rapidly absorbed , with peak plasma concentrations of unchanged drug attained at a mean time of 1 . 8 - h postdose .", "entity": [{"entity": "Anagliptin", "entity_type": "Chemical", "pos": [4, 14]}], "task": "NER"}
{"text": "Mean fraction of the dose absorbed was > 73 % .", "entity": [], "task": "NER"}
{"text": "Unchanged drug and a carboxylate metabolite ( M1 ) were the major components in plasma , accounting for 66 . 0 and 23 . 4 % of total plasma radioactivity area under the curve , respectively .", "entity": [{"entity": "carboxylate", "entity_type": "Chemical", "pos": [21, 32]}], "task": "NER"}
{"text": "3 . Anagliptin was incompletely metabolized , with about 50 % dose eliminated as unchanged drug ( 46 . 6 % in urine and 4 . 1 % in faeces ) .", "entity": [{"entity": "Anagliptin", "entity_type": "Chemical", "pos": [4, 14]}], "task": "NER"}
{"text": "Metabolism to M1 accounted for 29 . 2 % of the dose .", "entity": [], "task": "NER"}
{"text": "No other metabolite accounted for > 1 % dose in excreta or yielded measurable systemic exposure .", "entity": [], "task": "NER"}
{"text": "Terminal half - life of anagliptin and M1 was 4 . 37 and 9 . 88 h , respectively .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [24, 34]}], "task": "NER"}
{"text": "Renal clearance of unbound anagliptin and unbound M1 far exceeded glomerular filtration rate , indicating active renal elimination : that might reflect the fact that anagliptin may be a substrate of OAT1 , OAT3 , MDR1 and MRP2 , and M1 a substrate of OAT3 , BCRP , MRP2 and MRP4 .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [27, 37]}, {"entity": "anagliptin", "entity_type": "Chemical", "pos": [166, 176]}], "task": "NER"}
{"text": "Substrate effect on the plasmonic sensing ability of hollow nanoparticles of different shapes .", "entity": [], "task": "NER"}
{"text": "Gold hollow nanospheres ( AuHSs ) and gold hollow nanocubes ( AuHCs ) were synthesized by the galvanic replacement technique using silver nano templates .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [131, 137]}], "task": "NER"}
{"text": "Colloidal AuHSs are found to have a higher sensitivity factor than that of AuHCs .", "entity": [], "task": "NER"}
{"text": "This value decreases for both shapes when the nanoparticles are assembled on a quartz substrate by using the Langmuir - Blodgett technique .", "entity": [{"entity": "quartz", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "AuHSs are observed to have the larger effect .", "entity": [], "task": "NER"}
{"text": "It is observed that as the separation gap between AuHCs nanoparticles decreases , their localized surface plasmon resonance band red shifts more than AuHSs .", "entity": [], "task": "NER"}
{"text": "This is accounted for by the discrete dipole approximation ( DDA ) calculations .", "entity": [], "task": "NER"}
{"text": "The coupling between the plasmon fields of the AuHCs pair is stronger than that between AuHSs pair .", "entity": [], "task": "NER"}
{"text": "Using the DDA calculation , this is found to be due to geometric factors , as well as to the difference in the plasmonic field intensity .", "entity": [], "task": "NER"}
{"text": "The calculation also showed that the plasmon field distributions of both AuHCs and AuHSs were distorted by the quartz substrate in a different manner .", "entity": [{"entity": "quartz", "entity_type": "Chemical", "pos": [111, 117]}], "task": "NER"}
{"text": "It is also observed that the surface - enhanced Raman spectrum of thiophenol is stronger when measured on AuHCs than on AuHSs .", "entity": [{"entity": "thiophenol", "entity_type": "Chemical", "pos": [66, 76]}], "task": "NER"}
{"text": "This is due to the difference in the plasmon field distribution as well as the fact that the AuHCs have a higher scattering / absorption yield ratio .", "entity": [], "task": "NER"}
{"text": "Noncanonical suppression of GH - dependent isoforms of cytochrome P450 by the somatostatin analog octreotide .", "entity": [{"entity": "somatostatin", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "octreotide", "entity_type": "Chemical", "pos": [98, 108]}], "task": "NER"}
{"text": "Octreotide is a potent somatostatin analog therapeutically used to treat several conditions including hyper GH secretion in patients with acromegaly .", "entity": [{"entity": "Octreotide", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "We infused , over 30 s , octreotide into male rats every 12 h for 6 days at levels considerably greater than typical human therapeutic doses .", "entity": [{"entity": "octreotide", "entity_type": "Chemical", "pos": [25, 35]}], "task": "NER"}
{"text": "Unexpectedly , resulting circulating GH profile was characterized by pulses of higher amplitudes , longer durations , and greater total content than normal , but still contained an otherwise male - like episodic secretory profiles .", "entity": [], "task": "NER"}
{"text": "In apparent disaccord , the normally elevated masculine expression levels ( protein and / or mRNA ) of CYP2C11 ( accounting for > 50 % of the total hepatic cytochrome P450 content ) , CYP3A2 , CYP2C7 , and IGF1 , dependent on the episodic GH profile , were considerably downregulated .", "entity": [], "task": "NER"}
{"text": "We explain this contradiction by proposing that the requisite minimal GH - devoid interpulse durations in the masculine profile that solely regulate expression of at least CYP2C11 and IGF1 may be sufficiently reduced to suppress transcription of the hepatic genes .", "entity": [], "task": "NER"}
{"text": "Alternatively , we observed that octreotide infusion may have acted directly on the hepatocytes to induce expression of immune response factors postulated to suppress CYP transcription and / or upregulate expression of several negative regulators ( e . g . phosphatases and SOCS proteins ) of the JAK2 / STAT5B signaling pathway that normally mediates the upregulation of CYP2C11 and IGF1 by the masculine episodic GH profile .", "entity": [{"entity": "octreotide", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "Effects of alpha 7 positive allosteric modulators in murine inflammatory and chronic neuropathic pain models .", "entity": [], "task": "NER"}
{"text": "Agonists and positive allosteric modulators ( PAMs ) of alpha 7 nicotinic acetylcholine receptors ( nAChRs ) are currently being considered as novel therapeutic approaches for managing cognitive deficits in schizophrenia and Alzheimer ' s disease .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [74, 87]}], "task": "NER"}
{"text": "Though alpha 7 agonists were recently found to possess antinociceptive and anti - inflammatory properties in rodent models of chronic neuropathic pain and inflammation , the effects of alpha 7 nAChRs PAMs on chronic pain and inflammation remain largely unknown .", "entity": [], "task": "NER"}
{"text": "The present study investigated whether PAMs , by increasing endogenous cholinergic tone , potentiate alpha 7 nAChRs function to attenuate inflammatory and chronic neuropathic pain in mice .", "entity": [], "task": "NER"}
{"text": "We tested two types of PAMS , type I ( NS1738 ) and type II ( PNU - 120596 ) in carrageenan - induced inflammatory pain and chronic constriction injury ( CCI ) neuropathic pain models .", "entity": [{"entity": "NS1738", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [62, 74]}], "task": "NER"}
{"text": "We found that both NS1738 and PNU - 120596 significantly reduced thermal hyperalgesia , while only PNU - 120596 significantly reduced edema caused by a hind paw infusion of carrageenan .", "entity": [{"entity": "NS1738", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [99, 111]}], "task": "NER"}
{"text": "Importantly , PNU - 120596 reversed established thermal hyperalgesia and edema induced by carrageenan .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [14, 26]}], "task": "NER"}
{"text": "In the CCI model , PNU - 120596 had long - lasting ( up to 6 h ) , dose - dependent anti - hyperalgesic and anti - allodynic effects after a single injection , while NS1738 was inactive .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [19, 31]}, {"entity": "NS1738", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "Systemic administration of the alpha 7 nAChR antagonist MLA reversed PNU - 120596 ' s effects , suggesting the involvement of central and peripheral alpha 7 nAChRs .", "entity": [{"entity": "MLA", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [69, 81]}], "task": "NER"}
{"text": "Furthermore , PNU - 120596 enhanced an ineffective dose of selective agonist PHA - 543613 to produce anti - allodynic effects in the CCI model .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "PHA - 543613", "entity_type": "Chemical", "pos": [77, 89]}], "task": "NER"}
{"text": "Our results indicate that the type II alpha 7 nAChRs PAM PNU - 120596 , but not the type I alpha 7 nAChRs PAM NS1738 , shows significant anti - edematous and anti - allodynic effects in inflammatory and CCI pain models in mice .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [57, 69]}, {"entity": "NS1738", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "Tandem inverse - electron - demand hetero - / retro - Diels - Alder reactions for aromatic nitrogen heterocycle synthesis .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "The merged inverse - electron - demand hetero - Diels - Alder ( ihDA ) / retro - Diels - Alder ( rDA ) reaction sequence can be used to rapidly synthesise highly functionalised nitrogen heteroaromatics .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "The reaction offers many advantages : high atom economy , high levels of regioselectivity , it rarely requires a catalyst and , in some cases , can be performed in the absence of solvent .", "entity": [], "task": "NER"}
{"text": "In this tutorial review we discuss the range of commonly used dienophiles and aza - dienes for this process whilst highlighting the reactivity trends , and illustrating their applications .", "entity": [{"entity": "aza - dienes", "entity_type": "Chemical", "pos": [78, 90]}], "task": "NER"}
{"text": "Use of transgenic GFP reporter strains of the nematode Caenorhabditis elegans to investigate the patterns of stress responses induced by pesticides and by organic extracts from agricultural soils .", "entity": [], "task": "NER"}
{"text": "As a free - living nematode , C . elegans is exposed to various pesticides used in agriculture , as well as to persistent organic residues which may contaminate the soil for long periods .", "entity": [], "task": "NER"}
{"text": "Following on from our previous study of metal effects on 24 GFP - reporter strains representing four different stress - response pathways in C . elegans ( Anbalagan et al . Ecotoxicology 21 : 439 - 455 , 2012 ) , we now present parallel data on the responses of these same strains to several commonly used pesticides .", "entity": [], "task": "NER"}
{"text": "Some of these , like dichlorvos , induced multiple stress genes in a concentration - dependent manner .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "Unusually , endosulfan induced only one gene ( cyp - 34A9 ) to very high levels ( 8 - 10 - fold ) even at the lowest test concentration , with a clear plateau at higher doses .", "entity": [{"entity": "endosulfan", "entity_type": "Chemical", "pos": [12, 22]}], "task": "NER"}
{"text": "Other pesticides , like diuron , did not alter reporter gene expression detectably even at the highest test concentration attainable , while others ( such as glyphosate ) did so only at very high concentrations .", "entity": [{"entity": "diuron", "entity_type": "Chemical", "pos": [24, 30]}, {"entity": "glyphosate", "entity_type": "Chemical", "pos": [158, 168]}], "task": "NER"}
{"text": "We have also used five responsive GFP reporters to investigate the toxicity of soil pore water from two agricultural sites in south - east Spain , designated P74 ( used for cauliflower production , but significantly metal contaminated ) and P73 ( used for growing lettuce , but with only background levels of metals ) .", "entity": [], "task": "NER"}
{"text": "Both soil pore water samples induced all five test genes to varying extents , yet artificial mixtures containing all major metals present had essentially no effect on these same transgenes .", "entity": [], "task": "NER"}
{"text": "Soluble organic contaminants present in the pore water were extracted with acetone and dichloromethane , then after evaporation of the solvents , the organic residues were redissolved in ultrapure water to reconstitute the soluble organic components of the original soil pore water .", "entity": [{"entity": "acetone", "entity_type": "Chemical", "pos": [75, 82]}, {"entity": "dichloromethane", "entity_type": "Chemical", "pos": [87, 102]}], "task": "NER"}
{"text": "These organic extracts induced transgene expression at similar or higher levels than the original pore water .", "entity": [], "task": "NER"}
{"text": "Addition of the corresponding metal mixtures had either no effect , or reduced transgene expression towards the levels seen with soil pore water only .", "entity": [], "task": "NER"}
{"text": "We conclude that the main toxicants present in these soil pore water samples are organic rather than metallic in nature .", "entity": [], "task": "NER"}
{"text": "Organic extracts from a control standard soil ( Lufa 2 . 2 ) had negligible effects on expression of these genes , and similarly several pesticides had little effect on the expression of a constitutive myo - 3 : : GFP transgene .", "entity": [], "task": "NER"}
{"text": "Both the P73 and P74 sites have been treated regularly with ( undisclosed ) pesticides , as permitted under EU regulations , though other ( e . g . industrial ) organic residues may also be present .", "entity": [], "task": "NER"}
{"text": "Mineralocorticoid receptor antagonists and renal involvement in primary aldosteronism : opening of a new era .", "entity": [], "task": "NER"}
{"text": "Primary aldosteronism ( PA ) is one of the commonest forms of curable hypertension , and use of the plasma aldosterone - to - renin ratio as a screening test has led to a more efficient identification of this condition .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [107, 118]}], "task": "NER"}
{"text": "Both animal and human studies have indicated that PA is associated with a variety of cardiovascular and renal complications that reflect the capability of elevated aldosterone to induce tissue damage exceeding that induced by hypertension itself .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [164, 175]}], "task": "NER"}
{"text": "Involvement of the kidney in PA is highly relevant because structural renal damage is associated with less favorable outcome , both in terms of blood pressure response to treatment and possibility to develop progressive renal failure .", "entity": [], "task": "NER"}
{"text": "However , early involvement of the kidney in PA is characterized by functional changes that are largely reversible with treatment .", "entity": [], "task": "NER"}
{"text": "Unilateral adrenalectomy or administration of mineralocorticoid receptor antagonists are the current options for treating an aldosterone - producing adenoma or idiopathic adrenal hyperplasia .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [125, 136]}], "task": "NER"}
{"text": "Both treatments are effective in correcting hypertension and hypokalemia , and currently available information on their capability to prevent deterioration of renal function indicates that both surgery and medical treatment are of considerable value .", "entity": [], "task": "NER"}
{"text": "Immune regulation toward immunomodulation for neuroprotection in glaucoma .", "entity": [], "task": "NER"}
{"text": "Although the immune system functions to preserve and restore tissue homeostasis , accumulating risk factors , prolonged glial activation , and sustained release of pro - inflammatory mediators in glaucoma may lead to a failure in the regulation of stress - induced immune response , and innate immune cells , autoreactive T cells , autoantibodies , and excess complement attack may exhibit potent stimuli that harm retinal ganglion cell somas , axons , and synapses .", "entity": [], "task": "NER"}
{"text": "Identification of the cellular and molecular components of immune response pathways can provide immunomodulatory treatment strategies to attenuate neuroinflammation , protect neural tissue from collateral injury , and enhance endogenous recovery processes .", "entity": [], "task": "NER"}
{"text": "This review highlights the current knowledge of molecular mechanisms regulating neuroinflammation in glaucoma .", "entity": [], "task": "NER"}
{"text": "Bis ( 12 ) - hupyridone , a novel acetylcholinesterase inhibitor , protects against glutamate - induced neuronal excitotoxicity via activating alpha 7 nicotinic acetylcholine receptor / phosphoinositide 3 - kinase / Akt cascade .", "entity": [{"entity": "Bis ( 12 ) - hupyridone", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [84, 93]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [161, 174]}, {"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [186, 202]}], "task": "NER"}
{"text": "Bis ( 12 ) - hupyridone ( B12H ) , derived from the Chinese medicinal component huperzine A , was originally designed as a novel acetylcholinesterase ( AChE ) inhibitor .", "entity": [{"entity": "Bis ( 12 ) - hupyridone", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "B12H", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "huperzine A", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "In this paper , we report that B12H ( 24 - h pretreatment ) effectively blocked glutamate - induced neuronal excitotoxicity in cerebellar granule neurons ( CGNs ) .", "entity": [{"entity": "B12H", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [80, 89]}], "task": "NER"}
{"text": "However , the huge discrepancy between the EC50 value and IC50 value of B12H , to protect against neuronal toxicity ( 0 . 09 mu M ) and to block the NMDA receptor ( 21 . 8 mu M ) respectively , suggests that the neuroprotection of B12H might be not primarily due to the blockade of the NMDA receptor .", "entity": [{"entity": "B12H", "entity_type": "Chemical", "pos": [72, 76]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [149, 153]}, {"entity": "B12H", "entity_type": "Chemical", "pos": [231, 235]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [286, 290]}], "task": "NER"}
{"text": "Pretreatment by specific antagonists of alpha7 - nicotinic acetylcholine receptor ( alpha 7nAChR ) , but not muscarinic acetylcholine receptor ( mAChR ) or alpha 4 beta 2nAChR , decreased the neuroprotection of B12H .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [59, 72]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [120, 133]}, {"entity": "B12H", "entity_type": "Chemical", "pos": [211, 215]}], "task": "NER"}
{"text": "The neuroprotection of B12H could also be abolished by the pretreatment of specific PI3 - K inhibitors .", "entity": [{"entity": "B12H", "entity_type": "Chemical", "pos": [23, 27]}], "task": "NER"}
{"text": "Furthermore , B12H restored the suppressed activation of the Akt pathway caused by glutamate as evidenced by the decreased expressions of pSer473 - Akt and pSer9 - GSK3 beta .", "entity": [{"entity": "B12H", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [83, 92]}, {"entity": "pSer473", "entity_type": "Chemical", "pos": [138, 145]}, {"entity": "pSer9", "entity_type": "Chemical", "pos": [156, 161]}], "task": "NER"}
{"text": "All these results suggest that B12H substantially protected CGNs against glutamate - induced neuronal excitotoxicity via activating alpha 7nAChR / PI3 - K / Akt cascade .", "entity": [{"entity": "B12H", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production .", "entity": [], "task": "NER"}
{"text": "Inflammatory mediators are thought to be involved in the systemic and local immune response induced by the Tityus serrulatus scorpion envenomation .", "entity": [], "task": "NER"}
{"text": "New functional aspects of lipid mediators have recently been described .", "entity": [], "task": "NER"}
{"text": "Here , we examine the unreported role of lipid mediators in cell recruitment to the peritoneal cavity after an injection with Ts2 or Ts6 toxins isolated from the T . serrulatus scorpion venom .", "entity": [], "task": "NER"}
{"text": "In this report , we demonstrate that following a single intraperitoneal ( i . p . ) injection of Ts2 or Ts6 ( 250 mu g / kg ) in mice , there was an induction of leukocytosis with a predominance of neutrophils observed at 4 , 24 , 48 and 96 h .", "entity": [], "task": "NER"}
{"text": "Moreover , total protein , leukotriene ( LT ) B ( 4 ) , prostaglandin ( PG ) E ( 2 ) and pro - inflammatory cytokine levels were increased .", "entity": [{"entity": "leukotriene ( LT ) B ( 4 )", "entity_type": "Chemical", "pos": [27, 53]}, {"entity": "prostaglandin ( PG ) E ( 2 )", "entity_type": "Chemical", "pos": [56, 84]}], "task": "NER"}
{"text": "We also observed an increase of regulatory cytokines , including interleukin ( IL ) - 10 , after the Ts2 injection .", "entity": [], "task": "NER"}
{"text": "Finally , we observed that Ts2 or Ts6 injection in 5 - lipoxygenase ( LO ) deficient mice and in wild type ( WT ) 129sv mice pre - treated with LTs and PGs inhibitors ( MK - 886 and celecoxib , respectively ) a reduction the influx of leukocytes occurs in comparison to WT .", "entity": [{"entity": "MK - 886", "entity_type": "Chemical", "pos": [169, 177]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [182, 191]}], "task": "NER"}
{"text": "The recruitment of these cells demonstrated a phenotype characteristic of neutrophils , macrophages , CD4 and CD8 lymphocytes expressing GR1 + , F4 / 80 + , CD3 + / CD4 + and CD3 + / CD8 + , respectively .", "entity": [], "task": "NER"}
{"text": "In conclusion , our data demonstrate that Ts2 and Ts6 induce inflammation by mechanisms dependent on lipid mediators and cytokine production .", "entity": [], "task": "NER"}
{"text": "Ts2 may play a regulatory role whereas Ts6 exhibits pro - inflammatory activity exclusively .", "entity": [], "task": "NER"}
{"text": "Xanthohumol induces phase II enzymes via Nrf2 in human hepatocytes in vitro .", "entity": [{"entity": "Xanthohumol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The aim of this study was to investigate whether xanthohumol may exert chemoprotective activity through the modulation of the nuclear factor erythroid - 2 - related factor 2 ( Nrf2 ) pathway in immortalized normal THLE - 2 hepatocytes and a hepatocellular carcinoma HepG2 cell line .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Cells were incubated in the presence of xanthohumol and the activation of Nrf2 and expression of genes controlled by this transcription factor were evaluated .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [40, 51]}], "task": "NER"}
{"text": "Additionally , p53 level was assessed .", "entity": [], "task": "NER"}
{"text": "Xanthohumol increased the expression and led to the activation of Nrf2 in both cell lines .", "entity": [{"entity": "Xanthohumol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "However , in contrast to normal cells the expression of genes controlled by this transcription factor was not affected in HepG2 cells , except for GSTA and GSTP .", "entity": [], "task": "NER"}
{"text": "Xanthohumol , beside the induction of GSTs and HO - 1 , significantly elevated NQO1 expression in concert with p53 level in normal hepatocytes .", "entity": [{"entity": "Xanthohumol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The activation of Nrf2 pathway and subsequently phase II enzymes in concert with p53 induction in normal hepatocytes may account for the molecular mechanism of the chemopreventive activity of xanthohumol .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [192, 203]}], "task": "NER"}
{"text": "On the other hand its cytotoxicity towards HCC cells shown in this study indicates that it may also be considered as potentially chemotherapeutic .", "entity": [], "task": "NER"}
{"text": "Deriving an explicit hepatic clearance equation accounting for plasma protein binding and hepatocellular uptake .", "entity": [], "task": "NER"}
{"text": "High throughput in vitro biochemical and cell - based assays have the promise to provide more mechanism - based assessments of the adverse effects of large numbers of chemicals .", "entity": [], "task": "NER"}
{"text": "One of the most challenging hurdles for interpreting in vitro toxicity findings is the need for reverse dosimetry tools that estimate the exposures that will give concentrations in vivo similar to the active concentrations in vitro .", "entity": [], "task": "NER"}
{"text": "Recent experience using IVIVE approaches to estimate in vivo pharmacokinetics ( Wetmore et al . , 2012 ) identified the need to develop a hepatic clearance equation that explicitly accounted for a broader set of protein binding and membrane transport processes and did not depend on a well - mixed description of the liver compartment .", "entity": [], "task": "NER"}
{"text": "Here we derive an explicit steady - state hepatic clearance equation that includes these factors .", "entity": [], "task": "NER"}
{"text": "In addition to the derivation , we provide simple computer code to calculate steady - state extraction for any combination of blood flow , membrane transport processes and plasma protein - chemical binding rates .", "entity": [], "task": "NER"}
{"text": "This expanded equation provides a tool to estimate hepatic clearance for a more diverse array of compounds .", "entity": [], "task": "NER"}
{"text": "Growth differentiation factor 15 stimulates rapamycin - sensitive ovarian cancer cell growth and invasion .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "Identification of novel molecular markers and therapeutic targets may improve survival rates for patients with ovarian cancer .", "entity": [], "task": "NER"}
{"text": "In the current study , immunohistochemical ( IHC ) analysis of two human ovarian tumor tissue arrays showed high staining for GDF15 in a majority of tissues .", "entity": [], "task": "NER"}
{"text": "Exogenous stimulation of ovarian cancer cell lines with recombinant human GDF15 ( rhGDF15 ) or stable over - expression of a GDF15 expression plasmid promoted anchorage - independent growth , increased invasion , and up - regulation of matrix metalloproteinases ( MMPs ) and vascular endothelial growth factor ( VEGF ) .", "entity": [], "task": "NER"}
{"text": "MMP inhibition suppressed GDF15 - mediated invasion .", "entity": [], "task": "NER"}
{"text": "In addition , IHC analysis of human ovarian tumor tissue arrays indicated that GDF15 expression correlated significantly with high MMP2 and MMP9 expression .", "entity": [], "task": "NER"}
{"text": "Exogenous and endogenous GDF15 over - expression stimulated phosphorylation of p38 , Erk1 / 2 , and Akt .", "entity": [], "task": "NER"}
{"text": "Pharmacologic inhibition of p38 , MEK , or PI3K suppressed GDF15 - stimulated growth .", "entity": [], "task": "NER"}
{"text": "Further , proliferation , growth , and invasion of GDF15 stable clones were blocked by rapamycin .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [87, 96]}], "task": "NER"}
{"text": "IHC analysis demonstrated significant correlation between GDF15 expression and phosphorylation of mTOR .", "entity": [], "task": "NER"}
{"text": "Finally , knockdown of endogenous GDF15 or neutralization of secreted GDF15 suppressed invasion and growth of a GDF15 - over - expressing ovarian cancer cell line .", "entity": [], "task": "NER"}
{"text": "These data indicate that GDF15 over - expression , which occurred in a majority of human ovarian cancers , promoted rapamycin - sensitive invasion and growth of ovarian cancer cells .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [116, 125]}], "task": "NER"}
{"text": "Inhibition of mTOR may be an effective therapeutic strategy for ovarian cancers that over - express GDF15 .", "entity": [], "task": "NER"}
{"text": "Future studies should examine GDF15 as a novel molecular target for blocking ovarian cancer progression .", "entity": [], "task": "NER"}
{"text": "Solid - state dependent dissolution and oral bioavailability of piroxicam in rats .", "entity": [{"entity": "piroxicam", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "The aim of this study was to gain understanding about the effects of different solid - state forms of a poorly water - soluble piroxicam on drug dissolution and oral bioavailability in rats .", "entity": [{"entity": "piroxicam", "entity_type": "Chemical", "pos": [127, 136]}], "task": "NER"}
{"text": "Three different solid - state forms of piroxicam were studied : anhydrate I ( AH ) , monohydrate ( MH ) , and amorphous form in solid dispersion ( SD ) .", "entity": [{"entity": "piroxicam", "entity_type": "Chemical", "pos": [39, 48]}], "task": "NER"}
{"text": "In addition , the effect of a new polymeric excipient Soluplus (R) ( polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer ) on oral bioavailability of piroxicam was investigated .", "entity": [{"entity": "Soluplus", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer", "entity_type": "Chemical", "pos": [69, 148]}, {"entity": "piroxicam", "entity_type": "Chemical", "pos": [178, 187]}], "task": "NER"}
{"text": "Significant differences in the dissolution and oral bioavailability were found between the solid - state forms of piroxicam .", "entity": [{"entity": "piroxicam", "entity_type": "Chemical", "pos": [114, 123]}], "task": "NER"}
{"text": "Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid - state transformation to MH in the dissolution medium .", "entity": [{"entity": "piroxicam", "entity_type": "Chemical", "pos": [10, 19]}], "task": "NER"}
{"text": "Despite the presence of solid - state transformation , SD exhibited the highest rate and extent of oral absorption in rats .", "entity": [], "task": "NER"}
{"text": "Oral bioavailability of other two solid - state forms decreased in the order AH and MH .", "entity": [], "task": "NER"}
{"text": "The use of Soluplus (R) was found to enhance the dissolution and oral bioavailability of piroxicam in rats .", "entity": [{"entity": "Soluplus", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "piroxicam", "entity_type": "Chemical", "pos": [89, 98]}], "task": "NER"}
{"text": "The present study shows the importance of solid - state form selection for oral bioavailability of a poorly water - soluble drug .", "entity": [], "task": "NER"}
{"text": "Fetal muscle - type nicotinic acetylcholine receptor activation in TE - 671 cells and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [30, 43]}, {"entity": "piperidine alkaloid", "entity_type": "Chemical", "pos": [173, 192]}, {"entity": "coniine", "entity_type": "Chemical", "pos": [193, 200]}], "task": "NER"}
{"text": "Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor ( nAChR ) agonist found in poison hemlock ( Conium maculatum L . ) .", "entity": [{"entity": "Coniine", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "piperidine alkaloid", "entity_type": "Chemical", "pos": [37, 56]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [71, 84]}], "task": "NER"}
{"text": "Coniine teratogenicity is hypothesized to be attributable to the binding , activation , and prolonged desensitization of fetal muscle - type nAChR , which results in the complete inhibition of fetal movement .", "entity": [{"entity": "Coniine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "However , pharmacological evidence of coniine actions at fetal muscle - type nAChR is lacking .", "entity": [{"entity": "coniine", "entity_type": "Chemical", "pos": [38, 45]}], "task": "NER"}
{"text": "The present study compared ( - ) - coniine , ( + ) - coniine , and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE - 671 cells that express fetal muscle - type nAChR .", "entity": [{"entity": "( - ) - coniine", "entity_type": "Chemical", "pos": [27, 42]}, {"entity": "( + ) - coniine", "entity_type": "Chemical", "pos": [45, 60]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "Furthermore , alpha - conotoxins ( CTx ) EI and GI were used to antagonize the actions of ( + ) - and ( - ) - coniine in TE - 671 cells .", "entity": [{"entity": "( + ) - and ( - ) - coniine", "entity_type": "Chemical", "pos": [90, 117]}], "task": "NER"}
{"text": "( - ) - Coniine was more effective at eliciting electrical changes in TE - 671 cells and inhibiting fetal movement than was ( + ) - coniine , suggesting stereoselectivity by the receptor .", "entity": [{"entity": "( - ) - Coniine", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "( + ) - coniine", "entity_type": "Chemical", "pos": [124, 139]}], "task": "NER"}
{"text": "The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model , suggesting agonist specificity for the inhibition of fetal movement .", "entity": [{"entity": "pyridine alkaloid", "entity_type": "Chemical", "pos": [4, 21]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [22, 30]}], "task": "NER"}
{"text": "Low concentrations of both CTxs potentiated the TE - 671 cell response and higher concentrations of CTx EI , and GI antagonized the actions of both coniine enantiomers demonstrating concentration - dependent coagonism and selective antagonism .", "entity": [{"entity": "coniine", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "These results provide pharmacological evidence that the piperidine alkaloid coniine is acting at fetal muscle - type nAChR in a concentration - dependent manner .", "entity": [{"entity": "piperidine alkaloid", "entity_type": "Chemical", "pos": [56, 75]}, {"entity": "coniine", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "Review and discussion of tubular biomarkers in the diagnosis and management of diabetic nephropathy .", "entity": [], "task": "NER"}
{"text": "The prevalence of diabetic nephropathy has tremendously increased with the relentless rise in the incidence of diabetes over the last couple decades .", "entity": [], "task": "NER"}
{"text": "Diabetic nephropathy is a leading cause of morbidity and mortality , and it invariably leads to an end - stage renal disease ( ESRD ) .", "entity": [], "task": "NER"}
{"text": "In an effort to delay the onset of ESRD systematic screening and appropriate management are needed to evaluate the progression of renal damage in diabetic nephropathy .", "entity": [], "task": "NER"}
{"text": "The reliability of current tests in predicting the onset , progression and response to various regimens for diabetic nephropathy is still under debate ; and it has engendered a search for more sensitive and specific urinary biomarkers , especially those reflective of tubular dysfunctions .", "entity": [], "task": "NER"}
{"text": "It is well - known that there is a good correlation between the degree of damage to the tubulo - interstitial compartment and the deterioration of renal functions .", "entity": [], "task": "NER"}
{"text": "In view of this , the utility of urinary biomarkers , reflective of tubular injury , reported in the literature is discussed in this brief review .", "entity": [], "task": "NER"}
{"text": "Density functional conformational study of 2 - O - sulfated 3 , 6 anhydro - alpha - D - galactose and of neo - kappa - and iota - carrabiose molecules in gas phase and water .", "entity": [{"entity": "2 - O - sulfated 3 , 6 anhydro - alpha - D - galactose", "entity_type": "Chemical", "pos": [43, 97]}, {"entity": "neo - kappa - and iota - carrabiose", "entity_type": "Chemical", "pos": [105, 140]}], "task": "NER"}
{"text": "We examined the conformational preferences of the 2 - O - sulfated - 3 , 6 - alpha - D - anhydrogalactose ( compound I ) and two 1 , 3 linked disaccharides constituting - kappa or iota - carrageenans using density functional and ab initio methods in gas phase and aqueous solution .", "entity": [{"entity": "2 - O - sulfated - 3 , 6 - alpha - D - anhydrogalactose", "entity_type": "Chemical", "pos": [50, 105]}, {"entity": "disaccharides", "entity_type": "Chemical", "pos": [142, 155]}], "task": "NER"}
{"text": "Systematic modifications of two torsion angles leading to 324 and 144 starting geometries for the compound I and each disaccharide were used to generate adiabatic maps using B3LYP / 6 - 31G ( d ) .", "entity": [{"entity": "disaccharide", "entity_type": "Chemical", "pos": [118, 130]}], "task": "NER"}
{"text": "The lower energy conformers were then fully optimized using B3LYP , B3PW91 and MP2 with several basis sets .", "entity": [], "task": "NER"}
{"text": "Overall , we discuss the impact of full relaxation on the energy and structure of the dominant conformations , present the performance comparison with previous molecular mechanics calculations if available , and determine whether our results are impacted , when polarization and diffuse functions are added to the 6 - 31G ( d ) basis set , or when the MP2 level of theory is used .", "entity": [], "task": "NER"}
{"text": "Effects of silver nanoparticles on the liver and hepatocytes in vitro .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [11, 17]}], "task": "NER"}
{"text": "With the increasing use and incorporation of nanoparticles ( NPs ) into consumer products , screening for potential toxicity is necessary to ensure customer safety .", "entity": [], "task": "NER"}
{"text": "NPs have been shown to translocate to the bloodstream following inhalation and ingestion , and such studies demonstrate that the liver is an important organ for accumulation .", "entity": [], "task": "NER"}
{"text": "Silver ( Ag ) NPs are highly relevant for human exposure due to their use in food contact materials , dietary supplements , and antibacterial wound treatments .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [9, 11]}], "task": "NER"}
{"text": "Due to the large number of different NPs already used in various products and being developed for new applications , it is essential that relevant , quick , and cheap methods of in vitro risk assessment suitable for these new materials are established .", "entity": [], "task": "NER"}
{"text": "Therefore , this study used a simple hepatocytes model combined with an in vivo injection model to simulate the passage of a small amount of NPs into the bloodstream following exposure , e . g . , via ingestion or inhalation , and examined the potential of Ag NPs of 20 nm diameter to cause toxicity , inflammation , and oxidative stress in the liver following in vivo exposures of female Wistar rats via iv injection to 50 mu g of NPs and in vitro exposures using the human hepatocyte cell line C3A .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [257, 259]}], "task": "NER"}
{"text": "We found that Ag NPs were highly cytotoxic to hepatocytes ( LC ( 50 ) lactate dehydrogenase : 2 . 5 mu g / cm ( 2 ) ) and affected hepatocyte homeostasis by reducing albumin release .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [14, 16]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "At sublethal concentrations with normal cell or tissue morphology , Ag NPs were detected in cytoplasm and nuclei of hepatocytes .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [68, 70]}], "task": "NER"}
{"text": "We observed similar effects of Ag NPs on inflammatory mediator expression in vitro and in vivo with increase of interleukin - 8 ( IL - 8 ) / macrophage inflammatory protein 2 , IL - 1RI , and tumor necrosis factor - alpha expression in both models and increased IL - 8 protein release in vitro .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [31, 33]}], "task": "NER"}
{"text": "This article presents evidence of the potential toxicity and inflammogenic potential of Ag NPs in the liver following ingestion .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [88, 90]}], "task": "NER"}
{"text": "In addition , the similarities between in vitro and in vivo responses are striking and encouraging for future reduction , refinement , and replacement of animal studies by the use of hepatocyte cell lines in particle risk assessment .", "entity": [], "task": "NER"}
{"text": "Comment on real - time observation on dynamic growth / dissolution of conductive filaments in oxide - electrolyte - based ReRAM .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [94, 99]}], "task": "NER"}
{"text": "Filament formation and dissolution in the system Ag ( Cu ) / ZrO ( 2 ) / Pt were observed by Liu et al .", "entity": [{"entity": "Ag ( Cu )", "entity_type": "Chemical", "pos": [49, 58]}, {"entity": "ZrO ( 2 )", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [73, 75]}], "task": "NER"}
{"text": "[ Adv . Mater . 2012 , 24 , 1844 ] .", "entity": [], "task": "NER"}
{"text": "Their explanation of the phenomena is shown here to be inappropriate .", "entity": [], "task": "NER"}
{"text": "Various situations , including the \" bipolar electrode \" shown in the figure , are considered and the difference between the behavior in electrochemical metallization memories ( ECMs ) and valence change memories ( VCMs ) outlined .", "entity": [], "task": "NER"}
{"text": "Of crucial importance for distinguishing ECM from VCM behavior , that is , the effects of cation and anion migration , is the choice of the solid materials used to transport metal cations .", "entity": [], "task": "NER"}
{"text": "A possible explanation of the phenomena is proposed .", "entity": [], "task": "NER"}
{"text": "Extracellular loop II modulates GTP sensitivity of the prostaglandin EP3 receptor .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [32, 35]}, {"entity": "prostaglandin", "entity_type": "Chemical", "pos": [55, 68]}], "task": "NER"}
{"text": "Unlike the majority of G protein - coupled receptors , the prostaglandin E ( 2 ) ( PGE ( 2 ) ) E - prostanoid 3 ( EP3 ) receptor binds agonist with high affinity that is insensitive to the presence of guanosine 5 [ prime ] - O - ( 3 - thio ) triphosphate ( GTP gamma S ) .", "entity": [{"entity": "prostaglandin E ( 2 )", "entity_type": "Chemical", "pos": [59, 80]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [83, 92]}, {"entity": "E - prostanoid", "entity_type": "Chemical", "pos": [95, 109]}, {"entity": "guanosine 5 [ prime ] - O - ( 3 - thio ) triphosphate", "entity_type": "Chemical", "pos": [201, 254]}, {"entity": "GTP gamma S", "entity_type": "Chemical", "pos": [257, 268]}], "task": "NER"}
{"text": "We report the identification of mutations that confer GTP gamma S sensitivity to agonist binding .", "entity": [{"entity": "GTP gamma S", "entity_type": "Chemical", "pos": [54, 65]}], "task": "NER"}
{"text": "Seven point mutations were introduced into the conserved motif in the second extracellular loop ( ECII ) of EP3 , resulting in acquisition of GTP - sensitive agonist binding .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "One receptor mutation W203A was studied in detail .", "entity": [], "task": "NER"}
{"text": "Loss of agonist binding was observed on intact human embryonic kidney 293 cells expressing the W203A receptor , conditions where high GTP levels are present ; however , high affinity binding [ ( 3 ) H ] PGE ( 2 ) was observed in broken cell preparations washed free of GTP .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "[ ( 3 ) H ] PGE ( 2 )", "entity_type": "Chemical", "pos": [191, 212]}, {"entity": "GTP", "entity_type": "Chemical", "pos": [269, 272]}], "task": "NER"}
{"text": "The [ ( 3 ) H ] PGE ( 2 ) binding of W203A in broken cell membrane fractions was inhibited by addition of GTP gamma S ( IC ( 50 ) 21 +/- 1 . 8 nM ) .", "entity": [{"entity": "[ ( 3 ) H ] PGE ( 2 )", "entity_type": "Chemical", "pos": [4, 25]}, {"entity": "GTP gamma S", "entity_type": "Chemical", "pos": [106, 117]}], "task": "NER"}
{"text": "Taken together , these results suggest that the wild - type EP3 receptor displays unusual characteristics of the complex coupled equilibria between agonist - receptor and receptor - G protein interaction .", "entity": [], "task": "NER"}
{"text": "Moreover , mutation of ECII can alter this coupled equilibrium from GTP - insensitive agonist binding to more conventional GTP - sensitive binding .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [68, 71]}, {"entity": "GTP", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "This suggests that for the mutant receptors , ECII plays a critical role in linking the agonist bound receptor conformation to the G protein nucleotide bound state .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [141, 151]}], "task": "NER"}
{"text": "Mesoscopic model parametrization of hydrogen bonds and stacking interactions of RNA from melting temperatures .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Information about molecular interactions in DNA can be obtained from experimental melting temperature data by using mesoscopic statistical physics models .", "entity": [], "task": "NER"}
{"text": "Here , we extend the technique to RNA and show that the new parameters correctly reproduce known properties such as the stronger hydrogen bonds of AU base pairs .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [129, 137]}], "task": "NER"}
{"text": "We also were able to calculate a complete set of elastic constants for all 10 irreducible combinations of nearest neighbours ( NNs ) .", "entity": [], "task": "NER"}
{"text": "We believe that this is particularly useful as experimentally derived information about RNA elasticity is relatively scarce .", "entity": [], "task": "NER"}
{"text": "The melting temperature prediction using the present model improves over those from traditional NN model , providing thus an alternative way to calculate these temperatures for RNA .", "entity": [], "task": "NER"}
{"text": "Additionally , we calculated the site - dependent base pair oscillation to explain why RNA shows larger oscillation amplitudes despite having stronger AU hydrogen bonds .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [154, 162]}], "task": "NER"}
{"text": "Carbaryl exposure and recovery modify the interrenal and thyroidal activities and the mitochondria - rich cell function in the climbing perch Anabas testudineus Bloch .", "entity": [{"entity": "Carbaryl", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "We examined the effects of carbaryl ( 1 - naphthyl methylcarbamate ; sevin ) , a carbamate pesticide , on interrenal and thyroid activities and mitochondrial rich ( MR ) cell function in climbing perch to understand the physiological basis of toxicity acclimation in this fish to the chemical stressor .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "1 - naphthyl methylcarbamate", "entity_type": "Chemical", "pos": [38, 66]}, {"entity": "sevin", "entity_type": "Chemical", "pos": [69, 74]}, {"entity": "carbamate", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "Carbaryl exposure ( 5 - 20 mg L ( - 1 ) ) for 48 h increased cortisol and glucose , but decreased the T ( 3 ) level without affecting T ( 4 ) concentration in the plasma .", "entity": [{"entity": "Carbaryl", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "cortisol", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "These responses of the carbaryl - exposed fish were nullified and a rise in plasma T ( 4 ) occurred in these fish when they were kept for 96 h recovery in clean water .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "A tight plasma mineral control was indicated in the carbaryl - exposed fish as reflected by the unchanged plasma Na , K , Ca and inorganic phosphate levels .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "Na", "entity_type": "Chemical", "pos": [113, 115]}, {"entity": "K", "entity_type": "Chemical", "pos": [118, 119]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [122, 124]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [139, 148]}], "task": "NER"}
{"text": "The ouabain - sensitive Na ( + ) , K ( + ) - ATPase activity showed an increase in the gills but the intestinal and renal tissues showed little response to carbaryl treatment .", "entity": [{"entity": "ouabain", "entity_type": "Chemical", "pos": [4, 11]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "carbaryl", "entity_type": "Chemical", "pos": [156, 164]}], "task": "NER"}
{"text": "However , substantial increases in the intestinal and renal Na ( + ) , K ( + ) - ATPase activities occurred in the recovery fish .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "The MR cells in the branchial epithelia showed a strong Na ( + ) , K ( + ) - ATPase immunoreactivity to carbaryl treatment indicating an activated MR cell function .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "carbaryl", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "The numerical MR cell density remained unchanged , but stretching of secondary gill lamellae as part of gill remodeling occurred during carbaryl exposure .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "The increased surface of these lamellae with abundant MR cells as a result of its migration into the lamellar surface points to marked structural and functional modifications of these cells in the carbaryl - treated fish which is likely to a target for carbaryl action .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [197, 205]}, {"entity": "carbaryl", "entity_type": "Chemical", "pos": [253, 261]}], "task": "NER"}
{"text": "The rise in plasma T ( 4 ) and the restoration of normal branchial epithelia in the recovery fish indicate a thyroidal involvement in the recovery response and survival .", "entity": [], "task": "NER"}
{"text": "Our data thus provide evidence that carbaryl exposure and its recovery evoke interrenal and thyroid disruption in this fish leading to a modified osmotic response including an altered MR cell function .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Liquid crystal pump .", "entity": [], "task": "NER"}
{"text": "We report a dielectrically actuated liquid crystal ( LC ) pump .", "entity": [], "task": "NER"}
{"text": "A small volume of LC forms a pillar - like droplet in a cylindrical hole which partially touches the bottom substrate with embedded interdigitated electrodes .", "entity": [], "task": "NER"}
{"text": "By applying a voltage , the LC droplet can be largely stretched along the electrode direction by the generated dielectric force , which in turn exerts a pressure to displace a small volume of fluid on the opposite side of the chamber .", "entity": [], "task": "NER"}
{"text": "Once the voltage is removed , the LC droplet returns to its initial state .", "entity": [], "task": "NER"}
{"text": "The LC droplet with such a reciprocating movement behaves like a pump .", "entity": [], "task": "NER"}
{"text": "In this work , the actuation mechanism of the LC pump is presented and the performance evaluated experimentally .", "entity": [], "task": "NER"}
{"text": "Our LC pump has the following advantages : simple structure , easy fabrication , compact size , high precision , low power consumption , and relatively fast response time .", "entity": [], "task": "NER"}
{"text": "It is promising for applications in lens actuators , biotechnology , drug delivery , and other lab - on - a - chip devices .", "entity": [], "task": "NER"}
{"text": "Costs of living in metal polluted areas : respiration rate of the ground beetle Pterostichus oblongopunctatus from two gradients of metal pollution .", "entity": [], "task": "NER"}
{"text": "To address the question about costs of living in polluted areas , biomarkers linked to metabolism were measured in Pterostichus oblongopunctatus ( Coleoptera : Carabidae ) collected along two metal - pollution gradients in the vicinity of the two largest Polish zinc smelters : ' Boles l aw ' and ' Miasteczko S l a skie ' in southern Poland .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [262, 266]}], "task": "NER"}
{"text": "Both gradients covered a broad range of Zn and Cd concentrations in the humus layer ( 109 - 6151 and 1 . 48 - 71 . 4 mg kg ( - 1 ) , respectively ) and body metal concentrations increased with increasing soil metal concentrations .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [47, 49]}], "task": "NER"}
{"text": "The whole - organism respiration rate was measured as oxygen consumption with Micro - Oxymax respirometer , and cellular energy consumption - as the activity of electron transport system , which is linked to cellular respiration rate .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [54, 60]}], "task": "NER"}
{"text": "The significant increase in the whole - organism respiration rate with the body metal concentration was found when taking into account other factors such as body mass , gradient ( or year of sampling as the beetles were collected on the gradients in different years ) and the interactions : body metal concentrations x collection date , body metal concentrations x body mass , and body mass x gradient / sampling year .", "entity": [], "task": "NER"}
{"text": "However , no relationships between metal concentrations in soil or body metal concentrations and the whole - organism or cellular respiration rate could be detected when using mean values per site , underlining the crucial importance of incorporating individual variability in such analyses .", "entity": [], "task": "NER"}
{"text": "The observed increase of the whole - organism respiration rate with increasing body contamination with metals suggests that P . oblongopunctatus incurs energetic expenditures resulting from the necessity to facilitate metal elimination or repair of toxicant - induced damage .", "entity": [], "task": "NER"}
{"text": "Pharmacologic properties , metabolism , and disposition of linaclotide , a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation .", "entity": [{"entity": "linaclotide", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "Linaclotide , a potent guanylate cyclase C agonist , is a therapeutic peptide approved in the United States for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation .", "entity": [{"entity": "Linaclotide", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "guanylate", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "We present for the first time the metabolism , degradation , and disposition of linaclotide in animals and humans .", "entity": [{"entity": "linaclotide", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM - 419447 ( CCEYCCNPACTGC ) , which contributes to the pharmacologic effects of linaclotide .", "entity": [{"entity": "linaclotide", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "MM - 419447", "entity_type": "Chemical", "pos": [136, 147]}, {"entity": "linaclotide", "entity_type": "Chemical", "pos": [218, 229]}], "task": "NER"}
{"text": "Systemic exposure to these active peptides is low in rats and humans , and the low systemic and portal vein concentrations of linaclotide and MM - 419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration .", "entity": [{"entity": "linaclotide", "entity_type": "Chemical", "pos": [126, 137]}, {"entity": "MM - 419447", "entity_type": "Chemical", "pos": [142, 153]}], "task": "NER"}
{"text": "Linaclotide is stable in the acidic environment of the stomach and is converted to MM - 419447 in the small intestine .", "entity": [{"entity": "Linaclotide", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "MM - 419447", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "The disulfide bonds of both peptides are reduced in the small intestine , where they are subsequently proteolyzed and degraded .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [4, 13]}], "task": "NER"}
{"text": "After oral administration of linaclotide , < 1 % of the dose was excreted as active peptide in rat feces and a mean of 3 - 5 % in human feces ; in both cases MM - 419447 was the predominant peptide recovered .", "entity": [{"entity": "linaclotide", "entity_type": "Chemical", "pos": [29, 40]}, {"entity": "MM - 419447", "entity_type": "Chemical", "pos": [158, 169]}], "task": "NER"}
{"text": "MM - 419447 exhibits high - affinity binding in vitro to T84 cells , resulting in a significant , concentration - dependent accumulation of intracellular cyclic guanosine - 3 ' , 5 ' - monophosphate ( cGMP ) .", "entity": [{"entity": "MM - 419447", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "cyclic guanosine - 3 ' , 5 ' - monophosphate", "entity_type": "Chemical", "pos": [154, 198]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [201, 205]}], "task": "NER"}
{"text": "In rat models of gastrointestinal function , orally dosed MM - 419447 significantly increased fluid secretion into small intestinal loops , increased intraluminal cGMP , and caused a dose - dependent acceleration in gastrointestinal transit .", "entity": [{"entity": "MM - 419447", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [163, 167]}], "task": "NER"}
{"text": "These results demonstrate the importance of the active metabolite in contributing to linaclotide ' s pharmacology .", "entity": [{"entity": "linaclotide", "entity_type": "Chemical", "pos": [85, 96]}], "task": "NER"}
{"text": "Lanthanum ( III ) regulates the nitrogen assimilation in soybean seedlings under ultraviolet - B radiation .", "entity": [{"entity": "Lanthanum ( III )", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "Ultraviolet - B ( UV - B , 280 - 320 nm ) radiation has seriously affected the growth of plants .", "entity": [], "task": "NER"}
{"text": "Finding the technology / method to alleviate the damage of UV - B radiation has become a frontal topic in the field of environmental science .", "entity": [], "task": "NER"}
{"text": "The pretreatment with rare earth elements ( REEs ) is an effective method , but the regulation mechanism of REEs is unknown .", "entity": [], "task": "NER"}
{"text": "Here , the regulation effects of lanthanum ( La ( III ) ) on nitrogen assimilation in soybean seedlings ( Glycine max L . ) under ultraviolet - B radiation were investigated to elucidate the regulation mechanism of REEs on plants under UV - B radiation .", "entity": [{"entity": "lanthanum", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "La ( III )", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "UV - B radiation led to the inhibition in the activities of the key enzymes ( nitrate reductase , glutamine synthetase , glutamate synthase ) in the nitrogen assimilation , the decrease in the contents of nitrate and soluble proteins , as well as the increase in the content of amino acid in soybean seedlings .", "entity": [{"entity": "nitrate", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [121, 130]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [149, 157]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [205, 212]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [278, 288]}], "task": "NER"}
{"text": "The change degree of UV - B radiation at the high level ( 0 . 45 W m ( - 2 ) ) was higher than that of UV - B radiation at the low level ( 0 . 15 W m ( - 2 ) ) .", "entity": [], "task": "NER"}
{"text": "The pretreatment with 20 mg L ( - 1 ) La ( III ) could alleviate the effects of UV - B radiation on the activities of nitrate reductase , glutamine synthetase , glutamate synthase , and glutamate dehydrogenase , promoting amino acid conversion and protein synthesis in soybean seedlings .", "entity": [{"entity": "La ( III )", "entity_type": "Chemical", "pos": [38, 48]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [118, 125]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [138, 147]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [161, 170]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [186, 195]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [222, 232]}], "task": "NER"}
{"text": "The regulation effect of La ( III ) under UV - B radiation at the low level was better than that of UV - B radiation at the high level .", "entity": [{"entity": "La ( III )", "entity_type": "Chemical", "pos": [25, 35]}], "task": "NER"}
{"text": "The results indicated that the pretreatment with 20 mg L ( - 1 ) La ( III ) could alleviate the inhibition of UV - B radiation on nitrogen assimilation in soybean seedlings .", "entity": [{"entity": "La ( III )", "entity_type": "Chemical", "pos": [65, 75]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [130, 138]}], "task": "NER"}
{"text": "Neutrophil and eosinophil granulocytes as key players in a mouse model of chemical - induced asthma .", "entity": [], "task": "NER"}
{"text": "Diisocyanates are an important cause of chemical - induced occupational asthma .", "entity": [{"entity": "Diisocyanates", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "This type of immunologically mediated asthma is often characterized by a predominant granulocytic inflammation in the airways , rather than an infiltration by lymphocytes .", "entity": [], "task": "NER"}
{"text": "We sought to determine the contribution of granulocytes in the outcome of chemical - induced asthma using general and specific leukocyte depletion strategies in an established mouse model of isocyanate asthma .", "entity": [{"entity": "isocyanate", "entity_type": "Chemical", "pos": [191, 201]}], "task": "NER"}
{"text": "On days 1 and 8 , BALB / c mice received dermal applications with toluene - 2 , 4 - diisocyanate ( TDI ) or vehicle ( acetone olive oil ) , followed by two ip injections of cyclophosphamide ( CP , days 11 and 13 ) , or one iv injection of antigranulocyte receptor 1 ( aGR1 , day 13 ) monoclonal antibody ( mAb ) , or two ip injections of Ly6G - specific mAb ( 1A8 , days 13 and 14 ) .", "entity": [{"entity": "toluene - 2 , 4 - diisocyanate", "entity_type": "Chemical", "pos": [66, 96]}, {"entity": "TDI", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [118, 125]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [173, 189]}], "task": "NER"}
{"text": "On day 15 , the mice were challenged ( oropharyngeal administration ) with TDI or vehicle .", "entity": [{"entity": "TDI", "entity_type": "Chemical", "pos": [75, 78]}], "task": "NER"}
{"text": "The next day , we assessed methacholine airway hyperreactivity ( AHR ) ; bronchoalveolar lavage differential cell count ; histopathology and total serum IgE ; and auricular lymphocyte subpopulations and release of interleukin ( IL ) - 2 , IL - 4 , IL - 10 , IL - 13 , and gamma interferon by these lymphocytes .", "entity": [{"entity": "methacholine", "entity_type": "Chemical", "pos": [27, 39]}], "task": "NER"}
{"text": "CP depleted all leukocyte types and completely prevented AHR and airway inflammation .", "entity": [], "task": "NER"}
{"text": "aGR1 depleted granulocytes and CD8 ( + ) lymphocytes , which resulted in a partial prevention in AHR but no decrease in airway inflammation .", "entity": [], "task": "NER"}
{"text": "Depletion of Ly6G - positive granulocytes , i . e . , both neutrophils and eosinophils , prevented AHR and lung epithelial damage and significantly reduced airway inflammation .", "entity": [], "task": "NER"}
{"text": "Injection of aGR1 or 1A8 led to significantly changed cytokine release patterns in TDI - treated mice .", "entity": [{"entity": "TDI", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Granulocytes , both neutrophils and eosinophils , are key cellular players in this model of chemical - induced asthma .", "entity": [], "task": "NER"}
{"text": "Thermosensitive polymeric hydrogels as drug delivery systems .", "entity": [], "task": "NER"}
{"text": "Thermosensitive hydrogels are very important biomaterials used in drug delivery systems ( DDSs ) , which gained increasing attention of researchers .", "entity": [], "task": "NER"}
{"text": "Thermosensitive hydrogels have great potential in various applications , such as drug delivery , cell encapsulation , tissue engineering , and etc .", "entity": [], "task": "NER"}
{"text": "Especially , injectable thermosensitive hydrogels with lower sol - gel transition temperature around physiological temperature have been extensively studied .", "entity": [], "task": "NER"}
{"text": "By in vivo injection , the hydrogels formed non - flowing gel at body temperature .", "entity": [], "task": "NER"}
{"text": "Upon incorporation of pharmaceutical agents , the hydrogel systems could act as sustained drug release depot in situ .", "entity": [], "task": "NER"}
{"text": "Injectable thermosensitive hydrogel systems have a number of advantages , including simplicity of drug formulation , protective environment for drugs , prolonged and localized drug delivery , and ease of application .", "entity": [], "task": "NER"}
{"text": "The objective of this review is to summarize fundamentals , applications , and recent advances of injectable thermosensitive hydrogel as DDSs , including chitosan and related derivatives , poly ( N - isopropylacrylamide ) - based ( PNIPAAM ) copolymers , poly ( ethylene oxide ) / poly ( propylene oxide ) ( PEO / PPO ) copolymers and its derivatives , and poly ( ethylene glycol ) / biodegradable polyester copolymers .", "entity": [{"entity": "poly ( N - isopropylacrylamide )", "entity_type": "Chemical", "pos": [189, 221]}, {"entity": "PNIPAAM", "entity_type": "Chemical", "pos": [232, 239]}, {"entity": "poly ( ethylene oxide )", "entity_type": "Chemical", "pos": [255, 278]}, {"entity": "poly ( propylene oxide )", "entity_type": "Chemical", "pos": [281, 305]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [308, 311]}, {"entity": "PPO", "entity_type": "Chemical", "pos": [314, 317]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [357, 381]}, {"entity": "polyester", "entity_type": "Chemical", "pos": [398, 407]}], "task": "NER"}
{"text": "New insights in the pathogenesis and treatment of normal tension glaucoma .", "entity": [], "task": "NER"}
{"text": "Increased intraocular pressure ( IOP ) is a major risk factor for glaucomatous damage and reducing IOP improves prognosis .", "entity": [], "task": "NER"}
{"text": "Nevertheless , there is little doubt that other risk factors besides IOP such as unstable ocular perfusion are involved .", "entity": [], "task": "NER"}
{"text": "Blood flow is unstable if either the IOP fluctuates at a high level ( or blood pressure fluctuates at a low level ) or if the autoregulation of blood flow disturbed .", "entity": [], "task": "NER"}
{"text": "A common cause for a disturbed OBF autoregulation is a primary vascular dysregulation ( PVD ) frequently observed in normal tension glaucoma patients .", "entity": [], "task": "NER"}
{"text": "An unstable blood flow leads to recurrent mild reperfusion injury ( chronic oxidative stress ) affecting particularly the mitochondria of the optic nerve head .", "entity": [], "task": "NER"}
{"text": "OBF regulation can be improved by magnesium , calcium channel blockers as well as with carbonic anhydrase inhibitors .", "entity": [{"entity": "magnesium", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Upregulation of phagocyte - like NADPH oxidase by cytokines in pancreatic beta - cells : attenuation of oxidative and nitrosative stress by 2 - bromopalmitate .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [33, 38]}, {"entity": "2 - bromopalmitate", "entity_type": "Chemical", "pos": [140, 158]}], "task": "NER"}
{"text": "Phagocyte - like NADPH oxidase ( Nox2 ) has been shown to play regulatory roles in the metabolic dysfunction of the islet beta - cell under the duress of glucolipotoxic conditions and exposure to proinflammatory cytokines .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [17, 22]}], "task": "NER"}
{"text": "However , the precise mechanisms underlying Nox2 activation by these stimuli remain less understood .", "entity": [], "task": "NER"}
{"text": "To this end , we report a time - dependent phosphorylation of p47phox , a cytosolic subunit of Nox2 , by cytomix ( IL - 1 beta + TNF alpha + IFN gamma ) in insulin - secreting INS - 1 832 / 13 cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , cytomix induced the expression of gp91phox , a membrane component of Nox2 .", "entity": [], "task": "NER"}
{"text": "2 - Bromopalmitate ( 2 - BP ) , a known inhibitor of protein palmitoylation , markedly attenuated cytokine - induced , Nox2 - mediated reactive oxygen species ( ROS ) generation and inducible nitric oxide synthase ( iNOS ) - mediated nitric oxide ( NO ) generation .", "entity": [{"entity": "2 - Bromopalmitate", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "2 - BP", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [144, 150]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [192, 204]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [234, 246]}, {"entity": "NO", "entity_type": "Chemical", "pos": [249, 251]}], "task": "NER"}
{"text": "However , 2 - BP failed to exert any significant effects on cytomix - induced CHOP expression , a marker for endoplasmic reticulum stress .", "entity": [{"entity": "2 - BP", "entity_type": "Chemical", "pos": [10, 16]}], "task": "NER"}
{"text": "Together , our findings identify palmitoyltransferase as a target for inhibition of cytomix - induced oxidative ( ROS generation ) and nitrosative ( NO generation ) stress in the pancreatic beta - cell .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [149, 151]}], "task": "NER"}
{"text": "mTOR inhibition modulates epileptogenesis , seizures and depressive behavior in a genetic rat model of absence epilepsy .", "entity": [], "task": "NER"}
{"text": "Several signaling pathways are believed to be involved in the epileptogenic process that triggers the subsequent changes in the brain causing epilepsy .", "entity": [], "task": "NER"}
{"text": "The mammalian target of rapamycin ( mTOR ) is a serine / threonine kinase that in the brain , regulates several important physiological functions such as neuronal development and synaptic plasticity , and also seems to be involved in many pathologies , including epilepsy and psychiatric disorders .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "serine", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "threonine", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "Previous work in animal models of both genetic and acquired generalized convulsive epilepsies , has suggested that modulators of the mTOR signaling pathway may have beneficial neuroprotective and antiepileptogenic effects .", "entity": [], "task": "NER"}
{"text": "Here , we investigated for the first time , the effect of some treatment schedules ( i . e . early chronic , sub - chronic and acute ) with the specific mTOR inhibitor rapamycin , on the development of absence seizures and seizure parameters as well as depressive - like behavior in WAG / Rij rats , a genetic model of absence epilepsy , epileptogenesis and mild - depression comorbidity .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [168, 177]}], "task": "NER"}
{"text": "In addition , we studied the possible interaction between rapamycin treatment and the effects of bacterial lipopolysaccharide ( LPS ) endotoxin administration , which is known to aggravate absence seizures through generation of increased neuroinflammatory responses .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "We found that rapamycin ( early chronic treatment for 17 weeks , starting at P45 ) exhibited clear antiepileptogenic properties also in this animal epilepsy model ; however , this effect was accompanied by unexpected prodepressant effects .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Both acute and sub - chronic ( 7 day ) treatments also had anti - absence properties , but the sub - chronic treatment produced contrasting antidepressant properties in the WAG / Rij rats that were not seen in control Wistar rats .", "entity": [], "task": "NER"}
{"text": "The rapamycin / LPS co - administration studies showed that rapamycin blocked or prevented the LPS - dependent increase in absence seizures , suggesting an anti - inflammatory - like protective action .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "In conclusion , we have demonstrated a novel antiepileptogenic effect of rapamycin in a well - established animal model of absence epilepsy , and we suggest that this effect may be mediated by the inhibition of inflammatory processes that are developed in the brain of these specific animals during epileptogenesis and during seizures .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "Our experiments here suggest new insights into this intriguing field , which deserves to be further explored .", "entity": [], "task": "NER"}
{"text": "The pyridyl group in ligand design for selective metal ion complexation and sensing .", "entity": [{"entity": "pyridyl", "entity_type": "Chemical", "pos": [4, 11]}], "task": "NER"}
{"text": "Factors in polypyridyl ligands that control their thermodynamic metal ion selectivity in aqueous solution , and their use in selective fluorescent sensing , are examined .", "entity": [{"entity": "polypyridyl", "entity_type": "Chemical", "pos": [11, 22]}], "task": "NER"}
{"text": "Preorganization of polypyridyl ligands ranging from bidentate to tetradentate by bridging benzo groups , as are present in 1 , 10 - phenanthroline ( phen ) compared to 2 , 2 ' - bipyridyl ( bpy ) , is discussed .", "entity": [{"entity": "polypyridyl", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "benzo", "entity_type": "Chemical", "pos": [90, 95]}, {"entity": "1 , 10 - phenanthroline", "entity_type": "Chemical", "pos": [123, 146]}, {"entity": "phen", "entity_type": "Chemical", "pos": [149, 153]}, {"entity": "2 , 2 ' - bipyridyl", "entity_type": "Chemical", "pos": [168, 187]}, {"entity": "bpy", "entity_type": "Chemical", "pos": [190, 193]}], "task": "NER"}
{"text": "The role of solvation is considered in relation to the relative affinity of ligands containing pyridyl groups for divalent and trivalent metal ions in aqueous solution .", "entity": [{"entity": "pyridyl", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "The effects of steric clashes between H atoms on polypyridyl ligands in decreasing complex stability are evaluated , as well as the effect of chelate ring size on metal ion selectivity .", "entity": [{"entity": "H", "entity_type": "Chemical", "pos": [38, 39]}, {"entity": "polypyridyl", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Phen ligands with other donor groups present at the 2 and 9 positions , such as alcohols , amides , carboxylates , and oximes are discussed .", "entity": [{"entity": "Phen", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "alcohols", "entity_type": "Chemical", "pos": [80, 88]}, {"entity": "amides", "entity_type": "Chemical", "pos": [91, 97]}, {"entity": "carboxylates", "entity_type": "Chemical", "pos": [100, 112]}, {"entity": "oximes", "entity_type": "Chemical", "pos": [119, 125]}], "task": "NER"}
{"text": "The design of pyridyl - based ligands for the separation of Am ( III ) from lanthanide ( III ) ions is considered , as well as ligands for the removal of metal ions such as Cu ( II ) or Zn ( II ) in neurological diseases such as Alzheimer ' s .", "entity": [{"entity": "pyridyl", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "Am ( III )", "entity_type": "Chemical", "pos": [60, 70]}, {"entity": "lanthanide ( III )", "entity_type": "Chemical", "pos": [76, 94]}, {"entity": "Cu ( II )", "entity_type": "Chemical", "pos": [173, 182]}, {"entity": "Zn ( II )", "entity_type": "Chemical", "pos": [186, 195]}], "task": "NER"}
{"text": "The design of pyridyl - based fluorescent sensors for selective sensing of metal ions is examined in terms of the role of spin - orbit coupling constants ( zeta ) , paramagnetism , and steric effects in the development of selective fluorescent sensors that operate via chelation enhanced fluorescence ( CHEF ) .", "entity": [{"entity": "pyridyl", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "It is concluded that for lighter metal ions with smaller zeta values such as Zn ( II ) and Ca ( II ) , and to a lesser extent Cd ( II ) , that the CHEF effect can be achieved with pyridyl - containing fluorophores that coordinate directly to the metal ion .", "entity": [{"entity": "Zn ( II )", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "Ca ( II )", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "Cd ( II )", "entity_type": "Chemical", "pos": [126, 135]}, {"entity": "pyridyl", "entity_type": "Chemical", "pos": [180, 187]}], "task": "NER"}
{"text": "The way in which steric effects can be used to decrease the CHEF effect in Zn ( II ) relative to Cd ( II ) to enable selective sensing of the latter is analyzed .", "entity": [{"entity": "Zn ( II )", "entity_type": "Chemical", "pos": [75, 84]}, {"entity": "Cd ( II )", "entity_type": "Chemical", "pos": [97, 106]}], "task": "NER"}
{"text": "For heavier metal ions such as Hg ( II ) and Pb ( II ) , because of their large zeta values which quench fluorescence , it is concluded that the fluorophore should be tethered to the metal - binding part of the sensor , and prevented from binding to the metal ion by steric and electronic factors .", "entity": [{"entity": "Hg ( II )", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "Pb ( II )", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "How Hg ( II ) can quench the CHEF effect by pi - contact with fluorophores such as the anthracenyl group , which at first sight might not seem able to bond with metal ions , is examined .", "entity": [{"entity": "Hg ( II )", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "anthracenyl", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Positive selection within a diatom species acts on putative protein interactions and transcriptional regulation .", "entity": [], "task": "NER"}
{"text": "Diatoms are the most species - rich group of microalgae , and their contribution to marine primary production is important on a global scale .", "entity": [], "task": "NER"}
{"text": "Diatoms can form dense blooms through rapid asexual reproduction ; mutations acquired and propagated during blooms likely provide the genetic , and thus phenotypic , variability upon which natural selection may act .", "entity": [], "task": "NER"}
{"text": "Positive selection was tested using genome and transcriptome - wide pair - wise comparisons of homologs in three genera of diatoms ( Pseudo - nitzschia , Ditylum , and Thalassiosira ) that represent decreasing phylogenetic distances .", "entity": [], "task": "NER"}
{"text": "The signal of positive selection was greatest between two strains of Thalassiosira pseudonana .", "entity": [], "task": "NER"}
{"text": "Further testing among seven strains of T . pseudonana yielded 809 candidate genes of positive selection , which are 7 % of the protein - coding genes .", "entity": [], "task": "NER"}
{"text": "Orphan genes and genes encoding protein - binding domains and transcriptional regulators were enriched within the set of positively selected genes relative to the genome as a whole .", "entity": [], "task": "NER"}
{"text": "Positively selected genes were linked to the potential selective pressures of nutrient limitation and sea surface temperature based on analysis of gene expression profiles and identification of positively selected genes in subsets of strains from locations with similar environmental conditions .", "entity": [], "task": "NER"}
{"text": "The identification of positively selected genes presents an opportunity to test new hypotheses in natural populations and the laboratory that integrate selected genotypes in T . pseudonana with their associated phenotypes and selective forces .", "entity": [], "task": "NER"}
{"text": "Negative regulation of inflammation by SIRT1 .", "entity": [], "task": "NER"}
{"text": "Sirtuin 1 ( SIRT1 ) , the mammalian Sir2 homologue , is a class III histone deacetylase shown to act on a wide range of histones and non - histone substrates .", "entity": [], "task": "NER"}
{"text": "Numerous studies have demonstrated that SIRT1 regulates critical metabolic and physiological processes including senescence , stress resistance , metabolism and apoptosis .", "entity": [], "task": "NER"}
{"text": "Recently , SIRT1 was also found to play an important role in modulating the development and progression of inflammation through deacetylating histones and critical transcription factor such as nuclear factor kappa B ( NF - kappa B ) and activator protein 1 ( AP - 1 ) , thus leading to transcriptional repression of various inflammation - related genes .", "entity": [], "task": "NER"}
{"text": "There is increasing evidence that reduction of SIRT1 levels is closely correlated with many inflammatory diseases while pharmacologic activation of SIRT1 would be a promising therapeutic strategy for inflammation - related diseases .", "entity": [], "task": "NER"}
{"text": "Four disruptive strategies for removing drug discovery bottlenecks .", "entity": [], "task": "NER"}
{"text": "Drug discovery is shifting focus from industry to outside partners and , in the process , creating new bottlenecks .", "entity": [], "task": "NER"}
{"text": "Technologies like high throughput screening ( HTS ) have moved to a larger number of academic and institutional laboratories in the USA , with little coordination or consideration of the outputs and creating a translational gap .", "entity": [], "task": "NER"}
{"text": "Although there have been collaborative public - private partnerships in Europe to share pharmaceutical data , the USA has seemingly lagged behind and this may hold it back .", "entity": [], "task": "NER"}
{"text": "Sharing precompetitive data and models may accelerate discovery across the board , while finding the best collaborators , mining social media and mobile approaches to open drug discovery should be evaluated in our efforts to remove drug discovery bottlenecks .", "entity": [], "task": "NER"}
{"text": "We describe four strategies to rectify the current unsustainable situation .", "entity": [], "task": "NER"}
{"text": "Converging levels of analysis on a genomic hotspot for psychosis : insights from 22q11 . 2 deletion syndrome .", "entity": [], "task": "NER"}
{"text": "Schizophrenia is a devastating neurodevelopmental disorder that , despite extensive research , still poses a considerable challenge to attempts to unravel its heterogeneity , and the complex biochemical mechanisms by which it arises .", "entity": [], "task": "NER"}
{"text": "While the majority of cases are of unknown etiology , accumulating evidence suggests that rare genetic mutations , such as 22q11 . 2 Deletion Syndrome ( 22qDS ) , can play a significant role in predisposition to the illness .", "entity": [], "task": "NER"}
{"text": "Up to 25 % of individuals with 22qDS eventually develop schizophrenia ; conversely , this deletion is estimated to account for 1 - 2 % of schizophrenia cases overall .", "entity": [], "task": "NER"}
{"text": "This locus of Chromosome 22q11 . 2 contains genes that encode for proteins and enzymes involved in regulating neurotransmission , neuronal development , myelination , microRNA processing , and post - translational protein modifications .", "entity": [], "task": "NER"}
{"text": "As a consequence of the deletion , affected individuals exhibit cognitive dysfunction , structural and functional brain abnormalities , and neurodevelopmental anomalies that parallel many of the phenotypic characteristics of schizophrenia .", "entity": [], "task": "NER"}
{"text": "As an illustration of the value of rare , highly penetrant genetic subtypes for elucidating pathological mechanisms of complex neuropsychiatric disorders , we provide here an overview of the cellular , network , and systems - level anomalies found in 22qDS , and review the intriguing evidence for this disorder ' s association with schizophrenia .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic study of Growth Hormone - Releasing Peptide 6 ( GHRP - 6 ) in nine male healthy volunteers .", "entity": [{"entity": "Growth Hormone - Releasing Peptide 6", "entity_type": "Chemical", "pos": [25, 61]}, {"entity": "GHRP - 6", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "GHRP - 6 is a growth hormone secretagogue that also enhances tissue viability in different organs .", "entity": [{"entity": "GHRP - 6", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "In the present work , we studied the pharmacokinetics of this short therapeutic hexapeptide ( His - ( D - Trp ) - Ala - Trp - ( D - Phe ) - Lys - NH ( 2 , ) MW = 872 . 44 Da ) in nine male healthy volunteers after a single intravenous bolus administration of 100 , 200 and 400 mu g / kg of body weight .", "entity": [{"entity": "His - ( D - Trp ) - Ala - Trp - ( D - Phe ) - Lys - NH ( 2 , )", "entity_type": "Chemical", "pos": [94, 156]}], "task": "NER"}
{"text": "GHRP - 6 was quantified in human plasma by a specific LC - MS method , previously developed and validated following FDA guidelines , using ( 13 ) C ( 3 ) Ala - GHRP - 6 as internal standard ( Gil et al . , 2012 , J . Pharm . Biomed . Anal . 60 , 19 - 25 ) .", "entity": [{"entity": "GHRP - 6", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "( 13 ) C ( 3 ) Ala - GHRP - 6", "entity_type": "Chemical", "pos": [139, 168]}], "task": "NER"}
{"text": "The Lower Limit of Quantification ( 5 ng / mL ) was reached in all subjects at 12h post - administration , which was sufficient for modeling a pharmacokinetic profile including over 85 % of the Area under the Curve ( AUC ) .", "entity": [], "task": "NER"}
{"text": "Disposition of GHRP - 6 best fitted a bi - exponential function with R ( 2 ) higher than 0 . 99 , according to a mathematic modeling and confirmed by an Akaike index ( AIC ) lower than that of the corresponding one - compartment model for all subjects .", "entity": [{"entity": "GHRP - 6", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "Averaging all three dose levels , the distribution and elimination half - life of GHRP - 6 were 7 . 6 +/- 1 . 9 min and 2 . 5 +/- 1 . 1h , respectively .", "entity": [{"entity": "GHRP - 6", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "These values are coherent with existing data for other drugs whose disposition also fits this model .", "entity": [], "task": "NER"}
{"text": "Dose dependence analysis revealed a noticeable trend for AUC to increase proportionally with administered dose .", "entity": [], "task": "NER"}
{"text": "Atypical GHRP - 6 concentration spikes were observed during the elimination phase in four out of the nine subjects studied .", "entity": [{"entity": "GHRP - 6", "entity_type": "Chemical", "pos": [9, 17]}], "task": "NER"}
{"text": "Apoptosis initiation of beta - ionone in SGC - 7901 gastric carcinoma cancer cells via a PI3K - AKT pathway .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [24, 37]}], "task": "NER"}
{"text": "beta - ionone has been shown to hold potent anti - proliferative and apoptosis induction properties in vitro and in vivo .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "To investigate the effects of beta - ionone on apoptosis initiation and its possible mechanisms of action , we qualified cell apoptosis , proteins related to apoptosis and a phosphatidylinositol 3 - kinase ( PI3K ) - AKT pathway in human gastric adenocarcinoma cancer SGC - 7901 cells .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [30, 43]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [174, 194]}], "task": "NER"}
{"text": "The results demonstrated that beta - ionone - induced apoptosis in a dose - dependent manner in SGC - 7901 cells treated with beta - ionone ( 25 , 50 , 100 and 200 mu mol / L ) for 24 h .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [30, 43]}, {"entity": "beta - ionone", "entity_type": "Chemical", "pos": [126, 139]}], "task": "NER"}
{"text": "beta - ionone was also shown to induce the expression of cleaved - caspase - 3 and inhibit bcl - 2 expression in SGC - 7901 cells in a dose - dependent manner .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "The significantly decreased levels of p - PI3K and p - AKT expression were observed in SGC - 7901 cells after beta - ionone treatments in a time - and dose - dependent manner ( P < 0 . 01 ) .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [110, 123]}], "task": "NER"}
{"text": "Thus , the apoptosis induction in SGC - 7901 cells by beta - ionone may be regulated through a PI3K - AKT pathway .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [54, 67]}], "task": "NER"}
{"text": "These results demonstrate a potential mechanism by which beta - ionone to induce apoptosis initiation in SGC - 7901 cells .", "entity": [{"entity": "beta - ionone", "entity_type": "Chemical", "pos": [57, 70]}], "task": "NER"}
{"text": "Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "iron", "entity_type": "Chemical", "pos": [54, 58]}], "task": "NER"}
{"text": "Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic - polluted well water , especially in Bangladesh .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "Although well drinking water in the cancer - prone areas contains various elements , very little is known about the effects of elements except arsenic on carcinogenicity .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [143, 150]}], "task": "NER"}
{"text": "In order to clarify the carcinogenic effects of coexposure to arsenic and iron , anchorage - independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "iron", "entity_type": "Chemical", "pos": [74, 78]}], "task": "NER"}
{"text": "Since the mean ratio of arsenic and iron in well water was 1 : 10 in cancer - prone areas of Bangladesh , effects of 1 mu M arsenic and 10 mu M iron were investigated .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [24, 31]}, {"entity": "iron", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [124, 131]}, {"entity": "iron", "entity_type": "Chemical", "pos": [144, 148]}], "task": "NER"}
{"text": "Iron synergistically promoted arsenic - mediated anchorage - independent growth in untransformed and transformed keratinocytes .", "entity": [{"entity": "Iron", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Iron additionally increased invasion in both types of keratinocytes .", "entity": [{"entity": "Iron", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Activities of c - SRC and ERK that regulate anchorage - independent growth and invasion were synergistically enhanced in both types of keratinocytes .", "entity": [], "task": "NER"}
{"text": "Our results suggest that iron promotes arsenic - mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [25, 29]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "We then developed a low - cost and high - performance adsorbent composed of a hydrotalcite - like compound for arsenic and iron .", "entity": [{"entity": "hydrotalcite", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [111, 118]}, {"entity": "iron", "entity_type": "Chemical", "pos": [123, 127]}], "task": "NER"}
{"text": "The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer - prone areas of Bangladesh to levels less than those in WHO health - based guidelines for drinking water .", "entity": [], "task": "NER"}
{"text": "Thus , we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [94, 101]}, {"entity": "iron", "entity_type": "Chemical", "pos": [106, 110]}], "task": "NER"}
{"text": "The effect of oxygen heteroatoms on the single molecule conductance of saturated chains .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [14, 20]}], "task": "NER"}
{"text": "Single molecule conductance measurements on alkanedithiols and alkoxydithiols ( dithiolated oligoethers ) were performed using the STM - controlled break junction method in order to ascertain how the oxygen heteroatoms in saturated linear chains impact the molecular conductance .", "entity": [{"entity": "alkanedithiols", "entity_type": "Chemical", "pos": [44, 58]}, {"entity": "alkoxydithiols", "entity_type": "Chemical", "pos": [63, 77]}, {"entity": "dithiolated oligoethers", "entity_type": "Chemical", "pos": [80, 103]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [200, 206]}], "task": "NER"}
{"text": "The experimental results show that the difference in conductance increases with chain length , over the range studied .", "entity": [], "task": "NER"}
{"text": "Comparisons with electronic structure calculations and previous work on alkanes indicate that the conductance of the oligoethers is lower than that of alkane chains with the same length .", "entity": [{"entity": "alkanes", "entity_type": "Chemical", "pos": [72, 79]}, {"entity": "oligoethers", "entity_type": "Chemical", "pos": [117, 128]}, {"entity": "alkane", "entity_type": "Chemical", "pos": [151, 157]}], "task": "NER"}
{"text": "Electronic structure calculations allow the difference in the conductance of these two families of molecules to be traced to differences in the spatial distribution of the molecular orbitals that contribute most to the conductance .", "entity": [], "task": "NER"}
{"text": "A pathway analysis of the electronic coupling through the chain is used to explain how the difference in conductance between the alkane and oligoether molecules depends on the chain length .", "entity": [{"entity": "alkane", "entity_type": "Chemical", "pos": [129, 135]}], "task": "NER"}
{"text": "Efficacy of asiatic acid , a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin - induced diabetic rats .", "entity": [{"entity": "asiatic acid", "entity_type": "Chemical", "pos": [12, 24]}, {"entity": "pentacyclic triterpene", "entity_type": "Chemical", "pos": [29, 51]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [97, 109]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [124, 138]}], "task": "NER"}
{"text": "Asiatic acid ( AA ) , a triterpenoid derivative of Centella asiatica , has shown significant biological effects of antioxidant and anti - inflammatory activities .", "entity": [{"entity": "Asiatic acid", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "triterpenoid", "entity_type": "Chemical", "pos": [24, 36]}], "task": "NER"}
{"text": "Aim of this investigation was to evaluate the antihyperglycemic effect of AA on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin ( STZ ) - induced diabetic rats .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [117, 129]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [144, 158]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [161, 164]}], "task": "NER"}
{"text": "To induce diabetes mellitus , rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg / kg b . w .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [54, 68]}], "task": "NER"}
{"text": "Diabetic rats showed significant ( p < 0 . 05 ) increased in plasma glucose , glycosylated hemoglobin and significant ( p < 0 . 05 ) decreased in circulating insulin and hemoglobin .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [68, 75]}], "task": "NER"}
{"text": "The altered activities of key enzymes such as glucose - 6 - phosphatase and fructose - 1 , 6 - bisphosphatase of carbohydrate metabolism significantly ( p < 0 . 05 ) increased whereas hexokinase , pyruvate kinase , glucose - 6 - phosphate dehydrogenase and glycogen content significantly ( p < 0 . 05 ) decreased in the liver of diabetic rats and also increased activities of aspartate transaminase ( AST ) , alanine transaminase ( ALT ) and alkaline phosphatase ( ALP ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [113, 125]}, {"entity": "pyruvate", "entity_type": "Chemical", "pos": [197, 205]}, {"entity": "glucose - 6 - phosphate", "entity_type": "Chemical", "pos": [215, 238]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [376, 385]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [409, 416]}], "task": "NER"}
{"text": "Oral administration of AA ( 5 , 10 and 20 mg / kg b . w . ) and glibenclamide ( 600 mu g / kg b . w . ) to diabetic rats for 45 days prevented the above alteration and reverted to near normalcy .", "entity": [{"entity": "glibenclamide", "entity_type": "Chemical", "pos": [64, 77]}], "task": "NER"}
{"text": "Protection of body weight loss of diabetic rats by AA was also observed .", "entity": [], "task": "NER"}
{"text": "No significant effect was observed in normal rats treated with AA ( 20 mg / kg b . w . ) .", "entity": [], "task": "NER"}
{"text": "In this search , AA found to be potential bioactive compound to regulate the carbohydrate metabolism by modulating the key regulatory enzymes in diabetic rats .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [77, 89]}], "task": "NER"}
{"text": "These findings merit further research in this field .", "entity": [], "task": "NER"}
{"text": "Mancozeb - induced behavioral deficits precede structural neural degeneration .", "entity": [{"entity": "Mancozeb", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Manganese - containing fungicides like Mancozeb have been associated with neurodegenerative conditions like Parkinson ' s disease .", "entity": [{"entity": "Manganese", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Mancozeb", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "We examined the behavioral damage and differential neuronal vulnerability resulting from Mancozeb exposure using Caenorhabditis elegans , an important mid - trophic level soil organism that is also a powerful model for studying mechanisms of environmental pollutant - induced neurodegenerative disease .", "entity": [{"entity": "Mancozeb", "entity_type": "Chemical", "pos": [89, 97]}], "task": "NER"}
{"text": "The dopamine - mediated swim to crawl locomotory transition behavior is exquisitely vulnerable to Mancozeb , with functional impairment preceding markers of neuronal structural damage .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "Mancozeb", "entity_type": "Chemical", "pos": [98, 106]}], "task": "NER"}
{"text": "The damage is partially rescued in mutants lacking the divalent metal transporter , SMF - 1 , demonstrating that some , but not all , of the damage is mediated by manganese .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [163, 172]}], "task": "NER"}
{"text": "Increasing concentrations of Mancozeb recruit additional behavioral dysfunction , notably serotonin - mediated egg - laying behavior , but without evident serotonergic neuronal structural damage .", "entity": [{"entity": "Mancozeb", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [90, 99]}], "task": "NER"}
{"text": "Thus , measurements of behavioral dysfunction are a sensitive early marker of fungicide toxicity that could be exploited to examine further mechanisms of neuron damage and possible therapeutic interventions .", "entity": [], "task": "NER"}
{"text": "These results also provide important insight into the consequences of fungicide use on the ecological behavior of nematodes .", "entity": [], "task": "NER"}
{"text": "In vitro metabolism , permeation , and brain availability of six major boswellic acids from Boswellia serrata gum resins .", "entity": [{"entity": "boswellic acids", "entity_type": "Chemical", "pos": [71, 86]}], "task": "NER"}
{"text": "Boswellia serrata gum resin extracts ( BSE ) revealed potent anti - inflammatory actions in preclinical and clinical studies .", "entity": [], "task": "NER"}
{"text": "In 2002 BSE was assigned an orphan drug status by the European Medicines Agency ( EMA ) for the treatment of peritumoral edema .", "entity": [], "task": "NER"}
{"text": "In the past pharmacological effects of BSE were mainly attributed to 11 - keto - beta - boswellic acid ( KBA ) and 3 - acetyl - 11 - keto - beta - boswellic acid ( AKBA ) .", "entity": [{"entity": "11 - keto - beta - boswellic acid", "entity_type": "Chemical", "pos": [69, 102]}, {"entity": "KBA", "entity_type": "Chemical", "pos": [105, 108]}, {"entity": "3 - acetyl - 11 - keto - beta - boswellic acid", "entity_type": "Chemical", "pos": [115, 161]}, {"entity": "AKBA", "entity_type": "Chemical", "pos": [164, 168]}], "task": "NER"}
{"text": "Therefore pharmacokinetic and pharmacodynamic studies focused mainly on these two boswellic acids ( BAs ) .", "entity": [{"entity": "boswellic acids", "entity_type": "Chemical", "pos": [82, 97]}], "task": "NER"}
{"text": "However , other BAs , like beta - boswellic acid ( beta BA ) , might also contribute to the anti - inflammatory actions of BSE .", "entity": [{"entity": "beta - boswellic acid", "entity_type": "Chemical", "pos": [27, 48]}, {"entity": "beta BA", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "Here , we determined the metabolic stability , permeability and brain availability of six major BAs , that is , KBA , AKBA , beta BA , 3 - acetyl - beta - boswellic acid ( A beta BA ) , alpha - boswellic acid ( alpha BA ) , and 3 - acetyl - alpha - boswellic acid ( A alpha BA ) .", "entity": [{"entity": "KBA", "entity_type": "Chemical", "pos": [112, 115]}, {"entity": "AKBA", "entity_type": "Chemical", "pos": [118, 122]}, {"entity": "beta BA", "entity_type": "Chemical", "pos": [125, 132]}, {"entity": "3 - acetyl - beta - boswellic acid", "entity_type": "Chemical", "pos": [135, 169]}, {"entity": "A beta BA", "entity_type": "Chemical", "pos": [172, 181]}, {"entity": "alpha - boswellic acid", "entity_type": "Chemical", "pos": [186, 208]}, {"entity": "alpha BA", "entity_type": "Chemical", "pos": [211, 219]}, {"entity": "3 - acetyl - alpha - boswellic acid", "entity_type": "Chemical", "pos": [228, 263]}, {"entity": "A alpha BA", "entity_type": "Chemical", "pos": [266, 276]}], "task": "NER"}
{"text": "For permeability studies , the Caco - 2 model was adapted to physiological conditions by the addition of bovine serum albumin ( BSA ) to the basolateral side and the use of modified fasted state simulated intestinal fluid ( FaSSIF ) on the apical side .", "entity": [], "task": "NER"}
{"text": "Under these conditions the four BAs lacking the 11 - keto moiety revealed moderate permeability .", "entity": [{"entity": "11 - keto", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "Furthermore the permeability of AKBA and KBA was improved compared to earlier studies .", "entity": [{"entity": "AKBA", "entity_type": "Chemical", "pos": [32, 36]}, {"entity": "KBA", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "In contrast to A alpha - and A beta BA , beta BA and alpha BA were intensively metabolized after incubation with human and rat liver microsomes .", "entity": [{"entity": "A alpha - and A beta BA", "entity_type": "Chemical", "pos": [15, 38]}, {"entity": "beta BA", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "alpha BA", "entity_type": "Chemical", "pos": [53, 61]}], "task": "NER"}
{"text": "Finally , the availability of all six major BAs could be confirmed in rat brain 8h after oral administration of 240mg / kg BSE to rats showing mean concentrations of 11 . 6ng / g for KBA , 37 . 5ng / g for AKBA , 485 . 1ng / g for alpha BA , 1066 . 6ng / g for beta BA , 43 . 0ng / g for A alpha BA and 163 . 7ng / g for A beta BA .", "entity": [{"entity": "KBA", "entity_type": "Chemical", "pos": [183, 186]}, {"entity": "AKBA", "entity_type": "Chemical", "pos": [206, 210]}, {"entity": "alpha BA", "entity_type": "Chemical", "pos": [231, 239]}, {"entity": "beta BA", "entity_type": "Chemical", "pos": [261, 268]}, {"entity": "A alpha BA", "entity_type": "Chemical", "pos": [288, 298]}, {"entity": "A beta BA", "entity_type": "Chemical", "pos": [321, 330]}], "task": "NER"}
{"text": "Possible ways of fagopyrin biosynthesis and production in buckwheat plants .", "entity": [{"entity": "fagopyrin", "entity_type": "Chemical", "pos": [17, 26]}], "task": "NER"}
{"text": "The present work extends knowledge about possible biosynthesis of fagopyrin in buckwheat plants by providing possible candidate genes for its biosynthesis and the role of type III polyketide synthases ( PKSs ) .", "entity": [{"entity": "fagopyrin", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "Moreover , new information is presented about the possible connection between naphthodianthrones and phenolic biosynthesis .", "entity": [{"entity": "naphthodianthrones", "entity_type": "Chemical", "pos": [78, 96]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "Possible regulation of fagopyrin biosynthesis and production under different growth conditions is also discussed .", "entity": [{"entity": "fagopyrin", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "Adolescent male rats are less sensitive than adults to the anxiogenic and serotonin - releasing effects of fenfluramine .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [74, 83]}, {"entity": "fenfluramine", "entity_type": "Chemical", "pos": [107, 119]}], "task": "NER"}
{"text": "Risk taking behavior increases during adolescence , which is also a critical period for the onset of drug abuse .", "entity": [], "task": "NER"}
{"text": "The central serotonergic system matures during the adolescent period , and its immaturity during early adolescence may contribute to adolescent risk taking , as deficits in central serotonergic function have been associated with impulsivity , aggression , and risk taking .", "entity": [], "task": "NER"}
{"text": "We investigated serotonergic modulation of behavior and presynaptic serotonergic function in adult ( 67 - 74 days old ) and adolescent ( 28 - 34 days old ) male rats .", "entity": [], "task": "NER"}
{"text": "Fenfluramine ( 2 mg / kg , i . p . ) produced greater anxiogenic effects in adult rats in both the light / dark and elevated plus maze tests for anxiety - like behavior , and stimulated greater increases in extracellular serotonin in the adult medial prefrontal cortex ( mPFC ) ( 1 , 2 . 5 , and 10 mg / kg , i . p . ) .", "entity": [{"entity": "Fenfluramine", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [221, 230]}], "task": "NER"}
{"text": "Local infusion of 100 mM potassium chloride into the mPFC also stimulated greater serotonin efflux in adult rats .", "entity": [{"entity": "potassium chloride", "entity_type": "Chemical", "pos": [25, 43]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "Adult rats had higher tissue serotonin content than adolescents in the prefrontal cortex , amygdala , and hippocampus , but the rate of serotonin synthesis was similar between age groups .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [136, 145]}], "task": "NER"}
{"text": "Serotonin transporter ( SERT ) immunoreactivity and SERT radioligand binding were comparable between age groups in all three brain regions .", "entity": [{"entity": "Serotonin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "These data suggest that lower tissue serotonin stores in adolescents limit fenfluramine - stimulated serotonin release and so contribute to the lesser anxiogenic effects of fenfluramine .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "fenfluramine", "entity_type": "Chemical", "pos": [75, 87]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [101, 110]}, {"entity": "fenfluramine", "entity_type": "Chemical", "pos": [173, 185]}], "task": "NER"}
{"text": "Arsenic trioxide - induced hERG K ( + ) channel deficiency can be rescued by matrine and oxymatrine through up - regulating transcription factor Sp1 expression .", "entity": [{"entity": "Arsenic trioxide", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "matrine", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "oxymatrine", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "The human ether - a - go - go - related gene ( hERG ) encodes the rapidly activating , delayed rectifier potassium channel ( IKr ) important for cardiac repolarization .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [10, 15]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "Dysfunction of the hERG channel can cause Long QT Syndrome ( LQTS ) .", "entity": [], "task": "NER"}
{"text": "A wide variety of structurally diverse therapeutic compounds reduce the hERG current by acute direct inhibition of the hERG current or / and selective disruption of hERG protein expression .", "entity": [], "task": "NER"}
{"text": "Arsenic trioxide ( As ( 2 ) O ( 3 ) ) , which is used to treat acute promyelocytic leukemia , can cause LQTS type 2 ( LQT2 ) by reducing the hERG current through the diversion of hERG trafficking to the cytoplasmic membrane .", "entity": [{"entity": "Arsenic trioxide", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "As ( 2 ) O ( 3 )", "entity_type": "Chemical", "pos": [19, 35]}], "task": "NER"}
{"text": "This cardiotoxicity limits its clinical applications .", "entity": [], "task": "NER"}
{"text": "Our aim was to develop cardioprotective agents to decrease As ( 2 ) O ( 3 ) - induced cardiotoxicity .", "entity": [{"entity": "As ( 2 ) O ( 3 )", "entity_type": "Chemical", "pos": [59, 75]}], "task": "NER"}
{"text": "We reported that superfusion of hERG - expressing HEK293 ( hERG - HEK ) cells with matrine ( 1 , 10 mu M ) increased the hERG current by promoting hERG channel activation .", "entity": [{"entity": "matrine", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "Long - term treatment with 1 mu M matrine or oxymatrine increased expression of the hERG protein and rescued the hERG surface expression disrupted by As ( 2 ) O ( 3 ) .", "entity": [{"entity": "matrine", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "oxymatrine", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "As ( 2 ) O ( 3 )", "entity_type": "Chemical", "pos": [150, 166]}], "task": "NER"}
{"text": "In addition , Matrine and oxymatrine significantly shortened action potential duration prolonged by As ( 2 ) O ( 3 ) in guinea pig ventricular myocytes .", "entity": [{"entity": "Matrine", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "oxymatrine", "entity_type": "Chemical", "pos": [26, 36]}, {"entity": "As ( 2 ) O ( 3 )", "entity_type": "Chemical", "pos": [100, 116]}], "task": "NER"}
{"text": "These results were ascribed to the up - regulation of hERG at both mRNA and protein levels via an increase in the expression of transcription factor Sp1 , an established transactivator of the hERG gene .", "entity": [], "task": "NER"}
{"text": "Therefore , matrine and oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression .", "entity": [{"entity": "matrine", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "oxymatrine", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "TNF - alpha - mediated NF - kappa B survival signaling impairment by cisplatin enhances JNK activation allowing synergistic apoptosis of renal proximal tubular cells .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [69, 78]}], "task": "NER"}
{"text": "Cisplatin - induced nephrotoxicity is an important limiting factor for cisplatin use .", "entity": [{"entity": "Cisplatin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "Tumor necrosis factor - alpha ( TNF - alpha ) is known to contribute to cisplatin - induced nephrotoxicity by inducing an inflammatory process aggravating the primary injury , thereby resulting in acute kidney injury ( AKI ) .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [72, 81]}], "task": "NER"}
{"text": "The present study investigates the pathways synergistically activated by cisplatin and TNF - alpha responsible for TNF - alpha - enhanced cisplatin - induced renal cell injury .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [73, 82]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [138, 147]}], "task": "NER"}
{"text": "To do so , immortalized renal proximal tubular epithelial cells ( IM - PTECs ) were co - treated with TNF - alpha and cisplatin .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [118, 127]}], "task": "NER"}
{"text": "Under these conditions , cisplatin induced dose - dependent apoptosis in IM - PTECs , which was significantly enhanced by TNF - alpha .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [25, 34]}], "task": "NER"}
{"text": "Transcriptomic analysis revealed that cisplatin inhibited the typical TNF - alpha response and cisplatin / TNF - alpha treatment up - regulated cell death pathways while it down - regulated survival pathways compared to cisplatin alone .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [95, 104]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [220, 229]}], "task": "NER"}
{"text": "In concordance , the gene expression levels of kidney injury markers combined with activation of specific inflammatory mediators were enhanced by cisplatin / TNF - alpha treatment , resembling the in vivo cisplatin - induced nephrotoxicity response .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [146, 155]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [205, 214]}], "task": "NER"}
{"text": "Furthermore , combined cisplatin / TNF - alpha treatment inhibited NF - kappa B nuclear translocation and NF - kappa B - mediated gene transcription leading to enhanced and prolonged JNK and c - Jun phosphorylation .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "JNK sustained activation further inhibited NF - kappa B signaling via a feedback loop mechanism .", "entity": [], "task": "NER"}
{"text": "This led to an alteration in the transcription of the NF - kappa B - induced anti - apoptotic genes c - IAP2 , Bcl - XL , Bruce and Bcl2 and pro - apoptotic genes Bfk and Xaf1 and consequently to sensitization of the IM - PTECs toward cisplatin / TNF - alpha - induced toxicity .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [235, 244]}], "task": "NER"}
{"text": "In conclusion , our findings support a model whereby renal cells exposed to both cisplatin and TNF - alpha switch into a more pro - apoptotic and inflammatory program by altering their NF - kappa B / JNK / c - Jun balance .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "Ibandronate increases the expression of the pro - apoptotic gene FAS by epigenetic mechanisms in tumor cells .", "entity": [{"entity": "Ibandronate", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "There is growing evidence that aminobisphosphonates like ibandronate show anticancer activity by an unknown mechanism .", "entity": [{"entity": "aminobisphosphonates", "entity_type": "Chemical", "pos": [31, 51]}, {"entity": "ibandronate", "entity_type": "Chemical", "pos": [57, 68]}], "task": "NER"}
{"text": "Biochemically , they prevent posttranslational isoprenylation of small GTPases , thus inhibiting their activity .", "entity": [], "task": "NER"}
{"text": "In tumor cells , activated RAS - GTPase , the founding member of the gene family , down - regulates the expression of the pro - apoptotic gene FAS via epigenetic DNA - methylation by DNMT1 .", "entity": [], "task": "NER"}
{"text": "We compared ibandronate treatment in neoplastic human U - 2 osteosarcoma and in mouse CCL - 51 breast cancer cells as well as in the immortalized non - neoplastic MC3T3 - E1 osteoblastic cells .", "entity": [{"entity": "ibandronate", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Ibandronate attenuated cell proliferation in all cell lines tested .", "entity": [{"entity": "Ibandronate", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In the neoplastic cells we found up - regulation of caspases suggesting apoptosis .", "entity": [], "task": "NER"}
{"text": "Further we found stimulation of FAS - expression as a result of epigenetic DNA demethylation that was due to down - regulation of DNMT1 , which was rescued by re - isoprenylation by both geranylgeranyl - pyrophosphate and farnesylpyrophosphate .", "entity": [{"entity": "geranylgeranyl - pyrophosphate", "entity_type": "Chemical", "pos": [187, 217]}, {"entity": "farnesylpyrophosphate", "entity_type": "Chemical", "pos": [222, 243]}], "task": "NER"}
{"text": "In contrast , ibandronate did not affect FAS and DNMT1 expression in MC3T3 - E1 non - neoplastic cells .", "entity": [{"entity": "ibandronate", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Data suggest that bisphosphonates via modulation of the activity of small - GTPases induce apoptosis in neoplastic cells by DNA - CpG - demethylation and stimulation of FAS - expression .", "entity": [{"entity": "bisphosphonates", "entity_type": "Chemical", "pos": [18, 33]}, {"entity": "CpG", "entity_type": "Chemical", "pos": [130, 133]}], "task": "NER"}
{"text": "In conclusion the shown epigenetic mechanism underlying the anti - neoplastic activity of farnesyl - transferase - inhibition , also explains the clinical success of other drugs , which target this pathway .", "entity": [{"entity": "farnesyl", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "Interorgan metabolism of ornithine phenylacetate ( OP ) - - a novel strategy for treatment of hyperammonemia .", "entity": [{"entity": "ornithine phenylacetate", "entity_type": "Chemical", "pos": [25, 48]}], "task": "NER"}
{"text": "Combined administration of ornithine and phenylacetate ( OP ) is proposed as a novel treatment of hyperammonemia and hepatic encephalopathy .", "entity": [{"entity": "ornithine", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "phenylacetate", "entity_type": "Chemical", "pos": [41, 54]}], "task": "NER"}
{"text": "Ornithine is believed to increase ammonia fixation into glutamine in muscle tissue and glutamine is subsequently thought to react with phenylacetate forming phenylacetylglutamine ( PAGN ) which is excreted in urine .", "entity": [{"entity": "Ornithine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [87, 96]}, {"entity": "phenylacetate", "entity_type": "Chemical", "pos": [135, 148]}, {"entity": "phenylacetylglutamine", "entity_type": "Chemical", "pos": [157, 178]}, {"entity": "PAGN", "entity_type": "Chemical", "pos": [181, 185]}], "task": "NER"}
{"text": "The aim of the present study was to elucidate the interorgan metabolism of ornithine and ammonia in cirrhotic rats treated with OP in order to obtain an understanding of the underlying mechanisms of the beneficial effect of the treatment , which are largely unknown .", "entity": [{"entity": "ornithine", "entity_type": "Chemical", "pos": [75, 84]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "Bile duct ligated cirrhotic rats and SHAM rats were treated with OP or saline for five days .", "entity": [], "task": "NER"}
{"text": "[ 2 , 5 - ( 15 ) N ] Ornithine or ( 15 ) NH ( 4 ) ( + ) were administered intravenously and the incorporation of ( 15 ) N in amino acids as well as the content of the amino acids were subsequently determined in plasma , skeletal muscle , liver and kidney .", "entity": [{"entity": "[ 2 , 5 - ( 15 ) N ] Ornithine", "entity_type": "Chemical", "pos": [0, 30]}, {"entity": "( 15 ) NH ( 4 ) ( + )", "entity_type": "Chemical", "pos": [34, 55]}, {"entity": "( 15 ) N", "entity_type": "Chemical", "pos": [113, 121]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [125, 136]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [167, 178]}], "task": "NER"}
{"text": "In BDL rats , OP treatment reduced arterial ammonia concentration and increased that of glutamine 30 min after the treatment but not after 15 h .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [44, 51]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "OP treatment did not increase ( 15 ) N labeling in glutamine from [ 2 , 5 - ( 15 ) N ] ornithine and ( 15 ) NH ( 4 ) ( + ) in skeletal muscle or liver .", "entity": [{"entity": "( 15 ) N", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "[ 2 , 5 - ( 15 ) N ] ornithine", "entity_type": "Chemical", "pos": [66, 96]}, {"entity": "( 15 ) NH ( 4 ) ( + )", "entity_type": "Chemical", "pos": [101, 122]}], "task": "NER"}
{"text": "However , the extent of glutamine labeling from [ 2 , 5 - ( 15 ) N ] ornithine or ( 15 ) NH ( 4 ) ( + ) was similar in arterial blood and liver and higher than that in skeletal muscle .", "entity": [{"entity": "glutamine", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "[ 2 , 5 - ( 15 ) N ] ornithine", "entity_type": "Chemical", "pos": [48, 78]}, {"entity": "( 15 ) NH ( 4 ) ( + )", "entity_type": "Chemical", "pos": [82, 103]}], "task": "NER"}
{"text": "These findings suggest that the effect of OP was related to hepatic metabolism of ornithine .", "entity": [{"entity": "ornithine", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "PAGN could not be detected in urine or blood in any of the rats which may explain why OP treatment only reduced arterial ammonia transiently .", "entity": [{"entity": "PAGN", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [121, 128]}], "task": "NER"}
{"text": "Platelet - derived growth factor triggers PKA - mediated signalling by a redox - dependent mechanism in rat renal mesangial cells .", "entity": [], "task": "NER"}
{"text": "Inflammatory glomerular kidney diseases are often accompanied with a massive production of reactive oxygen species ( ROS ) that affect the function of the glomerular filtration barrier and contribute to mesangiolysis via the induction of cell death in mesangial cells .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [100, 106]}], "task": "NER"}
{"text": "Intriguingly , ROS also trigger fine - tuned signalling processes that affect gene expression and cell proliferation or migration .", "entity": [], "task": "NER"}
{"text": "To define such redox - driven signalling devices , a proteomics approach was performed to identify the formation of protein complexes induced by ROS .", "entity": [], "task": "NER"}
{"text": "To this end , protein lysates of human podocytes were treated with or without hydrogen peroxide ( 250 mu M ) .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [78, 95]}], "task": "NER"}
{"text": "Thereafter cell lysates were subjected to diagonal 2D gel electrophoresis and putative redox - affected proteins were analysed by MS / MS analysis .", "entity": [], "task": "NER"}
{"text": "Among others , the regulatory subunit of protein kinase A ( PKA ) could be identified that forms homodimers under oxidative conditions .", "entity": [], "task": "NER"}
{"text": "To evaluate whether ROS dependent dimerization of PKA also occurs in a more physiological setting , rat mesangial cells were treated with platelet - derived growth factor - BB ( PDGF - BB ) to induce ROS formation .", "entity": [], "task": "NER"}
{"text": "This regimen resulted in a redox dependent dimerization of the R - subunits of PKA .", "entity": [], "task": "NER"}
{"text": "To demonstrate whether PDGF - BB induced ROS formation affects PKA dependent pathways , the effects of PDGF - BB on phosphorylation of serine 157 of vasodilator stimulated protein ( VASP ) a classical target of PKA were analysed .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [135, 141]}], "task": "NER"}
{"text": "Interestingly PDGF - BB induced VASP phosphorylation in a ROS dependent manner but independent of changes in cAMP levels .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [109, 113]}], "task": "NER"}
{"text": "Taken together , we demonstrate a redox - mediated activation of PKA by PDGF - BB thus highlighting a physiological role of ROS as regulator of PKA activity in rat mesangial cells .", "entity": [], "task": "NER"}
{"text": "Chloroacetic acid induced neuronal cells death through oxidative stress - mediated p38 - MAPK activation pathway regulated mitochondria - dependent apoptotic signals .", "entity": [{"entity": "Chloroacetic acid", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Chloroacetic acid ( CA ) , a toxic chlorinated analog of acetic acid , is widely used in chemical industries as an herbicide , detergent , and disinfectant , and chemical intermediates that are formed during the synthesis of various products .", "entity": [{"entity": "Chloroacetic acid", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [57, 68]}], "task": "NER"}
{"text": "In addition , CA has been found as a by - product of chlorination disinfection of drinking water .", "entity": [], "task": "NER"}
{"text": "However , there is little known about neurotoxic injuries of CA on the mammalian , the toxic effects and molecular mechanisms of CA - induced neuronal cell injury are mostly unknown .", "entity": [], "task": "NER"}
{"text": "In this study , we examined the cytotoxicity of CA on cultured Neuro - 2a cells and investigated the possible mechanisms of CA - induced neurotoxicity .", "entity": [], "task": "NER"}
{"text": "Treatment of Neuro - 2a cells with CA significantly reduced the number of viable cells ( in a dose - dependent manner with a range from 0 . 1 to 3mM ) , increased the generation of ROS , and reduced the intracellular levels of glutathione depletion .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [227, 238]}], "task": "NER"}
{"text": "CA also increased the number of sub - G1 hypodiploid cells ; increased mitochondrial dysfunction ( loss of MMP , cytochrome c release , and accompanied by Bcl - 2 and Mcl - 1 down - regulation and Bax up - regulation ) , and activated the caspase cascades activations , which displayed features of mitochondria - dependent apoptosis pathway .", "entity": [], "task": "NER"}
{"text": "These CA - induced apoptosis - related signals were markedly prevented by the antioxidant N - acetylcysteine ( NAC ) .", "entity": [{"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [90, 108]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [111, 114]}], "task": "NER"}
{"text": "Moreover , CA activated the JNK and p38 - MAPK pathways , but did not that ERK1 / 2 pathway , in treated Neuro - 2a cells .", "entity": [], "task": "NER"}
{"text": "Pretreatment with NAC and specific p38 - MAPK inhibitor ( SB203580 ) , but not JNK inhibitor ( SP600125 ) effectively abrogated the phosphorylation of p38 - MAPK and attenuated the apoptotic signals ( including : decrease in cytotoxicity , caspase - 3 / - 7 activation , the cytosolic cytochrome c release , and the reversed alteration of Bcl - 2 and Bax mRNA ) in CA - treated Neuro - 2a cells .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "SB203580", "entity_type": "Chemical", "pos": [58, 66]}, {"entity": "SP600125", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "Taken together , these data suggest that oxidative stress - induced p38 - MAPK activated pathway - regulated mitochondria - dependent apoptosis plays an important role in CA - caused neuronal cell death .", "entity": [], "task": "NER"}
{"text": "Bioassay - guided isolation of urease and alpha - chymotrypsin inhibitory constituents from the stems of Lawsonia alba Lam .", "entity": [], "task": "NER"}
{"text": "( Henna ) .", "entity": [], "task": "NER"}
{"text": "Seven constituents were isolated from the stems of Lawsonia alba Lam . , following an activity - guided isolation , which include two new constituents , namely lawsorosemarinol ( 1 ) and lawsofructose ( 2 ) , one known compound 2 - ( beta - d - glucopyranosyloxy ) - 1 , 4 - naphthoquinone ( 3 ) and four compounds , 4 - hydroxy coumarine ( 4 ) , 3 - ( 4 - hyroxyphenyl ) - triacontyl - ( Z ) - propenoate ( 5 ) , 3 - ( 4 - hydroxy - 3 - methoxyphenyl ) - triacontyl - ( Z ) - propenoate ( 6 ) and 7 - hydroxy - 4 - methyl coumarin ( 7 ) first time isolated from Lawsonia alba .", "entity": [{"entity": "lawsorosemarinol", "entity_type": "Chemical", "pos": [160, 176]}, {"entity": "lawsofructose", "entity_type": "Chemical", "pos": [187, 200]}, {"entity": "2 - ( beta - d - glucopyranosyloxy ) - 1 , 4 - naphthoquinone", "entity_type": "Chemical", "pos": [228, 289]}, {"entity": "4 - hydroxy coumarine", "entity_type": "Chemical", "pos": [317, 338]}, {"entity": "3 - ( 4 - hyroxyphenyl ) - triacontyl - ( Z ) - propenoate", "entity_type": "Chemical", "pos": [347, 405]}, {"entity": "3 - ( 4 - hydroxy - 3 - methoxyphenyl ) - triacontyl - ( Z ) - propenoate", "entity_type": "Chemical", "pos": [414, 487]}, {"entity": "7 - hydroxy - 4 - methyl coumarin", "entity_type": "Chemical", "pos": [498, 531]}], "task": "NER"}
{"text": "Their structure elucidation was based on spectroscopic data analyses .", "entity": [], "task": "NER"}
{"text": "Compounds 3 and 7 showed a moderate inhibition of urease activity , while rest of them showed less than 50 % inhibition .", "entity": [], "task": "NER"}
{"text": "These compounds did not show any significant inhibition against alpha - chymotrypsin .", "entity": [], "task": "NER"}
{"text": "Active self - healing encapsulation of vaccine antigens in PLGA microspheres .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [59, 63]}], "task": "NER"}
{"text": "Herein , we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly ( lactic - co - glycolic acid ) ( PLGA ) by simple mixing of preformed active self - microencapsulating ( SM ) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature ( 10 - 38 degrees C ) .", "entity": [{"entity": "poly ( lactic - co - glycolic acid )", "entity_type": "Chemical", "pos": [119, 155]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [158, 162]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [235, 239]}], "task": "NER"}
{"text": "Co - encapsulating protein - sorbing vaccine adjuvants and polymer plasticizers were used to \" actively \" load the protein in the polymer pores and facilitate polymer self - healing at a temperature > the hydrated polymer glass transition temperature , respectively .", "entity": [], "task": "NER"}
{"text": "The microsphere formulation parameters and loading conditions to provide optimal active self - healing microencapsulation of vaccine antigens in PLGA was investigated .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [145, 149]}], "task": "NER"}
{"text": "Active self - healing encapsulation of two antigens , ovalbumin and tetanus toxoid ( TT ) , in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvants ( aluminum hydroxide ( Al ( OH ) 3 ) or calcium phosphate ) .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [95, 99]}, {"entity": "aluminum hydroxide", "entity_type": "Chemical", "pos": [199, 217]}, {"entity": "Al ( OH ) 3", "entity_type": "Chemical", "pos": [220, 231]}, {"entity": "calcium phosphate", "entity_type": "Chemical", "pos": [237, 254]}], "task": "NER"}
{"text": "Active loading of vaccine antigen in Al ( OH ) 3 - PLGA microspheres was found to : a ) increase with an increasing loading of Al ( OH ) 3 ( 0 . 88 - 3 wt . % ) and addition of porosigen , b ) decrease when the inner Al ( OH ) 3 / trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0 . 2 mL and 63 mu m , and c ) change negligibly by PLGA concentration and initial incubation ( loading ) temperature .", "entity": [{"entity": "Al ( OH ) 3", "entity_type": "Chemical", "pos": [37, 48]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "Al ( OH ) 3", "entity_type": "Chemical", "pos": [127, 138]}, {"entity": "Al ( OH ) 3", "entity_type": "Chemical", "pos": [217, 228]}, {"entity": "trehalose", "entity_type": "Chemical", "pos": [231, 240]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [367, 371]}], "task": "NER"}
{"text": "Encapsulation of protein sorbing Al ( OH ) 3 in PLGA microspheres resulted in suppression of self - healing of PLGA pores , which was then overcome by improving polymer chain mobility , which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA .", "entity": [{"entity": "Al ( OH ) 3", "entity_type": "Chemical", "pos": [33, 44]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [111, 115]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [264, 268]}], "task": "NER"}
{"text": "Active self - healing microencapsulation of manufacturing process - labile TT in PLGA was found to : a ) obviate micronization - and organic solvent - induced TT degradation , b ) improve antigen loading ( 1 . 4 - 1 . 8 wt . % TT ) and encapsulation efficiency ( ~ 97 % ) , c ) provide nearly homogeneous distribution and stabilization of antigen in polymer , and d ) provide improved in vitro controlled release of antigenic TT .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "N - Arachidonyl glycine does not activate G protein - coupled receptor 18 signaling via canonical pathways .", "entity": [{"entity": "N - Arachidonyl glycine", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "Recent studies propose that N - arachidonyl glycine ( NAGly ) , a carboxylic analogue of anandamide , is an endogenous ligand of the G alpha ( i / o ) protein - coupled receptor 18 ( GPR18 ) .", "entity": [{"entity": "N - arachidonyl glycine", "entity_type": "Chemical", "pos": [28, 51]}, {"entity": "NAGly", "entity_type": "Chemical", "pos": [54, 59]}, {"entity": "carboxylic", "entity_type": "Chemical", "pos": [66, 76]}, {"entity": "anandamide", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "However , a high - throughput beta - arrestin - based screen failed to detect activation of GPR18 by NAGly ( Yin et al . , 2009 ; JBC , 18 : 12328 ) .", "entity": [{"entity": "NAGly", "entity_type": "Chemical", "pos": [101, 106]}], "task": "NER"}
{"text": "To address this inconsistency , this study investigated GPR18 coupling in a native neuronal system with endogenous signaling pathways and effectors .", "entity": [], "task": "NER"}
{"text": "GPR18 was heterologously expressed in rat sympathetic neurons , and the modulation of N - type ( Ca ( v ) 2 . 2 ) calcium channels was examined .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [86, 87]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [97, 99]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "Proper expression and trafficking of receptor were confirmed by the \" rim - like \" fluorescence of fluorescently tagged receptor and the positive staining of external hemagglutinin - tagged GPR18 - expressing cells .", "entity": [], "task": "NER"}
{"text": "Application of NAGly on GPR18 - expressing neurons did not inhibit calcium currents but instead potentiated currents in a voltage - dependent manner , similar to what has previously been reported ( Guo et al . , 2008 ; J Neurophysiol , 100 : 1147 ) .", "entity": [{"entity": "NAGly", "entity_type": "Chemical", "pos": [15, 20]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [67, 74]}], "task": "NER"}
{"text": "Other proposed agonists of GPR18 , including anandamide and abnormal cannabidiol , also failed to induce inhibition of calcium currents .", "entity": [{"entity": "anandamide", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "cannabidiol", "entity_type": "Chemical", "pos": [69, 80]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [119, 126]}], "task": "NER"}
{"text": "Mutants of GPR18 , designed to constitutively activate receptors , did not tonically inhibit calcium currents , indicating a lack of GPR18 activation or coupling to endogenous G proteins .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [93, 100]}], "task": "NER"}
{"text": "Other downstream effectors of G alpha ( i / o ) - coupled receptors , G protein - coupled inwardly rectifying potassium channels and adenylate cyclase , were not modulated by GPR18 signaling .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [110, 119]}, {"entity": "adenylate", "entity_type": "Chemical", "pos": [133, 142]}], "task": "NER"}
{"text": "Furthermore , GPR18 did not couple to other G proteins tested : G alpha ( s ) , G alpha ( z ) , and G alpha ( 15 ) .", "entity": [], "task": "NER"}
{"text": "These results suggest NAGly is not an agonist for GPR18 or that GPR18 signaling involves noncanonical pathways not examined in these studies .", "entity": [{"entity": "NAGly", "entity_type": "Chemical", "pos": [22, 27]}], "task": "NER"}
{"text": "Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid .", "entity": [{"entity": "valproic acid", "entity_type": "Chemical", "pos": [131, 144]}], "task": "NER"}
{"text": "Ginseng is one of the most widely used medicinal plants , which belongs to the genus Panax .", "entity": [], "task": "NER"}
{"text": "Compared to uncured white ginseng , red ginseng has been generally regarded to produce superior pharmacological effects with lesser side / adverse effects , which made it popular in a variety of formulation from tea to oriental medicine .", "entity": [], "task": "NER"}
{"text": "Using the prenatal valproic acid ( VPA ) - injection model of autism spectrum disorder ( ASD ) in rats , which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype , we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA - exposed rat offspring .", "entity": [{"entity": "valproic acid", "entity_type": "Chemical", "pos": [19, 32]}, {"entity": "VPA", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "VPA", "entity_type": "Chemical", "pos": [405, 408]}], "task": "NER"}
{"text": "VPA - induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng ( KRG ) in a dose dependent manner .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open - field test .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level .", "entity": [], "task": "NER"}
{"text": "These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [149, 152]}], "task": "NER"}
{"text": "The crystal structure of human telomeric DNA complexed with berberine : an interesting case of stacked ligand to G - tetrad ratio higher than 1 : 1 .", "entity": [{"entity": "berberine", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "The first crystal structure of human telomeric DNA in complex with the natural alkaloid berberine , produced by different plant families and used in folk medicine for millennia , was solved by X - ray diffraction method .", "entity": [{"entity": "berberine", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "The G - quadruplex unit features all - parallel strands .", "entity": [], "task": "NER"}
{"text": "The overall folding assumed by DNA is the same found in previously reported crystal structures .", "entity": [], "task": "NER"}
{"text": "Similarly to previously reported structures the ligand molecules were found to be stacked onto the external 5 ' and 3 ' - end G - tetrads .", "entity": [], "task": "NER"}
{"text": "However , the present crystal structure highlighted for the first time , the presence of two berberine molecules in the two binding sites , directly interacting with each tetrad .", "entity": [{"entity": "berberine", "entity_type": "Chemical", "pos": [93, 102]}], "task": "NER"}
{"text": "As a consequence , our structural data point out a 2 : 1 ligand to G - tetrad molar ratio , which has never been reported before in a telomeric intramolecular quadruplex structure .", "entity": [], "task": "NER"}
{"text": "Arsenic increases Pi - mediated vascular calcification and induces premature senescence in vascular smooth muscle cells .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Several mechanisms have been proposed to explain the vascular toxicity of arsenic .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "Some of them are described in this work , such as stress - induced premature senescence ( SIPS ) , dedifferentiation , and medial vascular calcification , and they all affect vascular smooth muscle cells ( VSMC ) .", "entity": [], "task": "NER"}
{"text": "Rat aortic VSMC were treated with 1 - 100 micro M of either sodium arsenate ( As ( V ) ) , sodium arsenite ( As ( III ) ) , monomethylarsonic acid , or dimethylarsinic acid .", "entity": [{"entity": "sodium arsenate", "entity_type": "Chemical", "pos": [60, 75]}, {"entity": "As ( V )", "entity_type": "Chemical", "pos": [78, 86]}, {"entity": "sodium arsenite", "entity_type": "Chemical", "pos": [91, 106]}, {"entity": "As ( III )", "entity_type": "Chemical", "pos": [109, 119]}, {"entity": "monomethylarsonic acid", "entity_type": "Chemical", "pos": [124, 146]}, {"entity": "dimethylarsinic acid", "entity_type": "Chemical", "pos": [152, 172]}], "task": "NER"}
{"text": "None of the treatments induced VSMC calcification in the presence of 1mM inorganic phosphate ( Pi ) , but 1 micro M As ( III ) did increase calcification when induced with 2 . 5mM Pi .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [83, 92]}, {"entity": "As ( III )", "entity_type": "Chemical", "pos": [116, 126]}], "task": "NER"}
{"text": "A lactate dehydrogenase assay revealed that this increase was explained by a rise in cytotoxicity due to simultaneous incubation with 1 micro M As ( III ) and 2 . 5mM Pi .", "entity": [{"entity": "lactate", "entity_type": "Chemical", "pos": [2, 9]}, {"entity": "As ( III )", "entity_type": "Chemical", "pos": [144, 154]}], "task": "NER"}
{"text": "This calcification increase was also observed in the aortas of a vascular calcification model : 5 / 6 nephrectomized rats fed with a high Pi diet and treated with vitamin D ( 3 ) .", "entity": [{"entity": "vitamin D ( 3 )", "entity_type": "Chemical", "pos": [163, 178]}], "task": "NER"}
{"text": "Several known mechanisms that might explain arsenic toxicity in our experimental model were discarded : apoptosis , oxidative stress , and inflammasome activation .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "Nevertheless , both senescence - associated beta - galactosidase activity and p21 expression were increased by As ( III ) , which reveals the induction of SIPS .", "entity": [{"entity": "As ( III )", "entity_type": "Chemical", "pos": [111, 121]}], "task": "NER"}
{"text": "As ( III ) also caused dedifferentiation of VSMC , as shown by the reduced expression of the VSMC markers SM22 alpha and calponin .", "entity": [{"entity": "As ( III )", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Senescence and gene expression were also observed in the aortas of healthy rats treated with 50 ppm As ( V ) in drinking water for 1 month .", "entity": [{"entity": "As ( V )", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "In conclusion , both premature senescence in aortic VSMC with phenotypic dedifferentiation and the increase of Pi - induced calcification are novel mechanisms of arsenic vasculotoxicity .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [162, 169]}], "task": "NER"}
{"text": "Consideration of rat chronic progressive nephropathy in regulatory evaluations for carcinogenicity .", "entity": [], "task": "NER"}
{"text": "Chronic progressive nephropathy ( CPN ) is a spontaneous renal disease of rats which can be a serious confounder in toxicology studies .", "entity": [], "task": "NER"}
{"text": "It is a progressive disease with known physiological factors that modify disease progression , such as high dietary protein .", "entity": [], "task": "NER"}
{"text": "The weight of evidence supports an absence of a renal counterpart in humans .", "entity": [], "task": "NER"}
{"text": "There is extensive evidence that advanced CPN , particularly end - stage kidney , is a risk factor for development of a background incidence of atypical tubule hyperplasia and renal tubule tumors ( RTT ) .", "entity": [], "task": "NER"}
{"text": "The likely cause underlying this association with tubule neoplasia is the long - term increased tubule cell proliferation that occurs throughout CPN progression .", "entity": [], "task": "NER"}
{"text": "As a variety of chemicals are able to exacerbate CPN , there is a potential for those exacerbating the severity up to and including end - stage kidney to cause a marginal increase in RTT and their precursor lesions .", "entity": [], "task": "NER"}
{"text": "Extensive statistical analysis of National Toxicology Program studies shows a strong correlation between high - grade CPN , especially end - stage CPN , and renal tumor development .", "entity": [], "task": "NER"}
{"text": "CPN as a mode of action ( MOA ) for rat RTT has received attention from regulatory authorities only recently .", "entity": [], "task": "NER"}
{"text": "In the absence of toxic effects elsewhere , this does not constitute a carcinogenic effect of the chemical but can be addressed through a proposed MOA approach for regulatory purposes to reach a decision that RTT , developing as a result of CPN exacerbation in rats , have no relevance for human risk assessment .", "entity": [], "task": "NER"}
{"text": "Guidelines are proposed for evaluation of exacerbation of CPN and RTT as a valid MOA for a given chemical .", "entity": [], "task": "NER"}
{"text": "Differential influences of ethanol on early exposure to racemic methylphenidate compared with dexmethylphenidate in humans .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "methylphenidate", "entity_type": "Chemical", "pos": [64, 79]}, {"entity": "dexmethylphenidate", "entity_type": "Chemical", "pos": [94, 112]}], "task": "NER"}
{"text": "Enantioselective hydrolysis of oral racemic methylphenidate ( dl - MPH ) by carboxylesterase 1 ( CES1 ) limits the absolute bioavailability of the pharmacologically active d - MPH isomer to approximately 30 % and that of the inactive l - MPH to only 1 - 2 % .", "entity": [{"entity": "racemic methylphenidate", "entity_type": "Chemical", "pos": [36, 59]}, {"entity": "dl - MPH", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [172, 179]}, {"entity": "l - MPH", "entity_type": "Chemical", "pos": [234, 241]}], "task": "NER"}
{"text": "Coadministration of dl - MPH with ethanol results in elevated d - MPH plasma concentrations accompanied by CES1 - mediated enantioselective transesterification of l - MPH to l - ethylphenidate ( EPH ) .", "entity": [{"entity": "dl - MPH", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "l - MPH", "entity_type": "Chemical", "pos": [163, 170]}, {"entity": "l - ethylphenidate", "entity_type": "Chemical", "pos": [174, 192]}, {"entity": "EPH", "entity_type": "Chemical", "pos": [195, 198]}], "task": "NER"}
{"text": "The present study tested the hypothesis that administration of the pure isomer dexmethylphenidate ( d - MPH ) will overcome the influence of ethanol on d - MPH absorption by eliminating competitive CES1 - mediated presystemic metabolism of l - MPH to l - EPH .", "entity": [{"entity": "dexmethylphenidate", "entity_type": "Chemical", "pos": [79, 97]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [100, 107]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [141, 148]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [152, 159]}, {"entity": "l - MPH", "entity_type": "Chemical", "pos": [240, 247]}, {"entity": "l - EPH", "entity_type": "Chemical", "pos": [251, 258]}], "task": "NER"}
{"text": "Twenty - four healthy volunteers received dl - MPH ( 0 . 3 mg / kg ) or d - MPH ( 0 . 15 mg / kg ) , with or without ethanol ( 0 . 6 g / kg ) .", "entity": [{"entity": "dl - MPH", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [72, 79]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [117, 124]}], "task": "NER"}
{"text": "During the absorption phase of dl - MPH , concomitant ethanol significantly elevated d - MPH plasma concentrations ( 44 - 99 % ; P < 0 . 005 ) .", "entity": [{"entity": "dl - MPH", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [85, 92]}], "task": "NER"}
{"text": "Furthermore , immediately following the ethanol drink the subjective effects of \" high , \" \" good , \" \" like , \" \" stimulated , \" and overall \" effect \" were significantly potentiated ( P <= 0 . 01 ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [40, 47]}], "task": "NER"}
{"text": "Plasma l - EPH concentrations exceeded those of l - MPH .", "entity": [{"entity": "l - EPH", "entity_type": "Chemical", "pos": [7, 14]}, {"entity": "l - MPH", "entity_type": "Chemical", "pos": [48, 55]}], "task": "NER"}
{"text": "Ethanol combined with pure d - MPH did not elevate plasma d - MPH concentrations during the absorption phase , and the ethanol - induced potentiation of subjective effects was delayed relative to dl - MPH - ethanol .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [119, 126]}, {"entity": "dl - MPH", "entity_type": "Chemical", "pos": [196, 204]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [207, 214]}], "task": "NER"}
{"text": "These findings are consistent with l - MPH competitively inhibiting presystemic CES1 metabolism of d - MPH .", "entity": [{"entity": "l - MPH", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "Ethanol increased the d - MPH area under the curve ( AUC ) ( 0 - inf ) by 21 % following dl - MPH ( P < 0 . 001 ) and 14 % for d - MPH ( P = 0 . 001 ) .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "dl - MPH", "entity_type": "Chemical", "pos": [89, 97]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "In men receiving d - MPH - ethanol , the d - MPH absorption partial AUC ( 0 . 5 - 2 hours ) was 2 . 1 times greater and the time to maximum concentration ( T ( max ) ) occurred 1 . 1 hours earlier than in women , consistent with an increased rate of d - MPH absorption reducing hepatic extraction .", "entity": [{"entity": "d - MPH", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "d - MPH", "entity_type": "Chemical", "pos": [250, 257]}], "task": "NER"}
{"text": "More rapid absorption of d - MPH carries implications for increased abuse liability .", "entity": [{"entity": "d - MPH", "entity_type": "Chemical", "pos": [25, 32]}], "task": "NER"}
{"text": "Evolution and diversity of Arsenophonus endosymbionts in aphids .", "entity": [], "task": "NER"}
{"text": "Endosymbiotic bacteria are important drivers of insect evolutionary ecology , acting both as partners that contribute to host adaptation and as subtle parasites that manipulate host reproduction .", "entity": [], "task": "NER"}
{"text": "Among them , the genus Arsenophonus is emerging as one of the most widespread lineages .", "entity": [], "task": "NER"}
{"text": "Its biology is , however , entirely unknown in most cases , and it is therefore unclear how infections spread through insect populations .", "entity": [], "task": "NER"}
{"text": "Here we examine the incidence and evolutionary history of Arsenophonus in aphid populations from 86 species , characterizing the processes that shape their diversity .", "entity": [], "task": "NER"}
{"text": "We identify aphids as harbouring an important diversity of Arsenophonus strains .", "entity": [], "task": "NER"}
{"text": "Present in 7 % of the sampled species , incidence was especially high in the Aphis genus with more than 31 % of the infected species .", "entity": [], "task": "NER"}
{"text": "Phylogenetic investigations revealed that these Arseno - phonus strains do not cluster within an aphid - specific clade but rather exhibit distinct evolutionary origins showing that they undergo repeated horizontal transfers ( HT ) between distantly related host species .", "entity": [], "task": "NER"}
{"text": "Their diversity pattern strongly suggests that ecological interactions , such as plant mediation and parasitism , are major drivers for Arsenophonus dispersal , dictating global incidence across insect communities .", "entity": [], "task": "NER"}
{"text": "Notably , plants hosting aphids may be important ecological arenas for global exchange of Arsenophonus , serving as reservoirs for HT .", "entity": [], "task": "NER"}
{"text": "Methotrexate - conjugated and hyperbranched polyglycerol - grafted Fe 3 O 4 magnetic nanoparticles for targeted anticancer effects .", "entity": [{"entity": "Methotrexate", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "polyglycerol", "entity_type": "Chemical", "pos": [44, 56]}, {"entity": "Fe 3 O 4", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "Superparamagnetic nanoparticles grafted with hyperbranched polyglycerol ( HPG ) and conjugated with methotrexate ( MTX ) ( MNP - g - HPG - MTX ) were synthesized via a sol - gel reaction followed by thiol - ene click chemistry and esterification reaction .", "entity": [{"entity": "polyglycerol", "entity_type": "Chemical", "pos": [59, 71]}, {"entity": "methotrexate", "entity_type": "Chemical", "pos": [100, 112]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [115, 118]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [139, 142]}, {"entity": "thiol - ene", "entity_type": "Chemical", "pos": [199, 210]}], "task": "NER"}
{"text": "The successful grafting of MTX and HPG onto the nanoparticles was confirmed by X - ray photoelectron spectroscopy ( XPS ) , Fourier transform infrared ( FT - IR ) spectroscopy , and UV - visible spectroscopy .", "entity": [{"entity": "MTX", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "The HPG - graft layer confers the magnetic nanoparticles with good dispersibility and stability in aqueous medium and macrophage - evasive property while the MTX acts as a chemotherapeutic drug as well as a tumor targeting ligand .", "entity": [{"entity": "MTX", "entity_type": "Chemical", "pos": [158, 161]}], "task": "NER"}
{"text": "The dose - dependent targeting and anticancer effect of the MNP - g - HPG - MTX nanoparticles were evaluated , and the results showed that depending on the amount of conjugated MTX and the concentration of the incubated nanoparticles , the uptake of MNP - g - HPG - MTX nanoparticles by human head and neck cancer ( KB ) cells can be eight times or more higher than those by 3T3 fibroblasts and RAW macrophages .", "entity": [{"entity": "MTX", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [177, 180]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [266, 269]}], "task": "NER"}
{"text": "As a result , the MNP - g - HPG - MTX nanoparticles are capable of killing ~ 50 % of the KB cells while at the same time exhibiting low cytotoxicity towards 3T3 fibroblasts and RAW macrophages .", "entity": [{"entity": "MTX", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "Thus , such nanoparticles can potentially be used as active targeting anticancer agents .", "entity": [], "task": "NER"}
{"text": "Promoting effect of polysaccharide isolated from Mori fructus on dendritic cell maturation .", "entity": [], "task": "NER"}
{"text": "Maturation of dendritic cells ( DCs ) is usually attenuated in the tumor microenvironment , which is an important immunological problem in DC - based immunotherapy of cancer .", "entity": [], "task": "NER"}
{"text": "In this study , we report the effect of a Mori fructus polysaccharide ( MFP ) on DC maturation .", "entity": [], "task": "NER"}
{"text": "MFP was treated to DCs generated from mouse BM cells .", "entity": [], "task": "NER"}
{"text": "MFP induced phenotypic maturation of DCs , as proven by the increased expression of CD40 , CD80 / 86 , and MHC - I / II molecules .", "entity": [], "task": "NER"}
{"text": "MFP induced functional maturation of DCs , in that MFP increased the expression of IL - 12 , IL - 1 beta , TNF - alpha , and IFN - beta , decreased antigen capture capacity , and enhanced allogenic T cell stimulation .", "entity": [], "task": "NER"}
{"text": "MFP efficiently induced maturation of DCs from C3H / HeN mice having normal toll - like receptor4 ( TLR4 ) , but not DCs from C3H / HeJ mice having mutated TLR4 , suggesting that TLR4 might be one of the membrane receptors of MFP .", "entity": [], "task": "NER"}
{"text": "As a mechanism of action , MFP increased phosphorylation of mitogen - activated protein kinase ( MAPKs ) , and nuclear translocation of NF - kappa B p65 subunit , which were important signal molecules downstream from TLR4 .", "entity": [], "task": "NER"}
{"text": "These data suggest that MFP induces DC maturation through TLR4 and MFP can be used as an adjuvant in DC - based cancer immunotherapy .", "entity": [], "task": "NER"}
{"text": "The hypothalamus - adipose axis is a key target of developmental programming by maternal nutritional manipulation .", "entity": [], "task": "NER"}
{"text": "Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life .", "entity": [], "task": "NER"}
{"text": "High birth weight due to maternal obesity or diabetes , inappropriate early post - natal nutrition and rapid catch - up growth may also sensitise to increased risk of obesity .", "entity": [], "task": "NER"}
{"text": "As stated by the Developmental Origin of Health and Disease concept , the perinatal perturbation of foetus / neonate nutrient supply might be a crucial determinant of individual programming of body weight set point .", "entity": [], "task": "NER"}
{"text": "The hypothalamus - adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level .", "entity": [], "task": "NER"}
{"text": "The perinatal period largely corresponds to the period of brain maturation , neuronal differentiation and active adipogenesis in rodents .", "entity": [], "task": "NER"}
{"text": "Numerous dams and / or foetus / neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents .", "entity": [], "task": "NER"}
{"text": "These models showed several common offspring hypothalamic consequences such as impaired neurogenesis , neuronal functionality , nuclei structural organisation and feeding circuitry hardwiring .", "entity": [], "task": "NER"}
{"text": "These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways , leptin / insulin resistance and hyperphagia .", "entity": [], "task": "NER"}
{"text": "Impaired hypothalamic sympathetic outflow to adipose tissue and / or reduced innervation may also account for modified fat cell metabolism .", "entity": [], "task": "NER"}
{"text": "Thus , enhanced adipogenesis and / or lipogenesis capacities may predispose the offspring to fat accumulation .", "entity": [], "task": "NER"}
{"text": "Abnormal hypothalamus - adipose axis circadian rhythms were also evidenced .", "entity": [], "task": "NER"}
{"text": "This review mainly focuses on studies in rodents .", "entity": [], "task": "NER"}
{"text": "It highlights hormonal and epigenetic mechanisms responsible for long - lasting programming of energy balance in the offspring .", "entity": [], "task": "NER"}
{"text": "Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans .", "entity": [], "task": "NER"}
{"text": "Large - area fabrication of periodic sub - 15 nm - width single - layer graphene nanorings .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "A periodically aligned array of graphene nanorings ( GRNRs ) with a sub - 15 nm linewidth at a pitch of 450 nm is fabricated with a large area , 9 cm ( 2 ) , through conventional nanoimprint lithography coupled with sophisticated metal deposition and plasma - etching processes .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "The existence of the single - layer GRNRs is verified by various techniques .", "entity": [], "task": "NER"}
{"text": "Flexible and stretchable polymers with embedded magnetic nanostructures .", "entity": [], "task": "NER"}
{"text": "A novel pathway is presented to transfer and embed functional patterned magnetic nanostructures into flexible and stretchable polymeric membranes .", "entity": [], "task": "NER"}
{"text": "The geometrical and magnetic properties are maintained through the process , realized even directly inside a microfluidic channel .", "entity": [], "task": "NER"}
{"text": "These results pave the way to the realization of smart biomedical systems and devices based on the integration of magnetic nanostructures into new classes of substrates .", "entity": [], "task": "NER"}
{"text": "Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading .", "entity": [], "task": "NER"}
{"text": "Sclerostin , a product of the SOST gene produced mainly by osteocytes , is a potent negative regulator of bone formation that appears to be responsive to mechanical loading , with SOST expression increasing following mechanical unloading .", "entity": [], "task": "NER"}
{"text": "We tested the ability of a murine sclerostin antibody ( SclAbII ) to prevent bone loss in adult mice subjected to hindlimb unloading ( HLU ) via tail suspension for 21 days .", "entity": [], "task": "NER"}
{"text": "Mice ( n = 11 - 17 / group ) were assigned to control ( CON , normal weight bearing ) or HLU and injected with either SclAbII ( subcutaneously , 25 mg / kg ) or vehicle ( VEH ) twice weekly .", "entity": [], "task": "NER"}
{"text": "SclAbII completely inhibited the bone deterioration due to disuse , and induced bone formation such that bone properties in HLU - SclAbII were at or above values of CON - VEH mice .", "entity": [], "task": "NER"}
{"text": "For example , hindlimb bone mineral density ( BMD ) decreased - 9 . 2 % +/- 1 . 0 % in HLU - VEH , whereas it increased 4 . 2 % +/- 0 . 7 % , 13 . 1 % +/- 1 . 0 % , and 30 . 6 % +/- 3 . 0 % in CON - VEH , HLU - SclAbII , and CON - SclAbII , respectively ( p < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "Trabecular bone volume , assessed by micro - computed tomography ( micro CT ) imaging of the distal femur , was lower in HLU - VEH versus CON - VEH ( p < 0 . 05 ) , and was 2 - to 3 - fold higher in SclAbII groups versus VEH ( p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "Midshaft femoral strength , assessed by three - point bending , and distal femoral strength , assessed by micro - finite element analysis ( micro FEA ) , were significantly higher in SclAbII versus VEH - groups in both loading conditions .", "entity": [], "task": "NER"}
{"text": "Serum sclerostin was higher in HLU - VEH ( 134 +/- 5 pg / mL ) compared to CON - VEH ( 116 +/- 6 pg / mL , p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Serum osteocalcin was decreased by hindlimb suspension and increased by SclAbII treatment .", "entity": [], "task": "NER"}
{"text": "Interestingly , the anabolic effects of sclerostin inhibition on some bone outcomes appeared to be enhanced by normal mechanical loading .", "entity": [], "task": "NER"}
{"text": "Altogether , these results confirm the ability of SclAbII to abrogate disuse - induced bone loss and demonstrate that sclerostin antibody treatment increases bone mass by increasing bone formation in both normally loaded and underloaded environments .", "entity": [], "task": "NER"}
{"text": "Effects of bisphenol A on growth and nitrogen nutrition of roots of soybean seedlings .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [11, 22]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is an environmental endocrine disruptor that seriously threatens ecological systems .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "Plants are the primary producers in ecological systems , but little information is available concerning the toxic effect of BPA on plants .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "In the present study , the effects of BPA on the growth and nitrogen nutrition of roots of soybean seedlings were investigated by using a root automatic scan apparatus and biochemical methods .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [38, 41]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "It was found that when soybean seedlings were treated with 1 . 5 mg / L BPA , the growth of roots was improved , the content of nitrate in roots was increased , the content of ammonium in roots was decreased , and the activities of nitrate reductase and nitrite reductase in roots were not changed .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [128, 135]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [176, 184]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [232, 239]}, {"entity": "nitrite", "entity_type": "Chemical", "pos": [254, 261]}], "task": "NER"}
{"text": "The opposite effects were observed in roots treated with 17 . 2 mg / L and 50 . 0 mg / L BPA , except for an increase in the content of nitrate in roots treated with 17 . 2 mg / L BPA and a decrease in the activities of nitrate reductase and nitrite reductase in roots of soybeans seedlings .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [136, 143]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [180, 183]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [220, 227]}, {"entity": "nitrite", "entity_type": "Chemical", "pos": [242, 249]}], "task": "NER"}
{"text": "Statistical analysis indicated that the change in the nitrogen nutrition of roots of soybean seedlings treated with BPA was one reason why the growth of roots was changed .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "The authors suggest that the potential environmental and ecological risk of BPA to plants should receive more consideration .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "Piccolo NuA4 - catalyzed acetylation of nucleosomal histones : critical roles of an Esa1 Tudor / chromo barrel loop and an Epl1 enhancer of polycomb A ( EPcA ) basic region .", "entity": [], "task": "NER"}
{"text": "Piccolo NuA4 is an essential yeast histone acetyltransferase ( HAT ) complex that targets histones H4 and H2A in nucleosome substrates .", "entity": [], "task": "NER"}
{"text": "While Piccolo NuA4 ' s catalytic subunit Esa1 alone is unable to acetylate nucleosomal histones , its accessory subunits , Yng2 and Epl1 , enable Esa1 to bind to and to act on nucleosomes .", "entity": [], "task": "NER"}
{"text": "We previously determined that the Tudor domain of Esa1 and the EPcA homology domain of Epl1 play critical roles in Piccolo NuA4 ' s ability to act on the nucleosome .", "entity": [], "task": "NER"}
{"text": "In this work , we pinpoint a loop within the Esa1 Tudor domain and a short basic region at the N terminus of the Epl1 EPcA domain as necessary for this nucleosomal HAT activity .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [95, 96]}], "task": "NER"}
{"text": "We also show that this Esa1 Tudor domain loop region is positioned close to nucleosomal DNA and that the Epl1 EPcA basic region is in proximity to the N - terminal histone H2A tail , the globular region of histone H4 , and also to nucleosomal DNA when Piccolo NuA4 interacts with the nucleosome .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [89, 90]}], "task": "NER"}
{"text": "Since neither region identified is required for Piccolo NuA4 to bind to nucleosomes and yet both are needed to acetylate nucleosomes , these regions may function after the enzyme binds nucleosomes to disengage substrate histone tails from nucleosomal DNA .", "entity": [], "task": "NER"}
{"text": "Highly predictive ligand - based pharmacophore and homology models of ABHD6 .", "entity": [], "task": "NER"}
{"text": "alpha / beta - Hydrolase domain - containing 6 ( ABHD6 ) represents a potentially attractive therapeutic target for indirectly potentiating 2 - arachidonoylglycerol signaling ; however , the enzyme is currently largely uncharacterized .", "entity": [{"entity": "2 - arachidonoylglycerol", "entity_type": "Chemical", "pos": [140, 164]}], "task": "NER"}
{"text": "Here , we describe a five element , ligand - based pharmacophore model along with a refined homology model of ABHD6 .", "entity": [], "task": "NER"}
{"text": "Following a virtual screen of a modest database , both the pharmacophore and homology models were found to be highly predictive , preferentially identifying ABHD6 inhibitors over drug - like non - inhibitors .", "entity": [], "task": "NER"}
{"text": "The models yield insight into the features required for optimal ligand binding to ABHD6 and the atomic structure of the binding site .", "entity": [], "task": "NER"}
{"text": "In combination , the two models should be very helpful not only in high - throughput virtual screening , but also in lead optimization , and will facilitate the development of novel , selective ABHD6 inhibitors as potential drugs .", "entity": [], "task": "NER"}
{"text": "Toosendanin induces apoptosis through suppression of JNK signaling pathway in HL - 60 cells .", "entity": [{"entity": "Toosendanin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Toosendanin ( TSN ) , a triterpenoid isolated from Melia toosendan Sieb .", "entity": [{"entity": "Toosendanin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "TSN", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "triterpenoid", "entity_type": "Chemical", "pos": [24, 36]}], "task": "NER"}
{"text": "et Zucc . , has been found to suppress proliferation and induce apoptosis in a variety of human cancer cells .", "entity": [], "task": "NER"}
{"text": "However , the mechanism how TSN induces apoptosis remains poorly understood .", "entity": [{"entity": "TSN", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "In this study , we examined the effects of TSN on the growth , cell cycle arrest , induction of apoptosis and the involved signaling pathway in human promyelocytic leukemia HL - 60 cells .", "entity": [{"entity": "TSN", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "Proliferation of HL - 60 cells was inhibited in a dose - dependent manner with the IC ( 50 ( 48 h ) ) of 28 ng / mL .", "entity": [], "task": "NER"}
{"text": "The growth inhibition was due primarily to the S phase arrest and cell apoptosis .", "entity": [], "task": "NER"}
{"text": "Cell apoptosis induced by TSN was confirmed by Annexin V - FITC / propidium iodide staining .", "entity": [{"entity": "TSN", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [59, 63]}, {"entity": "propidium iodide", "entity_type": "Chemical", "pos": [66, 82]}], "task": "NER"}
{"text": "The increase of the pro - apoptotic protein Bax , cleaved PARP and caspase - 3 , and the decrease of anti - apoptotic protein Bcl - 2 were observed .", "entity": [], "task": "NER"}
{"text": "Western blot analysis indicated that TSN inhibits the CDC42 / MEKK1 / JNK pathway .", "entity": [{"entity": "TSN", "entity_type": "Chemical", "pos": [37, 40]}], "task": "NER"}
{"text": "Taken together , our study suggested , for the first time , that the pro - apoptotic effects of TSN on HL - 60 cells were mediated through JNK signaling pathway .", "entity": [{"entity": "TSN", "entity_type": "Chemical", "pos": [96, 99]}], "task": "NER"}
{"text": "Griseofulvin inhibits the growth of adrenocortical cancer cells in vitro .", "entity": [{"entity": "Griseofulvin", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Supernumerary centrosomes and aneuploidy are associated with a malignant phenotype of tumor cells .", "entity": [], "task": "NER"}
{"text": "Centrosomal clustering is a mechanism used by cancer cells with supernumerary centrosomes to solve the threatening problem of multipolar spindles .", "entity": [], "task": "NER"}
{"text": "Griseofulvin is an antifungal substance that interferes with the microtubule apparatus and inhibits centrosomal clustering .", "entity": [{"entity": "Griseofulvin", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "It has also been demonstrated that griseofulvin inhibits the growth of tumor cells in vitro and in vivo .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [35, 47]}], "task": "NER"}
{"text": "However , it is not yet known whether treatment with griseofulvin inhibits growth of adrenocortical tumor cells .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [53, 65]}], "task": "NER"}
{"text": "We studied the viability and antiproliferative effects of griseofulvin on cultured NCI - H295R adrenocortical carcinoma cells using Wst - 1 - , BrdUrd - , and [ 3H ] - thymidine assays .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [58, 70]}, {"entity": "Wst - 1", "entity_type": "Chemical", "pos": [132, 139]}, {"entity": "BrdUrd", "entity_type": "Chemical", "pos": [144, 150]}, {"entity": "[ 3H ] - thymidine", "entity_type": "Chemical", "pos": [159, 177]}], "task": "NER"}
{"text": "For the detection of apoptosis we used a caspase 3 / 7 cleavage assay and light microscopy techniques .", "entity": [], "task": "NER"}
{"text": "We observed that incubation with griseofulvin for 24 - 48 h leads to a decrease in the viability and proliferation of NCI - H295R cells in a dose - dependent manner .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [33, 45]}], "task": "NER"}
{"text": "Significant effects could be observed after incubation with griseofulvin as measured by Wst - 1 - , BrdUrd - , and [ 3H ] dT - uptake assays .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [60, 72]}, {"entity": "Wst - 1", "entity_type": "Chemical", "pos": [88, 95]}, {"entity": "BrdUrd", "entity_type": "Chemical", "pos": [100, 106]}, {"entity": "[ 3H ] dT", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "Apoptosis of NCI - H295R cells was increased in a dose - dependent manner up to 4 . 5 - fold after incubation with griseofulvin 40 mu M for 24 h as shown by caspase 3 / 7 cleavage assay and light microscopy .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [115, 127]}], "task": "NER"}
{"text": "With regard to new treatment strategies for adrenocortical cancer , griseofulvin , and possibly other agents , which interfere with the microtubule apparatus and inhibit centrosomal clustering , may turn out to be interesting targets for further research .", "entity": [{"entity": "griseofulvin", "entity_type": "Chemical", "pos": [68, 80]}], "task": "NER"}
{"text": "Nano - titanium dioxide induces genotoxicity and apoptosis in human lung cancer cell line , A549 .", "entity": [{"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [7, 23]}], "task": "NER"}
{"text": "The increased inhaled application of titanium dioxide nanoparticles ( TiO ( 2 ) NPs ) increases the potential pulmonary health risks .", "entity": [{"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [37, 53]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "The present investigations were carried out to study the TiO ( 2 ) NPs - induced apoptosis , oxidative stress and genotoxicity in the human lung cancer cell line , A549 , a widely used cell system for pulmonary toxicity studies .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "Tetrazolium bromide salt and lactate dehydrogenase release assays were used to study the cytotoxicity .", "entity": [{"entity": "Tetrazolium bromide salt", "entity_type": "Chemical", "pos": [0, 24]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "The genotoxicity studies were carried out using cytokinesis block micronucleus assay .", "entity": [], "task": "NER"}
{"text": "Apoptosis was confirmed by the formation of apoptotic bodies and altered expression ( messenger RNA ( mRNA ) and protein ) of markers such as P ( 53 ) , P ( 21 ) , Bax , Bcl ( 2 ) and cleaved caspase - 3 .", "entity": [], "task": "NER"}
{"text": "Cells exposed to TiO ( 2 ) NPs ( 10 and 50 mu g / ml ) for 6 - 24 h shows significant induction in oxidative stress , that is , the production of reactive oxygen species and malondialdehyde and decrease in the activity of catalase and glutathione .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [17, 26]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [155, 161]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [174, 189]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [235, 246]}], "task": "NER"}
{"text": "TiO ( 2 ) NPs exposure also induces the formation of apoptotic bodies and micronucleus as marker of genotoxicity .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "A significant up - regulation in the expression of apoptosis markers such as P ( 53 ) , P ( 21 ) and cleaved caspase - 3 was observed , while the levels were down - regulated for Bcl ( 2 ) at both mRNA and protein levels .", "entity": [], "task": "NER"}
{"text": "TiO ( 2 ) NPs exposure could not pose significant effects on Bax expression .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Data indicate that nano - TiO ( 2 ) induces oxidative stress , genotoxicity and apoptosis in human lung cancer cell line , A549 .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [26, 35]}], "task": "NER"}
{"text": "Our result also identifies the mechanisms involved in TiO ( 2 ) NP - induced changes in A549 cells .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "Perhaps , reporting for the first time , the association of TiO ( 2 ) NPs - induced genotoxicity and apoptosis at transcriptional and translational level in the human lung cancer cell line , A549 cells .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "The antinociceptive effects of nicotinic receptors alpha 7 - positive allosteric modulators in murine acute and tonic pain models .", "entity": [], "task": "NER"}
{"text": "The alpha 7 nicotinic acetylcholine receptor ( nAChR ) subtype is abundantly expressed in the central nervous system and in the periphery .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [22, 35]}], "task": "NER"}
{"text": "Recent evidence suggests that alpha 7 nAChR subtypes , which can be activated by an endogenous cholinergic tone , comprising acetylcholine and the alpha 7 nAChR agonist choline , play an important role in subchronic pain and inflammation .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [125, 138]}, {"entity": "choline", "entity_type": "Chemical", "pos": [169, 176]}], "task": "NER"}
{"text": "This study ' s objective was to test whether alpha 7 nAChR positive allosteric modulators ( PAMs ) produce antinociception in in vivo mouse models of acute and persistent pain .", "entity": [], "task": "NER"}
{"text": "Testing type I [ N - ( 5 - chloro - 2 - hydroxyphenyl ) - N ' - [ 2 - chloro - 5 - ( trifluoromethyl ) phenyl ] ( NS1738 ) ] and type II [ 1 - ( 5 - chloro - 2 , 4 - dimethoxy - phenyl ) - 3 - ( 5 - methyl - isoxazol - 3 - yl ) ( PNU - 120596 ) ] alpha 7 nAChR PAMs in acute and persistent pain , we found that , although neither reduced acute thermal pain , only PNU - 120596 dose - dependently attenuated paw - licking behavior in the formalin test .", "entity": [{"entity": "N - ( 5 - chloro - 2 - hydroxyphenyl ) - N ' - [ 2 - chloro - 5 - ( trifluoromethyl ) phenyl", "entity_type": "Chemical", "pos": [17, 109]}, {"entity": "NS1738", "entity_type": "Chemical", "pos": [114, 120]}, {"entity": "1 - ( 5 - chloro - 2 , 4 - dimethoxy - phenyl ) - 3 - ( 5 - methyl - isoxazol - 3 - yl )", "entity_type": "Chemical", "pos": [139, 227]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [230, 242]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [364, 376]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [437, 445]}], "task": "NER"}
{"text": "The long - acting effect of PNU - 120596 in this test was in discordance with its pharmacokinetic profile in mice , which suggests the involvement of postreceptor signaling mechanisms .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "Our results with selective mitogen - activated protein kinase kinase inhibitor 1 , 4 - diamino - 2 , 3 - dicyano - 1 , 4 - bis ( o - aminophenylmercapto ) butadiene monoethanolate ( U0126 ) argues for an important role of extracellular signal - regulated kinase - 1 / 2 pathways activation in PNU - 120596 ' s antinociceptive effects .", "entity": [{"entity": "1 , 4 - diamino - 2 , 3 - dicyano - 1 , 4 - bis ( o - aminophenylmercapto ) butadiene monoethanolate", "entity_type": "Chemical", "pos": [79, 179]}, {"entity": "U0126", "entity_type": "Chemical", "pos": [182, 187]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [293, 305]}], "task": "NER"}
{"text": "The alpha 7 antagonist MLA , administered intrathecally , reversed PNU - 120596 ' s effects , confirming PNU - 120596 ' s action , in part , through central alpha 7 nAChRs .", "entity": [{"entity": "MLA", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [67, 79]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [105, 117]}], "task": "NER"}
{"text": "Importantly , tolerance to PNU - 120596 was not developed after subchronic treatment of the drug .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [27, 39]}], "task": "NER"}
{"text": "Surprisingly , PNU - 120596 ' s antinociceptive effects were blocked by NS1738 .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [15, 27]}, {"entity": "NS1738", "entity_type": "Chemical", "pos": [72, 78]}], "task": "NER"}
{"text": "Our results indicate that type II alpha 7 nAChR PAM PNU - 120596 , but not type I alpha 7 nAChR PAM NS1738 , shows significant antinociception effects in persistent pain models in mice .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [52, 64]}, {"entity": "NS1738", "entity_type": "Chemical", "pos": [100, 106]}], "task": "NER"}
{"text": "A cyclometallated iridium ( III ) complex as a c - myc G - quadruplex stabilizer and down - regulator of c - myc oncogene expression .", "entity": [{"entity": "cyclometallated iridium ( III )", "entity_type": "Chemical", "pos": [2, 33]}], "task": "NER"}
{"text": "A new cyclometallated iridium ( III ) complex with the 2 , 2 ' - biquinoline N - donor ligand has been synthesized and characterized .", "entity": [{"entity": "cyclometallated iridium ( III )", "entity_type": "Chemical", "pos": [6, 37]}, {"entity": "2 , 2 ' - biquinoline", "entity_type": "Chemical", "pos": [55, 76]}, {"entity": "N", "entity_type": "Chemical", "pos": [77, 78]}], "task": "NER"}
{"text": "The interaction and affinity of the complex towards c - myc G - quadruplex and duplex DNA have been investigated using UV / Vis spectroscopy and gel mobility shift assay .", "entity": [], "task": "NER"}
{"text": "These studies revealed that complex 1 binds to c - myc G - quadruplexes ( Pu22 and Pu27 ) with high affinity but does not interact with duplex DNA either by intercalation or groove binding .", "entity": [], "task": "NER"}
{"text": "The ability of 1 to stabilize c - myc G - quadruplex DNA in vitro has also been examined through a PCR stop assay and a cell - based luciferase reporter assay .", "entity": [], "task": "NER"}
{"text": "Complex 1 displays promising cytotoxic activity against the HeLa cell line with sub - micromolar potency .", "entity": [], "task": "NER"}
{"text": "Platycodin D attenuates bile duct ligation - induced hepatic injury and fibrosis in mice .", "entity": [{"entity": "Platycodin D", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Platycodin D ( PD ) is the major triterpene saponin in the root of Platycodon grandiflorum .", "entity": [{"entity": "Platycodin D", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "triterpene saponin", "entity_type": "Chemical", "pos": [33, 51]}], "task": "NER"}
{"text": "The aim of the present study was to evaluate the protective effects of PD on bile duct ligation ( BDL ) - induced cholestasis in mice .", "entity": [], "task": "NER"}
{"text": "Mice were allocated to five groups : sham , BDL alone , and BDL with PD treatment at 1 , 2 , and 4mg / kg .", "entity": [], "task": "NER"}
{"text": "PD was administered to the mice for 28 consecutive days after the BDL operation .", "entity": [], "task": "NER"}
{"text": "PD treatment of BDL - operated mice decreased serum alanine aminotransferase , serum aspartate aminotransferase , and total bilirubin levels by up to 37 % , 31 % , and 41 % , respectively , in comparison with the levels in mice that underwent BDL alone .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [85, 94]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [124, 133]}], "task": "NER"}
{"text": "PD treatment attenuated oxidative stress , as evidenced by an increase in anti - oxidative enzyme levels glutathione and superoxide dismutase together with a decrease in lipid peroxidation and oxidative stress indices levels of malondialdehyde and nitric oxide .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [105, 116]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [121, 131]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [228, 243]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [248, 260]}], "task": "NER"}
{"text": "Histopathological studies further confirmed the protective effects of PD on cholestasis - induced hepatic injury and liver fibrosis in mice .", "entity": [], "task": "NER"}
{"text": "In addition , nuclear factor - kappa B and inducible nitric oxide synthase levels significantly decreased after PD treatment , as did the levels of hepatocyte apoptosis .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [53, 65]}], "task": "NER"}
{"text": "Taken together , these results suggest that PD treatment might be beneficial in cholestasis - induced hepatotoxicity .", "entity": [], "task": "NER"}
{"text": "Endocrine disruptive potential of endosulfan on the reproductive axis of Cichlasoma dimerus ( Perciformes , Cichlidae ) .", "entity": [{"entity": "endosulfan", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "Endosulfan ( ES ) , a persistent organochlorine pesticide , is widely used despite its toxicity to non - target animals .", "entity": [{"entity": "Endosulfan", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [33, 47]}], "task": "NER"}
{"text": "Upon reaching water bodies , ES can cause negative effects on aquatic animals , including disruption of hormonal systems .", "entity": [], "task": "NER"}
{"text": "However , the action of ES on fish reproductive axis has been hardly studied thus far .", "entity": [], "task": "NER"}
{"text": "The aim of the present work was to assess the endocrine disruptive potential of endosulfan on the pituitary gonadotropins levels and on the testes function due to ES in the South American freshwater fish Cichlasoma dimerus , using in vitro and in vivo approaches .", "entity": [{"entity": "endosulfan", "entity_type": "Chemical", "pos": [80, 90]}], "task": "NER"}
{"text": "In vitro experiments showed that ES inhibited the LH - stimulated steroidogenesis in gonads ; no change was observed in gonadotropins release from pituitaries in culture .", "entity": [], "task": "NER"}
{"text": "Laboratory waterborne ES ( 0 . 1 , 0 . 3 and 1 mu g / L ) exposure for two months caused decrease in beta FSH pituitary content and gamma GT activity in the testes ( Sertoli cell function marker ) .", "entity": [], "task": "NER"}
{"text": "Testicular histology revealed pathologies such as scarce intermediate stages of spermatogenesis , release of immature germ cells into the lobular lumen , presence of foam cells and interstitial fibrosis .", "entity": [], "task": "NER"}
{"text": "As FSH and FSH - mediated steroidogenesis regulate spermatogenesis and Sertoli cell function , the effect of ES on FSH could be responsible for the morphological alterations observed in testes .", "entity": [], "task": "NER"}
{"text": "In vitro , ES disrupted steroidogenesis in gonads , therefore similar effects in vivo cannot be ruled out .", "entity": [], "task": "NER"}
{"text": "Based on this evidence , ES exhibits an endocrine disruptive action on the reproductive axis of C . dimerus , causing disruption at the pituitary and / or at the gonad level .", "entity": [], "task": "NER"}
{"text": "These effects could acquire ecological significance under prolonged exposure to the pesticide in nature .", "entity": [], "task": "NER"}
{"text": "Antiarrhythmic effects of ( - ) - epicatechin - 3 - gallate , a novel sodium channel agonist in cultured neonatal rat ventricular myocytes .", "entity": [{"entity": "( - ) - epicatechin - 3 - gallate", "entity_type": "Chemical", "pos": [26, 59]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "( - ) - Epicatechin - 3 - gallate ( ECG ) , a polyphenol extracted from green tea , has been proposed as an effective compound for improving cardiac contractility .", "entity": [{"entity": "( - ) - Epicatechin - 3 - gallate", "entity_type": "Chemical", "pos": [0, 33]}, {"entity": "ECG", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "polyphenol", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "However , the therapeutic potential of ECG on the treatment of arrhythmia remains unknown .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "We investigated the direct actions of ECG on the modulation of ion currents and cardiac cell excitability in the primary culture of neonatal rat ventricular myocyte ( NRVM ) , which is considered a hypertrophic model for analysis of myocardial arrhythmias .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "By using the whole - cell patch - clamp configurations , we found ECG enhanced the slowly inactivating component of voltage - gated Na ( + ) currents ( I ( Na ) ) in a concentration - dependent manner ( 0 . 1 - 100 mu M ) with an EC ( 50 ) value of 3 . 8 mu M .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [132, 140]}, {"entity": "Na", "entity_type": "Chemical", "pos": [156, 158]}], "task": "NER"}
{"text": "ECG not only shifted the current - voltage relationship of peak I ( Na ) to the hyperpolarizing direction but also accelerated I ( Na ) recovery kinetics .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "Na", "entity_type": "Chemical", "pos": [68, 70]}, {"entity": "Na", "entity_type": "Chemical", "pos": [131, 133]}], "task": "NER"}
{"text": "Working at a concentration level of I ( Na ) enhancement , ECG has no notable effect on voltage - gated K ( + ) currents and L - type Ca ( 2 + ) currents .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "ECG", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [104, 111]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [134, 144]}], "task": "NER"}
{"text": "With culture time increment , the firing rate of spontaneous action potential ( sAP ) in NRVMs was gradually decreased until spontaneous early after - depolarization ( EAD ) was observed after about one week culture .", "entity": [], "task": "NER"}
{"text": "ECG increased the firing rate of normal sAP about two - fold without waveform alteration .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Interestingly , the bradycardia - dependent EAD could be significantly restored by ECG in fast firing rate to normal sAP waveform .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "The expression of dominant cardiac sodium channel subunit , Nav1 . 5 , was consistently detected throughout the culture periods .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [35, 41]}], "task": "NER"}
{"text": "Our results reveal how ECG , the novel I ( Na ) agonist , may act as a promising candidate in clinical applications on cardiac arrhythmias .", "entity": [{"entity": "ECG", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "Na", "entity_type": "Chemical", "pos": [43, 45]}], "task": "NER"}
{"text": "Acetylcholinesterase and agrin : Different functions , similar expression patterns , multiple roles .", "entity": [], "task": "NER"}
{"text": "Acetylcholinesterase ( AChE ) and agrin play unique functional roles in the neuromuscular junction ( NMJ ) .", "entity": [], "task": "NER"}
{"text": "AChE is a cholinergic and agrin a synaptogenetic component .", "entity": [], "task": "NER"}
{"text": "In spite of their different functions , they share several common features : their targeting is determined by alternative splicing ; unlike most other NMJ components they are expressed in both , muscle and motor neuron and both reside on the synaptic basal lamina of the NMJ .", "entity": [], "task": "NER"}
{"text": "Also , both were reported to play various nonjunctional roles .", "entity": [], "task": "NER"}
{"text": "However , while the origin of basal lamina bound agrin is undoubtedly neural , the neural origin of AChE , which is anchored to the basal lamina with collagenic tail ColQ , is elusive .", "entity": [], "task": "NER"}
{"text": "Hypothesizing that motor neuron proteins targeted to the NMJ basal lamina share common temporal pattern of expression , which is coordinated with the formation of basal lamina , we compared expression of agrin isoforms with the expression of AChE - T and ColQ in the developing rat spinal cord at the stages before and after the formation of NMJ basal lamina .", "entity": [], "task": "NER"}
{"text": "Cellular origin of AChE - T and agrin was determined by in situ hybridization and their quantitative levels by RT PCR .", "entity": [], "task": "NER"}
{"text": "We found parallel increase in expression of the synaptogenetic ( agrin 8 ) isoform of agrin and ColQ after the formation of basal lamina supporting the view that ColQ bound AChE and agrin 8 isoform are destined to the basal lamina .", "entity": [], "task": "NER"}
{"text": "Catalytic AChE - T subunit and agrin isoforms 19 and 0 followed different expression patterns .", "entity": [], "task": "NER"}
{"text": "In accordance with the reports of other authors , our investigations also revealed various alternative functions for AChE and agrin .", "entity": [], "task": "NER"}
{"text": "We have already demonstrated participation of AChE in myoblast apoptosis ; here we present the evidence that agrin promotes the maturation of heavy myosin chains and the excitation - contraction coupling .", "entity": [], "task": "NER"}
{"text": "These results show that common features of AChE and agrin extend to their capacity to play multiple roles in muscle development .", "entity": [], "task": "NER"}
{"text": "Sodium / iodide symporter is expressed in the majority of seminomas and embryonal testicular carcinomas .", "entity": [{"entity": "Sodium", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [9, 15]}], "task": "NER"}
{"text": "Testicular cancer is the most frequent cancer in young men .", "entity": [], "task": "NER"}
{"text": "The large majority of patients have a good prognosis , but in a small group of tumors , the current treatments are not effective .", "entity": [], "task": "NER"}
{"text": "Radioiodine is routinely used in the treatment of thyroid cancer and is currently investigated as a potential therapeutic tool even for extra - thyroid tumors able to concentrate this radioisotope .", "entity": [{"entity": "Radioiodine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Expression of Na ( + ) / I ( - ) symporter ( NIS ( SLC5A5 ) ) , the glycoprotein responsible for iodide transport , has been demonstrated in normal testicular tissue .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "I ( - )", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [97, 103]}], "task": "NER"}
{"text": "In this study , we analyzed NIS expression in a large series of testicular carcinomas .", "entity": [], "task": "NER"}
{"text": "Our retrospective series included 107 patients operated for testicular tumors : 98 typical seminomas , six embryonal carcinomas , one mixed embryonal choriocarcinoma , and two Leydig cells tumors .", "entity": [], "task": "NER"}
{"text": "Expression and regulation of NIS mRNA and protein levels were also investigated in human embryonal testicular carcinoma cells ( NTERA ) by real - time RT - PCR and western blotting respectively .", "entity": [], "task": "NER"}
{"text": "Immunohistochemical analysis showed the presence of NIS in the large majority of seminomas ( 90 / 98 ) and embryonal carcinomas ( 5 / 7 ) of the testis but not in Leydig cell carcinomas .", "entity": [], "task": "NER"}
{"text": "Expression of NIS protein was significantly associated with lymphovascular invasion .", "entity": [], "task": "NER"}
{"text": "In NTERA cells treated with the histone deacetylase inhibitors SAHA and valproic acid , a significant increase in NIS mRNA ( about 60 - and 30 - fold vs control , P < 0 . 001 and P < 0 . 01 respectively ) and protein levels , resulting in enhanced ability to uptake radioiodine , was observed .", "entity": [{"entity": "SAHA", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "valproic acid", "entity_type": "Chemical", "pos": [72, 85]}, {"entity": "radioiodine", "entity_type": "Chemical", "pos": [266, 277]}], "task": "NER"}
{"text": "Finally , NIS expression in testicular tumors with the more aggressive behavior is of interest for the potential use of targeting NIS to deliver radioiodine in malignant cells .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [145, 156]}], "task": "NER"}
{"text": "Evaluation of the relationship between sex , polymorphisms in CYP2C8 and CYP2C9 , and pharmacokinetics of angiotensin receptor blockers .", "entity": [], "task": "NER"}
{"text": "Angiotensin II receptor blockers ( ARBs ) are used to treat hypertension .", "entity": [], "task": "NER"}
{"text": "Most ARBs are metabolized by CYP2C9 .", "entity": [], "task": "NER"}
{"text": "The aim of this study is to evaluate the possible association between sex , polymorphisms in the CYP2C8 and CYP2C9 genes , and the pharmacokinetics of losartan , valsartan , candesartan , and telmisartan .", "entity": [{"entity": "losartan", "entity_type": "Chemical", "pos": [151, 159]}, {"entity": "valsartan", "entity_type": "Chemical", "pos": [162, 171]}, {"entity": "candesartan", "entity_type": "Chemical", "pos": [174, 185]}, {"entity": "telmisartan", "entity_type": "Chemical", "pos": [192, 203]}], "task": "NER"}
{"text": "The study population comprised 246 healthy volunteers from seven single - dose clinical trials : 64 from two candesartan studies , 43 from a telmisartan study , 36 from a losartan study , and 103 from three valsartan studies .", "entity": [{"entity": "candesartan", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "telmisartan", "entity_type": "Chemical", "pos": [141, 152]}, {"entity": "losartan", "entity_type": "Chemical", "pos": [171, 179]}, {"entity": "valsartan", "entity_type": "Chemical", "pos": [207, 216]}], "task": "NER"}
{"text": "DNA was extracted from blood samples and single - nucleotide polymorphisms in the CYP2C8 ( CYP2C8 * 2 , CYP2C8 * 3 , CYP2C8 * 4 , CYP2C8 * 5 ) and CYP2C9 ( CYP2C9 * 2 , CYP2C9 * 3 ) genes were evaluated using real - time polymerase chain reaction .", "entity": [], "task": "NER"}
{"text": "Sex only affected telmisartan pharmacokinetics , since women showed a higher telmisartan C ( max ) than men ( 590 . 5 +/- 75 . 8 ng / ml versus 282 . 1 +/- 30 . 8 ng / ml ; P <= 0 . 01 ) .", "entity": [{"entity": "telmisartan", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "telmisartan", "entity_type": "Chemical", "pos": [77, 88]}], "task": "NER"}
{"text": "CYP2C9 variants were associated only with losartan pharmacokinetics : the half - life of losartan was higher in CYP2C9 * 3 allele carriers ( 3 . 1 +/- 0 . 4 hours ) than in volunteers with the wild - type genotype ( 2 . 3 +/- 0 . 1 hours ) ( P <= 0 . 05 ) .", "entity": [{"entity": "losartan", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "losartan", "entity_type": "Chemical", "pos": [89, 97]}], "task": "NER"}
{"text": "CYP2C8 polymorphisms were associated only with valsartan pharmacokinetics , since * 2 allele carriers showed faster clearance ( 1 . 07 +/- 0 . 57 l / h . kg ) than those with the wild - type genotype ( 0 . 48 +/- 0 . 72 l / h . kg ; P <= 0 . 01 ) and carriers of the * 3 allele ( 0 . 35 +/- 0 . 49 l / h . kg ; P <= 0 . 001 ) .", "entity": [{"entity": "valsartan", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "These results suggest that genotypes for CYP2C9 and CYP2C8 are relevant to the pharmacokinetics of losartan and valsartan , respectively , but not the pharmacokinetics of candesartan or telmisartan .", "entity": [{"entity": "losartan", "entity_type": "Chemical", "pos": [99, 107]}, {"entity": "valsartan", "entity_type": "Chemical", "pos": [112, 121]}, {"entity": "candesartan", "entity_type": "Chemical", "pos": [171, 182]}, {"entity": "telmisartan", "entity_type": "Chemical", "pos": [186, 197]}], "task": "NER"}
{"text": "SpliceAid - F : a database of human splicing factors and their RNA - binding sites .", "entity": [], "task": "NER"}
{"text": "A comprehensive knowledge of all the factors involved in splicing , both proteins and RNAs , and of their interaction network is crucial for reaching a better understanding of this process and its functions .", "entity": [], "task": "NER"}
{"text": "A large part of relevant information is buried in the literature or collected in various different databases .", "entity": [], "task": "NER"}
{"text": "By hand - curated screenings of literature and databases , we retrieved experimentally validated data on 71 human RNA - binding splicing regulatory proteins and organized them into a database called ' SpliceAid - F ' ( http : / / www . caspur . it / SpliceAidF / ) .", "entity": [], "task": "NER"}
{"text": "For each splicing factor ( SF ) , the database reports its functional domains , its protein and chemical interactors and its expression data .", "entity": [], "task": "NER"}
{"text": "Furthermore , we collected experimentally validated RNA - SF interactions , including relevant information on the RNA - binding sites , such as the genes where these sites lie , their genomic coordinates , the splicing effects , the experimental procedures used , as well as the corresponding bibliographic references .", "entity": [], "task": "NER"}
{"text": "We also collected information from experiments showing no RNA - SF binding , at least in the assayed conditions .", "entity": [], "task": "NER"}
{"text": "In total , SpliceAid - F contains 4227 interactions , 2590 RNA - binding sites and 1141 ' no - binding ' sites , including information on cellular contexts and conditions where binding was tested .", "entity": [], "task": "NER"}
{"text": "The data collected in SpliceAid - F can provide significant information to explain an observed splicing pattern as well as the effect of mutations in functional regulatory elements .", "entity": [], "task": "NER"}
{"text": "Mapping of Saccharomyces cerevisiae metabolites in fermenting wheat straight - dough reveals succinic acid as pH - determining factor .", "entity": [{"entity": "succinic acid", "entity_type": "Chemical", "pos": [93, 106]}], "task": "NER"}
{"text": "Fermenting yeast does not merely cause dough leavening , but also contributes to the bread aroma and might alter dough rheology .", "entity": [], "task": "NER"}
{"text": "Here , the yeast carbon metabolism was mapped during bread straight - dough fermentation .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [17, 23]}], "task": "NER"}
{"text": "The concentration of most metabolites changed quasi linearly as a function of fermentation time .", "entity": [], "task": "NER"}
{"text": "Ethanol and carbon dioxide concentrations reached up to 60 mmol / 100g flour .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "carbon dioxide", "entity_type": "Chemical", "pos": [12, 26]}], "task": "NER"}
{"text": "Interestingly , high levels of glycerol ( up to 10 mmol / 100g flour ) and succinic acid ( up to 1 . 6 mmol / 100g flour ) were produced during dough fermentation .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "succinic acid", "entity_type": "Chemical", "pos": [75, 88]}], "task": "NER"}
{"text": "Further tests showed that , contrary to current belief , the pH decrease in fermenting dough is primarily caused by the production of succinic acid by the yeast instead of carbon dioxide dissolution or bacterial organic acids .", "entity": [{"entity": "succinic acid", "entity_type": "Chemical", "pos": [134, 147]}, {"entity": "carbon dioxide", "entity_type": "Chemical", "pos": [172, 186]}], "task": "NER"}
{"text": "Together , our results provide a comprehensive overview of metabolite production during dough fermentation and yield insight into the importance of some of these metabolites for dough properties .", "entity": [], "task": "NER"}
{"text": "Preparative separation and purification of sulforaphene from radish seeds by high - speed countercurrent chromatography .", "entity": [{"entity": "sulforaphene", "entity_type": "Chemical", "pos": [43, 55]}], "task": "NER"}
{"text": "Sulforaphene , a kind of isothiocyanates , derived from glucoraphenin which is the important ingredient of radish ( Raphanus sativus L . ) seeds , has shown significant pharmacological activities .", "entity": [{"entity": "Sulforaphene", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "isothiocyanates", "entity_type": "Chemical", "pos": [25, 40]}, {"entity": "glucoraphenin", "entity_type": "Chemical", "pos": [56, 69]}], "task": "NER"}
{"text": "In this paper , the separation and purification of sulforaphene from radish seeds , was achieved by high - speed countercurrent chromatography ( HSCCC ) .", "entity": [{"entity": "sulforaphene", "entity_type": "Chemical", "pos": [51, 63]}], "task": "NER"}
{"text": "A two - phase solvent system consisted of n - hexane - ethyl acetate - methanol - water ( 35 : 100 : 35 : 100 , v / v / v / v ) was applied .", "entity": [{"entity": "n - hexane", "entity_type": "Chemical", "pos": [42, 52]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [55, 68]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [71, 79]}], "task": "NER"}
{"text": "The revolution speed of the separation column , flow rate of the mobile phase and separation temperature were 800 rpm , 2 ml / min and 30 degrees C , respectively .", "entity": [], "task": "NER"}
{"text": "From about 1000 mg amount of the crude plant extract , 249 . 4 mg of pure sulforaphene was obtained by one - step separation on a 280 ml HSCCC column .", "entity": [{"entity": "sulforaphene", "entity_type": "Chemical", "pos": [74, 86]}], "task": "NER"}
{"text": "The purified sulforaphene was at a high purity of 96 . 9 % and the mass recovery was more than 95 % .", "entity": [{"entity": "sulforaphene", "entity_type": "Chemical", "pos": [13, 25]}], "task": "NER"}
{"text": "The purity of sulforaphene was determined by HPLC analysis and its chemical structure was assessed by MS , ( 1 ) H NMR , ( 13 ) C NMR and DEPT - 135 NMR .", "entity": [{"entity": "sulforaphene", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [107, 114]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [121, 129]}], "task": "NER"}
{"text": "Separation and quantification of water buffalo milk protein fractions and genetic variants by RP - HPLC .", "entity": [], "task": "NER"}
{"text": "A RP - HPLC method , developed for the separation and quantification of the most common genetic variants of bovine milk proteins , was successfully applied to the analysis of water buffalo milk .", "entity": [], "task": "NER"}
{"text": "All the most common buffalo casein and whey proteins fractions , as well as their genetic variants , were detected and separated simultaneously in 40 min .", "entity": [], "task": "NER"}
{"text": "Purified buffalo proteins were used as calibration standards and a total of 536 individual milk samples were analysed for protein composition .", "entity": [], "task": "NER"}
{"text": "alpha ( S1 ) - , alpha ( S2 ) - , beta gamma - , and kappa - casein were 32 . 2 % , 15 . 8 % , 36 . 5 % , and 15 . 5 % , respectively , of total casein content , whereas content of beta - Lactoglobulin was approximately 1 . 3 times as high as that of alpha - Lactalbumin .", "entity": [], "task": "NER"}
{"text": "The existence of a polymorphism of kappa - casein was demonstrated in Mediterranean water buffalo and alpha ( S1 ) - and kappa - casein genetic variants were successfully detected by RP - HPLC .", "entity": [], "task": "NER"}
{"text": "Lead and cadmium concentrations in goat , cow , sheep , and buffalo milks from different regions of Iran .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [9, 16]}], "task": "NER"}
{"text": "In total , 137 goat , cow , sheep , and buffalo milk samples were collected in different regions of Iran and analysed to determine concentrations of lead and cadmium by a graphite furnace atomic absorption spectrometric method .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [158, 165]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [171, 179]}], "task": "NER"}
{"text": "The mean recovery of the analytical method was 96 . 3 % and 104 % for cadmium and lead , respectively .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "The mean lead and cadmium contents obtained from 137 samples were 1 . 93 +/- 1 . 48 ( range : 0 . 18 - 6 . 11 ng / ml ) and 9 . 51 +/- 4 . 93 ng / ml ( range : 1 . 84 ng / ml - 30 . 50 ng / ml ) , respectively .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [18, 25]}], "task": "NER"}
{"text": "Lead concentration in 8 . 1 % of sheep and 1 . 9 % of cow milk samples was higher than the newly established Codex standard .", "entity": [], "task": "NER"}
{"text": "The mean concentrations of cadmium and lead in animals aged <= 3 years ( n = 80 ; 1 . 40 +/- 1 . 05 ng / ml and 7 . 91 +/- 3 . 60 ng / ml , respectively ) were lower than in animals aged > 3 years ( n = 58 ; 2 . 69 +/- 1 . 67 ng / ml and 11 . 8 +/- 5 . 71 ng / ml , respectively ) .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "Purification and characterization of membrane - bound polyphenoloxidase ( mPPO ) from Snake fruit [ Salacca zalacca ( Gaertn . ) Voss ] .", "entity": [], "task": "NER"}
{"text": "Membrane - bound polyphenoloxidase ( mPPO ) an oxidative enzyme which is responsible for the undesirable browning reaction in Snake fruit ( Salacca zalacca ( Gaertn . ) Voss ) was investigated .", "entity": [], "task": "NER"}
{"text": "The enzyme was extracted using a non - ionic detergent ( Triton X - 114 ) , followed by temperature - induced phase partitioning technique which resulted in two separate layers ( detergent - poor phase at the upper layer and detergent - rich phase at the lower layer ) .", "entity": [{"entity": "Triton X - 114", "entity_type": "Chemical", "pos": [57, 71]}], "task": "NER"}
{"text": "The upper detergent - poor phase extract was subsequently fractionated by 40 - 80 % ammonium sulfate and chromatographed on HiTrap Phenyl Sepharose and Superdex 200 HR 10 / 30 .", "entity": [{"entity": "ammonium sulfate", "entity_type": "Chemical", "pos": [84, 100]}, {"entity": "Phenyl", "entity_type": "Chemical", "pos": [131, 137]}], "task": "NER"}
{"text": "The mPPO was purified to 14 . 1 folds with a recovery of 12 . 35 % .", "entity": [], "task": "NER"}
{"text": "A single prominent protein band appeared on native - PAGE and SDS - PAGE implying that the mPPO is a monomeric protein with estimated molecular weight of 38kDa .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [62, 65]}], "task": "NER"}
{"text": "Characterization study showed that mPPO from Snake fruit was optimally active at pH 6 . 5 , temperature 30 degrees C and active towards diphenols as substrates .", "entity": [{"entity": "diphenols", "entity_type": "Chemical", "pos": [136, 145]}], "task": "NER"}
{"text": "The K ( m ) and V ( max ) values were calculated to be 5 . 46 mM and 0 . 98 U / ml / min , respectively , when catechol was used as substrate .", "entity": [{"entity": "catechol", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "Among the chemical inhibitors tested , l - cysteine showed the best inhibitory effect , with an IC ( 50 ) of 1 . 3 +/- 0 . 002 mM followed by ascorbic acid ( 1 . 5 +/- 0 . 06 mM ) , glutathione ( 1 . 5 +/- 0 . 07 mM ) , EDTA ( 100 +/- 0 . 02 mM ) and citric acid ( 186 +/- 0 . 16 mM ) .", "entity": [{"entity": "l - cysteine", "entity_type": "Chemical", "pos": [39, 51]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [142, 155]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [182, 193]}, {"entity": "EDTA", "entity_type": "Chemical", "pos": [220, 224]}, {"entity": "citric acid", "entity_type": "Chemical", "pos": [251, 262]}], "task": "NER"}
{"text": "Toona sinensis and its major bioactive compound gallic acid inhibit LPS - induced inflammation in nuclear factor - kappa B transgenic mice as evaluated by in vivo bioluminescence imaging .", "entity": [{"entity": "gallic acid", "entity_type": "Chemical", "pos": [48, 59]}], "task": "NER"}
{"text": "In the present study , we investigated the anti - inflammatory effects of a nutritious vegetable Toona sinensis ( leaf extracts , TS ) and its major bioactive compound gallic acid ( GA ) by analysing LPS - induced NF - kappa B activation in transgenic mice , using bioluminescence imaging .", "entity": [{"entity": "gallic acid", "entity_type": "Chemical", "pos": [168, 179]}], "task": "NER"}
{"text": "Mice were challenged intraperitoneally with LPS ( 1mg / kg ) and treated orally with TS or GA ( 100 or 5mg / kg , respectively ) .", "entity": [], "task": "NER"}
{"text": "In vivo and ex vivo imaging showed that LPS increased NF - kappa B luminescence in the abdominal region , which was significantly inhibited by TS or GA .", "entity": [], "task": "NER"}
{"text": "Immunohistochemical and ELISA analyses confirmed that TS and GA inhibited LPS - induced NF - kappa B , interleukin - 1 beta , and tumour necrosis factor - alpha expression .", "entity": [], "task": "NER"}
{"text": "Microarray analysis revealed that biological pathways associated with metabolism and the immune responses were affected by TS or GA .", "entity": [], "task": "NER"}
{"text": "Particularly , LPS - induced thioredoxin - like 4B ( TXNL4B ) 2 expression in the small intestine , and TXNL4B , iNOS , and COX - 2 expression in RAW 264 . 7 cells were significantly inhibited by TS or GA .", "entity": [], "task": "NER"}
{"text": "Thus , the anti - inflammatory potential of TS was mediated by the downregulation of NF - kappa B pathway .", "entity": [], "task": "NER"}
{"text": "HPLC confirmatory method development for the determination of seven quinolones in salmon tissue ( Salmo salar L . ) validated according to the European Union Decision 2002 / 657 / EC .", "entity": [{"entity": "quinolones", "entity_type": "Chemical", "pos": [68, 78]}], "task": "NER"}
{"text": "A confirmatory high pressure liquid chromatographic method for the determination of seven quinolone antibiotics in tissue of Atlantic salmon ( Salmo salar L . ) was developed .", "entity": [{"entity": "quinolone", "entity_type": "Chemical", "pos": [90, 99]}], "task": "NER"}
{"text": "Ciprofloxacin ( CIP ) , danofloxacin ( DAN ) , enrofloxacin ( ENR ) , sarafloxacin ( SAR ) , oxolinic acid ( OXO ) , nalidixic acid ( NAL ) and flumequine ( FLU ) were separated on a Perfectsil ODS - 2 120 ( 250 mm x 4 mm , 5 mu m ) column by gradient elution with a mobile phase consisting of 0 . 1 % trifluoroacetic acid ( pH = 1 ) , acetonitrile and methanol at 25 degrees C within 22 min .", "entity": [{"entity": "Ciprofloxacin", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "CIP", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "danofloxacin", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "DAN", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "enrofloxacin", "entity_type": "Chemical", "pos": [47, 59]}, {"entity": "ENR", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "sarafloxacin", "entity_type": "Chemical", "pos": [70, 82]}, {"entity": "SAR", "entity_type": "Chemical", "pos": [85, 88]}, {"entity": "oxolinic acid", "entity_type": "Chemical", "pos": [93, 106]}, {"entity": "OXO", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "nalidixic acid", "entity_type": "Chemical", "pos": [117, 131]}, {"entity": "NAL", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "flumequine", "entity_type": "Chemical", "pos": [144, 154]}, {"entity": "FLU", "entity_type": "Chemical", "pos": [157, 160]}, {"entity": "trifluoroacetic acid", "entity_type": "Chemical", "pos": [302, 322]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [336, 348]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [353, 361]}], "task": "NER"}
{"text": "Analytes were monitored at 255 nm ( for the determination of OXO , NAL and FLU ) and 275 nm ( for CIP , DAN , ENR and SAR ) by means of photodiode array detector .", "entity": [{"entity": "OXO", "entity_type": "Chemical", "pos": [61, 64]}, {"entity": "NAL", "entity_type": "Chemical", "pos": [67, 70]}, {"entity": "FLU", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "CIP", "entity_type": "Chemical", "pos": [98, 101]}, {"entity": "DAN", "entity_type": "Chemical", "pos": [104, 107]}, {"entity": "ENR", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "SAR", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "Examined quinolones were isolated from salmon tissue by extraction with citrate buffer solution ( pH = 4 . 7 ) and purified by solid phase extraction using Oasis HLB ( 200mg / 6 mL ) cartridges .", "entity": [{"entity": "quinolones", "entity_type": "Chemical", "pos": [9, 19]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [72, 79]}], "task": "NER"}
{"text": "The developed method was fully validated in terms of selectivity , linearity , accuracy , precision , stability and sensitivity according to the European Union Decision 2002 / 657 / EC .", "entity": [], "task": "NER"}
{"text": "The accuracy of the method was additionally proved by its application to certified reference material of salmon tissue ( BCR (R) 725 ) .", "entity": [], "task": "NER"}
{"text": "Chemical analysis and anti - inflammatory comparison of the cell culture of Glycyrrhiza with its field cultivated variety .", "entity": [], "task": "NER"}
{"text": "Suspended cells of Glycyrrhiza ( CG ) possessed a similar content of flavonoids and a lower content of triterpenes , when compared with its field cultivated equivalent ( NG ) .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "triterpenes", "entity_type": "Chemical", "pos": [103, 114]}], "task": "NER"}
{"text": "Xylene - induced ear oedema and ovalbumin - induced mouse paw oedema were applied , to compare the effects of CG and NG on the acute inflammatory response .", "entity": [{"entity": "Xylene", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Extracts of the cell culture of Glycyrrhiza possessed a similar anti - inflammatory effect to those of NG , through the enhancement of the SOD activity of plasma and liver tissues .", "entity": [], "task": "NER"}
{"text": "The use of a cell culture of liquorice instead of field cultivation would be potentially profitable .", "entity": [], "task": "NER"}
{"text": "Antiproliferative and immunoactivatory ability of an enzymatic extract from rice bran .", "entity": [], "task": "NER"}
{"text": "The validation of natural products as source of functional foods or nutraceuticals has become an important issue in current health research .", "entity": [], "task": "NER"}
{"text": "Thus , the present work has tested on MOLT - 4 cells ( human T cell acute lymphoblastic leukemic ) the antiproliferative effect of a water - soluble enzymatic extract from rice bran ( EERB ) .", "entity": [], "task": "NER"}
{"text": "Present work shows that EERB induces cellular death in MOLT - 4 cells in a dose - dependent way ( 0 - 10mg / mL ) but not in non - tumoral lymphocytes .", "entity": [], "task": "NER"}
{"text": "Flow cytometric analysis of MOLT - 4 cells treated with EERB showed the presence of death cells by apoptosis rather than necrosis .", "entity": [], "task": "NER"}
{"text": "Additionally , EERB also exerts an immunoactivatory effect on N13 microglia cells , by inducing TNF - alpha ( tumour necrosis factor - alpha ) expression , which plays a key role in the innate immune response to infection .", "entity": [], "task": "NER"}
{"text": "Accordingly , we can propose EERB as a useful natural standardized extract with antiproliferative and immunoactivatory ability that would be beneficial to apply in the functional food field .", "entity": [], "task": "NER"}
{"text": "Effect of extrusion conditions on physicochemical and sensorial properties of corn - broad beans ( Vicia faba ) spaghetti type pasta .", "entity": [], "task": "NER"}
{"text": "Corn - broad bean spaghetti type pasta was made with a corn / broad bean flour blend in a 70 : 30 ratio , through an extrusion - cooking process ( Brabender 10 DN single - screw extruder with a 3 : 1 compression ratio ) .", "entity": [], "task": "NER"}
{"text": "The effect of temperature ( T = 80 , 90 and 100 degrees C ) and moisture ( M = 28 % , 31 % and 34 % ) on the extrusion responses ( specific consumption of mechanical energy and pressure ) and the quality of this pasta - like product ( expansion , cooking - related losses , water absorption , firmness and stickiness ) was assessed .", "entity": [], "task": "NER"}
{"text": "The structural changes of starch were studied by means of DSC and XRD .", "entity": [], "task": "NER"}
{"text": "The extrusion - cooking process , at M = 28 % and T = 100 degrees C , is appropriate to obtain corn - broad bean spaghetti - type pasta with high protein and dietary fibre content and adequate quality .", "entity": [], "task": "NER"}
{"text": "The cooking characteristics and resistance to overcooking depended on the degree of gelatinisation and formation of amylose - lipid complexes .", "entity": [], "task": "NER"}
{"text": "The critical gelatinisation point was 46 . 55 % ; beyond that point , the quality of the product declines .", "entity": [], "task": "NER"}
{"text": "Quantitative determination of fatty acid chain composition in pork meat products by high resolution 1H NMR spectroscopy .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "1H", "entity_type": "Chemical", "pos": [100, 102]}], "task": "NER"}
{"text": "High resolution ( 1 ) H NMR spectroscopy was proposed for the determination of the fatty acid chain profile of lipids in pork meat products during ripening .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [83, 93]}], "task": "NER"}
{"text": "Two typical Mediterranean PDO salami produced in Calabria , a region in the Southern Italy , were chosen as a case of study .", "entity": [], "task": "NER"}
{"text": "Quantitative NMR analysis provided the fatty acid chain profiles of total lipid extracts .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "The transesterification of total lipid extracts furnished FAME mixtures that enabled quantitation of fatty acid acyl chains in the acylglycerol and FFA portions .", "entity": [{"entity": "FAME", "entity_type": "Chemical", "pos": [58, 62]}, {"entity": "fatty acid acyl", "entity_type": "Chemical", "pos": [101, 116]}, {"entity": "acylglycerol", "entity_type": "Chemical", "pos": [131, 143]}], "task": "NER"}
{"text": "In all cases , oleyl chains were predominant , and high amounts of polyunsaturated fatty acid chains were observed .", "entity": [{"entity": "oleyl", "entity_type": "Chemical", "pos": [15, 20]}, {"entity": "polyunsaturated fatty acid", "entity_type": "Chemical", "pos": [67, 93]}], "task": "NER"}
{"text": "The proposed spectroscopic method allowed also the estimation of the most important nutritional parameters of dry fermented meat products .", "entity": [], "task": "NER"}
{"text": "Identification of a novel phenolic compound in litchi ( Litchi chinensis Sonn . ) pericarp and bioactivity evaluation .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "Litchi ( Litchi chinensis Sonn . ) is a delicious fruit widely accepted by consumers all over the world .", "entity": [], "task": "NER"}
{"text": "In this work , phytochemical investigation of litchi pericarp methanol extracts led to the isolation of a novel phenolic , 2 - ( 2 - hydroxyl - 5 - ( methoxycarbonyl ) phenoxy ) benzoic acid , together with kaempferol , isolariciresinol , stigmasterol , butylated hydroxytoluene , 3 , 4 - dihydroxyl benzoate , methyl shikimate and ethyl shikimate .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [112, 120]}, {"entity": "2 - ( 2 - hydroxyl - 5 - ( methoxycarbonyl ) phenoxy ) benzoic acid", "entity_type": "Chemical", "pos": [123, 190]}, {"entity": "kaempferol", "entity_type": "Chemical", "pos": [207, 217]}, {"entity": "isolariciresinol", "entity_type": "Chemical", "pos": [220, 236]}, {"entity": "stigmasterol", "entity_type": "Chemical", "pos": [239, 251]}, {"entity": "butylated hydroxytoluene", "entity_type": "Chemical", "pos": [254, 278]}, {"entity": "3 , 4 - dihydroxyl benzoate", "entity_type": "Chemical", "pos": [281, 308]}, {"entity": "methyl shikimate", "entity_type": "Chemical", "pos": [311, 327]}, {"entity": "ethyl shikimate", "entity_type": "Chemical", "pos": [332, 347]}], "task": "NER"}
{"text": "Most were found in litchi pericarp for the first time .", "entity": [], "task": "NER"}
{"text": "Their structures were mainly elucidated by NMR and MS evidences .", "entity": [], "task": "NER"}
{"text": "Antioxidant activities of the eight compounds were determined by a DPPH radical scavenging assay and the results showed that 2 - ( 2 - hydroxy - 5 - ( methoxycarbonyl ) phenoxy ) benzoic acid , kaempferol , isolariciresinol , butylated hydroxytoluene and 3 , 4 - dihydroxy benzoate exhibited good antioxidant activities .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [67, 71]}, {"entity": "2 - ( 2 - hydroxy - 5 - ( methoxycarbonyl ) phenoxy ) benzoic acid", "entity_type": "Chemical", "pos": [125, 191]}, {"entity": "kaempferol", "entity_type": "Chemical", "pos": [194, 204]}, {"entity": "isolariciresinol", "entity_type": "Chemical", "pos": [207, 223]}, {"entity": "butylated hydroxytoluene", "entity_type": "Chemical", "pos": [226, 250]}, {"entity": "3 , 4 - dihydroxy benzoate", "entity_type": "Chemical", "pos": [255, 281]}], "task": "NER"}
{"text": "An interesting finding was that butylated hydroxytoluene was detected as a natural antioxidant in this work , which was usually taken as a synthesized antioxidant .", "entity": [{"entity": "butylated hydroxytoluene", "entity_type": "Chemical", "pos": [32, 56]}], "task": "NER"}
{"text": "Furthermore , the novel compound exhibited no inhibitory effects against tyrosinase and alpha - glucosidase activities .", "entity": [], "task": "NER"}
{"text": "Rapid resolution liquid chromatography - electrospray ionisation tandem mass spectrometry method for identification of chemical constituents in Citri Reticulatae Pericarpium .", "entity": [], "task": "NER"}
{"text": "Citri Reticulatae Pericarpium ( CRP ) is one of the most commonly used traditional Chinese medicines with great medicinal and dietary values .", "entity": [], "task": "NER"}
{"text": "In this work , we developed an approach utilising rapid resolution liquid chromatography / electrospray ionisation tandem mass spectrometry ( RRLC - ESI - MS / MS ) for the identification and profiling of chemical composition in CRP .", "entity": [], "task": "NER"}
{"text": "On the basis of RRLC retention times , cochromatography with available authentic standards , mass spectral fragmentation patterns and literature information , a total of 41 chemical compounds , including 4 flavone - C - glycosides , 7 flavonoid - O - glycosides and 19 polymethoxyflavones were unambiguously identified or tentatively characterised in CRP .", "entity": [{"entity": "flavone - C - glycosides", "entity_type": "Chemical", "pos": [206, 230]}, {"entity": "flavonoid - O - glycosides", "entity_type": "Chemical", "pos": [235, 261]}, {"entity": "polymethoxyflavones", "entity_type": "Chemical", "pos": [269, 288]}], "task": "NER"}
{"text": "The occurrence of 1 flavone - C - glycoside and 3 cyclic peptides in particular has not yet been described .", "entity": [{"entity": "flavone - C - glycoside", "entity_type": "Chemical", "pos": [20, 43]}], "task": "NER"}
{"text": "The results indicated that the developed method could serve as a rapid , effective tool for structural characterisation of chemical constituents in CRP .", "entity": [], "task": "NER"}
{"text": "Resveratrols in Vitis berry skins and leaves : their extraction and analysis by HPLC .", "entity": [{"entity": "Resveratrols", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "An orthogonal L ( 36 ) ( 6 ) ( 5 ) test design was applied to select the optimum conditions for extracting resveratrols from grape berry skins and leaves .", "entity": [{"entity": "resveratrols", "entity_type": "Chemical", "pos": [107, 119]}], "task": "NER"}
{"text": "Solvent choice was the most important factor in the extraction of resveratrols , and mixed methanol and ethyl acetate [ 50 : 50 ( v / v ) ] had much higher extraction efficiency than the other five solvents tested .", "entity": [{"entity": "resveratrols", "entity_type": "Chemical", "pos": [66, 78]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [104, 117]}], "task": "NER"}
{"text": "For extracting resveratrols , 1g of berry skins or leaf tissue extracted in 10 mL methanol and ethyl acetate [ 50 : 50 ( v / v ) ] for 24h at 25 degrees C in darkness was the optimized extraction condition .", "entity": [{"entity": "resveratrols", "entity_type": "Chemical", "pos": [15, 27]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "The optimized analytical method for HPLC was a multi - step gradient elution using acetonitrile and water .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [83, 95]}], "task": "NER"}
{"text": "The optimized method was used to determine resveratrols among three different cultivars .", "entity": [{"entity": "resveratrols", "entity_type": "Chemical", "pos": [43, 55]}], "task": "NER"}
{"text": "The cultivar ' Zhi 168 ' had the highest total resveratrols in berry skins while ' Saint - Emilion ' had the lowest resveratrols .", "entity": [{"entity": "resveratrols", "entity_type": "Chemical", "pos": [47, 59]}, {"entity": "resveratrols", "entity_type": "Chemical", "pos": [116, 128]}], "task": "NER"}
{"text": "The resveratrol content of ' Beta ' was between that of ' Zhi 168 ' and ' Saint - Emilion ' .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [4, 15]}], "task": "NER"}
{"text": "Electronic nose and GC - MS analysis of volatile compounds in Tuber magnatum Pico : evaluation of different storage conditions .", "entity": [], "task": "NER"}
{"text": "The characteristic aromatic composition of white truffles ( Tuber magnatum Pico ) determines its culinary and commercial value .", "entity": [], "task": "NER"}
{"text": "However modifications of truffle organoleptic proprieties occur during preservation .", "entity": [], "task": "NER"}
{"text": "A study of headspace of white truffles by using Electronic nose ( E - nose ) , gas chromatography - mass spectrometry ( GC - MS ) and sensory analyses was performed .", "entity": [], "task": "NER"}
{"text": "Truffles were stored at different conditions for 7 days : + 4 and + 8 degrees C wrapped in blotting paper or covered by rice or none of the above .", "entity": [], "task": "NER"}
{"text": "Headspace E - nose measurements and sensory analyses were performed each day .", "entity": [], "task": "NER"}
{"text": "Statistical multivariate analysis of the data showed the capability of E - nose to predict sensorial analysis scores and to monitor aroma profile changes during storage .", "entity": [], "task": "NER"}
{"text": "Truffle ' s volatile molecules were also extracted by headspace solid phase microextraction technique and separated and identified by GC - MS .", "entity": [], "task": "NER"}
{"text": "Partial Components Analysis of data was performed .", "entity": [], "task": "NER"}
{"text": "E - nose and GC - MS results were in agreement and showed that truffle storage in paper at + 8 degrees C seemed to be the best storage condition .", "entity": [], "task": "NER"}
{"text": "Comparison of different methods to quantify fat classes in bakery products .", "entity": [], "task": "NER"}
{"text": "The definition of fat differs in different countries ; thus whether fat is listed on food labels depends on the country .", "entity": [], "task": "NER"}
{"text": "Some countries list crude fat content in the ' Fat ' section on the food label , whereas other countries list total fat .", "entity": [], "task": "NER"}
{"text": "In this study , three methods were used for determining fat classes and content in bakery products : the Folch method , the automated Soxhlet method , and the AOAC 996 . 06 method .", "entity": [], "task": "NER"}
{"text": "The results using these methods were compared .", "entity": [], "task": "NER"}
{"text": "Fat ( crude ) extracted by the Folch and Soxhlet methods was gravimetrically determined and assessed by fat class using capillary gas chromatography ( GC ) .", "entity": [], "task": "NER"}
{"text": "In most samples , fat ( total ) content determined by the AOAC 996 . 06 method was lower than the fat ( crude ) content determined by the Folch or automated Soxhlet methods .", "entity": [], "task": "NER"}
{"text": "Furthermore , monounsaturated fat or saturated fat content determined by the AOAC 996 . 06 method was lowest .", "entity": [], "task": "NER"}
{"text": "Almost no difference was observed between fat ( crude ) content determined by the Folch method and that determined by the automated Soxhlet method for nearly all samples .", "entity": [], "task": "NER"}
{"text": "In three samples ( wheat biscuits , butter cookies - 1 , and chocolate chip cookies ) , monounsaturated fat , saturated fat , and trans fat content obtained by the automated Soxhlet method was higher than that obtained by the Folch method .", "entity": [], "task": "NER"}
{"text": "The polyunsaturated fat content obtained by the automated Soxhlet method was not higher than that obtained by the Folch method in any sample .", "entity": [], "task": "NER"}
{"text": "Nutrients , phytochemicals and bioactivity of wild Roman chamomile : a comparison between the herb and its preparations .", "entity": [], "task": "NER"}
{"text": "Roman chamomile , Chamaemelum nobile L .", "entity": [], "task": "NER"}
{"text": "( Asteraceae ) , has been used for medicinal applications , mainly through oral dosage forms ( decoctions and infusions ) .", "entity": [], "task": "NER"}
{"text": "Herein , the nutritional characterisation of C . nobile was performed , and herbal material and its decoction and infusion were submitted to an analysis of phytochemicals and bioactivity evaluation .", "entity": [], "task": "NER"}
{"text": "The antioxidant activity was determined by free radicals scavenging activity , reducing power and inhibition of lipid peroxidation , the antitumour potential was tested in human tumour cell lines ( breast , lung , colon , cervical and hepatocellular carcinomas ) , and the hepatotoxicity was evaluated using a porcine liver primary cell culture .", "entity": [], "task": "NER"}
{"text": "C . nobile proved to be an equilibrated valuable herb rich in carbohydrates and proteins , and poor in fat , providing tocopherols , carotenoids and essential fatty acids ( C18 : 2n6 and C18 : 3n3 ) .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "tocopherols", "entity_type": "Chemical", "pos": [119, 130]}, {"entity": "fatty acids", "entity_type": "Chemical", "pos": [159, 170]}], "task": "NER"}
{"text": "Moreover , the herb and its infusion are a source of phenolic compounds ( flavonoids such as flavonols and flavones , phenolic acids and derivatives ) and organic acids ( oxalic , quinic , malic , citric and fumaric acids ) that showed antioxidant and antitumour activities , without hepatotoxicity .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [93, 102]}, {"entity": "flavones", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [118, 132]}, {"entity": "oxalic , quinic , malic , citric and fumaric acids", "entity_type": "Chemical", "pos": [171, 221]}], "task": "NER"}
{"text": "The most abundant compounds in the plant extract and infusion were 5 - O - caffeoylquinic acid and an apigenin derivative .", "entity": [{"entity": "5 - O - caffeoylquinic acid", "entity_type": "Chemical", "pos": [67, 94]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "These , as well as other bioactive compounds , are affected in C . nobile decoction , leading to a lower antioxidant potential and absence of antitumour potential .", "entity": [], "task": "NER"}
{"text": "The plant bioactivity could be explored in the medicine , food , and cosmetic industries .", "entity": [], "task": "NER"}
{"text": "' Emerging ' mycotoxins in cereals processing chains : changes of enniatins during beer and bread making .", "entity": [{"entity": "enniatins", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "Enniatins represent an emerging food safety issue because of their extensive incidence , documented in recent decades , in various small grain cereals .", "entity": [{"entity": "Enniatins", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "This study was concerned with the fate of these Fusarium mycotoxins within malting , brewing , milling and baking , when employed for the processing of contaminated barley and wheat .", "entity": [], "task": "NER"}
{"text": "Besides enniatins A , A1 , B and B1 , also deoxynivalenol and its conjugated form ( deoxynivalenol - 3 - glucoside ) were determined in almost all tested cereal - based samples .", "entity": [{"entity": "enniatins A , A1 , B and B1", "entity_type": "Chemical", "pos": [8, 35]}, {"entity": "deoxynivalenol", "entity_type": "Chemical", "pos": [43, 57]}, {"entity": "deoxynivalenol - 3 - glucoside", "entity_type": "Chemical", "pos": [84, 114]}], "task": "NER"}
{"text": "Significant decline of enniatins occurred within all technologies , with the largest drop in their concentrations observed in the brewing process .", "entity": [{"entity": "enniatins", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "While enniatins were not detectable in final beers , they were almost quantitatively transferred to spent grains , probably because of their limited water solubility .", "entity": [{"entity": "enniatins", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "Regarding bread baking , levels of enniatins decreased down to 30 % of their concentration in the initial flour used for baking .", "entity": [{"entity": "enniatins", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "In this case , degradation at higher temperatures might be assumed .", "entity": [], "task": "NER"}
{"text": "Dietary Monascus adlay supplements facilitate suppression of cigarette smoke - induced pulmonary endoplasmic reticulum stress , autophagy , apoptosis and emphysema - related PLGF in the rat .", "entity": [], "task": "NER"}
{"text": "Cigarette smoke ( CS ) exposure may cause oxidative stress in the lung , leading to cell death and long - term injury .", "entity": [], "task": "NER"}
{"text": "Monascus adlay ( MA ) with antioxidant components produced by inoculating adlay ( Cois lachrymal - jobi L . var . ma - yuen Stapf ) with Monascus purpureus may protect lung against CS - induced lung injuries in rats .", "entity": [], "task": "NER"}
{"text": "MA and lovastatin had higher antioxidant activities than either M . purpureus or adlay .", "entity": [{"entity": "lovastatin", "entity_type": "Chemical", "pos": [7, 17]}], "task": "NER"}
{"text": "CS exposure caused significant lung damage , as evidenced by higher levels of reactive oxygen species ( ROS ) , neutrophil infiltration , dityrosine and 4 - HNE , as well as lower levels of Mn - superoxide dismutase and catalase expression .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [87, 93]}, {"entity": "dityrosine", "entity_type": "Chemical", "pos": [138, 148]}, {"entity": "4 - HNE", "entity_type": "Chemical", "pos": [153, 160]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [190, 192]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [195, 205]}], "task": "NER"}
{"text": "Lung tissues with CS exposure had higher levels of ER stress , apoptosis , autophagy and emphysema - related placenta growth factor ( PlGF ) expressions .", "entity": [], "task": "NER"}
{"text": "All CS - induced injuries were significantly suppressed by MA supplements .", "entity": [], "task": "NER"}
{"text": "MA would be a beneficial nutritional therapy to ameliorate CS - induced lung injury via preserving antioxidant defense mechanisms , decreasing oxidative stress and inhibiting ER stress , autophagy , apoptosis and emphysema - related risk factor .", "entity": [], "task": "NER"}
{"text": "An extract procedure for studying the free and glycosilated aroma compounds in grapes .", "entity": [], "task": "NER"}
{"text": "In this study seven published methods of extraction of skin free and bound volatile compounds have been compared .", "entity": [], "task": "NER"}
{"text": "The free and bound volatiles were separated by solid phase extraction ( SPE ) and then analysed by gas chromatography coupled with mass spectrometry ( GC - MS ) .", "entity": [], "task": "NER"}
{"text": "The results showed that the extraction of volatile compounds from grapes is highly affected by extraction solution features .", "entity": [], "task": "NER"}
{"text": "The solution at pH 3 . 2 and 0 % ethanol resulted the most effective as it led to the extraction of a higher number and amount of free and glycosilated volatile compounds .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [33, 40]}], "task": "NER"}
{"text": "The selected extraction method of grape skin and the process of pulp juice were validated for quantitative determination of a wide range of grape aroma compounds .", "entity": [], "task": "NER"}
{"text": "A total of 37 free and bound grape aroma compounds were quantified by GC - MS in selective ion monitoring modality ( SIM ) .", "entity": [], "task": "NER"}
{"text": "Among them , 26 volatile compounds resulted validated in grape skin and pulp juice .", "entity": [], "task": "NER"}
{"text": "One - step purification of lactoperoxidase from bovine milk by affinity chromatography .", "entity": [], "task": "NER"}
{"text": "Sulphanilamide was determined to be a new inhibitor of lactoperoxidase ( LPO ) with an IC ( 50 ) of 0 . 848 . 10 ( - 5 ) M .", "entity": [{"entity": "Sulphanilamide", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "The K ( i ) for sulphanilamide was determined to be 3 . 57 . 10 ( - 5 ) M and sulphanilamide showed competitive inhibition , which makes it a suitable ligand for constructing a Sepharose 4B - L - tyrosine affinity matrix .", "entity": [{"entity": "sulphanilamide", "entity_type": "Chemical", "pos": [16, 30]}, {"entity": "sulphanilamide", "entity_type": "Chemical", "pos": [78, 92]}, {"entity": "Sepharose 4B", "entity_type": "Chemical", "pos": [177, 189]}, {"entity": "L - tyrosine", "entity_type": "Chemical", "pos": [192, 204]}], "task": "NER"}
{"text": "The affinity matrix was synthesised by coupling sulphanilamide as the ligand and L - tyrosine as the spacer arm to a cyanogen bromide ( CNBr ) - activated - Sepharose 4B matrix .", "entity": [{"entity": "sulphanilamide", "entity_type": "Chemical", "pos": [48, 62]}, {"entity": "L - tyrosine", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "cyanogen bromide", "entity_type": "Chemical", "pos": [117, 133]}, {"entity": "CNBr", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "Sepharose 4B", "entity_type": "Chemical", "pos": [157, 169]}], "task": "NER"}
{"text": "Lactoperoxidase was purified 409 - fold from the synthesized affinity matrix in a single step , with a yield of 62 . 3 % and a specific activity of 40 . 9 EU / mg protein .", "entity": [], "task": "NER"}
{"text": "The enzyme activity was measured using ABTS as a chromogenic substrate ( pH 6 . 0 ) .", "entity": [{"entity": "ABTS", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "The degree of LPO purification was monitored by SDS - PAGE and its R ( z ) ( A ( 412 ) / A ( 280 ) ) value .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "The R ( z ) value for the purified LPO was found to be 0 . 7 .", "entity": [], "task": "NER"}
{"text": "Maximum binding was achieved and K ( m ) and V ( max ) values were determined .", "entity": [], "task": "NER"}
{"text": "Infusion and decoction of wild German chamomile : bioactivity and characterization of organic acids and phenolic compounds .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Natural products represent a rich source of biologically active compounds and are an example of molecular diversity , with recognised potential in drug discovery .", "entity": [], "task": "NER"}
{"text": "Herein , the methanol extract of Matricaria recutita L .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [13, 21]}], "task": "NER"}
{"text": "( German chamomile ) and its decoction and infusion ( the most consumed preparations of this herb ) were submitted to an analysis of phytochemicals and bioactivity evaluation .", "entity": [], "task": "NER"}
{"text": "The antioxidant activity was determined by free radicals scavenging activity , reducing power and inhibition of lipid peroxidation ; the antitumour potential was tested in human tumour cell lines ( breast , lung , colon , cervical and hepatocellular carcinomas ) , and the hepatotoxicity was evaluated using a porcine liver primary cell culture ( non - tumour cells ) .", "entity": [], "task": "NER"}
{"text": "All the samples revealed antioxidant properties .", "entity": [], "task": "NER"}
{"text": "The decoction exhibited no antitumour activity ( GI ( 50 ) > 400 mu g / mL ) which could indicate that this bioactivity might be related to compounds ( including phenolic compounds ) that were not extracted or that were affected by the decoction procedure .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [162, 170]}], "task": "NER"}
{"text": "Both plant methanol extract and infusion showed inhibitory activity to the growth of HCT - 15 ( GI ( 50 ) 250 . 24 and 298 . 23 mu g / mL , respectively ) and HeLa ( GI ( 50 ) 259 . 36 and 277 . 67 mu g / mL , respectively ) cell lines , without hepatotoxicity ( GI ( 50 ) > 400 mu g / mL ) .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "Infusion and decoction gave higher contents of organic acids ( 24 . 42 and 23 . 35 g / 100g dw ) .", "entity": [], "task": "NER"}
{"text": "Otherwise , the plant methanol extract contained the highest amounts of both phenolic acids ( 3 . 99 g / 100g dw ) and flavonoids ( 2 . 59 g / 100g dw ) .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [77, 91]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [119, 129]}], "task": "NER"}
{"text": "The major compound found in all the preparations was luteolin O - acylhexoside .", "entity": [{"entity": "luteolin O - acylhexoside", "entity_type": "Chemical", "pos": [53, 78]}], "task": "NER"}
{"text": "Overall , German chamomile contains important phytochemicals with bioactive properties ( mainly antitumour potential selective to colon and cervical carcinoma cell lines ) to be explored in the pharmaceutical , food and cosmetics industries .", "entity": [], "task": "NER"}
{"text": "Authentication of beeswax ( Apis mellifera ) by high - temperature gas chromatography and chemometric analysis .", "entity": [], "task": "NER"}
{"text": "Chemical characterization and authentication of beeswax of Apis mellifera was performed by high temperature capillary gas chromatography coupled to electron impact mass spectrometry or to flame ionisation detection and chemometric analysis .", "entity": [], "task": "NER"}
{"text": "Many major components ( > 50 ) of beeswax , odd and even hydrocarbons , oleofin , palmitate , oleate and hydroxypalmitate monoesters were detected , and for the first time palmitate and oleate monoesters esterified with 1 - octadecanol and 1 - eicosanol are reported to be present in beeswax .", "entity": [{"entity": "hydrocarbons", "entity_type": "Chemical", "pos": [57, 69]}, {"entity": "oleofin", "entity_type": "Chemical", "pos": [72, 79]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "oleate", "entity_type": "Chemical", "pos": [94, 100]}, {"entity": "hydroxypalmitate monoesters", "entity_type": "Chemical", "pos": [105, 132]}, {"entity": "palmitate and oleate monoesters", "entity_type": "Chemical", "pos": [172, 203]}, {"entity": "1 - octadecanol", "entity_type": "Chemical", "pos": [220, 235]}, {"entity": "1 - eicosanol", "entity_type": "Chemical", "pos": [240, 253]}], "task": "NER"}
{"text": "Unsupervised pattern recognition procedures , cluster analysis and principal component analysis , were used to find data patterns and successfully differentiate authentic and paraffin adulterated beeswax based on the chemical profile obtained .", "entity": [{"entity": "paraffin", "entity_type": "Chemical", "pos": [175, 183]}], "task": "NER"}
{"text": "Independent assessment of beeswax quality and performance of the unsupervised classification methods were performed using classical analytical parameters .", "entity": [], "task": "NER"}
{"text": "The discrimination power of the chemometric unsupervised methods for detection of paraffin adulterated beeswax was superior to the discriminating power of classical analytical parameters .", "entity": [{"entity": "paraffin", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "Using linear discriminant analysis , classification rules for authentic and paraffin adulterated beeswax samples were developed .", "entity": [{"entity": "paraffin", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "The model was validated by leave - one - out cross validation and showed good recognition and prediction abilities , 100 % and 99 % , respectively .", "entity": [], "task": "NER"}
{"text": "Antioxidant activity comparison between [ 6S ] - 5 - methyltetrahydrofolic acid calcium salt and the related racemate form .", "entity": [{"entity": "[ 6S ] - 5 - methyltetrahydrofolic acid calcium", "entity_type": "Chemical", "pos": [40, 87]}], "task": "NER"}
{"text": "Folates , such as [ 6S ] - 5 - methyltetrahydrofolic acid , have been introduced in the market both in vitamin pills and in fortified foods .", "entity": [{"entity": "Folates", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "[ 6S ] - 5 - methyltetrahydrofolic acid", "entity_type": "Chemical", "pos": [18, 57]}], "task": "NER"}
{"text": "Their antioxidant activity has been evaluated , but stereoisomer influence on activity has not been proven .", "entity": [], "task": "NER"}
{"text": "In this study , a comparison between [ 6S ] - 5 - methyltetrahydrofolic acid ( 5 - MTHF ) and its racemate [ 6R , S ] form was made by TEAC assay at different pHs , FRAP assay , and ORAC assay .", "entity": [{"entity": "[ 6S ] - 5 - methyltetrahydrofolic acid", "entity_type": "Chemical", "pos": [37, 76]}, {"entity": "5 - MTHF", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "The results showed that the [ 6S ] form had higher antioxidant activity than its racemate form in the TEAC assay at all pHs , with similar values in the FRAP and ORAC assays .", "entity": [], "task": "NER"}
{"text": "Results suggest that stereoisomeric difference could influence the antioxidant activity of 5 - MTHF and hence should be taken into account when folates are added to foodstuffs to improve their nutritional value .", "entity": [{"entity": "5 - MTHF", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "folates", "entity_type": "Chemical", "pos": [144, 151]}], "task": "NER"}
{"text": "Use of viscera extract from hybrid catfish ( Clarias macrocephalus x Clarias gariepinus ) for the production of protein hydrolysate from toothed ponyfish ( Gazza minuta ) muscle .", "entity": [], "task": "NER"}
{"text": "Proteolytic activity of viscera extract from hybrid catfish ( Clarias macrocephalus x Clarias gariepinus ) was studied .", "entity": [], "task": "NER"}
{"text": "The optimal pH and temperature were 9 . 0 and 50 degrees C , respectively , when toothed ponyfish ( Gazza minuta ) muscle was used as a substrate .", "entity": [], "task": "NER"}
{"text": "When viscera extract from hybrid catfish was used for the production of protein hydrolysate from toothed ponyfish muscle , extract concentration , reaction time , and fish muscle / buffer ratio affected the hydrolysis and nitrogen recovery ( NR ) ( p < 0 . 05 ) .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [222, 230]}], "task": "NER"}
{"text": "Optimum conditions for toothed ponyfish muscle hydrolysis were 3 . 5 % hybrid catfish viscera extract , 15 min reaction time and fish muscle / buffer ratio of 1 : 3 ( w / v ) .", "entity": [], "task": "NER"}
{"text": "High correlation between the degree of hydrolysis ( DH ) and NR ( R ( 2 ) = 0 . 974 ) was observed .", "entity": [], "task": "NER"}
{"text": "Freeze - dried hydrolysate had a high protein content ( 89 . 02 % , dry weight basis ) and it was brownish yellow in colour ( L ( * ) = 63 . 67 , a ( * ) = 6 . 33 , b ( * ) = 22 . 41 ) .", "entity": [], "task": "NER"}
{"text": "The protein hydrolysate contained a high amount of essential amino acids ( 48 . 22 % ) and had arginine and lysine as the dominant amino acids .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [61, 72]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [108, 114]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [131, 142]}], "task": "NER"}
{"text": "Simultaneous separation and purification of total polyphenols , chlorogenic acid and phlorizin from thinned young apples .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [50, 61]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [64, 80]}, {"entity": "phlorizin", "entity_type": "Chemical", "pos": [85, 94]}], "task": "NER"}
{"text": "An efficient preparative separation of polyphenols from thinned young apples ( TYA ) has been developed in the present study .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [39, 50]}], "task": "NER"}
{"text": "X - 5 resin was verified to offer the best adsorption capacity and desorption ratio for total polyphenols among the eight macroporous resins investigated .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "Influential factors , such as pH value and concentration of feeding solution , strippant , and adsorption isotherm to the separation of total polyphenols , were successively investigated on X - 5 resin .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [142, 153]}], "task": "NER"}
{"text": "After one run treatment , the phenolic content was increased 2 . 12 - fold from 35 . 17 % to 74 . 64 % , with a recovery yield of 89 . 35 % .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "Chlorogenic acid and phlorizin were selectively purified using X - 5 and polyamide resins .", "entity": [{"entity": "Chlorogenic acid", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "phlorizin", "entity_type": "Chemical", "pos": [21, 30]}, {"entity": "polyamide", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "The contents of chlorogenic acid and phlorizin were 15 . 20 % and 97 . 52 % with recovery yields of 89 . 16 % and 64 . 95 % , respectively .", "entity": [{"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [16, 32]}, {"entity": "phlorizin", "entity_type": "Chemical", "pos": [37, 46]}], "task": "NER"}
{"text": "The method developed will provide a potential approach for its wide industrial and pharmaceutical use .", "entity": [], "task": "NER"}
{"text": "Antioxidant and antihypertensive properties of liquid and solid state fermented lentils .", "entity": [], "task": "NER"}
{"text": "The effect of liquid ( LSF ) and solid state fermentation ( SSF ) of lentils for production of water - soluble fractions with antioxidant and antihypertensive properties was studied .", "entity": [], "task": "NER"}
{"text": "LSF was performed either spontaneously ( NF ) or by Lactobacillus plantarum ( LP ) while SSF was performed by Bacillus subtilis ( BS ) .", "entity": [], "task": "NER"}
{"text": "Native lactic flora in NF adapted better than L . plantarum to fermentative broth and BS counts increased 4 . 0 logCFU / g up to 48 h of SSF .", "entity": [], "task": "NER"}
{"text": "LSF water - soluble fractions had higher ( P <= 0 . 05 ) free amino groups , GABA content , antioxidant and angiotensin I - converting enzyme inhibitory ( ACEI ) activities than SSF .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [62, 67]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "In addition , GABA and ACEI activity of LSF increased in a time - dependent manner .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "Proteolysis by BS was limited , with slight changes in free amino groups , while GABA , total phenolic compounds and antioxidant capacity increased throughout fermentation .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [60, 65]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [81, 85]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "Higher antihypertensive potential was observed in NF ( 96 h ) characterised by the highest GABA content ( 10 . 42 mg / g extract ) , ACE - inhibitory potency ( expressed as IC ( 50 ) ) of 0 . 18 mg protein / ml and antioxidant capacity of 0 . 26 mmol Trolox equivalents / g extract .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [91, 95]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [251, 257]}], "task": "NER"}
{"text": "Therefore , water - soluble fermented lentil extracts obtained by LSF are particularly promising as functional ingredients in preventing hypertension .", "entity": [], "task": "NER"}
{"text": "Fucoxanthin content and antioxidant properties of Undaria pinnatifida .", "entity": [{"entity": "Fucoxanthin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "This study investigated the fucoxanthin content of New Zealand ( NZ ) Undaria pinnatifida harvested from two locations in the Marlborough Sounds , New Zealand across its growing season .", "entity": [{"entity": "fucoxanthin", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "Fucoxanthin content and antioxidant properties of processed New Zealand U . pinnatifida and commercial wakame from Japan and Korea were further compared .", "entity": [{"entity": "Fucoxanthin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Results showed that U . pinnatifida harvested from Port Underwood had higher fucoxanthin content in the blade compared to Pelorus Sound .", "entity": [{"entity": "fucoxanthin", "entity_type": "Chemical", "pos": [77, 88]}], "task": "NER"}
{"text": "The sporophyll also contained a significant amount of fucoxanthin throughout the harvest season , although lower than in the blade .", "entity": [{"entity": "fucoxanthin", "entity_type": "Chemical", "pos": [54, 65]}], "task": "NER"}
{"text": "Two antioxidant measurement methods , DPPH and CUPRAC , were utilised to measure antioxidant activities .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [38, 42]}], "task": "NER"}
{"text": "Processed NZ U . pinnatifida had a lower fucoxanthin content and antioxidant activity than freeze - dried Undaria .", "entity": [{"entity": "fucoxanthin", "entity_type": "Chemical", "pos": [41, 52]}], "task": "NER"}
{"text": "Fucoxanthin content and antioxidant activities of NZ processed U . pinnatifida were not significantly different from other commercial samples from Japan and Korea .", "entity": [{"entity": "Fucoxanthin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In conclusion , U . pinnatifida in New Zealand has a great potential to be a food and nutraceutical resource .", "entity": [], "task": "NER"}
{"text": "Structure and composition of model cheeses influence sodium NMR mobility , kinetics of sodium release and sodium partition coefficients .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [53, 59]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [87, 93]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [106, 112]}], "task": "NER"}
{"text": "The mobility and release of sodium ions were assessed in model cheeses with three different lipid / protein ratios , with or without added NaCl .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [28, 34]}, {"entity": "NaCl", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "The rheological properties of the cheeses were analysed using uniaxial compression tests .", "entity": [], "task": "NER"}
{"text": "Microstructure was characterised by confocal laser scanning microscopy .", "entity": [], "task": "NER"}
{"text": "( 23 ) Na nuclear magnetic resonance ( NMR ) spectroscopy was used to study the molecular mobility of sodium ions in model cheeses through measurements of the relaxation and creation times .", "entity": [{"entity": "( 23 ) Na", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [102, 108]}], "task": "NER"}
{"text": "Greater mobility was observed in cheeses containing a lower protein content and with added NaCl .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "The kinetics of sodium release from the cheese to an aqueous phase was correlated with the mobility of sodium ions .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "The highest rates of sodium release were observed with a lower protein content and with added NaCl .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "NaCl", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "The water / cheese partition coefficients of sodium increased when NaCl was added or the protein content was higher .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [45, 51]}, {"entity": "NaCl", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "The study highlighted the effect of model cheese characteristics on molecular and macroscopic behaviours of sodium .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "A combination of [ + ] and [ - ] - Huperzine A improves protection against soman toxicity compared to [ + ] - Huperzine A in guinea pigs .", "entity": [{"entity": "[ + ] and [ - ] - Huperzine A", "entity_type": "Chemical", "pos": [17, 46]}, {"entity": "[ + ] - Huperzine A", "entity_type": "Chemical", "pos": [102, 121]}], "task": "NER"}
{"text": "The neuropathologic mechanisms after exposure to lethal doses of nerve agent are complex and involve multiple biochemical pathways .", "entity": [], "task": "NER"}
{"text": "Effective treatment requires drugs that can simultaneously protect by reversible binding to the acetylcholinesterase ( AChE ) and blocking cascades of seizure related brain damage , inflammation , neuronal degeneration as well as promoting induction of neuroregeneration .", "entity": [], "task": "NER"}
{"text": "[ - ] - Huperzine A ( [ - ] - Hup A ) , is a naturally occurring potent reversible AChE inhibitor that penetrates the blood - brain barrier .", "entity": [{"entity": "[ - ] - Huperzine A", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "[ - ] - Hup A", "entity_type": "Chemical", "pos": [22, 35]}], "task": "NER"}
{"text": "It also has several neuroprotective effects including modification of beta - amyloid peptide , reduction of oxidative stress , anti - inflammatory , anti - apoptotic and induction and regulation of nerve growth factor .", "entity": [], "task": "NER"}
{"text": "Toxicities at higher doses restrict the neuroporotective ability of [ - ] - Hup A for treatment .", "entity": [{"entity": "[ - ] - Hup A", "entity_type": "Chemical", "pos": [68, 81]}], "task": "NER"}
{"text": "The synthetic stereoisomer , [ + ] - Hup A , is less toxic due to poor AChE inhibition and is suitable for both pre - / post - exposure treatments of nerve agent toxicity .", "entity": [{"entity": "[ + ] - Hup A", "entity_type": "Chemical", "pos": [29, 42]}], "task": "NER"}
{"text": "[ + ] - Hup A block the N - methyl - d - aspartate ( NMDA ) - induced seizure in rats , reduce excitatory amino acid induced neurotoxicity and also prevent soman induced toxicity with minimum performance decrement .", "entity": [{"entity": "[ + ] - Hup A", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "N - methyl - d - aspartate", "entity_type": "Chemical", "pos": [24, 50]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [53, 57]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [106, 116]}], "task": "NER"}
{"text": "Unique combinations of two stereo - isomers of Hup A may provide an excellent pre / post - treatment drug for the nerve agent induced seizure / status epilepticus .", "entity": [{"entity": "Hup A", "entity_type": "Chemical", "pos": [47, 52]}], "task": "NER"}
{"text": "We investigated a combination of [ + ] - Hup A with a small dose of [ - ] - Hup A ( [ + ] and [ - ] - Hup A ) against soman toxicity .", "entity": [{"entity": "[ + ] - Hup A", "entity_type": "Chemical", "pos": [33, 46]}, {"entity": "[ - ] - Hup A", "entity_type": "Chemical", "pos": [68, 81]}, {"entity": "[ + ] and [ - ] - Hup A", "entity_type": "Chemical", "pos": [84, 107]}, {"entity": "soman", "entity_type": "Chemical", "pos": [118, 123]}], "task": "NER"}
{"text": "Our data showed that pretreatment with a combination [ + ] and [ - ] - Hup A significantly increased the survival rate and reduced behavioral abnormalities after exposure to 1 . 2 x LD50 soman compared to [ + ] - Hup A in guinea pigs .", "entity": [{"entity": "[ + ] and [ - ] - Hup A", "entity_type": "Chemical", "pos": [53, 76]}, {"entity": "[ + ] - Hup A", "entity_type": "Chemical", "pos": [205, 218]}], "task": "NER"}
{"text": "In addition , [ + ] and [ - ] - Hup A pretreatment inhibited the development of high power of EEG better than [ + ] - Hup A pretreatment alone .", "entity": [{"entity": "[ + ] and [ - ] - Hup A", "entity_type": "Chemical", "pos": [14, 37]}, {"entity": "[ + ] - Hup A", "entity_type": "Chemical", "pos": [110, 123]}], "task": "NER"}
{"text": "These data suggest that a combination of [ + ] and [ - ] - Hup A offers better protection than [ + ] - Hup A and serves as a potent medical countermeasure against lethal dose nerve agent toxicity in guinea pigs .", "entity": [{"entity": "[ + ] and [ - ] - Hup A", "entity_type": "Chemical", "pos": [41, 64]}, {"entity": "[ + ] - Hup A", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "Organophosphorus compound esterase profiles as predictors of therapeutic and toxic effects .", "entity": [{"entity": "Organophosphorus", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Certain organophosphorus compounds ( OPCs ) inhibit various serine esterases ( EOHs ) via phosphorylation of their active site serines .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [8, 24]}, {"entity": "serine", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "serines", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "We focused on 4 EOHs of particular toxicological interest : acetylcholinesterase ( AChE : acute neurotoxicity ; cognition enhancement ) , butyrylcholinesterase ( BChE : inhibition of drug metabolism and / or stoichiometric scavenging of EOH inhibitors ; cognition enhancement ) , carboxylesterase ( CaE : inhibition of drug metabolism and / or stoichiometric scavenging of EOH inhibitors ) , and neuropathy target esterase ( NTE : delayed neurotoxicity , OPIDN ) .", "entity": [], "task": "NER"}
{"text": "The relative degree of inhibition of these EOHs constitutes the \" esterase profile \" of an OPC and serves as a major determinant of its net physiological effects .", "entity": [], "task": "NER"}
{"text": "Thus , understanding and controlling the esterase profile of OPC activity and selectivity toward these 4 target enzymes is a significant undertaking .", "entity": [], "task": "NER"}
{"text": "In the present study , we analyzed the inhibitor properties of 52 OPCs against the 4 EOHs , along with pairwise and multitarget selectivities between them , using 2 QSAR approaches : Hansch modeling and Molecular Field Topology Analysis ( MFTA ) .", "entity": [], "task": "NER"}
{"text": "The general formula of the OPCs was ( RO ) 2P ( O ) X , where R = alkyl , X = - SCH ( Hal ) COOEt ( Hal = Cl , Br ) , - SCHCl2 , - SCH2Br , - OCH ( CF3 ) R ( 1 ) ( R ( 1 ) = C6H5 , CF3 , COOEt , COOMe ) .", "entity": [{"entity": "( RO ) 2P ( O ) X", "entity_type": "Chemical", "pos": [36, 53]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [66, 71]}, {"entity": "SCH ( Hal ) COOEt", "entity_type": "Chemical", "pos": [80, 97]}, {"entity": "Hal", "entity_type": "Chemical", "pos": [100, 103]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [106, 108]}, {"entity": "Br", "entity_type": "Chemical", "pos": [111, 113]}, {"entity": "SCHCl2", "entity_type": "Chemical", "pos": [120, 126]}, {"entity": "SCH2Br", "entity_type": "Chemical", "pos": [131, 137]}, {"entity": "OCH ( CF3 ) R ( 1 )", "entity_type": "Chemical", "pos": [142, 161]}, {"entity": "C6H5", "entity_type": "Chemical", "pos": [174, 178]}, {"entity": "CF3", "entity_type": "Chemical", "pos": [181, 184]}, {"entity": "COOEt", "entity_type": "Chemical", "pos": [187, 192]}, {"entity": "COOMe", "entity_type": "Chemical", "pos": [195, 200]}], "task": "NER"}
{"text": "The Hansch model showed that increasing neuropathic potential correlated with rising R hydrophobicity ; moreover , OPC binding to scavenger EOHs ( BChE and CaE ) had different effects on potential acute and delayed neurotoxicity .", "entity": [], "task": "NER"}
{"text": "Predicted protective roles of BChE and CaE against acute toxicity were enhanced with increasing hydrophobicity , but projected protection against OPIDN was decreased .", "entity": [], "task": "NER"}
{"text": "Next , Molecular Field Topology Analysis ( MFTA ) models were built , considering atomic descriptors , e . g . , effective charge , van der Waals radius of environment , and group lipophilicity .", "entity": [], "task": "NER"}
{"text": "Activity / selectivity maps confirmed predictions from Hansch models and revealed other structural factors affecting activity and selectivity .", "entity": [], "task": "NER"}
{"text": "Virtual screening based on multitarget selectivity MFTA models was used to design libraries of OPCs with favorable esterase profiles for potential application as selective inhibitors of CaE without untoward side effects .", "entity": [], "task": "NER"}
{"text": "New tools in diagnosis and biomonitoring of intoxications with organophosphorothioates : Case studies with chlorpyrifos and diazinon .", "entity": [{"entity": "organophosphorothioates", "entity_type": "Chemical", "pos": [63, 86]}, {"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [107, 119]}, {"entity": "diazinon", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "Organophosphate ( OP ) pesticides are neurotoxic compounds that are widely used in agriculture .", "entity": [{"entity": "Organophosphate", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Classical methods for monitoring OP exposure comprise the measurement of intact OP , its metabolites or cholinesterase activity .", "entity": [], "task": "NER"}
{"text": "Newly developed methods focus on the analysis of the OP adduct bound to proteins such as butyrylcholinesterase ( BuChE ) and albumin .", "entity": [], "task": "NER"}
{"text": "These adducts can be analyzed by means of fluoride reactivation or by analysis with LC - MS / MS of the pepsin or pronase digest of butyrylcholinesterase and albumin , respectively .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "The utility of these methods is illustrated through the analysis of plasma samples obtained from patients taken 1 - 49days after ingestion of the organophosphate pesticides chlorpyrifos and / or diazinon .", "entity": [{"entity": "organophosphate", "entity_type": "Chemical", "pos": [146, 161]}, {"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [173, 185]}, {"entity": "diazinon", "entity_type": "Chemical", "pos": [195, 203]}], "task": "NER"}
{"text": "Thus , in this particular case several independent methodologies were applied to the biomedical samples , all pointing to the same exposure .", "entity": [], "task": "NER"}
{"text": "Strategies for the selection of catalytic antibodies against organophosphorus nerve agents .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [61, 77]}], "task": "NER"}
{"text": "Among the strategies aimed at biocompatible means for organophosphorus nerve agents neutralization , immunoglobulins have attracted attention in the 1990 ' s and 2000 ' s both for their ability to immobilize the toxicants , but also for their ability to be turned into enzymatically active antibodies known as catalytic antibodies or abzymes ( antibodies - enzymes ) .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [54, 70]}], "task": "NER"}
{"text": "We will present here a critical review of the successive strategies used for the selection of these nerve agent - hydrolyzing abzymes , based on hapten design , namely antibodies raised against a wide variety of transition state analogs , and eventually the strategies based on anti - idiotypic antibodies and reactibodies .", "entity": [], "task": "NER"}
{"text": "Reduced in vitro and in vivo toxicity of siRNA - lipoplexes with addition of polyglutamate .", "entity": [{"entity": "polyglutamate", "entity_type": "Chemical", "pos": [77, 90]}], "task": "NER"}
{"text": "We previously designed a new siRNA vector that efficiently silences genes in vitro and in vivo .", "entity": [], "task": "NER"}
{"text": "The vector originality is based on the fact that , in addition to the siRNA molecule , it contains two components : 1 ) a cationic liposome that auto - associates with the siRNA to form particles called \" lipoplexes \" and , 2 ) an anionic polymer which enhances the lipoplex ' s efficiency .", "entity": [], "task": "NER"}
{"text": "This anionic polymer can be a nucleic acid , a polypeptide or a polysaccharide .", "entity": [], "task": "NER"}
{"text": "We show here how the nature of the added anionic polymer into our siRNA delivery system impacts the toxic effects induced by siRNA lipoplexes .", "entity": [], "task": "NER"}
{"text": "We first observed that : ( i ) siRNA lipoplexes - induced toxicity was cell line dependent , tumoral cell lines being the more sensitive ; and ( ii ) plasmid DNA - containing siRNA lipoplexes were more toxic than polyglutamate - containing ones or cationic liposomes .", "entity": [{"entity": "polyglutamate", "entity_type": "Chemical", "pos": [213, 226]}], "task": "NER"}
{"text": "We next determined that the toxicity induced by plasmid - containing lipoplexes is a long - lasting effect that decreased cell survival capacity for several generations .", "entity": [], "task": "NER"}
{"text": "We also found that treated cells underwent death following apoptosis pathway .", "entity": [], "task": "NER"}
{"text": "Systemic injection to mice of siRNA lipoplexes , rather than of cationic liposome , triggered a production of several cytokines in mice and replacement of plasmid by polyglutamate reduced the elevation of all assayed cytokines .", "entity": [{"entity": "polyglutamate", "entity_type": "Chemical", "pos": [166, 179]}], "task": "NER"}
{"text": "In order to enhance siRNA lipoplexes efficiency , the addition of polyglutamate as anionic polymer should be preferred to plasmid DNA as far as in vitro as well as in vivo toxicity is concerned .", "entity": [{"entity": "polyglutamate", "entity_type": "Chemical", "pos": [66, 79]}], "task": "NER"}
{"text": "Helenalin - induced apoptosis is dependent on production of reactive oxygen species and independent of induction of endoplasmic reticulum stress in renal cell carcinoma .", "entity": [{"entity": "Helenalin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [69, 75]}], "task": "NER"}
{"text": "Helenalin , a sesquiterpene lactone , exhibits anti - inflammatory and anti - tumor activities .", "entity": [{"entity": "Helenalin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "sesquiterpene lactone", "entity_type": "Chemical", "pos": [14, 35]}], "task": "NER"}
{"text": "Here , we investigated whether helenalin could induce apoptosis in human renal carcinoma Caki cells .", "entity": [{"entity": "helenalin", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Helenalin increased apoptosis in dose dependent manner in Caki cells , and also induced apoptosis in other carcinoma cells , such as human renal carcinoma ACHN cells , human colon carcinoma HT29 and HCT116 cells .", "entity": [{"entity": "Helenalin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "We found that helenalin markedly induced endoplasmic reticulum ( ER ) stress - related genes , such as regulated in development and DNA damage responses ( REDD ) 1 , activating transcription factor - 4 ( ATF4 ) and / or the CCAAT enhancer - binding protein - homologous protein ( CHOP ) .", "entity": [{"entity": "helenalin", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "However , down - regulation of ATF4 and / or CHOP expression by siRNA had no effect on helenalin - induced apoptosis in Caki and HCT116 cells .", "entity": [{"entity": "helenalin", "entity_type": "Chemical", "pos": [87, 96]}], "task": "NER"}
{"text": "Helenalin increased production of intracellular reactive oxygen species ( ROS ) .", "entity": [{"entity": "Helenalin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [57, 63]}], "task": "NER"}
{"text": "Furthermore , ROS scavengers , N - acetylcystine ( NAC ) , and glutathione ethyl ester ( GEE ) , reduced helenalin - induced apoptosis .", "entity": [{"entity": "N - acetylcystine", "entity_type": "Chemical", "pos": [31, 48]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "glutathione ethyl ester", "entity_type": "Chemical", "pos": [63, 86]}, {"entity": "GEE", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "helenalin", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "Taken together , helenalin induced apoptosis via ROS generation in human renal carcinoma Caki cells .", "entity": [{"entity": "helenalin", "entity_type": "Chemical", "pos": [17, 26]}], "task": "NER"}
{"text": "Dietary quercetin ameliorates nonalcoholic steatohepatitis induced by a high - fat diet in gerbils .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [8, 17]}], "task": "NER"}
{"text": "Dietary quercetin is highly abundant in edible plants , which possesses a wide range of pharmacological properties .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [8, 17]}], "task": "NER"}
{"text": "This study was to investigate hepatoprotective effects of quercetin in the nonalcoholic steatohepatitis ( NASH ) gerbils induced by a high - fat diet ( HFD ) , and to evaluate its regulatory mechanism on hepatic inflammatory response .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "The gerbils were fed with HFD for 28 days to induce NASH .", "entity": [], "task": "NER"}
{"text": "From 15th day to 28th day , the treated drugs were given daily to each animal , respectively .", "entity": [], "task": "NER"}
{"text": "The lipid profiles and biochemical markers were determined at the end of the experiment .", "entity": [], "task": "NER"}
{"text": "The expressions of Sirt1 , NF - kappa B p65 and iNOS were detected by immunohistochemistry and Western blot analysis .", "entity": [], "task": "NER"}
{"text": "The results showed that oral administration of quercetin at doses of 30 - 60 mg / kg to hyperlipidemia rats for 14 days were highly effective in decreasing the levels of serum total cholesterol ( TC ) , triglycerides ( TG ) , low - density lipoprotein cholesterol ( LDL - C ) , alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [47, 56]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [182, 193]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [203, 216]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [252, 263]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [278, 285]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [315, 324]}], "task": "NER"}
{"text": "It could decrease lipid accumulation in the hepatocytes , and reduce serum levels of pro - inflammatory cytokines TNF - alpha and IL - 6 via regulating the expressions of Sirt1 , NF - kappa B p65 and iNOS .", "entity": [], "task": "NER"}
{"text": "Thus , dietary quercetin had significant therapeutic benefits and could be explored as a potential promising candidate for the prevention of NASH .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "Neuroprotective role of ATP - sensitive potassium channels in cerebral ischemia .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "ATP - sensitive potassium ( K ( ATP ) ) channels are weak , inward rectifiers that couple metabolic status to cell membrane electrical activity , thus modulating many cellular functions .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "K", "entity_type": "Chemical", "pos": [28, 29]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "An increase in the ADP / ATP ratio opens K ( ATP ) channels , leading to membrane hyperpolarization .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "K", "entity_type": "Chemical", "pos": [41, 42]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "K ( ATP ) channels are ubiquitously expressed in neurons located in different regions of the brain , including the hippocampus and cortex .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [0, 1]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "Brief hypoxia triggers membrane hyperpolarization in these central neurons .", "entity": [], "task": "NER"}
{"text": "In vivo animal studies confirmed that knocking out the Kir6 . 2 subunit of the K ( ATP ) channels increases ischemic infarction , and overexpression of the Kir6 . 2 subunit reduces neuronal injury from ischemic insults .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [55, 56]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "These findings provide the basis for a practical strategy whereby activation of endogenous K ( ATP ) channels reduces cellular damage resulting from cerebral ischemic stroke .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [91, 92]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "K ( ATP ) channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [0, 1]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "The kinase activity of EphA4 mediates homeostatic scaling - down of synaptic strength via activation of Cdk5 .", "entity": [], "task": "NER"}
{"text": "Neurons within a network have the ability to homeostatically scale - down their excitatory synaptic strength under conditions of persistent neuronal activity elevation , a process pivotal to neural circuit stability .", "entity": [], "task": "NER"}
{"text": "How this homeostatic regulation is achieved at the molecular level in developing neural circuits , which face gradually elevated neuronal activity as part of circuit wiring , is not well - understood .", "entity": [], "task": "NER"}
{"text": "Using dissociated hippocampal neuronal cultures , we identified a critical and cell autonomous role for the receptor tyrosine kinase EphA4 in mediating activity - induced homeostatic down - regulation of excitatory synaptic strength .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [117, 125]}], "task": "NER"}
{"text": "Reducing the endogenous level of EphA4 in individual neurons by RNAi effectively blocked activity - induced scaling - down of excitatory synaptic strength , while co - transfection of RNAi resistant EphA4 rescued this effect .", "entity": [], "task": "NER"}
{"text": "Furthermore , interfering with EphA4 forward signaling using EphA4 - Fc blocked activity - induced homeostatic synaptic scaling - down , while direct activation of EphA4 with its ligand EphrinA1 weakened excitatory synaptic strength .", "entity": [], "task": "NER"}
{"text": "Up - or down - regulating EphA4 function in individual neurons also did not affect the density of excitatory synapses .", "entity": [], "task": "NER"}
{"text": "The kinase activities of EphA4 and its downstream effector Cdk5 were both required for homeostatic synaptic scaling , as overexpression of EphA4 with constitutively active kinase activity reduced excitatory synaptic strength , while interfering with either the kinase activity of EphA4 or Cdk5 blocked activity - induced synaptic scaling .", "entity": [], "task": "NER"}
{"text": "Consistently , the activities of EphA4 and Cdk5 increased significantly during global and persistent activity elevation .", "entity": [], "task": "NER"}
{"text": "Together , our work demonstrated that the kinase activity of EphA4 , via activation of downstream Cdk5 activity , mediates the scaling - down of excitatory synaptic strength under conditions of global activity elevation .", "entity": [], "task": "NER"}
{"text": "A missense polymorphism ( rs11466653 , Met326Thr ) of toll - like receptor 10 ( TLR10 ) is associated with tumor size of papillary thyroid carcinoma in the Korean population .", "entity": [], "task": "NER"}
{"text": "Toll - like receptors ( TLRs ) are important components of innate immune response .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to investigate whether TLR gene cluster ( TLR10 - TLR1 - TLR6 ) polymorphisms are associated with the etiology of papillary thyroid carcinoma ( PTC ) and its clinicopathologic characteristics .", "entity": [], "task": "NER"}
{"text": "We recruited 94 PTC patients and 325 control subjects .", "entity": [], "task": "NER"}
{"text": "Genotypes for each SNP were determined by direct sequencing .", "entity": [], "task": "NER"}
{"text": "SNPStats and SPSS 18 . 0 were used to evaluate odds ratios ( ORs ) , 95 % confidence intervals ( CIs ) , and P values .", "entity": [], "task": "NER"}
{"text": "Multiple logistic regression analyzes of genetic data were performed .", "entity": [], "task": "NER"}
{"text": "The missense SNP rs11466653 was associated with small tumor size ( < 1 cm ) in PTC .", "entity": [], "task": "NER"}
{"text": "The frequency of the rs11466653 T allele was higher in PTC patients with tumors < 1 cm in size than in the control group ( 95 . 8 vs . 87 . 2 % ; P = 0 . 021 , OR = 0 . 30 , 95 % CI = 0 . 11 - 0 . 83 ) .", "entity": [], "task": "NER"}
{"text": "The T allele of rs11466653 ( T / C , Met326Thr ) in TLR10 may be a risk factor for the development of tumors in PTC in the Korean population .", "entity": [], "task": "NER"}
{"text": "First - principles calculations of lithium - ion migration at a coherent grain boundary in a cathode material , LiCoO ( 2 ) .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "LiCoO ( 2 )", "entity_type": "Chemical", "pos": [112, 123]}], "task": "NER"}
{"text": "Results of theoretical calculations are reported , examining the effect of a coherent twin boundary on the electrical properties of LiCoO ( 2 ) .", "entity": [{"entity": "LiCoO ( 2 )", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "This study suggests that internal interfaces in LiCoO ( 2 ) strongly affect the battery voltage , battery capacity , and power density of this material , which is of particular concern if it is used in all - solid - state Li - ion batteries .", "entity": [{"entity": "LiCoO ( 2 )", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "Li", "entity_type": "Chemical", "pos": [222, 224]}], "task": "NER"}
{"text": "Cross - species transcriptomic analysis of mouse and rat lung exposed to chloroprene .", "entity": [{"entity": "chloroprene", "entity_type": "Chemical", "pos": [73, 84]}], "task": "NER"}
{"text": "beta - Chloroprene ( 2 - chloro - 1 , 3 - butadiene ) , a monomer used in the production of neoprene elastomers , is of regulatory interest due to the production of multiorgan tumors in mouse and rat cancer bioassays .", "entity": [{"entity": "beta - Chloroprene", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "2 - chloro - 1 , 3 - butadiene", "entity_type": "Chemical", "pos": [21, 51]}, {"entity": "neoprene", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "A significant increase in female mouse lung tumors was observed at the lowest exposure concentration of 12 . 8 ppm , whereas a small , but not statistically significant increase was observed in female rats only at the highest exposure concentration of 80 ppm .", "entity": [], "task": "NER"}
{"text": "The metabolism of chloroprene results in the generation of reactive epoxides , and the rate of overall chloroprene metabolism is highly species dependent .", "entity": [{"entity": "chloroprene", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "epoxides", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "chloroprene", "entity_type": "Chemical", "pos": [103, 114]}], "task": "NER"}
{"text": "To identify potential key events in the mode of action of chloroprene lung tumorigenesis , dose - response and time - course gene expression microarray measurements were made in the lungs of female mice and female rats .", "entity": [{"entity": "chloroprene", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "The gene expression changes were analyzed using both a traditional ANOVA approach followed by pathway enrichment analysis and a pathway - based benchmark dose ( BMD ) analysis approach .", "entity": [], "task": "NER"}
{"text": "Pathways related to glutathione biosynthesis and metabolism were the primary pathways consistent with cross - species differences in tumor incidence .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [20, 31]}], "task": "NER"}
{"text": "Transcriptional BMD values for the pathway were more similar to differences in tumor response than were estimated target tissue dose surrogates based on the total amount of chloroprene metabolized per unit mass of lung tissue per day .", "entity": [{"entity": "chloroprene", "entity_type": "Chemical", "pos": [173, 184]}], "task": "NER"}
{"text": "The closer correspondence of the transcriptional changes with the tumor response is likely due to their reflection of the overall balance between metabolic activation and detoxication reactions , whereas the current tissue dose surrogate reflects only oxidative metabolism .", "entity": [], "task": "NER"}
{"text": "Trans - chromosomic mice containing a human CYP3A cluster for prediction of xenobiotic metabolism in humans .", "entity": [], "task": "NER"}
{"text": "Human CYP3A is the most abundant P450 isozyme present in the human liver and small intestine , and metabolizes around 50 % of medical drugs on the market .", "entity": [], "task": "NER"}
{"text": "The human CYP3A subfamily comprises four members ( CYP3A4 , CYP3A5 , CYP3A7 , CYP3A43 ) encoded on human chromosome 7 .", "entity": [], "task": "NER"}
{"text": "However , transgenic mouse lines carrying the entire human CYP3A cluster have not been constructed because of limitations in conventional cloning techniques .", "entity": [], "task": "NER"}
{"text": "Here , we show that the introduction of a human artificial chromosome ( HAC ) containing the entire genomic human CYP3A locus recapitulates tissue - and stage - specific expression of human CYP3A genes and xenobiotic metabolism in mice .", "entity": [], "task": "NER"}
{"text": "About 700 kb of the entire CYP3A genomic segment was cloned into a HAC ( CYP3A - HAC ) , and trans - chromosomic ( Tc ) mice carrying a single copy of germline - transmittable CYP3A - HAC were generated via a chromosome - engineering technique .", "entity": [], "task": "NER"}
{"text": "The tissue - and stage - specific expression profiles of CYP3A genes were consistent with those seen in humans .", "entity": [], "task": "NER"}
{"text": "We further generated mice carrying the CYP3A - HAC in the background homozygous for targeted deletion of most endogenous Cyp3a genes .", "entity": [], "task": "NER"}
{"text": "In this mouse strain with ' fully humanized ' CYP3A genes , the kinetics of triazolam metabolism , CYP3A - mediated mechanism - based inactivation effects and formation of fetal - specific metabolites of dehydroepiandrosterone observed in humans were well reproduced .", "entity": [{"entity": "triazolam", "entity_type": "Chemical", "pos": [76, 85]}, {"entity": "dehydroepiandrosterone", "entity_type": "Chemical", "pos": [204, 226]}], "task": "NER"}
{"text": "Thus , these mice are likely to be valuable in evaluating novel drugs metabolized by CYP3A enzymes and in studying the regulation of human CYP3A gene expression .", "entity": [], "task": "NER"}
{"text": "Furthermore , this system can also be used for generating Tc mice carrying other human metabolic genes .", "entity": [], "task": "NER"}
{"text": "FlyBase : improvements to the bibliography .", "entity": [], "task": "NER"}
{"text": "An accurate , comprehensive , non - redundant and up - to - date bibliography is a crucial component of any Model Organism Database ( MOD ) .", "entity": [], "task": "NER"}
{"text": "Principally , the bibliography provides a set of references that are specific to the field served by the MOD .", "entity": [], "task": "NER"}
{"text": "Moreover , it serves as a backbone to which all curated biological data can be attributed .", "entity": [], "task": "NER"}
{"text": "Here , we describe the organization and main features of the bibliography in FlyBase ( flybase . org ) , the MOD for Drosophila melanogaster .", "entity": [], "task": "NER"}
{"text": "We present an overview of the current content of the bibliography , the pipeline for identifying and adding new references , the presentation of data within Reference Reports and effective methods for searching and retrieving bibliographic data .", "entity": [], "task": "NER"}
{"text": "We highlight recent improvements in these areas and describe the advantages of using the FlyBase bibliography over alternative literature resources .", "entity": [], "task": "NER"}
{"text": "Although this article is focused on bibliographic data , many of the features and tools described are applicable to browsing and querying other datasets in FlyBase .", "entity": [], "task": "NER"}
{"text": "Enhancement on oral absorption of paclitaxel by multifunctional pluronic micelles .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "The aim of the present study is to synthesize Pluronic F127 - polyethylenimine - folate ( PF127 - PEI - FA ) copolymer , construct a mixed micelle system with PF127 - PEI - FA copolymer and Pluronic P123 ( PP123 ) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel ( PTX ) .", "entity": [{"entity": "Pluronic F127 - polyethylenimine - folate", "entity_type": "Chemical", "pos": [46, 87]}, {"entity": "PF127 - PEI - FA", "entity_type": "Chemical", "pos": [90, 106]}, {"entity": "PF127 - PEI - FA", "entity_type": "Chemical", "pos": [159, 175]}, {"entity": "Pluronic P123", "entity_type": "Chemical", "pos": [190, 203]}, {"entity": "PP123", "entity_type": "Chemical", "pos": [206, 211]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [304, 314]}, {"entity": "PTX", "entity_type": "Chemical", "pos": [317, 320]}], "task": "NER"}
{"text": "The results of intestinal absorption revealed that the PTX - loaded micelles displayed superior permeability across intestinal barrier than free drug and PF127 - PEI - FA / PP123 mixed micelles exhibited the strongest permeability across intestinal barrier .", "entity": [{"entity": "PTX", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "PF127 - PEI - FA", "entity_type": "Chemical", "pos": [154, 170]}, {"entity": "PP123", "entity_type": "Chemical", "pos": [173, 178]}], "task": "NER"}
{"text": "These results were also proved by the studies on cytotoxicity and cell uptake tests .", "entity": [], "task": "NER"}
{"text": "The mechanism was demonstrated in connection with inhibition of the efflux mediated by intestinal P - glycoprotein ( P - gp ) and enhancement of the electrostatic interaction of positive micelles with the negative intestinal epithelial cells , thereby promoting the permeation across the intestinal wall .", "entity": [], "task": "NER"}
{"text": "The presence of verapamil and Pluronic both improved the intestinal absorption of PTX , which further certified the effect of Pluronic on P - gp inhibition .", "entity": [{"entity": "verapamil", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "Pluronic", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "PTX", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "Pluronic", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "Pharmacokinetic study demonstrated that the area under the plasma concentration - time curve ( AUC ( 0 --> 36 h ) ) of PTX - loaded micelles was three times greater than the PTX solution ( dissolved in a 50 / 50 ( vol / vol ) mixture of Cremophore EL / dehydrated ethanol ) ( p < 0 . 05 ) .", "entity": [{"entity": "PTX", "entity_type": "Chemical", "pos": [119, 122]}, {"entity": "PTX", "entity_type": "Chemical", "pos": [174, 177]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [264, 271]}], "task": "NER"}
{"text": "In general PF127 - PEI - FA / PP123 mixed micelles were proved to be potential oral drug delivery system for PTX .", "entity": [{"entity": "PF127 - PEI - FA", "entity_type": "Chemical", "pos": [11, 27]}, {"entity": "PP123", "entity_type": "Chemical", "pos": [30, 35]}, {"entity": "PTX", "entity_type": "Chemical", "pos": [109, 112]}], "task": "NER"}
{"text": "Is polycystic ovary syndrome , a state of relative estrogen excess , a real risk factor for estrogen - dependant malignancies ?", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "Polycystic ovary syndrome ( PCOS ) is a common endocrinopathy affecting women of fertile age .", "entity": [], "task": "NER"}
{"text": "It is associated with several risk factors and long - term health consequences .", "entity": [], "task": "NER"}
{"text": "Chronic anovulation combined with relative estrogen excess and consequent prolonged stimulatory effect on the endometrium can lead to the pathogenesis of hormonal dependant carcinoma .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "PCOS is thus traditionally reported to be associated with increased risk of endometrial , as well as breast and ovarian cancers .", "entity": [], "task": "NER"}
{"text": "This article provides a critical literature review of the relationship between PCOS and the incidence of estrogen - dependant gynecological tumours , and it then discusses whether the commonly cited risk factor association can be substantiated by high quality studies which comply with the requirements of \" evidence - based medicine . \"", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [105, 113]}], "task": "NER"}
{"text": "Distribution , fate and histopathological effects of ethion insecticide on selected organs of the crayfish , Procambarus clarkii .", "entity": [{"entity": "ethion", "entity_type": "Chemical", "pos": [53, 59]}], "task": "NER"}
{"text": "This study aims to investigate the fate and histopathological effects of ethion on selected organs of the crayfish , Procamabrus clarkii .", "entity": [{"entity": "ethion", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "Crayfish were exposed to 1 mg l ( - 1 ) ( 14 ) C - ethion and the concentrations of ethion and its possible degradation products were measured in water and different organs of the crayfish over both the exposure and recovery periods .", "entity": [{"entity": "( 14 ) C - ethion", "entity_type": "Chemical", "pos": [40, 57]}, {"entity": "ethion", "entity_type": "Chemical", "pos": [84, 90]}], "task": "NER"}
{"text": "Chromatographic analysis revealed that ethion was degraded into ethion monooxon , ethion dioxon , O , O - diethyl phosphorothioate , O - ethyl phosphorothioate and one unknown compound .", "entity": [{"entity": "ethion", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "ethion monooxon", "entity_type": "Chemical", "pos": [64, 79]}, {"entity": "ethion dioxon", "entity_type": "Chemical", "pos": [82, 95]}, {"entity": "O , O - diethyl phosphorothioate", "entity_type": "Chemical", "pos": [98, 130]}, {"entity": "O - ethyl phosphorothioate", "entity_type": "Chemical", "pos": [133, 159]}], "task": "NER"}
{"text": "At the end of exposure period , ethion was accumulated in different organs of the crayfish especially in the hepatopancreas and gills .", "entity": [{"entity": "ethion", "entity_type": "Chemical", "pos": [32, 38]}], "task": "NER"}
{"text": "Following the transfer of crayfish to clean water for seven days , the concentration of insecticide residues were decreased in both the hepatopancreas and gills suggesting that these organs play an important role in elimination of ethion .", "entity": [{"entity": "ethion", "entity_type": "Chemical", "pos": [231, 237]}], "task": "NER"}
{"text": "On the other hand , the exposure of the crayfish to (1/4) 96 h - LC ( 50 ) ( 0 . 36 mg l ( - 1 ) ) of ethion caused extensive ultrastructural alterations to both hepatopancreas and gill epithelial cells .", "entity": [{"entity": "ethion", "entity_type": "Chemical", "pos": [102, 108]}], "task": "NER"}
{"text": "In the hepatopancreas , the most notable pathological features included vacuolation , degradation and distinct cell lysis .", "entity": [], "task": "NER"}
{"text": "In the gill epithelium , the histopathological alterations included infiltration of hemocytes , cytoplasmic vacuolation and a decrease in the number of basal plasma membrane infoldings .", "entity": [], "task": "NER"}
{"text": "Synthesis and antitumor activity of N - sulfonyl - 3 , 7 - dioxo - 5 beta - cholan - 24 - amides , ursodeoxycholic acid derivatives .", "entity": [{"entity": "N - sulfonyl - 3 , 7 - dioxo - 5 beta - cholan - 24 - amides", "entity_type": "Chemical", "pos": [36, 96]}, {"entity": "ursodeoxycholic acid", "entity_type": "Chemical", "pos": [99, 119]}], "task": "NER"}
{"text": "A series of N - sulfonyl - 3 , 7 - dioxo - 5 beta - cholan - 24 - amides , ursodeoxycholic acid derivatives , have been designed and synthesized in nine steps starting from ursodeoxycholic acid .", "entity": [{"entity": "N - sulfonyl - 3 , 7 - dioxo - 5 beta - cholan - 24 - amides", "entity_type": "Chemical", "pos": [12, 72]}, {"entity": "ursodeoxycholic acid", "entity_type": "Chemical", "pos": [75, 95]}, {"entity": "ursodeoxycholic acid", "entity_type": "Chemical", "pos": [173, 193]}], "task": "NER"}
{"text": "The in vitro antitumor activity of the target compounds has been evaluated against HCT - 116 , MCF - 7 , K562 , and SGC - 7901 cell lines .", "entity": [], "task": "NER"}
{"text": "The pharmacological results showed that most of the prepared compounds display excellent selective cytotoxicity toward HCT - 116 , MCF - 7 , and K562 cell lines .", "entity": [], "task": "NER"}
{"text": "Particularly , compounds 10c , 10f and 10g show high inhibitory activity on these human cancer cell lines ( IC50 : 2 . 39 - 9 . 34 mu M ) .", "entity": [], "task": "NER"}
{"text": "Conversely , all compounds are generally inactive against SGC - 7901 , with only 10b having IC 5 0 below 50 mu M .", "entity": [], "task": "NER"}
{"text": "Precipitation of Ibuprofen Sodium using compressed carbon dioxide as antisolvent .", "entity": [{"entity": "Ibuprofen Sodium", "entity_type": "Chemical", "pos": [17, 33]}, {"entity": "carbon dioxide", "entity_type": "Chemical", "pos": [51, 65]}], "task": "NER"}
{"text": "Precipitation with compressed antisolvent ( PCA ) process was used to produce fine particles of Ibuprofen Sodium with the ultimate goal of obtaining controlled particle size and size distribution of this non - steroidal anti - inflammatory drug .", "entity": [{"entity": "Ibuprofen Sodium", "entity_type": "Chemical", "pos": [96, 112]}], "task": "NER"}
{"text": "This systematic investigation shows that particle size and size distribution of the final product can be controlled reproducibly by varying a number operating parameters such as antisolvent addition rate , temperature , concentration , and solution addition rate .", "entity": [], "task": "NER"}
{"text": "The mechanisms that control particle size and particle size distribution were explained by invoking the differences in the relative weight of primary , secondary nucleation and growth kinetic phenomena .", "entity": [], "task": "NER"}
{"text": "A number of techniques were used for the characterization of the generated particles .", "entity": [], "task": "NER"}
{"text": "In addition to scanning electron microscope ( SEM ) , dynamic light scattering measurements were conducted to determine the size of the particles in terms of number - weighted size distribution .", "entity": [], "task": "NER"}
{"text": "The influence of process parameters on the Ibuprofen Sodium crystallinity was investigated using X - ray diffraction ( XRD ) .", "entity": [{"entity": "Ibuprofen Sodium", "entity_type": "Chemical", "pos": [43, 59]}], "task": "NER"}
{"text": "Moreover , the ' ' in vitro ' ' drug performance was tested .", "entity": [], "task": "NER"}
{"text": "The results showed an improvement of the PCA processed Ibuprofen Sodium ' ' in vitro ' ' drug activity .", "entity": [{"entity": "Ibuprofen Sodium", "entity_type": "Chemical", "pos": [55, 71]}], "task": "NER"}
{"text": "In addition , dissolution investigations demonstrated that the flow rate , in combination with the particle size distribution , substantially influence the drug \" in vitro \" dissolution .", "entity": [], "task": "NER"}
{"text": "Angiotensin - ( 1 - 7 ) modulates renin - angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats .", "entity": [{"entity": "Angiotensin - ( 1 - 7 )", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "Angiotensin - ( 1 - 7 ) [ Ang - ( 1 - 7 ) ] has beneficial effects against hypertension - induced damage in heart and kidney , but its effects in brain are not clear as yet .", "entity": [{"entity": "Angiotensin - ( 1 - 7 )", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [26, 41]}], "task": "NER"}
{"text": "The present study aimed to investigate the protective effects of Ang - ( 1 - 7 ) on the physiopathologic changes caused by hypertension in brain of spontaneously hypertensive rats ( SHRs ) .", "entity": [{"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [65, 80]}], "task": "NER"}
{"text": "Wistar - Kyoto rats received intracerebroventricular ( I . C . V . ) infusion of artificial cerebrospinal fluid ( aCSF ) while SHRs received I . C . V . infusion of Ang - ( 1 - 7 ) , Mas receptor antagonist A - 779 and aCSF for 4 weeks .", "entity": [{"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [165, 180]}], "task": "NER"}
{"text": "Brain tissues were collected and analyzed by western blot , enzyme immunoassay , spectrophotometric assays and terminal deoxynucleotidyl transferase - mediated dUTP end - labeling ( TUNEL ) staining .", "entity": [{"entity": "deoxynucleotidyl", "entity_type": "Chemical", "pos": [120, 136]}, {"entity": "dUTP", "entity_type": "Chemical", "pos": [160, 164]}], "task": "NER"}
{"text": "Our study showed that infusion of Ang - ( 1 - 7 ) for 4 weeks significantly reduced the expression of Angiotensin II and Angiotensin II type 1 receptors in SHR brain .", "entity": [{"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [34, 49]}, {"entity": "Angiotensin II", "entity_type": "Chemical", "pos": [102, 116]}, {"entity": "Angiotensin II", "entity_type": "Chemical", "pos": [121, 135]}], "task": "NER"}
{"text": "Additionally , it decreased the levels of malondialdehyde and elevated total superoxide dismutase activity , which was accompanied by reductions of NADPH oxidase subunit gp91 ( phox ) and inducible nitric oxide synthase in the brain of SHR .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [42, 57]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [77, 87]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [148, 153]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [198, 210]}], "task": "NER"}
{"text": "The increases of the percentage of TUNEL - positive neurons and Bax to Bcl - 2 ratio in SHR brain were also attenuated by Ang - ( 1 - 7 ) .", "entity": [{"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [122, 137]}], "task": "NER"}
{"text": "The anti - oxidative and anti - apoptosis effects of Ang - ( 1 - 7 ) are independent of blood pressure reduction and can be partially abolished by A - 779 .", "entity": [{"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [53, 68]}], "task": "NER"}
{"text": "These findings suggest that chronic treatment with Ang - ( 1 - 7 ) is beneficial to attenuate hypertension - induced physiopathologic changes in brain and may be helpful to prevent hypertension - related cerebrovascular diseases .", "entity": [{"entity": "Ang - ( 1 - 7 )", "entity_type": "Chemical", "pos": [51, 66]}], "task": "NER"}
{"text": "Cell cycle regulation by glucosamine in human pulmonary epithelial cells .", "entity": [{"entity": "glucosamine", "entity_type": "Chemical", "pos": [25, 36]}], "task": "NER"}
{"text": "Airway epithelial cells play an important role against intruding pathogens .", "entity": [], "task": "NER"}
{"text": "Glucosamine , a commonly used supplemental compound , has recently begun to be regarded as a potential anti - inflammatory molecule .", "entity": [{"entity": "Glucosamine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "This study aimed to uncover how glucosamine impacts on cellular proliferation in human alveolar epithelial cells ( A549 ) and bronchial epithelial cells ( HBECs ) .", "entity": [{"entity": "glucosamine", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "With trypan blue - exclusion assay , we observed that glucosamine ( 10 , 20 , 50 mM ) caused a decrease in cell number at 24 and 48 h ; with a flow cytometric analysis , we also noted an enhanced cell accumulation within the G ( 0 ) / G ( 1 ) phase at 24 h and induction of late apoptosis at 24 and 48 h by glucosamine ( 10 , 20 , 50 mM ) in A549 cells and HBECs .", "entity": [{"entity": "trypan blue", "entity_type": "Chemical", "pos": [5, 16]}, {"entity": "glucosamine", "entity_type": "Chemical", "pos": [54, 65]}, {"entity": "glucosamine", "entity_type": "Chemical", "pos": [307, 318]}], "task": "NER"}
{"text": "Examination of phosphorylation in retinoblastoma ( Rb ) protein , we found an inhibitory effect by glucosamine at 20 and 50 mM .", "entity": [{"entity": "glucosamine", "entity_type": "Chemical", "pos": [99, 110]}], "task": "NER"}
{"text": "Glucosamine at 50 mM was demonstrated to elevate both the mRNA and protein expression of p53 and heme oxygenase - 1 ( HO - 1 ) , but also caused a reduction in p21 protein expression .", "entity": [{"entity": "Glucosamine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "heme", "entity_type": "Chemical", "pos": [97, 101]}], "task": "NER"}
{"text": "In addition , glucosamine attenuated p21 protein stability via the proteasomal proteolytic pathway , as well as inducing p21 nuclear accumulation .", "entity": [{"entity": "glucosamine", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Altogether , our results suggest that a high dose of glucosamine may inhibit cell proliferation through apoptosis and disturb cell cycle progression with a halt at G ( 0 ) / G ( 1 ) phase , and that this occurs , at least in part , by a reduction in Rb phosphorylation together with modulation of p21 , p53 and HO - 1 expression , and nuclear p21 accumulation .", "entity": [{"entity": "glucosamine", "entity_type": "Chemical", "pos": [53, 64]}], "task": "NER"}
{"text": "Symmetrically reduced stiffness and increased extensibility in compression and tension at the mineralized fibrillar level in rachitic bone .", "entity": [], "task": "NER"}
{"text": "In metabolic bone diseases , the alterations in fibrillar level bone - material quality affecting macroscopic mechanical competence are not well - understood quantitatively .", "entity": [], "task": "NER"}
{"text": "Here , we quantify the fibrillar level deformation in cantilever bending in a mouse model for hereditary rickets ( Hpr ) .", "entity": [], "task": "NER"}
{"text": "Microfocus in - situ synchrotron small - angle X - ray scattering ( SAXS ) combined with cantilever bending was used to resolve nanoscale fibril strain in tensile - and compressive tissue regions separately , with quantitative backscattered scanning electron microscopy used to measure microscale mineralization .", "entity": [], "task": "NER"}
{"text": "Tissue - level flexural moduli for Hpr mice were significantly ( p < 0 . 01 ) smaller compared to wild - type ( ~ 5 to 10 - fold reduction ) .", "entity": [], "task": "NER"}
{"text": "At the fibrillar level , the fibril moduli within the tensile and compressive zones were significantly ( p < 0 . 05 ) lower by ~ 3 - to 5 - fold in Hpr mice compared to wild - type mice .", "entity": [], "task": "NER"}
{"text": "Hpr mice have a lower mineral content ( 24 . 2 +/- 2 . 1Cawt . % versus 27 . 4 +/- 3 . 3Ca wt . % ) and its distribution was more heterogeneous compared to wild - type animals .", "entity": [], "task": "NER"}
{"text": "However , the average effective fibril modulus did not differ significantly ( p > 0 . 05 ) over ages ( 4 , 7 and 10weeks ) between tensile and compressive zones .", "entity": [], "task": "NER"}
{"text": "Our results indicate that incompletely mineralized fibrils in Hpr mice have greater deformability and lower moduli in both compression and tension , and those compressive and tensile zones have similar moduli at the fibrillar level .", "entity": [], "task": "NER"}
{"text": "Prediction of crizotinib - midazolam interaction using the Simcyp population - based simulator : comparison of CYP3A time - dependent inhibition between human liver microsomes versus hepatocytes .", "entity": [{"entity": "crizotinib", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "midazolam", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "Crizotinib ( Xalkori ) is an orally available potent inhibitor of multiple tyrosine kinases , including anaplastic lymphoma kinase and mesenchymal - epithelial transition factor .", "entity": [{"entity": "Crizotinib", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "Xalkori", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "Objectives of the present study were as follows : 1 ) to characterize crizotinib time - dependent inhibition ( TDI ) potency for CYP3A in human liver microsomes ( HLM ) and cryopreserved human hepatocytes suspended in human plasma ( HSP ) ; 2 ) to characterize crizotinib enzyme induction potency on CYP3A4 in cryopreserved human hepatocytes ; 3 ) to predict crizotinib steady - state plasma concentrations in patients ( e . g . , autoinhibition and autoinduction ) using the mechanistic dynamic model , Simcyp population - based simulator ; and 4 ) to predict a clinical crizotinib - midazolam interaction using the dynamic model as well as the static mathematical model .", "entity": [{"entity": "crizotinib", "entity_type": "Chemical", "pos": [70, 80]}, {"entity": "crizotinib", "entity_type": "Chemical", "pos": [261, 271]}, {"entity": "crizotinib", "entity_type": "Chemical", "pos": [359, 369]}, {"entity": "crizotinib", "entity_type": "Chemical", "pos": [572, 582]}, {"entity": "midazolam", "entity_type": "Chemical", "pos": [585, 594]}], "task": "NER"}
{"text": "Crizotinib inactivation constant ( K ( I ) ) and maximum inactivation rate constant ( k ( inact ) ) for TDI were estimated as , respectively , 0 . 37 micro M and 6 . 9 h ( - 1 ) in HLM and 0 . 89 micro M and 0 . 78 h ( - 1 ) in HSP .", "entity": [{"entity": "Crizotinib", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Thus , crizotinib inactivation efficiency ( k ( inact ) / K ( I ) ) was ~ 20 - fold lower in HSP relative to HLM .", "entity": [{"entity": "crizotinib", "entity_type": "Chemical", "pos": [7, 17]}], "task": "NER"}
{"text": "Crizotinib E ( max ) and EC ( 50 ) for CYP3A4 induction ( measured as mRNA expression ) were estimated as 6 . 4 - to 29 - fold and 0 . 47 to 3 . 1 micro M , respectively .", "entity": [{"entity": "Crizotinib", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Based on these in vitro parameters , the predicted crizotinib steady - state area under plasma concentration - time curve ( AUC ) with HLM - TDI was 2 . 1 - fold higher than the observed AUC , whereas that with HSP - TDI was consistent with the observed result ( <= 1 . 1 - fold ) .", "entity": [{"entity": "crizotinib", "entity_type": "Chemical", "pos": [51, 61]}], "task": "NER"}
{"text": "The increase in midazolam AUC with coadministration of crizotinib ( 21 - fold ) was significantly overpredicted using HLM - TDI , whereas the prediction using HSP - TDI ( 3 . 6 - fold ) was consistent with the observed result ( 3 . 7 - fold ) .", "entity": [{"entity": "midazolam", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "crizotinib", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "Collectively , the present study demonstrated the value of HSP to predict in vivo CYP3A - mediated drug - drug interaction .", "entity": [], "task": "NER"}
{"text": "Arsenic and arsenic species in cultured oyster ( Crassostrea gigas and C . corteziensis ) from coastal lagoons of the SE Gulf of California , Mexico .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [12, 19]}], "task": "NER"}
{"text": "The aim of this study was to evaluate the bioavailability of arsenic ( As ) through cultured oyster Crassostrea gigas and Crassostrea corteziensis from four coastal lagoons ( SE Gulf of California ) .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "As", "entity_type": "Chemical", "pos": [71, 73]}], "task": "NER"}
{"text": "Organisms were collected in two seasons ( rainy and dry season ) , and they were analyzed for total arsenic and chemical speciation of this element .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "The concentrations of As in oyster soft tissue fluctuated between 5 . 44 and 9 . 56 mu g / g for rainy season and 6 . 46 and 8 . 33 mu g / g for dry season ( dry weight ) in C . gigas .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [22, 24]}], "task": "NER"}
{"text": "In C . corteziensis , the As concentrations were < 5 mu g / g for both seasons ( dry weight ) .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [26, 28]}], "task": "NER"}
{"text": "Arsenic speciation indicated arsenobetaine as the major arseno - compound accounting for 43 . 2 - 76 . 3 % of total content of As .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "arsenobetaine", "entity_type": "Chemical", "pos": [29, 42]}, {"entity": "arseno", "entity_type": "Chemical", "pos": [56, 62]}, {"entity": "As", "entity_type": "Chemical", "pos": [127, 129]}], "task": "NER"}
{"text": "Lower contributions were obtained for non - extractable As ( 11 . 3 - 17 . 5 % ) and other molecules such as arsenocholine and methyl - arsonate ( < 5 % ) .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "arsenocholine", "entity_type": "Chemical", "pos": [109, 122]}, {"entity": "methyl - arsonate", "entity_type": "Chemical", "pos": [127, 144]}], "task": "NER"}
{"text": "Inorganic arsenic was detectable in only two samples , at concentrations lower than < 0 . 1 mu g / g .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [10, 17]}], "task": "NER"}
{"text": "These As data are the first generated for these mollusks in NW Mexico and indicate that C . gigas and C . corteziensis farmed in this area are safe for human consumption in terms of arseno - compounds .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [6, 8]}, {"entity": "arseno", "entity_type": "Chemical", "pos": [182, 188]}], "task": "NER"}
{"text": "Probing the binding of cationic lipids with dendrimers .", "entity": [], "task": "NER"}
{"text": "Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell .", "entity": [], "task": "NER"}
{"text": "We report the bindings of several lipids cholesterol ( Chol ) , 1 , 2 - dioleoyl - 3 - trimethylammonium - propane ( DOTAP ) , dioctadecyldimethylammoniumbromide ( DDAB ) , and dioleoylphosphatidylethanolamine ( DOPE ) to dendrimers of different compositions such as mPEG - PAMAM ( G3 ) , mPEG - PAMAM ( G4 ) , and PAMAM ( G4 ) under physiological conditions .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [41, 52]}, {"entity": "Chol", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "1 , 2 - dioleoyl - 3 - trimethylammonium - propane", "entity_type": "Chemical", "pos": [64, 114]}, {"entity": "DOTAP", "entity_type": "Chemical", "pos": [117, 122]}, {"entity": "dioctadecyldimethylammoniumbromide", "entity_type": "Chemical", "pos": [127, 161]}, {"entity": "DDAB", "entity_type": "Chemical", "pos": [164, 168]}, {"entity": "dioleoylphosphatidylethanolamine", "entity_type": "Chemical", "pos": [177, 209]}, {"entity": "DOPE", "entity_type": "Chemical", "pos": [212, 216]}, {"entity": "mPEG - PAMAM", "entity_type": "Chemical", "pos": [267, 279]}, {"entity": "mPEG - PAMAM", "entity_type": "Chemical", "pos": [289, 301]}, {"entity": "PAMAM", "entity_type": "Chemical", "pos": [315, 320]}], "task": "NER"}
{"text": "FTIR , UV - visible spectroscopic , methods and molecular modeling were used to analyze the lipid binding mode , the binding constant , and the effects of lipid complexation on the dendrimer structure .", "entity": [], "task": "NER"}
{"text": "The structural analysis showed that lipids bind dendrimers through both hydrophilic and hydrophobic contacts with overall binding constants of K ( chol - mPEG - G3 ) = 1 . 7 x 10 ( 3 ) M ( - 1 ) , K ( chol - mPEG - PAMAM - G4 ) = 2 . 7 x 10 ( 3 ) M ( - 1 ) , K ( chol - PAMAM - G4 ) = 1 . 0 x 10 ( 3 ) M ( - 1 ) , K ( DOPE - mPEG - G3 ) = 1 . 5 x 10 ( 3 ) M ( - 1 ) , K ( DOPE - mPEG - PAMAM - G4 ) = 1 . 6 x 10 ( 3 ) M ( - 1 ) , K ( DOPE - PAMAM - G4 ) = 5 . 3 x 10 ( 2 ) M ( - 1 ) , K ( DDAB - mPEG - G3 ) = 1 . 5 x 10 ( 3 ) M ( - 1 ) , K ( DDAB - mPEG - PAMAM - G4 ) = 1 . 9 x 10 ( 2 ) M ( - 1 ) , K ( DDAB - PAMAM - G4 ) = 7 . 0 x 10 ( 2 ) M ( - 1 ) , K ( DOTAP - mPEG - G3 ) = 1 . 9 x 10 ( 3 ) M ( - 1 ) , K ( DOTAP - mPEG - PAMAM - G4 ) = 1 . 5 x 10 ( 3 ) M ( - 1 ) , and K ( DOTAP - PAMAM - G4 ) = 5 . 7 x 10 ( 2 ) M ( - 1 ) .", "entity": [{"entity": "chol - mPEG - G3", "entity_type": "Chemical", "pos": [147, 163]}, {"entity": "chol - mPEG - PAMAM - G4", "entity_type": "Chemical", "pos": [201, 225]}, {"entity": "chol - PAMAM - G4", "entity_type": "Chemical", "pos": [263, 280]}, {"entity": "DOPE - mPEG - G3", "entity_type": "Chemical", "pos": [318, 334]}, {"entity": "DOPE - mPEG - PAMAM - G4", "entity_type": "Chemical", "pos": [372, 396]}, {"entity": "DOPE - PAMAM - G4", "entity_type": "Chemical", "pos": [434, 451]}, {"entity": "DDAB - mPEG - G3", "entity_type": "Chemical", "pos": [489, 505]}, {"entity": "DDAB - mPEG - PAMAM - G4", "entity_type": "Chemical", "pos": [543, 567]}, {"entity": "DDAB - PAMAM - G4", "entity_type": "Chemical", "pos": [605, 622]}, {"entity": "DOTAP - mPEG - G3", "entity_type": "Chemical", "pos": [660, 677]}, {"entity": "DOTAP - mPEG - PAMAM - G4", "entity_type": "Chemical", "pos": [715, 740]}, {"entity": "DOTAP - PAMAM - G4", "entity_type": "Chemical", "pos": [782, 800]}], "task": "NER"}
{"text": "Weaker interaction was observed as dendrimer cationic charges increased .", "entity": [], "task": "NER"}
{"text": "The free binding energies from docking were - 5 . 15 ( cholesterol ) , - 5 . 79 ( DDAB ) , and - 5 . 36 kcal / mol ( DOTAP ) with the order of stability DDAB - PAMAM - G - 4 > DOTAP - PAMAM - G4 > cholesterol - PAMAM - G4 , consistent with the spectroscopic results .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [55, 66]}, {"entity": "DDAB", "entity_type": "Chemical", "pos": [82, 86]}, {"entity": "DOTAP", "entity_type": "Chemical", "pos": [117, 122]}, {"entity": "DDAB - PAMAM - G - 4", "entity_type": "Chemical", "pos": [153, 173]}, {"entity": "DOTAP - PAMAM - G4", "entity_type": "Chemical", "pos": [176, 194]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [197, 208]}, {"entity": "PAMAM - G4", "entity_type": "Chemical", "pos": [211, 221]}], "task": "NER"}
{"text": "Dendrimers might act as carriers to transport lipids in vitro .", "entity": [], "task": "NER"}
{"text": "Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPAR gamma in breast cancer pathophysiology .", "entity": [], "task": "NER"}
{"text": "Peroxisome proliferator - activated receptor gamma ( PPAR gamma ) is a nuclear receptor and plays important roles in breast cancer cell proliferation .", "entity": [], "task": "NER"}
{"text": "The complexity of the underlying biochemical and molecular mechanisms of breast cancer and the involvement of PPAR gamma in breast cancer pathophysiology are unclear .", "entity": [], "task": "NER"}
{"text": "In this study , we carried out prediction of the peroxisome proliferator response element ( PPRE ) motifs in 2332 genes reported to be involved in breast cancer in literature .", "entity": [], "task": "NER"}
{"text": "A total of 178 genes were found to have PPRE ( DR1 / DR2 ) and / or PPAR - associated conserved motif ( PACM ) motifs .", "entity": [], "task": "NER"}
{"text": "We further constructed protein - protein interaction network , disease gene network and gene ontology ( GO ) analyses to identify novel key genes for experimental validation .", "entity": [], "task": "NER"}
{"text": "We identified two genes in the glycolytic pathway ( phosphoglycerate kinase 1 ( PGK1 ) and pyruvate kinase M2 ( PKM2 ) ) at the ATP production steps and experimentally validated their repression by PPAR gamma in two breast cancer cell lines MDA - MB - 231 and MCF - 7 .", "entity": [{"entity": "phosphoglycerate", "entity_type": "Chemical", "pos": [52, 68]}, {"entity": "pyruvate", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "Further analysis suggested that this repression leads to decrease in ATP levels and apoptosis .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "These investigations will help us in understanding the molecular mechanisms by which PPAR gamma regulates the cellular energy pathway and the use of its ligands in human breast cancer therapeutics .", "entity": [], "task": "NER"}
{"text": "Evaluation of the metabolism and hepatotoxicity of xenobiotics utilizing precision - cut slices .", "entity": [], "task": "NER"}
{"text": "1 .", "entity": [], "task": "NER"}
{"text": "Precision - cut liver slices are a valuable in vitro model system to study the metabolism and toxicity of xenobiotics .", "entity": [], "task": "NER"}
{"text": "Liver slices retain tissue architecture so that all cell types are present and intercellular communication between the various cell types is retained .", "entity": [], "task": "NER"}
{"text": "Precision - cut liver slices from humans and other species have been used to study pathways of phase I ( e . g . cytochrome P450 - dependent biotransformations ) and II ( e . g . conjugation with D - glucuronic acid , sulphate and glutathione ) metabolism of a wide range of xenobiotics .", "entity": [{"entity": "D - glucuronic acid", "entity_type": "Chemical", "pos": [196, 215]}, {"entity": "sulphate", "entity_type": "Chemical", "pos": [218, 226]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [231, 242]}], "task": "NER"}
{"text": "Liver slices can also be employed to investigate the induction and inhibition of xenobiotic metabolizing enzymes and to obtain kinetic data on the rates of metabolism of xenobiotics .", "entity": [], "task": "NER"}
{"text": "4 .", "entity": [], "task": "NER"}
{"text": "Precision - cut liver slices from humans and other species have been used to study the toxicity of a wide variety of xenobiotics .", "entity": [], "task": "NER"}
{"text": "Toxicity can be assessed by various techniques including gene expression , morphological examination and a wide range of biochemical endpoints .", "entity": [], "task": "NER"}
{"text": "5 .", "entity": [], "task": "NER"}
{"text": "Precision - cut liver slices can be utilized to examine species differences in hepatic xenobiotic metabolism and xenobiotic - induced toxicity , thus permitting comparisons between animal species and humans .", "entity": [], "task": "NER"}
{"text": "In vitro and in vivo evaluation of an in situ gel forming system for the delivery of PEGylated octreotide .", "entity": [{"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [85, 105]}], "task": "NER"}
{"text": "The objective of this study was to develop a controlled delivery system for PEGylated octreotide using a Poloxamer based in situ gel forming polymer .", "entity": [{"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [76, 96]}, {"entity": "Poloxamer", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "PEGylated octreotide kept its full biological activity and higher serum half - life compared to the original octreotide .", "entity": [{"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "octreotide", "entity_type": "Chemical", "pos": [109, 119]}], "task": "NER"}
{"text": "The designed drug delivery system contained low concentration of Poloxamer 407 ( P407 ) ( < 0 . 16 % ) with polyvinyl alcohol ( PVA ) as a polymeric additive .", "entity": [{"entity": "Poloxamer 407", "entity_type": "Chemical", "pos": [65, 78]}, {"entity": "P407", "entity_type": "Chemical", "pos": [81, 85]}, {"entity": "polyvinyl alcohol", "entity_type": "Chemical", "pos": [108, 125]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "Rheological measurements of gel vehicle formulations indicated that the in situ gel forming system with optimum sol - gel transition temperature of 28 . 7 degrees C could be formed using a combination of P407 and PVA at ratio of 15 - 10 % ( w / v ) .", "entity": [{"entity": "P407", "entity_type": "Chemical", "pos": [204, 208]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [213, 216]}], "task": "NER"}
{"text": "The effect of formulation additives such as buffering agents on rheological behavior demonstrated that sodium bicarbonate and lactic acid have opposite effect on sol - gel transition temperature of the system .", "entity": [{"entity": "sodium bicarbonate", "entity_type": "Chemical", "pos": [103, 121]}, {"entity": "lactic acid", "entity_type": "Chemical", "pos": [126, 137]}], "task": "NER"}
{"text": "Using buffering agents , it was possible to shift the sol - gel transition to lower or higher temperatures .", "entity": [], "task": "NER"}
{"text": "The in vitro release profiles of octreotide and PEGylated octreotide from the selected P407 / PVA formulations were measured using a membrane - less device .", "entity": [{"entity": "octreotide", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [48, 68]}, {"entity": "P407", "entity_type": "Chemical", "pos": [87, 91]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "PEGylated octreotide showed slower release rate from the gel system with different release kinetic compared to octreotide .", "entity": [{"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "octreotide", "entity_type": "Chemical", "pos": [111, 121]}], "task": "NER"}
{"text": "In animal studies , a sustained release rate was achieved with both PEGylated and non - PEGylated octreotide , but longer delivery was observed for PEGylated octreotide .", "entity": [{"entity": "PEGylated and non - PEGylated octreotide", "entity_type": "Chemical", "pos": [68, 108]}, {"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [148, 168]}], "task": "NER"}
{"text": "Tissue histopathological studies confirmed the biocompatibility of the delivery system for PEGylated octreotide , supporting the suitability of P407 / PVA mixture as an injectable drug delivery system .", "entity": [{"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [91, 111]}, {"entity": "P407", "entity_type": "Chemical", "pos": [144, 148]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [151, 154]}], "task": "NER"}
{"text": "The total effects of increasing PEGylated peptide half - life and prolonged release from thermoresponsive gel system offer the potential for sustained delivery of PEGylated octreotide .", "entity": [{"entity": "PEGylated octreotide", "entity_type": "Chemical", "pos": [163, 183]}], "task": "NER"}
{"text": "Regulation of glycogen synthase from mammalian skeletal muscle - - a unifying view of allosteric and covalent regulation .", "entity": [], "task": "NER"}
{"text": "It is widely accepted that insufficient insulin - stimulated activation of muscle glycogen synthesis is one of the major components of non - insulin - dependent ( type 2 ) diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "Glycogen synthase , a key enzyme in muscle glycogen synthesis , is extensively regulated , both allosterically ( by glucose - 6 - phosphate , ATP , and others ) and covalently ( by phosphorylation ) .", "entity": [{"entity": "glucose - 6 - phosphate", "entity_type": "Chemical", "pos": [116, 139]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "Although glycogen synthase has been a topic of intense study for more than 50 years , its kinetic characterization has been confounded by its large number of phosphorylation states .", "entity": [], "task": "NER"}
{"text": "Questions remain regarding the function of glycogen synthase regulation and the relative importance of allosteric and covalent modification in fulfilling this function .", "entity": [], "task": "NER"}
{"text": "In this review , we consider both earlier kinetic studies and more recent site - directed mutagenesis and crystal structure studies in a detailed qualitative discussion of the effects of regulation on the kinetics of glycogen synthase .", "entity": [], "task": "NER"}
{"text": "We propose that both allosteric and covalent modification of glycogen synthase may be described by a Monod - Wyman - Changeux model in terms of apparent changes to L , the equilibrium constant for transition between the T and R conformers .", "entity": [], "task": "NER"}
{"text": "As , with the exception of L , all parameters of this model are independent of the glycogen synthase phosphorylation state , the need to determine kinetic parameters for all possible states is eliminated ; only the relationship between a particular state and L must be established .", "entity": [], "task": "NER"}
{"text": "We conclude by suggesting that renewed efforts to characterize the relationship between phosphorylation and the kinetics of glycogen synthase are essential in order to obtain a better quantitative understanding of the function of glycogen synthesis regulation .", "entity": [], "task": "NER"}
{"text": "The model we propose may prove useful in this regard .", "entity": [], "task": "NER"}
{"text": "LARGE2 generates the same xylose - and glucuronic acid - containing glycan structures as LARGE .", "entity": [{"entity": "xylose", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "glucuronic acid", "entity_type": "Chemical", "pos": [39, 54]}], "task": "NER"}
{"text": "LARGE ( like - glycosyltransferase ) and LARGE2 ( glycosyltransferase - like 1B ( GYLTL1B ) ) are homologous Golgi glycosyltransferases possessing two catalytic domains with homology to members of glycosyltransferase families GT8 and GT49 .", "entity": [], "task": "NER"}
{"text": "Mutations in human and mouse Large result in muscular dystrophy due to underglycosylation of dystroglycan .", "entity": [], "task": "NER"}
{"text": "The systemic function of LARGE2 is unknown , but at a cellular level the enzyme can substitute for LARGE in glycosylating dystroglycan .", "entity": [], "task": "NER"}
{"text": "Here , we show that LARGE2 catalyzes the same glycosylation reaction as LARGE .", "entity": [], "task": "NER"}
{"text": "It is a bifunctional glycosyltransferase using uridine diphosphate ( UDP ) - xylose ( Xyl ) and UDP - glucuronic acid ( GlcA ) as donor sugars to produce a xyloglucuronan with alternating Xyl and GlcA residues .", "entity": [{"entity": "uridine diphosphate", "entity_type": "Chemical", "pos": [47, 66]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "xylose", "entity_type": "Chemical", "pos": [77, 83]}, {"entity": "Xyl", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [96, 99]}, {"entity": "glucuronic acid", "entity_type": "Chemical", "pos": [102, 117]}, {"entity": "GlcA", "entity_type": "Chemical", "pos": [120, 124]}, {"entity": "sugars", "entity_type": "Chemical", "pos": [136, 142]}, {"entity": "Xyl", "entity_type": "Chemical", "pos": [188, 191]}, {"entity": "GlcA", "entity_type": "Chemical", "pos": [196, 200]}], "task": "NER"}
{"text": "Electric field - induced dipole switching at the donor / acceptor interface in organic solar cells .", "entity": [], "task": "NER"}
{"text": "Order of dipole moment layers at donor and acceptor interfaces in bilayer organic solar cells is manipulated reversibly by applying bias voltages .", "entity": [], "task": "NER"}
{"text": "The energy level shifts at the interfaces induce reversible changes in the open circuit voltage and the diode properties .", "entity": [], "task": "NER"}
{"text": "This finding could lead to a better understanding of the structure - property relationship at the materials interfaces in organic optoelectronic devices .", "entity": [], "task": "NER"}
{"text": "Reversible and cyclical transformations between solid and hollow nanostructures in confined reactions of manganese oxide and silica within nanosized spheres .", "entity": [{"entity": "manganese oxide", "entity_type": "Chemical", "pos": [105, 120]}, {"entity": "silica", "entity_type": "Chemical", "pos": [125, 131]}], "task": "NER"}
{"text": "Annealing of MnO @ SiO ( 2 ) nanospheres in a reducing gas environment resulted in the transformation of the core - shell structure into a hollow structure as a result of outward diffusion of MnO species into the thermodynamically more stable silicate phase .", "entity": [{"entity": "MnO", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "SiO ( 2 )", "entity_type": "Chemical", "pos": [19, 28]}, {"entity": "MnO", "entity_type": "Chemical", "pos": [192, 195]}, {"entity": "silicate", "entity_type": "Chemical", "pos": [243, 251]}], "task": "NER"}
{"text": "When the hollow silicate nanospheres were oxidized , the interior cavities were refilled with a Mn ( 3 ) O ( 4 ) phase segregated from the silicate phase , and the hollow structure reverted to the initial core - shell structure .", "entity": [{"entity": "silicate", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "Mn ( 3 ) O ( 4 )", "entity_type": "Chemical", "pos": [96, 112]}, {"entity": "silicate", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "More interestingly , when catalytically active Pt nanocrystals were introduced into the manganese oxide / silica system , the Mn ( 3 ) O ( 4 ) was readily reduced to the chemically reactive MnO , even at low temperature , which enabled reconversion of the solid nanospheres with a Mn ( 3 ) O ( 4 ) core to hollow nanostructures during reductive annealing .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [47, 49]}, {"entity": "manganese oxide", "entity_type": "Chemical", "pos": [88, 103]}, {"entity": "silica", "entity_type": "Chemical", "pos": [106, 112]}, {"entity": "Mn ( 3 ) O ( 4 )", "entity_type": "Chemical", "pos": [126, 142]}, {"entity": "MnO", "entity_type": "Chemical", "pos": [190, 193]}, {"entity": "Mn ( 3 ) O ( 4 )", "entity_type": "Chemical", "pos": [281, 297]}], "task": "NER"}
{"text": "Therefore , when MnO @ SiO ( 2 ) / Pt ( II ) nanospheres were subjected to an oxidation / reduction cycle by repeatedly switching the flowing gas between air and hydrogen , the nanospheres underwent a reversible change between solid and hollow structures , depending on the gas environment .", "entity": [{"entity": "MnO", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "SiO ( 2 )", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "Pt ( II )", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [162, 170]}], "task": "NER"}
{"text": "The solid - to - hollow - to - solid transformation was successfully cycled many times simply by repeatedly switching the flowing gas during annealing .", "entity": [], "task": "NER"}
{"text": "Polydatin ameliorates renal injury by attenuating oxidative stress - related inflammatory responses in fructose - induced urate nephropathic mice .", "entity": [{"entity": "Polydatin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [103, 111]}, {"entity": "urate", "entity_type": "Chemical", "pos": [122, 127]}], "task": "NER"}
{"text": "A series of studies have recently demonstrated that the oxidative stress , nuclear factor - kappa B ( NF - kappa B ) activation and the subsequent coordinated inflammatory responses played an important role in the pathogenesis of urate nephropathy ( UN ) .", "entity": [{"entity": "urate", "entity_type": "Chemical", "pos": [230, 235]}], "task": "NER"}
{"text": "Polydatin has been suggested to have the properties of anti - oxidative , anti - inflammatory and nephroprotective effects .", "entity": [{"entity": "Polydatin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "However , the possible protective and beneficial effects of polydatin on UN are not fully elucidated .", "entity": [{"entity": "polydatin", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "Therefore , we investigated the potential beneficial effects and possible mechanisms of polydatin on UN .", "entity": [{"entity": "polydatin", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "In this study , polydatin showed inhibitory activities on xanthine oxidase to repress the level of serum uric acid in vivo and in vitro .", "entity": [{"entity": "polydatin", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "xanthine", "entity_type": "Chemical", "pos": [58, 66]}, {"entity": "uric acid", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "Further investigations revealed that polydatin displayed little toxic effects and significantly ameliorated the renal function in fructose - induced UN mice .", "entity": [{"entity": "polydatin", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [130, 138]}], "task": "NER"}
{"text": "The nephroprotective activities of polydatin was not only due to the effects on remarkably attenuating the oxidative stress induced by uric acid , but also on markedly suppressing the oxidative stress - related inflammatory cascade , including decreasing the expressions of NF - kappa B p65 , COX - 2 and iNOS proteins and inhibiting the productions of TNF - alpha , PGE ( 2 ) and IL - 1 beta .", "entity": [{"entity": "polydatin", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "uric acid", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "These findings elucidated that polydatin exhibited prominent nephroprotective activities and low toxic effects .", "entity": [{"entity": "polydatin", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Alleviation effects of magnesium on copper toxicity and accumulation in grapevine roots evaluated with biotic ligand models .", "entity": [{"entity": "magnesium", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "copper", "entity_type": "Chemical", "pos": [36, 42]}], "task": "NER"}
{"text": "Copper toxicity and accumulation in plants are affected by physicochemical characteristics of soil solutions such as the concentrations of coexistent cations ( e . g . , Ca ( 2 + ) , Mg ( 2 + ) , K ( + ) , Na ( + ) , and H ( + ) ) .", "entity": [{"entity": "Copper", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [170, 180]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [183, 193]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [196, 203]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [206, 214]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [221, 228]}], "task": "NER"}
{"text": "The biotic ligand model ( BLM ) approach has been proposed to predict metal phyto - toxicity and - accumulation by taking into account the effects of coexistent cations , given the assumption of the partition equilibrium of metal ions between soil solution and solid phase .", "entity": [], "task": "NER"}
{"text": "The alleviation effects of Mg on Cu toxicity and accumulation in grapevine roots were the main concerns in this study and were investigated by using a hydroponic experiment of grapevine cuttings .", "entity": [{"entity": "Mg", "entity_type": "Chemical", "pos": [27, 29]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [33, 35]}], "task": "NER"}
{"text": "The BLM approach , which incorporated competition of Mg ( 2 + ) with Cu ( 2 + ) to occupy the biotic ligands on root surfaces , was developed to predict Cu rhizotoxicity and accumulation by grapevine roots .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "Cu ( 2 + )", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [153, 155]}], "task": "NER"}
{"text": "In the results , the effective activity of Cu , { Cu ( 2 + ) } , resulting in a 50 % reduction of root elongation ( EA ( 50 ) ) , linearly increased with increments of Mg activity , { Mg ( 2 + ) } .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [43, 45]}, {"entity": "Cu ( 2 + )", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [168, 170]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [184, 194]}], "task": "NER"}
{"text": "In addition , the Cu concentration in root , Cu ( root ) , was retarded by an increase of { Mg ( 2 + ) } .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [45, 47]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [92, 102]}], "task": "NER"}
{"text": "The linear model was significantly fitted to the relationship between { Cu ( 2 + ) } / Cu ( root ) and { Mg ( 2 + ) } .", "entity": [{"entity": "Cu ( 2 + )", "entity_type": "Chemical", "pos": [72, 82]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [87, 89]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "According to the concept of BLM , the present results revealed that the amelioration effects of Mg on Cu toxicity and accumulation in roots could arise from competition between Mg ( 2 + ) and Cu ( 2 + ) on the binding sites ( i . e . , the biotic ligands ) .", "entity": [{"entity": "Mg", "entity_type": "Chemical", "pos": [96, 98]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [102, 104]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [177, 187]}, {"entity": "Cu ( 2 + )", "entity_type": "Chemical", "pos": [192, 202]}], "task": "NER"}
{"text": "Then , the developed Cu - BLMs incorporating the Mg ( 2 + ) competition effectiveness were validated provide accurate predictions of Cu toxicity and accumulation in grapevine roots .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [49, 59]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [133, 135]}], "task": "NER"}
{"text": "To our knowledge this is the first report of the successful development of BLMs for a woody plant .", "entity": [], "task": "NER"}
{"text": "This BLM approach shows promise of being widely applicable for various terrestrial plants .", "entity": [], "task": "NER"}
{"text": "High yield , reproducible and quasi - automated bilayer formation in a microfluidic format .", "entity": [], "task": "NER"}
{"text": "A microfluidic platform is reported for various experimentation schemes on cell membrane models and membrane proteins using a combination of electrical and optical measurements , including confocal microscopy .", "entity": [], "task": "NER"}
{"text": "Bilayer lipid membranes ( BLMs ) are prepared in the device upon spontaneous and instantaneous thinning of the lipid solution in a 100 - mu m dry - etched aperture in a 12 . 5 - mu m thick Teflon foil .", "entity": [{"entity": "Teflon", "entity_type": "Chemical", "pos": [189, 195]}], "task": "NER"}
{"text": "Using this quasi - automated approach , a remarkable 100 % membrane formation yield is reached ( including reflushing in 4 % of the cases ) , and BLMs are stable for up to 36 h .", "entity": [], "task": "NER"}
{"text": "Furthermore , the potential of this platform is demonstrated for ( i ) the in - depth characterization of BLMs comprising both synthetic and natural lipids ( 1 , 2 - diphytanoyl - sn - glycero - 3 - phosphocholine ( DPhPC ) and L - alpha - phosphatidylcholine ( L - alpha - PC ) / cholesterol , respectively ) in terms of seal resistance , capacitance , surface area , specific capacitance , and membrane hydrophobic thickness ; ( ii ) confocal microscopy imaging of phase separation in sphingomyelin / L - alpha - PC / cholesterol ternary membranes ; ( iii ) electrical measurements of individual nanopores ( alpha - hemolysin , gramicidin ) ; and ( iv ) indirect assessment of the alteration of membrane properties upon exposure to chemical stimuli using the natural nanopore gramicidin as a sensor .", "entity": [{"entity": "1 , 2 - diphytanoyl - sn - glycero - 3 - phosphocholine", "entity_type": "Chemical", "pos": [158, 213]}, {"entity": "DPhPC", "entity_type": "Chemical", "pos": [216, 221]}, {"entity": "L - alpha - phosphatidylcholine", "entity_type": "Chemical", "pos": [228, 259]}, {"entity": "L - alpha - PC", "entity_type": "Chemical", "pos": [262, 276]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [281, 292]}, {"entity": "sphingomyelin", "entity_type": "Chemical", "pos": [487, 500]}, {"entity": "L - alpha - PC", "entity_type": "Chemical", "pos": [503, 517]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [520, 531]}, {"entity": "gramicidin", "entity_type": "Chemical", "pos": [630, 640]}, {"entity": "gramicidin", "entity_type": "Chemical", "pos": [778, 788]}], "task": "NER"}
{"text": "Hierarchical porous materials : catalytic applications .", "entity": [], "task": "NER"}
{"text": "In this review , we discuss the phenomenon of complementary macropore incorporation into mesoporous and / or microporous solids in order to enhance their catalytic performance in fuels and chemicals synthesis .", "entity": [], "task": "NER"}
{"text": "C3 ' / C4 ' - Stereochemical Effects of Digitoxigenin alpha - L - / alpha - D - Glycoside in Cancer Cytotoxicity .", "entity": [{"entity": "Digitoxigenin", "entity_type": "Chemical", "pos": [40, 53]}, {"entity": "alpha - L - / alpha - D - Glycoside", "entity_type": "Chemical", "pos": [54, 89]}], "task": "NER"}
{"text": "Sweet ' n low in stereo : A Wharton reaction was employed along with a diastereoselective palladium - catalyzed glycosylation and other post - glycosylation transformations to synthesize digitoxin analogues .", "entity": [{"entity": "palladium", "entity_type": "Chemical", "pos": [90, 99]}, {"entity": "digitoxin", "entity_type": "Chemical", "pos": [187, 196]}], "task": "NER"}
{"text": "Cytotoxic evaluation against a panel of cancer cell lines uncovered the stereochemical and substitutional limits of the C3 ' / C4 ' - hydroxy functionality in digitoxin monosaccharide .", "entity": [{"entity": "C3 ' / C4 ' - hydroxy", "entity_type": "Chemical", "pos": [120, 141]}, {"entity": "digitoxin", "entity_type": "Chemical", "pos": [159, 168]}, {"entity": "monosaccharide", "entity_type": "Chemical", "pos": [169, 183]}], "task": "NER"}
{"text": "Investigating the motion of diblock copolymer assemblies in ionic liquids by in situ electron microscopy .", "entity": [], "task": "NER"}
{"text": "The movement of individual block copolymer micelles in free - standing films of ionic liquids is investigated by transmission electron microscopy with the aim of providing an easily accessible high - resolution imaging tool for the in situ observation of particle movement in a liquid environment .", "entity": [], "task": "NER"}
{"text": "A proof of concept and first studies on the behavior of individual particles in the fluid are demonstrated .", "entity": [], "task": "NER"}
{"text": "The peri - islet basement membrane , a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human .", "entity": [], "task": "NER"}
{"text": "We provide the first comprehensive analysis of the extracellular matrix ( ECM ) composition of peri - islet capsules , composed of the peri - islet basement membrane ( BM ) and subjacent interstitial matrix ( IM ) , in development of type 1 diabetes in NOD mice and in human type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "Our data demonstrate global loss of peri - islet BM and IM components only at sites of leukocyte infiltration into the islet .", "entity": [], "task": "NER"}
{"text": "Stereological analyses reveal a correlation between incidence of insulitis and the number of islets showing loss of peri - islet BM versus islets with intact BMs , suggesting that leukocyte penetration of the peri - islet BM is a critical step .", "entity": [], "task": "NER"}
{"text": "Protease - and protease inhibitor - specific microarray analyses ( CLIP - CHIP ) of laser - dissected leukocyte infiltrated and noninfiltrated pancreatic islets and confirmatory quantitative real time PCR and protein analyses identified cathepsin S , W , and C activity at sites of leukocyte penetration of the peri - islet BM in association with a macrophage subpopulation in NOD mice and human type 1 diabetic samples and , hence , potentially a novel therapeutic target specifically acting at the islet penetration stage .", "entity": [], "task": "NER"}
{"text": "Interestingly , the peri - islet BM and underlying IM are reconstituted once inflammation subsides , indicating that the peri - islet BM - producing cells are not lost due to the inflammation , which has important ramifications to islet transplantation studies .", "entity": [], "task": "NER"}
{"text": "Neuronal androgen receptor regulates insulin sensitivity via suppression of hypothalamic NF - kappa B - mediated PTP1B expression .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [9, 17]}], "task": "NER"}
{"text": "Clinical investigations highlight the increased incidence of metabolic syndrome in prostate cancer ( PCa ) patients receiving androgen deprivation therapy ( ADT ) .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "Studies using global androgen receptor ( AR ) knockout mice demonstrate that AR deficiency results in the development of insulin resistance in males .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [21, 29]}], "task": "NER"}
{"text": "However , mechanisms by which AR in individual organs coordinately regulates insulin sensitivity remain unexplored .", "entity": [], "task": "NER"}
{"text": "Here we tested the hypothesis that functional AR in the brain contributes to whole - body insulin sensitivity regulation and to the metabolic abnormalities developed in AR - deficient male mice .", "entity": [], "task": "NER"}
{"text": "The mouse model selectively lacking AR in the central nervous system and AR - expressing GT1 - 7 neuronal cells were established and used to delineate molecular mechanisms in insulin signaling modulated by AR .", "entity": [], "task": "NER"}
{"text": "Neuronal AR deficiency leads to reduced insulin sensitivity in middle - aged mice .", "entity": [], "task": "NER"}
{"text": "Neuronal AR regulates hypothalamic insulin signaling by repressing nuclear factor - kappa B ( NF - kappa B ) - mediated induction of protein - tyrosine phosphatase 1B ( PTP1B ) .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [143, 151]}], "task": "NER"}
{"text": "Hypothalamic insulin resistance leads to hepatic insulin resistance , lipid accumulation , and visceral obesity .", "entity": [], "task": "NER"}
{"text": "The functional deficiency of AR in the hypothalamus leads to male mice being more susceptible to the effects of high - fat diet consumption on PTP1B expression and NF - kappa B activation .", "entity": [], "task": "NER"}
{"text": "These findings suggest that in men with PCa undergoing ADT , reduction of AR function in the brain may contribute to insulin resistance and visceral obesity .", "entity": [], "task": "NER"}
{"text": "Pharmacotherapies targeting neuronal AR and NF - kappa B may be developed to combat the metabolic syndrome in men receiving ADT and in elderly men with age - associated hypogonadism .", "entity": [], "task": "NER"}
{"text": "Identification of cross - species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli .", "entity": [], "task": "NER"}
{"text": "Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy ( DN ) , but they only partially recapitulate disease manifestations of human DN , limiting their utility .", "entity": [], "task": "NER"}
{"text": "To define the molecular similarities and differences between human and murine DN , we performed a cross - species comparison of glomerular transcriptional networks .", "entity": [], "task": "NER"}
{"text": "Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models ( streptozotocin DBA / 2 , C57BLKS db / db , and eNOS - deficient C57BLKS db / db mice ) .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [101, 115]}], "task": "NER"}
{"text": "Species - specific transcriptional networks were generated and compared with a novel network - matching algorithm .", "entity": [], "task": "NER"}
{"text": "Three shared human - mouse cross - species glomerular transcriptional networks containing 143 ( Human - DBA STZ ) , 97 ( Human - BKS db / db ) , and 162 ( Human - BKS eNOS ( - / - ) db / db ) gene nodes were generated .", "entity": [{"entity": "STZ", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications , such as elements of Janus kinase ( JAK ) / signal transducer and activator of transcription ( STAT ) and vascular endothelial growth factor receptor ( VEGFR ) signaling pathways .", "entity": [], "task": "NER"}
{"text": "In addition , novel pathways not previously associated with DN and cross - species gene nodes and pathways unique to each of the human - mouse networks were discovered .", "entity": [], "task": "NER"}
{"text": "The human - mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest .", "entity": [], "task": "NER"}
{"text": "Moreover , they will allow identification of new pathways shared between mice and humans .", "entity": [], "task": "NER"}
{"text": "Metabolite profiling reveals normal metabolic control in carriers of mutations in the glucokinase gene ( MODY2 ) .", "entity": [], "task": "NER"}
{"text": "Mutations in the gene encoding glucokinase ( GCK ) cause a mild hereditary form of diabetes termed maturity - onset diabetes of the young ( MODY ) 2 or GCK - MODY .", "entity": [], "task": "NER"}
{"text": "The disease does not progress over time , and diabetes complications rarely develop .", "entity": [], "task": "NER"}
{"text": "It has therefore been suggested that GCK - MODY represents a metabolically compensated condition , but experimental support for this notion is lacking .", "entity": [], "task": "NER"}
{"text": "Here , we profiled metabolites in serum from patients with MODY1 ( HNF4A ) , MODY2 ( GCK ) , MODY3 ( HNF1A ) , and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations .", "entity": [], "task": "NER"}
{"text": "Analysis of four GCK - MODY patients revealed a metabolite pattern similar to that of healthy individuals , while other forms of diabetes differed markedly in their metabolite profiles .", "entity": [], "task": "NER"}
{"text": "Furthermore , despite elevated glucose concentrations , carriers of GCK mutations showed lower levels of free fatty acids and triglycerides than healthy control subjects .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "fatty acids", "entity_type": "Chemical", "pos": [110, 121]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [126, 139]}], "task": "NER"}
{"text": "The metabolite profiling was confirmed by enzymatic assays and replicated in a cohort of 11 GCK - MODY patients .", "entity": [], "task": "NER"}
{"text": "Elevated levels of fatty acids are known to associate with beta - cell dysfunction , insulin resistance , and increased incidence of late complications .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [19, 30]}], "task": "NER"}
{"text": "Our results show that GCK - MODY represents a metabolically normal condition , which may contribute to the lack of late complications and the nonprogressive nature of the disease .", "entity": [], "task": "NER"}
{"text": "Intrahypothalamic estradiol regulates glucose metabolism via the sympathetic nervous system in female rats .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [38, 45]}], "task": "NER"}
{"text": "Long - term reduced hypothalamic estrogen signaling leads to increased food intake and decreased locomotor activity and energy expenditure , and ultimately results in obesity and insulin resistance .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "In the current study , we aimed to determine the acute obesity - independent effects of hypothalamic estrogen signaling on glucose metabolism .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [101, 109]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "We studied endogenous glucose production ( EGP ) and insulin sensitivity during selective modulation of systemic or intrahypothalamic estradiol ( E2 ) signaling in rats 1 week after ovariectomy ( OVX ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [134, 143]}], "task": "NER"}
{"text": "OVX caused a 17 % decrease in plasma glucose , which was completely restored by systemic E2 .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [37, 44]}], "task": "NER"}
{"text": "Likewise , the administration of E2 by microdialysis , either in the hypothalamic paraventricular nucleus ( PVN ) or in the ventromedial nucleus ( VMH ) , restored plasma glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [171, 178]}], "task": "NER"}
{"text": "The infusion of an E2 antagonist via reverse microdialysis into the PVN or VMH attenuated the effect of systemic E2 on plasma glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Furthermore , E2 administration in the VMH , but not in the PVN , increased EGP and induced hepatic insulin resistance .", "entity": [], "task": "NER"}
{"text": "E2 administration in both the PVN and the VMH resulted in peripheral insulin resistance .", "entity": [], "task": "NER"}
{"text": "Finally , sympathetic , but not parasympathetic , hepatic denervation blunted the effect of E2 in the VMH on both EGP and hepatic insulin sensitivity .", "entity": [], "task": "NER"}
{"text": "In conclusion , intrahypothalamic estrogen regulates peripheral and hepatic insulin sensitivity via sympathetic signaling to the liver .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "Comparative analysis of four oxidized guanine lesions from reactions of DNA with peroxynitrite , singlet oxygen , and gamma - radiation .", "entity": [{"entity": "guanine", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [81, 94]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [105, 111]}], "task": "NER"}
{"text": "Oxidative damage to DNA has many origins , including irradiation , inflammation , and oxidative stress , but the chemistries are not the same .", "entity": [], "task": "NER"}
{"text": "The most oxidizable base in DNA is 2 - deoxyguanosine ( dG ) , and the primary oxidation products are 8 - oxodG and 2 - amino - imidazolone .", "entity": [{"entity": "2 - deoxyguanosine", "entity_type": "Chemical", "pos": [35, 53]}, {"entity": "8 - oxodG", "entity_type": "Chemical", "pos": [102, 111]}, {"entity": "2 - amino - imidazolone", "entity_type": "Chemical", "pos": [116, 139]}], "task": "NER"}
{"text": "The latter rapidly converts to 2 , 2 - diamino - oxazolone ( Ox ) , and 8 - oxodG is further oxidized to spiroiminodihydantoin ( Sp ) and guanidinohydantoin ( Gh ) .", "entity": [{"entity": "2 , 2 - diamino - oxazolone", "entity_type": "Chemical", "pos": [31, 58]}, {"entity": "8 - oxodG", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "spiroiminodihydantoin", "entity_type": "Chemical", "pos": [105, 126]}, {"entity": "guanidinohydantoin", "entity_type": "Chemical", "pos": [138, 156]}], "task": "NER"}
{"text": "In this study , we have examined the dose - response relationship for the formation of the above four products arising in calf thymus DNA exposed to gamma irradiation , photoactivated rose bengal , and two sources of peroxynitrite .", "entity": [{"entity": "rose bengal", "entity_type": "Chemical", "pos": [184, 195]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [217, 230]}], "task": "NER"}
{"text": "In order to carry out these experiments , we developed a chromatographic system and synthesized isotopomeric internal standards to enable accurate and precise analysis based upon selected reaction monitoring mass spectrometry .", "entity": [], "task": "NER"}
{"text": "8 - OxodG was the most abundant products in all cases , but its accumulation was highly dependent on the nature of the oxidizing agent and the subsequent conversion to Sp and Gh .", "entity": [{"entity": "8 - OxodG", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Among the other oxidation products , Ox was the most abundant , and Sp was formed in significantly greater yield than Gh .", "entity": [], "task": "NER"}
{"text": "Inactivation of Escherichia coli by sonoelectrocatalytic disinfection using TiO2 as electrode .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "This is the first study to demonstrate sonoelectrocatalytic disinfection using titanium dioxide ( TiO ( 2 ) ) as an anode for effective inactivation of Escherichia coli .", "entity": [{"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [79, 95]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "In brief , a non - woven TiO ( 2 ) fabric used as an anode and a platinum cathode were immersed in an E . coli suspension in which a positive potential was applied to TiO ( 2 ) concomitant with ultrasound ( US ) irradiation .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [25, 34]}, {"entity": "platinum", "entity_type": "Chemical", "pos": [65, 73]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [167, 176]}], "task": "NER"}
{"text": "Two control experiments were performed using E . coli suspensions to exhibit the effects of the sonoelectrocatalytic disinfection .", "entity": [], "task": "NER"}
{"text": "One was disinfection by applying a positive potential to a TiO ( 2 ) electrode , but without US irradiation ( electrochemical disinfection ) .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [59, 68]}], "task": "NER"}
{"text": "The other was disinfection without applying a potential , but with US irradiation in the presence of TiO ( 2 ) ( sonocatalytic disinfection ) .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "The cell inactivation rate in sonoelectrocatalytic disinfection was synergistically much more enhanced than the combined inactivation rates in electrochemical disinfection and sonocatalytic disinfection .", "entity": [], "task": "NER"}
{"text": "This synergistically enhanced inactivation rate of E . coli cells was attributable to effective reaction of the sonocatalytically generated OH radicals with E . coli cells at the surface of the TiO ( 2 ) anode , which resulted from the electroadsorption of E . coli cells toward the TiO ( 2 ) anode .", "entity": [{"entity": "OH", "entity_type": "Chemical", "pos": [140, 142]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [194, 203]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [283, 292]}], "task": "NER"}
{"text": "Recurrent major depressive disorder : Imbalance of neurokinin ( NK ) - 1 and NK - 2 receptor expression in monocytes .", "entity": [], "task": "NER"}
{"text": "Increasing evidence suggests that tachykinins are involved in the control of different pathological conditions , including psychiatric disorders .", "entity": [], "task": "NER"}
{"text": "In this study we evaluated the expression of NK ( 1 ) and NK ( 2 ) receptors ( NK - 1R and NK - 2R ) , as well as the effects of substance P ( SP ) and neurokinin A ( NKA ) , in monocytes isolated from 15 healthy subjects and 15 patients with recurrent major depressive disorder ( RMDD ) , under stable antidepressant therapy .", "entity": [{"entity": "substance P", "entity_type": "Chemical", "pos": [129, 140]}, {"entity": "neurokinin A", "entity_type": "Chemical", "pos": [152, 164]}, {"entity": "NKA", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "NK - 1R expression in monocytes from RMDD patients was significantly decreased as compared to healthy subjects , whereas NK - 2R expression was markedly increased .", "entity": [], "task": "NER"}
{"text": "Both NK - 1R and NK - 2R expression correlated with HAM - D , but not HAM - A , score .", "entity": [], "task": "NER"}
{"text": "SP , NKA and selective NK - 1R and NK - 2R agonists stimulated TNF - alpha release in monocytes of both groups , with a significant higher effect observed in RMDD .", "entity": [{"entity": "NKA", "entity_type": "Chemical", "pos": [5, 8]}], "task": "NER"}
{"text": "Moreover they induced NF - kappa B activation , which was reversed by selective NK - 1R and NK - 2R antagonists , so demonstrating that it was receptor - mediated .", "entity": [], "task": "NER"}
{"text": "The occurrence of a profound alteration in NK receptor expression in RMDD is a novel finding that suggests NK - 1R and NK - 2R pathways as possible relevant players in major depressive disorder , so improving our understanding of the complex pathogenesis of the disease .", "entity": [], "task": "NER"}
{"text": "The role of mitochondria and biotransformation in abamectin - induced cytotoxicity in isolated rat hepatocytes .", "entity": [{"entity": "abamectin", "entity_type": "Chemical", "pos": [50, 59]}], "task": "NER"}
{"text": "Abamectin ( ABA ) , which belongs to the family of avermectins , is used as a parasiticide ; however , ABA poisoning can impair liver function .", "entity": [{"entity": "Abamectin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ABA", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "avermectins", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "ABA", "entity_type": "Chemical", "pos": [103, 106]}], "task": "NER"}
{"text": "In a previous study using isolated rat liver mitochondria , we observed that ABA inhibited the activity of adenine nucleotide translocator and FoF1 - ATPase .", "entity": [{"entity": "ABA", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "adenine nucleotide", "entity_type": "Chemical", "pos": [107, 125]}], "task": "NER"}
{"text": "The aim of this study was to characterize the mechanism of ABA toxicity in isolated rat hepatocytes and to evaluate whether this effect is dependent on its metabolism .", "entity": [{"entity": "ABA", "entity_type": "Chemical", "pos": [59, 62]}], "task": "NER"}
{"text": "The toxicity of ABA was assessed by monitoring oxygen consumption and mitochondrial membrane potential , intracellular ATP concentration , cell viability , intracellular Ca ( 2 + ) homeostasis , release of cytochrome c , caspase 3 activity and necrotic cell death .", "entity": [{"entity": "ABA", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [47, 53]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [119, 122]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [170, 180]}], "task": "NER"}
{"text": "ABA reduces cellular respiration in cells energized with glutamate and malate or succinate .", "entity": [{"entity": "ABA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [57, 66]}, {"entity": "malate", "entity_type": "Chemical", "pos": [71, 77]}, {"entity": "succinate", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "The hepatocytes that were previously incubated with proadifen , a cytochrome P450 inhibitor , are more sensitive to the compound as observed by a rapid decrease in the mitochondrial membrane potential accompanied by reductions in ATP concentration and cell viability and a disruption of intracellular Ca ( 2 + ) homeostasis followed by necrosis .", "entity": [{"entity": "proadifen", "entity_type": "Chemical", "pos": [52, 61]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [230, 233]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [301, 311]}], "task": "NER"}
{"text": "Our results indicate that ABA biotransformation reduces its toxicity , and its toxic action is related to the inhibition of mitochondrial activity , which leads to decreased synthesis of ATP followed by cell death .", "entity": [{"entity": "ABA", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [187, 190]}], "task": "NER"}
{"text": "4 - ( Methylnitrosamino ) - 1 - ( 3 - pyridyl ) - 1 - butanone ( NNK ) metabolism - related enzymes gene polymorphisms , NNK metabolites levels and urothelial carcinoma .", "entity": [{"entity": "4 - ( Methylnitrosamino ) - 1 - ( 3 - pyridyl ) - 1 - butanone", "entity_type": "Chemical", "pos": [0, 62]}, {"entity": "NNK", "entity_type": "Chemical", "pos": [65, 68]}, {"entity": "NNK", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "Gene polymorphisms of the 4 - ( methylnitrosamino ) - 1 - ( 3 - pyridyl ) - 1 - butanone ( NNK ) metabolism - related enzymes - cytochrome P450 ( CYP ) monooxygenase 2A13 ( CYP2A13 ) and UDP - glucuronosyltransferases ( UGT ) - 2B7 could contribute to the levels of NNK - related metabolites in urine , thereby increasing the susceptibility to urothelial carcinoma ( UC ) .", "entity": [{"entity": "4 - ( methylnitrosamino ) - 1 - ( 3 - pyridyl ) - 1 - butanone", "entity_type": "Chemical", "pos": [26, 88]}, {"entity": "NNK", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [187, 190]}, {"entity": "NNK", "entity_type": "Chemical", "pos": [266, 269]}], "task": "NER"}
{"text": "Therefore , our study aimed to evaluate the roles of two gene polymorphisms ( CYP2A13 and UGT2B7 ) of NNK metabolism - related enzymes in the carcinogenesis of UC in Taiwan .", "entity": [{"entity": "NNK", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "A hospital - based pilot case - control study was conducted .", "entity": [], "task": "NER"}
{"text": "There were 121 UC cases and 121 age - and sex - matched healthy participants recruited from March 2007 to April 2009 .", "entity": [], "task": "NER"}
{"text": "Urine samples were analyzed for NNK - related metabolites using the liquid chromatography - tandem mass spectrometry method .", "entity": [{"entity": "NNK", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Genotyping was conducted using a polymerase chain reaction - restriction fragment length polymorphism technique .", "entity": [], "task": "NER"}
{"text": "ANCOVA and multivariate logistic regression were applied for data analyses .", "entity": [], "task": "NER"}
{"text": "In healthy controls , former smokers had significantly higher total NNAL and higher NNAL - Gluc than never smokers or current smokers .", "entity": [{"entity": "NNAL", "entity_type": "Chemical", "pos": [68, 72]}, {"entity": "NNAL - Gluc", "entity_type": "Chemical", "pos": [84, 95]}], "task": "NER"}
{"text": "Subjects carrying the UGT2B7 268 His / Tyr or Tyr / Tyr genotype had significantly lower total NNAL than those carrying His / His genotype .", "entity": [{"entity": "His", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [52, 55]}, {"entity": "NNAL", "entity_type": "Chemical", "pos": [95, 99]}, {"entity": "His", "entity_type": "Chemical", "pos": [120, 123]}, {"entity": "His", "entity_type": "Chemical", "pos": [126, 129]}], "task": "NER"}
{"text": "However , no association was seen between gene polymorphisms of CYP2A13 and UGT2B7 and UC risk after adjustment for age and sex .", "entity": [], "task": "NER"}
{"text": "Significant dose - response associations between total NNAL , free NNAL , the ratios of free NNAL / total NNAL and NNAL - Gluc / total NNAL and UC risk were observed .", "entity": [{"entity": "NNAL", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "NNAL", "entity_type": "Chemical", "pos": [67, 71]}, {"entity": "NNAL", "entity_type": "Chemical", "pos": [93, 97]}, {"entity": "NNAL", "entity_type": "Chemical", "pos": [106, 110]}, {"entity": "NNAL - Gluc", "entity_type": "Chemical", "pos": [115, 126]}, {"entity": "NNAL", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "In the future , large - scale studies will be required to verify the association between the single nucleotide polymorphisms of NNK metabolism - related enzymes and UC risk .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [100, 110]}, {"entity": "NNK", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "Novel potassium channel blocker venom peptides from Mesobuthus gibbosus ( Scorpiones : Buthidae ) .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "In the present study , we report for the first time , the molecular , biochemical and electrophysiological characterization of the components present in the soluble venom from Mesobuthus gibbosus ( Brull e , 1832 ) .", "entity": [], "task": "NER"}
{"text": "According to the epidemiological and clinical situation of scorpion envenomation cases M . gibbosus scorpion is one of the most important health - threatening species of Turkey .", "entity": [], "task": "NER"}
{"text": "Despite the medical importance reported for M . gibbosus , there is no additional information on toxin peptides and venom components to clarify the toxic effect of the M . gibbosus sting .", "entity": [], "task": "NER"}
{"text": "Biochemical characterization of the venom was performed using different protocols and techniques following a bioassay - guided strategy ( HPLC , mass spectrometry and Edman degradation sequencing ) .", "entity": [], "task": "NER"}
{"text": "Venom fractions were tested in electrophysiological assays on a panel of six K ( + ) channels ( K ( v ) 1 . 1 - 1 . 6 ) by using the two - electrode voltage clamp technique .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "K", "entity_type": "Chemical", "pos": [96, 97]}], "task": "NER"}
{"text": "Three new alpha - KTx peptides were found and called MegKTx1 , MegKTx2 and MegKTx3 ( M . gibbosus , K ( + ) channel toxin number 1 - 3 ) .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "A cDNA library from the telson was constructed and specific screening of transcripts was performed .", "entity": [], "task": "NER"}
{"text": "Biochemical and molecular characterization of MegKTx peptides and transcripts shows a relation with toxins of three different alpha - KTx subfamilies ( alpha - KTx3 . x , alpha - KTx9 . x and alpha - KTx16 . x ) .", "entity": [], "task": "NER"}
{"text": "Use of high content image analyses to detect chemical - mediated effects on neurite sub - populations in primary rat cortical neurons .", "entity": [], "task": "NER"}
{"text": "Traditional developmental neurotoxicity tests performed in vivo are costly , time - consuming and utilize a large number of animals .", "entity": [], "task": "NER"}
{"text": "In order to address these inefficiencies , in vitro models of neuronal development have been used in a first tier screening approach for developmental neurotoxicity hazard identification .", "entity": [], "task": "NER"}
{"text": "One commonly used endpoint for assessing developmental neurotoxicity in vitro is measurement of neurite outgrowth .", "entity": [], "task": "NER"}
{"text": "This biological process is amenable to high - throughput measurement using high content imaging ( HCI ) based methodologies .", "entity": [], "task": "NER"}
{"text": "To date , a majority of HCI studies of neurite outgrowth have focused on measurements of total neurite outgrowth without examining whether stereotypic neuronal growth patterns are disrupted or whether specific sub - populations of neurites ( i . e . axons or dendrites ) are selectively affected .", "entity": [], "task": "NER"}
{"text": "The present study describes the development and implementation of two HCI based analysis methods for assessing chemical effects on neuronal maturation .", "entity": [], "task": "NER"}
{"text": "These methods utilize the stereotypical growth pattern of primary rat cortical neurons in culture ( i . e . the Staging Method ) , as well as the differential cytoplasmic distribution of beta ( III ) - tubulin and MAP2 ( i . e . the Subtraction Method ) , to quantify inhibition of neurite initiation , axon outgrowth and secondary neurite ( or dendrite ) outgrowth in response to chemical exposure .", "entity": [], "task": "NER"}
{"text": "Results demonstrate that these distinct maturational processes are differentially affected by pharmacological compounds ( K252a , Na ( 3 ) VO ( 4 ) , Bis - 1 ) known to inhibit neurite outgrowth .", "entity": [{"entity": "K252a", "entity_type": "Chemical", "pos": [122, 127]}, {"entity": "Na ( 3 ) VO ( 4 )", "entity_type": "Chemical", "pos": [130, 147]}, {"entity": "Bis - 1", "entity_type": "Chemical", "pos": [150, 157]}], "task": "NER"}
{"text": "Furthermore , a group of known developmental neurotoxicants also differentially affected the growth of axons and secondary neurites in primary cortical culture .", "entity": [], "task": "NER"}
{"text": "This work improves upon previous HCI methods by providing a means in which to rapidly and specifically quantify chemical effects on the growth of axons and dendrites in vitro .", "entity": [], "task": "NER"}
{"text": "Therapeutic RNA aptamers in clinical trials .", "entity": [], "task": "NER"}
{"text": "RNA aptamers can fold into complex structures and bind with high affinity and selectivity to various macromolecules , viruses , and cells .", "entity": [], "task": "NER"}
{"text": "They are isolated from a large pool of nucleic acids by a conceptually straightforward iterative selection process called SELEX .", "entity": [], "task": "NER"}
{"text": "Aptamers have enormous potential as therapeutics due to their ability to bind to proteins and specifically inhibit their functions with minimal or no harmful side - effects .", "entity": [], "task": "NER"}
{"text": "The first aptamer therapeutic was FDA approved in 2005 and a number of novel aptamer - based therapeutics are currently undergoing clinical trials for treating diseases such as macular degeneration , choroidal neovascularization , intravascular thrombus , acute coronary syndrome , von Willebrand factor related disorders , von Hippel - Lindau syndrome ( VHL ) , angiomas , acute myeloid leukemia , renal cell carcinoma , non - small cell lung cancer , thrombotic thrombocytopenic purpura , and several others .", "entity": [], "task": "NER"}
{"text": "In this review , we present aptamers in on - going , completed , and terminated clinical studies highlighting their mechanism of action as well as the inherent challenges of aptamer production and use .", "entity": [], "task": "NER"}
{"text": "Superoxide anion mediates the L - selectin down - regulation induced by non - steroidal anti - inflammatory drugs in human neutrophils .", "entity": [{"entity": "Superoxide", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Non - steroidal anti - inflammatory drugs ( NSAIDs ) induce the shedding of L - selectin in human neutrophils through a mechanism still not well understood .", "entity": [], "task": "NER"}
{"text": "In this work we studied both the functional effect of NSAIDs on the neutrophils / endothelial cells dynamic interaction , and the potential involvement of reactive oxygen species ( ROS ) in the NSAIDs - mediated down - regulation of L - selectin .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [164, 170]}], "task": "NER"}
{"text": "When human neutrophils were incubated with diclofenac , a significant reduction in the number of cells that rolled on activated endothelial cells was observed .", "entity": [{"entity": "diclofenac", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "Different NSAIDs ( flufenamic acid , meclofenamic acid , diclofenac , indomethacin , nimesulide , flurbiprofen , meloxicam , phenylbutazone , piroxicam , ketoprofen and aspirin ) caused variable increase in neutrophil intracellular ROS concentration , which was inversely proportional to the change produced in L - selectin surface expression .", "entity": [{"entity": "flufenamic acid", "entity_type": "Chemical", "pos": [19, 34]}, {"entity": "meclofenamic acid", "entity_type": "Chemical", "pos": [37, 54]}, {"entity": "diclofenac", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "indomethacin", "entity_type": "Chemical", "pos": [70, 82]}, {"entity": "nimesulide", "entity_type": "Chemical", "pos": [85, 95]}, {"entity": "flurbiprofen", "entity_type": "Chemical", "pos": [98, 110]}, {"entity": "meloxicam", "entity_type": "Chemical", "pos": [113, 122]}, {"entity": "phenylbutazone", "entity_type": "Chemical", "pos": [125, 139]}, {"entity": "piroxicam", "entity_type": "Chemical", "pos": [142, 151]}, {"entity": "ketoprofen", "entity_type": "Chemical", "pos": [154, 164]}, {"entity": "aspirin", "entity_type": "Chemical", "pos": [169, 176]}], "task": "NER"}
{"text": "Pre - incubation of neutrophils with superoxide dismutase , but not with catalase , showed both a significant protective effect on the L - selectin down - regulation induced by several NSAIDs and a diminished effect of diclofenac on neutrophil rolling .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "diclofenac", "entity_type": "Chemical", "pos": [219, 229]}], "task": "NER"}
{"text": "Interestingly , diclofenac and flufenamic acid but not piroxicam significantly increased the extracellular superoxide anion production by neutrophils , and inhibition of nicotinamide adenine dinucleotide phosphate ( NADPH ) - oxidase activity with diphenyleneiodonium prevented the down - regulation of L - selectin by diclofenac .", "entity": [{"entity": "diclofenac", "entity_type": "Chemical", "pos": [16, 26]}, {"entity": "flufenamic acid", "entity_type": "Chemical", "pos": [31, 46]}, {"entity": "piroxicam", "entity_type": "Chemical", "pos": [55, 64]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "nicotinamide adenine dinucleotide phosphate", "entity_type": "Chemical", "pos": [170, 213]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [216, 221]}, {"entity": "diphenyleneiodonium", "entity_type": "Chemical", "pos": [248, 267]}, {"entity": "diclofenac", "entity_type": "Chemical", "pos": [319, 329]}], "task": "NER"}
{"text": "In accordance with these results , neutrophils from patients with chronic granulomatous disease , a hereditary disease in which neutrophils show a reduced capacity to form superoxide radicals , exhibited a lower down - regulation of L - selectin ( IC50 : 15 . 3 mu g / ml ) compared to normal controls ( IC50 : 5 . 6 mu g / ml ) in response to diclofenac .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [172, 182]}, {"entity": "diclofenac", "entity_type": "Chemical", "pos": [344, 354]}], "task": "NER"}
{"text": "CONCLUSION : A group of NSAIDs is capable of interfering with the ability of neutrophils to interact with endothelial cells by triggering L - selectin - shedding through the NADPH - oxidase - dependent generation of superoxide anion at the plasma membrane .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [174, 179]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [216, 226]}], "task": "NER"}
{"text": "Proteasome inhibition attenuates heart failure during the late stages of pressure overload through alterations in collagen expression .", "entity": [], "task": "NER"}
{"text": "Although the role of the ubiquitin - proteasome system ( UPS ) in cardiac hypertrophy induced by pressure overload has been consistently studied , the fundamental importance of the UPS in cardiac fibrosis has received much less attention .", "entity": [], "task": "NER"}
{"text": "Our previous study found that proteasome inhibitor ( MG132 ) treatment attenuated cardiac fibrosis and heart failure during the early and middle stages of pressure overload .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [53, 58]}], "task": "NER"}
{"text": "However , the effects of this inhibitor on late - stage pressure overload hearts remain unclear and controversial .", "entity": [], "task": "NER"}
{"text": "The present study was designed to investigate the effects and possible mechanisms of MG132 on cardiac fibrosis and dysfunction during the late stages of pressure overload .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [85, 90]}], "task": "NER"}
{"text": "Male Sprague Dawley rats with abdominal aortic constriction ( AAC ) or a sham operation received an intraperitoneal injection of MG132 ( 0 . 1 mg kg - (1) day - (1) ) or vehicle for 16 weeks .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [129, 134]}], "task": "NER"}
{"text": "Left ventricular ( LV ) function , collagen deposition and Ang II levels were evaluated at study termination .", "entity": [], "task": "NER"}
{"text": "Ang II - stimulated adult rat cardiac fibroblasts were utilized to examine the effects of MG132 on collagen synthesis and the relationship between the renin - angiotensin - aldosterone system ( RAAS ) and the UPS .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [90, 95]}, {"entity": "aldosterone", "entity_type": "Chemical", "pos": [173, 184]}], "task": "NER"}
{"text": "MG132 treatment attenuated ventricular dysfunction by suppressing cardiac fibrosis rather than inhibiting cardiac hypertrophy during the late - stages of pressure overload .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "We also found that Ang II activates UPS in the heart and MG132 attenuates Ang II - induced collagen synthesis via suppression of the NF - kappa B / TGF - beta / Smad2 signaling pathways .", "entity": [{"entity": "MG132", "entity_type": "Chemical", "pos": [57, 62]}], "task": "NER"}
{"text": "Proteasome inhibition therefore could provide a new promising therapeutic strategy to prevent cardiac fibrosis and progression of heart failure even during the late - stages of pressure overload .", "entity": [], "task": "NER"}
{"text": "Yuwen02f1 suppresses LPS - induced endotoxemia and adjuvant - induced arthritis primarily through blockade of ROS formation , NFkB and MAPK activation .", "entity": [{"entity": "Yuwen02f1", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Phagocytes release inflammatory mediators to defense harmful stimuli upon bacterial invasion , however , excessive inflammatory reaction leads to tissue damage and manifestation of pathological states .", "entity": [], "task": "NER"}
{"text": "Therefore , targeting on uncontrolled inflammation seems feasible to control numerous inflammation - associated diseases .", "entity": [], "task": "NER"}
{"text": "Under the drug screening process of synthetic diphenylpyrazole derivatives , we discovered compound yuwen02f1 possesses anti - inflammatory effects in decreasing the release of pro - inflammatory cytokines including TNF alpha and IL - 6 , nitric oxide , reactive oxygen species ( ROS ) as well as inhibiting migration of LPS - stimulated phagocytes .", "entity": [{"entity": "diphenylpyrazole", "entity_type": "Chemical", "pos": [46, 62]}, {"entity": "yuwen02f1", "entity_type": "Chemical", "pos": [100, 109]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [239, 251]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [263, 269]}], "task": "NER"}
{"text": "In addition , we observed that the molecular mechanism of yuwen02f1 - mediated anti - inflammation is associated with decreasing phosphorylation of MAPK molecules including ERK1 / 2 , JNK and p38 , and attenuating translocation of p47 ( phox ) and p67 ( phox ) to the cell membrane .", "entity": [{"entity": "yuwen02f1", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "Yuwen02f1 also reverses I kappa B alpha degradation and attenuates the expression of NF kappa B - related downstream inducible enzymes like iNOS and COX - 2 .", "entity": [{"entity": "Yuwen02f1", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Furthermore , we found that yuwen02f1 attenuates some pathological syndromes of LPS - induced sepsis and adjuvant - induced arthritis in mice , as evidenced by decreasing the cytokine production , reversing thrombocytopenic syndrome , protecting the mice from tissue injury in septic mice , and attenuating paw edema in arthritic mice as well .", "entity": [{"entity": "yuwen02f1", "entity_type": "Chemical", "pos": [28, 37]}], "task": "NER"}
{"text": "These results suggest that yuwen02f1 is a potential anti - inflammatory agent for alleviating syndromes of acute and chronic inflammatory diseases as evidenced by attenuating the generation of cytokines and down - regulating the expression of iNOS and COX - 2 through the blockade of ROS generation and NADPH oxidase , NF kappa B and MAPK activation pathways in LPS - stimulated phagocytes .", "entity": [{"entity": "yuwen02f1", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [303, 308]}], "task": "NER"}
{"text": "Protective effects of erythropoietin on astrocytic swelling after oxygen - glucose deprivation and reoxygenation : mediation through AQP4 expression and MAPK pathway .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [75, 82]}], "task": "NER"}
{"text": "Recent in vivo studies have shown that erythropoietin ( EPO ) offers strong protection against brain edema .", "entity": [], "task": "NER"}
{"text": "However , the intracellular and molecular mechanisms behind this beneficial effect have not been specified .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine whether human erythropoietin ( rhEPO ) reduces the astrocytic swelling created by oxygen - glucose deprivation followed by reoxygenation ( OGD / Reox ) in vitro and whether this effect can be mediated through the modulation of aquaporin4 ( AQP4 ) expression in the plasma membrane ( PM ) and phosphorylation of the mitogen - activated protein kinase pathway ( MAPK ) pathway .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [121, 127]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [130, 137]}], "task": "NER"}
{"text": "Our results showed that OGD / Reox produced increase in cell volume , morphological swelling , and mitochondrial swelling .", "entity": [], "task": "NER"}
{"text": "These changes were associated with the up - regulation of AQP4 in PM and the over - activation of MAPK .", "entity": [], "task": "NER"}
{"text": "Silencing AQP4 expression using small interfering ribonucleic acid for AQP4 was found to block astrocytic swelling .", "entity": [], "task": "NER"}
{"text": "Inhibition of the over - activation of MAPK mitigated the PM AQP4 overabundance and cellular swelling .", "entity": [], "task": "NER"}
{"text": "As expected , treatment with rhEPO significantly reduced the OGD / Reox - induced increase in cell volume , morphological swelling , and mitochondrial swelling as well as the up - regulation of AQP4 in PM .", "entity": [], "task": "NER"}
{"text": "In addition , cultures treated with the neutralizing anti - EPO antibody worsened the PM AQP4 abundance and cellular swelling , abolishing the protective effects mediated by rhEPO treatment .", "entity": [], "task": "NER"}
{"text": "Furthermore , the over - activation of these MAPK after OGD / Reox was attenuated by rhEPO treatment significantly .", "entity": [], "task": "NER"}
{"text": "In conclusion , our data strongly suggest that rhEPO can protect astrocytes from swelling caused by ischemia and reperfusion - like injury .", "entity": [], "task": "NER"}
{"text": "This neuroprotective capacity is partially mediated by diminishing the MAPK - activity - dependent overabundance of AQP4 in PM .", "entity": [], "task": "NER"}
{"text": "Toxicogenomic biomarkers for renal papillary injury in rats .", "entity": [], "task": "NER"}
{"text": "Renal papillary injury is a common side effect observed during nonclinical and clinical investigations in drug development .", "entity": [], "task": "NER"}
{"text": "The present study aimed to identify genomic biomarkers for early and sensitive detection of renal papillary injury in rats .", "entity": [], "task": "NER"}
{"text": "We hypothesized that previously identified genomic biomarkers for tubular injury might be applicable for the sensitive detection of papillary injury in rats .", "entity": [], "task": "NER"}
{"text": "We selected 18 genes as candidate biomarkers for papillary injury based on previously published studies and analyzed their expression profiles by RT - PCR in each kidney region , namely the cortex , cortico - medullary junction , and papilla in various nephrotoxicity models .", "entity": [], "task": "NER"}
{"text": "Comparative analysis of gene expression profiles revealed that some genes were commonly upregulated or downregulated in the renal papilla , reflecting papillary injuries induced by 2 - bromoethylamine hydrobromide , phenylbutazone , or n - phenylanthranilic acid .", "entity": [{"entity": "2 - bromoethylamine hydrobromide", "entity_type": "Chemical", "pos": [181, 213]}, {"entity": "phenylbutazone", "entity_type": "Chemical", "pos": [216, 230]}, {"entity": "n - phenylanthranilic acid", "entity_type": "Chemical", "pos": [236, 262]}], "task": "NER"}
{"text": "By applying receiver operator characteristics analysis , six candidate biomarkers were identified and their usefulness was confirmed by using an independent data set .", "entity": [], "task": "NER"}
{"text": "The three top - ranked genes , Timp1 , Igf1 , and Lamc2 , exhibited the best prediction performance in an external data set with area under the curve ( AUC ) values of greater than 0 . 91 .", "entity": [], "task": "NER"}
{"text": "An optimized support vector machine model consisting of three genes achieved the highest AUC value of 0 . 99 .", "entity": [], "task": "NER"}
{"text": "In conclusion , even though definitive validation studies are required for the establishment of their usefulness and reliability , these identified genes may prove to be the most promising candidate genomic biomarkers of renal papillary injury in rats .", "entity": [], "task": "NER"}
{"text": "Differential responses in ammonia excretion , sodium fluxes and gill permeability explain different sensitivities to acute high environmental ammonia in three freshwater teleosts .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [26, 33]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [142, 149]}], "task": "NER"}
{"text": "We examined the acute physiological responses to high environmental ammonia ( HEA ) , particularly the linkages between branchial ammonia fluxes and unidirectional Na ( + ) fluxes , as well as urea excretion , cortisol , and indicators of gill permeability in three freshwater teleosts differing in their sensitivities to ammonia ; the highly sensitive salmonid Oncorhynchus mykiss ( rainbow trout ) , the less sensitive cyprinid Cyprinus carpio ( common carp ) and the highly resistant cyprinid Carassius auratus ( goldfish ) .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [164, 172]}, {"entity": "urea", "entity_type": "Chemical", "pos": [193, 197]}, {"entity": "cortisol", "entity_type": "Chemical", "pos": [210, 218]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [322, 329]}], "task": "NER"}
{"text": "Fish were acutely exposed to two sub - lethal ammonia concentrations ( as NH ( 4 ) HCO ( 3 ) ) at pH 7 . 9 : 1 mM for a period of 12 h , identical for all species , and 5 mM for the cyprinids and 1 . 4 mM for the trout for 3 h .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "NH ( 4 ) HCO ( 3 )", "entity_type": "Chemical", "pos": [74, 92]}], "task": "NER"}
{"text": "Elevation of plasma cortisol at both levels of HEA was apparent in all species .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "At 1 mM , ammonia excretion ( J ( amm ) ) was inhibited to a greater extent in trout than cyprinids and concurrently a significantly higher plasma ammonia level was evident in trout .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [10, 17]}, {"entity": "amm", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [147, 154]}], "task": "NER"}
{"text": "However J ( amm ) was reversed in all species at 5 or 1 . 4 mM .", "entity": [{"entity": "amm", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "Goldfish showed a significant increase in urea excretion rate ( J ( urea ) ) during HEA exposure .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [42, 46]}, {"entity": "urea", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "In carp and trout , neither level of HEA elevated J ( urea ) but urea production was increased as evidenced by a considerable elevation of plasma urea .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "urea", "entity_type": "Chemical", "pos": [65, 69]}, {"entity": "urea", "entity_type": "Chemical", "pos": [146, 150]}], "task": "NER"}
{"text": "At 1mM HEA , Na ( + ) imbalance became progressively more severe in trout and carp due to a stimulation of unidirectional Na ( + ) efflux ( J ( out ) ( Na ) ) without a concomitant increase in unidirectional Na ( + ) influx ( J ( in ) ( Na ) ) .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [13, 21]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [122, 130]}, {"entity": "Na", "entity_type": "Chemical", "pos": [152, 154]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [208, 216]}, {"entity": "Na", "entity_type": "Chemical", "pos": [237, 239]}], "task": "NER"}
{"text": "Additionally , a transient reduction of J ( in ) ( Na ) was evident in trout .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [51, 53]}], "task": "NER"}
{"text": "Goldfish showed an opposite trend for J ( out ) ( Na ) with reduced efflux rates and a positive Na ( + ) balance during the first few hours of HEA .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [50, 52]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "However , after 12 h of exposure , both J ( in ) ( Na ) and J ( out ) ( Na ) were also increased in both carp and goldfish , whereas only J ( out ) ( Na ) was increased in trout , leading to a net Na ( + ) loss .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "Na", "entity_type": "Chemical", "pos": [72, 74]}, {"entity": "Na", "entity_type": "Chemical", "pos": [150, 152]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [197, 205]}], "task": "NER"}
{"text": "Na ( + ) homeostasis was entirely disrupted in all three species when subjected to the 5 or 1 . 4 mM ammonia for 3 h : J ( in ) ( Na ) was significantly inhibited while considerable activation of J ( out ) ( Na ) was observed .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [101, 108]}, {"entity": "Na", "entity_type": "Chemical", "pos": [130, 132]}, {"entity": "Na", "entity_type": "Chemical", "pos": [208, 210]}], "task": "NER"}
{"text": "Diffusive water efflux rates and net K ( + ) loss rates across the gills were enhanced during HEA only in trout , indicating an increment in gill transcellular permeability .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [37, 44]}], "task": "NER"}
{"text": "Transepithelial potential was increased in all the species during ammonia exposure , but to the least extent in goldfish .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [66, 73]}], "task": "NER"}
{"text": "Overall , for several different physiological systems , trout were most disturbed , and goldfish were least disturbed by HEA , helping to explain the differential ammonia tolerance of the three species .", "entity": [{"entity": "ammonia", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes .", "entity": [], "task": "NER"}
{"text": "Asthma is one of the most prevalent diseases in the world , for which the mainstay treatment has been inhaled glucocorticoids ( GCs ) .", "entity": [], "task": "NER"}
{"text": "Despite the widespread use of these drugs , approximately 30 % of asthma sufferers exhibit some degree of steroid insensitivity or are refractory to inhaled GCs .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds .", "entity": [], "task": "NER"}
{"text": "The objective of this research is to determine how metabolism of GCs by the CYP3A family of enzymes could affect their effectiveness in asthmatic patients .", "entity": [], "task": "NER"}
{"text": "In this work , the metabolism of four frequently prescribed inhaled GCs , triamcinolone acetonide , flunisolide , budesonide , and fluticasone propionate , by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites .", "entity": [{"entity": "triamcinolone acetonide", "entity_type": "Chemical", "pos": [74, 97]}, {"entity": "flunisolide", "entity_type": "Chemical", "pos": [100, 111]}, {"entity": "budesonide", "entity_type": "Chemical", "pos": [114, 124]}, {"entity": "fluticasone propionate", "entity_type": "Chemical", "pos": [131, 153]}], "task": "NER"}
{"text": "Both interenzyme and interdrug variability in rates of metabolism and metabolic fate were observed .", "entity": [], "task": "NER"}
{"text": "CYP3A4 was the most efficient metabolic catalyst for all the compounds , and CYP3A7 had the slowest rates .", "entity": [], "task": "NER"}
{"text": "CYP3A5 , which is particularly relevant to GC metabolism in the lungs , was also shown to efficiently metabolize triamcinolone acetonide , budesonide , and fluticasone propionate .", "entity": [{"entity": "triamcinolone acetonide", "entity_type": "Chemical", "pos": [113, 136]}, {"entity": "budesonide", "entity_type": "Chemical", "pos": [139, 149]}, {"entity": "fluticasone propionate", "entity_type": "Chemical", "pos": [156, 178]}], "task": "NER"}
{"text": "In contrast , flunisolide was only metabolized via CYP3A4 , with no significant turnover by CYP3A5 or CYP3A7 .", "entity": [{"entity": "flunisolide", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Common metabolites included 6 beta - hydroxylation and Delta ( 6 ) - dehydrogenation for triamcinolone acetonide , budesonide , and flunisolide .", "entity": [{"entity": "triamcinolone acetonide", "entity_type": "Chemical", "pos": [89, 112]}, {"entity": "budesonide", "entity_type": "Chemical", "pos": [115, 125]}, {"entity": "flunisolide", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "The structure of Delta ( 6 ) - flunisolide was unambiguously established by NMR analysis .", "entity": [{"entity": "Delta ( 6 ) - flunisolide", "entity_type": "Chemical", "pos": [17, 42]}], "task": "NER"}
{"text": "Metabolism also occurred on the D - ring substituents , including the 21 - carboxy metabolites for triamcinolone acetonide and flunisolide .", "entity": [{"entity": "21 - carboxy", "entity_type": "Chemical", "pos": [70, 82]}, {"entity": "triamcinolone acetonide", "entity_type": "Chemical", "pos": [99, 122]}, {"entity": "flunisolide", "entity_type": "Chemical", "pos": [127, 138]}], "task": "NER"}
{"text": "The novel metabolite 21 - nortriamcinolone acetonide was also identified by liquid chromatography - mass spectrometry and NMR analysis .", "entity": [{"entity": "21 - nortriamcinolone acetonide", "entity_type": "Chemical", "pos": [21, 52]}], "task": "NER"}
{"text": "IsoDGR - tagged albumin : a new alpha v beta 3 selective carrier for nanodrug delivery to tumors .", "entity": [], "task": "NER"}
{"text": "A new cyclic peptide containing the isoDGR motif that , after coupling to albumin , selectively binds alpha v beta 3 , an integrin overexpressed in the tumor vasculature .", "entity": [], "task": "NER"}
{"text": "IsoDGR - tagged albumin binds tumor vessels and can be exploited as a carrier for the preparation of tumor vasculature - selective nanomedicines , such as gold nanoparticles ( Au ) carrying tumor necrosis factor alpha ( TNF ) , a potent vascular damaging agent .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [176, 178]}], "task": "NER"}
{"text": "Enhancing the photocatalytic activity of anatase TiO2 by improving the specific facet - induced spontaneous separation of photogenerated electrons and holes .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [49, 53]}], "task": "NER"}
{"text": "Recently , it has been proven that directional flow of photogenerated charge carriers occurs on specific facets of TiO ( 2 ) nanocrystals .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "Herein , we demonstrate that the photocatalytic activity of anatase TiO ( 2 ) nanocrystals in both photoreduction and photooxidation processes can be enhanced by selectively depositing Pt nanoparticles on the { 101 } facets , which strengthens spontaneously surface - induced separation between photogenerated electrons and holes in the photocatalysis process .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [185, 187]}], "task": "NER"}
{"text": "An optimal ratio of the oxidative { 001 } facets to the reductive { 101 } facets exists with regard to the photocatalysis of the faceted TiO ( 2 ) nanocrystals , and this is crucial for balancing the recombination and redox reaction rates of photogenerated electrons and holes .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [137, 146]}], "task": "NER"}
{"text": "The present work might help us gain deeper insight into the relation between the specific surface of semiconductor photocatalysts and their photocatalytic activities and provides us with a new route to design photocatalysts with high photocatalytic activity .", "entity": [], "task": "NER"}
{"text": "Noncompetitive , voltage - dependent NMDA receptor antagonism by hydrophobic anions .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "NMDA receptor ( NMDAR ) antagonists are dissociative anesthetics , drugs of abuse , and are of therapeutic interest in neurodegeneration and neuropsychiatric disease .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Many well - known NMDAR antagonists are positively charged , voltage - dependent channel blockers .", "entity": [], "task": "NER"}
{"text": "We recently showed that the hydrophobic anion dipicrylamine ( DPA ) negatively regulates GABA ( A ) receptor function by a mechanism indistinguishable from that of sulfated neurosteroids .", "entity": [{"entity": "dipicrylamine", "entity_type": "Chemical", "pos": [46, 59]}, {"entity": "DPA", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [89, 93]}, {"entity": "sulfated neurosteroids", "entity_type": "Chemical", "pos": [164, 186]}], "task": "NER"}
{"text": "Because sulfated neurosteroids also modulate NMDARs , here we examined the effects of DPA on NMDAR function .", "entity": [{"entity": "neurosteroids", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "DPA", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "In rat hippocampal neurons DPA inhibited currents gated by 300 micro M NMDA with an IC ( 50 ) of 2 . 3 micro M .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [71, 75]}], "task": "NER"}
{"text": "Neither onset nor offset of antagonism exhibited dependence on channel activation but exhibited a noncompetitive profile .", "entity": [], "task": "NER"}
{"text": "DPA antagonism was independent of NMDAR subunit composition and was similar at extrasynaptic and total receptor populations .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Surprisingly , similar to cationic channel blockers but unlike sulfated neurosteroids , DPA antagonism was voltage dependent .", "entity": [{"entity": "sulfated neurosteroids", "entity_type": "Chemical", "pos": [63, 85]}, {"entity": "DPA", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "Onset and offset of DPA antagonism were nearly 10 - fold faster than DPA - induced increases in membrane capacitance , suggesting that membrane interactions do not directly explain antagonism .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "DPA", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "Furthermore , voltage dependence did not derive from association of DPA with a site on NMDARs directly accessible to the outer membrane leaflet , assessed by DPA translocation experiments .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [68, 71]}, {"entity": "DPA", "entity_type": "Chemical", "pos": [158, 161]}], "task": "NER"}
{"text": "Consistent with the expected lack of channel block , DPA antagonism did not interact with permeant ions .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [53, 56]}], "task": "NER"}
{"text": "Therefore , we speculate that voltage dependence may arise from interactions of DPA with the inherent voltage dependence of channel gating .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [80, 83]}], "task": "NER"}
{"text": "Overall , we conclude that DPA noncompetitively inhibits NMDA - induced current by a novel voltage - dependent mechanism and represents a new class of anionic NMDAR antagonists .", "entity": [{"entity": "DPA", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "Structural optimization of 2 , 5 - thiophene amides as highly potent and selective 17 beta - hydroxysteroid dehydrogenase type 2 inhibitors for the treatment of osteoporosis .", "entity": [{"entity": "2 , 5 - thiophene amides", "entity_type": "Chemical", "pos": [27, 51]}, {"entity": "17 beta - hydroxysteroid", "entity_type": "Chemical", "pos": [83, 107]}], "task": "NER"}
{"text": "Inhibition of 17 beta - HSD2 is an attractive mechanism for the treatment of osteoporosis .", "entity": [], "task": "NER"}
{"text": "We report here the optimization of human 17 beta - HSD2 inhibitors in the 2 , 5 - thiophene amide class by varying the size of the linker ( n equals 0 and 2 ) between the amide moiety and the phenyl group .", "entity": [{"entity": "2 , 5 - thiophene amide", "entity_type": "Chemical", "pos": [74, 97]}, {"entity": "amide", "entity_type": "Chemical", "pos": [171, 176]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [192, 198]}], "task": "NER"}
{"text": "While none of the phenethylamides ( n = 2 ) were active , most of the anilides ( n = 0 ) turned out to moderately or strongly inhibit 17 beta - HSD2 .", "entity": [{"entity": "phenethylamides", "entity_type": "Chemical", "pos": [18, 33]}, {"entity": "anilides", "entity_type": "Chemical", "pos": [70, 78]}], "task": "NER"}
{"text": "The four most active compounds showed an IC 5 0 of around 60 nM and a very good selectivity toward 17 beta - HSD1 , 17 beta - HSD4 , 17 beta - HSD5 , 11 beta - HSD1 , 11 beta - HSD2 and the estrogen receptors alpha and beta .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [190, 198]}], "task": "NER"}
{"text": "The investigated compounds inhibited monkey 17 beta - HSD2 moderately , and one of them showed good inhibitory activity on mouse 17 beta - HSD2 .", "entity": [], "task": "NER"}
{"text": "SAR studies allowed a first characterization of the human 17 beta - HSD2 active site , which is predicted to be considerably larger than that of 17 beta - HSD1 .", "entity": [], "task": "NER"}
{"text": "P2Y purinergic receptors : new targets for analgesic and antimigraine drugs .", "entity": [], "task": "NER"}
{"text": "Millions of individuals worldwide suffer from acute and , more severely , chronic pain conditions ( e . g . , neuropathic pain , and migraine ) .", "entity": [], "task": "NER"}
{"text": "The latter bear tremendous personal , familial , and social costs , since sufferers and their relatives undergo a complete turnaround of their lives with the search of relief from pain becoming their pivotal thought .", "entity": [], "task": "NER"}
{"text": "Sadly , to date no effective pharmacological approaches are available which can alleviate chronic pain significantly or in the long run in all patients .", "entity": [], "task": "NER"}
{"text": "The current central strategy for the development of new and effective painkillers lies in the hypothesis that cellular and / or molecular players in nociception must exists that are not targeted by \" classical \" analgesics , and therefore researchers have put tremendous efforts into the in - depth analysis of the pathways leading to pain development and maintenance over time .", "entity": [], "task": "NER"}
{"text": "In this complex scenario , two outsiders are now taking the center stage : glial cells in sensory ganglia and in the central nervous system , thanks to their ability to communicate with neurons and to modulate their firing , and the purinergic system .", "entity": [], "task": "NER"}
{"text": "Extracellular purine and pyrimidine nucleotides are involved in the physiology of virtually every body district , and their extracellular concentrations massively increase under pathological situations , suggesting that they might represent potential targets for the modulation of disease - associated symptoms , like pain .", "entity": [{"entity": "purine and pyrimidine nucleotides", "entity_type": "Chemical", "pos": [14, 47]}], "task": "NER"}
{"text": "Here , we provide an overview of the present knowledge of the role of nucleotides in nociception , with a particular emphasis on G protein - coupled P2Y receptors and their involvement in the communication between first - and second - order neurons in sensory nerve pathways and surrounding glial cells .", "entity": [{"entity": "nucleotides", "entity_type": "Chemical", "pos": [70, 81]}], "task": "NER"}
{"text": "Answers to critics : Why there is a long term toxicity due to a Roundup - tolerant genetically modified maize and to a Roundup herbicide .", "entity": [], "task": "NER"}
{"text": "Our recent work ( S e ralini et al . , 2012 ) remains to date the most detailed study involving the life - long consumption of an agricultural genetically modified organism ( GMO ) .", "entity": [], "task": "NER"}
{"text": "This is true especially for NK603 maize for which only a 90 - day test for commercial release was previously conducted using the same rat strain ( Hammond et al . , 2004 ) .", "entity": [], "task": "NER"}
{"text": "It is also the first long term detailed research on mammals exposed to a highly diluted pesticide in its total formulation with adjuvants .", "entity": [], "task": "NER"}
{"text": "This may explain why 75 % of our first criticisms arising within a week , among publishing authors , come from plant biologists , some developing patents on GMOs , even if it was a toxicological paper on mammals , and from Monsanto Company who owns both the NK603 GM maize and Roundup herbicide ( R ) .", "entity": [], "task": "NER"}
{"text": "Our study has limits like any one , and here we carefully answer to all criticisms from agencies , consultants and scientists , that were sent to the Editor or to ourselves .", "entity": [], "task": "NER"}
{"text": "At this level , a full debate is biased if the toxicity tests on mammals of NK603 and R obtained by Monsanto Company remain confidential and thus unavailable in an electronic format for the whole scientific community to conduct independent scrutiny of the raw data .", "entity": [], "task": "NER"}
{"text": "In our article , the conclusions of long - term NK603 and Roundup toxicities came from the statistically highly discriminant findings at the biochemical level in treated groups in comparison to controls , because these findings do correspond in an blinded analysis to the pathologies observed in organs , that were in turn linked to the deaths by anatomopathologists .", "entity": [], "task": "NER"}
{"text": "GM NK603 and R cannot be regarded as safe to date .", "entity": [], "task": "NER"}
{"text": "Decreased levels of AKR1B1 and AKR1B10 in cancerous endometrium compared to adjacent non - cancerous tissue .", "entity": [], "task": "NER"}
{"text": "Endometrial cancer is associated with enhanced cell proliferation due to high concentrations of estrogens , and decreased cell differentiation due to low levels of progesterone and retinoic acid .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [96, 105]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [164, 176]}, {"entity": "retinoic acid", "entity_type": "Chemical", "pos": [181, 194]}], "task": "NER"}
{"text": "It is also associated with aberrant inflammatory responses and concomitant increased production of prostaglandins .", "entity": [{"entity": "prostaglandins", "entity_type": "Chemical", "pos": [99, 113]}], "task": "NER"}
{"text": "The human members of the aldo - keto reductase 1B ( AKR1B ) subfamily , AKR1B1 and AKR1B10 , have roles in these processes and can thus be implicated in endometrial cancer .", "entity": [], "task": "NER"}
{"text": "To date , there have been no reports on the expression of AKR1B1 in endometrial cancer , while AKR1B10 has only been studied at the cellular level .", "entity": [], "task": "NER"}
{"text": "To evaluate the roles of these AKR1B enzymes , we investigated expression of AKR1B1 and AKR1B10 in 47 paired samples of cancerous and adjacent control endometrium at the mRNA and protein levels , by quantitative PCR , Western blotting and immunohistochemistry staining .", "entity": [], "task": "NER"}
{"text": "There were significantly lower mRNA and protein levels of AKR1B1 in cancerous tissues compared to adjacent endometrium .", "entity": [], "task": "NER"}
{"text": "The gene expression of AKR1B10 at the mRNA level was significantly increased , while there were significantly decreased protein levels .", "entity": [], "task": "NER"}
{"text": "Immunohistochemistry revealed that both of these enzymes were present in all of the samples , and are located in epithelial cells of cancerous and control endometrial glands .", "entity": [], "task": "NER"}
{"text": "Elevated levels in adjacent non - cancerous tissues imply that these enzymes are more important in the initiation of endometrial cancer than in its progression .", "entity": [], "task": "NER"}
{"text": "To the best of our knowledge , this is the first report on the expression of AKR1B1 and AKR1B10 in endometrial cancer .", "entity": [], "task": "NER"}
{"text": "Further studies are needed to define the precise roles of these enzymes in the pathogenesis of endometrial cancer .", "entity": [], "task": "NER"}
{"text": "Effects of arsenite in astrocytes on neuronal signaling transduction .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "The main purpose of this study was to test the hypothesis that arsenite induces neurotoxicity via effects on astrocytes .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "Astrocytes were exposed to 0 , 5 or 10 mu M arsenite in medium for 24 h , and then astrocyte - conditioned medium ( ACM ) was collected after incubation with fresh medium for 6 h .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "Primary neuron cultures were divided into four groups due to ACM , which were neurons without ACM exposure ( group I ) and neurons exposed to ACM from 0 , 5 or 10 mu M arsenite treated astrocytes ( group II - IV ) .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [168, 176]}], "task": "NER"}
{"text": "Protein expression of N - methyl - d - aspartate receptors ( NR1 , NR2A , NR2B ) , calmodulin - dependent protein kinase II ( CaMKII ) and adenylate cyclase ( AC ) in neurons were measured after incubation with ACM for 4 , 8 or 12 h .", "entity": [{"entity": "N - methyl - d - aspartate", "entity_type": "Chemical", "pos": [22, 48]}, {"entity": "adenylate", "entity_type": "Chemical", "pos": [139, 148]}], "task": "NER"}
{"text": "Morphological changes and synaptic formation were observed after a 72 h - incubation with ACM .", "entity": [], "task": "NER"}
{"text": "Compared to group II , synaptic formation and protein expression of NR2A , NR2B , CaMKII and AC in group III and IV were significantly suppressed .", "entity": [], "task": "NER"}
{"text": "Moreover , synaptic formation and protein expression of CaMKII and AC in group II were significantly enhanced when compared with group I .", "entity": [], "task": "NER"}
{"text": "Taken together , findings from this study suggested that arsenic in astrocytes might impair synaptic formation through disturbing astrocytic effects on neuronal signal transduction .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "Toxicity of the synthetic polymeric 3 - alkylpyridinium salt ( APS3 ) is due to specific block of nicotinic acetylcholine receptors .", "entity": [{"entity": "3 - alkylpyridinium salt", "entity_type": "Chemical", "pos": [36, 60]}, {"entity": "APS3", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [108, 121]}], "task": "NER"}
{"text": "The in vivo and in vitro toxic effects of the synthetic polymeric 3 - alkylpyridinium salt ( APS3 ) , from the Mediterranean marine sponge Reniera sarai , were evaluated on mammals , with emphasis to determine its mode of action .", "entity": [{"entity": "3 - alkylpyridinium salt", "entity_type": "Chemical", "pos": [66, 90]}, {"entity": "APS3", "entity_type": "Chemical", "pos": [93, 97]}], "task": "NER"}
{"text": "The median lethal doses of APS3 were 7 . 25 and higher that 20mg / kg in mouse and rat , respectively .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [27, 31]}], "task": "NER"}
{"text": "Intravenous administration of 7 . 25 and 20mg / kg APS3 to rat caused a significant fall followed by an increase in mean arterial blood pressure accompanied by tachycardia .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "In addition , cumulative doses of APS3 ( up to 60 mg / kg ) inhibited rat nerve - evoked skeletal muscle contraction in vivo , with a median inhibitory dose ( ID ( 50 ) ) of 37 . 25mg / kg .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "When administrated locally by intramuscular injection to mouse , APS3 decreased the compound muscle action potential recorded in response to in vivo nerve stimulation , with an ID ( 50 ) of 0 . 5mg / kg .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "In vitro experiments confirmed the inhibitory effect of APS3 on mouse hemidiaphragm nerve - evoked muscle contraction with a median inhibitory concentration ( IC ( 50 ) ) of 20 . 3 mu M , without affecting directly elicited muscle contraction .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "The compound inhibited also miniature endplate potentials and nerve - evoked endplate potentials with an IC ( 50 ) of 7 . 28 mu M in mouse hemidiaphragm .", "entity": [], "task": "NER"}
{"text": "Finally , APS3 efficiently blocked acetylcholine - activated membrane inward currents flowing through Torpedo nicotinic acetylcholine receptors ( nAChRs ) incorporated to Xenopus oocytes , with an IC ( 50 ) of 0 . 19 mu M .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [10, 14]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [35, 48]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [120, 133]}], "task": "NER"}
{"text": "In conclusion , our results strongly suggest that APS3 blocks muscle - type nAChRs , and show for the first time that in vivo toxicity of APS3 is likely to occur through an antagonist action of the compound on these receptors .", "entity": [{"entity": "APS3", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "APS3", "entity_type": "Chemical", "pos": [138, 142]}], "task": "NER"}
{"text": "Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver .", "entity": [{"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [77, 109]}], "task": "NER"}
{"text": "Predictions of toxicity are central for the assessment of chemical toxicity , and the effects of environmental toxic compounds are still a major issue for predicting potential human health risks .", "entity": [], "task": "NER"}
{"text": "Among the various environmental toxicants , polycyclic aromatic hydrocarbons ( PAHs ) are an important class of environmental pollutant , and many PAHs are known or suspected carcinogens .", "entity": [{"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [44, 76]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [79, 83]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "In the present study , to investigate whether characteristic expression profiles of PAHs exist in rat liver and whether a characteristic molecular signature can discriminate and predict among different PAHs at an early exposure time , we analyzed the genome - wide expression profiles of rat livers exposed to PAHs [ benzo [ a ] anthracene ( BA ) , benzo [ a ] pyrene ( BP ) , phenanthrene ( PA ) and naphthalene ( NT ) ] .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [84, 88]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [202, 206]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [310, 314]}, {"entity": "benzo [ a ] anthracene", "entity_type": "Chemical", "pos": [317, 339]}, {"entity": "benzo [ a ] pyrene", "entity_type": "Chemical", "pos": [349, 367]}, {"entity": "phenanthrene", "entity_type": "Chemical", "pos": [377, 389]}, {"entity": "naphthalene", "entity_type": "Chemical", "pos": [401, 412]}], "task": "NER"}
{"text": "At early time - point PAH exposure , large - scale gene expression analysis resulted in characteristic molecular signatures for each PAH , and supervised analysis identified 1183 outlier genes as a distinct molecular signature discerning PAHs from the normal control group .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [133, 136]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [238, 242]}], "task": "NER"}
{"text": "We identified 158 outlier genes as early predictive and surrogate markers for predicting each tested PAH by combination of two different multi - classification algorithms with 100 % accuracy through a leave - one out cross - validation method .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "In conclusion , the characteristic gene expression signatures from a rat model system could be used as predictable and discernible gene - based biomarkers for the detection and prediction of PAHs , and these molecular markers may provide insights into the underlying mechanisms for genotoxicity of exposure to PAHs from environmental aspect .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [191, 195]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [310, 314]}], "task": "NER"}
{"text": "Combined and interactive effects of global climate change and toxicants on populations and communities .", "entity": [], "task": "NER"}
{"text": "Increased temperature and other environmental effects of global climate change ( GCC ) have documented impacts on many species ( e . g . , polar bears , amphibians , coral reefs ) as well as on ecosystem processes and species interactions ( e . g . , the timing of predator - prey interactions ) .", "entity": [], "task": "NER"}
{"text": "A challenge for ecotoxicologists is to predict how joint effects of climatic stress and toxicants measured at the individual level ( e . g . , reduced survival and reproduction ) will be manifested at the population level ( e . g . , population growth rate , extinction risk ) and community level ( e . g . , species richness , food - web structure ) .", "entity": [], "task": "NER"}
{"text": "The authors discuss how population - and community - level responses to toxicants under GCC are likely to be influenced by various ecological mechanisms .", "entity": [], "task": "NER"}
{"text": "Stress due to GCC may reduce the potential for resistance to and recovery from toxicant exposure .", "entity": [], "task": "NER"}
{"text": "Long - term toxicant exposure can result in acquired tolerance to this stressor at the population or community level , but an associated cost of tolerance may be the reduced potential for tolerance to subsequent climatic stress ( or vice versa ) .", "entity": [], "task": "NER"}
{"text": "Moreover , GCC can induce large - scale shifts in community composition , which may affect the vulnerability of communities to other stressors .", "entity": [], "task": "NER"}
{"text": "Ecological modeling based on species traits ( representing life - history traits , population vulnerability , sensitivity to toxicants , and sensitivity to climate change ) can be a promising approach for predicting combined impacts of GCC and toxicants on populations and communities .", "entity": [], "task": "NER"}
{"text": "Linking GABA ( A ) receptor subunits to alcohol - induced conditioned taste aversion and recovery from acute alcohol intoxication .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [8, 12]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [40, 47]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [109, 116]}], "task": "NER"}
{"text": "GABA type A receptors ( GABA ( A ) - R ) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [24, 28]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "We studied null mutant mice for six different GABA ( A ) - R subunits ( alpha 1 , alpha 2 , alpha 3 , alpha 4 , alpha 5 and delta ) .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "Only mice lacking the alpha 2 subunit showed reduction of conditioned taste aversion ( CTA ) to ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [96, 103]}], "task": "NER"}
{"text": "These results are in agreement with data from knock - in mice with mutation of the ethanol - sensitive site in the alpha 2 - subunit ( Blednov et al . , 2011 ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "All together , they indicate that aversive property of ethanol is dependent on ethanol action on alpha 2 - containing GABA ( A ) - R .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [118, 122]}], "task": "NER"}
{"text": "Deletion of the alpha 2 - subunit led to faster recovery whereas absence of the alpha 3 - subunit slowed recovery from ethanol - induced incoordination ( rotarod ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [119, 126]}], "task": "NER"}
{"text": "Deletion of the other four subunits did not affect this behavior .", "entity": [], "task": "NER"}
{"text": "Similar changes in this behavior for the alpha 2 and alpha 3 null mutants were found for flurazepam motor incoordination .", "entity": [{"entity": "flurazepam", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "However , no differences in recovery were found in motor - incoordinating effects of an alpha 1 - selective modulator ( zolpidem ) or an alpha 4 - selective agonist ( gaboxadol ) .", "entity": [{"entity": "zolpidem", "entity_type": "Chemical", "pos": [120, 128]}, {"entity": "gaboxadol", "entity_type": "Chemical", "pos": [167, 176]}], "task": "NER"}
{"text": "Therefore , recovery of rotarod incoordination is under control of two GABA ( A ) - R subunits : alpha 2 and alpha 3 .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [71, 75]}], "task": "NER"}
{"text": "For motor activity , alpha 3 null mice demonstrated higher activation by ethanol ( 1 g / kg ) whereas both alpha 2 ( - / - ) and alpha 3 ( - / Y ) knockout mice were less sensitive to ethanol - induced reduction of motor activity ( 1 . 5 g / kg ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [184, 191]}], "task": "NER"}
{"text": "These studies demonstrate that the effects of ethanol at GABAergic synapses containing alpha 2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the alpha 2 subunit with human alcoholism .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [152, 159]}], "task": "NER"}
{"text": "Orexin A regulates cardiovascular responses in stress - induced hypertensive rats .", "entity": [], "task": "NER"}
{"text": "Several pieces of evidence indicate that the rostral ventrolateral medulla ( RVLM ) is probably one of the key neural structures mediating the pressor effects of orexins in the brain .", "entity": [], "task": "NER"}
{"text": "Nitric oxide synthase / nitric oxide ( NOS / NO ) system in the RVLM modulates cardiovascular activities .", "entity": [{"entity": "Nitric oxide", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "NO", "entity_type": "Chemical", "pos": [39, 41]}], "task": "NER"}
{"text": "Our experiments were designed to test the hypothesis that orexin - A ( OXA ) is involved in the mechanism of stress - induced hypertension ( SIH ) by adjusting NOS / NO system in the RVLM .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [160, 162]}], "task": "NER"}
{"text": "The stress - induced hypertensive rats ( SIHR ) model was established by electric foot - shocks and noises .", "entity": [], "task": "NER"}
{"text": "Here we examined the expression of OXA immunoreactive ( OXA - IR ) cells in the lateral hypothalamus ( LH ) and the protein level of orexin 1 receptor ( OX1R ) in the RVLM of SIHR , and we found that the expressions of OXA - IR and OX1R were higher than those of the control group .", "entity": [], "task": "NER"}
{"text": "The double - staining immunohistochemical evidence showed that OX1R immunoreactive ( OX1R - IR ) cells and neuronal nitric oxide synthase ( nNOS ) or inducible nitric oxide synthase ( iNOS ) immunoreactive ( IR ) cells were co - localizated in the RVLM .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [116, 128]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [160, 172]}], "task": "NER"}
{"text": "Microinjection of OXA ( 10 , 50 , 100 pmol / 100 nl ) into the unilateral ( right ) RVLM of control rats or SIHR produced pressor and tachycardiac effects in a dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "SB - 408124 ( 100 pmol / 100 nl , an antagonist of OX1R ) or TCS OX2 29 ( 100 pmol / 100 nl , an antagonist of OX2R ) partly abolished the cardiovascular effects of exogenously - administrated OXA into the RVLM of control rats and SIHR , and lowered the increased systolic blood pressure ( SBP ) and heart rate ( HR ) of SIHR , with no difference in statistical significance between the two antagonists ' effects .", "entity": [{"entity": "SB - 408124", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "TCS OX2 29", "entity_type": "Chemical", "pos": [61, 71]}], "task": "NER"}
{"text": "Microinjection into the RVLM of both control and SIHR groups of 7 - Ni ( 0 . 05 pmol / 100 nl , nNOS inhibitor ) or Methylene Blue [ 100 pmol / 100 nl , an inhibitor of soluble guanylate cyclase ( sGC ) ] suppressed the OXA - induced increase of SBP and HR , whereas microinjection of AG ( 1 , 10 , 100 pmol / 100 nl ) had no obvious effects on the OXA - induced increase of SBP and HR .", "entity": [{"entity": "Methylene Blue", "entity_type": "Chemical", "pos": [116, 130]}, {"entity": "guanylate", "entity_type": "Chemical", "pos": [177, 186]}], "task": "NER"}
{"text": "Our results indicate that OXA in the RVLM may participate in the central regulation of cardiovascular activities in SIHR , and OX1R and OX2R both have important roles in it .", "entity": [], "task": "NER"}
{"text": "The cardiovascular effects of OXA in the RVLM may be induced by nNOS - derived NO , which activated sGC - associated signaling pathway .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [65, 67]}], "task": "NER"}
{"text": "Implications of global climate change for the assessment and management of human health risks of chemicals in the natural environment .", "entity": [], "task": "NER"}
{"text": "Global climate change ( GCC ) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures , meaning that risks of pollutants could change in the future .", "entity": [], "task": "NER"}
{"text": "The present study , therefore , explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk - assessment and management practices .", "entity": [], "task": "NER"}
{"text": "In certain parts of the world , GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals .", "entity": [], "task": "NER"}
{"text": "Changes in human behavior will also affect how humans come into contact with contaminated air , water , and food .", "entity": [], "task": "NER"}
{"text": "Dietary changes , psychosocial stress , and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals .", "entity": [], "task": "NER"}
{"text": "These changes are likely to have significant implications for current practices for chemical assessment .", "entity": [], "task": "NER"}
{"text": "Assumptions used in current exposure - assessment models may no longer apply , and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures .", "entity": [], "task": "NER"}
{"text": "Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes .", "entity": [], "task": "NER"}
{"text": "Biological network inference for drug discovery .", "entity": [], "task": "NER"}
{"text": "A better understanding of the pathophysiology should help deliver drugs whose targets are involved in the causative processes underlying a disease .", "entity": [], "task": "NER"}
{"text": "Biological network inference uses computational methods for deducing from high - throughput experimental data , the topology and the causal structure of the interactions among the drugs and their targets .", "entity": [], "task": "NER"}
{"text": "Therefore , biological network inference can support and contribute to the experimental identification of both gene and protein networks causing a disease as well as the biochemical networks of drugs metabolism and mechanisms of action .", "entity": [], "task": "NER"}
{"text": "The resulting high - level networks serve as a foundational basis for more detailed mechanistic models and are increasingly used in drug discovery by pharmaceutical and biotechnology companies .", "entity": [], "task": "NER"}
{"text": "We review and compare recent computational technologies for network inference applied to drug discovery .", "entity": [], "task": "NER"}
{"text": "Spontaneous electric fields in films of CF3Cl , CF2Cl2 and CFCl3 .", "entity": [{"entity": "CF3Cl", "entity_type": "Chemical", "pos": [40, 45]}, {"entity": "CF2Cl2", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "CFCl3", "entity_type": "Chemical", "pos": [59, 64]}], "task": "NER"}
{"text": "Data are presented showing the spontaneous formation of electric fields within solid films of the chlorofluorocarbons ( CFCs ) CF ( 3 ) Cl , CF ( 2 ) Cl ( 2 ) and CFCl ( 3 ) as a function of film deposition temperature from 40 K and above .", "entity": [{"entity": "chlorofluorocarbons", "entity_type": "Chemical", "pos": [98, 117]}, {"entity": "CFCs", "entity_type": "Chemical", "pos": [120, 124]}, {"entity": "CF ( 3 ) Cl", "entity_type": "Chemical", "pos": [127, 138]}, {"entity": "CF ( 2 ) Cl ( 2 )", "entity_type": "Chemical", "pos": [141, 158]}, {"entity": "CFCl ( 3 )", "entity_type": "Chemical", "pos": [163, 173]}], "task": "NER"}
{"text": "Electric fields , which arise through dipole alignment and lie in the range of a few times 10 ( 7 ) V m ( - 1 ) to a few times 10 ( 6 ) V m ( - 1 ) , decrease as the degree of chlorination increases .", "entity": [], "task": "NER"}
{"text": "Maximum deposition temperatures for display of an electric field lie at ~ 50 K , ~ 65 K and ~ 52 K for CF ( 3 ) Cl , CF ( 2 ) Cl ( 2 ) and CFCl ( 3 ) respectively .", "entity": [{"entity": "CF ( 3 ) Cl", "entity_type": "Chemical", "pos": [103, 114]}, {"entity": "CF ( 2 ) Cl ( 2 )", "entity_type": "Chemical", "pos": [117, 134]}, {"entity": "CFCl ( 3 )", "entity_type": "Chemical", "pos": [139, 149]}], "task": "NER"}
{"text": "CFCl ( 3 ) films possess electric fields which show an onset of temporal metastability between deposition temperatures of 46 K and 50 K .", "entity": [{"entity": "CFCl ( 3 )", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "CF ( 3 ) Cl and CF ( 2 ) Cl ( 2 ) demonstrate temperatures of ~ 65 K and ~ 80 K at which the electric field in the film is removed by heating , so - called Curie points , with decay of the field spread over more than 10 K .", "entity": [{"entity": "CF ( 3 ) Cl", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "CF ( 2 ) Cl ( 2 )", "entity_type": "Chemical", "pos": [16, 33]}], "task": "NER"}
{"text": "CFCl ( 3 ) displays a comparatively sharp Curie point at 55 K .", "entity": [{"entity": "CFCl ( 3 )", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "This variety of behaviour arises despite the resemblance of these three species in terms of electronic structure and gas phase dipole moment , emphasising the requirement for detailed chemical models of this phenomenon .", "entity": [], "task": "NER"}
{"text": "Toxicity of diesel contaminated soils to the subantarctic earthworm Microscolex macquariensis .", "entity": [], "task": "NER"}
{"text": "Several fuel spills have occurred on subantarctic Macquarie Island ( 54 degrees 30 ' S 158 degrees 57 ' E ) associated with storing fuel and generating power for the island ' s research station .", "entity": [], "task": "NER"}
{"text": "The Australian Antarctic Division began full - scale , on - site remediation of these sites in 2009 .", "entity": [], "task": "NER"}
{"text": "To develop appropriate target concentrations for remediation , acute and chronic tests were developed with the endemic earthworm , Microscolex macquariensis , using avoidance , survival , and reproduction as endpoints .", "entity": [], "task": "NER"}
{"text": "Uncontaminated low ( 3 % ) , medium ( 11 % ) , and high ( 38 - 48 % ) carbon content soils from Macquarie Island were used to examine the influence of soil carbon on toxicity .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [70, 76]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [156, 162]}], "task": "NER"}
{"text": "Soils were spiked with Special Antarctic Blend ( SAB ) diesel and used either immediately to simulate a fresh spill or after four weeks to simulate an aged spill .", "entity": [], "task": "NER"}
{"text": "Earthworms were sensitive to fresh SAB , with significant avoidance at 181 mg / kg ; acute 14 - d survival median lethal concentration ( LC50 ) of 103 mg / kg for low carbon soil ; and juvenile production median effective concentration ( EC50 ) of 317 mg / kg for high carbon soil .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [167, 173]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [269, 275]}], "task": "NER"}
{"text": "Earthworms were less sensitive to aged SAB than to fresh SAB in high carbon soil for juvenile production ( EC50 of 1 , 753 and 317 mg / kg , respectively ) , but were more sensitive for adult survival ( LC50 of 2 , 322 and 1 , 364 mg / kg , respectively ) .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [69, 75]}], "task": "NER"}
{"text": "Using M . macquariensis as a surrogate for soil quality , approximately 50 to 200 mg SAB / kg soil would be a sufficiently protective remediation target .", "entity": [], "task": "NER"}
{"text": "Extraction of sediment - associated polycyclic aromatic hydrocarbons with granular activated carbon .", "entity": [{"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [36, 68]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [93, 99]}], "task": "NER"}
{"text": "Addition of activated carbon ( AC ) to sediments has been proposed as a method to reduce ecotoxicological risks of sediment - bound contaminants .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [22, 28]}], "task": "NER"}
{"text": "The present study explores the effectiveness of granular AC ( GAC ) in extracting polycyclic aromatic hydrocarbon ( PAH ) from highly contaminated sediments .", "entity": [{"entity": "polycyclic aromatic hydrocarbon", "entity_type": "Chemical", "pos": [82, 113]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "Four candidate GAC materials were screened in terms of PAH extraction efficiency using single - step 24 - h GAC extractions , with traditional 24 - h Tenax extraction as a reference .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "Subsequently , sorption of native PAHs to the best performing GAC 1240W ( 0 . 45 - 1 . 70 mm ) was studied for sediment only and for GAC - sediment mixtures at different GAC - sediment weight ratios , using 76 - micro m polyoxymethylene ( POM ) passive samplers .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "polyoxymethylene", "entity_type": "Chemical", "pos": [220, 236]}, {"entity": "POM", "entity_type": "Chemical", "pos": [239, 242]}], "task": "NER"}
{"text": "Granular AC sorption parameters for PAHs were determined by subtracting the contribution of PAH sorption to sediment from PAH sorption to the GAC - sediment mixture .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "It appears that the binding of PAHs and the effectiveness of GAC to reduce sediment porewater concentrations were highly dependent on the GAC - sediment mixing ratio and hydrophobicity of the PAH .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [192, 195]}], "task": "NER"}
{"text": "Despite the considerable fouling of GAC by organic matter and oil , 50 to 90 % of the most available PAH was extracted by the GAC during a 28 - d contact time , at a dose as low as 4 % , which also is a feasible dose in field - scale applications aimed at cleaning the sediment by GAC addition and removal .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Runt - related transcription factor 1 ( RUNX1 ) stimulates tumor suppressor p53 protein in response to DNA damage through complex formation and acetylation .", "entity": [], "task": "NER"}
{"text": "Representative tumor suppressor p53 plays a critical role in the regulation of proper DNA damage response .", "entity": [], "task": "NER"}
{"text": "In this study , we have found for the first time that Runt - related transcription factor 1 ( RUNX1 ) contributes to p53 - dependent DNA damage response .", "entity": [], "task": "NER"}
{"text": "Upon adriamycin ( ADR ) exposure , p53 as well as RUNX1 were strongly induced in p53 - proficient HCT116 and U2OS cells , which were closely associated with significant transactivation of p53 target genes , such as p21 ( WAF ) ( 1 ) , BAX , NOXA , and PUMA .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [5, 15]}, {"entity": "ADR", "entity_type": "Chemical", "pos": [18, 21]}], "task": "NER"}
{"text": "RUNX1 was exclusively expressed in the cell nucleus and formed a complex with p53 in response to ADR .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "Chromatin immunoprecipitation assay demonstrated that p53 together with RUNX1 are efficiently recruited onto p53 target gene promoters following ADR exposure , indicating that RUNX1 is involved in p53 - mediated transcriptional regulation .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [145, 148]}], "task": "NER"}
{"text": "Indeed , forced expression of RUNX1 stimulated the transcriptional activity of p53 in response to ADR .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [98, 101]}], "task": "NER"}
{"text": "Consistent with these observations , knockdown of RUNX1 attenuated ADR - mediated induction of p53 target genes and suppressed ADR - dependent apoptosis .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [67, 70]}, {"entity": "ADR", "entity_type": "Chemical", "pos": [127, 130]}], "task": "NER"}
{"text": "Furthermore , RUNX1 was associated with p300 histone acetyltransferase , and ADR - dependent acetylation of p53 at Lys - 373 / 382 was markedly inhibited in RUNX1 knockdown cells .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "Lys", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "In addition , knockdown of RUNX1 resulted in a significant decrease in the amount of p53 - p300 complex following ADR exposure .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [114, 117]}], "task": "NER"}
{"text": "Taken together , our present results strongly suggest that RUNX1 is required for the stimulation of p53 in response to DNA damage and also provide novel insight into understanding the molecular mechanisms behind p53 - dependent DNA damage response .", "entity": [], "task": "NER"}
{"text": "Control of stem cells and cancer stem cells by Hedgehog signaling : pharmacologic clues from pathway dissection .", "entity": [], "task": "NER"}
{"text": "Hedgehog is a key morphogen regulating embryonic development and tissue repair .", "entity": [], "task": "NER"}
{"text": "Remarkably , when misregulated , it leads to tumorigenesis .", "entity": [], "task": "NER"}
{"text": "Hedgehog signaling is triggered by binding of ligands with transmembrane receptor Ptch and is subsequently mediated by transcriptional effectors belonging to the Gli family , whose functions is tuned by a number of molecular interactions and post - synthetic modifications .", "entity": [], "task": "NER"}
{"text": "The complex of these regulatory circuitries provides a tight control of developmental processes , mainly involving the modulation of genes determining the fate of stem cells .", "entity": [], "task": "NER"}
{"text": "Similarly , Hedgehog regulates cancer stem cells fostering tumorigenesis .", "entity": [], "task": "NER"}
{"text": "To this regard , these processes represent promising targets for novel therapeutic strategies aiming at the control of stemness reactivation and maintenance in cancer .", "entity": [], "task": "NER"}
{"text": "Hydrogen sulfide increases nitric oxide production with calcium - dependent activation of endothelial nitric oxide synthase in endothelial cells .", "entity": [{"entity": "Hydrogen sulfide", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [102, 114]}], "task": "NER"}
{"text": "Hydrogen sulfide ( H ( 2 ) S ) was recently discovered to be synthesized in mammalian tissues by several different enzymes .", "entity": [{"entity": "Hydrogen sulfide", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "H ( 2 ) S", "entity_type": "Chemical", "pos": [19, 28]}], "task": "NER"}
{"text": "Numerous studies have shown that H ( 2 ) S has vasodilator and antihypertensive effects in the cardiovascular system .", "entity": [{"entity": "H ( 2 ) S", "entity_type": "Chemical", "pos": [33, 42]}], "task": "NER"}
{"text": "However , intracellular mechanisms of the H ( 2 ) S - induced vasodilation and its interactions with other endothelium - derived relaxing factors , such as nitric oxide ( NO ) , remain unclear .", "entity": [{"entity": "H ( 2 ) S", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [156, 168]}, {"entity": "NO", "entity_type": "Chemical", "pos": [171, 173]}], "task": "NER"}
{"text": "We investigated whether H ( 2 ) S directly regulates endothelial NO synthase ( eNOS ) activity and NO production in endothelial cells .", "entity": [{"entity": "H ( 2 ) S", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "NO", "entity_type": "Chemical", "pos": [65, 67]}, {"entity": "NO", "entity_type": "Chemical", "pos": [80, 82]}], "task": "NER"}
{"text": "NaHS , a H ( 2 ) S donor , dose - dependently increased NO production in cultured endothelial cells .", "entity": [{"entity": "NaHS", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "H ( 2 ) S", "entity_type": "Chemical", "pos": [9, 18]}, {"entity": "NO", "entity_type": "Chemical", "pos": [56, 58]}], "task": "NER"}
{"text": "This effect was abolished by a calcium chelator ( BAPTA - AM ) , but not by the absence of extracellular calcium .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "BAPTA - AM", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [105, 112]}], "task": "NER"}
{"text": "The NaHS - induced NO production was partially blocked by inhibitors of ryanodine receptor ( dantrolene ) or inositol 1 , 4 , 5 - triphosphate receptor ( xestospongin C ) .", "entity": [{"entity": "NaHS", "entity_type": "Chemical", "pos": [4, 8]}, {"entity": "NO", "entity_type": "Chemical", "pos": [19, 21]}, {"entity": "ryanodine", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "dantrolene", "entity_type": "Chemical", "pos": [93, 103]}, {"entity": "inositol 1 , 4 , 5 - triphosphate", "entity_type": "Chemical", "pos": [109, 142]}, {"entity": "xestospongin C", "entity_type": "Chemical", "pos": [154, 168]}], "task": "NER"}
{"text": "NaHS significantly increased intracellular calcium concentrations , and this effect was attenuated by dantrolene or xestospongin C .", "entity": [{"entity": "NaHS", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [43, 50]}, {"entity": "dantrolene", "entity_type": "Chemical", "pos": [102, 112]}, {"entity": "xestospongin C", "entity_type": "Chemical", "pos": [116, 130]}], "task": "NER"}
{"text": "NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179 .", "entity": [{"entity": "NaHS", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "phosphoserine", "entity_type": "Chemical", "pos": [55, 68]}], "task": "NER"}
{"text": "The NaHS - induced eNOS phosphorylation and NO production were not affected by a PI3K / Akt inhibitor ( wortmannin ) .", "entity": [{"entity": "NaHS", "entity_type": "Chemical", "pos": [4, 8]}, {"entity": "NO", "entity_type": "Chemical", "pos": [20, 22]}, {"entity": "wortmannin", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "The data of this study suggest that H ( 2 ) S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum , which may explain one of mechanisms of its vasodilator function .", "entity": [{"entity": "H ( 2 ) S", "entity_type": "Chemical", "pos": [36, 45]}, {"entity": "NO", "entity_type": "Chemical", "pos": [92, 94]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "Efficient serum - resistant lipopolyplexes targeted to the folate receptor .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [59, 65]}], "task": "NER"}
{"text": "In this work , we have developed and evaluated a new targeted lipopolyplex ( LPP ) , by combining polyethylenimine ( PEI ) , 1 , 2 - dioleoyl - 3 - ( trimethylammonium ) propane ( DOTAP ) / Chol liposomes , the plasmids pCMVLuc / pCMVIL - 12 , and the ligand folic acid ( FA ) , able to transfect HeLa and B16 - F10 cells in the presence of very high concentration of serum ( 60 % FBS ) .", "entity": [{"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [98, 114]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [117, 120]}, {"entity": "1 , 2 - dioleoyl - 3 - ( trimethylammonium ) propane", "entity_type": "Chemical", "pos": [125, 177]}, {"entity": "DOTAP", "entity_type": "Chemical", "pos": [180, 185]}, {"entity": "folic acid", "entity_type": "Chemical", "pos": [259, 269]}], "task": "NER"}
{"text": "These complexes ( Fol - LPP ) have a net positive surface charge .", "entity": [], "task": "NER"}
{"text": "The combination of folic acid with lipopolyplexes also enhanced significantly the transfection activity of the therapeutic gene interleukin - 12 ( IL - 12 ) , without any significant cytotoxicity .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "The specificity of the folate receptor ( FR ) - mediated gene transfer was corroborated by employing a folate receptor deficient cell line ( HepG2 ) .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "folate", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "This formulation improved gene delivery showed by conventional lipoplexes or polyplexes resulting an efficient , simple , and nontoxic method for gene delivery of therapeutic genes in vitro and very probably in vivo .", "entity": [], "task": "NER"}
{"text": "Ferulic acid modulates fluoride - induced oxidative hepatotoxicity in male Wistar rats .", "entity": [{"entity": "Ferulic acid", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "The present study is aimed to evaluate the protective effect of ferulic acid ( FA ) on fluoride - induced oxidative hepatotoxicity in male Wistar rats .", "entity": [{"entity": "ferulic acid", "entity_type": "Chemical", "pos": [64, 76]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Fluoride ( 25 mg / L ) was given orally to induce hepatotoxicity for 12 weeks .", "entity": [{"entity": "Fluoride", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Hepatic damage were assessed using status of pathophysiological markers like serum marker enzymes like aspartate transaminase , alanine transaminase , alkaline phosphatase , acid phosphatase , gamma glutamyl transferase , lactate dehydrogenase , bilirubin , lipid profile , total protein content levels , and histopathological studies .", "entity": [{"entity": "aspartate", "entity_type": "Chemical", "pos": [103, 112]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [128, 135]}, {"entity": "gamma glutamyl", "entity_type": "Chemical", "pos": [193, 207]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [222, 229]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [246, 255]}], "task": "NER"}
{"text": "Treatment with FA significantly reduced the degree of histological aberrations and rescued lipid peroxidation , as observed from reduced levels of lipid hydroperoxides , nitric oxide , restored levels of enzymic and non - enzymic antioxidants , and total protein content , with a concomitant decline in the levels of marker enzymes and lipid profile in fluoride - induced rats .", "entity": [{"entity": "hydroperoxides", "entity_type": "Chemical", "pos": [153, 167]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [170, 182]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [353, 361]}], "task": "NER"}
{"text": "These results suggest that ferulic acid has the ability to protect fluoride - induced hepatic damage .", "entity": [{"entity": "ferulic acid", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "The clinical relevance of plasma protein binding changes .", "entity": [], "task": "NER"}
{"text": "Controversy reigns as to how protein binding changes alter the time course of unbound drug concentrations in patients .", "entity": [], "task": "NER"}
{"text": "Given that the unbound concentration is responsible for drug efficacy and potential drug toxicity , this area is of significant interest to clinicians and academics worldwide .", "entity": [], "task": "NER"}
{"text": "The present uncertainty means that many questions relating to this area exist , including \" How important is protein binding ? \" , \" Is protein binding always constant ? \" , \" Do pH and temperature changes alter binding ? \" and \" How do protein binding changes affect dosing requirements ? \" .", "entity": [], "task": "NER"}
{"text": "In this paper , we seek to address these questions and consider the data associated with altered pharmacokinetics in the presence of changes in protein binding and the clinical consequences that these may have on therapy , using examples from the critical care area .", "entity": [], "task": "NER"}
{"text": "The published literature consistently indicates that a change in the protein binding and unbound concentrations of some drugs are common in certain specific patient groups such as the critically ill .", "entity": [], "task": "NER"}
{"text": "Changes in pharmacokinetic parameters , including clearance and apparent volume of distribution ( V ( d ) ) , may be dramatic .", "entity": [], "task": "NER"}
{"text": "Drugs with high protein binding , high intrinsic clearance ( e . g . clearance by glomerular filtration ) and where dosing is not titrated to effect are most likely to be affected in a clinical context .", "entity": [], "task": "NER"}
{"text": "Drugs such as highly protein bound antibacterials with multiple half - lives within a dosing interval and that have some level of renal clearance , such as ertapenem , teicoplanin , ceftriaxone and flucloxacillin , are commonly affected .", "entity": [{"entity": "ertapenem", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "teicoplanin", "entity_type": "Chemical", "pos": [168, 179]}, {"entity": "ceftriaxone", "entity_type": "Chemical", "pos": [182, 193]}, {"entity": "flucloxacillin", "entity_type": "Chemical", "pos": [198, 212]}], "task": "NER"}
{"text": "In response to these challenges , clinicians need to adapt dosing regimens rationally based on the pharmacokinetic / pharmacodynamic characteristics of the drug .", "entity": [], "task": "NER"}
{"text": "We propose that further pharmacokinetic modelling - based research is required to enable the design of robust dosing regimens for drugs affected by altered protein binding .", "entity": [], "task": "NER"}
{"text": "In vitro cytochrome p450 activity decreases in children with high pediatric end - stage liver disease scores .", "entity": [], "task": "NER"}
{"text": "To improve the modeling and simulation of pharmacokinetics in pediatric patients , research into developmental and disease - specific determinants is needed .", "entity": [], "task": "NER"}
{"text": "This article describes the evaluation of the activity of in vitro cytochrome P450 ( P450 ) , an important enzyme family in drug metabolism , in children with hepatic dysfunction .", "entity": [], "task": "NER"}
{"text": "The activity of six P450 isoforms ( CYP1A2 , 2C9 , 2C19 , 2D6 , 2E1 , and 3A4 ) was evaluated in 31 patients with different pathologies , predominantly biliary atresia ( n = 23 ) .", "entity": [], "task": "NER"}
{"text": "Hypervariable activity was observed for all the isoforms .", "entity": [], "task": "NER"}
{"text": "Compared with average adult activity , low activity levels were seen for CYP1A2 , 2C19 , 2E1 , and 3A4 .", "entity": [], "task": "NER"}
{"text": "For CYP2E1 and 3A4 , a positive correlation between activity and abundance was observed .", "entity": [], "task": "NER"}
{"text": "Age , comedication , and genotype could not be used as predictors for P450 activity in this patient population .", "entity": [], "task": "NER"}
{"text": "In contrast , the pediatric end - stage liver disease score was negatively correlated with the ln ( activity ) .", "entity": [], "task": "NER"}
{"text": "This finding suggests a decrease in P450 activity with deteriorating hepatic function .", "entity": [], "task": "NER"}
{"text": "Moreover , the activity of all isoforms was correlated , demonstrating a concomitant decrease of all isoforms in young patients with liver disease .", "entity": [], "task": "NER"}
{"text": "To our knowledge , this is the first study to evaluate P450 activity in children with hepatic impairment .", "entity": [], "task": "NER"}
{"text": "The presented data may provide support in the further optimization of a disease - specific model in this patient population .", "entity": [], "task": "NER"}
{"text": "Induction of multidrug resistance transporter ABCG2 by prolactin in human breast cancer cells .", "entity": [], "task": "NER"}
{"text": "The multidrug transporter , breast cancer resistance protein , ABCG2 , is up - regulated in certain chemoresistant cancer cells and in the mammary gland during lactation .", "entity": [], "task": "NER"}
{"text": "We investigated the role of the lactogenic hormone prolactin ( PRL ) in the regulation of ABCG2 .", "entity": [], "task": "NER"}
{"text": "PRL dose - dependently induced ABCG2 expression in T - 47D human breast cancer cells .", "entity": [], "task": "NER"}
{"text": "This induction was significantly reduced by short - interfering RNA - mediated knockdown of Janus kinase 2 ( JAK2 ) .", "entity": [], "task": "NER"}
{"text": "Knockdown or pharmacologic inhibition of the down - stream signal transducer and activator of transcription - 5 ( STAT5 ) also blunted the induction of ABCG2 by PRL , suggesting a role for the JAK2 / STAT5 pathway in PRL - induced ABCG2 expression .", "entity": [], "task": "NER"}
{"text": "Corroborating these findings , we observed PRL - stimulated STAT5 recruitment to a region containing a putative gamma - interferon activation sequence ( GAS ) element at - 434 base pairs upstream of the ABCG2 transcription start site .", "entity": [], "task": "NER"}
{"text": "Introduction of a single mutation to the - 434 GAS element significantly attenuated PRL - stimulated activity of a luciferase reporter driven by the ABCG2 gene promoter and 5 ' - flanking region containing the - 434 GAS motif .", "entity": [], "task": "NER"}
{"text": "In addition , this GAS element showed strong copy number dependency in its response to PRL treatment .", "entity": [], "task": "NER"}
{"text": "Interestingly , inhibitors against the mitogen - activated protein kinase and phosphoinositide - 3 - kinase signaling pathways significantly decreased the induction of ABCG2 by PRL without altering STAT5 recruitment to the GAS element .", "entity": [{"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [78, 94]}], "task": "NER"}
{"text": "We conclude that the JAK2 / STAT5 pathway is required but not sufficient for the induction of ABCG2 by PRL .", "entity": [], "task": "NER"}
{"text": "Obtusilactone B from Machilus Thunbergii targets barrier - to - autointegration factor to treat cancer .", "entity": [{"entity": "Obtusilactone B", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes .", "entity": [], "task": "NER"}
{"text": "This strategy led to the development of therapeutics that use monoclonal antibodies or small - molecule inhibitors .", "entity": [], "task": "NER"}
{"text": "However , the continued development of novel molecular targeting inhibitors is required to target the various oncogenes associated with the diverse types and stages of cancer .", "entity": [], "task": "NER"}
{"text": "Obtusilactone B is a butanolide derivative purified from Machilus thunbergii .", "entity": [{"entity": "Obtusilactone B", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "butanolide", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "In this study , we show that obtusilactone B functions as a small - molecule inhibitor that causes abnormal nuclear envelope dynamics and inhibits growth by suppressing vaccinia - related kinase 1 ( VRK1 ) - mediated phosphorylation of barrier - to - autointegration factor ( BAF ) .", "entity": [{"entity": "obtusilactone B", "entity_type": "Chemical", "pos": [29, 44]}], "task": "NER"}
{"text": "BAF is important in maintaining lamin integrity , which is closely associated with diseases that include cancer .", "entity": [], "task": "NER"}
{"text": "Specific binding of obtusilactone B to BAF suppressed VRK1 - mediated BAF phosphorylation and the subsequent dissociation of the nuclear envelope from DNA that allows cells to progress through the cell cycle .", "entity": [{"entity": "obtusilactone B", "entity_type": "Chemical", "pos": [20, 35]}], "task": "NER"}
{"text": "Obtusilactone B potently induced tumor cell death in vitro , indicating that specific targeting of BAF to block cell cycle progression can be an effective anticancer strategy .", "entity": [{"entity": "Obtusilactone B", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment .", "entity": [], "task": "NER"}
{"text": "Synthesis and antitubercular activity of 2 - ( substituted phenyl / benzyl - amino ) - 6 - ( 4 - chlorophenyl ) - 5 - ( methoxycarbonyl ) - 4 - methyl - 3 , 6 - dihydropyrimidin - 1 - ium chlorides .", "entity": [{"entity": "2 - ( substituted phenyl / benzyl - amino ) - 6 - ( 4 - chlorophenyl ) - 5 - ( methoxycarbonyl ) - 4 - methyl - 3 , 6 - dihydropyrimidin - 1 - ium chlorides", "entity_type": "Chemical", "pos": [41, 197]}], "task": "NER"}
{"text": "A series of 2 - ( substituted phenyl / benzyl - amino ) - 6 - ( 4 - chlorophenyl ) - 5 - ( methoxycarbonyl ) - 4 - methyl - 3 , 6 - dihydropyrimidin - 1 - ium chlorides 7 - 13 and 15 was synthesized in their hydrochloride salt form .", "entity": [{"entity": "2 - ( substituted phenyl / benzyl - amino ) - 6 - ( 4 - chlorophenyl ) - 5 - ( methoxycarbonyl ) - 4 - methyl - 3 , 6 - dihydropyrimidin - 1 - ium chlorides", "entity_type": "Chemical", "pos": [12, 168]}, {"entity": "hydrochloride", "entity_type": "Chemical", "pos": [208, 221]}], "task": "NER"}
{"text": "The title compounds were characterized by FT - IR , NMR ( ( 1 ) H and ( 13 ) C ) and elemental analysis .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [70, 78]}], "task": "NER"}
{"text": "They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv , multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [287, 290]}], "task": "NER"}
{"text": "Among all the tested compounds in the series , compounds 7 and 11 emerged as promising antitubercular agents at 16 mu g / mL against multidrug resistance tuberculosis and over 64 mu g / mL against extensively drug resistance tuberculosis .", "entity": [], "task": "NER"}
{"text": "The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X - ray study .", "entity": [], "task": "NER"}
{"text": "A dual role of Se on Cd toxicity : evidences from the uptake of Cd and some essential elements and the growth responses in paddy rice .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [15, 17]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [64, 66]}], "task": "NER"}
{"text": "This study was carried out to investigate the effects of selenium ( Se ) on the uptake and translocation of cadmium ( Cd ) and essential elements in paddy rice ( Oryza sativa L . , Shuangyou 998 ) .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [57, 65]}, {"entity": "Se", "entity_type": "Chemical", "pos": [68, 70]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [108, 115]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [118, 120]}], "task": "NER"}
{"text": "Selenium could alleviate / aggravate Cd toxicity in paddy rice , which depended on the dosages of Se and / or Cd .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [37, 39]}, {"entity": "Se", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [110, 112]}], "task": "NER"}
{"text": "When Cd treatment level was as low as 35 . 6 mu M , <= 12 . 7 mu M Se could inhibit the uptake of Cd in paddy rice and increase the biomass of paddy rice ; however , with Cd levels reaching 89 - 178 mu M , the addition of Se resulted in increases in Cd uptake and exacerbated the growth of paddy rice .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [5, 7]}, {"entity": "Se", "entity_type": "Chemical", "pos": [67, 69]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [171, 173]}, {"entity": "Se", "entity_type": "Chemical", "pos": [222, 224]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [250, 252]}], "task": "NER"}
{"text": "Cd always inhibited the uptake of Se .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Se", "entity_type": "Chemical", "pos": [34, 36]}], "task": "NER"}
{"text": "Cd alone suppressed the uptake of Ca , Mg , Mn , Cu , and Zn ; however , Se reversed the decreases in the concentrations of the said elements , suggesting an element regulation mechanism to relieve Cd toxicity .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [34, 36]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [49, 51]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [58, 60]}, {"entity": "Se", "entity_type": "Chemical", "pos": [73, 75]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [198, 200]}], "task": "NER"}
{"text": "Without Cd in the solution , low doses of Se increased the biomasses of shoots and roots at the expense of the more or less decreases in the concentrations of Ca , Mg , K , Fe , Mn , Cu , and shoot Zn , indicating an antagonistic effect of Se on these cations .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [8, 10]}, {"entity": "Se", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [159, 161]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [164, 166]}, {"entity": "K", "entity_type": "Chemical", "pos": [169, 170]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [173, 175]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [178, 180]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [183, 185]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [198, 200]}, {"entity": "Se", "entity_type": "Chemical", "pos": [240, 242]}], "task": "NER"}
{"text": "The presence of Cd could also reverse these decreases especially at the highest treatment levels for both Se and Cd , also suggesting an element regulation mechanism responsible for the detoxification of high dosages of Se .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [16, 18]}, {"entity": "Se", "entity_type": "Chemical", "pos": [106, 108]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [113, 115]}, {"entity": "Se", "entity_type": "Chemical", "pos": [220, 222]}], "task": "NER"}
{"text": "Consequently , when Se is used to alleviate Cd toxicity , attention must be paid to the Cd pollution extent and doses of Se supplement .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [20, 22]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [88, 90]}, {"entity": "Se", "entity_type": "Chemical", "pos": [121, 123]}], "task": "NER"}
{"text": "Diatom frustules as light traps enhance DSSC efficiency .", "entity": [], "task": "NER"}
{"text": "Diatoms are one of the most successful photosynthetic organisms and given the important role that their shells ( frustules ) play in light trapping we explored their use in multilayered materials for application as photoanodes in dye sensitised solar cells ( DSSCs ) .", "entity": [], "task": "NER"}
{"text": "We find a substantial improvement in energy conversion efficiency of 30 % , increasing from 3 . 5 % to 4 . 6 % with diatom incorporation .", "entity": [], "task": "NER"}
{"text": "Involvement of lysosomal exocytosis in the excretion of mesoporous silica nanoparticles and enhancement of the drug delivery effect by exocytosis inhibition .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [67, 73]}], "task": "NER"}
{"text": "The exocytosis of phosphonate modified mesoporous silica nanoparticles ( P - MSNs ) is demonstrated and lysosomal exocytosis is identified as the mechanism responsible for this event .", "entity": [{"entity": "phosphonate", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "silica", "entity_type": "Chemical", "pos": [50, 56]}], "task": "NER"}
{"text": "Regulation of P - MSN exocytosis can be achieved by inhibiting or accelerating lysosomal exocytosis .", "entity": [], "task": "NER"}
{"text": "Slowing down P - MSN exocytosis enhances the drug delivery effect of CPT - loaded P - MSNs by improving cell killing .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "Overexpression of ATP - binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF ( V600E ) mutant cancer cells .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "vemurafenib", "entity_type": "Chemical", "pos": [110, 121]}], "task": "NER"}
{"text": "Melanoma is the most serious type of skin cancer with a high potential for metastasis and very low survival rates .", "entity": [], "task": "NER"}
{"text": "The discovery of constitutive activation of the BRAF kinase caused by activating BRAF ( V600E ) kinase mutation in most melanoma patients led to the discovery of the first potent BRAF ( V600E ) signaling inhibitor , vemurafenib .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [216, 227]}], "task": "NER"}
{"text": "Vemurafenib was effective in treating advanced melanoma patients and was proposed for the treatment of other BRAF ( V600E ) mutant cancers as well .", "entity": [{"entity": "Vemurafenib", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Unfortunately , the success of vemurafenib was hampered by the rapid development of acquired resistance in different types of BRAF ( V600E ) mutant cancer cells .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [31, 42]}], "task": "NER"}
{"text": "It becomes important to identify and evaluate all of the potential mechanisms of cellular resistance to vemurafenib .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [104, 115]}], "task": "NER"}
{"text": "In this study , we characterized the interactions of vemurafenib with three major ATP - binding cassette ( ABC ) transporters , ABCB1 , ABCC1 and ABCG2 .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [53, 64]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "We found that vemurafenib stimulated the ATPase activity and potently inhibited drug efflux mediated by ABCB1 and ABCG2 .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Vemurafenib also restored drug sensitivity in ABCG2 - overexpressing cells .", "entity": [{"entity": "Vemurafenib", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Moreover , we revealed that in the presence of functional ABCG2 , BRAF kinase inhibition by vemurafenib is reduced in BRAF ( V600E ) mutant A375 cells .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [92, 103]}], "task": "NER"}
{"text": "Taken together , our findings indicate that ABCG2 confers resistance to vemurafenib in A375 cells , suggesting involvement of this transporter in acquired resistance to vemurafenib .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [72, 83]}, {"entity": "vemurafenib", "entity_type": "Chemical", "pos": [169, 180]}], "task": "NER"}
{"text": "Thus , combination chemotherapy targeting multiple pathways could be an effective therapeutic strategy to overcome acquired resistance to vemurafenib for cancers harboring the BRAF ( V600E ) mutation .", "entity": [{"entity": "vemurafenib", "entity_type": "Chemical", "pos": [138, 149]}], "task": "NER"}
{"text": "New developments in the pharmacological modulation of wound healing after glaucoma filtration surgery .", "entity": [], "task": "NER"}
{"text": "Despite the advent of many new devices for glaucoma surgery , scarring is the main cause of suboptimal pressure control and surgical failure in all forms of surgery .", "entity": [], "task": "NER"}
{"text": "The cytotoxic antimetabolites , 5 - flurouracil and mitomycin C both prolong success but with the increased risk of blinding complications .", "entity": [{"entity": "5 - flurouracil", "entity_type": "Chemical", "pos": [32, 47]}, {"entity": "mitomycin C", "entity_type": "Chemical", "pos": [52, 63]}], "task": "NER"}
{"text": "A greater understanding of the cellular mechanisms of the wound healing response has led to the identification and modulation of potential therapeutic targets .", "entity": [], "task": "NER"}
{"text": "These include transforming factor beta , inflammatory mediators , the acute phase protein serum amyloid P , vascular endothelial growth factor and the matrix metallaproteinases .", "entity": [], "task": "NER"}
{"text": "While optimal drug delivery is still a major challenge , modulating these effects either directly or through downstream signalling promises to yield anti - scarring efficacy , while minimising side effects .", "entity": [], "task": "NER"}
{"text": "An antioxidant regenerating system for continuous quenching of free radicals in chronic wounds .", "entity": [], "task": "NER"}
{"text": "A novel antioxidant regenerating system consisting of cellobiose dehydrogenase ( CDH ) , cellobiose , and phenolic antioxidants with potential application for continuous quenching of free radical species in chronic wounds was developed .", "entity": [{"entity": "cellobiose", "entity_type": "Chemical", "pos": [54, 64]}, {"entity": "cellobiose", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "This antioxidant regenerating system , continuously quenched in situ produced . NO , O ( 2 ) ( . - ) and OH . radicals and the produced oxidized phenolic antioxidants were regenerated back to their original parent compounds by CDH using cellobiose as electron donor .", "entity": [{"entity": ". NO", "entity_type": "Chemical", "pos": [78, 82]}, {"entity": "O ( 2 ) ( . - )", "entity_type": "Chemical", "pos": [85, 100]}, {"entity": "OH .", "entity_type": "Chemical", "pos": [105, 109]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [145, 153]}, {"entity": "cellobiose", "entity_type": "Chemical", "pos": [237, 247]}], "task": "NER"}
{"text": "This system therefore prevented the accumulation of oxidized phenolic antioxidants .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "Interestingly , this study also challenges the relevance of using total antioxidant capacities values of plant crude extracts obtained using biologically none relevant radical species like ( 2 , 2 - diphenyl - 1 - picrylhydrazyl ( DPPH ) ) , Trolox Equivalent Antioxidant Capacity ( TEAC ) , etc . when applied as medicinal remedies .", "entity": [{"entity": "2 , 2 - diphenyl - 1 - picrylhydrazyl", "entity_type": "Chemical", "pos": [191, 228]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [231, 235]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [242, 248]}], "task": "NER"}
{"text": "This is because methoxylated phenolic antioxidants like sinapic acid , ferulic acid ; 2 , 6 - dimethoxyphenol readily donate their electrons to these radicals ( DPPH , TEAC , etc . ) , thereby greatly influencing the total antioxidant values although this study showed that they are not at all effective in quenching O ( 2 ) ( . - ) radicals and again are not the most effective quenchers of NO and OH radicals as demonstrated during this study .", "entity": [{"entity": "methoxylated phenolic", "entity_type": "Chemical", "pos": [16, 37]}, {"entity": "sinapic acid", "entity_type": "Chemical", "pos": [56, 68]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [71, 83]}, {"entity": "2 , 6 - dimethoxyphenol", "entity_type": "Chemical", "pos": [86, 109]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [161, 165]}, {"entity": "O ( 2 ) ( . - )", "entity_type": "Chemical", "pos": [317, 332]}, {"entity": "NO", "entity_type": "Chemical", "pos": [392, 394]}, {"entity": "OH", "entity_type": "Chemical", "pos": [399, 401]}], "task": "NER"}
{"text": "Combination treatment with progesterone and vitamin D hormone is more effective than monotherapy in ischemic stroke : The role of BDNF / TrkB / Erk1 / 2 signaling in neuroprotection .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "We investigated whether combinatorial post - injury treatment with progesterone ( P4 ) and vitamin D hormone ( VDH ) would reduce ischemic injury more effectively than P4 alone in an oxygen glucose deprivation ( OGD ) model in primary cortical neurons and in a transient middle cerebral artery occlusion ( tMCAO ) model in rats .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [67, 79]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [183, 189]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [190, 197]}], "task": "NER"}
{"text": "In the OGD model , P4 and VDH each showed neuroprotection individually , but combination of the \" best \" doses did not show substantial efficacy ; instead , the lower dose of VDH in combination with P4 was the most effective .", "entity": [], "task": "NER"}
{"text": "In the tMCAO model , P4 and VDH were given alone or in combination at different times post - occlusion for 7 days .", "entity": [], "task": "NER"}
{"text": "In vivo data confirmed the in vitro findings and showed better infarct reduction at day 7 and functional outcomes ( at 3 , 5 and 7 days post - occlusion ) after combinatorial treatment than when either agent was given alone .", "entity": [], "task": "NER"}
{"text": "VDH , but not P4 , upregulated heme oxygenase - 1 , suggesting a pathway for the neuroprotective effects of VDH differing from that of P4 .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "The combination of P4 and VDH activated brain - derived neurotrophic factor and its specific receptor , tyrosine kinase receptor - B .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Under specific conditions VDH potentiates P4 ' s neuroprotective efficacy and should be considered as a potential partner of P4 in a low - cost , safe and effective combinatorial treatment for stroke .", "entity": [], "task": "NER"}
{"text": "The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates intestinal microbiota .", "entity": [{"entity": "hydroxypropyl", "entity_type": "Chemical", "pos": [33, 46]}], "task": "NER"}
{"text": "Diet influences host metabolism and intestinal microbiota ; however , detailed understanding of this tripartite interaction is limited .", "entity": [], "task": "NER"}
{"text": "To determine whether the nonfermentable fiber hydroxypropyl methylcellulose ( HPMC ) could alter the intestinal microbiota and whether such changes correlated with metabolic improvements , C57B / L6 mice were normalized to a high - fat diet ( HFD ) , then either maintained on HFD ( control ) , or switched to HFD supplemented with 10 % HPMC , or a low - fat diet ( LFD ) .", "entity": [{"entity": "hydroxypropyl", "entity_type": "Chemical", "pos": [46, 59]}], "task": "NER"}
{"text": "Compared to control treatment , both LFD and HPMC reduced weight gain ( 11 . 8 and 5 . 7 g , respectively ) , plasma cholesterol ( 23 . 1 and 19 . 6 % ) , and liver triglycerides ( 73 . 1 and 44 . 6 % ) , and , as revealed by 454 - pyrosequencing of the microbial 16S rRNA gene , decreased microbial alpha - diversity and differentially altered intestinal microbiota .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [117, 128]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [165, 178]}], "task": "NER"}
{"text": "Both LFD and HPMC increased intestinal Erysipelotrichaceae ( 7 . 3 - and 12 . 4 - fold ) and decreased Lachnospiraceae ( 2 . 0 - and 2 . 7 - fold ) , while only HPMC increased Peptostreptococcaceae ( 3 . 4 - fold ) and decreased Ruminococcaceae ( 2 . 7 - fold ) .", "entity": [], "task": "NER"}
{"text": "Specific microorganisms were directly linked with weight change and metabolic parameters in HPMC and HFD mice , but not in LFD mice , indicating that the intestinal microbiota may play differing roles during the two dietary modulations .", "entity": [], "task": "NER"}
{"text": "This work indicates that HPMC is a potential prebiotic fiber that influences intestinal microbiota and improves host metabolism .", "entity": [], "task": "NER"}
{"text": "Inhibition of glycogen synthase kinase - 3 ameliorates beta - amyloid pathology and restores lysosomal acidification and mammalian target of rapamycin activity in the Alzheimer disease mouse model : in vivo and in vitro studies .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [141, 150]}], "task": "NER"}
{"text": "Accumulation of beta - amyloid ( A beta ) deposits is a primary pathological feature of Alzheimer disease that is correlated with neurotoxicity and cognitive decline .", "entity": [], "task": "NER"}
{"text": "The role of glycogen synthase kinase - 3 ( GSK - 3 ) in Alzheimer disease pathogenesis has been debated .", "entity": [], "task": "NER"}
{"text": "To study the role of GSK - 3 in A beta pathology , we used 5XFAD mice co - expressing mutated amyloid precursor protein and presenilin - 1 that develop massive cerebral A beta loads .", "entity": [], "task": "NER"}
{"text": "Both GSK - 3 isozymes ( alpha / beta ) were hyperactive in this model .", "entity": [], "task": "NER"}
{"text": "Nasal treatment of 5XFAD mice with a novel substrate competitive GSK - 3 inhibitor , L803 - mts , reduced A beta deposits and ameliorated cognitive deficits .", "entity": [], "task": "NER"}
{"text": "Analyses of 5XFAD hemi - brain samples indicated that L803 - mts restored the activity of mammalian target of rapamycin ( mTOR ) and inhibited autophagy .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [110, 119]}], "task": "NER"}
{"text": "Lysosomal acidification was impaired in the 5XFAD brains as indicated by reduced cathepsin D activity and decreased N - glycoyslation of the vacuolar ATPase subunit V0a1 , a modification required for lysosomal acidification .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [116, 117]}], "task": "NER"}
{"text": "Treatment with L803 - mts restored lysosomal acidification in 5XFAD brains .", "entity": [], "task": "NER"}
{"text": "Studies in SH - SY5Y cells confirmed that GSK - 3 alpha and GSK - 3 beta impair lysosomal acidification and that treatment with L803 - mts enhanced the acidic lysosomal pool as demonstrated in LysoTracker Red - stained cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , L803 - mts restored impaired lysosomal acidification caused by dysfunctional presenilin - 1 .", "entity": [], "task": "NER"}
{"text": "We provide evidence that mTOR is a target activated by GSK - 3 but inhibited by impaired lysosomal acidification and elevation in amyloid precursor protein / A beta loads .", "entity": [], "task": "NER"}
{"text": "Taken together , our data indicate that GSK - 3 is a player in A beta pathology .", "entity": [], "task": "NER"}
{"text": "Inhibition of GSK - 3 restores lysosomal acidification that in turn enables clearance of A beta burdens and reactivation of mTOR .", "entity": [], "task": "NER"}
{"text": "These changes facilitate amelioration in cognitive function .", "entity": [], "task": "NER"}
{"text": "MetalPDB : a database of metal sites in biological macromolecular structures .", "entity": [], "task": "NER"}
{"text": "We present here MetalPDB ( freely accessible at http : / / metalweb . cerm . unifi . it ) , a novel resource aimed at conveying the information available on the three - dimensional ( 3D ) structures of metal - binding biological macromolecules in a consistent and effective manner .", "entity": [], "task": "NER"}
{"text": "This is achieved through the systematic and automated representation of metal - binding sites in proteins and nucleic acids by way of Minimal Functional Sites ( MFSs ) .", "entity": [], "task": "NER"}
{"text": "MFSs are 3D templates that describe the local environment around the metal ( s ) independently of the larger context of the macromolecular structure embedding the site ( s ) , and are the central objects of MetalPDB design .", "entity": [], "task": "NER"}
{"text": "MFSs are grouped into equistructural ( broadly defined as sites found in corresponding positions in similar structures ) and equivalent sites ( equistructural sites that contain the same metals ) , allowing users to easily analyse similarities and variations in metal - macromolecule interactions , and to link them to functional information .", "entity": [], "task": "NER"}
{"text": "The web interface of MetalPDB allows access to a comprehensive overview of metal - containing biological structures , providing a basis to investigate the basic principles governing the properties of these systems .", "entity": [], "task": "NER"}
{"text": "MetalPDB is updated monthly in an automated manner .", "entity": [], "task": "NER"}
{"text": "Influence of coadministration of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative stress indices in female Wistar rats .", "entity": [{"entity": "artemether", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [48, 60]}], "task": "NER"}
{"text": "Among the artemisinin - based combination therapy ( ACT ) regimens , artemisinin derivative , artemether in combination with lumefantrine ( artemether - lumefantrine , AL ) has achieved excellent results in the fight against malarial scourge .", "entity": [{"entity": "artemisinin", "entity_type": "Chemical", "pos": [10, 21]}, {"entity": "artemisinin", "entity_type": "Chemical", "pos": [69, 80]}, {"entity": "artemether", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [125, 137]}, {"entity": "artemether", "entity_type": "Chemical", "pos": [140, 150]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [153, 165]}], "task": "NER"}
{"text": "In this study , we evaluated the toxic potential of these drugs at the therapeutic doses in female Wistar rats .", "entity": [], "task": "NER"}
{"text": "Animals were randomly divided into four groups : those administered 1 % Tween 80 ( control ) , those administered artemether ( 4 mg / kg body weight ) , those administered lumefantrine ( 24 mg / kg body weight ) , and those coadministered artemether ( 4 mg / kg body weight ) and lumefantrine ( 24 mg / kg body weight ) .", "entity": [{"entity": "Tween 80", "entity_type": "Chemical", "pos": [72, 80]}, {"entity": "artemether", "entity_type": "Chemical", "pos": [114, 124]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [172, 184]}, {"entity": "artemether", "entity_type": "Chemical", "pos": [239, 249]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [280, 292]}], "task": "NER"}
{"text": "The drugs were orally administered twice daily for 3 days by gastric intubation after which selected plasma biochemical indices , and erythrocytes antioxidant defence and lipid peroxidation markers were evaluated .", "entity": [], "task": "NER"}
{"text": "Coadministration of artemether and lumefantrine raised liver and renal function markers and increased atherogenic index .", "entity": [{"entity": "artemether", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [35, 47]}], "task": "NER"}
{"text": "While reduced glutathione , glucose - 6 - phosphate dehydrogenase ( G6PD ) and catalase activities were reduced , glutathione peroxidase and glutathione - s - transferase activities increased in all the treated groups compared to the control group .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "glucose - 6 - phosphate", "entity_type": "Chemical", "pos": [28, 51]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [114, 125]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [141, 152]}], "task": "NER"}
{"text": "The drugs caused significant ( p < 0 . 05 ) elevation of malondialdehyde ( MDA ) levels compared to the control group .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [57, 72]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [75, 78]}], "task": "NER"}
{"text": "These results imply that coadministration of artemether and lumefantrine may increase the risks of atherosclerosis as well as liver and renal function impairments in the users .", "entity": [{"entity": "artemether", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "lumefantrine", "entity_type": "Chemical", "pos": [60, 72]}], "task": "NER"}
{"text": "In addition , the drugs may also promote oxidative stress in the erythrocytes .", "entity": [], "task": "NER"}
{"text": "Different fates of Alzheimer ' s disease amyloid - beta fibrils remodeled by biocompatible small molecules .", "entity": [], "task": "NER"}
{"text": "Amyloid fibrils implicated in numerous human diseases are thermodynamically very stable .", "entity": [], "task": "NER"}
{"text": "Stringent conditions that would not be possible in a physiological environment are often required to disrupt the stable fibrils .", "entity": [], "task": "NER"}
{"text": "Recently , there is increasing evidence that small molecules can remodel amyloid fibrils in a physiologically relevant manner .", "entity": [], "task": "NER"}
{"text": "In order to investigate possible fibril remodeling mechanisms using this approach , we performed comparative studies on the structural features of the different amyloid - beta ( A beta ) aggregates remodeled from A beta fibrils by three biocompatible small molecules : methylene blue ; brilliant blue G ; and erythrosine B .", "entity": [{"entity": "methylene blue", "entity_type": "Chemical", "pos": [269, 283]}, {"entity": "brilliant blue G", "entity_type": "Chemical", "pos": [286, 302]}, {"entity": "erythrosine B", "entity_type": "Chemical", "pos": [309, 322]}], "task": "NER"}
{"text": "Combined with circular dichroism ( CD ) , immuno - blotting , transmission electron microscopy ( TEM ) , and atomic force microscopy ( AFM ) results , it was found that brilliant blue G - and erythrosine B - treatment generate fragmented A beta fibrils and protofibrils , respectively .", "entity": [{"entity": "brilliant blue G", "entity_type": "Chemical", "pos": [169, 185]}, {"entity": "erythrosine B", "entity_type": "Chemical", "pos": [192, 205]}], "task": "NER"}
{"text": "In contrast , incubation of the A beta fibrils with methylene blue perturbs fibrillar structure , leading to amorphous A beta aggregates .", "entity": [{"entity": "methylene blue", "entity_type": "Chemical", "pos": [52, 66]}], "task": "NER"}
{"text": "Our findings provide insights on the molecular mechanism of amyloid fibril formation and remodeling and also illustrate the possibility of controlled changes in biomolecule nanostructures .", "entity": [], "task": "NER"}
{"text": "Neurotransmitters , psychotropic drugs and microglia : clinical implications for psychiatry .", "entity": [], "task": "NER"}
{"text": "Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters .", "entity": [], "task": "NER"}
{"text": "Thus , the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [197, 205]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [210, 219]}], "task": "NER"}
{"text": "Recently , microglia , immunological / inflammatory cells in the brain , have been indicated to have positive links to psychiatric disorders .", "entity": [], "task": "NER"}
{"text": "Positron emission tomography ( PET ) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia , depression and autism .", "entity": [], "task": "NER"}
{"text": "Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies .", "entity": [], "task": "NER"}
{"text": "In addition , various psychotropic drugs have been suggested to have direct effects on microglia .", "entity": [], "task": "NER"}
{"text": "Until now , the relationship between microglia , neurotransmitters and psychiatric disorders has not been well understood .", "entity": [], "task": "NER"}
{"text": "Therefore , in this review , at first , we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine , serotonin , norepinephrine , acetylcholine and glutamate .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [132, 140]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [143, 152]}, {"entity": "norepinephrine", "entity_type": "Chemical", "pos": [155, 169]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [172, 185]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [190, 199]}], "task": "NER"}
{"text": "Next , we introduce up - to - date knowledge of the effects of psychotropic drugs such as antipsychotics , antidepressants and antiepileptics on microglial modulation .", "entity": [], "task": "NER"}
{"text": "Finally , we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders .", "entity": [], "task": "NER"}
{"text": "Further investigations and clinical trials should be conducted to clarify this perspective , using animal in vivo studies and imaging studies with human subjects .", "entity": [], "task": "NER"}
{"text": "Recent developments in neurochemical imaging in schizophrenia : an update .", "entity": [], "task": "NER"}
{"text": "The advent of neurochemical brain imaging methods has provided an opportunity to study the neurochemistry of the human brain in normal and abnormal development .", "entity": [], "task": "NER"}
{"text": "The aim of this article is to provide an update on recent major developments in neurochemical imaging in schizophrenia research .", "entity": [], "task": "NER"}
{"text": "In this concise review , we discuss the major findings on three neurotransmitters , namely dopamine , serotonin and glutamate .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [102, 111]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [116, 125]}], "task": "NER"}
{"text": "The most promising radioligand for D ( 2 ) / D ( 3 ) neuroreceptor imaging is the agonist [ ( 11 ) C ] PHNO , with higher in vivo affinity for D ( 3 ) than D ( 2 ) receptors , which can be used to measure amphetamine - induced release of dopamine , and therefore a potential model of dopaminergic alterations in schizophrenia .", "entity": [{"entity": "[ ( 11 ) C ] PHNO", "entity_type": "Chemical", "pos": [90, 107]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [205, 216]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [238, 246]}], "task": "NER"}
{"text": "Recent development of selective radiotracers allow imaging of the serotonin transporter ( SERT ) using positron emission tomography ( PET ) with selective tracers such as [ ( 11 ) C ] DASB .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [66, 75]}, {"entity": "[ ( 11 ) C ] DASB", "entity_type": "Chemical", "pos": [171, 188]}], "task": "NER"}
{"text": "Additionally , the glutamatergic hypothesis has evolved from theory to phase III clinical trials of newer agents with novel mechanisms .", "entity": [], "task": "NER"}
{"text": "With the development of newer radioligands and the in vivo application of magnetic resonance spectroscopy ( MRS ) at relatively high magnetic field strengths , there is ample scope for further neuroimaging advances .", "entity": [], "task": "NER"}
{"text": "Serotonin receptors of type 6 ( 5 - HT6 ) : from neuroscience to clinical pharmacology .", "entity": [{"entity": "Serotonin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The serotonin ( 5 - HT ) receptors of type 6 ( 5 - HT6 ) are quite different from all other 5 - HT receptors , as they include a short third cytoplasmatic loop and a long C - terminal tail , and one intron located in the middle of the third cytoplasmatic loop .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [47, 53]}, {"entity": "C", "entity_type": "Chemical", "pos": [171, 172]}], "task": "NER"}
{"text": "A lot of controversies still exist regarding their binding affinity , effects of 5 - HT6 ligands on brain catecholamines , behavioral syndromes regulated by them , and brain distribution .", "entity": [{"entity": "catecholamines", "entity_type": "Chemical", "pos": [106, 120]}], "task": "NER"}
{"text": "In spite of the lack of information on metabolic pattern of the various compounds , some of 5 - HT6 receptor ligands entered the clinical development as potential anti - dementia , antipsychotic , antidepressant and anti - obese drugs .", "entity": [], "task": "NER"}
{"text": "The present paper is a comprehensive review on the state of art of the 5 - HT6 receptors , while highlighting the potential clinical applications of 5 - HT6 receptor agonists / antagonists .", "entity": [], "task": "NER"}
{"text": "Transcranial brain stimulation in schizophrenia : targeting cortical excitability , connectivity and plasticity .", "entity": [], "task": "NER"}
{"text": "Transcranial magnetic stimulation ( TMS ) is a very popular tool used within neuroscience .", "entity": [], "task": "NER"}
{"text": "This and other associated techniques allow the in vivo investigation of cortical excitability , cortical connectivity and cortical plasticity .", "entity": [], "task": "NER"}
{"text": "Schizophrenia is a brain disorder and various theories other than the dopamine hypothesis have been developed to describe its underlying neurobiology .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [70, 78]}], "task": "NER"}
{"text": "Supported by animal and post mortem studies , findings from TMS studies indicate that schizophrenia is a disease of reduced cortical inhibition and impaired intra - and intercortical connectivity .", "entity": [], "task": "NER"}
{"text": "Further studies using repetitive TMS and other plasticity - inducing techniques have shown that cortical plasticity is altered in schizophrenia patients , supporting the recently discussed plasticity deficiency theory of schizophrenia .", "entity": [], "task": "NER"}
{"text": "This review gives an introduction to the most frequently applied techniques , describes findings in schizophrenia patients and discusses these findings with regard to the neurotransmitters and associated receptors involved .", "entity": [], "task": "NER"}
{"text": "In summary , there is emerging evidence of an important pathophysiological interplay between reduced inhibition , impaired connectivity and reduced plasticity in schizophrenia patients .", "entity": [], "task": "NER"}
{"text": "Gamma - aminobutyric - acid - receptors and glutamtergic N - Methyl - D - aspartic - acid - receptors are most likely to be involved in this complex interplay , which may reflect a disturbed signal - to - noise ratio in schizophrenia patients .", "entity": [{"entity": "Gamma - aminobutyric - acid", "entity_type": "Chemical", "pos": [0, 27]}, {"entity": "N - Methyl - D - aspartic - acid", "entity_type": "Chemical", "pos": [57, 89]}], "task": "NER"}
{"text": "This review will discuss this issue with regard to the available treatment options and will give implications for future research and therapeutic strategies regarding disinhibition and neuroplasticity in schizophrenia .", "entity": [], "task": "NER"}
{"text": "A general approach for combining voxel - based meta - analyses conducted in different neuroimaging modalities .", "entity": [], "task": "NER"}
{"text": "Meta - analyses are useful to summarize the exponential amount of inconsistent and conflicting neuroimaging data .", "entity": [], "task": "NER"}
{"text": "However , they are usually separately conducted for each different neuroimaging modality , preventing the multimodal integration of different imaging findings in a given neuropsychiatric disorder .", "entity": [], "task": "NER"}
{"text": "Here , we describe an innovative method to meta - analytically combine the results of different imaging modalities , such as structural and functional paradigms .", "entity": [], "task": "NER"}
{"text": "The method accounts for the presence of noise in the estimation of the p - values , and can be easily applied to any meta - analytical software .", "entity": [], "task": "NER"}
{"text": "We hope that with this advanced imaging tool , researchers will be able to provide more complete multimodal pictures of the brain regions affected in different neuropsychiatric disorders .", "entity": [], "task": "NER"}
{"text": "Distinct roles of methamphetamine in modulating spatial memory consolidation , retrieval , reconsolidation and the accompanying changes of ERK and CREB activation in hippocampus and prefrontal cortex .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [18, 33]}], "task": "NER"}
{"text": "Drugs of abuse modulated learning and memory in humans yet the underlying mechanism remained unclear .", "entity": [], "task": "NER"}
{"text": "The extracellular signal - regulated kinase ( ERK ) and the transcription factor cAMP response element - binding protein ( CREB ) were involved in neuroplastic changes associated with learning and memory .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "In the current study , we used a Morris water maze to examine the effect of methamphetamine ( METH ) on different processes of spatial memory in mice .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [76, 91]}, {"entity": "METH", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "We then investigated the status of ERK and CREB in the hippocampus and prefrontal cortex ( PFC ) .", "entity": [], "task": "NER"}
{"text": "We found that 1 . 0 mg / kg dose of METH facilitated spatial memory consolidation when it was injected immediately after the last learning trial .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [36, 40]}], "task": "NER"}
{"text": "In contrast , the same dose of METH had no effect on spatial memory retrieval when it was injected 30 min before the test .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "Furthermore , 1 . 0 mg / kg dose of METH injected immediately after retrieval had no effect on spatial memory reconsolidation .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [36, 40]}], "task": "NER"}
{"text": "Activation of both ERK and CREB in the hippocampus was found following memory consolidation but not after retrieval or reconsolidation in METH - treated mouse groups .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [138, 142]}], "task": "NER"}
{"text": "In contrast , activation of both ERK and CREB in the PFC was found following memory retrieval but not other processes in METH - treated mouse groups .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "These results suggested that METH facilitated spatial memory consolidation but not retrieval or reconsolidation .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "Moreover , activation of the ERK and CREB signaling pathway in the hippocampus might be involved in METH - induced spatial memory changes .", "entity": [{"entity": "METH", "entity_type": "Chemical", "pos": [100, 104]}], "task": "NER"}
{"text": "Development of a repeated exposure protocol of human bronchial epithelium in vitro to study the long - term effects of atmospheric particles .", "entity": [], "task": "NER"}
{"text": "Chronic exposure to atmospheric particles is suspected of exacerbating chronic inflammatory respiratory diseases but the underlying mechanisms remain poorly understood .", "entity": [], "task": "NER"}
{"text": "An experimental strategy using human bronchial epithelial cells ( NHBE ) known to be one of the main target cells of particles in the lung was developed to investigate the long term effects of repeated exposure to particles .", "entity": [], "task": "NER"}
{"text": "Primary cultures of NHBE cells were grown at an air - liquid interface and subjected to repeated treatments to particles .", "entity": [], "task": "NER"}
{"text": "Fate of particles , pro inflammatory response and epithelial differentiation were studied during the 5 weeks following the final treatment .", "entity": [], "task": "NER"}
{"text": "Ultrastructural observations revealed the biopersistence of particles in the bronchial epithelium .", "entity": [], "task": "NER"}
{"text": "The expression of cytochrome P450 1A1 , was transiently induced , suggesting that organic compounds could have been metabolized .", "entity": [], "task": "NER"}
{"text": "The release of GM - CSF and IL - 6 ( biomarkers of pro - inflammatory response ) , was induced by particle treatments and was maintained up to 5weeks after treatments .", "entity": [], "task": "NER"}
{"text": "The release of amphiregulin and TGF alpha ( Growth Factor ) was induced after each treatment .", "entity": [], "task": "NER"}
{"text": "The number of cells expressing the mucin MUC5AC , a differentiation marker , was increased in particle - exposed epithelium .", "entity": [], "task": "NER"}
{"text": "The experimental strategy we developed is suitable for investigating in greater depth the long term effects of particles on bronchial epithelial cells repeatedly exposed to atmospheric particles in vitro .", "entity": [], "task": "NER"}
{"text": "Nano and microparticulate chitosan - based systems for antiviral topical delivery .", "entity": [], "task": "NER"}
{"text": "Acyclovir ( ACV ) is one of the drugs of choice for the treatment of epidermal , ocular or systemic herpetic infections .", "entity": [{"entity": "Acyclovir", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ACV", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "Nevertheless , its trans - mucosal limited absorption and the scarce contact time of the formulation with the mucosal surface - especially in the ocular mucosa - constitute a big limitation of the antiviral efficiency .", "entity": [], "task": "NER"}
{"text": "The most effective way to solve these problems is to increase the quantity and the residence time of the drug over the ocular surface .", "entity": [], "task": "NER"}
{"text": "In order to cope with all these requirements , micro - particles ( MPs ) and nano - particles ( NPs ) containing ACV have been developed using cross - linked chitosan with tripolyphosphate ( TPP ) due to the biocompatibility , bio - adhesion ability and the potential power as penetration enhancer of this polymer .", "entity": [{"entity": "ACV", "entity_type": "Chemical", "pos": [113, 116]}, {"entity": "tripolyphosphate", "entity_type": "Chemical", "pos": [172, 188]}, {"entity": "TPP", "entity_type": "Chemical", "pos": [191, 194]}], "task": "NER"}
{"text": "Particles were characterized by Fourier - transformed infrared ( FTIR ) spectroscopy , X - ray diffraction , SEM , Zeta potential and particle size .", "entity": [], "task": "NER"}
{"text": "Encapsulation efficiency and release profiles in flow through diffusion cells were also determined .", "entity": [], "task": "NER"}
{"text": "Besides the Slug Mucosal Irritation ( SMI ) assay has been applied as an alternative to the Draize test to predict the mucosal irritation of the selected formulation .", "entity": [], "task": "NER"}
{"text": "FTIR and X - ray results suggested an electrostatic interaction ACV - Chitosan that made ACV be molecularly dispersed within the polymer matrix .", "entity": [{"entity": "ACV", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "ACV", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Encapsulation efficiency was 75 % for MP and 16 % for NP .", "entity": [], "task": "NER"}
{"text": "Release profiles in flow through diffusion cells were also determined .", "entity": [], "task": "NER"}
{"text": "From the diffusion profiles , it was found that the amounts of ACV effectively diffused in 24h were 30 , 430 and 80 mu g for the ACV solution , MP and NP respectively .", "entity": [{"entity": "ACV", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "ACV", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "SMI results showed that chitosan - based particles induced moderate irritation and mild tissue damage , what supposes that ACV - MP constitute a promising alternative for further development of an antiviral formulation .", "entity": [{"entity": "ACV", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "A novel permeation enhancer : N - succinyl chitosan on the intranasal absorption of isosorbide dinitrate in rats .", "entity": [{"entity": "N - succinyl", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "isosorbide dinitrate", "entity_type": "Chemical", "pos": [84, 104]}], "task": "NER"}
{"text": "The purpose of this paper is to study the potential of N - succinyl chitosan as a novel permeation enhancer for the intranasal absorption of isosorbide dinitrate ( ISDN ) .", "entity": [{"entity": "N - succinyl", "entity_type": "Chemical", "pos": [55, 67]}, {"entity": "isosorbide dinitrate", "entity_type": "Chemical", "pos": [141, 161]}, {"entity": "ISDN", "entity_type": "Chemical", "pos": [164, 168]}], "task": "NER"}
{"text": "A series of N - succinyl chitosan ( NSCS ) with different degree of succinylation ( DS ) and molecular weight were synthesized .", "entity": [{"entity": "N - succinyl", "entity_type": "Chemical", "pos": [12, 24]}], "task": "NER"}
{"text": "An in situ nasal perfusion technique in rats was utilized to investigate the effect of NSCS substitution degree , NSCS molecular weight and concentration on the intranasal absorption of ISDN .", "entity": [{"entity": "ISDN", "entity_type": "Chemical", "pos": [186, 190]}], "task": "NER"}
{"text": "The absorption enhancing effect of NSCS was compared with that of chitosan .", "entity": [], "task": "NER"}
{"text": "It was found that all the NSCS investigated improved the intranasal absorption of ISDN remarkably .", "entity": [{"entity": "ISDN", "entity_type": "Chemical", "pos": [82, 86]}], "task": "NER"}
{"text": "Better promoting effect was observed for 0 . 1 % NSCS 50 ( 63 ) compared with 0 . 5 % chitosan 50 .", "entity": [], "task": "NER"}
{"text": "In nasal ciliotoxicity test , both NSCS and chitosan investigated showed good safety profiles .", "entity": [], "task": "NER"}
{"text": "Thereafter , in vivo studies of the selected formulations were carried out in rats and the pharmacokinetic parameters were calculated and compared with that of intravenous injection .", "entity": [], "task": "NER"}
{"text": "Both in situ and in vivo studies demonstrated that NSCS is more effective than chitosan in promoting intranasal absorption of ISDN .", "entity": [{"entity": "ISDN", "entity_type": "Chemical", "pos": [126, 130]}], "task": "NER"}
{"text": "Taking both absorption enhancing and safety reason into account , we suggest NSCS is a promising intranasal absorption enhancer .", "entity": [], "task": "NER"}
{"text": "Implementation and evaluation of an optical fiber system as novel process monitoring tool during lyophilization .", "entity": [], "task": "NER"}
{"text": "Lyophilization is an important and well - established pharmaceutical drying process .", "entity": [], "task": "NER"}
{"text": "Product temperature is the most critical process parameter during lyophilization as it impacts both product quality and process efficiency .", "entity": [], "task": "NER"}
{"text": "Traditionally , thermocouples ( TCs ) or resistance temperature detectors ( RTDs ) and recently , manometric temperatures measurements ( MTMs ) have been used to monitor the product temperature .", "entity": [], "task": "NER"}
{"text": "But , all of these techniques have several drawbacks .", "entity": [], "task": "NER"}
{"text": "The objective of this study was the implementation and evaluation of an optical fiber system as novel process monitoring tool during lyophilization .", "entity": [], "task": "NER"}
{"text": "Therefore , temperature profiles of mannitol , sucrose , or trehalose were recorded with various prototypes of the optical fiber sensors ( OFSs ) and compared to data obtained with conventional TCs or Pirani / capacitance manometry with respect to the endpoint of primary drying .", "entity": [{"entity": "mannitol", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "sucrose", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "trehalose", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "The OFS allowed easy handling and easy center bottom positioning .", "entity": [], "task": "NER"}
{"text": "Data obtained with the OFS in contact with product were in good agreement with data obtained via TCs or Pirani / capacitance manometry .", "entity": [], "task": "NER"}
{"text": "The OFSs showed significantly higher sensitivity , faster response , and better resolution compared to TCs .", "entity": [], "task": "NER"}
{"text": "This allowed for the detection of additional excipient crystallization events .", "entity": [], "task": "NER"}
{"text": "It was found that force effects on unshielded sensors enabled to detect glass transitions .", "entity": [], "task": "NER"}
{"text": "Three - dimensional temperature profiles were obtained with an OFS helix configuration .", "entity": [], "task": "NER"}
{"text": "The possible integration of a glass fiber with several OFSs in series into the shelf surface enables non - invasive , automatic loading compatible monitoring of the drying process .", "entity": [], "task": "NER"}
{"text": "In conclusion , these advantages turn the novel optical fiber systems into a highly attractive process monitoring tool during lyophilization .", "entity": [], "task": "NER"}
{"text": "Establishment of a triple co - culture in vitro cell models to study intestinal absorption of peptide drugs .", "entity": [], "task": "NER"}
{"text": "In vitro cell culture models for studying oral drug absorption during early stages of drug development have become a useful tool in drug discovery and development , with respect to substance throughput and reproducibility .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to establish an in vitro cellular model based on human colon carcinoma Caco - 2 , mucus - producing HT29 , and Raji B cells in order to design a model that more accurately mimics the small intestinal epithelial layer .", "entity": [], "task": "NER"}
{"text": "Normal oriented model was set up by seeding co - cultures of Caco - 2 and HT29 cells into Transwell filters and maintained under identical conditions following addition of Raji B to the basolateral chamber .", "entity": [], "task": "NER"}
{"text": "Inverted model was set up seeding Caco - 2 and HT29 cells on the basolateral chamber and then transferred in the Transwell device with the epithelial cells facing the basolateral chamber following Raji B addition to the apical compartment .", "entity": [], "task": "NER"}
{"text": "Morphological differences on size and thickness of cell membranes were detected between the models studied by using fluorescence microscopy .", "entity": [], "task": "NER"}
{"text": "On the triple co - culture models , cell membranes were increasing in size and thickness from the Caco - 2 to Caco - 2 / HT29 and Caco - 2 / Raji B . Also , the nuclei seem to be larger than in the other studied models .", "entity": [], "task": "NER"}
{"text": "Insulin permeation was higher on the triple co - culture model when compared to the Caco - 2 / HT29 co - culture model .", "entity": [], "task": "NER"}
{"text": "Also , insulin permeation as mediated by nanoparticles and insulin solution permeation was higher on the normal oriented Caco - 2 / HT29 / Raji B model as compared to the inverted model .", "entity": [], "task": "NER"}
{"text": "Overall , our results suggest that Caco - 2 / HT29 / Raji B triple co - culture normal oriented cellular model may be reliable to obtain a more physiological , functional , and reproducible in vitro model of the intestinal barrier to study protein absorption , both in solution and when delivered by nanocarriers .", "entity": [], "task": "NER"}
{"text": "Triclosan exposure alters postembryonic development in a Pacific tree frog ( Pseudacris regilla ) Amphibian Metamorphosis Assay ( TREEMA ) .", "entity": [{"entity": "Triclosan", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The Amphibian Metamorphosis Assay ( AMA ) , developed for Xenopus laevis , is designed to identify chemicals that disrupt thyroid hormone ( TH ) - mediated biological processes .", "entity": [{"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [122, 137]}], "task": "NER"}
{"text": "We adapted the AMA for use on an ecologically - relevant North American species , the Pacific tree frog ( Pseudacris regilla ) , and applied molecular endpoints to evaluate the effects of the antibacterial agent , triclosan ( TCS ) .", "entity": [{"entity": "triclosan", "entity_type": "Chemical", "pos": [214, 223]}, {"entity": "TCS", "entity_type": "Chemical", "pos": [226, 229]}], "task": "NER"}
{"text": "Premetamorphic ( Gosner stage 26 - 28 ) tadpoles were immersed for 21 days in solvent control , 1 . 5 mu g / L thyroxine ( T ( 4 ) ) , 0 . 3 , 3 and 30 mu g / L ( nominal ) TCS , or combined T ( 4 ) / TCS treatments .", "entity": [{"entity": "thyroxine", "entity_type": "Chemical", "pos": [111, 120]}, {"entity": "TCS", "entity_type": "Chemical", "pos": [173, 176]}, {"entity": "TCS", "entity_type": "Chemical", "pos": [201, 204]}], "task": "NER"}
{"text": "Exposure effects were scored by morphometric ( developmental stage , wet weight , and body , snout - vent and hindlimb lengths ) and molecular ( mRNA abundance using quantitative real time polymerase chain reaction ) criteria .", "entity": [], "task": "NER"}
{"text": "T ( 4 ) treatment alone accelerated development concomitant with altered levels of TH receptors alpha and beta , proliferating cell nuclear antigen , and gelatinase B mRNAs in the brain and tail .", "entity": [], "task": "NER"}
{"text": "We observed TCS - induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development .", "entity": [{"entity": "TCS", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "TCS", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21 .", "entity": [], "task": "NER"}
{"text": "Although TCS alone ( 3 and 30 mu g / L ) was protective against tadpole mortality , this protection was lost in the presence of T ( 4 ) .", "entity": [{"entity": "TCS", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH - mediated development by a common antimicrobial agent .", "entity": [], "task": "NER"}
{"text": "Human paraoxonase double mutants hydrolyze V and G class organophosphorus nerve agents .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [57, 73]}], "task": "NER"}
{"text": "Variants of human paraoxonase 1 ( PON1 ) are being developed as catalytic bioscavengers for the organophosphorus chemical warfare agents ( OP ) .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [96, 112]}], "task": "NER"}
{"text": "It is preferable that the new PON1 variants have broad spectrum hydrolase activities to hydrolyze both G - and V - class OPs .", "entity": [], "task": "NER"}
{"text": "H115W PON1 has shown improvements over wild type PON1 in its capacity to hydrolyze some OP compounds .", "entity": [], "task": "NER"}
{"text": "We improved upon these activities either by substituting a tryptophan ( F347W ) near the putative active site residues for enhanced substrate binding or by reducing a bulky group ( Y71A ) at the periphery of the putative enzyme active site .", "entity": [{"entity": "tryptophan", "entity_type": "Chemical", "pos": [59, 69]}], "task": "NER"}
{"text": "When compared to H115W alone , we found that H115W / Y71A and H115W / F347W maintained VX catalytic efficiency but showed mixed results for the capacity to hydrolyze paraoxon .", "entity": [{"entity": "paraoxon", "entity_type": "Chemical", "pos": [166, 174]}], "task": "NER"}
{"text": "Testing our double mutants against racemic sarin , we observed reduced values of KM for H115W / F347W that modestly improved catalytic efficiency over wild type and H115W .", "entity": [{"entity": "racemic sarin", "entity_type": "Chemical", "pos": [35, 48]}], "task": "NER"}
{"text": "Contrary to previous reports , we show that H115W can hydrolyze soman , and the double mutant H115W / Y71A is nearly 4 - fold more efficient than H115W for paraoxon hydrolysis .", "entity": [{"entity": "soman", "entity_type": "Chemical", "pos": [64, 69]}, {"entity": "paraoxon", "entity_type": "Chemical", "pos": [156, 164]}], "task": "NER"}
{"text": "We also observed modest stereoselectivity for hydrolysis of the P ( - ) stereoisomer of tabun by H115W / F347W .", "entity": [{"entity": "tabun", "entity_type": "Chemical", "pos": [88, 93]}], "task": "NER"}
{"text": "These data demonstrate enhancements made in PON1 for the purpose of developing an improved catalytic bioscavenger to protect cholinesterase against chemical warfare agents .", "entity": [], "task": "NER"}
{"text": "Expression of cAMP - responsive element binding proteins ( CREBs ) in fast - and slow - twitch muscles : A signaling pathway to account for the synaptic expression of collagen - tailed subunit ( ColQ ) of acetylcholinesterase at the rat neuromuscular junction .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "The gene encoding the collagen - tailed subunit ( ColQ ) of acetylcholinesterase ( AChE ) contains two distinct promoters that drive the production of two ColQ mRNAs , ColQ - 1 and ColQ - 1a , in slow - and fast - twitch muscles , respectively .", "entity": [], "task": "NER"}
{"text": "ColQ - 1a is expressed at the neuromuscular junction ( NMJ ) in fast - twitch muscle , and this expression depends on trophic factors supplied by motor neurons signaling via a cAMP - dependent pathway in muscle .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [176, 180]}], "task": "NER"}
{"text": "To further elucidate the molecular basis of ColQ - 1a ' s synaptic expression , here we investigated the expression and localization of cAMP - responsive element binding protein ( CREB ) at the synaptic and extra - synaptic regions of fast - and slow - twitch muscles from adult rats .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [136, 140]}], "task": "NER"}
{"text": "The total amount of active , phosphorylated CREB ( P - CREB ) present in slow - twitch soleus muscle was higher than that in fast - twitch tibialis muscle , but P - CREB was predominantly expressed in the fast - twitch muscle at NMJs .", "entity": [], "task": "NER"}
{"text": "In contrast , P - CREB was detected in both synaptic and extra - synaptic regions of slow - twitch muscle .", "entity": [], "task": "NER"}
{"text": "These results reveal , for the first time , the differential distribution of P - CREB in fast - and slow - twitch muscles , which might support the crucial role of cAMP - dependent signaling in controlling the synapse - specific expression of ColQ - 1a in fast - twitch muscles .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [164, 168]}], "task": "NER"}
{"text": "The determination of exogenous formaldehyde in blood of rats during and after inhalation exposure .", "entity": [{"entity": "formaldehyde", "entity_type": "Chemical", "pos": [31, 43]}], "task": "NER"}
{"text": "Formaldehyde ( FA ) is suspected of being associated with the development of leukemia .", "entity": [{"entity": "Formaldehyde", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "An inhalation experiment with FA was performed in rats to study whether FA can enter the blood and could thus cause systemic toxicity in remote tissues such as the bone marrow .", "entity": [], "task": "NER"}
{"text": "Therefore , a sophisticated analytical method was developed to detect blood concentrations of FA during and after single 6 - h exposure by inhalation .", "entity": [], "task": "NER"}
{"text": "In order to differentiate between exogenous and endogenous FA the rats were exposed to stable isotope ( ( 13 ) C ) labeled FA by inhalation .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "During and after exposure of the rats to ( 13 ) C - FA their blood was analyzed to determine the ratio between labeled and natural FA in blood and the total blood concentration of FA .", "entity": [{"entity": "( 13 ) C - FA", "entity_type": "Chemical", "pos": [41, 54]}], "task": "NER"}
{"text": "With respect to sensitivity , with the applied method exogenous ( 13 ) C - FA could have been detected in blood at a concentration approximately 1 . 5 % of the endogenous FA blood concentration .", "entity": [{"entity": "( 13 ) C - FA", "entity_type": "Chemical", "pos": [64, 77]}], "task": "NER"}
{"text": "Exogenous ( 13 ) C - FA was not detectable in the blood of rats either during or up to 30 min after the exposure .", "entity": [{"entity": "( 13 ) C - FA", "entity_type": "Chemical", "pos": [10, 23]}], "task": "NER"}
{"text": "It was concluded that the inhalation of ( 13 ) C - FA at 10 ppm for 6h did not result in an increase of the total FA concentration in blood .", "entity": [{"entity": "( 13 ) C - FA", "entity_type": "Chemical", "pos": [40, 53]}], "task": "NER"}
{"text": "Analysis of microRNA and gene expression profiling in triazole fungicide - treated HepG2 cell line .", "entity": [{"entity": "triazole", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "MicroRNA ( miRNA ) plays an important role in various diseases and in cellular and molecular responses to toxicants .", "entity": [], "task": "NER"}
{"text": "In the present study , we investigated differential expression of miRNAs in response to three triazole fungicides ( myclobutanil , propiconazole , and triadimefon ) .", "entity": [{"entity": "triazole", "entity_type": "Chemical", "pos": [94, 102]}, {"entity": "myclobutanil", "entity_type": "Chemical", "pos": [116, 128]}, {"entity": "propiconazole", "entity_type": "Chemical", "pos": [131, 144]}, {"entity": "triadimefon", "entity_type": "Chemical", "pos": [151, 162]}], "task": "NER"}
{"text": "The human hepatoma cell line ( HepG2 ) was treated with the above triazoles for 3 h or 48 h .", "entity": [{"entity": "triazoles", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "miRNA - based microarray experiments were carried out using the Agilent human miRNA v13 array .", "entity": [], "task": "NER"}
{"text": "At early exposure ( 3h ) , six miRNAs were differentially expressed and at late exposure ( 48 h ) , three miRNAs were significantly expressed .", "entity": [], "task": "NER"}
{"text": "Overall , this study provides an array of potential biomarkers for the above triazole fungicides .", "entity": [{"entity": "triazole", "entity_type": "Chemical", "pos": [77, 85]}], "task": "NER"}
{"text": "Furthermore , these miRNAs induced by triazoles could be the foundation for the development of a miRNA - based toxic biomarker library that can predict environmental toxicity .", "entity": [{"entity": "triazoles", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "Hydroxysafflor yellow a inhibits lipopolysaccharide - induced inflammatory signal transduction in human alveolar epithelial A549 cells .", "entity": [{"entity": "Hydroxysafflor yellow a", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "Hydroxysafflor yellow A ( HSYA ) is an active ingredient obtained from the flower of Carthamus tinctorius L .", "entity": [{"entity": "Hydroxysafflor yellow A", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "HSYA", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "The present study investigated the effects of HSYA on lipopolysaccharide ( LPS ) - induced inflammatory signal transduction in human alveolar epithelial A549 cells .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "A549 cells stimulated with LPS were incubated with three doses of HSYA ( 1 , 4 and 16 mu mol / L ) .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [66, 70]}], "task": "NER"}
{"text": "HSYA suppressed the expression of TLR - 4 , Myd88 , ICAM - 1 , TNF alpha , IL - 1 beta and IL - 6 at the mRNA and protein level , and inhibited the adhesion of leukocytes to A549 cells .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "HSYA treatment also decreased NF - kappa B p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen - activated protein kinase ( p38 MAPK ) .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "These findings suggest that HSYA effectively inhibits LPS - induced inflammatory signal transduction in A549 cells .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "CD36 homolog divergence is responsible for the selectivity of carotenoid species migration to the silk gland of the silkworm Bombyx mori .", "entity": [], "task": "NER"}
{"text": "Dietary carotenoids are absorbed in the intestine and delivered to various tissues by circulating lipoproteins ; however , the mechanism underlying selective delivery of different carotenoid species to individual tissues remains elusive .", "entity": [], "task": "NER"}
{"text": "The products of the Yellow cocoon ( C ) gene and the Flesh ( F ) gene of the silkworm Bombyx mori determine the selectivity for transport of lutein and beta - carotene , respectively , to the silk gland .", "entity": [{"entity": "lutein", "entity_type": "Chemical", "pos": [141, 147]}, {"entity": "beta - carotene", "entity_type": "Chemical", "pos": [152, 167]}], "task": "NER"}
{"text": "We previously showed that the C gene encodes Cameo2 , a CD36 family member , which is thought to function as a transmembrane lipoprotein receptor .", "entity": [], "task": "NER"}
{"text": "Here , we elucidated the molecular identity of the F gene product by positional cloning , as SCRB15 , a paralog of Cameo2 with 26 % amino acid identity .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [132, 142]}], "task": "NER"}
{"text": "In the F mutant , SCRB15 mRNA structure was severely disrupted , due to a 1 . 4 kb genomic insertion in a coding exon .", "entity": [], "task": "NER"}
{"text": "Transgenic expression of SCRB15 in the middle silk gland using the binary GAL4 - UAS expression system enhanced selective beta - carotene uptake by the middle silk gland , while transgenic expression of Cameo2 enhanced selective lutein uptake under the same GAL4 driver .", "entity": [{"entity": "beta - carotene", "entity_type": "Chemical", "pos": [122, 137]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [229, 235]}], "task": "NER"}
{"text": "Our findings indicate that divergence of genes in the CD36 family determines the selectivity of carotenoid species uptake by silk gland tissue and that CD36 - homologous proteins can discriminate among carotenoid species .", "entity": [], "task": "NER"}
{"text": "Emergence of superconductivity from the dynamically heterogeneous insulating state in La ( 2 - x ) Sr ( x ) CuO4 .", "entity": [{"entity": "La ( 2 - x ) Sr ( x ) CuO4", "entity_type": "Chemical", "pos": [86, 112]}], "task": "NER"}
{"text": "A central issue for copper oxides is the nature of the insulating ground state at low carrier densities and the emergence of high - temperature superconductivity from that state with doping .", "entity": [{"entity": "copper oxides", "entity_type": "Chemical", "pos": [20, 33]}], "task": "NER"}
{"text": "Even though this superconductor - insulator transition ( SIT ) is a zero - temperature transition , measurements are not usually carried out at low temperatures .", "entity": [], "task": "NER"}
{"text": "Here we use magnetoresistance to probe both the insulating state at very low temperatures and the presence of superconducting fluctuations in La ( 2 - x ) Sr ( x ) CuO ( 4 ) films , for doping levels that range from the insulator to the superconductor ( x = 0 . 03 - 0 . 08 ) .", "entity": [{"entity": "La ( 2 - x ) Sr ( x ) CuO ( 4 )", "entity_type": "Chemical", "pos": [142, 173]}], "task": "NER"}
{"text": "We observe that the charge glass behaviour , characteristic of the insulating state , is suppressed with doping , but it coexists with superconducting fluctuations that emerge already on the insulating side of the SIT .", "entity": [], "task": "NER"}
{"text": "The unexpected quenching of the superconducting fluctuations by the competing charge order at low temperatures provides a new perspective on the mechanism for the SIT .", "entity": [], "task": "NER"}
{"text": "M1 . 3 - - a small scaffold for DNA origami .", "entity": [], "task": "NER"}
{"text": "The DNA origami method produces programmable nanoscale objects that form when one long scaffold strand hybridizes to numerous oligonucleotide staple strands .", "entity": [], "task": "NER"}
{"text": "One scaffold strand is dominating the field : M13mp18 , a bacteriophage - derived vector 7249 nucleotides in length .", "entity": [{"entity": "nucleotides", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "The full - length M13 is typically folded by using over 200 staple oligonucleotides .", "entity": [], "task": "NER"}
{"text": "Here we report the convenient preparation of a 704 nt fragment dubbed \" M1 . 3 \" as a linear or cyclic scaffold and the assembly of small origami structures with just 15 - 24 staple strands .", "entity": [], "task": "NER"}
{"text": "A typical M1 . 3 origami is large enough to be visualized by TEM , but small enough to show a cooperativity in its assembly and thermal denaturation that is reminiscent of oligonucleotide duplexes .", "entity": [], "task": "NER"}
{"text": "Due to its medium size , M1 . 3 origami with globally modified staples is affordable .", "entity": [], "task": "NER"}
{"text": "As a proof of principle , two origami structures with globally 5 ' - capped staples were prepared and were shown to give higher UV - melting points than the corresponding assembly with unmodified DNA .", "entity": [], "task": "NER"}
{"text": "M1 . 3 has the size of a gene , not a genome , and may function as a model for gene - based nanostructures .", "entity": [], "task": "NER"}
{"text": "Small origami with M1 . 3 as a scaffold may serve as a workbench for chemical , physical , and biological experiments .", "entity": [], "task": "NER"}
{"text": "RBCK1 , an E3 ubiquitin ligase , interacts with and ubiquinates the human pregnane X receptor .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "The pregnane X receptor ( PXR , NR1I2 ) plays a pivotal role in the disposition and detoxification of numerous foreign and endogenous chemicals by increasing transcription of numerous target genes , including phase I and II drug - metabolizing enzymes and transporters .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "In the present study , yeast two - hybrid screening identified an E3 ubiquitin ligase , RBCK1 ( Ring - B - box - coiled - coil protein interacting with protein kinase C - 1 ) , as a human pregnane X receptor ( hPXR ) - interacting protein .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [188, 196]}], "task": "NER"}
{"text": "Coimmunoprecipitation studies confirmed the interaction between RBCK1 and hPXR when both were ectopically expressed in AD - 293 cells .", "entity": [], "task": "NER"}
{"text": "Domain mapping studies showed that the interaction between RBCK1 and hPXR involves all RBCK1 domains .", "entity": [], "task": "NER"}
{"text": "We further demonstrate that RBCK1 ubiquitinates hPXR , and this may target hPXR for degradation by the ubiquitin - proteasome pathway .", "entity": [], "task": "NER"}
{"text": "Simultaneous ectopic overexpression of RBCK1 and PXR decreased PXR levels in AD - 293 cells , and this decrease was inhibited by the proteasomal inhibitor MG - 132 ( carbobenzoxy - Leu - Leu - leucinal ) .", "entity": [{"entity": "MG - 132", "entity_type": "Chemical", "pos": [155, 163]}, {"entity": "carbobenzoxy - Leu - Leu - leucinal", "entity_type": "Chemical", "pos": [166, 201]}], "task": "NER"}
{"text": "Furthermore , overexpression of RBCK1 decreased endogenous levels of PXR in HepG2 cells .", "entity": [], "task": "NER"}
{"text": "Of importance , ectopic overexpression and silencing of endogenous RBCK1 in primary human hepatocytes resulted in a decrease and increase , respectively , in endogenous PXR protein levels and in the induction of PXR target genes by rifampicin .", "entity": [{"entity": "rifampicin", "entity_type": "Chemical", "pos": [232, 242]}], "task": "NER"}
{"text": "These results suggest that RBCK1 is important for the ubiquitination of PXR and may play a role in its proteasomal degradation .", "entity": [], "task": "NER"}
{"text": "The effect of C - vacancy on hydrogen storage and characterization of H2 modes on Ti functionalized C60 fullerene a first principles study .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [14, 15]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "H2", "entity_type": "Chemical", "pos": [70, 72]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [82, 84]}, {"entity": "C60 fullerene", "entity_type": "Chemical", "pos": [100, 113]}], "task": "NER"}
{"text": "Density functional theory calculations were performed to examine the effect of a C vacancy on the physisorption of H ( 2 ) onto Ti - functionalized C ( 60 ) fullerene when H ( 2 ) is oriented along the x - , y - , and z - axes of the fullerene .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [81, 82]}, {"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [115, 122]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [128, 130]}, {"entity": "C ( 60 ) fullerene", "entity_type": "Chemical", "pos": [148, 166]}, {"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [172, 179]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [234, 243]}], "task": "NER"}
{"text": "The effect of the C vacancy on the physisorption modes of H ( 2 ) was investigated as a function of H ( 2 ) binding energy within the energy window ( - 0 . 2 to - 0 . 6 eV ) targeted by the Department of Energy ( DOE ) , and as functions of a variety of other physicochemical properties .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [18, 19]}, {"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "The results indicate that the preferential orientations of H ( 2 ) in the defect - free ( i . e . , no C vacancy ) C ( 60 ) TiH ( 2 ) complex are along the x - and y - axes of C ( 60 ) ( with adsorption energies of - 0 . 23 and - 0 . 21 eV , respectively ) , making these orientations the most suitable ones for hydrogen storage , in contrast to the results obtained for defect - containing fullerenes .", "entity": [{"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "C", "entity_type": "Chemical", "pos": [103, 104]}, {"entity": "C ( 60 ) TiH ( 2 )", "entity_type": "Chemical", "pos": [115, 133]}, {"entity": "C ( 60 )", "entity_type": "Chemical", "pos": [176, 184]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [312, 320]}], "task": "NER"}
{"text": "The defect - containing ( i . e . , containing a C vacancy ) C ( 59 ) TiH ( 2 ) complex do not exhibit adsorption energies within the targeted energy range .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [49, 50]}, {"entity": "C ( 59 ) TiH ( 2 )", "entity_type": "Chemical", "pos": [61, 79]}], "task": "NER"}
{"text": "Charge transfer occurs from Ti 3d to C 2p of the fullerene .", "entity": [{"entity": "Ti", "entity_type": "Chemical", "pos": [28, 30]}, {"entity": "C", "entity_type": "Chemical", "pos": [37, 38]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "The binding of H ( 2 ) is dominated by the pairwise support - metal interaction energy E ( i ) ( Cn . . . Ti ) , and the role of the fullerene is not restricted to supporting the metal .", "entity": [{"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [15, 22]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [106, 108]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [133, 142]}], "task": "NER"}
{"text": "The C vacancy enhances the adsorption energy of Ti , in contrast to that of H ( 2 ) .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [48, 50]}, {"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "A significant reduction in the energy gap of the pristine C ( 60 ) fullerene is observed when TiH ( 2 ) is adsorbed by it .", "entity": [{"entity": "C ( 60 ) fullerene", "entity_type": "Chemical", "pos": [58, 76]}, {"entity": "TiH ( 2 )", "entity_type": "Chemical", "pos": [94, 103]}], "task": "NER"}
{"text": "While the C ( n ) fullerene readily participates in nucleophilic processes , the adjacent TiH ( 2 ) fragment is available for electrophilic processes .", "entity": [{"entity": "C ( n ) fullerene", "entity_type": "Chemical", "pos": [10, 27]}, {"entity": "TiH ( 2 )", "entity_type": "Chemical", "pos": [90, 99]}], "task": "NER"}
{"text": "Functional characterization of three mouse formyl peptide receptors .", "entity": [{"entity": "formyl", "entity_type": "Chemical", "pos": [43, 49]}], "task": "NER"}
{"text": "The evolutionary relationship and functional correlation between human formyl peptide receptors ( FPRs ) and their mouse counterparts remain incompletely understood .", "entity": [{"entity": "formyl", "entity_type": "Chemical", "pos": [71, 77]}], "task": "NER"}
{"text": "We examined three members of the mouse formyl peptide receptor subfamily ( mFprs ) and found that they differ in agonist preference and cellular distributions .", "entity": [{"entity": "formyl", "entity_type": "Chemical", "pos": [39, 45]}], "task": "NER"}
{"text": "When stably expressed in transfected rat basophilic leukemia ( RBL - 2H3 ) cells , mFpr1 was readily activated by N - formylated peptides derived from Listeria monocytogenes ( fMIVTLF ) , Staphylococcus aureus ( fMIFL ) , and mitochondria ( fMMYALF ) .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [114, 115]}], "task": "NER"}
{"text": "In contrast , the Escherichia coli - derived fMLF was 1000 - fold less potent .", "entity": [], "task": "NER"}
{"text": "The aforementioned peptides were much less efficacious at mFpr2 , which responded better to the synthetic hexapeptide WKYMVm , the synthetic agonists Quin - C1 ( a substituted quinazolinone ) , and compound 43 ( a nitrosylated pyrazolone derivative ) .", "entity": [{"entity": "hexapeptide", "entity_type": "Chemical", "pos": [106, 117]}, {"entity": "Quin - C1", "entity_type": "Chemical", "pos": [150, 159]}, {"entity": "quinazolinone", "entity_type": "Chemical", "pos": [176, 189]}, {"entity": "nitrosylated pyrazolone", "entity_type": "Chemical", "pos": [214, 237]}], "task": "NER"}
{"text": "Saturation binding assays showed that mFpr1 and mFpr2 were expressed at similar levels on the cell surface , although their affinity for N - formyl - Met - Leu - Phe - Ile - Ile - Lys - fluorescein isothiocyanate varied by more than 1000 - fold [ dissociation constant ( K ( d ) ) values of 2 . 8 nM for mFpr1 and 4 . 8 mu M for mFpr2 ] ) .", "entity": [{"entity": "N - formyl - Met - Leu - Phe - Ile - Ile - Lys - fluorescein isothiocyanate", "entity_type": "Chemical", "pos": [137, 212]}], "task": "NER"}
{"text": "Contrary to these receptors , mFpr - rs1 responded poorly to all the previously mentioned peptides that were tested .", "entity": [], "task": "NER"}
{"text": "Fluorescent microscopy revealed an intracellular distribution pattern of mFpr - rs1 .", "entity": [], "task": "NER"}
{"text": "On the basis of these results , we conclude that mFpr1 is an ortholog of human FPR1 with certain pharmacologic properties of human FPR2 / ALX , whereas mFpr2 has much lower affinity for formyl peptides .", "entity": [{"entity": "formyl", "entity_type": "Chemical", "pos": [186, 192]}], "task": "NER"}
{"text": "The intracellular distribution of mFpr - rs1 suggests an evolutionary correlation with human FPR3 .", "entity": [], "task": "NER"}
{"text": "The role of voltage - gated potassium channels Kv2 . 1 and Kv2 . 2 in the regulation of insulin and somatostatin release from pancreatic islets .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [28, 37]}], "task": "NER"}
{"text": "The voltage - gated potassium channels Kv2 . 1 and Kv2 . 2 are highly expressed in pancreatic islets , yet their contribution to islet hormone secretion is not fully understood .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [20, 29]}], "task": "NER"}
{"text": "Here we investigate the role of Kv2 channels in pancreatic islets using a combination of genetic and pharmacologic approaches .", "entity": [], "task": "NER"}
{"text": "Pancreatic beta - cells from Kv2 . 1 ( - / - ) mice possess reduced Kv current and display greater glucose - stimulated insulin secretion ( GSIS ) relative to WT beta - cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "Inhibition of Kv2 . x channels with selective peptidyl [ guangxitoxin - 1E ( GxTX - 1E ) ] or small molecule ( RY796 ) inhibitors enhances GSIS in isolated wild - type ( WT ) mouse and human islets , but not in islets from Kv2 . 1 ( - / - ) mice .", "entity": [{"entity": "RY796", "entity_type": "Chemical", "pos": [111, 116]}], "task": "NER"}
{"text": "However , in WT mice neither inhibitor improved glucose tolerance in vivo .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [48, 55]}], "task": "NER"}
{"text": "GxTX - 1E and RY796 enhanced somatostatin release in isolated human and mouse islets and in situ perfused pancreata from WT and Kv2 . 1 ( - / - ) mice .", "entity": [{"entity": "RY796", "entity_type": "Chemical", "pos": [14, 19]}, {"entity": "somatostatin", "entity_type": "Chemical", "pos": [29, 41]}], "task": "NER"}
{"text": "Kv2 . 2 silencing in mouse islets by adenovirus - small hairpin RNA ( shRNA ) specifically enhanced islet somatostatin , but not insulin , secretion .", "entity": [{"entity": "somatostatin", "entity_type": "Chemical", "pos": [106, 118]}], "task": "NER"}
{"text": "In mice lacking somatostatin receptor 5 , GxTX - 1E stimulated insulin secretion and improved glucose tolerance .", "entity": [{"entity": "somatostatin", "entity_type": "Chemical", "pos": [16, 28]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Collectively , these data show that Kv2 . 1 regulates insulin secretion in beta - cells and Kv2 . 2 modulates somatostatin release in delta - cells .", "entity": [{"entity": "somatostatin", "entity_type": "Chemical", "pos": [110, 122]}], "task": "NER"}
{"text": "Development of selective Kv2 . 1 inhibitors without cross inhibition of Kv2 . 2 may provide new avenues to promote GSIS for the treatment of type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Effects of a bioassay - derived ivermectin lowest observed effect concentration on life - cycle traits of the nematode Caenorhabditis elegans .", "entity": [{"entity": "ivermectin", "entity_type": "Chemical", "pos": [32, 42]}], "task": "NER"}
{"text": "The pharmaceutical ivermectin is used to treat parasitic infections , such as those caused by nematodes .", "entity": [{"entity": "ivermectin", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "While several studies have demonstrated the severe effects of ivermectin on non - target organisms , little is known about the drug ' s impact on free - living nematodes .", "entity": [{"entity": "ivermectin", "entity_type": "Chemical", "pos": [62, 72]}], "task": "NER"}
{"text": "In the present work , a full life - cycle experiment was conducted to estimate how an ivermectin lowest observed effect concentration derived from a Caenorhabditis elegans bioassay ( endpoint reproduction ) might translate into effects at the population level of this free - living nematode .", "entity": [{"entity": "ivermectin", "entity_type": "Chemical", "pos": [86, 96]}], "task": "NER"}
{"text": "The results showed that fecundity decreased to levels similar to those determined in the bioassay after a time of corresponding duration ( 18 . 6 % inhibition compared to the control ) , but the impact then rather weakened until the end of the experiment , at which point the net reproductive rate ( R ( 0 ) ) was still , but not significantly , reduced by 12 . 4 % .", "entity": [], "task": "NER"}
{"text": "Moreover , the average lifespan , length of the reproductive period , maximum daily reproduction rate , and intrinsic rate of increase ( r ( m ) ) were significantly reduced by 30 . 0 , 25 . 9 , 11 . 2 , and 3 . 5 % , respectively .", "entity": [], "task": "NER"}
{"text": "The experiment revealed that a 4 - day bioassay is protective enough for C . elegans with respect to ivermectin ' s effects on fecundity .", "entity": [{"entity": "ivermectin", "entity_type": "Chemical", "pos": [101, 111]}], "task": "NER"}
{"text": "However , the pronounced effects of a low drug concentration on survival , a highly elastic trait , may better account for the observed population - level response , i . e . , a decrease of r ( m ) , than the effects on fecundity .", "entity": [], "task": "NER"}
{"text": "These results emphasize that full life - cycle experiments are valuable for assessment of pollutants , because the effects on several life - cycle traits can be simultaneously measured and integrated into an ecologically relevant parameter , the population growth rate , that reflects a population ' s response to a specific pollutant .", "entity": [], "task": "NER"}
{"text": "Interspecific effects of 4A - DNT ( 4 - amino - 2 , 6 - dinitrotoluene ) and RDX ( 1 , 3 , 5 - trinitro - 1 , 3 , 5 - triazine ) in Japanese quail , Northern bobwhite , and Zebra finch .", "entity": [{"entity": "4A - DNT", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "4 - amino - 2 , 6 - dinitrotoluene", "entity_type": "Chemical", "pos": [36, 70]}, {"entity": "RDX", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "1 , 3 , 5 - trinitro - 1 , 3 , 5 - triazine", "entity_type": "Chemical", "pos": [83, 126]}], "task": "NER"}
{"text": "The purpose of this study was to assess the toxicological effects of two munition compounds , 4 - amino - 2 , 6 - dinitrotoluene ( 4A - DNT ) and 1 , 3 , 5 - trinitro - 1 , 3 , 5 - triazine ( RDX ) , on three different bird species : two common toxicological model species - the Northern Bobwhite ( Colinus virginianus ) and the Japanese Quail ( Coturnix japonica ) , and a representative passerine - the Zebra Finch ( Taeniopygia guttata ) .", "entity": [{"entity": "4 - amino - 2 , 6 - dinitrotoluene", "entity_type": "Chemical", "pos": [94, 128]}, {"entity": "4A - DNT", "entity_type": "Chemical", "pos": [131, 139]}, {"entity": "1 , 3 , 5 - trinitro - 1 , 3 , 5 - triazine", "entity_type": "Chemical", "pos": [146, 189]}, {"entity": "RDX", "entity_type": "Chemical", "pos": [192, 195]}], "task": "NER"}
{"text": "Bobwhite were exposed to 4A - DNT at 0 , 8 , 15 , 30 , 60 , or 150 mg / kg body weight ( bw ) d by oral gavage for seven days ; because the high dose of 4A - DNT was lethal to bobwhite , the maximum dose was changed to 100 mg / kg bw d for Japanese quail and finches to ensure tissue could be used for future toxicogenomic work .", "entity": [{"entity": "4A - DNT", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "4A - DNT", "entity_type": "Chemical", "pos": [153, 161]}], "task": "NER"}
{"text": "RDX was similarly administered at 0 , 0 . 5 , 1 . 5 , 3 , 6 , or 12 mg / kg bw d .", "entity": [{"entity": "RDX", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Blood was drawn prior to euthanasia for blood cellularity and chemistry analyses .", "entity": [], "task": "NER"}
{"text": "Finches were clearly least affected by 4A - DNT as evidenced by a lack of observable effects .", "entity": [{"entity": "4A - DNT", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "Bobwhite appeared to be the most sensitive species to 4A - DNT as observed through changes in blood cellularity and plasma chemistry effects .", "entity": [{"entity": "4A - DNT", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "Bobwhite appeared to be more sensitive to RDX than Japanese Quail due to increased effects on measures of plasma chemistries .", "entity": [{"entity": "RDX", "entity_type": "Chemical", "pos": [42, 45]}], "task": "NER"}
{"text": "Finches exhibited the greatest sensitivity to RDX through increased mortality and seizure activity .", "entity": [{"entity": "RDX", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "This study suggests that sensitivity among species is chemical - specific and provides data that could be used to refine current avian sensitivity models used in ecological risk assessments .", "entity": [], "task": "NER"}
{"text": "Ilexpublesnins C - M , eleven new triterpene saponins from the roots of Ilex pubescens .", "entity": [{"entity": "Ilexpublesnins C - M", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [34, 53]}], "task": "NER"}
{"text": "Eleven new triterpene saponins , ilexpublesnins C - M ( 1 - 11 ) , along with ten known analogues were isolated from the roots of Ilex pubescens .", "entity": [{"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [11, 30]}, {"entity": "ilexpublesnins C - M", "entity_type": "Chemical", "pos": [33, 53]}], "task": "NER"}
{"text": "Their structures were elucidated on the basis of extensive spectroscopic analysis , including 1D and 2D NMR experiments .", "entity": [], "task": "NER"}
{"text": "Compounds 1 , 2 , 10 , and 11 contain a 24 - aldehyde , which is rare for triterpene saponins from Ilex .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [45, 53]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [74, 93]}], "task": "NER"}
{"text": "These compounds were evaluated in vitro for their cytotoxic effects on human cancer cell lines HepG2 , HLE , BEL7402 , BEL7403 , BEL7405 , MCF - 7 , and HeLa .", "entity": [], "task": "NER"}
{"text": "Among them , only compounds 6 and 19 showed cytotoxicity against the MCF - 7 cell line [ inhibition ( % ) : 33 . 14 and 34 . 03 , respectively ] .", "entity": [], "task": "NER"}
{"text": "Two - stage metal - catalyst - free growth of high - quality polycrystalline graphene films on silicon nitride substrates .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "silicon nitride", "entity_type": "Chemical", "pos": [95, 110]}], "task": "NER"}
{"text": "By using two - stage , metal - catalyst - free chemical vapor deposition ( CVD ) , it is demonstrated that high - quality polycrystalline graphene films can directly grow on silicon nitride substrates .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [138, 146]}, {"entity": "silicon nitride", "entity_type": "Chemical", "pos": [174, 189]}], "task": "NER"}
{"text": "The carrier mobility can reach about 1500 cm ( 2 ) V ( - 1 ) s ( - 1 ) , which is about three times the value of those grown on SiO ( 2 ) / Si substrates , and also is better than some examples of metal - catalyzed graphene , reflecting the good quality of the graphene lattice .", "entity": [{"entity": "SiO ( 2 )", "entity_type": "Chemical", "pos": [128, 137]}, {"entity": "Si", "entity_type": "Chemical", "pos": [140, 142]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [215, 223]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [261, 269]}], "task": "NER"}
{"text": "Relationship of land use and elevated ionic strength in Appalachian watersheds .", "entity": [], "task": "NER"}
{"text": "Coal mining activities have been implicated as sources that increase stream specific conductance in Central Appalachia .", "entity": [{"entity": "Coal", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The present study characterized potential sources of elevated ionic strength for small subwatersheds within the Coal , Upper Kanawha , Gauley , and New Rivers in West Virginia .", "entity": [{"entity": "Coal", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "From a large monitoring data set developed by the West Virginia Department of Environmental Protection , 162 < 20 - km ( 2 ) - watersheds were identified that had detailed land cover information in southwestern West Virginia with at least one water chemistry sample .", "entity": [], "task": "NER"}
{"text": "Scatter plots of specific conductance were generated for nine land cover classifications : open water , agriculture , forest , residential , barren , total mining , valley fill , abandoned mine lands , and mining excluding valley fill and abandoned mine lands .", "entity": [], "task": "NER"}
{"text": "Conductivity was negatively correlated with the percentage of forest area and positively associated with other land uses .", "entity": [], "task": "NER"}
{"text": "In a multiple regression , the percentage of area in valley fill was the strongest contributor to increased ionic strength , followed by percentage of area in urban ( residential / buildings ) land use and other mining land use .", "entity": [], "task": "NER"}
{"text": "Based on the 10th quantile regression , 300 micro S / cm was exceeded at 3 . 3 % of area in valley fill .", "entity": [], "task": "NER"}
{"text": "In most catchments , HCO 3 ( - ) and SO 4 ( 2 - ) concentrations were greater than Cl ( - ) concentration .", "entity": [{"entity": "HCO 3 ( - )", "entity_type": "Chemical", "pos": [21, 32]}, {"entity": "SO 4 ( 2 - )", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "Cl ( - )", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "These findings confirm coal mining activities as the primary source of high conductivity waters .", "entity": [], "task": "NER"}
{"text": "Such activities might be redressed with the goal of protecting sources of dilute freshwater in the region .", "entity": [], "task": "NER"}
{"text": "Next generation sequencing in predicting gene function in podophyllotoxin biosynthesis .", "entity": [{"entity": "podophyllotoxin", "entity_type": "Chemical", "pos": [58, 73]}], "task": "NER"}
{"text": "Podophyllum species are sources of ( - ) - podophyllotoxin , an aryltetralin lignan used for semi - synthesis of various powerful and extensively employed cancer - treating drugs .", "entity": [{"entity": "( - ) - podophyllotoxin", "entity_type": "Chemical", "pos": [35, 58]}, {"entity": "aryltetralin lignan", "entity_type": "Chemical", "pos": [64, 83]}], "task": "NER"}
{"text": "Its biosynthetic pathway , however , remains largely unknown , with the last unequivocally demonstrated intermediate being ( - ) - matairesinol .", "entity": [{"entity": "( - ) - matairesinol", "entity_type": "Chemical", "pos": [123, 143]}], "task": "NER"}
{"text": "Herein , massively parallel sequencing of Podophyllum hexandrum and Podophyllum peltatum transcriptomes and subsequent bioinformatics analyses of the corresponding assemblies were carried out .", "entity": [], "task": "NER"}
{"text": "Validation of the assembly process was first achieved through confirmation of assembled sequences with those of various genes previously established as involved in podophyllotoxin biosynthesis as well as other candidate biosynthetic pathway genes .", "entity": [{"entity": "podophyllotoxin", "entity_type": "Chemical", "pos": [164, 179]}], "task": "NER"}
{"text": "This contribution describes characterization of two of the latter , namely the cytochrome P450s , CYP719A23 from P . hexandrum and CYP719A24 from P . peltatum .", "entity": [], "task": "NER"}
{"text": "Both enzymes were capable of converting ( - ) - matairesinol into ( - ) - pluviatolide by catalyzing methylenedioxy bridge formation and did not act on other possible substrates tested .", "entity": [{"entity": "( - ) - matairesinol", "entity_type": "Chemical", "pos": [40, 60]}, {"entity": "( - ) - pluviatolide", "entity_type": "Chemical", "pos": [66, 86]}, {"entity": "methylenedioxy", "entity_type": "Chemical", "pos": [101, 115]}], "task": "NER"}
{"text": "Interestingly , the enzymes described herein were highly similar to methylenedioxy bridge - forming enzymes from alkaloid biosynthesis , whereas candidates more similar to lignan biosynthetic enzymes were catalytically inactive with the substrates employed .", "entity": [{"entity": "methylenedioxy", "entity_type": "Chemical", "pos": [68, 82]}, {"entity": "lignan", "entity_type": "Chemical", "pos": [172, 178]}], "task": "NER"}
{"text": "This overall strategy has thus enabled facile further identification of enzymes putatively involved in ( - ) - podophyllotoxin biosynthesis and underscores the deductive power of next generation sequencing and bioinformatics to probe and deduce medicinal plant biosynthetic pathways .", "entity": [{"entity": "( - ) - podophyllotoxin", "entity_type": "Chemical", "pos": [103, 126]}], "task": "NER"}
{"text": "Phosphorylation of dopamine transporter serine 7 modulates cocaine analog binding .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "serine", "entity_type": "Chemical", "pos": [40, 46]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "As an approach to elucidating dopamine transporter ( DAT ) phosphorylation characteristics , we examined in vitro phosphorylation of a recombinant rat DAT N - terminal peptide ( NDAT ) using purified protein kinases .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "N", "entity_type": "Chemical", "pos": [155, 156]}], "task": "NER"}
{"text": "We found that NDAT becomes phosphorylated at single distinct sites by protein kinase A ( Ser - 7 ) and calcium - calmodulin - dependent protein kinase II ( Ser - 13 ) and at multiple sites ( Ser - 4 , Ser - 7 , and Ser - 13 ) by protein kinase C ( PKC ) , implicating these residues as potential sites of DAT phosphorylation by these kinases .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [103, 110]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [156, 159]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [191, 194]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [201, 204]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [215, 218]}], "task": "NER"}
{"text": "Mapping of rat striatal DAT phosphopeptides by two - dimensional thin layer chromatography revealed basal and PKC - stimulated phosphorylation of the same peptide fragments and comigration of PKC - stimulated phosphopeptide fragments with NDAT Ser - 7 phosphopeptide markers .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [244, 247]}], "task": "NER"}
{"text": "We further confirmed by site - directed mutagenesis and mass spectrometry that Ser - 7 is a site for PKC - stimulated phosphorylation in heterologously expressed rat and human DATs .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "Mutation of Ser - 7 and nearby residues strongly reduced the affinity of rat DAT for the cocaine analog ( - ) - 2 beta - carbomethoxy - 3 beta - ( 4 - fluorophenyl ) tropane ( CFT ) , whereas in rat striatal tissue , conditions that promote DAT phosphorylation caused increased CFT affinity .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "( - ) - 2 beta - carbomethoxy - 3 beta - ( 4 - fluorophenyl ) tropane", "entity_type": "Chemical", "pos": [104, 173]}, {"entity": "CFT", "entity_type": "Chemical", "pos": [176, 179]}, {"entity": "CFT", "entity_type": "Chemical", "pos": [278, 281]}], "task": "NER"}
{"text": "Ser - 7 mutation also affected zinc modulation of CFT binding , with Ala and Asp substitutions inducing opposing effects .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "CFT", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "Ala", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "Asp", "entity_type": "Chemical", "pos": [77, 80]}], "task": "NER"}
{"text": "These results identify Ser - 7 as a major site for basal and PKC - stimulated phosphorylation of native and expressed DAT and suggest that Ser - 7 phosphorylation modulates transporter conformational equilibria , shifting the transporter between high and low affinity cocaine binding states .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [139, 142]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [268, 275]}], "task": "NER"}
{"text": "A method for assessing causation of field exposure - response relationships .", "entity": [], "task": "NER"}
{"text": "Because associations between agents and environmental effects are not necessarily causal , it is necessary to assess causation before using such relationships in environmental management .", "entity": [], "task": "NER"}
{"text": "The authors adapted epidemiological methods to assess general causal hypotheses .", "entity": [], "task": "NER"}
{"text": "General causation establishes that an agent is capable of causing an effect .", "entity": [], "task": "NER"}
{"text": "The method uses all relevant and good - quality evidence in a weight - of - evidence system .", "entity": [], "task": "NER"}
{"text": "The system is credible due to its explicit a priori criteria .", "entity": [], "task": "NER"}
{"text": "The evidence is organized in terms of six characteristics of causation : co - occurrence , preceding causation , interaction , alteration , sufficiency , and time order .", "entity": [], "task": "NER"}
{"text": "The causal assessment proceeds through six steps that generate , organize , and score evidence to determine whether causation is adequately supported by the body of evidence .", "entity": [], "task": "NER"}
{"text": "Application of multiple geochemical markers to investigate organic pollution in a dynamic coastal zone .", "entity": [], "task": "NER"}
{"text": "Multiple geochemical markers , including aliphatic hydrocarbons ( n - alkanes ) , linear alkylbenzenes ( LABs ) , and polycyclic aromatic hydrocarbons ( PAHs ) , were employed to relate sediment organic chemical pollution in the coastal zone off South China to socioeconomic development there .", "entity": [{"entity": "aliphatic hydrocarbons", "entity_type": "Chemical", "pos": [41, 63]}, {"entity": "n - alkanes", "entity_type": "Chemical", "pos": [66, 77]}, {"entity": "linear alkylbenzenes", "entity_type": "Chemical", "pos": [82, 102]}, {"entity": "LABs", "entity_type": "Chemical", "pos": [105, 109]}, {"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [118, 150]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [153, 157]}], "task": "NER"}
{"text": "Concentrations of Sigma n - C ( 15 - 35 ) ( n - alkanes with 15 - 35 carbon atoms ) , Sigma LAB ( sum of C ( 10 ) to C ( 13 ) LABs ) , and Sigma ( 26 ) PAH ( sum of 26 PAH compounds ) ranged from 110 to 3 , 160 , 11 to 160 , and 26 to 600 ng / g , with medians of 730 , 40 , and 230 ng / g , respectively .", "entity": [{"entity": "n - C ( 15 - 35 )", "entity_type": "Chemical", "pos": [24, 41]}, {"entity": "n - alkanes", "entity_type": "Chemical", "pos": [44, 55]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [69, 75]}, {"entity": "LAB", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "C ( 10 ) to C ( 13 ) LABs", "entity_type": "Chemical", "pos": [105, 130]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [152, 155]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [168, 171]}], "task": "NER"}
{"text": "Natural hydrocarbons were mainly derived from terrestrial higher plant waxes , and in minor amounts from aquatic plankton and bacteria .", "entity": [{"entity": "hydrocarbons", "entity_type": "Chemical", "pos": [8, 20]}], "task": "NER"}
{"text": "Compositions of LABs indicated that considerable amounts of poorly treated wastewater had been directly discharged or transported to the eastern and western coastal areas of Guangdong Province .", "entity": [{"entity": "LABs", "entity_type": "Chemical", "pos": [16, 20]}], "task": "NER"}
{"text": "In addition , anthropogenic hydrocarbons were derived largely from vehicular emissions and combustion of domestic coal and biomass and to a lesser extent from oil spills .", "entity": [{"entity": "hydrocarbons", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "Eastern and western coastal sediments contained higher levels of LABs but lower levels of PAHs than those of the Pearl River Estuary , a coastal area of the Pearl River Delta .", "entity": [{"entity": "LABs", "entity_type": "Chemical", "pos": [65, 69]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [90, 94]}], "task": "NER"}
{"text": "This spatial pattern of organic pollution was consistent with chemical use patterns .", "entity": [], "task": "NER"}
{"text": "The eastern and western regions of Guangdong Province are economically less developed than the Pearl River Delta region , where more domestic wastewater treatment plants have been built .", "entity": [], "task": "NER"}
{"text": "However , greater amounts of energy are consumed in the latter region to produce more combustion - derived PAH contamination .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "Comparison of gel - based phosphoproteomic approaches to analyse scarce oviductal epithelial cell samples .", "entity": [], "task": "NER"}
{"text": "The reversible change of the phosphorylation state of proteins regulates key cellular processes .", "entity": [], "task": "NER"}
{"text": "In the present study , three different gel - based approaches were compared with regard to their applicability to quantitatively analyse the phosphoproteome of scarce biological material obtained ex vivo .", "entity": [], "task": "NER"}
{"text": "Our results show that the phosphoproteome characterisation of oviductal epithelial cells isolated from the female reproductive tract requires affinity enrichment and pre - electrophoretic labelling using fluorescence dyes .", "entity": [], "task": "NER"}
{"text": "Using this approach , 30 mu g of enriched phosphoproteins proved to be sufficient for the phosphoproteome characterisation .", "entity": [], "task": "NER"}
{"text": "In contrast , sequential fluorescence staining of 2D - separated total cell lysates as well as sequential staining in conjunction with a pre - enrichment step led to detection discrepancies and excluded further analysis steps .", "entity": [], "task": "NER"}
{"text": "Information gained from this study provides a successful approach for the phosphoproteome analysis of scarce samples .", "entity": [], "task": "NER"}
{"text": "In addition , the cellular processes taking place in the female reproductive tract can be monitored ex vivo .", "entity": [], "task": "NER"}
{"text": "Large area resist - free soft lithographic patterning of graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [57, 65]}], "task": "NER"}
{"text": "Large area low - cost patterning is a challenging problem in graphene research .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "A resist - free , single - step , large area and cost effective soft lithographic patterning strategy is presented for graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "The technique is applicable on any arbitrary substrate that needs to be covered with a graphene film and provides a viable route to large - area patterning of graphene for device applications .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [87, 95]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [159, 167]}], "task": "NER"}
{"text": "Do Subtoxic levels of chlorate influence the desiccation tolerance of Egeria densa ?", "entity": [{"entity": "chlorate", "entity_type": "Chemical", "pos": [22, 30]}], "task": "NER"}
{"text": "Among the different factors hypothesized to be responsible for the virtual disappearance of Egeria densa , once a dominant aquatic macrophyte in a southern Chile wetland ecosystem , are the negative effects of certain chemical compounds ( mainly chlorate ) and harsh environmental conditions ( desiccation caused by prolonged atmospheric exposure ) .", "entity": [{"entity": "chlorate", "entity_type": "Chemical", "pos": [246, 254]}], "task": "NER"}
{"text": "The authors performed an integrated experiment in which E . densa plants were first exposed for four weeks inside a mesocosm system to levels of chlorate that existed in the wetland at the time of the plant ' s demise and then exposed to desiccation conditions that also resembled those that the system had experienced .", "entity": [{"entity": "chlorate", "entity_type": "Chemical", "pos": [145, 153]}], "task": "NER"}
{"text": "Hence , the authors tested the hypothesis that E . densa plants exposed to sublethal levels of chlorate are more susceptible to the deleterious effect of desiccation compared with plants that had not been exposed to chlorate .", "entity": [{"entity": "chlorate", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "chlorate", "entity_type": "Chemical", "pos": [216, 224]}], "task": "NER"}
{"text": "This hypothesis was tested by means of quantifying physiologically related parameters in plants right after the four weeks under water and then after the desiccation period of 6 h .", "entity": [], "task": "NER"}
{"text": "Their results rejected this hypothesis , because all plants , regardless of their history , are equally affected by desiccation .", "entity": [], "task": "NER"}
{"text": "Solid - state NMR structure determination of whole anchoring threads from the blue mussel Mytilus edulis .", "entity": [], "task": "NER"}
{"text": "The molecular structure of the blue mussel Mytilus edulis whole anchoring threads was studied by two - dimensional ( 13 ) C solid - state NMR on fully labeled fibers .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "This unique material proves to be well ordered at a molecular level despite its heterogeneous composition as evidenced by the narrow measured linewidths below 1 . 5 ppm .", "entity": [], "task": "NER"}
{"text": "The spectra are dominated by residues in collagen environments , as determined from chemical shift analysis , and a complete two - dimensional assignment ( including minor amino acids ) was possible .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [172, 183]}], "task": "NER"}
{"text": "The best agreement between predicted and experimental backbone chemical shifts was obtained for collagen helices with torsion angles ( - 75 degrees , + 150 degrees ) .", "entity": [], "task": "NER"}
{"text": "The abundant glycine and alanine residues can be resolved in up to five different structural environments .", "entity": [{"entity": "glycine", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [25, 32]}], "task": "NER"}
{"text": "Alanine peaks could be assigned to collagen triple - helices , beta - sheets ( parallel and antiparallel ) , beta - turns , and unordered structures .", "entity": [{"entity": "Alanine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "The use of ATR - FTIR microscopy confirmed the presence of these structural environments and enabled their location in the core of the thread ( collagen helices and antiparallel beta - sheets ) or its cuticle ( unordered structures ) .", "entity": [], "task": "NER"}
{"text": "The approach should enable characterization at the molecular level of a wide range of byssus macroscopic properties .", "entity": [], "task": "NER"}
{"text": "A question of time : the land snail Murella muralis ( Gastropoda : Pulmonata ) reveals constraints on past ecological speciation .", "entity": [], "task": "NER"}
{"text": "The lively debate about speciation currently focuses on the relative importance of factors driving population differentiation .", "entity": [], "task": "NER"}
{"text": "While many studies are increasingly producing results on the importance of selection , little is known about the interaction between drift and selection .", "entity": [], "task": "NER"}
{"text": "Moreover , there is still little knowledge on the spatial - temporal scales at which speciation occurs , that is , arrangement of habitat patches , abruptness of habitat transitions , climate and habitat changes interacting with selective forces .", "entity": [], "task": "NER"}
{"text": "To investigate these questions , we quantified variation on a fine geographical scale analysing morphological ( shell ) and genetic data sets coupled with environmental data in the land snail Murella muralis , endemic to the Mediterranean island of Sicily .", "entity": [], "task": "NER"}
{"text": "Analysis of a fragment of the mitochondrial DNA cytochrome oxidase I gene ( COI ) and eight nuclear microsatellite loci showed that genetic variation is highly structured at a very fine spatial scale by local palaeogeographical events and historical population dynamics .", "entity": [], "task": "NER"}
{"text": "Molecular clock estimates , calibrated here specifically for Tyrrhenian land snails , provided a framework of palaeogeographical events responsible for the observed geographical variations and migration routes .", "entity": [], "task": "NER"}
{"text": "Finally , we showed for the first time well - documented lines of evidence of selection in the past , which explains divergence of land snail shell shapes .", "entity": [], "task": "NER"}
{"text": "We suggest that time and palaeogeographical history acted as constraints in the progress along the ecological speciation continuum .", "entity": [], "task": "NER"}
{"text": "Our study shows that testing for correlation among palaeogeography , morphology and genetic data on a fine geographical scale provides information fundamental for a detailed understanding of ecological speciation processes .", "entity": [], "task": "NER"}
{"text": "The structure and properties of septin 3 : a possible missing link in septin filament formation .", "entity": [], "task": "NER"}
{"text": "The human genome codes for 13 members of a family of filament - forming GTP - binding proteins known as septins .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [72, 75]}], "task": "NER"}
{"text": "These have been divided into four different subgroups on the basis of sequence similarity .", "entity": [], "task": "NER"}
{"text": "The differences between the subgroups are believed to control their correct assembly into heterofilaments which have specific roles in membrane remodelling events .", "entity": [], "task": "NER"}
{"text": "Many different combinations of the 13 proteins are theoretically possible and it is therefore important to understand the structural basis of specific filament assembly .", "entity": [], "task": "NER"}
{"text": "However , three - dimensional structures are currently available for only three of the four subgroups .", "entity": [], "task": "NER"}
{"text": "In the present study we describe the crystal structure of a construct of human SEPT3 which belongs to the outstanding subgroup .", "entity": [], "task": "NER"}
{"text": "This construct ( SEPT3 - GC ) , which includes the GTP - binding and C - terminal domains , purifies as a nucleotide - free monomer , allowing for its characterization in terms of GTP - binding and hydrolysis .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "C", "entity_type": "Chemical", "pos": [69, 70]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [106, 116]}, {"entity": "GTP", "entity_type": "Chemical", "pos": [180, 183]}], "task": "NER"}
{"text": "In the crystal structure , SEPT3 - GC forms foreshortened filaments which employ the same NC and G interfaces observed in the heterotrimeric complex of human septins 2 , 6 and 7 , reinforcing the notion of ' promiscuous ' interactions described previously .", "entity": [], "task": "NER"}
{"text": "In the present study we describe these two interfaces and relate the structure to its tendency to form monomers and its efficiency in the hydrolysis of GTP .", "entity": [{"entity": "GTP", "entity_type": "Chemical", "pos": [152, 155]}], "task": "NER"}
{"text": "The relevance of these results is emphasized by the fact that septins from the SEPT3 subgroup may be important determinants of polymerization by occupying the terminal position in octameric units which themselves form the building blocks of at least some heterofilaments .", "entity": [], "task": "NER"}
{"text": "Receptors , endocytosis , and trafficking : the biological basis of targeted delivery of antisense and siRNA oligonucleotides .", "entity": [], "task": "NER"}
{"text": "The problem of targeted delivery of antisense and siRNA oligonucleotides can be resolved into two distinct aspects .", "entity": [], "task": "NER"}
{"text": "The first concerns devising ligand - oligonucleotide or ligand - carrier moieties that bind with high selectivity to receptors on the cell type of interest and that are efficiently internalized by endocytosis .", "entity": [], "task": "NER"}
{"text": "The second concerns releasing oligonucleotides from pharmacologically inert endomembrane compartments so that they can access RNA in the cytosol or nucleus .", "entity": [], "task": "NER"}
{"text": "In this review , we will address both of these aspects .", "entity": [], "task": "NER"}
{"text": "Thus , we present information on three important receptor families , the integrins , the receptor tyrosine kinases , and the G protein - coupled receptors in terms of their suitability for targeted delivery of oligonucleotides .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [98, 106]}], "task": "NER"}
{"text": "This includes discussion of receptor abundance , internalization and trafficking pathways , and the availability of suitable high affinity ligands .", "entity": [], "task": "NER"}
{"text": "We also consider the process of oligonucleotide uptake and intracellular trafficking and discuss approaches to modulating these processes in a pharmacologically productive manner .", "entity": [], "task": "NER"}
{"text": "Hopefully , the basic information presented in this review will be of value to investigators involved in designing delivery approaches for oligonucleotides .", "entity": [], "task": "NER"}
{"text": "A new ganoderic acid from Ganoderma lucidum mycelia and its stability .", "entity": [{"entity": "ganoderic acid", "entity_type": "Chemical", "pos": [6, 20]}], "task": "NER"}
{"text": "A new ganoderic acid ( GA ) , 3 alpha , 22 beta - diacetoxy - 7 alpha - hydroxyl - 5 alpha - lanost - 8 , 24E - dien - 26 - oic acid ( 1 ) , together with four known compounds GA - Mk ( 2 ) , - Mc ( 3 ) , - S ( 4 ) and - Mf ( 5 ) , was isolated and characterized from Ganoderma lucidum mycelia .", "entity": [{"entity": "ganoderic acid", "entity_type": "Chemical", "pos": [6, 20]}, {"entity": "3 alpha , 22 beta - diacetoxy - 7 alpha - hydroxyl - 5 alpha - lanost - 8 , 24E - dien - 26 - oic acid", "entity_type": "Chemical", "pos": [30, 132]}, {"entity": "GA - Mk", "entity_type": "Chemical", "pos": [176, 183]}], "task": "NER"}
{"text": "The structure of compound 1 was elucidated on the basis of interpretation of extensive spectroscopic data ( HRMS , IR , UV , 1D and 2D NMR ) .", "entity": [], "task": "NER"}
{"text": "Due to its apparent degradation during preparation procedures , the stability of compound 1 was assessed in several solvents in a short - term study that demonstrated the optimal stability in aproptic environment .", "entity": [], "task": "NER"}
{"text": "A possible mechanism of acid - catalyzed degradation of compound 1 in methanol was proposed , consisting of a fast protonation , followed by a committed step of hydroxyl group removal .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [70, 78]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [161, 169]}], "task": "NER"}
{"text": "In addition , all isolated compounds were tested in vitro for their cytotoxic activities against 95D and HeLa tumor cell lines , with IC ( 50 ) values ranging from14 . 7 to 38 . 5 mu M .", "entity": [], "task": "NER"}
{"text": "The results may improve the understanding of chemical stability of GAs and provide valuable information on their separation , analysis and application .", "entity": [], "task": "NER"}
{"text": "Ipsilateral feeding - specific circuits between the nucleus accumbens shell and the lateral hypothalamus : regulation by glutamate and GABA receptor subtypes .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [121, 130]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "The nucleus accumbens shell ( AcbSh ) and the lateral hypothalamus ( LH ) are both involved in the control of food intake .", "entity": [], "task": "NER"}
{"text": "Activation of GABA ( A ) receptors or blockade of AMPA and kainate receptors within the AcbSh induces feeding , as does blockade of GABA ( A ) receptors or activation of NMDA receptors in the LH .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "kainate", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [132, 136]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [170, 174]}], "task": "NER"}
{"text": "Further , evidence suggests that feeding induced via the AcbSh can be suppressed by LH inhibition .", "entity": [], "task": "NER"}
{"text": "However , it is unclear if this suppression is specific to feeding .", "entity": [], "task": "NER"}
{"text": "Adult male Sprague - Dawley rats with 3 intracranial guide cannulas , one unilaterally into the AcbSh and two bilaterally into the LH , were used to explore this issue .", "entity": [], "task": "NER"}
{"text": "DNQX ( 1 . 25 mu g ) or muscimol ( 100 ng ) infused into the AcbSh unilaterally elicited feeding , and this elicited intake was suppressed by bilateral LH injection of d - AP5 ( 2 mu g ) or muscimol ( 25 ng ) .", "entity": [{"entity": "DNQX", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "muscimol", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "d - AP5", "entity_type": "Chemical", "pos": [168, 175]}, {"entity": "muscimol", "entity_type": "Chemical", "pos": [190, 198]}], "task": "NER"}
{"text": "The effectiveness of d - AP5 or muscimol infusion into either the LH site ipsilateral or contralateral to the AcbSh injection was compared .", "entity": [{"entity": "d - AP5", "entity_type": "Chemical", "pos": [21, 28]}, {"entity": "muscimol", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "Ipsilateral LH injection of d - AP5 or muscimol was significantly more effective than contralateral injection in suppressing food intake initiated by AcbSh injection of DNQX or muscimol .", "entity": [{"entity": "d - AP5", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "muscimol", "entity_type": "Chemical", "pos": [39, 47]}, {"entity": "DNQX", "entity_type": "Chemical", "pos": [169, 173]}, {"entity": "muscimol", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "These results add to the prior evidence that inhibition of the LH through pharmacological modulation of NMDA or GABA ( A ) receptors specifically suppresses feeding initiated by AcbSh inhibition , and that these two regions communicate via an ipsilateral circuit to specifically regulate feeding .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [104, 108]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "The glycogen synthase kinase - 3 beta / nuclear factor - kappa B pathway is involved in cinobufagin - induced apoptosis in cultured osteosarcoma cells .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [88, 99]}], "task": "NER"}
{"text": "Cinobufagin , a major component of cinobufacini ( huachansu ) , is an important cardenolidal steroid .", "entity": [{"entity": "Cinobufagin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "cardenolidal steroid", "entity_type": "Chemical", "pos": [80, 100]}], "task": "NER"}
{"text": "Several studies have suggested that cinobufagin has potent anti - cancer effects .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [36, 47]}], "task": "NER"}
{"text": "The present study examines the apoptosis - inducing activity and the underlying mechanism of action of cinobufagin in osteosarcoma ( OS ) cells .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [103, 114]}], "task": "NER"}
{"text": "Our results showed that cinobufagin potently inhibited the proliferation of U2OS , MG63 and SaOS - 2 cells .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "Significant increases in G2 / M cell - cycle arrest and apoptosis in OS cells were also observed .", "entity": [], "task": "NER"}
{"text": "The expression levels of several apoptotic proteins were assessed after cinobufagin treatment in U2OS cells .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "Among them , xIAP , cIAP - 1 , survivin and Bcl - 2 levels decreased remarkably , while the levels of Bax and cleaved - PARP increased .", "entity": [], "task": "NER"}
{"text": "Furthermore , we validated the inhibition of GSK - 3 beta / NF - kappa B signaling following cinobufagin treatment .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of cinobufagin , while the phosphorylation of GSK - 3 beta was simultaneously increased .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [112, 123]}], "task": "NER"}
{"text": "Transduction with constitutively active forms of GSK - 3 beta could protect against the downregulation of p65 and upregulation of cleaved - PARP that are induced by cinobufagin treatment .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [165, 176]}], "task": "NER"}
{"text": "However , combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved - PARP in U2OS cells .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [34, 45]}, {"entity": "SB216367", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Altogether , these results show that cinobufagin is a promising agent for the treatment of OS .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [37, 48]}], "task": "NER"}
{"text": "These studies are the first to reveal the involvement of the GSK - 3 beta / NF - kappa B pathway in cinobufagin - induced apoptosis .", "entity": [{"entity": "cinobufagin", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "Pathophysiological roles of aldo - keto reductases ( AKR1C1 and AKR1C3 ) in development of cisplatin resistance in human colon cancers .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [91, 100]}], "task": "NER"}
{"text": "Cisplatin ( cis - diamminedichloroplatinum , CDDP ) is widely used for treatment of patients with solid tumors formed in various organs including the lung , prostate and cervix , but is much less sensitive in colon and breast cancers .", "entity": [{"entity": "Cisplatin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "cis - diamminedichloroplatinum", "entity_type": "Chemical", "pos": [12, 42]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "One major factor implicated in the ineffectiveness has been suggested to be acquisition of the CDDP resistance .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Here , we established the CDDP - resistant phenotypes of human colon HCT15 cells by continuously exposing them to incremental concentrations of the drug , and monitored expressions of aldo - keto reductases ( AKRs ) 1A1 , 1B1 , 1B10 , 1C1 , 1C2 and 1C3 .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "Among the six AKRs , AKR1C1 and AKR1C3 are highly induced with the CDDP resistance .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "The resistance lowered the sensitivity toward cellular damages evoked by oxidative stress - derived aldehydes , 4 - hydroxy - 2 - nonenal and 4 - oxo - 2 - nonenal that are detoxified by AKR1C1 and AKR1C3 .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [100, 109]}, {"entity": "4 - hydroxy - 2 - nonenal", "entity_type": "Chemical", "pos": [112, 137]}, {"entity": "4 - oxo - 2 - nonenal", "entity_type": "Chemical", "pos": [142, 163]}], "task": "NER"}
{"text": "Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigated the cytotoxicity of the aldehydes and CDDP .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [97, 106]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [111, 115]}], "task": "NER"}
{"text": "Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the AKRs increased the sensitivity to CDDP toxicity .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [151, 155]}], "task": "NER"}
{"text": "Thus , the two AKRs participate in the mechanism underlying the CDDP resistance probably via detoxification of the aldehydes resulting from enhanced oxidative stress .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [64, 68]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "The resistant cells also showed an enhancement in proteolytic activity of proteasome accompanied by overexpression of its catalytic subunits ( PSM beta 9 and PSM beta 10 ) .", "entity": [], "task": "NER"}
{"text": "Pretreatment of the resistant cells with a potent proteasome inhibitor Z - Leu - Leu - Leu - al augmented the CDDP sensitization elicited by the AKR inhibitors .", "entity": [{"entity": "Z - Leu - Leu - Leu - al", "entity_type": "Chemical", "pos": [71, 95]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [110, 114]}], "task": "NER"}
{"text": "Additionally , the treatment of the cells with Z - Leu - Leu - Leu - al and the AKR inhibitors induced the expressions of the two AKRs and proteasome subunits .", "entity": [{"entity": "Z - Leu - Leu - Leu - al", "entity_type": "Chemical", "pos": [47, 71]}], "task": "NER"}
{"text": "Collectively , these results suggest the involvement of up - regulated AKR1C1 , AKR1C3 and proteasome in CDDP resistance of colon cancers and support a chemotherapeutic role for their inhibitors .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [105, 109]}], "task": "NER"}
{"text": "Local structure and dynamics of benzene confined in the IRMOF - 1 nanocavity as studied by molecular dynamics simulation .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "IRMOF - 1", "entity_type": "Chemical", "pos": [56, 65]}], "task": "NER"}
{"text": "The local structure and dynamic behaviour of a benzene molecular assembly confined within the nano - cavities of a zinc - based metal - organic framework , [ Zn ( 4 ) O ( CO ( 2 ) C ( 6 ) H ( 4 ) CO ( 2 ) ) ( 3 ) ] ( n ) ( IRMOF - 1 ) , were investigated by means of molecular dynamics ( MD ) simulations .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [115, 119]}, {"entity": "[ Zn ( 4 ) O ( CO ( 2 ) C ( 6 ) H ( 4 ) CO ( 2 ) ) ( 3 ) ] ( n )", "entity_type": "Chemical", "pos": [156, 220]}, {"entity": "IRMOF - 1", "entity_type": "Chemical", "pos": [223, 232]}], "task": "NER"}
{"text": "The local structure of the confined benzene molecules was evaluated using radial distribution functions .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [36, 43]}], "task": "NER"}
{"text": "The sites for adsorption of benzene in IRMOF - 1 were well defined by the simulation .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "IRMOF - 1", "entity_type": "Chemical", "pos": [39, 48]}], "task": "NER"}
{"text": "The diffusion coefficients at ambient temperature suggested that the mobility of the confined benzene was high , comparable to the bulk fluid .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Decreasing the temperature gave rise to the aggregation of benzene in the IRMOF - 1 frameworks .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "IRMOF - 1", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "Molecular aggregation was attributed to the localization of benzene in the large and the small cavities of IRMOF - 1 , respectively .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "IRMOF - 1", "entity_type": "Chemical", "pos": [107, 116]}], "task": "NER"}
{"text": "Both the translational diffusion coefficient and the trajectory of benzene provided evidence that the localization of benzene in the large and the small cavities takes place at ca .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "200 K .", "entity": [], "task": "NER"}
{"text": "Furthermore , at high benzene loading , the migration of benzene in the small cavities was prevented ( frozen ) below 135 K .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "Thus , the translational degree of freedom of the benzene molecules changed drastically , depending on the temperature .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "Computer simulation study of nanoparticle interaction with a lipid membrane under mechanical stress .", "entity": [], "task": "NER"}
{"text": "Pore formation of lipid bilayers under mechanical stress is critical to biological processes .", "entity": [], "task": "NER"}
{"text": "A series of coarse grained molecular dynamics simulations of lipid bilayers with carbon nanoparticles different in size have been performed .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "Surface tension was applied to study the disruption of lipid bilayers by nanoparticles and the formation of pores inside the bilayers .", "entity": [], "task": "NER"}
{"text": "The presence of small nanoparticles enhances the probability of water penetration thus decreasing the membrane rupture tension , while big nanoparticles have the opposite effect .", "entity": [], "task": "NER"}
{"text": "Nanoparticle volume affects bilayer strength indirectly , and particle surface density can complicate the interaction .", "entity": [], "task": "NER"}
{"text": "The structural , dynamic , elastic properties and lateral densities of lipid bilayers with nanoparticles under mechanical stress were analyzed .", "entity": [], "task": "NER"}
{"text": "The results demonstrate the ability of nanoparticles to adjust the structural and dynamic properties of a lipid membrane , and to efficiently regulate the pore formation behavior and hydrophobicity of membranes .", "entity": [], "task": "NER"}
{"text": "Development of automated paper - based devices for sequential multistep sandwich enzyme - linked immunosorbent assays using inkjet printing .", "entity": [], "task": "NER"}
{"text": "To the best of our knowledge , this is the first report on paper - based devices for automating the sequential multistep procedures of a sandwich - type enzyme - linked immunosorbent assay ( ELISA ) that require only a single - step application of the sample solution .", "entity": [], "task": "NER"}
{"text": "The device was based on a piece of nitrocellulose ( NC ) membrane with specially designed channels , where all the reagents are applied at different locations in order to control the fluid travel to the detection region .", "entity": [], "task": "NER"}
{"text": "The inkjet printing method , a simple and low - cost process , was used to create the flow channel and device barrier patterns .", "entity": [], "task": "NER"}
{"text": "The fabricated barrier was found to be an efficient boundary for the liquid along the printed design in the NC membrane , enabling direct control of the reagent flow time .", "entity": [], "task": "NER"}
{"text": "ELISA results were obtained with a single - step sample application .", "entity": [], "task": "NER"}
{"text": "The developed devices ( so - called automated paper - based devices ) provided a simple procedure for the sandwich ELISA , while reducing assay time and reagent consumption .", "entity": [], "task": "NER"}
{"text": "Colorimetric results were measured using digital camera imaging with software processing .", "entity": [], "task": "NER"}
{"text": "The capability of the method developed herein was successfully used to determine the levels of human chorionic gonadotropin ( hCG ) by ELISA .", "entity": [], "task": "NER"}
{"text": "A VUV photoionization study of the multichannel reaction of phenyl radicals with 1 , 3 - butadiene under combustion relevant conditions .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "1 , 3 - butadiene", "entity_type": "Chemical", "pos": [81, 98]}], "task": "NER"}
{"text": "We studied the reaction of phenyl radicals ( C ( 6 ) H ( 5 ) ) with 1 , 3 - butadiene ( H ( 2 ) CCHCHCH ( 2 ) ) exploiting a high temperature chemical reactor under combustion - like conditions ( 300 Torr , 873 K ) .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [27, 33]}, {"entity": "C ( 6 ) H ( 5 )", "entity_type": "Chemical", "pos": [45, 60]}, {"entity": "1 , 3 - butadiene", "entity_type": "Chemical", "pos": [68, 85]}, {"entity": "H ( 2 ) CCHCHCH ( 2 )", "entity_type": "Chemical", "pos": [88, 109]}], "task": "NER"}
{"text": "The reaction products were probed in a supersonic beam by utilizing VUV radiation from the Advanced Light Source and by recording the experimental PIE curves at mass - to - charge ratios of m / z = 130 ( C ( 10 ) H ( 10 ) ( + ) ) , 116 ( C ( 9 ) H ( 8 ) ( + ) ) , and 104 ( C ( 8 ) H ( 8 ) ( + ) ) .", "entity": [{"entity": "C ( 10 ) H ( 10 ) ( + )", "entity_type": "Chemical", "pos": [204, 227]}, {"entity": "C ( 9 ) H ( 8 ) ( + )", "entity_type": "Chemical", "pos": [238, 259]}, {"entity": "C ( 8 ) H ( 8 ) ( + )", "entity_type": "Chemical", "pos": [274, 295]}], "task": "NER"}
{"text": "Our data suggest that the atomic hydrogen ( H ) , methyl ( CH ( 3 ) ) , and vinyl ( C ( 2 ) H ( 3 ) ) losses are open with estimated branching ratios of about 86 +/- 4 % , 8 +/- 2 % , and 6 +/- 2 % , respectively .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "H", "entity_type": "Chemical", "pos": [44, 45]}, {"entity": "methyl", "entity_type": "Chemical", "pos": [50, 56]}, {"entity": "CH ( 3 )", "entity_type": "Chemical", "pos": [59, 67]}, {"entity": "vinyl", "entity_type": "Chemical", "pos": [76, 81]}, {"entity": "C ( 2 ) H ( 3 )", "entity_type": "Chemical", "pos": [84, 99]}], "task": "NER"}
{"text": "The isomer distributions were probed further by fitting the experimentally recorded PIE curves with a linear combination of the PIE curves of individual C ( 10 ) H ( 10 ) , C ( 9 ) H ( 8 ) , and C ( 8 ) H ( 8 ) isomers .", "entity": [{"entity": "C ( 10 ) H ( 10 )", "entity_type": "Chemical", "pos": [153, 170]}, {"entity": "C ( 9 ) H ( 8 )", "entity_type": "Chemical", "pos": [173, 188]}, {"entity": "C ( 8 ) H ( 8 )", "entity_type": "Chemical", "pos": [195, 210]}], "task": "NER"}
{"text": "These fits indicate the formation of three C ( 10 ) H ( 10 ) isomers ( trans - 1 , 3 - butadienylbenzene , 1 , 4 - dihydronaphthalene , 1 - methylindene ) , three C ( 9 ) H ( 8 ) isomers ( indene , phenylallene , 1 - phenyl - 1 - methylacetylene ) , and a C ( 8 ) H ( 8 ) isomer ( styrene ) .", "entity": [{"entity": "C ( 10 ) H ( 10 )", "entity_type": "Chemical", "pos": [43, 60]}, {"entity": "trans - 1 , 3 - butadienylbenzene", "entity_type": "Chemical", "pos": [71, 104]}, {"entity": "1 , 4 - dihydronaphthalene", "entity_type": "Chemical", "pos": [107, 133]}, {"entity": "1 - methylindene", "entity_type": "Chemical", "pos": [136, 152]}, {"entity": "C ( 9 ) H ( 8 )", "entity_type": "Chemical", "pos": [163, 178]}, {"entity": "indene", "entity_type": "Chemical", "pos": [189, 195]}, {"entity": "phenylallene", "entity_type": "Chemical", "pos": [198, 210]}, {"entity": "1 - phenyl - 1 - methylacetylene", "entity_type": "Chemical", "pos": [213, 245]}, {"entity": "C ( 8 ) H ( 8 )", "entity_type": "Chemical", "pos": [256, 271]}, {"entity": "styrene", "entity_type": "Chemical", "pos": [281, 288]}], "task": "NER"}
{"text": "A comparison with results from recent crossed molecular beam studies of the 1 , 3 - butadiene - phenyl radical reaction and electronic structure calculations suggests that trans - 1 , 3 - butadienylbenzene ( 130 amu ) , 1 , 4 - dihydronaphthalene ( 130 amu ) , and styrene ( 104 amu ) are reaction products formed as a consequence of a bimolecular reaction between the phenyl radical and 1 , 3 - butadiene .", "entity": [{"entity": "1 , 3 - butadiene - phenyl", "entity_type": "Chemical", "pos": [76, 102]}, {"entity": "trans - 1 , 3 - butadienylbenzene", "entity_type": "Chemical", "pos": [172, 205]}, {"entity": "1 , 4 - dihydronaphthalene", "entity_type": "Chemical", "pos": [220, 246]}, {"entity": "styrene", "entity_type": "Chemical", "pos": [265, 272]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [369, 375]}, {"entity": "1 , 3 - butadiene", "entity_type": "Chemical", "pos": [388, 405]}], "task": "NER"}
{"text": "1 - Methylindene ( 130 amu ) , indene ( 116 amu ) , phenylallene ( 116 amu ) , and 1 - phenyl - 1 - methylacetylene ( 116 amu ) are synthesized upon reaction of the phenyl radical with three C ( 4 ) H ( 6 ) isomers : 1 , 2 - butadiene ( H ( 2 ) CCCH ( CH ( 3 ) ) ) , 1 - butyne ( HCCC ( 2 ) H ( 5 ) ) , and 2 - butyne ( CH ( 3 ) CCCH ( 3 ) ) ; these C ( 4 ) H ( 6 ) isomers can be formed from 1 , 3 - butadiene via hydrogen atom assisted isomerization reactions or via thermal rearrangements of 1 , 3 - butadiene involving hydrogen shifts in the high temperature chemical reactor .", "entity": [{"entity": "1 - Methylindene", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "indene", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "phenylallene", "entity_type": "Chemical", "pos": [52, 64]}, {"entity": "1 - phenyl - 1 - methylacetylene", "entity_type": "Chemical", "pos": [83, 115]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [165, 171]}, {"entity": "C ( 4 ) H ( 6 )", "entity_type": "Chemical", "pos": [191, 206]}, {"entity": "1 , 2 - butadiene", "entity_type": "Chemical", "pos": [217, 234]}, {"entity": "H ( 2 ) CCCH ( CH ( 3 ) )", "entity_type": "Chemical", "pos": [237, 262]}, {"entity": "1 - butyne", "entity_type": "Chemical", "pos": [267, 277]}, {"entity": "HCCC ( 2 ) H ( 5 )", "entity_type": "Chemical", "pos": [280, 298]}, {"entity": "2 - butyne", "entity_type": "Chemical", "pos": [307, 317]}, {"entity": "CH ( 3 ) CCCH ( 3 )", "entity_type": "Chemical", "pos": [320, 339]}, {"entity": "C ( 4 ) H ( 6 )", "entity_type": "Chemical", "pos": [350, 365]}, {"entity": "1 , 3 - butadiene", "entity_type": "Chemical", "pos": [393, 410]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [415, 423]}, {"entity": "1 , 3 - butadiene", "entity_type": "Chemical", "pos": [495, 512]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [523, 531]}], "task": "NER"}
{"text": "EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair .", "entity": [], "task": "NER"}
{"text": "Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand , ephrinB2 , as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "In the present study , we examined the role of EphB4 during bone repair after traumatic injury .", "entity": [], "task": "NER"}
{"text": "We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter ( Col1 - EphB4 ) and investigated the bone repair process up to 12 weeks postfracture .", "entity": [], "task": "NER"}
{"text": "The data indicated that Col1 - EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild - type mice .", "entity": [], "task": "NER"}
{"text": "The fractured bones of Col1 - EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild - type mice .", "entity": [], "task": "NER"}
{"text": "These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture , as demonstrated by increased safranin O and von Kossa staining , respectively .", "entity": [{"entity": "safranin O", "entity_type": "Chemical", "pos": [156, 166]}], "task": "NER"}
{"text": "Interestingly , Col1 - EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells ( CFU - F ) , with an increased capacity to form mineralized nodules in vitro under osteogenic conditions , when compared with those of the wild - type control mice .", "entity": [], "task": "NER"}
{"text": "Furthermore , Col1 - EphB4 mice had significantly lower numbers of TRAP - positive multinucleated osteoclasts within the callus site .", "entity": [], "task": "NER"}
{"text": "Taken together , these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones .", "entity": [], "task": "NER"}
{"text": "Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma , seminal plasma , and cerebrospinal fluid .", "entity": [{"entity": "efavirenz", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "Efavirenz ( EFV ) is one of the most commonly prescribed antiretrovirals for use in the treatment of human immunodeficiency virus ( HIV ) infection .", "entity": [{"entity": "Efavirenz", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "EFV", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "EFV is extensively metabolized by cytochrome P450 to a number of oxygenated products ; however , the pharmacologic activity and distribution of these metabolites in anatomic compartments have yet to be explored .", "entity": [{"entity": "EFV", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The systemic distribution of EFV oxidative metabolites was examined in blood plasma , seminal plasma , and cerebrospinal fluid from subjects on an EFV - based regimen .", "entity": [{"entity": "EFV", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "EFV", "entity_type": "Chemical", "pos": [147, 150]}], "task": "NER"}
{"text": "The 8 - hydroxy EFV metabolite was detected in blood plasma , seminal plasma , and cerebrospinal fluid , with median concentrations of 314 . 5 ng / ml , 358 . 5 ng / ml , and 3 . 37 ng / ml , respectively .", "entity": [{"entity": "8 - hydroxy EFV", "entity_type": "Chemical", "pos": [4, 19]}], "task": "NER"}
{"text": "In contrast , 7 - hydroxy and 8 , 14 - hydroxy EFV were only detected in blood plasma and seminal plasma with median concentrations of 8 . 84 ng / ml and 10 . 23 ng / ml , and 5 . 63 ng / ml and 5 . 43 ng / ml , respectively .", "entity": [{"entity": "7 - hydroxy and 8 , 14 - hydroxy EFV", "entity_type": "Chemical", "pos": [14, 50]}], "task": "NER"}
{"text": "Interestingly , protein - free concentrations of metabolites were only detectable in seminal plasma , where a novel dihdyroxylated metabolite of EFV was also detected .", "entity": [{"entity": "EFV", "entity_type": "Chemical", "pos": [145, 148]}], "task": "NER"}
{"text": "This accumulation of protein - free EFV metabolites was demonstrated to be the result of differential protein binding in seminal plasma compared with that of blood plasma .", "entity": [{"entity": "EFV", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "In addition , the oxidative metabolites of EFV did not present with any significant pharmacologic activity toward HIV - 1 as measured using an HIV green fluorescent protein single - round infectivity assay .", "entity": [{"entity": "EFV", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "This study is the first to report the physiologic distribution of metabolites of an antiretroviral into biologic compartments that the virus is known to distribute and to examine their anti - HIV activity .", "entity": [], "task": "NER"}
{"text": "These data suggest that the male genital tract may be a novel compartment that should be considered in the evaluation of drug metabolite exposure .", "entity": [], "task": "NER"}
{"text": "Molecular interaction studies of HIV - 1 matrix protein p17 and heparin : identification of the heparin - binding motif of p17 as a target for the development of multitarget antagonists .", "entity": [], "task": "NER"}
{"text": "Once released by HIV ( + ) cells , p17 binds heparan sulfate proteoglycans ( HSPGs ) and CXCR1 on leukocytes causing their dysfunction .", "entity": [{"entity": "sulfate", "entity_type": "Chemical", "pos": [53, 60]}], "task": "NER"}
{"text": "By exploiting an approach integrating computational modeling , site - directed mutagenesis of p17 , chemical desulfation of heparin , and surface plasmon resonance , we characterized the interaction of p17 with heparin , a HSPG structural analog , and CXCR1 .", "entity": [], "task": "NER"}
{"text": "p17 binds to heparin with an affinity ( K ( d ) = 190 nm ) that is similar to those of other heparin - binding viral proteins .", "entity": [], "task": "NER"}
{"text": "Two stretches of basic amino acids ( basic motifs ) are present in p17 N and C termini .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "N", "entity_type": "Chemical", "pos": [71, 72]}, {"entity": "C", "entity_type": "Chemical", "pos": [77, 78]}], "task": "NER"}
{"text": "Neutralization ( Arg --> Ala substitution ) of the N - terminal , but not of the C - terminal basic motif , causes the loss of p17 heparin - binding capacity .", "entity": [{"entity": "Arg", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "Ala", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "N", "entity_type": "Chemical", "pos": [51, 52]}, {"entity": "C", "entity_type": "Chemical", "pos": [81, 82]}], "task": "NER"}
{"text": "The N - terminal heparin - binding motif of p17 partially overlaps the CXCR1 - binding domain .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [4, 5]}], "task": "NER"}
{"text": "Accordingly , its neutralization prevents also p17 binding to the chemochine receptor .", "entity": [], "task": "NER"}
{"text": "Competition experiments demonstrated that free heparin and heparan sulfate ( HS ) , but not selectively 2 - O - , 6 - O - , and N - O desulfated heparins , prevent p17 binding to substrate - immobilized heparin , indicating that the sulfate groups of the glycosaminoglycan mediate p17 interaction .", "entity": [{"entity": "sulfate", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "O", "entity_type": "Chemical", "pos": [108, 109]}, {"entity": "O", "entity_type": "Chemical", "pos": [118, 119]}, {"entity": "N - O", "entity_type": "Chemical", "pos": [128, 133]}, {"entity": "sulfate", "entity_type": "Chemical", "pos": [136, 143]}], "task": "NER"}
{"text": "Evaluation of the p17 antagonist activity of a panel of biotechnological heparins derived by chemical sulfation of the Escherichia coli K5 polysaccharide revealed that the highly N , O - sulfated derivative prevents the binding of p17 to both heparin and CXCR1 , thus inhibiting p17 - driven chemotactic migration of human monocytes with an efficiency that is higher than those of heparin and HS .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [179, 180]}, {"entity": "O", "entity_type": "Chemical", "pos": [183, 184]}], "task": "NER"}
{"text": "Here , we characterized at a molecular level the interaction of p17 with its cellular receptors , laying the basis for the development of heparin - mimicking p17 antagonists .", "entity": [], "task": "NER"}
{"text": "Insight into tissue unbound concentration : utility in drug discovery and development .", "entity": [], "task": "NER"}
{"text": "In a preclinical setting , plasma or whole tissue drug concentrations are often correlated with pharmacodynamics , although according to the free drug hypothesis , unbound drug concentration should be more pharmacologically relevant .", "entity": [], "task": "NER"}
{"text": "Alternatively , blood concentrations may be a good surrogate for tissue concentration for passively permeable compounds .", "entity": [], "task": "NER"}
{"text": "However , for a large number of compounds that are substrates for uptake and / or efflux transporters expressed at the tissue level , significant discrepancies are expected between unbound concentrations in blood and those in tissues .", "entity": [], "task": "NER"}
{"text": "Consequently , attempts have been made to measure tissue unbound drug concentrations using tissue homogenates , slices and microdialysis .", "entity": [], "task": "NER"}
{"text": "Mathematical expressions for calculating the rate and extent of drug distribution into tissues have also been established .", "entity": [], "task": "NER"}
{"text": "For example , a ratio of unbound concentration in the tissue to that in plasma ( K ( p , uu ) ) is the best indicator of the extent of tissue distribution .", "entity": [], "task": "NER"}
{"text": "Despite these technical advances , however , very few examples demonstrate a focus on tissue unbound drug concentrations in a preclinical setting .", "entity": [], "task": "NER"}
{"text": "This review will illustrate various techniques to estimate tissue unbound drug concentrations , relevant parameters to calculate the rate and extent of tissue distribution and different factors affecting tissue unbound concentration .", "entity": [], "task": "NER"}
{"text": "The review will also highlight various examples from the literature where tissue unbound drug concentrations have demonstrated a superior correlation with efficacy .", "entity": [], "task": "NER"}
{"text": "The impact of tissue unbound drug concentrations on the projection of human efficacious dose is also discussed .", "entity": [], "task": "NER"}
{"text": "Positive allosteric modulator of alpha 7 nicotinic - acetylcholine receptors , PNU - 120596 augments the effects of donepezil on learning and memory in aged rodents and non - human primates .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [53, 66]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [79, 91]}, {"entity": "donepezil", "entity_type": "Chemical", "pos": [116, 125]}], "task": "NER"}
{"text": "The development of novel therapeutic agents for disorders of cognition such as Alzheimer ' s disease ( AD ) is of paramount importance given the ever - increasing elderly population , however ; there is also considerable interest in any strategy that might enhance the clinical efficacy of currently available treatments .", "entity": [], "task": "NER"}
{"text": "The purpose of this study was to evaluate an adjunctive treatment strategy to memory enhancement , namely combining the commonly prescribed acetylcholinesterase inhibitor ( AChEI ) donepezil , with a positive allosteric modulator ( PAM ) of alpha 7 nicotinic - acetylcholine receptors ( alpha 7 - nAChRs ) , PNU - 120596 .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [181, 190]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [261, 274]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [308, 320]}], "task": "NER"}
{"text": "The treatment strategy was evaluated in a ( non - spatial ) spontaneous novel object recognition ( NOR ) task in young rats ; a water maze spatial learning and recall procedure in aged , cognitively - impaired rats , and a delayed match to sample ( working / short term memory ) task in aged rhesus monkeys .", "entity": [], "task": "NER"}
{"text": "In all three experiments a similar drug response was observed , namely that donepezil administered alone improved task performance in a dose - dependent manner ; that PNU - 120596 administered alone was without significant effect , but that the combination of PNU - 120596 with a subthreshold dose of donepezil was effective .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [76, 85]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [167, 179]}, {"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [260, 272]}, {"entity": "donepezil", "entity_type": "Chemical", "pos": [301, 310]}], "task": "NER"}
{"text": "The positive effect of the drug combination appeared to be alpha 7 - nAChR mediated given that it was blocked in the NOR task by the selective alpha 7 - nAChR antagonist methyllycaconitine ( MLA ) .", "entity": [{"entity": "methyllycaconitine", "entity_type": "Chemical", "pos": [170, 188]}, {"entity": "MLA", "entity_type": "Chemical", "pos": [191, 194]}], "task": "NER"}
{"text": "Collectively , these data indicate that PNU - 120596 increases the effective dose range of donepezil in learning / memory - related tasks in young and age - impaired animal models .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [40, 52]}, {"entity": "donepezil", "entity_type": "Chemical", "pos": [91, 100]}], "task": "NER"}
{"text": "The results suggest that alpha 7 - nAChR - selective PAMs like PNU - 120596 have potential as adjunctive treatments with acetylcholinesterase inhibitors ( e . g . , donepezil ) for age - related illnesses such as AD as well memory disorders not necessarily associated with advanced age .", "entity": [{"entity": "PNU - 120596", "entity_type": "Chemical", "pos": [63, 75]}, {"entity": "donepezil", "entity_type": "Chemical", "pos": [165, 174]}], "task": "NER"}
{"text": "1H NMR spectra of ethane - 1 , 2 - diol and other vicinal diols in benzene : GIAO / DFT shift calculations .", "entity": [{"entity": "1H", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "ethane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [18, 39]}, {"entity": "vicinal diols", "entity_type": "Chemical", "pos": [50, 63]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [67, 74]}], "task": "NER"}
{"text": "The proton NMR spectra of several 1 , 2 - diols in benzene have been analysed so as to associate each magnetically nonequivalent proton with its chemical shift .", "entity": [{"entity": "1 , 2 - diols", "entity_type": "Chemical", "pos": [34, 47]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "The shifts and coupling constants of the OH and methylene protons of ethane - 1 , 2 - diol have been determined in a wide range of solvents .", "entity": [{"entity": "OH", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "methylene", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "ethane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [69, 90]}], "task": "NER"}
{"text": "The conformer distribution and the proton NMR shifts of these 1 , 2 - diols in benzene have been computed on the basis of density functional theory .", "entity": [{"entity": "1 , 2 - diols", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "The solvent is included using the integral - equation - formalism polarizable continuum model implemented in Gaussian 09 .", "entity": [], "task": "NER"}
{"text": "Relative Gibbs energies for all stable conformers are calculated at the Perdew , Burke and Enzerhof ( PBE ) 0 / 6 - 311 + G ( d , p ) level , and shifts are calculated using the gauge - including atomic orbital method with the PBE0 / 6 - 311 + G ( d , p ) geometry but using the cc - pVTZ basis set .", "entity": [], "task": "NER"}
{"text": "Previous calculations on ethane - 1 , 2 - diol and propane - 1 , 2 - diol have been corrected and extended .", "entity": [{"entity": "ethane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [25, 46]}, {"entity": "propane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [51, 73]}], "task": "NER"}
{"text": "New calculations on tert - butylethane - 1 , 2 - diol , phenylethane - 1 , 2 - diol , butane - 2 , 3 - diols ( dl and meso ) and cyclohexane - 1 , 2 - diols ( cis and trans ) are presented .", "entity": [{"entity": "tert - butylethane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [20, 53]}, {"entity": "phenylethane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [56, 83]}, {"entity": "butane - 2 , 3 - diols", "entity_type": "Chemical", "pos": [86, 108]}, {"entity": "cyclohexane - 1 , 2 - diols", "entity_type": "Chemical", "pos": [129, 156]}], "task": "NER"}
{"text": "Overall , the computed NMR shifts are in good agreement with experimental values for the OH protons but remain systematically high for CH protons .", "entity": [{"entity": "OH", "entity_type": "Chemical", "pos": [89, 91]}, {"entity": "CH", "entity_type": "Chemical", "pos": [135, 137]}], "task": "NER"}
{"text": "Some results based on the Gaussian 03 solvation model are included for comparison .", "entity": [], "task": "NER"}
{"text": "Discovery of Schaeffer ' s acid analogues as lead structures of mycobacterium tuberculosis type II dehydroquinase using a rational drug design approach .", "entity": [{"entity": "Schaeffer ' s acid", "entity_type": "Chemical", "pos": [13, 31]}], "task": "NER"}
{"text": "Rational ligand design : Schaeffer ' s acid analogues were identified as novel inhibitors of M . tuberculosis type II dehydroquinase , a key enzyme of the shikimate pathway .", "entity": [{"entity": "Schaeffer ' s acid", "entity_type": "Chemical", "pos": [25, 43]}], "task": "NER"}
{"text": "Their likely binding mode was predicted using a combination of ensemble docking and flexible active site residues .", "entity": [], "task": "NER"}
{"text": "Potentially , this scaffold could provide a good starting point for the design of antitubercular agents .", "entity": [], "task": "NER"}
{"text": "Stem cell - mediated gene delivering for the treatment of cerebral ischemia : progress and prospectives .", "entity": [], "task": "NER"}
{"text": "Ischemic stroke is one of the leading causes of death and disability worldwide .", "entity": [], "task": "NER"}
{"text": "There is no effective treatment for ischemic stroke apart from thrombolytic therapy , which has a narrow therapeutic time window .", "entity": [], "task": "NER"}
{"text": "Gene therapy has proven to be effective in experimental stroke , but it suffers from disadvantages that limit its clinical application , such as difficulty in intracranial delivering of therapeutic genes , low efficacy in transfecting host cells and long - term expression of exogenous genes .", "entity": [], "task": "NER"}
{"text": "Delivering therapeutic genes to the ischemic brain via stem cells is an alternative strategy of combined gene and stem cell therapy .", "entity": [], "task": "NER"}
{"text": "There are advantages for stem cell - mediated gene delivery as opposed to direct gene transfer .", "entity": [], "task": "NER"}
{"text": "In recent years , studies used stem cells that over - express different neurotrophic factors , such as BDNF , GDNT , or NT3 , and found that the delivery of these genetically - modified stem cells to animal models of ischemic stroke is safe and effective , thus suggesting that stem cell - based gene therapy may be a promising treatment for stroke .", "entity": [], "task": "NER"}
{"text": "This review summarizes the advantages and recent progress of stem cell - based gene therapy for ischemic stroke .", "entity": [], "task": "NER"}
{"text": "We also discuss the relevant strategy for optimizing stem cell - based gene therapy and discuss the potential strategies for its future application .", "entity": [], "task": "NER"}
{"text": "Structure Based Lead Optimization Approach in Discovery of Selective DPP4 Inhibitors .", "entity": [], "task": "NER"}
{"text": "Diabetes mellitus is a chronic progressive metabolic disorder that has profound consequences for individuals , families , and society .", "entity": [], "task": "NER"}
{"text": "To date , main available oral antidiabetic medications target either insulin resistance ( metformin , glitazones ) , or insulin deficiency ( sulfonylureas , glinides ) , but leading to shortfalls in medication .", "entity": [{"entity": "metformin", "entity_type": "Chemical", "pos": [90, 99]}, {"entity": "glitazones", "entity_type": "Chemical", "pos": [102, 112]}, {"entity": "sulfonylureas", "entity_type": "Chemical", "pos": [141, 154]}, {"entity": "glinides", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "Advancement in modern oral hypoglycemic agents may be encouraged with or in place of traditional therapies .", "entity": [], "task": "NER"}
{"text": "The lower risk for hypoglycemic events as compared with other insulinotropic or insulin - sensitizing agents make DPP - 4 inhibitors very promising candidates for a more physiological treatment of type - 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Only some DPP - 4 inhibitors are currently used for the treatment of type 2 diabetes ( T2DM ) and various inhibitors currently undergoing animal and human testing .", "entity": [], "task": "NER"}
{"text": "A number of catalytically active DPPs distinct from DPP - 4 ( DPP II , FAP , DPP - 8 , and DPP - 9 ) have been described that is associated with side - effect and toxicity .", "entity": [], "task": "NER"}
{"text": "To discover potent and selective and safer drugs in a shorter time frame and with reduced cost it requires using an innovative approach for designing novel inhibitors .", "entity": [], "task": "NER"}
{"text": "This review article focuses on the status of advanced lead candidates of DPP group and their binding affinity with the active site residue of target structure which help in discovery of potent and selective DPP - 4 inhibitors by lead optimization approach .", "entity": [], "task": "NER"}
{"text": "Metabolomics and mass isotopomer analysis as a strategy for pathway discovery : pyrrolyl and cyclopentenyl derivatives of the pro - drug of abuse , levulinate .", "entity": [{"entity": "pyrrolyl", "entity_type": "Chemical", "pos": [80, 88]}, {"entity": "cyclopentenyl", "entity_type": "Chemical", "pos": [93, 106]}, {"entity": "levulinate", "entity_type": "Chemical", "pos": [148, 158]}], "task": "NER"}
{"text": "We recently reported that levulinate ( 4 - ketopentanoate ) is converted in the liver to 4 - hydroxypentanoate , a drug of abuse , and that the formation of 4 - hydroxypentanoate is stimulated by ethanol oxidation .", "entity": [{"entity": "levulinate", "entity_type": "Chemical", "pos": [26, 36]}, {"entity": "4 - ketopentanoate", "entity_type": "Chemical", "pos": [39, 57]}, {"entity": "4 - hydroxypentanoate", "entity_type": "Chemical", "pos": [89, 110]}, {"entity": "4 - hydroxypentanoate", "entity_type": "Chemical", "pos": [157, 178]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [196, 203]}], "task": "NER"}
{"text": "We also identified 3 parallel beta - oxidation pathways by which levulinate and 4 - hydroxypentanoate are catabolized to propionyl - CoA and acetyl - CoA .", "entity": [{"entity": "levulinate", "entity_type": "Chemical", "pos": [65, 75]}, {"entity": "4 - hydroxypentanoate", "entity_type": "Chemical", "pos": [80, 101]}, {"entity": "propionyl - CoA", "entity_type": "Chemical", "pos": [121, 136]}, {"entity": "acetyl - CoA", "entity_type": "Chemical", "pos": [141, 153]}], "task": "NER"}
{"text": "We now report that levulinate forms three seven - carbon cyclical CoA esters by processes starting with the elongation of levulinyl - CoA by acetyl - CoA to 3 , 6 - diketoheptanoyl - CoA .", "entity": [{"entity": "levulinate", "entity_type": "Chemical", "pos": [19, 29]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [50, 56]}, {"entity": "levulinyl - CoA", "entity_type": "Chemical", "pos": [122, 137]}, {"entity": "acetyl - CoA", "entity_type": "Chemical", "pos": [141, 153]}, {"entity": "3 , 6 - diketoheptanoyl - CoA", "entity_type": "Chemical", "pos": [157, 186]}], "task": "NER"}
{"text": "The latter gamma - diketo CoA ester undergoes two parallel cyclization processes .", "entity": [{"entity": "gamma - diketo CoA ester", "entity_type": "Chemical", "pos": [11, 35]}], "task": "NER"}
{"text": "One process yields a mixture of tautomers , i . e . , cyclopentenyl - and cyclopentadienyl - acyl - CoAs .", "entity": [{"entity": "cyclopentenyl - and cyclopentadienyl - acyl - CoAs", "entity_type": "Chemical", "pos": [54, 104]}], "task": "NER"}
{"text": "The second cyclization process yields a methyl - pyrrolyl - acetyl - CoA containing a nitrogen atom derived from the epsilon - nitrogen of lysine but without carbons from lysine .", "entity": [{"entity": "methyl - pyrrolyl - acetyl - CoA", "entity_type": "Chemical", "pos": [40, 72]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [86, 94]}, {"entity": "epsilon - nitrogen", "entity_type": "Chemical", "pos": [117, 135]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [139, 145]}, {"entity": "carbons", "entity_type": "Chemical", "pos": [158, 165]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [171, 177]}], "task": "NER"}
{"text": "The cyclic CoA esters were identified in rat livers perfused with levulinate and in livers and brains from rats gavaged with calcium levulinate +/- ethanol .", "entity": [{"entity": "cyclic CoA esters", "entity_type": "Chemical", "pos": [4, 21]}, {"entity": "levulinate", "entity_type": "Chemical", "pos": [66, 76]}, {"entity": "calcium levulinate", "entity_type": "Chemical", "pos": [125, 143]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "Lastly , 3 , 6 - diketoheptanoyl - CoA , like 2 , 5 - diketohexane , pyrrolates free lysine and , presumably , lysine residues from proteins .", "entity": [{"entity": "3 , 6 - diketoheptanoyl - CoA", "entity_type": "Chemical", "pos": [9, 38]}, {"entity": "2 , 5 - diketohexane", "entity_type": "Chemical", "pos": [46, 66]}, {"entity": "pyrrolates", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [85, 91]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [111, 117]}], "task": "NER"}
{"text": "This may represent a new pathway for protein pyrrolation .", "entity": [], "task": "NER"}
{"text": "The cyclic CoA esters and related pyrrolation processes may play a role in the toxic effects of 4 - hydroxypentanoate .", "entity": [{"entity": "cyclic CoA esters", "entity_type": "Chemical", "pos": [4, 21]}, {"entity": "4 - hydroxypentanoate", "entity_type": "Chemical", "pos": [96, 117]}], "task": "NER"}
{"text": "The evolution of north - east Atlantic gadfly petrels using statistical phylogeography .", "entity": [], "task": "NER"}
{"text": "Macaronesia ( north - east Atlantic archipelagos ) has been host to complex patterns of colonization and differentiation in many groups of organisms including seabirds such as gadfly petrels ( genus Pterodroma ) .", "entity": [], "task": "NER"}
{"text": "Considering the subspecies of widely distributed soft - plumaged petrel for many years , the taxonomic status of the three gadfly petrel taxa breeding in Macaronesia is not yet settled , some authors advocating the presence of three , two or one species .", "entity": [], "task": "NER"}
{"text": "These birds have already been the subject of genetic studies with only one mtDNA gene and relatively modest sample sizes .", "entity": [], "task": "NER"}
{"text": "In this study , using a total of five genes ( two mitochondrial genes and three nuclear introns ) , we investigated the population and phylogeographical histories of petrel populations breeding on Madeira and Cape Verde archipelagos .", "entity": [], "task": "NER"}
{"text": "Despite confirming complete lineage sorting with mtDNA , analyses with nucDNA failed to reveal any population structuring and Isolation with Migration analysis revealed the absence of gene flow during the differentiation process of these populations .", "entity": [], "task": "NER"}
{"text": "It appears that the three populations diverged in the late Pleistocene in the last 150 000 years , that is 10 times more recently than previous estimates based solely on one mtDNA gene .", "entity": [], "task": "NER"}
{"text": "Finally , our results suggest that the Madeira petrel population is ancestral rather than that from Cape Verde .", "entity": [], "task": "NER"}
{"text": "This study strongly advocates the use of nuclear loci in addition to mtDNA in demographical and phylogeographical history studies .", "entity": [], "task": "NER"}
{"text": "WDDD : Worm Developmental Dynamics Database .", "entity": [], "task": "NER"}
{"text": "During animal development , cells undergo dynamic changes in position and gene expression .", "entity": [], "task": "NER"}
{"text": "A collection of quantitative information about morphological dynamics under a wide variety of gene perturbations would provide a rich resource for understanding the molecular mechanisms of development .", "entity": [], "task": "NER"}
{"text": "Here , we created a database , the Worm Developmental Dynamics Database ( http : / / so . qbic . riken . jp / wddd / ) , which stores a collection of quantitative information about cell division dynamics in early Caenorhabditis elegans embryos with single genes silenced by RNA - mediated interference .", "entity": [], "task": "NER"}
{"text": "The information contains the three - dimensional coordinate values of the outlines of nuclear regions and the dynamics of the outlines over time .", "entity": [], "task": "NER"}
{"text": "The database provides free access to 50 sets of quantitative data for wild - type embryos and 136 sets of quantitative data for RNA - mediated interference embryos corresponding to 72 of the 97 essential embryonic genes on chromosome III .", "entity": [], "task": "NER"}
{"text": "The database also provides sets of four - dimensional differential interference contrast microscopy images on which the quantitative data were based .", "entity": [], "task": "NER"}
{"text": "The database will provide a novel opportunity for the development of computational methods to obtain fresh insights into the mechanisms of development .", "entity": [], "task": "NER"}
{"text": "The quantitative information and microscopy images can be synchronously viewed through a web browser , which is designed for easy access by experimental biologists .", "entity": [], "task": "NER"}
{"text": "Atomically flat , large - sized , two - dimensional organic nanocrystals .", "entity": [], "task": "NER"}
{"text": "Large - sized , 2D single crystals of perylene are grown by both solution - cast and physical vapor transport methods .", "entity": [{"entity": "perylene", "entity_type": "Chemical", "pos": [38, 46]}], "task": "NER"}
{"text": "The crystals have a atomically flat parallelogram morphology and the aspect ratios of the lateral extension compared to the thickness are up to 10 ( 3 ) .", "entity": [], "task": "NER"}
{"text": "The atomically flat feature leads to good interface contact , making a single - crystal field - effect transistor with higher mobility .", "entity": [], "task": "NER"}
{"text": "The mobility of atomically flat crystals can be 10 ( 3 ) - 10 ( 4 ) times higher than rough crystals .", "entity": [], "task": "NER"}
{"text": "3D - QSAR - assisted drug design : identification of a potent quinazoline - based Aurora kinase inhibitor .", "entity": [{"entity": "quinazoline", "entity_type": "Chemical", "pos": [62, 73]}], "task": "NER"}
{"text": "We describe the 3D - QSAR - assisted design of an Aurora kinase A inhibitor with improved physicochemical properties , in vitro activity , and in vivo pharmacokinetic profiles over those of the initial lead .", "entity": [], "task": "NER"}
{"text": "Three different 3D - QSAR models were built and validated by using a set of 66 pyrazole ( Model I ) and furanopyrimidine ( Model II ) compounds with IC ( 50 ) values toward Aurora kinase A ranging from 33 nM to 10 . 5 mu M .", "entity": [{"entity": "pyrazole", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "furanopyrimidine", "entity_type": "Chemical", "pos": [104, 120]}], "task": "NER"}
{"text": "The best 3D - QSAR model , Model III , constructed with 24 training set compounds from both series , showed robustness ( r ( 2 ) ( CV ) = 0 . 54 and 0 . 52 for CoMFA and CoMSIA , respectively ) and superior predictive capacity for 42 test set compounds ( R ( 2 ) ( pred ) = 0 . 52 and 0 . 67 , CoMFA and CoMSIA ) .", "entity": [], "task": "NER"}
{"text": "Superimposition of CoMFA and CoMSIA Model III over the crystal structure of Aurora kinase A suggests the potential to improve the activity of the ligands by decreasing the steric clash with Val147 and Leu139 and by increasing hydrophobic contact with Leu139 and Gly216 residues in the solvent - exposed region of the enzyme .", "entity": [], "task": "NER"}
{"text": "Based on these suggestions , the rational redesign of furanopyrimidine 24 ( clog P = 7 . 41 ; Aurora A IC ( 50 ) = 43 nM ; HCT - 116 IC ( 50 ) = 400 nM ) led to the identification of quinazoline 67 ( clog P = 5 . 28 ; Aurora A IC ( 50 ) = 25 nM ; HCT - 116 IC ( 50 ) = 23 nM ) .", "entity": [{"entity": "furanopyrimidine", "entity_type": "Chemical", "pos": [54, 70]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [183, 194]}], "task": "NER"}
{"text": "Rat in vivo pharmacokinetic studies showed that 67 has better systemic exposure after i . v . administration than 24 , and holds potential for further development .", "entity": [], "task": "NER"}
{"text": "Assessing the potential effectiveness of food and beverage taxes and subsidies for improving public health : a systematic review of prices , demand and body weight outcomes .", "entity": [], "task": "NER"}
{"text": "Taxes and subsidies are increasingly being considered as potential policy instruments to incentivize consumers to improve their food and beverage consumption patterns and related health outcomes .", "entity": [], "task": "NER"}
{"text": "This study provided a systematic review of recent U . S . studies on the price elasticity of demand for sugar - sweetened beverages ( SSBs ) , fast food , and fruits and vegetables , as well as the direct associations of prices / taxes with body weight outcomes .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [104, 109]}], "task": "NER"}
{"text": "Based on the recent literature , the price elasticity of demand for SSBs , fast food , fruits and vegetables was estimated to be - 1 . 21 , - 0 . 52 , - 0 . 49 and - 0 . 48 , respectively .", "entity": [], "task": "NER"}
{"text": "The studies that linked soda taxes to weight outcomes showed minimal impacts on weight ; however , they were based on existing state - level sales taxes that were relatively low .", "entity": [], "task": "NER"}
{"text": "Higher fast - food prices were associated with lower weight outcomes particularly among adolescents , suggesting that raising prices would potentially impact weight outcomes .", "entity": [], "task": "NER"}
{"text": "Lower fruit and vegetable prices were generally found to be associated with lower body weight outcomes among both low - income children and adults , suggesting that subsidies that would reduce the cost of fruits and vegetables for lower - socioeconomic populations may be effective in reducing obesity .", "entity": [], "task": "NER"}
{"text": "Pricing instruments should continue to be considered and evaluated as potential policy instruments to address public health risks .", "entity": [], "task": "NER"}
{"text": "Cannabinoid agonists increase the interaction between beta - Arrestin 2 and ERK1 / 2 and upregulate beta - Arrestin 2 and 5 - HT ( 2A ) receptors .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [122, 128]}], "task": "NER"}
{"text": "We have recently reported that selective cannabinoid 2 ( CB ( 2 ) ) receptor agonists upregulate 5 - HT ( 2A ) receptors by enhancing ERK1 / 2 signaling in prefrontal cortex ( PFCx ) .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [97, 103]}], "task": "NER"}
{"text": "Increased activity of cortical 5 - HT ( 2A ) receptors has been associated with several neuropsychiatric disorders such as anxiety and schizophrenia .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [31, 37]}], "task": "NER"}
{"text": "Here we examine the mechanisms involved in this enhanced ERK1 / 2 activation in rat PFCx and in a neuronal cell model .", "entity": [], "task": "NER"}
{"text": "Sprague - Dawley rats treated with a non - selective cannabinoid agonist ( CP55940 , 50 mu g / kg , 7 days , i . p . ) showed enhanced co - immunoprecipitation of beta - Arrestin 2 and ERK1 / 2 , enhanced pERK protein levels , and enhanced expression of beta - Arrestin 2 mRNA and protein levels in PFCx .", "entity": [{"entity": "CP55940", "entity_type": "Chemical", "pos": [75, 82]}], "task": "NER"}
{"text": "In a neuronal cell line , we found that selective CB ( 2 ) receptor agonists upregulate beta - Arrestin 2 , an effect that was prevented by selective CB ( 2 ) receptor antagonist JTE - 907 and CB ( 2 ) shRNA lentiviral particles .", "entity": [{"entity": "JTE - 907", "entity_type": "Chemical", "pos": [179, 188]}], "task": "NER"}
{"text": "Additionally , inhibition of clathrin - mediated endocytosis , ERK1 / 2 , and the AP - 1 transcription factor also prevented the cannabinoid receptor - induced upregulation of beta - Arrestin 2 .", "entity": [], "task": "NER"}
{"text": "Our results suggest that sustained activation of CB ( 2 ) receptors would enhance beta - Arrestin 2 expression possibly contributing to its increased interaction with ERK1 / 2 , thereby driving the upregulation of 5 - HT ( 2A ) receptors .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [214, 220]}], "task": "NER"}
{"text": "The CB ( 2 ) receptor - mediated upregulation of beta - Arrestin 2 would be mediated , at least in part , by an ERK1 / 2 - dependent activation of AP - 1 .", "entity": [], "task": "NER"}
{"text": "These data could provide the rationale for some of the adverse effects associated with repeated cannabinoid exposure and shed light on some CB ( 2 ) receptor agonists that could represent an alternative therapeutic because of their minimal effect on serotonergic neurotransmission .", "entity": [], "task": "NER"}
{"text": "Beneficial effects of polyphenols on cardiovascular disease .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "In recent years , numerous studies have demonstrated the health benefits of polyphenols , and special attention has been paid to their beneficial effects against cardiovascular disease , the leading cause of death in the world today .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [76, 87]}], "task": "NER"}
{"text": "Polyphenols present vasodilator effects and are able to improve lipid profiles and attenuate the oxidation of low density lipoproteins .", "entity": [{"entity": "Polyphenols", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In addition , they present clear anti - inflammatory effects and can modulate apoptotic processes in the vascular endothelium .", "entity": [], "task": "NER"}
{"text": "It has been suggested that most of these effects are a consequence of the antioxidant properties of polyphenols , but this idea is not completely accepted , and many other mechanisms have been proposed recently to explain the health effects of these compounds .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "In fact , different signaling pathways have been linked to polyphenols .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "This review brings together some recent studies which establish the beneficial properties of polyphenols for cardiovascular disease and analyzes the mechanisms involved in these properties .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "Deficits in male sexual behavior in adulthood after social instability stress in adolescence in rats .", "entity": [], "task": "NER"}
{"text": "There is increasing evidence that exposure to stressors in adolescence has long - lasting effects on emotional and cognitive behavior , but little is known as to whether reproductive functions are affected .", "entity": [], "task": "NER"}
{"text": "We investigated appetitive and consummatory aspects of sexual behavior in male rats that were exposed to chronic social instability stress ( SS , n = 24 ) for 16 days in mid - adolescence compared to control rats ( CTL , n = 24 ) .", "entity": [], "task": "NER"}
{"text": "Over five sexual behavior test sessions with a receptive female , SS rats made fewer ejaculations ( p = 0 . 02 ) and had longer latencies to ejaculation ( p = 0 . 03 ) .", "entity": [], "task": "NER"}
{"text": "When only data from rats that ejaculated in the fifth session were analyzed , SS rats ( n = 18 ) had reduced copulatory efficiency ( more mounts and intromissions before ejaculation ) compared to CTL rats ( n = 19 ) ( p = 0 . 004 ) , and CTL rats were twice as likely as SS rats to make more than one ejaculation in the fifth session ( p = 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Further , more CTL ( 14 / 24 ) than SS ( 5 / 25 ) rats ejaculated in four or more sessions ( p = 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "SS rats had lower plasma testosterone concentrations than CTL rats ( p = 0 . 05 ) , but did not differ in androgen receptor , estrogen receptor alpha , or Fos immunoreactive cell counts in the medial preoptic area .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [106, 114]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "The groups did not differ in a partner preference test administered between the fourth and fifth sexual behavior session .", "entity": [], "task": "NER"}
{"text": "The results suggest that developmental history contributes to individual differences in reproductive behavior , and that stress exposures in adolescence may be a factor in sexual sluggishness .", "entity": [], "task": "NER"}
{"text": "Angiotensin AT2 receptor activates the cyclic - AMP signaling pathway in eel .", "entity": [{"entity": "cyclic - AMP", "entity_type": "Chemical", "pos": [39, 51]}], "task": "NER"}
{"text": "A unique angiotensin type 2 receptor ( AT2 ) that induces a cAMP signaling pathway was cloned and characterized for the first time in fish , Anguilla japonica .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [60, 64]}], "task": "NER"}
{"text": "Phylogeny and synteny results showed that the AT2s among fishes and tetrapods share the same origin despite a sub - cluster formation among eel , salmon , and zebrafish .", "entity": [], "task": "NER"}
{"text": "The eel AT2 was expressed abundantly in the spleen and localized at straight arterioles and ellipsoid regions prior to the sinusoid , suggesting a role in the regulation of microcirculation and / or immune response .", "entity": [], "task": "NER"}
{"text": "Various angiotensin ( Ang ) peptides , including Ang II , Ang III , and Ang IV , were detected in the spleen by a radioimmunoassay coupled with HPLC separation , and these endogenous peptides stimulated a cAMP signaling , which has no crosstalk with cGMP pathway .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [205, 209]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [250, 254]}], "task": "NER"}
{"text": "The common and contrasting features of AT2 between fishes and mammals imply some ancestral characters of AT2 , which are important information for receptor binding and evolutionary studies .", "entity": [], "task": "NER"}
{"text": "Intraindividual and interindividual variabilities in endogenous cortisol 6 beta - hydroxylation clearance as an index for in vivo CYP3A phenotyping in humans .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "This study was designed to evaluate the in vivo activity of cytochrome P450 3A ( CYP3A ) in 49 healthy Japanese subjects aged 22 - 58 years using endogenous cortisol 6 beta - hydroxylation clearance [ CLm ( 6 beta ) ] , a novel biomarker for CYP3A phenotyping .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "CLm ( 6 beta ) in the 49 healthy subjects was 2 . 40 +/- 0 . 79 ml / min with an approximately 4 - fold interindividual variability of CYP3A activity .", "entity": [], "task": "NER"}
{"text": "The mean clearance in the 24 women was 2 . 50 +/- 0 . 89 ml / min ; the value in the women was higher than in the 25 men ( 2 . 30 +/- 0 . 69 ml / min ) by approximately 9 % .", "entity": [], "task": "NER"}
{"text": "We also measured the change of CLm ( 6 beta ) in 14 healthy subjects in the morning at 10 : 00 - 12 : 00 every 2 or 3 days over a period of 36 - 53 days and observed a 1 . 5 - fold to 3 . 4 - fold day - to - day intraindividual variability in the CYP3A activity .", "entity": [], "task": "NER"}
{"text": "The mean value for CLm ( 6 beta ) in each subject for 36 - 53 days was 2 . 54 +/- 0 . 76 ml / min ( n = 14 ) .", "entity": [], "task": "NER"}
{"text": "We also evaluated the CLm ( 6 beta ) every 2 hours from 8 : 00 - 20 : 00 in 26 healthy subjects .", "entity": [], "task": "NER"}
{"text": "The within - day intraindividual clearance variability was 1 . 1 - fold to 2 . 5 - fold ( 2 . 45 +/- 0 . 91 ml / min , n = 26 ) .", "entity": [], "task": "NER"}
{"text": "No characteristic diurnal rhythms were observed in the in vivo activity of CYP3A .", "entity": [], "task": "NER"}
{"text": "Chemotherapy of leishmaniasis part X : synthesis and bioevaluation of novel terpenyl heterocycles .", "entity": [{"entity": "terpenyl heterocycles", "entity_type": "Chemical", "pos": [76, 97]}], "task": "NER"}
{"text": "Some novel alpha and beta ionone based chalcones and their dihydropyrazolidines / pyrazolidines have been synthesized and evaluated for their in vitro and in vivo antileishmanial activities against Leishmania donovani .", "entity": [{"entity": "alpha and beta ionone", "entity_type": "Chemical", "pos": [11, 32]}, {"entity": "chalcones", "entity_type": "Chemical", "pos": [39, 48]}, {"entity": "dihydropyrazolidines", "entity_type": "Chemical", "pos": [59, 79]}, {"entity": "pyrazolidines", "entity_type": "Chemical", "pos": [82, 95]}], "task": "NER"}
{"text": "Amongest all , one compound ( 4d ) exhibited significant in vitro activity against intracellular amastigotes of Leishmania donovani with IC ( 50 ) values of 7 . 49 mu M and was found promising as compared to reference drug , miltefosine .", "entity": [{"entity": "miltefosine", "entity_type": "Chemical", "pos": [225, 236]}], "task": "NER"}
{"text": "On the basis of good Selectivity Index ( S . I . ) , the compound was further tested for its in vivo response against Leishmania donovani / hamster model and has shown significant inhibition of parasite multiplication ( 81 % ) .", "entity": [], "task": "NER"}
{"text": "The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent .", "entity": [], "task": "NER"}
{"text": "Design , synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells .", "entity": [{"entity": "naringenin", "entity_type": "Chemical", "pos": [48, 58]}], "task": "NER"}
{"text": "Based on the previous result , several naringenin derivatives modified at position 7 with bulky substituents were designed and synthesized , and their inhibitory effects on HCT116 human colon cancer cells were tested using a clonogenic assay .", "entity": [{"entity": "naringenin", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "The half maximal inhibitory concentrations ( IC ( 50 ) ) of five naringenin derivatives ranged between 1 . 20 mu M and 20 . 01 mu M which are much better than naringenin used as a control .", "entity": [{"entity": "naringenin", "entity_type": "Chemical", "pos": [65, 75]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [159, 169]}], "task": "NER"}
{"text": "In addition , new structural modification at C - 4 of flavanone results in improving both the anti - cancer effect and anti - oxidative effect .", "entity": [{"entity": "flavanone", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "In vitro cyclin dependent kinase 2 ( CDK2 ) binding assay was carried out based on the previous results .", "entity": [], "task": "NER"}
{"text": "To elucidate the possible interaction between naringenin derivatives and CDK2 , in silico docking study was performed .", "entity": [{"entity": "naringenin", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "This result demonstrates the rationale for the different inhibitory activities of the naringenin derivatives .", "entity": [{"entity": "naringenin", "entity_type": "Chemical", "pos": [86, 96]}], "task": "NER"}
{"text": "These findings could be used for designing cancer therapeutic or preventive flavanone - derived agents .", "entity": [{"entity": "flavanone", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Triazoyl - phenyl linker system enhancing the aqueous solubility of a molecular probe and its efficiency in affinity labeling of a target protein for jasmonate glucoside .", "entity": [{"entity": "Triazoyl - phenyl", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "jasmonate glucoside", "entity_type": "Chemical", "pos": [150, 169]}], "task": "NER"}
{"text": "In methods employing molecular probes to explore the targets of bioactive small molecules , long or rigid linker moieties are thought to be critical factors for efficient tagging of target protein .", "entity": [], "task": "NER"}
{"text": "We previously reported the synthesis of a jasmonate glucoside probe with a highly rigid linker consisting of a triazoyl - phenyl ( TAzP ) moiety , and this probe demonstrated effective target tagging .", "entity": [{"entity": "jasmonate glucoside", "entity_type": "Chemical", "pos": [42, 61]}, {"entity": "triazoyl - phenyl", "entity_type": "Chemical", "pos": [111, 128]}, {"entity": "TAzP", "entity_type": "Chemical", "pos": [131, 135]}], "task": "NER"}
{"text": "Here we compare the TAzP probe with other rigid or flexible probes with respect to target tagging efficiency , hydrophobic parameters , aqueous solubility , and dihedral angles around the biaryl linkage by a combination of empirical and calculation methods .", "entity": [{"entity": "TAzP", "entity_type": "Chemical", "pos": [20, 24]}, {"entity": "biaryl", "entity_type": "Chemical", "pos": [188, 194]}], "task": "NER"}
{"text": "The rigid biaryl linkage of the TAzP probe has a skewed conformation that influences its aqueous solubility .", "entity": [{"entity": "biaryl", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "TAzP", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "Such features that include rigidness and good aqueous solubility resulted in highly efficient target tagging .", "entity": [], "task": "NER"}
{"text": "These findings provide a promising guideline toward designing of better linkers for improving molecular probe performance .", "entity": [], "task": "NER"}
{"text": "Discovery of a selective M 4 positive allosteric modulator based on the 3 - amino - thieno [ 2 , 3 - b ] pyridine - 2 - carboxamide scaffold : development of ML253 , a potent and brain penetrant compound that is active in a preclinical model of schizophrenia .", "entity": [{"entity": "3 - amino - thieno [ 2 , 3 - b ] pyridine - 2 - carboxamide", "entity_type": "Chemical", "pos": [72, 131]}, {"entity": "ML253", "entity_type": "Chemical", "pos": [158, 163]}], "task": "NER"}
{"text": "Herein we report a next generation muscarinic receptor 4 ( M ( 4 ) ) positive allosteric modulator ( PAM ) , ML253 which exhibits nanomolar activity at both the human ( EC ( 50 ) = 56 nM ) and rat ( EC ( 50 ) = 176 nM ) receptors and excellent efficacy by the left - ward shift of the ACh concentration response curve ( fold shift , human = 106 ; rat = 50 ) .", "entity": [{"entity": "ML253", "entity_type": "Chemical", "pos": [109, 114]}, {"entity": "ACh", "entity_type": "Chemical", "pos": [285, 288]}], "task": "NER"}
{"text": "In addition , ML253 is selective against the four other muscarinic subtypes , displays excellent CNS exposure and is active in an amphetamine - induced hyperlocomotion assay .", "entity": [{"entity": "ML253", "entity_type": "Chemical", "pos": [14, 19]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [130, 141]}], "task": "NER"}
{"text": "Protein tyrosine phosphatase 1B inhibitory effect by dammarane - type triterpenes from hydrolyzate of total Gynostemma pentaphyllum saponins .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [8, 16]}, {"entity": "dammarane", "entity_type": "Chemical", "pos": [53, 62]}, {"entity": "triterpenes", "entity_type": "Chemical", "pos": [70, 81]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [132, 140]}], "task": "NER"}
{"text": "Protein tyrosine phosphatase 1B ( PTP1B ) is an important factor in non - insulin - dependent diabetes mellitus ( type - 2 diabetes ) , and a promising target for treatment of diabetes and obesity .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [8, 16]}], "task": "NER"}
{"text": "Therefore , the aim of this study is to investigate the inhibitory activities of constituents ( three new together with twelve known triterpenes compounds ) isolated from the hydrolyzate of total saponins from Gynostemma pentaphyllum .", "entity": [{"entity": "triterpenes", "entity_type": "Chemical", "pos": [133, 144]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [196, 204]}], "task": "NER"}
{"text": "Their structures were accomplished mainly base on the spectroscopic methods , and then were further confirmed by X - ray crystal diffraction .", "entity": [], "task": "NER"}
{"text": "All the compounds were evaluated for inhibitory activity against PTP1B .", "entity": [], "task": "NER"}
{"text": "Current data suggested that the compounds 1 , 3 , 12 , 13 and 14 were considered to be potential as antidiabetic agents , in which they could significantly inhibit the PTP1B enzyme activity in a dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "Constant light disrupts the circadian rhythm of steroidogenic proteins in the rat adrenal gland .", "entity": [], "task": "NER"}
{"text": "The circadian rhythm of corticosterone ( CORT ) secretion from the adrenal cortex is regulated by the suprachiasmatic nucleus ( SCN ) , which is entrained to the light - dark cycle .", "entity": [{"entity": "corticosterone", "entity_type": "Chemical", "pos": [24, 38]}, {"entity": "CORT", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Since the circadian CORT rhythm is associated with circadian expression of the steroidogenic acute regulatory ( StAR ) protein , we investigated the 24h pattern of hormonal secretion ( ACTH and CORT ) , steroidogenic gene expression ( StAR , SF - 1 , DAX1 and Nurr77 ) and the expression of genes involved in ACTH signalling ( MC2R and MRAP ) in rats entrained to a normal light - dark cycle .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [20, 24]}, {"entity": "CORT", "entity_type": "Chemical", "pos": [194, 198]}], "task": "NER"}
{"text": "We found that circadian changes in ACTH and CORT were associated with the circadian expression of all gene targets ; with SF - 1 , Nurr77 and MRAP peaking in the evening , and DAX1 and MC2R peaking in the morning .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "Since disruption of normal SCN activity by exposure to constant light abolishes the circadian rhythm of CORT in the rat , we also investigated whether the AM - PM variation of our target genes was also disrupted in rats exposed to constant light conditions for 5weeks .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [104, 108]}], "task": "NER"}
{"text": "We found that the disruption of the AM - PM variation of ACTH and CORT secretion in rats exposed to constant light was accompanied by a loss of AM - PM variation in StAR , SF - 1 and DAX1 , and a reversed AM - PM variation in Nurr77 , MC2R and MRAP .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [66, 70]}], "task": "NER"}
{"text": "Our data suggest that circadian expression of StAR is regulated by the circadian expression of nuclear receptors and proteins involved in both ACTH signalling and StAR transcription .", "entity": [], "task": "NER"}
{"text": "We propose that ACTH regulates the secretion of CORT via the circadian control of steroidogenic gene pathways that become dysregulated under the influence of constant light .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "Synthesis and anti - tumor evaluation of novel 25 - hydroxyprotopanaxadiol analogs incorporating natural amino acids .", "entity": [{"entity": "25 - hydroxyprotopanaxadiol", "entity_type": "Chemical", "pos": [47, 74]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [105, 116]}], "task": "NER"}
{"text": "In the current study , derivatives of 25 - hydroxyprotopanaxadiol ( 25 - OH - PPD ) were prepared and their in vitro anti - tumor activities were tested on six different human tumor cell lines by standard MTT assay .", "entity": [{"entity": "25 - hydroxyprotopanaxadiol", "entity_type": "Chemical", "pos": [38, 65]}, {"entity": "25 - OH - PPD", "entity_type": "Chemical", "pos": [68, 81]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [205, 208]}], "task": "NER"}
{"text": "The results showed that combining an ester group combined with the presence of an amino acid moiety led to a 10 - fold improved anti - tumor activity .", "entity": [{"entity": "ester", "entity_type": "Chemical", "pos": [37, 42]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [82, 92]}], "task": "NER"}
{"text": "Compound 1c exhibited the best anti - tumor activity in the in vitro assays .", "entity": [], "task": "NER"}
{"text": "Compounds 2c , 3c , 4c , 5c , 6c and 8b showed better anti - tumor activities compared to the parent compound 25 - OH - PPD .", "entity": [{"entity": "25 - OH - PPD", "entity_type": "Chemical", "pos": [110, 123]}], "task": "NER"}
{"text": "The current results may provide useful data for researching and developing new anti - cancer agents .", "entity": [], "task": "NER"}
{"text": "Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques .", "entity": [{"entity": "paraoxon", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "Butyrylcholinesterase ( BChE ) is the leading pretreatment candidate against exposure to organophosphates ( OPs ) , which pose an ever increasing public and military health .", "entity": [{"entity": "organophosphates", "entity_type": "Chemical", "pos": [89, 105]}], "task": "NER"}
{"text": "Since respiratory failure is the primary cause of death following acute OP poisoning , an inhaled BChE therapeutic could prove highly efficacious in preventing acute toxicity as well as the associated delayed neuropathy .", "entity": [], "task": "NER"}
{"text": "To address this , studies have been performed in mice and macaques using Chinese Hamster Ovary cells ( CHO ) - derived recombinant ( r ) BChE delivered by the pulmonary route , to examine whether the deposition of both macaque ( Ma ) and human ( Hu ) rBChE administered as aerosols ( aer ) favored the creation and retention of an efficient protective \" pulmonary bioshield \" that could scavenge incoming ( inhaled ) OPs in situ thereby preventing entry into the circulation and inhibition of plasma BChE and AChE on red blood cells ( RBC - AChE ) and in cholinergic synapses .", "entity": [], "task": "NER"}
{"text": "In contrast to parenteral delivery of rBChE , which currently requires posttranslational modification for good plasma stability , an unmodified aer - rBChE pretreatment given 1 - 40h prior to > 1 LD50 of aer - paraoxon ( Px ) was able to prevent inhibition of circulating cholinesterase in a dose - dependent manner .", "entity": [{"entity": "paraoxon", "entity_type": "Chemical", "pos": [210, 218]}], "task": "NER"}
{"text": "These studies are the first to show protection by rBChE against a pesticide such as paraoxon when delivered directly into the lung and bode well for the use of a non - invasive and consumer friendly method of rHuBChE delivery as a human treatment to counteract OP toxicity .", "entity": [{"entity": "paraoxon", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "Aspidin PB , a phloroglucinol derivative , induces apoptosis in human hepatocarcinoma HepG2 cells by modulating PI3K / Akt / GSK3 beta pathway .", "entity": [{"entity": "Aspidin PB", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "phloroglucinol", "entity_type": "Chemical", "pos": [15, 29]}], "task": "NER"}
{"text": "Aspidin PB , a phloroglucinol derivative isolated from Dryopteris fragrans ( L . ) Schott , has been previously reported to exert high biological activities .", "entity": [{"entity": "Aspidin PB", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "phloroglucinol", "entity_type": "Chemical", "pos": [15, 29]}], "task": "NER"}
{"text": "In the present study , we analyzed the apoptotic mechanisms of aspidin PB on human hepatoma cell line , HepG2 .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [63, 73]}], "task": "NER"}
{"text": "Initially , aspidin PB was shown to inhibit the growth of HepG2 cells in a time and dose - dependent manner .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [12, 22]}], "task": "NER"}
{"text": "After treatment with aspidin PB for 72 h , 48 h and 24 h using MTT assay , the IC ( 50 ) values were 10 . 59 mu M , 20 . 86 mu M and 46 . 59 mu M , respectively .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [21, 31]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "Aspidin PB was capable to induce apoptosis , as measured by mitochondrial membrane potential ( Delta Psi m ) , acridine orange ( AO ) staining and propidium iodide ( PI ) / annexin V - FITC double staining .", "entity": [{"entity": "Aspidin PB", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "acridine orange", "entity_type": "Chemical", "pos": [111, 126]}, {"entity": "propidium iodide", "entity_type": "Chemical", "pos": [147, 163]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [185, 189]}], "task": "NER"}
{"text": "To further explore the signaling pathway of aspidin PB - mediated apoptosis , we examined PI3K / Akt related proteins .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [44, 54]}], "task": "NER"}
{"text": "Western blot analysis revealed that aspidin PB inhibited PI3K expression , phosphorylation of Ser473 Akt and Ser9 GSK3 beta followed by up - regulation of nonsteroidal anti - inflammatory drugs activated gene - 1 ( NAG - 1 ) expression .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "Ser473", "entity_type": "Chemical", "pos": [94, 100]}, {"entity": "Ser9", "entity_type": "Chemical", "pos": [109, 113]}], "task": "NER"}
{"text": "Similarly , the effects of aspidin PB on PI3K , Akt , GSK3 beta , NAG - 1 expression were abolished by treatment with the PI3K inhibitor , wortmannin .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [27, 37]}, {"entity": "wortmannin", "entity_type": "Chemical", "pos": [139, 149]}], "task": "NER"}
{"text": "Taken together , our data suggested that the PI3K / Akt / GSK3 beta signal pathway may represent one of the major mechanisms of the effects of aspidin PB on human hepatocarcinoma cells .", "entity": [{"entity": "aspidin PB", "entity_type": "Chemical", "pos": [143, 153]}], "task": "NER"}
{"text": "Adaptation of bifidobacteria to the gastrointestinal tract and functional consequences .", "entity": [], "task": "NER"}
{"text": "Members of the genus Bifidobacterium are considered to be important constituents of the microbiota of animals , from insects to mammals .", "entity": [], "task": "NER"}
{"text": "They are gut commensals extensively used by the food industry as probiotic microorganisms , since some strains have been shown to have specific beneficial effects .", "entity": [], "task": "NER"}
{"text": "However , the molecular processes underlying their functional capacities to promote a healthy status in the host , as well as those involved in survival , colonization and persistence of bifidobacteria in the gut , are far from being completely understood .", "entity": [], "task": "NER"}
{"text": "This review summarizes the current knowledge on the mechanisms used by bifidobacteria to cope with gastrointestinal factors and to adapt to them , and discusses the advantages of the adaptive traits acquired by these microorganisms as a consequence of their interactions with the gastrointestinal tract environment , as well as the impact of such adaptations in the functional characteristics of bifidobacteria .", "entity": [], "task": "NER"}
{"text": "Inhibition of CIP2A determines erlotinib - induced apoptosis in hepatocellular carcinoma .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Erlotinib is a small - molecular inhibitor of epidermal growth factor receptor ( EGFR ) .", "entity": [{"entity": "Erlotinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Here , we identify that cancerous inhibitor of protein phosphatase 2A ( CIP2A ) is a major determinant mediating erlotinib - induced apoptosis in hepatocellular carcinoma ( HCC ) .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [113, 122]}], "task": "NER"}
{"text": "Erlotinib showed differential effects on apoptosis in 4 human HCC cell lines .", "entity": [{"entity": "Erlotinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Erlotinib induced significant apoptosis in Hep3B and PLC5 cell lines ; however , Huh - 7 and HA59T cell lines showed resistance to erlotinib - induced apoptosis at all tested doses .", "entity": [{"entity": "Erlotinib", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [131, 140]}], "task": "NER"}
{"text": "Down - regulation of CIP2A , a cellular inhibitor of protein phosphatase 2A ( PP2A ) , mediated the apoptotic effect of erlotinib in HCC .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [120, 129]}], "task": "NER"}
{"text": "Erlotinib inhibited CIP2A in a dose - and time - dependent manner in all sensitive HCC cells whereas no alterations in CIP2A were found in resistant cells .", "entity": [{"entity": "Erlotinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Overexpression of CIP2A upregulated phospho - Akt and protected Hep3B cells from erlotinib - induced apoptosis .", "entity": [{"entity": "phospho", "entity_type": "Chemical", "pos": [36, 43]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "In addition , silencing CIP2A by siRNA restored the effects of erlotinib in Huh - 7 cells .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [63, 72]}], "task": "NER"}
{"text": "Moreover , adding okadaic acid , a PP2A inhibitor , abolished the effects of erlotinib on apoptosis in Hep3B cells ; and forskolin , a PP2A agonist enhanced the effect of erlotinib in resistant HA59T cells .", "entity": [{"entity": "okadaic acid", "entity_type": "Chemical", "pos": [18, 30]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "forskolin", "entity_type": "Chemical", "pos": [121, 130]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [171, 180]}], "task": "NER"}
{"text": "Combining Akt inhibitor MK - 2206 with erlotinib restored the sensitivity of HA59T cells to erlotinib .", "entity": [{"entity": "MK - 2206", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [39, 48]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [92, 101]}], "task": "NER"}
{"text": "Furthermore , in vivo xenograft data showed that erlotinib inhibited the growth of PLC5 tumor but had no effect on Huh - 7 tumor .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "Erlotinib downregulated CIP2A and upregulated PP2A activity in PLC5 tumors , but not in Huh - 7 tumors .", "entity": [{"entity": "Erlotinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "In conclusion , inhibition of CIP2A determines the effects of erlotinib on apoptosis in HCC .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "CIP2A may be useful as a therapeutic biomarker for predicting clinical response to erlotinib in HCC treatment .", "entity": [{"entity": "erlotinib", "entity_type": "Chemical", "pos": [83, 92]}], "task": "NER"}
{"text": "Boldine protects endothelial function in hyperglycemia - induced oxidative stress through an antioxidant mechanism .", "entity": [{"entity": "Boldine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Increased oxidative stress is involved in the pathogenesis and progression of diabetes .", "entity": [], "task": "NER"}
{"text": "Antioxidants are therapeutically beneficial for oxidative stress - associated diseases .", "entity": [], "task": "NER"}
{"text": "Boldine ( [ s ] - 2 , 9 - dihydroxy - 1 , 10 - dimethoxyaporphine ) is a major alkaloid present in the leaves and bark of the boldo tree ( Peumus boldus Molina ) , with known an antioxidant activity .", "entity": [{"entity": "Boldine", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "[ s ] - 2 , 9 - dihydroxy - 1 , 10 - dimethoxyaporphine", "entity_type": "Chemical", "pos": [10, 65]}], "task": "NER"}
{"text": "This study examined the protective effects of boldine against high glucose - induced oxidative stress in rat aortic endothelial cells ( RAEC ) and its mechanisms of vasoprotection related to diabetic endothelial dysfunction .", "entity": [{"entity": "boldine", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [67, 74]}], "task": "NER"}
{"text": "In RAEC exposed to high glucose ( 30 mM ) for 48 h , pre - treatment with boldine reduced the elevated ROS and nitrotyrosine formation , and preserved nitric oxide ( NO ) production .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [24, 31]}, {"entity": "boldine", "entity_type": "Chemical", "pos": [74, 81]}, {"entity": "nitrotyrosine", "entity_type": "Chemical", "pos": [111, 124]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [151, 163]}, {"entity": "NO", "entity_type": "Chemical", "pos": [166, 168]}], "task": "NER"}
{"text": "Pre - incubation with beta - NAPDH reduced the acetylcholine - induced endothelium - dependent relaxation ; this attenuation was reversed by boldine .", "entity": [{"entity": "beta - NAPDH", "entity_type": "Chemical", "pos": [22, 34]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [47, 60]}, {"entity": "boldine", "entity_type": "Chemical", "pos": [141, 148]}], "task": "NER"}
{"text": "Compared with control , endothelium - dependent relaxation in the aortas of streptozotocin ( STZ ) - treated diabetic rats was significantly improved by both acute ( 1 mu M , 30 min ) and chronic ( 20mg / kg / daily , i . p . , 7 days ) treatment with boldine .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [76, 90]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "boldine", "entity_type": "Chemical", "pos": [252, 259]}], "task": "NER"}
{"text": "Intracellular superoxide and peroxynitrite formation measured by DHE fluorescence or chemiluminescence assay were higher in sections of aortic rings from diabetic rats compared with control .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [29, 42]}, {"entity": "DHE", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "Chronic boldine treatment normalized ROS over - production in the diabetic group and this correlated with reduction of NAD ( P ) H oxidase subunits , NOX2 and p47 ( phox ) .", "entity": [{"entity": "boldine", "entity_type": "Chemical", "pos": [8, 15]}, {"entity": "NAD ( P ) H", "entity_type": "Chemical", "pos": [119, 130]}], "task": "NER"}
{"text": "The present study shows that boldine reversed the increased ROS formation in high glucose - treated endothelial cells and restored endothelial function in STZ - induced diabetes by inhibiting oxidative stress and thus increasing NO bioavailability .", "entity": [{"entity": "boldine", "entity_type": "Chemical", "pos": [29, 36]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [82, 89]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [155, 158]}, {"entity": "NO", "entity_type": "Chemical", "pos": [229, 231]}], "task": "NER"}
{"text": "Relationship between DNA damage in sperm after ex vivo exposure and abnormal embryo development in the progeny of the three - spined stickleback .", "entity": [], "task": "NER"}
{"text": "Many xenobiotics released in the aquatic environment exhibit a genotoxic potential toward organisms .", "entity": [], "task": "NER"}
{"text": "Long term exposure to such compounds is expected to lead to multigenerational reproductive defects , further influencing the recruitment rate and hence , the population dynamics .", "entity": [], "task": "NER"}
{"text": "Paternal exposure to genotoxicants was previously shown to increase abnormal development in the progeny of mammalian or aquatic species .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to evaluate the relationship between DNA damage in sperm of the fish three - spined stickleback and progeny developmental defects .", "entity": [], "task": "NER"}
{"text": "Spermatozoa were exposed ex vivo to an alkylating agent ( methyl methanesulfonate ) before in vitro fertilization and DNA damage was assessed by the alkaline comet assay .", "entity": [{"entity": "methyl methanesulfonate", "entity_type": "Chemical", "pos": [58, 81]}], "task": "NER"}
{"text": "A significant relationship between abnormal development and sperm DNA damage was underlined .", "entity": [], "task": "NER"}
{"text": "This study illustrates the interest to use germ cell DNA damage after ex vivo exposure to evaluate the impact of genotoxic compounds on progeny fitness in aquatic organisms .", "entity": [], "task": "NER"}
{"text": "Integrated pharmacokinetic - driven approach to screen candidate anticancer drugs for brain tumor chemotherapy .", "entity": [], "task": "NER"}
{"text": "The goal of the study was to develop an effective screening strategy to select new agents for brain tumor chemotherapy from a series of low molecular weight anticancer agents [ ON123x ] by the combined use of in silico , in vitro cytotoxicity , and in vitro ADME profiling studies .", "entity": [{"entity": "ON123x", "entity_type": "Chemical", "pos": [177, 183]}], "task": "NER"}
{"text": "The results of these studies were cast into a pipeline of tier 1 and tier 2 procedures that resulted in the identification of ON123300 as the lead compound .", "entity": [{"entity": "ON123300", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "Of the 154 ON123xx compounds , 13 met tier 1 screening criteria based on physicochemical properties [ i . e . , MW < 450 Da , predicted log P between 2 and 3 . 5 ] and in vitro glioma cell cytotoxicity [ i . e . , IC50 < 10 mu M ] and were further tested in tier 2 assays .", "entity": [{"entity": "ON123xx", "entity_type": "Chemical", "pos": [11, 18]}], "task": "NER"}
{"text": "The tier 2 profiling studies consisted of metabolic stability , MDCK - MDR1 cell permeability and plasma and brain protein binding that were combined to globally assess whether favorable pharmacokinetic properties and brain penetration could be achieved in vivo .", "entity": [], "task": "NER"}
{"text": "In vivo cassette dosing studies were conducted in mice for 12 compounds that permitted examination of in vitro / in vivo relationships that confirmed the suitability of the in vitro assays .", "entity": [], "task": "NER"}
{"text": "A parameter derived from the in vitro assays accurately predicted the extent of drug accumulation in the brain based on the area under the drug concentration - time curve in brain measured in the cassette dosing study ( r ( 2 ) = 0 . 920 ) .", "entity": [], "task": "NER"}
{"text": "Overall , the current studies demonstrated the value of an integrated pharmacokinetic - driven approach to identify potentially efficacious agents for brain tumor chemotherapy .", "entity": [], "task": "NER"}
{"text": "Two new C - benzylated dihydrochalcone derivatives from the leaves of Melodorum siamensis .", "entity": [{"entity": "C - benzylated dihydrochalcone", "entity_type": "Chemical", "pos": [8, 38]}], "task": "NER"}
{"text": "Two new C - benzylated dihydrochalcone derivatives , 4 , 2 ' , 4 ' - trihydroxy - 6 ' - methoxy - 3 ' ( 2 ' ' - hydroxybenzyl ) dihydrochalcone ( 1 ) and 2 ' , 4 ' - dihydroxy - 4 , 6 ' - dimethoxy - 3 ' ( 2 ' ' - hydroxybenzyl ) dihydrochalcone ( 2 ) , along with six known flavonoid derivatives ( 3 - 8 ) , a known dihydrochalcone dimer ( 9 ) , three known aromatic esters ( 10 - 12 ) , and one known aromatic amide ( 13 ) , were isolated from the leaves of Melodorum siamensis .", "entity": [{"entity": "C - benzylated dihydrochalcone", "entity_type": "Chemical", "pos": [8, 38]}, {"entity": "4 , 2 ' , 4 ' - trihydroxy - 6 ' - methoxy - 3 ' ( 2 ' ' - hydroxybenzyl ) dihydrochalcone", "entity_type": "Chemical", "pos": [53, 143]}, {"entity": "2 ' , 4 ' - dihydroxy - 4 , 6 ' - dimethoxy - 3 ' ( 2 ' ' - hydroxybenzyl ) dihydrochalcone", "entity_type": "Chemical", "pos": [154, 245]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [275, 284]}, {"entity": "dihydrochalcone", "entity_type": "Chemical", "pos": [317, 332]}, {"entity": "aromatic esters", "entity_type": "Chemical", "pos": [359, 374]}, {"entity": "aromatic amide", "entity_type": "Chemical", "pos": [403, 417]}], "task": "NER"}
{"text": "The structures of the compounds were elucidated by spectroscopic analysis , mainly 1D and 2D NMR techniques ( 1H , 13C , COSY , HMQC , and HMBC ) , as well as by comparison with literature data .", "entity": [{"entity": "1H", "entity_type": "Chemical", "pos": [110, 112]}, {"entity": "13C", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "The isolated compounds with a sufficient amount for biological assays were evaluated for their antimalarial , antimycobactirial , and cytotoxic activities .", "entity": [], "task": "NER"}
{"text": "Compounds 1 , 2 , and 13 exhibited strong cytotoxicity against human tumor cell lines KB and NCI - H187 , with IC50 values in the range of 0 . 66 - 7 . 16 micro g / mL .", "entity": [], "task": "NER"}
{"text": "Avoidance of contaminated sediments by an amphipod ( Melita plumulosa ) , A harpacticoid copepod ( Nitocra spinipes ) , and a snail ( Phallomedusa solida ) .", "entity": [], "task": "NER"}
{"text": "The distribution of contaminants is seldom homogeneous in aquatic systems .", "entity": [], "task": "NER"}
{"text": "In the present study , the avoidance response of Melita plumulosa , Nitocra spinipes , and Phallomedusa solida when exposed to contaminated sediments was investigated .", "entity": [], "task": "NER"}
{"text": "Test vessels were designed to allow the congruent placement of two sediments and assessment of the movement of organisms between the sediments .", "entity": [], "task": "NER"}
{"text": "When exposed to reference sediment , each species dispersed evenly between test chambers regardless of differences in sediment particle size .", "entity": [], "task": "NER"}
{"text": "In the presence of contaminated sediment , the magnitude and rate of avoidance varied .", "entity": [], "task": "NER"}
{"text": "Avoidance assays showed that test species avoided contaminated sediment as early as 6 , 6 , and 24 h following exposure for N . spinipes , P . solida , and M . plumulosa , respectively .", "entity": [], "task": "NER"}
{"text": "The 48 - h avoidance response of M . plumulosa for nine contaminated sediments of varying toxicity showed that avoidance was generally greater for sediments which elicited greater 10 - d lethality to this species .", "entity": [], "task": "NER"}
{"text": "The study demonstrated that each of these species has the ability to respond to chemical cues in the environment to inhabit sediment that provides the best opportunity for survival .", "entity": [], "task": "NER"}
{"text": "The avoidance response for each species indicates the potential for developing rapid screening methods to assess sediment quality .", "entity": [], "task": "NER"}
{"text": "Evidence suggests that avoidance was related to sediment toxicity and that static 10 - d toxicity methods are likely to overestimate toxicity for species , which would avoid contamination in heterogeneous field settings .", "entity": [], "task": "NER"}
{"text": "Facile and clean release of vertical Si nanowires by wet chemical etching based on alkali hydroxides .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [37, 39]}, {"entity": "alkali hydroxides", "entity_type": "Chemical", "pos": [83, 100]}], "task": "NER"}
{"text": "A simple method to release Si nanowires ( SiNWs ) from a substrate , with their original length almost intact , is demonstrated .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [27, 29]}], "task": "NER"}
{"text": "By exploiting the unique chemistry involved for the fabrication of vertical arrays of SiNWs in metal - assisted chemical etching ( MaCE ) based either on HF / AgNO3 or HF / H2O2 chemistries , wet etching with alkali hydroxides such as NaOH or KOH preferentially attacks the bottom part of the vertical SiNWs .", "entity": [{"entity": "HF", "entity_type": "Chemical", "pos": [154, 156]}, {"entity": "AgNO3", "entity_type": "Chemical", "pos": [159, 164]}, {"entity": "HF", "entity_type": "Chemical", "pos": [168, 170]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [173, 177]}, {"entity": "alkali hydroxides", "entity_type": "Chemical", "pos": [209, 226]}, {"entity": "NaOH", "entity_type": "Chemical", "pos": [235, 239]}, {"entity": "KOH", "entity_type": "Chemical", "pos": [243, 246]}], "task": "NER"}
{"text": "A protective layer of Si oxide is found to exist on the outer wall of the SiNWs and to play the key role of etch mask during the release - etching by alkali hydroxides .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [25, 30]}, {"entity": "alkali hydroxides", "entity_type": "Chemical", "pos": [150, 167]}], "task": "NER"}
{"text": "The clean release of SiNWs also enables the repeated use of the Si substrate for the fabrication of vertical SiNW arrays by MaCE .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [21, 23]}], "task": "NER"}
{"text": "The released SiNWs are further used for the fabrication of field - effect transistors on a flexible plastic substrate .", "entity": [], "task": "NER"}
{"text": "The method developed here , when combined with a suitable assembling technique , can be very useful in implementing flexible electronics , or in the fabrication of SiNW composites with other functional materials .", "entity": [], "task": "NER"}
{"text": "Enantioseparation of four organophosphonate derivatives on N - ( 3 , 5 - dinitrobenzoyl ) - L - leucine - n - propylamide stationary phase by molecular modeling .", "entity": [{"entity": "organophosphonate", "entity_type": "Chemical", "pos": [26, 43]}, {"entity": "N - ( 3 , 5 - dinitrobenzoyl ) - L - leucine - n - propylamide", "entity_type": "Chemical", "pos": [59, 121]}], "task": "NER"}
{"text": "Four groups of organophosphonate derivatives enantiomers were separated on N - ( 3 , 5 - dinitrobenzoyl ) - S - leucine chiral stationary phase .", "entity": [{"entity": "organophosphonate", "entity_type": "Chemical", "pos": [15, 32]}, {"entity": "N - ( 3 , 5 - dinitrobenzoyl ) - S - leucine", "entity_type": "Chemical", "pos": [75, 119]}], "task": "NER"}
{"text": "The three - dimensional structures of the complexes between the single enantiotopic chiral compounds and chiral stationary phase have been studied using molecular model and molecular dynamics simulation .", "entity": [], "task": "NER"}
{"text": "Detailed results regarding the conformation , auto - docking , and thermodynamic estimation are presented .", "entity": [], "task": "NER"}
{"text": "The elution order of the enantiomer could be determined from the energy .", "entity": [], "task": "NER"}
{"text": "The predicted chiral discrimination was obtained by computational results .", "entity": [], "task": "NER"}
{"text": "Lattice deformation and domain distortion in the self - assembly of block copolymer thin films on chemical patterns .", "entity": [], "task": "NER"}
{"text": "The self - assembly of cylinder - forming block copolymer ( BCP ) microdomains confined within chemical stripe patterns of widths incommensurate with the natural period of the copolymers , L0 , is studied .", "entity": [], "task": "NER"}
{"text": "It is shown that this incommensurability causes changes in both the shapes of the microdomains and their spatial period .", "entity": [], "task": "NER"}
{"text": "Specifically , a transition from n to n + 1 rows of microdomains is observed when the stripe width is about n +/- 1 / 2 L0 .", "entity": [], "task": "NER"}
{"text": "When the stripe ' s width is comparable to L0 , ellipticity of microdomains can be induced with an aspect ratio up to 2 . 2 .", "entity": [], "task": "NER"}
{"text": "Free energy models are applied to describe the energetic origin of such behavior .", "entity": [], "task": "NER"}
{"text": "Although our observations qualitatively resemble results in sphere - forming BCPs confined in topographical trenches , the quantitative difference is noteworthy and technologically important for the design of nanostructures with programmable shapes .", "entity": [], "task": "NER"}
{"text": "Enantioanalysis of pipecolic acid with stochastic and potentiometric microsensors .", "entity": [{"entity": "pipecolic acid", "entity_type": "Chemical", "pos": [19, 33]}], "task": "NER"}
{"text": "Stochastic and potentiometric microsensors based on porphyrins and polymeric surfactants such as polysodium N - undecanoyl - L - leucylvanilate and polysodium N - undecanoyl - L - vanilate were developed for enantioselective assay of pipecolic acid .", "entity": [{"entity": "porphyrins", "entity_type": "Chemical", "pos": [52, 62]}, {"entity": "polysodium N - undecanoyl - L - leucylvanilate", "entity_type": "Chemical", "pos": [97, 143]}, {"entity": "polysodium N - undecanoyl - L - vanilate", "entity_type": "Chemical", "pos": [148, 188]}, {"entity": "pipecolic acid", "entity_type": "Chemical", "pos": [234, 248]}], "task": "NER"}
{"text": "The matrices used for the design of the stochastic sensors were diamond paste and graphite paste , while the matrix used for the design of potentiometric sensors was carbon paste .", "entity": [{"entity": "diamond", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "The response characteristics of the microsensors were determined for the enantiomers of pipecolic acid .", "entity": [{"entity": "pipecolic acid", "entity_type": "Chemical", "pos": [88, 102]}], "task": "NER"}
{"text": "The response characteristics , selectivity , and enantioselectivity studies proved that the proposed microsensors can be used for clinical enantioanalysis of pipecolic acid in biological fluids , e . g . , urine and whole blood .", "entity": [{"entity": "pipecolic acid", "entity_type": "Chemical", "pos": [158, 172]}], "task": "NER"}
{"text": "Brewster angle microscopy of Langmuir films of athabasca bitumens , n - C5 asphaltenes , and SAGD bitumen during pressure - area hysteresis .", "entity": [], "task": "NER"}
{"text": "Bitumen films formed on water surfaces have negative consequences , both environmental and economic .", "entity": [], "task": "NER"}
{"text": "CanmetENERGY has placed considerable research emphasis on understanding the structures of the bitumen films on water as a necessary step before optimization of bitumen extraction .", "entity": [], "task": "NER"}
{"text": "The detailed structures of the adsorbed molecules and , especially , the role of asphaltene molecules at the interfaces are still under scrutiny and debate .", "entity": [], "task": "NER"}
{"text": "In the present study , we compared bitumen and asphaltene films as they were compressed and expanded under various surface pressures in order to achieve a clearer understanding of bitumen film structures .", "entity": [], "task": "NER"}
{"text": "We used a customized NIMA Langmuir trough interfaced to a Brewster angle microscope ( BAM ) and CCD camera ( Nanofilm _ ep3BAM , Accurion , previously Nanofilm Gmbh ) to study images of bitumen films at the air / water interface .", "entity": [], "task": "NER"}
{"text": "The bitumen film appeared uniform with high reflectivity at a surface pressure of 18 mN . m ( - 1 ) and exhibited a coarse pebblelike interface with reduced reflectivity in the liquid condensed ( LC ) phase at higher pressures ( 18 - 35 mN . m ( - 1 ) ) .", "entity": [], "task": "NER"}
{"text": "During the first cycle of compression asphaltene films showed well - defined phase transitions and a uniformly smooth interface in the LC phase between 9 and 35 mN . m ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "However , folding or buckling occurred at surface pressures from 35 to 44 mN . m ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "On expansion , asphaltene films appeared to break into islands .", "entity": [], "task": "NER"}
{"text": "The hysteresis of the pressure - area isotherm was much larger for asphaltenes than for bitumen .", "entity": [], "task": "NER"}
{"text": "In both compression and expansion cycles , BAM images for bitumen films appeared to be more reproducible than those of the asphaltene films at the same surface pressures .", "entity": [], "task": "NER"}
{"text": "Films for low - degrees API SAGD bitumen were almost identical to those for surface - mined bitumen .", "entity": [], "task": "NER"}
{"text": "Films formed from partially deasphalted surface - mined bitumens showed higher compressibility and lower rigidity than the original bitumen .", "entity": [], "task": "NER"}
{"text": "The BAM images illustrated significant differences between the partially deasphalted and original bitumen films .", "entity": [], "task": "NER"}
{"text": "Other components in bitumen also played important roles in determining the interfacial properties of bitumen films .", "entity": [], "task": "NER"}
{"text": "Novel 2 - aminooctahydrocyclopentalene - 3a - carboxamides as potent CCR2 antagonists .", "entity": [{"entity": "2 - aminooctahydrocyclopentalene - 3a - carboxamides", "entity_type": "Chemical", "pos": [6, 58]}], "task": "NER"}
{"text": "Novel CCR2 antagonists with a novel 2 - aminooctahydrocyclopentalene - 3a - carboxamide scaffold were designed .", "entity": [{"entity": "2 - aminooctahydrocyclopentalene - 3a - carboxamide", "entity_type": "Chemical", "pos": [36, 87]}], "task": "NER"}
{"text": "SAR studies led to a series of potent compounds .", "entity": [], "task": "NER"}
{"text": "For example , compound 51 had a good PK profile in both dog and monkey , and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice .", "entity": [], "task": "NER"}
{"text": "In addition , an asymmetric synthesis to the core structures was developed .", "entity": [], "task": "NER"}
{"text": "Assessing the chemical accuracy of protein structures via peptide acidity .", "entity": [], "task": "NER"}
{"text": "Although the protein native state is a Boltzmann conformational ensemble , practical applications often require a representative model from the most populated region of that distribution .", "entity": [], "task": "NER"}
{"text": "The acidity of the backbone amides , as reflected in hydrogen exchange rates , is exquisitely sensitive to the surrounding charge and dielectric volume distribution .", "entity": [{"entity": "amides", "entity_type": "Chemical", "pos": [28, 34]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [53, 61]}], "task": "NER"}
{"text": "For each of four proteins , three independently determined X - ray structures of differing crystallographic resolution were used to predict exchange for the static solvent - exposed amide hydrogens .", "entity": [{"entity": "amide hydrogens", "entity_type": "Chemical", "pos": [182, 197]}], "task": "NER"}
{"text": "The average correlation coefficients range from 0 . 74 for ubiquitin to 0 . 93 for Pyrococcus furiosus rubredoxin , reflecting the larger range of experimental exchange rates exhibited by the latter protein .", "entity": [], "task": "NER"}
{"text": "The exchange prediction errors modestly correlate with the crystallographic resolution .", "entity": [], "task": "NER"}
{"text": "MODELLER 9v6 - derived homology models at ~ 60 % sequence identity ( 36 % identity for chymotrypsin inhibitor CI2 ) yielded correlation coefficients that are ~ 0 . 1 smaller than for the cognate X - ray structures .", "entity": [], "task": "NER"}
{"text": "The most recently deposited NOE - based ubiquitin structure and the original NMR structure of CI2 fail to provide statistically significant predictions of hydrogen exchange .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [155, 163]}], "task": "NER"}
{"text": "However , the more recent RECOORD refinement study of CI2 yielded predictions comparable to the X - ray and homology model - based analyses .", "entity": [], "task": "NER"}
{"text": "Incidence and predictors of right paraesophageal lymph node metastasis of N0 papillary thyroid carcinoma located in the right lobe .", "entity": [], "task": "NER"}
{"text": "Papillary thyroid carcinoma ( PTC ) frequently metastasizes to the regional lymph nodes and , thus , guidelines edited by Japan Association of Endocrine Surgeons / Japanese Society of Thyroid Surgery routinely recommend central node dissection even for patients with no clinically detectable node metastasis ( N0 ) .", "entity": [], "task": "NER"}
{"text": "However , in the central compartment , metastasis to the right paraesophageal node has not been intensively investigated .", "entity": [], "task": "NER"}
{"text": "We investigated the incidence and predictors of right paraesophageal node metastasis based on pre - and intraoperative findings in 922 patients with N0 PTC in the right lobe .", "entity": [], "task": "NER"}
{"text": "Fourteen percent of patients were microscopically positive for right paraesophageal node metastasis , and the incidence was smaller than that for pre - and right paratracheal node metastasis ( 46 % ) .", "entity": [], "task": "NER"}
{"text": "On multivariate analysis , a tumor size >= 2 cm and significant extrathyroid extension were independent predictors of metastasis .", "entity": [], "task": "NER"}
{"text": "Microscopically pre - and right paratracheal node - positive PTC more often ( p < 0 . 0001 ) metastasized to the right paraesophageal node .", "entity": [], "task": "NER"}
{"text": "Taken together , in N0 PTC in the right lobe , right paraesophageal node dissection should be considered in tumors 2 cm or larger and / or with significant extrathyroid extension , or when pre - and right paratracheal node metastasis is suspected based on the intraoperative findings .", "entity": [], "task": "NER"}
{"text": "Effects of ozone and fine particulate matter ( PM ( 2 . 5 ) ) on rat system inflammation and cardiac function .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [11, 16]}], "task": "NER"}
{"text": "In order to understand the toxic mechanisms of cardiovascular system injuries induced by ambient PM ( 2 . 5 ) and / or ozone , a subacute toxicological animal experiment was designed with exposure twice a week for 3 continuous weeks .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [119, 124]}], "task": "NER"}
{"text": "Wistar rats were randomly categorized into 8 groups ( n = 6 ) : 1 control group , 3 groups exposed to fine particulate matters ( PM ( 2 . 5 ) ) alone at 3 doses ( 0 . 2 , 0 . 8 , or 3 . 2 mg / rat ) , 1 group to ozone ( 0 . 81 ppm ) alone and 3 groups to ozone plus PM ( 2 . 5 ) at 3 doses ( 0 . 2 , 0 . 8 , or 3 . 2 mg / rat ) .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [212, 217]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [255, 260]}], "task": "NER"}
{"text": "Heart rate ( HR ) and electrocardiogram ( ECG ) was monitored at approximately 24 - h both after the 3rd exposure and the last ( 6th ) exposure , and systolic blood pressure ( SBP ) was monitored at approximately 24 - h after the 6th exposure .", "entity": [], "task": "NER"}
{"text": "Biomarkers of systemic inflammation and injuries ( CRP , IL - 6 , LDH , CK ) , heart oxidative stress ( MDA , SOD ) and endothelial function ( ET - 1 , VEGF ) were analyzed after the 6th exposure .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [104, 107]}], "task": "NER"}
{"text": "Additionally , myocardial ultrastructural alterations were observed under transmission electron microscopy ( TEM ) for histopathological analyses .", "entity": [], "task": "NER"}
{"text": "Results showed that PM ( 2 . 5 ) alone exposure could trigger the significant increase of CRP , MDA , CK , ET - 1 and SBP and decrease of heart rate variability ( HRV ) , a marker of cardiac autonomic nervous system ( ANS ) function .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [96, 99]}], "task": "NER"}
{"text": "Ozone alone exposure in rats did not show significant alterations in any indicators .", "entity": [{"entity": "Ozone", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Ozone plus PM ( 2 . 5 ) exposure , however , induced CRP , IL - 6 , CK , LDH and MDA increase , SOD and HRV decrease significantly in a dose - response way .", "entity": [{"entity": "Ozone", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Meanwhile , abnormal ECG types were monitored in rats exposed to PM ( 2 . 5 ) with and without ozone and obvious myocardial ultrastructural changes were observed by TEM .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [95, 100]}], "task": "NER"}
{"text": "In conclusion , PM ( 2 . 5 ) alone exposure could cause inflammation , endothelial function and ANS injuries , and ozone potentiated these effects induced by PM ( 2 . 5 ) .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [115, 120]}], "task": "NER"}
{"text": "Dynamics of silver nanoparticle formation and agglomeration inside the cavitation bubble after pulsed laser ablation in liquid .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [12, 18]}], "task": "NER"}
{"text": "The formation of nanoparticles within the laser - induced cavitation bubble is studied in situ using small angle X - ray scattering with high spatiotemporal resolution .", "entity": [], "task": "NER"}
{"text": "Directly after laser ablation , two different particle fractions consisting of compact primary particles of 8 - 10 nm size and agglomerates of 40 - 60 nm size are formed .", "entity": [], "task": "NER"}
{"text": "The abundance of these species is strongly influenced by the dynamics of the oscillating cavitation bubble .", "entity": [], "task": "NER"}
{"text": "Primary particle mass is most abundant during maximal expansion of the first bubble and reappears a little weaker in the rebound .", "entity": [], "task": "NER"}
{"text": "In contrast to this , the mass abundance of agglomerates is relatively low in the first bubble but strongly increases during first bubble collapse and following rebound .", "entity": [], "task": "NER"}
{"text": "Although most of the ablated material is trapped inside the bubble and follows its oscillation , a minor fraction of both species could be detected outside the cavitation bubble even before its final collapse .", "entity": [], "task": "NER"}
{"text": "Limits of metastability in amorphous ices : 2H - NMR relaxation .", "entity": [{"entity": "2H", "entity_type": "Chemical", "pos": [44, 46]}], "task": "NER"}
{"text": "The high - frequency reorientation dynamics of O - ( 2 ) H bonds is investigated in various amorphous ices including eHDA ( expanded high density amorphous ice ) , LDA - II ( low density amorphous ice II ) and HGW ( hyperquenched glassy water ) using ( 2 ) H - NMR spin - lattice relaxation as a local probe .", "entity": [{"entity": "O - ( 2 ) H", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "( 2 ) H", "entity_type": "Chemical", "pos": [251, 258]}], "task": "NER"}
{"text": "Both low density forms , HGW and LDA - II , show similar spin - lattice relaxation but differ in the thermal stability with respect to the transition into crystalline cubic ice I ( c ) .", "entity": [], "task": "NER"}
{"text": "HGW already transforms slightly above 135 K whereas LDA - II crystallizes at 150 K .", "entity": [], "task": "NER"}
{"text": "eHDA is distinguishable from other high density amorphous ices in its thermal stability and spin - lattice relaxation .", "entity": [], "task": "NER"}
{"text": "Its relaxation times are much larger compared to those of VHDA ( very high density amorphous ice ) and uHDA ( unrelaxed high density amorphous ice ) .", "entity": [], "task": "NER"}
{"text": "eHDA does not show annealing effects , transforms sharply into LDA - II above 123 K and provides higher thermal stability as compared to other high density forms .", "entity": [], "task": "NER"}
{"text": "Nanoporous silicon networks as anodes for lithium ion batteries .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [42, 49]}], "task": "NER"}
{"text": "Nanoporous silicon ( Si ) networks with controllable porosity and thickness are fabricated by a simple and scalable electrochemical process , and then released from Si wafers and transferred to flexible and conductive substrates .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "Si", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Si", "entity_type": "Chemical", "pos": [165, 167]}], "task": "NER"}
{"text": "These nanoporous Si networks serve as high performance Li - ion battery electrodes , with an initial discharge capacity of 2570 mA h g ( - 1 ) , above 1000 mA h g ( - 1 ) after 200 cycles without any electrolyte additives .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [17, 19]}, {"entity": "Li", "entity_type": "Chemical", "pos": [55, 57]}], "task": "NER"}
{"text": "Recent progress in the development and use of organic ionic plastic crystal electrolytes .", "entity": [], "task": "NER"}
{"text": "Significant progress has been made recently in the development of Organic Ionic Plastic Crystals ( OIPCs ) , a unique family of solid state electrolytes with applications in electrochemical devices such as lithium batteries and dye - sensitised solar cells .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [206, 213]}], "task": "NER"}
{"text": "The negligible volatility of OIPCs renders them more suitable than molecular species for long - term device use , while the high thermal and electrochemical stability of many OIPCs fulfils an essential requirement for solid state electrolytes for many device applications .", "entity": [], "task": "NER"}
{"text": "However , the complex mechanisms of conduction through these materials , both in their pure state and in the presence of a small amount of a second component ( such as lithium salts to enable their use in lithium batteries ) are still not fully understood .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [168, 175]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [205, 212]}], "task": "NER"}
{"text": "At the same time , the range of anions and cations utilised in the synthesis of plastic crystal phases continues to increase .", "entity": [], "task": "NER"}
{"text": "This perspective concentrates on recent research into both fundamental and device - oriented aspects of these materials .", "entity": [], "task": "NER"}
{"text": "Important fundamental understanding of the physical properties and transport mechanisms of different OIPCs has been achieved through use of techniques including variable temperature solid - state NMR and crystallographic analysis , as well as detailed molecular dynamics simulations .", "entity": [], "task": "NER"}
{"text": "In parallel , the applicability of these materials as electrolytes for dye - sensitised solar cells and lithium batteries is being more widely demonstrated .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [104, 111]}], "task": "NER"}
{"text": "The possibility of using OIPCs as solid state electrolytes for fuel cells is also discussed .", "entity": [], "task": "NER"}
{"text": "Deep brain stimulation of the subthalamic nucleus , but not dopaminergic medication , improves proactive inhibitory control of movement initiation in Parkinson ' s disease .", "entity": [], "task": "NER"}
{"text": "Slowness in movement initiation is a cardinal feature of Parkinson ' s disease ( PD ) that is still poorly understood and unsuccessfully alleviated by standard therapies .", "entity": [], "task": "NER"}
{"text": "Here , we raise this major clinical issue within the framework of a novel theoretical model that allows a better understanding of the basic mechanisms involved in movement initiation .", "entity": [], "task": "NER"}
{"text": "This model assumes that movement triggering is inhibited by default to prevent automatic responses to unpredictable events .", "entity": [], "task": "NER"}
{"text": "We investigated to which extent the top - down control necessary to release this locking state before initiating actions is impaired in PD and restored by standard therapies .", "entity": [], "task": "NER"}
{"text": "We used a cue - target reaction time task to test both the ability to initiate fast responses to targets and the ability to refrain from reacting to cues .", "entity": [], "task": "NER"}
{"text": "Fourteen patients with dopaminergic ( DA ) medication and 11 with subthalamic nucleus ( STN ) stimulation were tested on and off treatment , and compared with 14 healthy controls .", "entity": [], "task": "NER"}
{"text": "We found evidence that patients withdrawn from treatment have trouble voluntarily releasing proactive inhibitory control ; while DA medication broadly reduces movement initiation latency , it does not reinstate a normal pattern of movement initiation ; and stimulation of the STN specifically re - establishes the efficiency of the top - down control of proactive inhibition .", "entity": [], "task": "NER"}
{"text": "These results suggest that movement initiation disorders that resist DA medication are due to executive , not motor , dysfunctions .", "entity": [], "task": "NER"}
{"text": "This conclusion is discussed with regard to the role the STN may play as an interface between non - DA executive and DA motor systems in cortico - basal ganglia loops .", "entity": [], "task": "NER"}
{"text": "High physical fitness in young adulthood reduces the risk of fractures later in life in men : A nationwide cohort study .", "entity": [], "task": "NER"}
{"text": "A few studies have indicated that self - reported physical activity is associated with the risk of fractures in middle - aged and elderly men .", "entity": [], "task": "NER"}
{"text": "We investigated whether objectively measured physical fitness in young adulthood was associated with the risk of low - energy fractures later in life in men .", "entity": [], "task": "NER"}
{"text": "Aerobic capacity and isometric muscle strength were measured in 435 , 445 Swedish men who were conscripted for military service from 1969 to 1978 .", "entity": [], "task": "NER"}
{"text": "Incident fractures were searched in national registers .", "entity": [], "task": "NER"}
{"text": "During a median follow - up period of 35 years ( range , 11 - 41 years ) , 8030 subjects sustained at least one fracture , increasing the risk of death 1 . 8 times ( 95 % CI , 1 . 6 - 2 . 0 ) during follow up .", "entity": [], "task": "NER"}
{"text": "When comparing men in the lowest and highest decile of physical fitness , the risk of a fracture was 1 . 8 times higher ( 95 % CI , 1 . 6 - 2 . 1 ) and that of hip fracture was 2 . 7 times higher ( 95 % CI , 1 . 6 - 4 . 7 ) .", "entity": [], "task": "NER"}
{"text": "The risk of fracture was also 1 . 4 to 1 . 5 times higher when comparing the extreme deciles of muscle strength ( p < 0 . 001 for all ) .", "entity": [], "task": "NER"}
{"text": "In a subcohort of 1009 twin pairs , up to 22 % of the variation in physical fitness and 27 % to 39 % of the variation in muscle strength was attributable to environmental factors unique to one twin ; eg , physical activity .", "entity": [], "task": "NER"}
{"text": "In conclusion , low aerobic capacity and muscle strength in young adulthood are associated with an increased risk of low - energy fractures later in life .", "entity": [], "task": "NER"}
{"text": "(c) 2013 American Society for Bone and Mineral Research .", "entity": [], "task": "NER"}
{"text": "Ion pair dynamics : solvolyses of chiral 1 , 3 - diarylallyl carboxylates as a case study .", "entity": [{"entity": "chiral 1 , 3 - diarylallyl carboxylates", "entity_type": "Chemical", "pos": [34, 73]}], "task": "NER"}
{"text": "Chiral ion pairs play a key role in modern enantioselective synthesis , though little is known about their properties .", "entity": [], "task": "NER"}
{"text": "We have now used the special features of unsymmetrically substituted allyl derivatives to obtain unprecedented insight into ion pair dynamics .", "entity": [{"entity": "allyl", "entity_type": "Chemical", "pos": [69, 74]}], "task": "NER"}
{"text": "By employing chiral high - performance liquid chromatography , it was possible to follow the time - dependent concentrations of all four isomeric esters ( two regioisomeric pairs of enantiomers ) and all four isomeric alcohols generated during the hydrolysis of enantiopure 1 - ( 4 - chlorophenyl ) - 3 - phenylallyl and 3 - ( 4 - chlorophenyl ) - 1 - phenylallyl 4 - nitrobenzoates .", "entity": [{"entity": "esters", "entity_type": "Chemical", "pos": [146, 152]}, {"entity": "alcohols", "entity_type": "Chemical", "pos": [218, 226]}, {"entity": "1 - ( 4 - chlorophenyl ) - 3 - phenylallyl and 3 - ( 4 - chlorophenyl ) - 1 - phenylallyl 4 - nitrobenzoates", "entity_type": "Chemical", "pos": [274, 382]}], "task": "NER"}
{"text": "Combination of these results with the directly measured rate constant for the reaction of the laser - flash photolytically generated 1 - ( 4 - chlorophenyl ) - 3 - phenylallyl cation with water provided a complete mechanistic scheme for allyl carboxylate solvolysis .", "entity": [{"entity": "1 - ( 4 - chlorophenyl ) - 3 - phenylallyl", "entity_type": "Chemical", "pos": [133, 175]}, {"entity": "allyl carboxylate", "entity_type": "Chemical", "pos": [237, 254]}], "task": "NER"}
{"text": "It is demonstrated that solvolysis and internal return can be explained by the same intermediates .", "entity": [], "task": "NER"}
{"text": "The correlation equation log k = s ( N ) ( N + E ) was used to elucidate the variable importance of external and internal return in the solvolysis reactions .", "entity": [], "task": "NER"}
{"text": "This information will be crucial for the interpretation of the ultrafast dynamics of ion pairs generated by femtosecond laser pulses .", "entity": [], "task": "NER"}
{"text": "Effects of ultrasound frequency and acoustic amplitude on the size of sonochemically active bubbles - Theoretical study .", "entity": [], "task": "NER"}
{"text": "Numerical simulation of chemical reactions inside an isolated spherical bubble of oxygen has been performed for various ambient bubble radii at different frequencies and acoustic amplitudes to study the effects of these two parameters on the range of ambient radius for an active bubble in sonochemical reactions .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [82, 88]}], "task": "NER"}
{"text": "The employed model combines the dynamic of bubble collapse with the chemical kinetics of single cavitation bubble .", "entity": [], "task": "NER"}
{"text": "Results from this model were compared with some experimental results presented in the literature and good apparent trends between them were observed .", "entity": [], "task": "NER"}
{"text": "The numerical calculations of this study showed that there always exists an optimal ambient bubble radius at which the production of oxidizing species at the end of the bubble collapse attained their upper limit .", "entity": [], "task": "NER"}
{"text": "It was shown that the range of ambient radius for an active bubble increased with increasing acoustic amplitude and decreased with increasing ultrasound frequency .", "entity": [], "task": "NER"}
{"text": "The optimal ambient radius decreased with increasing frequency .", "entity": [], "task": "NER"}
{"text": "Analysis of curves showing optimal ambient radius versus acoustic amplitude for different ultrasonic frequencies indicated that for 200 and 300kHz , the optimal ambient radius increased linearly with increasing acoustic amplitude up to 3atm .", "entity": [], "task": "NER"}
{"text": "However , slight minima of optimal radius were observed for the curves obtained at 500 and 1000kHz .", "entity": [], "task": "NER"}
{"text": "Decolourization of direct blue 15 by Fenton / ultrasonic process using a zero - valent iron aggregate catalyst .", "entity": [{"entity": "direct blue 15", "entity_type": "Chemical", "pos": [19, 33]}, {"entity": "zero - valent iron", "entity_type": "Chemical", "pos": [73, 91]}], "task": "NER"}
{"text": "Decolourization of direct azo dye , direct blue 15 ( DB15 ) , by an advanced Fenton process coupled with ultrasonic irradiation ( Fenton / US ) was investigated .", "entity": [{"entity": "azo", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "direct blue 15", "entity_type": "Chemical", "pos": [36, 50]}, {"entity": "DB15", "entity_type": "Chemical", "pos": [53, 57]}], "task": "NER"}
{"text": "Zero - valent iron ( ZVI ) aggregates were used as the catalyst .", "entity": [{"entity": "Zero - valent iron", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "ZVI", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "A positive synergistic effect occurred when Fenton ' s reagent was combined with ultrasonic irradiation .", "entity": [{"entity": "Fenton ' s reagent", "entity_type": "Chemical", "pos": [44, 62]}], "task": "NER"}
{"text": "Experimental results showed that the optimum conditions for decolourization were pH 3 . 0 , Fe ( 0 ) 1g / L , H ( 2 ) O ( 2 ) 5 . 15 x 10 ( - 3 ) mol / L with ultrasound density of 120W / L at 60kHz .", "entity": [{"entity": "Fe ( 0 )", "entity_type": "Chemical", "pos": [92, 100]}, {"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [110, 125]}], "task": "NER"}
{"text": "These conditions yielded 99 % decolouration of 4 . 7 x 10 ( - 5 ) M DB15 ( 4130 ADMI ) solution within 10min .", "entity": [], "task": "NER"}
{"text": "DB15 decolouration follows the first - order decolouration kinetics .", "entity": [{"entity": "DB15", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Although the solutions containing H ( 2 ) CO ( 3 ) , Cl ( - ) , ClO ( 4 ) ( - ) , NO ( 3 ) ( - ) and SO ( 4 ) ( 2 - ) ions did not have a significant effect on the decolouration , the H ( 2 ) PO ( 4 ) ( - ) ion did decrease the decolouration rate .", "entity": [{"entity": "H ( 2 ) CO ( 3 )", "entity_type": "Chemical", "pos": [34, 50]}, {"entity": "Cl ( - )", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "ClO ( 4 ) ( - )", "entity_type": "Chemical", "pos": [64, 79]}, {"entity": "NO ( 3 ) ( - )", "entity_type": "Chemical", "pos": [82, 96]}, {"entity": "SO ( 4 ) ( 2 - )", "entity_type": "Chemical", "pos": [101, 117]}, {"entity": "H ( 2 ) PO ( 4 ) ( - )", "entity_type": "Chemical", "pos": [184, 206]}], "task": "NER"}
{"text": "High ultrasonic input power accelerated the reaction and increased decolourization efficiency .", "entity": [], "task": "NER"}
{"text": "The cost effectiveness of this process at high ultrasound density could be controlled despite the high electricity costs incurred by the process .", "entity": [], "task": "NER"}
{"text": "ZVI aggregates were reusable ; however , an increase in the number of times ZVI was recycled decreased the decolourization rate .", "entity": [{"entity": "ZVI", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "ZVI", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "This study demonstrates that a Fenton / US process can effectively decolour the direct azo dye DB15 in wastewater .", "entity": [{"entity": "azo", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "DB15", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Effects of bidentate coordination on the molecular properties rapta - C based complex using theoretical approach .", "entity": [{"entity": "rapta - C", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "In this work several quantum properties including the NEDA and QTAIM are computed on three models of rapta - C complexes using DFT with hybrid functional and basis set with ECP and without ECP .", "entity": [{"entity": "rapta - C", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "Several interesting correlations within the observed properties and also with the reported experimental behaviors of these complexes including their biological activities are presented .", "entity": [], "task": "NER"}
{"text": "The study shows that the stability of the two complexes with bidentate ligands is associated with their high hydrogen bonding stability and existence of stronger non - covalent metal - ligand bonds .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "The energy decomposition analysis indicated that inter - atomic interactions in the three forms of rapta - C complexes and their stability are governed by the charge transfer term with significant contributions from polarization and electrostatic terms .", "entity": [{"entity": "rapta - C", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "The higher stability of complex 1 and 2 over 3 comes from the lower exchange repulsion and higher polarization contributions to their stability which agrees perfectly with the experimental observation .", "entity": [], "task": "NER"}
{"text": "Our results provide insight into the nature of intramolecular forces that influence the structural stability of the three complexes .", "entity": [], "task": "NER"}
{"text": "Genome - wide mapping of human DNA - replication origins : levels of transcription at ORC1 sites regulate origin selection and replication timing .", "entity": [], "task": "NER"}
{"text": "We report the genome - wide mapping of ORC1 binding sites in mammals , by chromatin immunoprecipitation and parallel sequencing ( ChIP - seq ) .", "entity": [], "task": "NER"}
{"text": "ORC1 binding sites in HeLa cells were validated as active DNA replication origins ( ORIs ) using Repli - seq , a method that allows identification of ORI - containing regions by parallel sequencing of temporally ordered replicating DNA .", "entity": [], "task": "NER"}
{"text": "ORC1 sites were universally associated with transcription start sites ( TSSs ) of coding or noncoding RNAs ( ncRNAs ) .", "entity": [], "task": "NER"}
{"text": "Transcription levels at the ORC1 sites directly correlated with replication timing , suggesting the existence of two classes of ORIs : those associated with moderate / high transcription levels ( >= 1 RNA copy / cell ) , firing in early S and mapping to the TSSs of coding RNAs ; and those associated with low transcription levels ( < 1 RNA copy / cell ) , firing throughout the entire S and mapping to TSSs of ncRNAs .", "entity": [], "task": "NER"}
{"text": "These findings are compatible with a scenario whereby TSS expression levels influence the efficiency of ORC1 recruitment at G ( 1 ) and the probability of firing during S .", "entity": [], "task": "NER"}
{"text": "Highlights on contemporary recognition and sensing of fluoride anion in solution and in the solid state .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "The fluoride anion has recently gained well deserved attention among the scientific community for its importance in many fields of human activities , but also for concerns on its effect on health and the environment .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "Although surprisingly overlooked in systematic studies in the past , fluoride has nowadays become a topical target in the field of anion recognition .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "A multitude of scientific reports are published every year where the establishment of efficient and specific interaction with fluoride is sought in polar and aqueous media .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "Here , the emphasis is directed to a detailed description of the most interesting contemporary studies in the field , with a particular focus given to those published in the last few years .", "entity": [], "task": "NER"}
{"text": "Phosphorylation of ribosomal protein S3 and antiapoptotic TRAF2 protein mediates radioresistance in non - small cell lung cancer cells .", "entity": [], "task": "NER"}
{"text": "Radioresistance is considered as a main factor restricting efficacy of radiotherapy .", "entity": [], "task": "NER"}
{"text": "However , the exact molecular mechanism of radioresistance has not been explained yet .", "entity": [], "task": "NER"}
{"text": "In this study , to elucidate radioresistance mechanism in lung cancer , we compared radiation responses in two types of non - small cell lung cancer ( NSCLC ) cells with different radiosensitivity and identified key molecules conferring radioresistance .", "entity": [], "task": "NER"}
{"text": "In radioresistant NSCLC cells , ionizing radiation ( IR ) led to casein kinase 2 alpha ( CK2 alpha ) - and PKC - mediated phosphorylation of rpS3 and TRAF2 , respectively , which induced dissociation of rpS3 - TRAF2 complex and NF - kappa B activation , resulting in significant up - regulation of prosurvival genes ( cIAP1 , cIAP2 , and survivin ) .", "entity": [], "task": "NER"}
{"text": "Also , dissociated phospho - rpS3 translocated into nucleus and bound with NF - kappa B complex ( p65 and p50 ) , contributing to p65 DNA binding property and specificity .", "entity": [{"entity": "phospho", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "However , in radiosensitive NSCLC cells , IR - mediated rpS3 phosphorylation was not detected due to the absence of CK2 alpha overexpression .", "entity": [], "task": "NER"}
{"text": "Consequently , IR - induced rpS3 - TRAF2 complex dissociation , NF - kappa B activation , and prosurvival gene expression were not presented .", "entity": [], "task": "NER"}
{"text": "Taken together , our findings revealed a novel radioresistance mechanism through functional orchestration of rpS3 , TRAF2 , and NF - kappa B in NSCLC cells .", "entity": [], "task": "NER"}
{"text": "Moreover , we provided the first evidence for the function of rpS3 as a new TRAF2 - binding protein and demonstrated that phosphorylation of both rpS3 and TRAF2 is a key control point of radioresistance in NSCLC cells .", "entity": [], "task": "NER"}
{"text": "These results suggest that regulation of rpS3 and TRAF2 in combination with radiotherapy could have high pharmacological therapeutic potency for radioresistance of NSCLC .", "entity": [], "task": "NER"}
{"text": "Theoretical studies on muti - hydroxyimides as highly efficient catalysts for aerobic oxidation .", "entity": [{"entity": "hydroxyimides", "entity_type": "Chemical", "pos": [30, 43]}], "task": "NER"}
{"text": "N , N - dihydroxypyromellitimide ( NDHPI ) and N , N ' , N ' ' - trihydroxyisocyanuric acid ( THICA ) have been recently demonstrated to act as better carbon - radical - producing catalysts than the popular N - hydroxyphthalimide ( NHPI ) .", "entity": [{"entity": "N , N - dihydroxypyromellitimide", "entity_type": "Chemical", "pos": [0, 32]}, {"entity": "NDHPI", "entity_type": "Chemical", "pos": [35, 40]}, {"entity": "N , N ' , N ' ' - trihydroxyisocyanuric acid", "entity_type": "Chemical", "pos": [47, 91]}, {"entity": "THICA", "entity_type": "Chemical", "pos": [94, 99]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [151, 157]}, {"entity": "N - hydroxyphthalimide", "entity_type": "Chemical", "pos": [207, 229]}, {"entity": "NHPI", "entity_type": "Chemical", "pos": [232, 236]}], "task": "NER"}
{"text": "To gain a mature understanding of these particular catalysts , herein their geometrical , electronic , and thermochemical properties , as well as their catalytic activities , have been systemically investigated by a theoretical analysis .", "entity": [], "task": "NER"}
{"text": "It appears that THICA , unlike NDHPI and NHPI , is unsuitable for solvent - free catalysis or catalysis in aprotic solvents due to its favorable coexistent planar conformer .", "entity": [{"entity": "THICA", "entity_type": "Chemical", "pos": [16, 21]}, {"entity": "NDHPI", "entity_type": "Chemical", "pos": [31, 36]}, {"entity": "NHPI", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Besides , the more remarkable catalytic efficiencies of NDHPI and THICA compared to NHPI can be ascribed to the lower barriers and the endothermicity in the H - abstraction processes by their radicals , especially by their multi - radicals which show stronger electron - withdrawing effects .", "entity": [{"entity": "NDHPI", "entity_type": "Chemical", "pos": [56, 61]}, {"entity": "THICA", "entity_type": "Chemical", "pos": [66, 71]}, {"entity": "NHPI", "entity_type": "Chemical", "pos": [84, 88]}, {"entity": "H", "entity_type": "Chemical", "pos": [157, 158]}], "task": "NER"}
{"text": "Furthermore , the generation of THICA radicals would be much feasible at high temperature without co - catalysts .", "entity": [{"entity": "THICA", "entity_type": "Chemical", "pos": [32, 37]}], "task": "NER"}
{"text": "This study provides a new perspective towards the rational design of reactive hydroxyimide organocatalysts for industrial applications .", "entity": [{"entity": "hydroxyimide", "entity_type": "Chemical", "pos": [78, 90]}], "task": "NER"}
{"text": "A novel adipose - specific gene deletion model demonstrates potential pitfalls of existing methods .", "entity": [], "task": "NER"}
{"text": "Adipose - specific gene deletion in mice is crucial in determining gene function in adipocyte homeostasis and the development of obesity .", "entity": [], "task": "NER"}
{"text": "We noted 100 % mortality when the Hdac3 gene was conditionally deleted using Fabp4 - Cre mice , the most commonly used model of adipose - targeted Cre recombinase .", "entity": [], "task": "NER"}
{"text": "However , this surprising result was not reproduced using other models of adipose targeting of Cre , including a novel Retn - Cre mouse .", "entity": [], "task": "NER"}
{"text": "These findings underscore the need for caution when interpreting data obtained using Fabp4 - Cre mice and should encourage the use of additional or alternative adipose - targeting Cre mouse models before drawing conclusions about in vivo adipocyte - specific functions .", "entity": [], "task": "NER"}
{"text": "High - dose resveratrol supplementation in obese men : an investigator - initiated , randomized , placebo - controlled clinical trial of substrate metabolism , insulin sensitivity , and body composition .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Obesity , diabetes , hypertension , and hyperlipidemia constitute risk factors for morbidity and premature mortality .", "entity": [], "task": "NER"}
{"text": "Based on animal and in vitro studies , resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 ( SIRT1 ) , but data in human subjects are scarce .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [39, 50]}], "task": "NER"}
{"text": "The objective of this study was to examine the metabolic effects of high - dose resveratrol in obese human subjects .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "In a randomized , placebo - controlled , double - blinded , and parallel - group design , 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity ( hyperinsulinemic euglycemic clamp ) were performed before and after the treatment .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "Insulin sensitivity , the primary outcome measure , deteriorated insignificantly in both groups .", "entity": [], "task": "NER"}
{"text": "Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "Resveratrol supplementation also had no effect on blood pressure ; resting energy expenditure ; oxidation rates of lipid ; ectopic or visceral fat content ; or inflammatory and metabolic biomarkers .", "entity": [{"entity": "Resveratrol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [122, 133]}], "task": "NER"}
{"text": "Islet alpha - , beta - , and delta - cell development is controlled by the Ldb1 coregulator , acting primarily with the islet - 1 transcription factor .", "entity": [], "task": "NER"}
{"text": "Ldb1 and Ldb2 are coregulators that mediate Lin11 - Isl1 - Mec3 ( LIM ) - homeodomain ( HD ) and LIM - only transcription factor - driven gene regulation .", "entity": [], "task": "NER"}
{"text": "Although both Ldb1 and Ldb2 mRNA were produced in the developing and adult pancreas , immunohistochemical analysis illustrated a broad Ldb1 protein expression pattern during early pancreatogenesis , which subsequently became enriched in islet and ductal cells perinatally .", "entity": [], "task": "NER"}
{"text": "The islet - enriched pattern of Ldb1 was similar to pan - endocrine cell - expressed Islet - 1 ( Isl1 ) , which was demonstrated in this study to be the primary LIM - HD transcription factor in developing and adult islet cells .", "entity": [], "task": "NER"}
{"text": "Endocrine cell - specific removal of Ldb1 during mouse development resulted in a severe reduction of hormone + cell numbers ( i . e . , alpha , beta , and delta ) and overt postnatal hyperglycemia , reminiscent of the phenotype described for the Isl1 conditional mutant .", "entity": [], "task": "NER"}
{"text": "In contrast , neither endocrine cell development nor function was affected in the pancreas of Ldb2 ( - / - ) mice .", "entity": [], "task": "NER"}
{"text": "Gene expression and chromatin immunoprecipitation ( ChIP ) analyses demonstrated that many important Isl1 - activated genes were coregulated by Ldb1 , including MafA , Arx , insulin , and Glp1r .", "entity": [], "task": "NER"}
{"text": "However , some genes ( i . e . , Hb9 and Glut2 ) only appeared to be impacted by Ldb1 during development .", "entity": [], "task": "NER"}
{"text": "These findings establish Ldb1 as a critical transcriptional coregulator during islet alpha - , beta - , and delta - cell development through Isl1 - dependent and potentially Isl1 - independent control .", "entity": [], "task": "NER"}
{"text": "Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21 .", "entity": [], "task": "NER"}
{"text": "In pregnant women , the diabetic condition results in a three - to fivefold increased risk for fetal cardiac malformations as a result of elevated glucose concentrations and the resultant osmotic stress in the developing embryo and fetus .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [147, 154]}], "task": "NER"}
{"text": "Heart development before septation in the chick embryo was studied under two hyperglycemic conditions .", "entity": [], "task": "NER"}
{"text": "Pulsed hyperglycemia induced by daily administration of glucose during 3 days of development caused daily spikes in plasma glucose concentration .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "In a second model , sustained hyperglycemia was induced with a single injection of glucose into the yolk on day 0 .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "The sustained model raised the average plasma glucose concentration from 70 mg / dL to 180 mg / dL and led to decreased gene expression of glucose transporter GLUT1 .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "Both models of hyperglycemia reduced embryo size , increased mortality , and delayed development .", "entity": [], "task": "NER"}
{"text": "Within the heart outflow tract , reduced proliferation of myocardial and endocardial cells resulted from the sustained hyperglycemia and hyperosmolarity .", "entity": [], "task": "NER"}
{"text": "The cell cycle inhibitor p21 was significantly increased , whereas cyclin D1 , a cell cycle promoter , decreased in sustained hyperglycemia compared with controls .", "entity": [], "task": "NER"}
{"text": "The evidence suggests that hyperglycemia - induced developmental delays are associated with slowed cell cycle progression , leading to reduced cellular proliferation .", "entity": [], "task": "NER"}
{"text": "The suppression of critical developmental steps may underlie the cardiac defects observed during late gestation under hyperglycemic conditions .", "entity": [], "task": "NER"}
{"text": "H2DB : a heritability database across multiple species by annotating trait - associated genomic loci .", "entity": [], "task": "NER"}
{"text": "H2DB ( http : / / tga . nig . ac . jp / h2db / ) , an annotation database of genetic heritability estimates for humans and other species , has been developed as a knowledge database to connect trait - associated genomic loci .", "entity": [], "task": "NER"}
{"text": "Heritability estimates have been investigated for individual species , particularly in human twin studies and plant / animal breeding studies .", "entity": [], "task": "NER"}
{"text": "However , there appears to be no comprehensive heritability database for both humans and other species .", "entity": [], "task": "NER"}
{"text": "Here , we introduce an annotation database for genetic heritabilities of various species that was annotated by manually curating online public resources in PUBMED abstracts and journal contents .", "entity": [], "task": "NER"}
{"text": "The proposed heritability database contains attribute information for trait descriptions , experimental conditions , trait - associated genomic loci and broad - and narrow - sense heritability specifications .", "entity": [], "task": "NER"}
{"text": "Annotated trait - associated genomic loci , for which most are single - nucleotide polymorphisms derived from genome - wide association studies , may be valuable resources for experimental scientists .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [72, 82]}], "task": "NER"}
{"text": "In addition , we assigned phenotype ontologies to the annotated traits for the purposes of discussing heritability distributions based on phenotypic classifications .", "entity": [], "task": "NER"}
{"text": "PTMcode : a database of known and predicted functional associations between post - translational modifications in proteins .", "entity": [], "task": "NER"}
{"text": "Post - translational modifications ( PTMs ) are involved in the regulation and structural stabilization of eukaryotic proteins .", "entity": [], "task": "NER"}
{"text": "The combination of individual PTM states is a key to modulate cellular functions as became evident in a few well - studied proteins .", "entity": [], "task": "NER"}
{"text": "This combinatorial setting , dubbed the PTM code , has been proposed to be extended to whole proteomes in eukaryotes .", "entity": [], "task": "NER"}
{"text": "Although we are still far from deciphering such a complex language , thousands of protein PTM sites are being mapped by high - throughput technologies , thus providing sufficient data for comparative analysis .", "entity": [], "task": "NER"}
{"text": "PTMcode ( http : / / ptmcode . embl . de ) aims to compile known and predicted PTM associations to provide a framework that would enable hypothesis - driven experimental or computational analysis of various scales .", "entity": [], "task": "NER"}
{"text": "In its first release , PTMcode provides PTM functional associations of 13 different PTM types within proteins in 8 eukaryotes .", "entity": [], "task": "NER"}
{"text": "They are based on five evidence channels : a literature survey , residue co - evolution , structural proximity , PTMs at the same residue and location within PTM highly enriched protein regions ( hotspots ) .", "entity": [], "task": "NER"}
{"text": "PTMcode is presented as a protein - based searchable database with an interactive web interface providing the context of the co - regulation of nearly 75 000 residues in > 10 000 proteins .", "entity": [], "task": "NER"}
{"text": "The chemopreventive effect of beta - cryptoxanthin from mandarin on human stomach cells ( BGC - 823 ) .", "entity": [{"entity": "beta - cryptoxanthin", "entity_type": "Chemical", "pos": [30, 50]}], "task": "NER"}
{"text": "beta - Cryptoxanthin , a provitaminic carotenoid , present in many fruits and vegetables , has been associated with decreased risk of chronic diseases , including cancer .", "entity": [{"entity": "beta - Cryptoxanthin", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "The influence of beta - cryptoxanthin derived from mandarin on the proliferation of the stomach tumor cell line BGC - 823 was tested using MTT and cell count assay at 72 h and dose - response ( from 0 . 01 to 20 mu M ) .", "entity": [{"entity": "beta - cryptoxanthin", "entity_type": "Chemical", "pos": [17, 37]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "beta - Cryptoxanthin suppressed the cell migration by the scratch assay .", "entity": [{"entity": "beta - Cryptoxanthin", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "Furthermore , beta - cryptoxanthin induced an accumulation of cells in the G1 / G0 phase of the cell cycle ( as detected by flow cytometry ) , which was in accordance with an increased expression of p21 and down regulations of cyclin D1 and cyclin E , detected by Western blot analysis , and beta - cryptoxanthin increased the mRNA levels of retinoic acid receptor beta ( RAR beta ) with the treatment at 10 mu M for 24 h .", "entity": [{"entity": "beta - cryptoxanthin", "entity_type": "Chemical", "pos": [14, 34]}, {"entity": "beta - cryptoxanthin", "entity_type": "Chemical", "pos": [292, 312]}, {"entity": "retinoic acid", "entity_type": "Chemical", "pos": [342, 355]}], "task": "NER"}
{"text": "Collectively , the above findings suggest that beta - cryptoxanthin could be therapeutic in the treatment of stomach cancer cell in vitro .", "entity": [{"entity": "beta - cryptoxanthin", "entity_type": "Chemical", "pos": [47, 67]}], "task": "NER"}
{"text": "Edible and non - edible olive oils discrimination by the application of a sensory olfactory system based on tin dioxide sensors .", "entity": [{"entity": "tin dioxide", "entity_type": "Chemical", "pos": [108, 119]}], "task": "NER"}
{"text": "An array of semiconductor sensors has been developed to discriminate virgin olive oil samples based on their organoleptic characteristics .", "entity": [], "task": "NER"}
{"text": "The multisensor , developed at laboratory , is composed by 14 sensing elements of tin dioxide thin layers ( doped with Cr and In , and undoped ) deposited by the reactive sputtering technique .", "entity": [{"entity": "tin dioxide", "entity_type": "Chemical", "pos": [82, 93]}, {"entity": "Cr", "entity_type": "Chemical", "pos": [119, 121]}, {"entity": "In", "entity_type": "Chemical", "pos": [126, 128]}], "task": "NER"}
{"text": "The sensors are stable and show good repeatability .", "entity": [], "task": "NER"}
{"text": "Off - flavors and extra - virgin olive oil samples , taken at the outlet of the vertical centrifuge of a small experimental olive oil mill and sensory evaluated , have been used .", "entity": [], "task": "NER"}
{"text": "A good discrimination of edible ( extra - virgin and virgin ) from non - edible ( lampante ) olive oils has been obtained through the statistical method of principal component analysis ( PCA ) .", "entity": [], "task": "NER"}
{"text": "Phenolic profiles and antioxidant activity of litchi pulp of different cultivars cultivated in Southern China .", "entity": [], "task": "NER"}
{"text": "The phenolic profiles and antioxidant activity of litchi pulp of 13 varieties were investigated .", "entity": [], "task": "NER"}
{"text": "The free , bound and total phenolic contents were 66 . 17 - 226 . 03 , 11 . 18 - 40 . 54 , and 101 . 51 - 259 . 18 mg of gallic acid equivalents / 100 g , respectively .", "entity": [{"entity": "gallic acid", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "The free , bound and total flavonoid contents were 16 . 68 - 110 . 33 , 10 . 48 - 22 . 75 , and 39 . 43 - 129 . 86 mg of catechin equivalents / 100 g , respectively .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "catechin", "entity_type": "Chemical", "pos": [121, 129]}], "task": "NER"}
{"text": "Free phenolics and flavonoids contributed averagely 80 . 1 % and 75 % to their total contents , respectively .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [5, 14]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "Six individual phenolics ( gallic acid , chlorogenic acid , ( + ) - catechin , caffeic acid , ( - ) - epicatechin , and rutin ) were detected in litchi pulp by HPLC .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [41, 57]}, {"entity": "( + ) - catechin", "entity_type": "Chemical", "pos": [60, 76]}, {"entity": "caffeic acid", "entity_type": "Chemical", "pos": [79, 91]}, {"entity": "( - ) - epicatechin", "entity_type": "Chemical", "pos": [94, 113]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [120, 125]}], "task": "NER"}
{"text": "The contents of each compound in free and bound fractions were determined .", "entity": [], "task": "NER"}
{"text": "Significant varietal discrepancy in antioxidant activity was also found by FRAP and DPPH scavenging capacity methods .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [84, 88]}], "task": "NER"}
{"text": "Antioxidant activity was significantly correlated with phenolic and flavonoid contents .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "Thus , phenolics and flavonoids exist mainly in the free form in litchi pulp .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [7, 16]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "There were significant varietal differences in phytochemical contents and antioxidant activity of litchi pulp .", "entity": [], "task": "NER"}
{"text": "Immunomodulatory effect of Ganoderma atrum polysaccharide on CT26 tumor - bearing mice .", "entity": [], "task": "NER"}
{"text": "Ganoderma atrum has attracted great attention for its antitumor activity .", "entity": [], "task": "NER"}
{"text": "However , the mechanism remains unclear .", "entity": [], "task": "NER"}
{"text": "A G . atrum polysaccharide ( PSG - 1 ) showed pronounced antitumor activity in this study .", "entity": [], "task": "NER"}
{"text": "PSG - 1 did not kill CT26 cells directly , but inhibited the proliferation of CT26 cells via the activation of peritoneal macrophages ( M Phi ) .", "entity": [], "task": "NER"}
{"text": "In vivo , PSG - 1 significantly suppressed the tumor growth in CT26 tumor - bearing mice .", "entity": [], "task": "NER"}
{"text": "The treatment caused a significant increase in the immune organ index and the phagocytosis of macrophages .", "entity": [], "task": "NER"}
{"text": "The production of TNF - alpha , IL - 1 beta and nitric oxide also increased .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [48, 60]}], "task": "NER"}
{"text": "Furthermore , we found that PSG - 1 acted on Toll - like receptor ( TLR ) 4 , signaled through p38 MAPK pathway , then activated NF - kappa B and stimulated TNF - alpha production .", "entity": [], "task": "NER"}
{"text": "We further found that PSG - 1 increased the expression of TLR4 and NF - kappa B , the degradation of I kappa B alpha and the phosphorylation of p38 MAPK .", "entity": [], "task": "NER"}
{"text": "In summary , we have demonstrated that PSG - 1 could activate macrophages via TLR4 - dependent signaling pathways , improve immunity and inhibit tumor growth .", "entity": [], "task": "NER"}
{"text": "Identification of hydroxychavicol and its dimers , the lipase inhibitors contained in the Indonesian spice , Eugenia polyantha .", "entity": [{"entity": "hydroxychavicol", "entity_type": "Chemical", "pos": [18, 33]}], "task": "NER"}
{"text": "Inhibition of pancreatic lipase is effective for a prevention of obesity .", "entity": [], "task": "NER"}
{"text": "Eugenia polyantha is a tropical tree whose leaves are known as a spice and also as an ingredient for Jamu , the traditional medicine of Indonesia .", "entity": [], "task": "NER"}
{"text": "We found inhibitory activity against pancreatic lipase in the extract of E . polyantha leaves .", "entity": [], "task": "NER"}
{"text": "Purification of the active principals resulted in isolation of hydroxychavicol , and two structurally new dimers .", "entity": [{"entity": "hydroxychavicol", "entity_type": "Chemical", "pos": [63, 78]}], "task": "NER"}
{"text": "All of the isolated compounds showed inhibitory activity against the porcine pancreatic lipase and high content of hydroxychavicol ( 1 . 83 wt . % ) indicated this compound to be responsible for the majority of inhibitory activity of E . polyantha extract .", "entity": [{"entity": "hydroxychavicol", "entity_type": "Chemical", "pos": [115, 130]}], "task": "NER"}
{"text": "Furthermore , hydroxychavicol is reported to possess anti - carcinogenic , anti - oxidant , anti - microbial and anti - inflammatory activity which is related to traditional usage of this plant .", "entity": [{"entity": "hydroxychavicol", "entity_type": "Chemical", "pos": [14, 29]}], "task": "NER"}
{"text": "These results offer this plant as an attractive material for treating various health problems including obesity .", "entity": [], "task": "NER"}
{"text": "Contents of dietary fibre components and their relation to associated bioactive components in whole grain wheat samples from the HEALTHGRAIN diversity screen .", "entity": [], "task": "NER"}
{"text": "A large and diverse material collection of whole grain wheat samples ( n = 129 ) was analysed for total dietary fibre ( TDF ) content and composition , including fructan ( 11 . 5 - 15 . 5 % ) .", "entity": [], "task": "NER"}
{"text": "Correlations between the dietary fibre components , associated bioactive components ( e . g . tocols , sterols , phenolic acids and folates ) and agronomic properties previously determined on the same samples were found with multivariate analysis ( PCA ) .", "entity": [{"entity": "tocols", "entity_type": "Chemical", "pos": [94, 100]}, {"entity": "sterols", "entity_type": "Chemical", "pos": [103, 110]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [113, 127]}, {"entity": "folates", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "Samples from the same countries had similar characteristics .", "entity": [], "task": "NER"}
{"text": "The first PC described variation in components concentrated in the starchy endosperm ( e . g . starch , beta - glucan and fructan ) and the dietary fibre components concentrated in the bran ( e . g . TDF , arabinoxylan and cellulose ) .", "entity": [], "task": "NER"}
{"text": "The second PC described the variation in kernel weight and other bran components such as alkylresorcinols , tocols and sterols .", "entity": [{"entity": "alkylresorcinols", "entity_type": "Chemical", "pos": [89, 105]}, {"entity": "tocols", "entity_type": "Chemical", "pos": [108, 114]}, {"entity": "sterols", "entity_type": "Chemical", "pos": [119, 126]}], "task": "NER"}
{"text": "Interestingly , there was no correlation among these different groups of bran components , which reflected their concentration in different bran tissues .", "entity": [], "task": "NER"}
{"text": "The results are of importance for plant breeders who wish to develop varieties with health - promoting effects .", "entity": [], "task": "NER"}
{"text": "Muscle composition slightly affects in vitro digestion of aged and cooked meat : identification of associated proteomic markers .", "entity": [], "task": "NER"}
{"text": "Meat is an appropriate source of proteins and minerals for human nutrition .", "entity": [], "task": "NER"}
{"text": "Technological treatments modify the physical - chemical properties of proteins , making them liable to decrease the nutritional potential of meat .", "entity": [], "task": "NER"}
{"text": "To counteract this damage , antioxidants and chaperone proteins in muscle cells can prevent oxidation , restore the function of denatured proteins , and thus prevent aggregation .", "entity": [], "task": "NER"}
{"text": "This study aimed to explore the impact of indoor vs outdoor - reared meat protein composition on digestion and to associate protein markers to in vitro digestion parameters .", "entity": [], "task": "NER"}
{"text": "Indoor - reared meat tended to show less oxidation and denaturation than outdoor - reared meat and was characterised by an overexpression of contractile and chaperone proteins .", "entity": [], "task": "NER"}
{"text": "Outdoor - reared meat showed amplification of antioxidant and detoxification metabolism defending against oxidised compounds .", "entity": [], "task": "NER"}
{"text": "Impacts on digestion remained minor .", "entity": [], "task": "NER"}
{"text": "Several protein markers of in vitro digestion parameters were found for aged and cooked meat , linked to the detoxification process and to muscle contraction .", "entity": [], "task": "NER"}
{"text": "Determination of herb authenticity by low - field NMR .", "entity": [], "task": "NER"}
{"text": "The safe use of herbal medicines requires prior authentication of the raw materials used to make them .", "entity": [], "task": "NER"}
{"text": "This is an important step , since the ingestion of herbal preparations or extracts can cause serious health problems .", "entity": [], "task": "NER"}
{"text": "Among the different analytical techniques , nuclear magnetic resonance ( NMR ) spectroscopy has the advantage of being non - invasive and therefore suitable for the characterization of natural products such as medicinal plants .", "entity": [], "task": "NER"}
{"text": "This work presents a characterisation study of the samples of the popular plant Maytenus ilicifolia , obtained from different commercial producers .", "entity": [], "task": "NER"}
{"text": "This plant is used for the treatment of gastrointestinal disorders , as it possesses antitumorigenic , analgesic , anti - inflammatory and antioxidant properties .", "entity": [], "task": "NER"}
{"text": "The differences in the chemical structure and molecular organisation detected by thermogravimetric analysis ( TGA ) , infrared spectroscopy ( FTIR ) and nuclear magnetic resonance spectroscopy ( NMR ) were also investigated by proton nuclear magnetic resonance relaxometry , in particular by fast field cycling ( FFC ) relaxometry , and relaxometry in the rotating frame .", "entity": [], "task": "NER"}
{"text": "All results confirmed the similarity between the control sample and only one of the plant investigated .", "entity": [], "task": "NER"}
{"text": "The differences detected between the samples could be related to their non - authenticity , due to the non recognise the plant due to the leaves similarity among plants from the same family and / or contamination , due to addition of similar other plants parts to the commercial ones , as they are mixed together this difficulties the acceptation of the plant .", "entity": [], "task": "NER"}
{"text": "Monitoring of Escherichia coli O157 : H7 in food samples using lectin based surface plasmon resonance biosensor .", "entity": [], "task": "NER"}
{"text": "A novel surface plasmon resonance ( SPR ) biosensor using lectin as bioreceptor was developed for the rapid detection of Escherichia coli ( E . coli ) O157 : H7 .", "entity": [], "task": "NER"}
{"text": "The selective interaction of lectins with carbohydrate components from bacterial cells surface was used as the recognition principle for the detection .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [42, 54]}], "task": "NER"}
{"text": "Five types of lectins from Triticum vulgaris , Canavailia ensiformis , Ulex europaeus , Arachis hypogaea , and Maackia amurensis , were employed to evaluate the selectivity of the approach for binding E . coli O157 : H7 effectively .", "entity": [], "task": "NER"}
{"text": "A detection limit of 3 x 10 ( 3 ) cfu mL ( - 1 ) was obtained for determination of E . coli O157 : H7 when used the lectin from T . vulgaris as the binding molecule .", "entity": [], "task": "NER"}
{"text": "Furthermore , the proposed biosensor was used to detect E . coli O157 : H7 in real food samples .", "entity": [], "task": "NER"}
{"text": "Results showed that the lectin based SPR biosensor was sensitive , reliable and effective for detection of E . coli O157 : H7 , which hold a great promise in food safety analysis .", "entity": [], "task": "NER"}
{"text": "Development and validation of an HPLC method for the determination of six penicillin and three amphenicol antibiotics in gilthead seabream ( Sparus Aurata ) tissue according to the European Union Decision 2002 / 657 / EC .", "entity": [{"entity": "penicillin", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "amphenicol", "entity_type": "Chemical", "pos": [95, 105]}], "task": "NER"}
{"text": "A confirmatory high performance liquid chromatography method for the determination of six penicillin antibiotics and three amphenicol antibiotics in gilthead seabream ( Sparus Aurata ) tissue was developed .", "entity": [{"entity": "penicillin", "entity_type": "Chemical", "pos": [90, 100]}, {"entity": "amphenicol", "entity_type": "Chemical", "pos": [123, 133]}], "task": "NER"}
{"text": "Ampicillin ( AMP ) , penicillin G ( PG ) , penicillin V ( PV ) , oxacillin ( OXA ) , cloxacillin ( CLO ) , dicloxacillin ( DICLO ) , thiamphenicol ( TAP ) , florfenicol ( FFC ) and chloramphenicol ( CAP ) were separated on an Inertsil , C ( 8 ) ( 250 x 4 mm , 5 mu m ) column by gradient elution with a mobile phase consisting of ammonium acetate 0 . 05 M and acetonitrile at 25 degrees C .", "entity": [{"entity": "Ampicillin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "AMP", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "penicillin G", "entity_type": "Chemical", "pos": [21, 33]}, {"entity": "penicillin V", "entity_type": "Chemical", "pos": [43, 55]}, {"entity": "oxacillin", "entity_type": "Chemical", "pos": [65, 74]}, {"entity": "OXA", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "cloxacillin", "entity_type": "Chemical", "pos": [85, 96]}, {"entity": "CLO", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "dicloxacillin", "entity_type": "Chemical", "pos": [107, 120]}, {"entity": "DICLO", "entity_type": "Chemical", "pos": [123, 128]}, {"entity": "thiamphenicol", "entity_type": "Chemical", "pos": [133, 146]}, {"entity": "TAP", "entity_type": "Chemical", "pos": [149, 152]}, {"entity": "florfenicol", "entity_type": "Chemical", "pos": [157, 168]}, {"entity": "FFC", "entity_type": "Chemical", "pos": [171, 174]}, {"entity": "chloramphenicol", "entity_type": "Chemical", "pos": [181, 196]}, {"entity": "CAP", "entity_type": "Chemical", "pos": [199, 202]}, {"entity": "ammonium acetate", "entity_type": "Chemical", "pos": [330, 346]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [360, 372]}], "task": "NER"}
{"text": "Diode array detection with monitoring at 225 nm ( for the determination of AMP , PG , PV , TAP and FFC ) , 240 nm ( for OXA , CLO and DICLO ) and 278 nm ( for CAP ) was applied .", "entity": [{"entity": "AMP", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "TAP", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "FFC", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "OXA", "entity_type": "Chemical", "pos": [120, 123]}, {"entity": "CLO", "entity_type": "Chemical", "pos": [126, 129]}, {"entity": "DICLO", "entity_type": "Chemical", "pos": [134, 139]}, {"entity": "CAP", "entity_type": "Chemical", "pos": [159, 162]}], "task": "NER"}
{"text": "Examined antibiotics were isolated from gilthead seabream tissue by liquid - liquid extraction and further clean - up was performed by solid phase extraction using Oasis HLB ( 200 mg / 6 mL ) cartridges .", "entity": [], "task": "NER"}
{"text": "Metabolite profiling of ginsenoside Re in rat urine and faeces after oral administration .", "entity": [{"entity": "ginsenoside Re", "entity_type": "Chemical", "pos": [24, 38]}], "task": "NER"}
{"text": "Following oral administration of ginsenoside Re , the compound and its metabolites were identified and quantified in rat urine and faeces by liquid chromatography coupled with triple quadrupole mass spectrometry ( LC - MS / MS ) .", "entity": [{"entity": "ginsenoside Re", "entity_type": "Chemical", "pos": [33, 47]}], "task": "NER"}
{"text": "Ginsenoside Re ( 200 mg / kg ) was orally administered to rats by gastric intubation , and urine and faeces samples were then collected during the next 24 h using metabolic cages .", "entity": [{"entity": "Ginsenoside Re", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Samples were prepared by solid phase extraction and analysed by LC - MS / MS .", "entity": [], "task": "NER"}
{"text": "The precursor - product ion pairs used for LC - MS / MS analysis were : m / z 945 --> 475 for ginsenoside Re , 799 --> 637 for ginsenoside Rg1 , 783 --> 475 for ginsenoside Rg2 , 637 --> 475 for ginsenosides Rh1 and F1 , 475 --> 391 for protopanaxatriol , and 779 --> 641 for digoxin ( internal standard ) .", "entity": [{"entity": "ginsenoside Re", "entity_type": "Chemical", "pos": [94, 108]}, {"entity": "ginsenoside Rg1", "entity_type": "Chemical", "pos": [127, 142]}, {"entity": "ginsenoside Rg2", "entity_type": "Chemical", "pos": [161, 176]}, {"entity": "ginsenosides Rh1 and F1", "entity_type": "Chemical", "pos": [195, 218]}, {"entity": "protopanaxatriol", "entity_type": "Chemical", "pos": [237, 253]}, {"entity": "digoxin", "entity_type": "Chemical", "pos": [276, 283]}], "task": "NER"}
{"text": "The major ginsenosides excreted in urine were ginsenosides Re and Rg1 , and only minimal amounts of ginsenosides Rg2 and Rh1 were found .", "entity": [{"entity": "ginsenosides", "entity_type": "Chemical", "pos": [10, 22]}, {"entity": "ginsenosides Re and Rg1", "entity_type": "Chemical", "pos": [46, 69]}, {"entity": "ginsenosides Rg2 and Rh1", "entity_type": "Chemical", "pos": [100, 124]}], "task": "NER"}
{"text": "Greater amounts of ginsenoside metabolites were detected in the faeces samples ; biotransformation to ginsenoside Rg1 was predominant but further deglycosylated metabolites including ginsenoside F1 and protopanaxatriol were additionally detected .", "entity": [{"entity": "ginsenoside", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "ginsenoside Rg1", "entity_type": "Chemical", "pos": [102, 117]}, {"entity": "ginsenoside F1", "entity_type": "Chemical", "pos": [183, 197]}, {"entity": "protopanaxatriol", "entity_type": "Chemical", "pos": [202, 218]}], "task": "NER"}
{"text": "The total recovery of ginsenosides over 24 h was approximately 46 % .", "entity": [{"entity": "ginsenosides", "entity_type": "Chemical", "pos": [22, 34]}], "task": "NER"}
{"text": "Characterization and identification of the chemical constituents from tartary buckwheat ( Fagopyrum tataricum Gaertn ) by high performance liquid chromatography / photodiode array detector / linear ion trap FTICR hybrid mass spectrometry .", "entity": [], "task": "NER"}
{"text": "In recent years tartary buckwheat has become popular healthful food due to its antioxidant , antidiabetic and antitumor activities .", "entity": [], "task": "NER"}
{"text": "However , its chemical constituents have not yet been fully characterized and identified .", "entity": [], "task": "NER"}
{"text": "In this paper , a novel high performance liquid chromatography coupled with photodiode array detector and linear ion trap FTICR hybrid mass spectrometry ( HPLC - PDA / LTQ - FTICRMS ) method was established to characterize and identify a total of 36 compounds by a single run .", "entity": [], "task": "NER"}
{"text": "The retention time , maximum UV absorption wavelength , accurate mass weight and characteristic fragment ions were collected on line .", "entity": [], "task": "NER"}
{"text": "To confirm the structures , 11 compounds were isolated and identified by MS and NMR experiments .", "entity": [], "task": "NER"}
{"text": "1 , 3 , 6 , 6 ' - tetra - feruloyl sucrose named taroside was a new phenlypropanoid glycoside , together with 3 , 6 - di - p - coumaroyl - 1 , 6 ' - di - feruloyl sucrose , 1 , 6 , 6 ' - tri - feruloyl - 3 - p - coumaroyl sucrose , N - trans - feruloyltyramine and quercetin - 3 - O - [ beta - D - xyloxyl - ( 1 --> 2 ) - alpha - L - rhamnoside ] were isolated for the first time from the Fagopyrum species .", "entity": [{"entity": "1 , 3 , 6 , 6 ' - tetra - feruloyl sucrose", "entity_type": "Chemical", "pos": [0, 42]}, {"entity": "phenlypropanoid glycoside", "entity_type": "Chemical", "pos": [68, 93]}, {"entity": "3 , 6 - di - p - coumaroyl - 1 , 6 ' - di - feruloyl sucrose", "entity_type": "Chemical", "pos": [110, 170]}, {"entity": "1 , 6 , 6 ' - tri - feruloyl - 3 - p - coumaroyl sucrose", "entity_type": "Chemical", "pos": [173, 229]}, {"entity": "N - trans - feruloyltyramine", "entity_type": "Chemical", "pos": [232, 260]}, {"entity": "quercetin - 3 - O - [ beta - D - xyloxyl - ( 1 --> 2 ) - alpha - L - rhamnoside ]", "entity_type": "Chemical", "pos": [265, 346]}], "task": "NER"}
{"text": "The research enriched the chemical information of tartary buckwheat .", "entity": [], "task": "NER"}
{"text": "Identification and thermal stability of purple - fleshed sweet potato anthocyanins in aqueous solutions with various pH values and fruit juices .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [70, 82]}], "task": "NER"}
{"text": "Thirteen anthocyanins were identified in the purple - fleshed sweet potato cultivar Jihei No . 1 .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [9, 21]}], "task": "NER"}
{"text": "The main anthocyanins were 3 - sophoroside - 5 - glucoside derivatives from cyanidin and peonidin , acylated with p - hydroxybenzoic acid , ferulic acid , or caffeic acid .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [9, 21]}, {"entity": "3 - sophoroside - 5 - glucoside", "entity_type": "Chemical", "pos": [27, 58]}, {"entity": "cyanidin", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "peonidin", "entity_type": "Chemical", "pos": [89, 97]}, {"entity": "p - hydroxybenzoic acid", "entity_type": "Chemical", "pos": [114, 137]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [140, 152]}, {"entity": "caffeic acid", "entity_type": "Chemical", "pos": [158, 170]}], "task": "NER"}
{"text": "A unique anthocyanin , delphinidin - 3 , 5 - diglucoside was also found .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [9, 20]}, {"entity": "delphinidin - 3 , 5 - diglucoside", "entity_type": "Chemical", "pos": [23, 56]}], "task": "NER"}
{"text": "The thermal stability of purple - fleshed sweet potato anthocyanins ( PSPAs ) followed a first - order kinetics model .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [55, 67]}], "task": "NER"}
{"text": "Aqueous solutions with various pH ( 2 , 3 , 4 , 5 , and 6 ) and fruit juices ( apple , pear , grapefruit , orange , tangerine , kiwifruit , and lemon ) were coloured with PSPAs .", "entity": [], "task": "NER"}
{"text": "The enrichment and degradation kinetics of anthocyanins in these matrices were investigated at 80 , 90 , and 100 degrees C .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [43, 55]}], "task": "NER"}
{"text": "A higher stability of anthocyanins was obtained in aqueous solutions with pH 3 and 4 and in apple and pear juices .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [22, 34]}], "task": "NER"}
{"text": "Moreover , the activation energies for PSPA degradation in aqueous solutions with various pH and fruit juices ranged from 66 . 56 kJ / mol to 111 . 57 kJ / mol and 46 . 76 kJ / mol to 75 . 68 kJ / mol , respectively .", "entity": [], "task": "NER"}
{"text": "Rapid analysis of sugars in honey by processing Raman spectrum using chemometric methods and artificial neural networks .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [18, 24]}], "task": "NER"}
{"text": "The aim of this study was to quantify glucose , fructose , sucrose and maltose contents of honey samples using Raman spectroscopy as a rapid method .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "sucrose", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "maltose", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "By performing a single measurement , quantifications of sugar contents have been said to be unaffordable according to the molecular similarities between sugar molecules in honey matrix .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [56, 61]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [153, 158]}], "task": "NER"}
{"text": "This bottleneck was overcome by coupling Raman spectroscopy with chemometric methods ( principal component analysis ( PCA ) and partial least squares ( PLS ) ) and an artificial neural network ( ANN ) .", "entity": [], "task": "NER"}
{"text": "Model solutions of four sugars were processed with PCA and significant separation was observed .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [24, 30]}], "task": "NER"}
{"text": "This operation , done with the spectral features by using PLS and ANN methods , led to the discriminant analysis of sugar contents .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [116, 121]}], "task": "NER"}
{"text": "Models / trained networks were created using a calibration data set and evaluated using a validation data set .", "entity": [], "task": "NER"}
{"text": "The correlation coefficient values between actual and predicted values of glucose , fructose , sucrose and maltose were determined as 0 . 964 , 0 . 965 , 0 . 968 and 0 . 949 for PLS and 0 . 965 , 0 . 965 , 0 . 978 and 0 . 956 for ANN , respectively .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [74, 81]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "sucrose", "entity_type": "Chemical", "pos": [95, 102]}, {"entity": "maltose", "entity_type": "Chemical", "pos": [107, 114]}], "task": "NER"}
{"text": "The requirement of rapid analysis of sugar contents of commercial honeys has been met by the data processed within this article .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [37, 42]}], "task": "NER"}
{"text": "Structural analysis of linear mixed - linkage glucooligosaccharides by tandem mass spectrometry .", "entity": [], "task": "NER"}
{"text": "Dextrans and glucooligosaccharides ( GLOS ) are produced by lactic acid bacteria ( LAB ) during sourdough fermentation .", "entity": [{"entity": "lactic acid", "entity_type": "Chemical", "pos": [60, 71]}], "task": "NER"}
{"text": "The dextrans can act as hydrocolloids in sourdough bread , while the GLOS may have antistaling and prebiotic properties , depending on their structure .", "entity": [], "task": "NER"}
{"text": "Development of high - throughput methods for screening the structural properties of dextrans and GLOS produced by different LAB in varying fermentation conditions is therefore of interest .", "entity": [], "task": "NER"}
{"text": "In this study we explored the possibility of using electrospray ionisation tandem mass spectroscopy ( ESI - MS / MS ) to unequivocally determine the structures of underivatised GLOS .", "entity": [], "task": "NER"}
{"text": "The emphasis was on linear mixed linked model GLOS , especially those containing ( 1 --> 3 ) linkages that are common in dextrans .", "entity": [], "task": "NER"}
{"text": "After evaluation of the model GLOS , the ESI - MS / MS method was used to determine the linkage positions of two mixed - linked tetrasaccharides obtained by hydrolysis of Weissella confusa and Leuconostoc citreum dextrans .", "entity": [{"entity": "tetrasaccharides", "entity_type": "Chemical", "pos": [128, 144]}], "task": "NER"}
{"text": "In positive mode , only the reducing end linkage could be determined because isomeric fragment ions , present in subsequent MS ( n ) cycles , hindered assignment of the remaining linkages .", "entity": [], "task": "NER"}
{"text": "By contrast , it was possible to unambiguously assign all the linkages in each GLOS using the negative mode spectra .", "entity": [], "task": "NER"}
{"text": "The present study thus shows that negative mode is the preferred method for ESI - MS / MS structural analysis of underivatised GLOS .", "entity": [], "task": "NER"}
{"text": "In combination with liquid chromatography this method will enable rapid profiling of the structural variation of dextrans and prebiotic GLOS .", "entity": [], "task": "NER"}
{"text": "Accumulation of heavy metals in edible parts of vegetables irrigated with waste water and their daily intake to adults and children , District Mardan , Pakistan .", "entity": [], "task": "NER"}
{"text": "Green vegetable crops irrigated with wastewater are highly contaminated with heavy metals and are the main source of human exposure to the contaminants .", "entity": [], "task": "NER"}
{"text": "In this study accumulation of eight heavy metals ( Cu , Ni , Zn , Cr , Fe , Mn , Co and Pb ) in green vegetables like Allium cepa , Allium sativum , Solanum lycopersicum and Solanum melongena , irrigated with wastewater in Mardan are studied using Atomic Absorption spectrophotometer .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [61, 63]}, {"entity": "Cr", "entity_type": "Chemical", "pos": [66, 68]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [71, 73]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [76, 78]}, {"entity": "Co", "entity_type": "Chemical", "pos": [81, 83]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [88, 90]}], "task": "NER"}
{"text": "The studied metals in vegetable grown on wastewater irrigated soil were significantly higher than those of tube well water irrigated soil and WHO / FAO permissible limits ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "The most heavily contaminated vegetable was wastewater irrigated A . cepa , where the accumulation of Mn ( 28 . 05 mg kg ( - 1 ) ) in the edible parts was 50 - fold greater than A . cepa irrigated with tube well water irrigated soil .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [102, 104]}], "task": "NER"}
{"text": "It may be concluded that both adults and children consuming these vegetables grown in wastewater irrigated soil ingest significant amount of these metals and thus can cause serious health problems .", "entity": [], "task": "NER"}
{"text": "Principal component analysis of proteolytic profiles as markers of authenticity of PDO cheeses .", "entity": [], "task": "NER"}
{"text": "The casein fraction of 13 Portuguese PDO cheeses were analysed using Urea - PAGE and reverse phase - high performance liquid chromatography ( RP - HPLC ) and then subjected to chemometric evaluation .", "entity": [{"entity": "Urea", "entity_type": "Chemical", "pos": [69, 73]}], "task": "NER"}
{"text": "The chemometric techniques of cluster analysis ( CA ) and principal component analysis ( PCA ) were used for the classification studies .", "entity": [], "task": "NER"}
{"text": "Peptide mapping using Urea - PAGE followed by CA revealed two major clusters according to the similarity of the proteolytic profile of the cheeses .", "entity": [{"entity": "Urea", "entity_type": "Chemical", "pos": [22, 26]}], "task": "NER"}
{"text": "PCA results were in accordance with the grouping performed using CA .", "entity": [], "task": "NER"}
{"text": "CA of RP - HPLC results of the matured cheeses revealed the presence of one major cluster comprising samples manufactured with only ovine milk or milk admixtures .", "entity": [], "task": "NER"}
{"text": "When the results of CA technique were compared with the two PCA approaches performed , it was found that the grouping of the samples was similar .", "entity": [], "task": "NER"}
{"text": "Both approaches , revealed the potential of proteolytic profiles ( which is an essential aspect of cheese maturation ) as markers of authenticity of PDO cheeses in terms of ripening time and milk admixtures not mentioned on the label .", "entity": [], "task": "NER"}
{"text": "Isotopic analysis of eggs : evaluating sample collection and preparation .", "entity": [], "task": "NER"}
{"text": "Egg traceability / authenticity is a worldwide concern .", "entity": [], "task": "NER"}
{"text": "Stable isotope techniques have been suggested as a tool to address this issue .", "entity": [], "task": "NER"}
{"text": "To further validate the use of these techniques , a research project was undertaken to evaluate what effect sample collection and preparation have on the measured isotopic composition of egg components .", "entity": [], "task": "NER"}
{"text": "The timing of egg collection , the timing of egg preparation after collection , and the use of pasteurisation were investigated .", "entity": [], "task": "NER"}
{"text": "The C , N , O , and S isotopic compositions of egg components from 7 different production systems were measured .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}, {"entity": "N", "entity_type": "Chemical", "pos": [8, 9]}, {"entity": "O", "entity_type": "Chemical", "pos": [12, 13]}, {"entity": "S", "entity_type": "Chemical", "pos": [20, 21]}], "task": "NER"}
{"text": "Two sets of eggs were collected ( 4 months apart ) .", "entity": [], "task": "NER"}
{"text": "It was found that the ' isotopic fingerprint ' of a particular production system was maintained over time , and that it may be possible to trace liquid egg products based on isotopic data from fresh eggs .", "entity": [], "task": "NER"}
{"text": "The findings from this study support the integration of stable isotope techniques in egg traceability / authenticity systems .", "entity": [], "task": "NER"}
{"text": "The application of Near - Infrared Reflectance Spectroscopy ( NIRS ) to detect melamine adulteration of soya bean meal .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "Soya bean products are used widely in the animal feed industry as a protein based feed ingredient and have been found to be adulterated with melamine .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "This was highlighted in the Chinese scandal of 2008 .", "entity": [], "task": "NER"}
{"text": "Dehulled soya ( GM and non - GM ) , soya hulls and toasted soya were contaminated with melamine and spectra were generated using Near Infrared Reflectance Spectroscopy ( NIRS ) .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "By applying chemometrics to the spectral data , excellent calibration models and prediction statistics were obtained .", "entity": [], "task": "NER"}
{"text": "The coefficients of determination ( R ( 2 ) ) were found to be 0 . 89 - 0 . 99 depending on the mathematical algorithm used , the data pre - processing applied and the sample type used .", "entity": [], "task": "NER"}
{"text": "The corresponding values for the root mean square error of calibration and prediction were found to be 0 . 081 - 0 . 276 % and 0 . 134 - 0 . 368 % , respectively , again depending on the chemometric treatment applied to the data and sample type .", "entity": [], "task": "NER"}
{"text": "In addition , adopting a qualitative approach with the spectral data and applying PCA , it was possible to discriminate between the four samples types and also , by generation of Cooman ' s plots , possible to distinguish between adulterated and non - adulterated samples .", "entity": [], "task": "NER"}
{"text": "Detection of pyrrolizidine alkaloids in commercial honey using liquid chromatography - ion trap mass spectrometry .", "entity": [{"entity": "pyrrolizidine alkaloids", "entity_type": "Chemical", "pos": [13, 36]}], "task": "NER"}
{"text": "Pyrrolizidine alkaloids ( PAs ) are known secondary plant metabolites which can cause hepatotoxicity in both humans and livestock .", "entity": [{"entity": "Pyrrolizidine alkaloids", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "PAs can be consumed through the use of plants for food , medicinal purposes and as contaminants of agricultural crops and food .", "entity": [], "task": "NER"}
{"text": "PA contaminated grain has posed the largest health risk , although any PA contamination in our food chain should be recognised as a potential health threat .", "entity": [], "task": "NER"}
{"text": "For this purpose , retail honeys were tested by LC - MS / MS .", "entity": [], "task": "NER"}
{"text": "The method allows for specific identification of toxic retronecine and otonecine - type PAs by comparison to reference compounds via a spectral library .", "entity": [{"entity": "retronecine", "entity_type": "Chemical", "pos": [55, 66]}, {"entity": "otonecine", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "In total , 50 honey samples were matched to the reference spectra within a set of tolerance parameters .", "entity": [], "task": "NER"}
{"text": "Accurate data analysis and quick detection of positive samples was possible .", "entity": [], "task": "NER"}
{"text": "Positive samples contained an average PA concentration of 1260 mu g kg ( - 1 ) of honey .", "entity": [], "task": "NER"}
{"text": "Good linear calibrations were obtained ( R ( 2 ) > 0 . 991 ) .", "entity": [], "task": "NER"}
{"text": "LOD and LOQ ranged from 0 . 0134 to 0 . 0305 and 0 . 0446 to 0 . 1018 mu g mL ( - 1 ) , respectively .", "entity": [], "task": "NER"}
{"text": "Endocrine disruptor activity in bottled mineral and flavoured water .", "entity": [], "task": "NER"}
{"text": "A panel of reporter gene assays ( RGAs ) coupled with a single solid phase extraction ( SPE ) step was developed and used to screen bottled mineral water for the presence of four classes of endocrine disruptors ( EDs ) , oestrogens , androgens , progestagens and glucocorticoids .", "entity": [{"entity": "oestrogens", "entity_type": "Chemical", "pos": [221, 231]}, {"entity": "androgens", "entity_type": "Chemical", "pos": [234, 243]}, {"entity": "progestagens", "entity_type": "Chemical", "pos": [246, 258]}], "task": "NER"}
{"text": "Fourteen brands of bottled mineral water in triplicate ( 42 samples ) were analysed .", "entity": [], "task": "NER"}
{"text": "Overall , hormonal activity was found in 78 % of the samples .", "entity": [], "task": "NER"}
{"text": "Oestrogenic , androgenic , progestagenic and glucocorticoid activity was found in 38 % , 38 % , 36 % and 55 % of the samples , respectively at an average concentration of 10 ng / l 17 beta - estradiol equivalent ( EEQ ) , 26 ng / l testosterone equivalent ( TEQ ) , 123 ng / l progesterone equivalent ( PEQ ) and 13 . 5 ng / l hydrocortisone equivalent ( HEQ ) .", "entity": [{"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [181, 200]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [232, 244]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [277, 289]}, {"entity": "hydrocortisone", "entity_type": "Chemical", "pos": [327, 341]}], "task": "NER"}
{"text": "The level of oestrogenic , androgenic and progestagenic activity observed is not considered a matter of concern for the consumers ' health .", "entity": [], "task": "NER"}
{"text": "It is unknown whether the glucocorticoid levels observed are safe .", "entity": [], "task": "NER"}
{"text": "The ED source , long term exposure and mixture effects remain to be investigated .", "entity": [], "task": "NER"}
{"text": "Comparison of consumer perception and acceptability for steaks cooked to different endpoints : validation of photographic approach .", "entity": [], "task": "NER"}
{"text": "Photographs have been used to enhance consumer reporting of preference of meat doneness , however , the use of photographs has not been validated for this purpose .", "entity": [], "task": "NER"}
{"text": "This study used standard cooking methods to produce steaks of five different degrees of doneness ( rare medium , medium well , well done and very well done ) to study the consumer ' s perception of doneness , from both the external and internal surface of the cooked steak and also from corresponding photographs of each sample .", "entity": [], "task": "NER"}
{"text": "Consumers evaluated each surface of the cooked steaks in relation to doneness for acceptability , ' just about right ' and perception of doneness .", "entity": [], "task": "NER"}
{"text": "Data were analysed using a split plot ANOVA and least significant test .", "entity": [], "task": "NER"}
{"text": "Perception scores ( for both external and internal surfaces ) between different presentation methods ( steak samples and corresponding photos ) , were not significantly different ( p > 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "The result indicates that photographs can be used as a valid approach for assessing preference for meat doneness .", "entity": [], "task": "NER"}
{"text": "Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation , oxidative stress and inflammation : plausible role of NF - kappa B .", "entity": [{"entity": "Chrysin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Flavonoid family is a rich source of polyphenolic compounds and hence possess strong antioxidant and anti inflammatory properties .", "entity": [{"entity": "Flavonoid", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "polyphenolic", "entity_type": "Chemical", "pos": [37, 49]}], "task": "NER"}
{"text": "The aim of this study was to determine the efficacy of chrysin ; a bio - active flavonoid as an anticancer agent .", "entity": [{"entity": "chrysin", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [80, 89]}], "task": "NER"}
{"text": "Renal cancer was initiated by single intraperitoneal ( i . p . ) injection of N - nitrosodiethylamine ( DEN 200 mg / kg BW body weight ) and promoted by twice weekly administration of ferric nitrilotriacetate ( Fe - NTA ) 9 mg Fe / kg BW for 16 wk .", "entity": [{"entity": "N - nitrosodiethylamine", "entity_type": "Chemical", "pos": [78, 101]}, {"entity": "DEN", "entity_type": "Chemical", "pos": [104, 107]}, {"entity": "ferric nitrilotriacetate", "entity_type": "Chemical", "pos": [184, 208]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [211, 219]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [227, 229]}], "task": "NER"}
{"text": "In the present study , we report the chemopreventive effects of chrysin against ( Fe - NTA ) induced renal oxidative stress , inflammation , hyperproliferative response , and two - stage renal carcinogenesis .", "entity": [{"entity": "chrysin", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "To ascertain the molecular mechanism implicated in the antitumor promoting activity of chrysin , its effect was investigated on markers of tumor promotion and inflammation : ornithine decarboxylase ( ODC ) activity , proliferating cell nuclear antigen ( PCNA ) , inducible nitric oxide synthase ( iNOS ) and cyclo - oxygenase - 2 ( COX - 2 ) expression , and on levels of proinflammatory cytokines interleukin - 6 ( IL - 6 ) , tumor necrosis factor - alpha ( TNF - alpha ) , and prostaglandin E ( 2 ) ( PGE ( 2 ) ) .", "entity": [{"entity": "chrysin", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "ornithine", "entity_type": "Chemical", "pos": [174, 183]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [273, 285]}, {"entity": "prostaglandin E ( 2 )", "entity_type": "Chemical", "pos": [479, 500]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [503, 512]}], "task": "NER"}
{"text": "Pretreatment of animals with chrysin at both doses ( 20 and 40 mg / kg body weight ) markedly inhibited all .", "entity": [{"entity": "chrysin", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "Further , Fe - NTA enhances renal lipid peroxidation , with concomitant reduction in reduced glutathione content ( GSH ) , antioxidant enzymes , and phase II metabolizing enzymes .", "entity": [{"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [93, 104]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "It induces serum toxicity markers , viz . , blood urea nitrogen ( BUN ) , creatinine and lactate dehydrogenase ( LDH ) .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "Prophylactic treatment of animals with chrysin before the administration of Fe - NTA was effective in modulating oxidative and renal injury markers and resulted in the diminution of Fe - NTA mediated injury .", "entity": [{"entity": "chrysin", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [182, 190]}], "task": "NER"}
{"text": "These results suggest chrysin as an effective chemopreventive agent having the capability to obstruct DEN initiated and Fe - NTA promoted renal cancer in the rat model .", "entity": [{"entity": "chrysin", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "DEN", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [120, 128]}], "task": "NER"}
{"text": "Effect of blood - retinal barrier development on formation of selenite nuclear cataract in rat .", "entity": [{"entity": "selenite", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "Selenite cataract , as an experimental animal model of nuclear cataract to mimic human senile cataract , is produced only when overdose selenite is injected to neonatal rats before eyelid opening .", "entity": [{"entity": "Selenite", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "selenite", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "To clarify the cause of age differences on selenite cataract formation in rats , mRNA expression of GPx1 , MsrA and MsrB1 , as well as GPx activity in Wistar rat lens at different ages were assayed , level of lipid peroxidation , extent of lens damage induced by sodium selenite and barricade function of blood - retinal barrier ( BRB ) were investigated .", "entity": [{"entity": "selenite", "entity_type": "Chemical", "pos": [43, 51]}, {"entity": "sodium selenite", "entity_type": "Chemical", "pos": [263, 278]}], "task": "NER"}
{"text": "The results showed that mRNA expressions and activity of antioxidant enzymes in neonatal rat lens before eyelid opening were the highest and then decreased with age , and revealed by transmission electron microscopy ( TEM ) using lanthanum hydroxide as tracer that higher selenite content entering eyes injured lens and resulted in cataract formation for immature BRB before eyelid opening , moreover , a little selenite content entering eyes was not enough to induce cataract formation after eyelid opening because of mature BRB .", "entity": [{"entity": "lanthanum hydroxide", "entity_type": "Chemical", "pos": [230, 249]}, {"entity": "selenite", "entity_type": "Chemical", "pos": [272, 280]}, {"entity": "selenite", "entity_type": "Chemical", "pos": [412, 420]}], "task": "NER"}
{"text": "The cucurbitacins E , D and I : investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver .", "entity": [{"entity": "cucurbitacins E , D and I", "entity_type": "Chemical", "pos": [4, 29]}], "task": "NER"}
{"text": "Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects .", "entity": [{"entity": "Cucurbitacins", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "The purpose of this work was to compare the cytotoxicity of three cucurbitacins I , D , E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man .", "entity": [{"entity": "cucurbitacins I , D , E", "entity_type": "Chemical", "pos": [66, 89]}], "task": "NER"}
{"text": "Cucurbitacins I and D showed a very strong cytotoxicity , which was higher than that of cytochalasin D , used as a drug reference .", "entity": [{"entity": "Cucurbitacins I and D", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "cytochalasin D", "entity_type": "Chemical", "pos": [88, 102]}], "task": "NER"}
{"text": "Almost 100 % of the cells were apoptotic as observed by DNA fragmentation ( TUNEL assay ) after 12 h with cucurbitacins I and D ( 1 mu M ) and cucurbitacin E ( 10 mu M ) .", "entity": [{"entity": "cucurbitacins I and D", "entity_type": "Chemical", "pos": [106, 127]}, {"entity": "cucurbitacin E", "entity_type": "Chemical", "pos": [143, 157]}], "task": "NER"}
{"text": "In terms of IC ( 50 ) values , cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D ( MTT assay ) .", "entity": [{"entity": "cucurbitacins I and E", "entity_type": "Chemical", "pos": [31, 52]}, {"entity": "cucurbitacin D", "entity_type": "Chemical", "pos": [101, 115]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "Cucurbitacin E was readily hydrolyzed by human hepatic microsomes , leading to cucurbitacin I ( K ( m ) 22 mu M , V ( max ) 571 nmol / mg proteins / min ) .", "entity": [{"entity": "Cucurbitacin E", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "cucurbitacin I", "entity_type": "Chemical", "pos": [79, 93]}], "task": "NER"}
{"text": "On the other hand , the three cucurbitacins were hydroxylated at a very low extent , but they were sulfated and glucuronidated .", "entity": [{"entity": "cucurbitacins", "entity_type": "Chemical", "pos": [30, 43]}], "task": "NER"}
{"text": "In terms of V ( max ) / K ( m ) , the cucurbitacin E was the best substrate of UDP - glucuronosyltransferases .", "entity": [{"entity": "cucurbitacin E", "entity_type": "Chemical", "pos": [38, 52]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "This study shows that cucurbitacins I , D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates .", "entity": [{"entity": "cucurbitacins I , D and E", "entity_type": "Chemical", "pos": [22, 47]}, {"entity": "sulfate", "entity_type": "Chemical", "pos": [151, 158]}, {"entity": "glucuronide", "entity_type": "Chemical", "pos": [163, 174]}], "task": "NER"}
{"text": "alpha C helix displacement as a general approach for allosteric modulation of protein kinases .", "entity": [], "task": "NER"}
{"text": "Owing to their crucial role in the modulation of cell pathways , protein kinases are important targets for several human diseases , including but not limited to cancer .", "entity": [], "task": "NER"}
{"text": "The classic approach of targeting the ATP active site has recently come up against selectivity issues , which can be considerably reduced by following an allosteric modulation approach .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Being closely related to protein kinase inactivation , allosteric targeting via displacement of the conserved structural alpha C helix enables a direct and specific modulation mechanism .", "entity": [], "task": "NER"}
{"text": "A structure - based survey of the allosteric regulation of alpha C helix conformation in various kinase families is provided , highlighting key allosteric pockets and modulation mechanisms that appear to be more broadly conserved than was previously thought .", "entity": [], "task": "NER"}
{"text": "Increased protein kinase A type I alpha regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism .", "entity": [], "task": "NER"}
{"text": "Protein kinase A ( PKA ) regulatory subunit type I alpha ( RI alpha ) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity .", "entity": [], "task": "NER"}
{"text": "We have previously demonstrated that elevated RI alpha expression is associated with diffuse - to - nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism .", "entity": [], "task": "NER"}
{"text": "The aim of the current study was to determine whether or not RI alpha expression is increased in adenomas of primary hyperparathyroidism ( PHPT ) , because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia .", "entity": [], "task": "NER"}
{"text": "Surgical specimens comprising 22 adenomas and 11 normal glands , obtained from 22 patients with PHPT , were analyzed .", "entity": [], "task": "NER"}
{"text": "Western blot and immunohistochemical analyses were employed to evaluate RI alpha expression .", "entity": [], "task": "NER"}
{"text": "PKA activities were determined in several adenomas highly expressing RI alpha .", "entity": [], "task": "NER"}
{"text": "RI alpha expression was also separately evaluated in chief and oxyphilic cells using the \" Allred score \" system .", "entity": [], "task": "NER"}
{"text": "Expression of proliferating cell nuclear antigen ( PCNA ) , a proliferation marker , was also immunohistochemically examined .", "entity": [], "task": "NER"}
{"text": "Western blot analysis revealed that 5 out of 8 adenomas highly expressed RI alpha , compared with normal glands .", "entity": [], "task": "NER"}
{"text": "PKA activity in adenomas was significantly less than in normal glands .", "entity": [], "task": "NER"}
{"text": "Immunohistochemical analysis further demonstrated high expression of RI alpha in 20 out of 22 adenomas .", "entity": [], "task": "NER"}
{"text": "In adenomas , the greater RI alpha expression and more PCNA positive cells were observed in both chief and oxyphilic cells .", "entity": [], "task": "NER"}
{"text": "The present study suggested that high RI alpha expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP / PKA signaling pathway .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [141, 145]}], "task": "NER"}
{"text": "Selenium ( Se ) seed priming induced growth and biochemical changes in wheat under water deficit conditions .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Se", "entity_type": "Chemical", "pos": [11, 13]}], "task": "NER"}
{"text": "Insufficient stand establishment at early growth stages in wheat ( Triticum aestivum L . ) due to drought stress is a major problem that limits overall efficiency and yield of crop .", "entity": [], "task": "NER"}
{"text": "Priming of seed is an effective method for raising seed performance and improving tolerance of crops to abiotic stresses especially drought .", "entity": [], "task": "NER"}
{"text": "The seeds of two local wheat cultivars ( Kohistan - 97 and Pasban - 90 ) were soaked in distilled water or sodium selenate solutions of 25 , 50 , 75 , and 100 mu M for 1 / 2 or 1 h at 25 degrees C and later re - dried to their original moisture levels before sowing .", "entity": [{"entity": "sodium selenate", "entity_type": "Chemical", "pos": [107, 122]}], "task": "NER"}
{"text": "One - hour priming significantly increased root length stress tolerance index , dry matter stress tolerance index , and total biomass of seedlings ; however , no significant effect of changing duration of Se seed priming was observed on plant height stress tolerance index and shoot / root ratio .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [205, 207]}], "task": "NER"}
{"text": "Among cultivars , Kohistan - 97 was found to be more responsive to Se seed treatment as 1 h priming at 100 mu M significantly increased its total biomass by 43 % as compared to control treatment .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [67, 69]}], "task": "NER"}
{"text": "Although biomass of seedlings was not affected with Se seed priming under normal conditions , but it increased significantly with increase in rates of Se under drought stress conditions .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "Se", "entity_type": "Chemical", "pos": [151, 153]}], "task": "NER"}
{"text": "One - hour priming at 75 mu M increased the total sugar content and total free amino acids in both wheat cultivars .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [50, 55]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [79, 90]}], "task": "NER"}
{"text": "A more significant decrease in soluble proteins of seedlings was observed by 1 h priming than 1 / 2 h priming under drought stress conditions .", "entity": [], "task": "NER"}
{"text": "Bisphenol A inhibits voltage - activated Ca ( 2 + ) channels in vitro : mechanisms and structural requirements .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) , a high volume production chemical compound attracts growing attention as a health - relevant xenobiotic in humans .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "It can directly bind to hormone receptors , enzymes , and ion channels to become biologically active .", "entity": [], "task": "NER"}
{"text": "In this study we show that BPA acts as a potent blocker of voltage - activated Ca ( 2 + ) channels .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [79, 89]}], "task": "NER"}
{"text": "We determined the mechanisms of block and the structural elements of BPA essential for its action .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "Macroscopic Ba ( 2 + ) / Ca ( 2 + ) currents through native L - , N - , P / Q - , T - type Ca ( 2 + ) channels in rat endocrine GH ( 3 ) cells , mouse dorsal root ganglion neurons or cardiac myocytes , and recombinant human R - type Ca ( 2 + ) channels expressed in human embryonic kidney ( HEK ) 293 cells were rapidly and reversibly inhibited by BPA with similar potency ( EC ( 50 ) values : 26 - 35 mu M ) .", "entity": [{"entity": "Ba ( 2 + )", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [25, 35]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [91, 101]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [233, 243]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [348, 351]}], "task": "NER"}
{"text": "Pharmacological and biophysical analysis of R - type Ca ( 2 + ) channels revealed that BPA interacts with the extracellular part of the channel protein .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "Its action does not require intracellular signaling pathways , is neither voltage - nor use - dependent , and does not affect channel gating .", "entity": [], "task": "NER"}
{"text": "This indicates that BPA interacts with the channel in its resting state by directly binding to an external site outside the pore - forming region .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [20, 23]}], "task": "NER"}
{"text": "Structure - effect analyses of various phenolic and bisphenolic compounds revealed that 1 ) a double - alkylated ( R - C ( CH ( 3 ) ) ( 2 ) - R , R - C ( CH ( 3 ) ) ( CH ( 2 ) CH ( 3 ) ) - R ) , or double - trifluoromethylated sp ( 3 ) - hybridized carbon atom between the two aromatic rings and 2 ) the two aromatic moieties in angulated orientation are optimal for BPA ' s effectiveness .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [39, 47]}, {"entity": "bisphenolic", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "R - C ( CH ( 3 ) ) ( 2 ) - R", "entity_type": "Chemical", "pos": [115, 143]}, {"entity": "R - C ( CH ( 3 ) ) ( CH ( 2 ) CH ( 3 ) ) - R", "entity_type": "Chemical", "pos": [146, 190]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [249, 255]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [367, 370]}], "task": "NER"}
{"text": "Since BPA highly pollutes the environment and is incorporated into the human organism , our data may provide a basis for future studies relevant for human health and development .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [6, 9]}], "task": "NER"}
{"text": "Electronic size effects in three - dimensional nanostructures .", "entity": [], "task": "NER"}
{"text": "We show that bismuth nanostructures form three - dimensional patterns governed by two - dimensional electronic effects .", "entity": [{"entity": "bismuth", "entity_type": "Chemical", "pos": [13, 20]}], "task": "NER"}
{"text": "Scanning tunneling microscopy reveals that both the vertical and the lateral dimensions of the structures strongly favor certain values and that the preferred widths are substantially different for each preferred height .", "entity": [], "task": "NER"}
{"text": "First - principles calculations demonstrate that this vertical - lateral correlation is governed by the Fermi surface topology and that this is itself sensitively dependent on the dimensions of the structure .", "entity": [], "task": "NER"}
{"text": "Physicochemical analysis from real - time imaging of liposome tubulation reveals the characteristics of individual F - BAR domain proteins .", "entity": [], "task": "NER"}
{"text": "The Fer - CIP4 homology - BAR ( F - BAR ) domain , which was identified as a biological membrane - deforming module , has been reported to transform lipid bilayer membranes into tubules .", "entity": [], "task": "NER"}
{"text": "However , details of the tubulation process , the mechanism , and the properties of the generated tubules remain unknown .", "entity": [], "task": "NER"}
{"text": "Here , we successfully monitored the entire process of tubulation and the behavior of elongated tubules caused by four different F - BAR domain family proteins ( FBP17 , CIP4 , PSTPIP1 , and Pacsin2 ) using direct real - time imaging of giant unilamellar liposomes with dark - field optical microscopy .", "entity": [], "task": "NER"}
{"text": "FBP17 and CIP4 develop many protrusions simultaneously over the entire surface of individual liposomes , whereas PSTPIP1 and Pacsin2 develop only a few protrusions from a narrow restricted part of the surface of individual liposomes .", "entity": [], "task": "NER"}
{"text": "Tubules formed by FBP17 or CIP4 have higher bending rigidities than those formed by PSTPIP1 or Pacsin2 .", "entity": [], "task": "NER"}
{"text": "The results provide striking evidence that these four F - BAR domain family proteins should be classified into two groups : one group of FBP17 and CIP4 and another group of PSTPIP1 and Pacsin2 .", "entity": [], "task": "NER"}
{"text": "This classification is consistent with the phylogenetic proximity among these proteins and suggests that the nature of the respective tubulation is associated with biological function .", "entity": [], "task": "NER"}
{"text": "These findings aid in the quantitative assessment with respect to manipulating the morphology of lipid bilayers using membrane - deforming proteins .", "entity": [], "task": "NER"}
{"text": "Polymethoxyflavones as agents that prevent formation of cataract : nobiletin congeners show potent growth inhibitory effects in human lens epithelial cells .", "entity": [{"entity": "Polymethoxyflavones", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "nobiletin", "entity_type": "Chemical", "pos": [67, 76]}], "task": "NER"}
{"text": "Posterior capsular opacification ( PCO ) is the most frequent complication and the primary reason for visual decrease after extracapsular cataract surgery .", "entity": [], "task": "NER"}
{"text": "The proliferation and migration of leftover lens epithelial cells ( LECs ) after surgery may contribute to the development of PCO .", "entity": [], "task": "NER"}
{"text": "To prevent PCO , a rational approach would be to inhibit both the proliferation and the migration of LECs using nontoxic xenobiotics .", "entity": [], "task": "NER"}
{"text": "Nobiletin , one of the most abundant polymethoxyflavones ( PMFs ) in citrus peel , and its synthetic congeners displayed a potent inhibition of LEC proliferation .", "entity": [{"entity": "Nobiletin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "polymethoxyflavones", "entity_type": "Chemical", "pos": [37, 56]}, {"entity": "PMFs", "entity_type": "Chemical", "pos": [59, 63]}], "task": "NER"}
{"text": "Structural features which enhance anti - proliferative activity have also been discussed .", "entity": [], "task": "NER"}
{"text": "Structural studies on matrices of deacylated gellan with polydextrose .", "entity": [], "task": "NER"}
{"text": "The effect of varying concentrations of co - solute ( polydextrose ) on thermomechanical and physicochemical properties of deacylated gellan matrices is presented .", "entity": [], "task": "NER"}
{"text": "Modulated differential scanning calorimetry , micro differential scanning calorimetry , small deformation dynamic oscillation in shear , Fourier transform infrared spectroscopy , wide angle X - ray diffraction and environmental scanning electron microscopy have been used to investigate the structural transformations in aqueous , low - solid and condensed systems .", "entity": [], "task": "NER"}
{"text": "There was a rise in values of storage modulus as the level of co - solute was increased , followed by a significant decline at intermediate concentrations , with high modulus values being regained as more of the co - solute was incorporated .", "entity": [], "task": "NER"}
{"text": "These results confirm the hypothesis of a structural transformation from a highly enthalpic aggregated assembly in the aqueous / low - solid environment to a lightly cross linked polysaccharide network in the high solids regime .", "entity": [], "task": "NER"}
{"text": "Time - temperature superposition ( TTS ) phenomena observed for amorphous synthetic polymers have been utilised to generate master curves of viscoelasticity , which afforded rationalisation of results on the basis of the free volume theory .", "entity": [], "task": "NER"}
{"text": "Determination of lead in milk and yoghurt samples by solid phase extraction using a novel aminothioazole - polymeric resin .", "entity": [{"entity": "aminothioazole", "entity_type": "Chemical", "pos": [90, 104]}], "task": "NER"}
{"text": "A preconcentration method was developed by using a new aminothioazole - containing sulfonamide resin in solid phase extraction for the determination of lead and nickel in milk and yoghurt samples .", "entity": [{"entity": "aminothioazole", "entity_type": "Chemical", "pos": [55, 69]}, {"entity": "sulfonamide", "entity_type": "Chemical", "pos": [83, 94]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [161, 167]}], "task": "NER"}
{"text": "The optimisation of experimental conditions was performed .", "entity": [], "task": "NER"}
{"text": "The optimum parameters for Pb and Ni were found to be 3 . 5 , 30 min and 2 . 5 mL for pH , contact time , eluate volume , respectively .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [27, 29]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [34, 36]}], "task": "NER"}
{"text": "After preconcentration step , atomic absorption spectrometry was used for the determinations .", "entity": [], "task": "NER"}
{"text": "The enhancement of 350 - and 50 - fold in the sensitivity of Pb and Ni were achieved by combination of the slotted tube atom trap - atomic absorption spectrometry with the optimised preconcentration method , respectively .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [61, 63]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [68, 70]}], "task": "NER"}
{"text": "Limits of detection were found to be 0 . 15 ng mL - (1) for Pb and 0 . 75 ng mL - (1) for Ni .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [60, 62]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [90, 92]}], "task": "NER"}
{"text": "The lead concentrations in the studied samples were found to be in the range of 15 - 61 ng Pb mL - (1) for milk and 21 - 42 ng Pb g - (1) for yoghurt samples .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [91, 93]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [127, 129]}], "task": "NER"}
{"text": "Sitosterol as an antioxidant in frying oils .", "entity": [{"entity": "Sitosterol", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The antioxidative effect of sitosterol at 1 , 2 and 5 % levels , in triolein , refined canola , high oleic sunflower and flaxseed oils , continuously heated for a period of up to 72 h at frying temperature of 180 degrees C , was studied .", "entity": [{"entity": "sitosterol", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "triolein", "entity_type": "Chemical", "pos": [68, 76]}], "task": "NER"}
{"text": "High Pressure Size Exclusion Chromatography ( HPSEC ) was used to monitor changes in peak areas of triacylglycerol ( TG ) polymer , monomer and ester hydrolysis products .", "entity": [{"entity": "triacylglycerol", "entity_type": "Chemical", "pos": [99, 114]}, {"entity": "ester", "entity_type": "Chemical", "pos": [144, 149]}], "task": "NER"}
{"text": "The presence of enhanced levels of sitosterol was found to significantly decrease TG polymer formation in triolein and the vegetable oil samples after heating at 180 degrees C for a period of 72 h .", "entity": [{"entity": "sitosterol", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "triolein", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "A corresponding increase in the level of intact TG monomer and the extent of TG ester hydrolysis was observed in all samples with enhanced levels of sitosterol .", "entity": [{"entity": "TG ester", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "sitosterol", "entity_type": "Chemical", "pos": [149, 159]}], "task": "NER"}
{"text": "Conversion of sterol to steradiene , by the 1 , 2 elimination of water , may be responsible for the antioxidative effect of sitosterol at frying temperatures .", "entity": [{"entity": "sterol", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "steradiene", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "sitosterol", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "Identification of high beta - glucan oat lines and localization and chemical characterization of their seed kernel beta - glucans .", "entity": [], "task": "NER"}
{"text": "Oat , ( Avena sativa ) is an excellent source of mixed linkage beta - glucans ( ( 1 --> 3 ) ( 1 --> 4 ) - beta - D - glucan ) , a dietary fibre with cholesterol lowering properties .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [149, 160]}], "task": "NER"}
{"text": "Using a mutagenized oat - population we screened 1700 different lines and identified ten lines that displayed beta - glucan levels above 6 . 7 % and 10 below 3 . 6 % . The extreme values were 1 . 8 % and 7 . 5 % .", "entity": [], "task": "NER"}
{"text": "We chose six lines with an increased - and four lines with a reduced beta - glucan content for further study .", "entity": [], "task": "NER"}
{"text": "By longitudinal - and cross - sections of seeds it was shown that localization of beta - glucan varied between the different lines .", "entity": [], "task": "NER"}
{"text": "In addition , beta - glucan quality parameters like molecular weight and solubility were also determined .", "entity": [], "task": "NER"}
{"text": "Although the selection was designed for quantitative differences , qualitative differences between the beta - glucans from the different lines were found .", "entity": [], "task": "NER"}
{"text": "The high and low beta - glucan lines will now be used as a model system to study molecular regulation of beta - glucan biosynthesis as well as possible links between fibre quality and biological activity .", "entity": [], "task": "NER"}
{"text": "Geographical provenance of palm oil by fatty acid and volatile compound fingerprinting techniques .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "Analytical methods are required in addition to administrative controls to verify the geographical origin of vegetable oils such as palm oil in an objective manner .", "entity": [], "task": "NER"}
{"text": "In this study the application of fatty acid and volatile organic compound fingerprinting in combination with chemometrics have been applied to verify the geographical origin of crude palm oil ( continental scale ) .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "For this purpose 94 crude palm oil samples were collected from South East Asia ( 55 ) , South America ( 11 ) and Africa ( 28 ) .", "entity": [], "task": "NER"}
{"text": "Partial least squares discriminant analysis ( PLS - DA ) was used to develop a hierarchical classification model by combining two consecutive binary PLS - DA models .", "entity": [], "task": "NER"}
{"text": "First , a PLS - DA model was built to distinguish South East Asian from non - South East Asian palm oil samples .", "entity": [], "task": "NER"}
{"text": "Then a second model was developed , only for the non - Asian samples , to discriminate African from South American crude palm oil .", "entity": [], "task": "NER"}
{"text": "Models were externally validated by using them to predict the identity of new authentic samples .", "entity": [], "task": "NER"}
{"text": "The fatty acid fingerprinting model revealed three misclassified samples .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [4, 14]}], "task": "NER"}
{"text": "The volatile compound fingerprinting models showed an 88 % , 100 % and 100 % accuracy for the South East Asian , African and American class , respectively .", "entity": [], "task": "NER"}
{"text": "The verification of the geographical origin of crude palm oil is feasible by fatty acid and volatile compound fingerprinting .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [77, 87]}], "task": "NER"}
{"text": "Further research is required to further validate the approach and to increase its spatial specificity to country / province scale .", "entity": [], "task": "NER"}
{"text": "Fluorescent ligands for adenosine receptors .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [24, 33]}], "task": "NER"}
{"text": "Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors ( ARs ) , which hold a promise of usefulness in the drug discovery process .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore .", "entity": [], "task": "NER"}
{"text": "The choice of dye moiety ( e . g . Alexa Fluor 488 ) , attachment point and linker length can alter the selectivity and potency of the parent molecule .", "entity": [{"entity": "Alexa Fluor 488", "entity_type": "Chemical", "pos": [35, 50]}], "task": "NER"}
{"text": "Fluorescent derivatives of adenosine agonists and antagonists ( e . g . XAC and other heterocyclic antagonist scaffolds ) have been synthesized and characterized pharmacologically .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "XAC", "entity_type": "Chemical", "pos": [72, 75]}], "task": "NER"}
{"text": "Some are useful AR probes for flow cytometry , fluorescence correlation spectroscopy , fluorescence microscopy , fluorescence polarization , fluorescence resonance energy transfer , and scanning confocal microscopy .", "entity": [], "task": "NER"}
{"text": "Thus , the approach of fluorescent labeled GPCR ligands , including those for ARs , is a growing dynamic research field .", "entity": [], "task": "NER"}
{"text": "Investigating the binding interactions of galantamine with beta - amyloid peptide .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [42, 53]}], "task": "NER"}
{"text": "The anti - Alzheimer ' s agent galantamine is known to possess anti - amyloid properties .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [31, 42]}], "task": "NER"}
{"text": "However the exact mechanisms are not clear .", "entity": [], "task": "NER"}
{"text": "We studied the binding interactions of galantamine with amyloid peptide dimer ( A beta ( 1 - 40 ) ) through molecular docking and molecular dynamics simulations .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [39, 50]}], "task": "NER"}
{"text": "Galantamine ' s binding site within the amyloid peptide dimer was identified by docking experiments and the most stable complex was analyzed by molecular dynamics simulation .", "entity": [{"entity": "Galantamine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "These studies show that galantamine was interacting with the central region of the amyloid dimer ( Lys16 - Ala21 ) and the C - terminal region ( Ile31 - Val36 ) with minimum structural drift of C alpha atom in those regions .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "Lys16", "entity_type": "Chemical", "pos": [99, 104]}, {"entity": "Ala21", "entity_type": "Chemical", "pos": [107, 112]}, {"entity": "C", "entity_type": "Chemical", "pos": [123, 124]}, {"entity": "Ile31", "entity_type": "Chemical", "pos": [145, 150]}, {"entity": "Val36", "entity_type": "Chemical", "pos": [153, 158]}], "task": "NER"}
{"text": "Strikingly , a significant drift was observed at the turn region from Asp23 - Gly29 ( C alpha atom RMSD = 9 . 2 A and 11 . 6 A at 50 fs and 100 fs respectively ) .", "entity": [{"entity": "Asp23", "entity_type": "Chemical", "pos": [70, 75]}, {"entity": "Gly29", "entity_type": "Chemical", "pos": [78, 83]}], "task": "NER"}
{"text": "Furthermore , galantamine ' s binding mode disrupts the key pi - pi stacking interaction between aromatic rings of Phe19 ( chain A ) and Phe19 ( chain B ) and intermolecular hydrogen bonds seen in unbound peptide dimer .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "Phe19", "entity_type": "Chemical", "pos": [115, 120]}, {"entity": "Phe19", "entity_type": "Chemical", "pos": [137, 142]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [174, 182]}], "task": "NER"}
{"text": "Noticeably , the azepine tertiary nitrogen of galantamine was in close proximity to backbone CO of Leu34 ( distance < 3 . 5 A ) to stabilize the dimer conformation .", "entity": [{"entity": "azepine", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [34, 42]}, {"entity": "galantamine", "entity_type": "Chemical", "pos": [46, 57]}, {"entity": "CO", "entity_type": "Chemical", "pos": [93, 95]}, {"entity": "Leu34", "entity_type": "Chemical", "pos": [99, 104]}], "task": "NER"}
{"text": "In summary , the results indicate that galantamine binding to amyloid peptide dimer leads to a significant conformational change at the turn region ( Asp23 - Gly29 ) that disrupts interactions between individual beta - strands and promotes a nontoxic conformation of A beta ( 1 - 40 ) to prevent the formation of neurotoxic oligomers .", "entity": [{"entity": "galantamine", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "Asp23", "entity_type": "Chemical", "pos": [150, 155]}, {"entity": "Gly29", "entity_type": "Chemical", "pos": [158, 163]}], "task": "NER"}
{"text": "Detection of designer steroid methylstenbolone in \" nutritional supplement \" using gas chromatography and tandem mass spectrometry : elucidation of its urinary metabolites .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "methylstenbolone", "entity_type": "Chemical", "pos": [30, 46]}], "task": "NER"}
{"text": "The use of \" nutritional supplements \" containing unapproved substances has become a regular practice in amateur and professional athletes .", "entity": [], "task": "NER"}
{"text": "This represents a dangerous habit for their health once no data about toxicological or pharmacological effects of these supplements are available .", "entity": [], "task": "NER"}
{"text": "Most of them are freely commercialized online and any person can buy them without medical surveillance .", "entity": [], "task": "NER"}
{"text": "Usually , the steroids intentionally added to the \" nutritional supplements \" are testosterone analogues with some structural modifications .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [82, 94]}], "task": "NER"}
{"text": "In this study , the analyzed product was bought online and a new anabolic steroid known as methylstenbolone ( 2 , 17 alpha - dimethyl - 17 beta - hydroxy - 5 alpha - androst - 1 - en - 3 - one ) was detected , as described on label .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [74, 81]}, {"entity": "methylstenbolone", "entity_type": "Chemical", "pos": [91, 107]}, {"entity": "2 , 17 alpha - dimethyl - 17 beta - hydroxy - 5 alpha - androst - 1 - en - 3 - one", "entity_type": "Chemical", "pos": [110, 192]}], "task": "NER"}
{"text": "Generally , anabolic steroids are extensively metabolized , thus in - depth knowledge of their metabolism is mandatory for doping control purposes .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [21, 29]}], "task": "NER"}
{"text": "For this reason , a human excretion study was carried out with four volunteers after a single oral dose to determine the urinary metabolites of the steroid .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "Urine samples were submitted to enzymatic hydrolysis of glucuconjugated metabolites followed by liquid - liquid extraction and analysis of the trimethylsilyl derivatives by gas chromatography coupled to tandem mass spectrometry .", "entity": [{"entity": "trimethylsilyl", "entity_type": "Chemical", "pos": [143, 157]}], "task": "NER"}
{"text": "Mass spectrometric data allowed the proposal of two plausible metabolites : 2 , 17 alpha - dimethyl - 16 xi , 17 beta - dihydroxy - 5 alpha - androst - 1 - en - 3 - one ( S1 ) , 2 , 17 alpha - dimethyl - 3 alpha , 16 xi , 17 beta - trihydroxy - 5 alpha - androst - 1 - ene ( S2 ) .", "entity": [{"entity": "2 , 17 alpha - dimethyl - 16 xi , 17 beta - dihydroxy - 5 alpha - androst - 1 - en - 3 - one", "entity_type": "Chemical", "pos": [76, 168]}, {"entity": "2 , 17 alpha - dimethyl - 3 alpha , 16 xi , 17 beta - trihydroxy - 5 alpha - androst - 1 - ene", "entity_type": "Chemical", "pos": [178, 272]}], "task": "NER"}
{"text": "Their electron impact mass spectra are compatible with 16 - hydroxylated steroids O - TMS derivatives presenting diagnostic ions such as m / z 231 and m / z 218 .", "entity": [{"entity": "16 - hydroxylated steroids O - TMS", "entity_type": "Chemical", "pos": [55, 89]}], "task": "NER"}
{"text": "These metabolites were detectable after one week post administration while unchanged methylstenbolone was only detectable in a brief period of 45 h .", "entity": [{"entity": "methylstenbolone", "entity_type": "Chemical", "pos": [85, 101]}], "task": "NER"}
{"text": "Tigecycline prevents LPS - induced release of pro - inflammatory and apoptotic mediators in neuronal cells .", "entity": [{"entity": "Tigecycline", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Pro - inflammatory and pro - apoptotic mediators have been involved in the pathogenesis of neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "Tigecycline ( Tig ) , a glycylcycline antibiotic and an analog of Minocycline , is shown to exert anti - inflammatory effects that are distinct from its anti - microbial activity .", "entity": [{"entity": "Tigecycline", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "Tig", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "glycylcycline", "entity_type": "Chemical", "pos": [24, 37]}, {"entity": "Minocycline", "entity_type": "Chemical", "pos": [66, 77]}], "task": "NER"}
{"text": "Its neuroprotective mechanism is unknown .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated the direct protective mechanisms of tigecycline against lipopolysaccharide ( LPS ) - induced Rat pheochromocytoma ( PC12 ) cells .", "entity": [{"entity": "tigecycline", "entity_type": "Chemical", "pos": [68, 79]}], "task": "NER"}
{"text": "The results showed that tigecycline significantly attenuated the expression and the release of nuclear factor - kappa beta ( NF - kappa B ) , tumor necrosis factor - alpha ( TNF - alpha ) and interleukin - 1beta ( IL - 1 beta ) , as well as nitric oxide ( NO ) levels in LPS - induced PC12 cells .", "entity": [{"entity": "tigecycline", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [241, 253]}, {"entity": "NO", "entity_type": "Chemical", "pos": [256, 258]}], "task": "NER"}
{"text": "In addition , tigecycline dose - dependently decreased cytochrome c release and caspase - 3 activity .", "entity": [{"entity": "tigecycline", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "This later finding corroborated the results of decreased pro - apoptotic Bad , and increased anti - apoptotic Bcl - 2 protein expression thus , confirming a neuroprotective effect of the drug in differentiated PC12 cells induced with LPS .", "entity": [], "task": "NER"}
{"text": "The findings of our study suggest new targets for tigecycline and support the potential for tigecycline to be investigated as a therapeutic agent for neurodegenerative disorders .", "entity": [{"entity": "tigecycline", "entity_type": "Chemical", "pos": [50, 61]}, {"entity": "tigecycline", "entity_type": "Chemical", "pos": [92, 103]}], "task": "NER"}
{"text": "Bradykinetic alcohol dehydrogenases make yeast fitter for growth in the presence of allyl alcohol .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "allyl alcohol", "entity_type": "Chemical", "pos": [84, 97]}], "task": "NER"}
{"text": "Previous studies showed that fitter yeast ( Saccharomyces cerevisiae ) that can grow by fermenting glucose in the presence of allyl alcohol , which is oxidized by alcohol dehydrogenase I ( ADH1 ) to toxic acrolein , had mutations in the ADH1 gene that led to decreased ADH activity .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [99, 106]}, {"entity": "allyl alcohol", "entity_type": "Chemical", "pos": [126, 139]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [163, 170]}, {"entity": "acrolein", "entity_type": "Chemical", "pos": [205, 213]}], "task": "NER"}
{"text": "These yeast may grow more slowly due to slower reduction of acetaldehyde and a higher NADH / NAD ( + ) ratio , which should decrease the oxidation of allyl alcohol .", "entity": [{"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [60, 72]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [86, 90]}, {"entity": "NAD ( + )", "entity_type": "Chemical", "pos": [93, 102]}, {"entity": "allyl alcohol", "entity_type": "Chemical", "pos": [150, 163]}], "task": "NER"}
{"text": "We determined steady - state kinetic constants for three yeast ADHs with new site - directed substitutions and examined the correlation between catalytic efficiency and growth on selective media of yeast expressing six different ADHs .", "entity": [], "task": "NER"}
{"text": "The H15R substitution ( a test for electrostatic effects ) is on the surface of ADH and has small effects on the kinetics .", "entity": [], "task": "NER"}
{"text": "The H44R substitution ( affecting interactions with the coenzyme pyrophosphate ) was previously shown to decrease affinity for coenzymes 2 - 4 - fold and turnover numbers ( V / Et ) by 4 - 6 - fold .", "entity": [{"entity": "pyrophosphate", "entity_type": "Chemical", "pos": [65, 78]}], "task": "NER"}
{"text": "The W82R substitution is distant from the active site , but decreases turnover numbers by 5 - 6 - fold , perhaps by effects on protein dynamics .", "entity": [], "task": "NER"}
{"text": "The E67Q substitution near the catalytic zinc was shown previously to increase the Michaelis constant for acetaldehyde and to decrease turnover for ethanol oxidation .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [41, 45]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [106, 118]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "The W54R substitution , in the substrate binding site , increases kinetic constants ( Ks , by > 10 - fold ) while decreasing turnover numbers by 2 - 7 - fold .", "entity": [], "task": "NER"}
{"text": "Growth of yeast expressing the different ADHs on YPD plates ( yeast extract , peptone and dextrose ) plus antimycin to require fermentation , was positively correlated with the log of catalytic efficiency for the sequential bi reaction ( V1 / KiaKb = KeqV2 / KpKiq , varying over 4 orders of magnitude , adjusted for different levels of ADH expression ) in the order : WT =~ H15R > H44R > W82R > E67Q > W54R .", "entity": [{"entity": "dextrose", "entity_type": "Chemical", "pos": [90, 98]}, {"entity": "antimycin", "entity_type": "Chemical", "pos": [106, 115]}], "task": "NER"}
{"text": "Growth on YPD plus 10mM allyl alcohol was inversely correlated with catalytic efficiency .", "entity": [{"entity": "allyl alcohol", "entity_type": "Chemical", "pos": [24, 37]}], "task": "NER"}
{"text": "The fitter yeast are \" bradytrophs \" ( slow growing ) because the ADHs have decreased catalytic efficiency .", "entity": [], "task": "NER"}
{"text": "Oligochitosan polyplexes as carriers for retinal gene delivery .", "entity": [], "task": "NER"}
{"text": "Non - viral gene therapy represents a promising approach for the treatment of retinal diseases .", "entity": [], "task": "NER"}
{"text": "However , the lack of an efficient carrier hampers the implementation of this therapy .", "entity": [], "task": "NER"}
{"text": "In this study , we evaluated low molecular weight ultrapure oligochitosans for the delivery of the pCMS - EGFP plasmid into the rat retina cells after subretinal and intravitreal administrations .", "entity": [], "task": "NER"}
{"text": "Polyplexes were technologically characterized .", "entity": [], "task": "NER"}
{"text": "Resulting polyplexes based on ultrapure oligochitosans were slightly spherical , protected the plasmid against enzymatic digestion , and their charge and size values ranged from 8 to 14 millivolts and from 150 to 69 nm respectively depending on the N / P ratio .", "entity": [], "task": "NER"}
{"text": "In HEK - 293 cultured cells , transfection efficiency significantly increased from 12 % to 30 % when pH decreased from 7 . 4 to 7 . 1 ( data normalized to Lipofectamine (TM) 2000 ) .", "entity": [], "task": "NER"}
{"text": "However , no significant transfection was detected in ARPE - 19 cultured cells .", "entity": [], "task": "NER"}
{"text": "Subretinal administrations transfected mainly the pigmented cells of the retinal pigment epithelium and the light sensitive photoreceptor cells , whereas intravitreal injections transfected cells in the ganglion cell layer , blood vessels in the inner layers of the retina and photoreceptors .", "entity": [], "task": "NER"}
{"text": "These results support the potential use of oligochitosans for delivering genetic material into retinal cells in vivo .", "entity": [], "task": "NER"}
{"text": "Effect of volume ratio of ultrafiltrate to sample solution on the analysis of free drug and measurement of free carbamazepine in clinical drug monitoring .", "entity": [{"entity": "carbamazepine", "entity_type": "Chemical", "pos": [112, 125]}], "task": "NER"}
{"text": "Traditional ultrafiltration ( UF ) usually has a large volume ratio of ultrafiltrate to sample solution , and this ratio cannot be well controlled .", "entity": [], "task": "NER"}
{"text": "It can break the balance of protein - binding equilibrium and exert an influence on the analysis of free drug .", "entity": [], "task": "NER"}
{"text": "In the present study , we evaluated the influence of volume ratio of ultrafiltrate to sample solution on the analysis of free drug in human plasma .", "entity": [], "task": "NER"}
{"text": "We used carbamazepine as a model drug and studied the effect of different centrifugation times on ultrafitrate volume and the related effects on unbound carbamazepine measurement .", "entity": [{"entity": "carbamazepine", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "carbamazepine", "entity_type": "Chemical", "pos": [153, 166]}], "task": "NER"}
{"text": "Moreover , we compared the hollow fiber centrifugal ultrafiltration ( HFCF - UF ) with traditional UF .", "entity": [], "task": "NER"}
{"text": "Our results showed that the ultrafiltrate volume was changed from 40 to 400 mu L with the increase of centrifugation time for the traditional UF , and the related changes in unbound concentration were significant .", "entity": [], "task": "NER"}
{"text": "The rate of protein binding ( BP ) was changed from 40 % to 70 % .", "entity": [], "task": "NER"}
{"text": "In contrast , a tiny and invariant ultrafiltrate yield ( 40 mu L ) was obtained using the HFCF - UF method , and the BP rate was around 72 % .", "entity": [], "task": "NER"}
{"text": "In addition , with the HFCF - UF method , the volume ratio of ultrafiltrate to sample solution could be also well controlled by the inner diameters of both the glass tube and hollow fiber .", "entity": [], "task": "NER"}
{"text": "The HFCF - UF method was a more accurate plasma pretreatment procedure , by which the in vivo balance of protein - binding equilibrium was hardly broken .", "entity": [], "task": "NER"}
{"text": "Therefore , this method was successfully employed to quantify the free fraction of carbamazepine in clinical samples .", "entity": [{"entity": "carbamazepine", "entity_type": "Chemical", "pos": [83, 96]}], "task": "NER"}
{"text": "Determination of aflatoxins , deoxynivalenol , ochratoxin A and zearalenone in wheat and oat based bran supplements sold in the Spanish market .", "entity": [{"entity": "aflatoxins", "entity_type": "Chemical", "pos": [17, 27]}, {"entity": "deoxynivalenol", "entity_type": "Chemical", "pos": [30, 44]}, {"entity": "ochratoxin A", "entity_type": "Chemical", "pos": [47, 59]}, {"entity": "zearalenone", "entity_type": "Chemical", "pos": [64, 75]}], "task": "NER"}
{"text": "The aflatoxins ( AFs ) , deoxynivalenol ( DON ) , ochratoxin A ( OTA ) and zearalenone ( ZEA ) are mycotoxins produced by fungal species which can contaminate , alone or simultaneously , cereal - based raw materials .", "entity": [{"entity": "aflatoxins", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "deoxynivalenol", "entity_type": "Chemical", "pos": [25, 39]}, {"entity": "DON", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "ochratoxin A", "entity_type": "Chemical", "pos": [50, 62]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [65, 68]}, {"entity": "zearalenone", "entity_type": "Chemical", "pos": [75, 86]}, {"entity": "ZEA", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Usually , the higher mycotoxins concentrations in cereals are found in the external layers of the grain ( bran ) .", "entity": [], "task": "NER"}
{"text": "Nowadays bran is increasingly consumed for its high fibre concentration .", "entity": [], "task": "NER"}
{"text": "The objectives of this study were determining the concentration of these mycotoxins in bran samples intended for direct human consumption and to study the influence of some characteristics of the samples that may affect the mycotoxins content , there are not studies about fibre for direct human consumption .", "entity": [], "task": "NER"}
{"text": "67 bran samples from shops and supermarkets from two different Spanish cities were analyzed , being 37 samples of wheat bran and the remaining of oat bran .", "entity": [], "task": "NER"}
{"text": "The results showed a major presence of DON in the analyzed samples , with levels above the EU legislation in some samples .", "entity": [{"entity": "DON", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "Presence of DON was more frequent in wheat samples , compared to oats ones ( p < 0 . 05 ) .", "entity": [{"entity": "DON", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "Extruded or toasted samples , subjected to a heat treatment during processing , presented a significantly lower concentration of OTA , and differences between the organically and conventionally produced samples were also detected in OTA , which showed higher levels in the organic samples .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [129, 132]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [233, 236]}], "task": "NER"}
{"text": "Co - occurrence was frequently found between the Fusarium mycotoxins ( ZEA and DON ) .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [71, 74]}, {"entity": "DON", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "Due to the high levels of DON in the analyzed samples , a calculation of DON intake has been made and it has been demonstrated that bran can account for an important percentage of DON exposure in the total diet .", "entity": [{"entity": "DON", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "DON", "entity_type": "Chemical", "pos": [73, 76]}, {"entity": "DON", "entity_type": "Chemical", "pos": [180, 183]}], "task": "NER"}
{"text": "Phyllanthus urinaria suppresses human osteosarcoma cell invasion and migration by transcriptionally inhibiting u - PA via ERK and Akt signaling pathways .", "entity": [], "task": "NER"}
{"text": "Phyllanthus urinaria is widely used as anti - inflammatory , antiviral , antibacterial , and anti - hepatotoxic medicines in almost every tropical country .", "entity": [], "task": "NER"}
{"text": "However , scientific evidence supporting its use in cancer metastasis is limited , particularly osteosarcoma .", "entity": [], "task": "NER"}
{"text": "We investigated the effect of P . urinaria extract ( PUE ) on cell viability , invasion , and migration in the human osteosarcoma Saos - 2 cell line , and looked at the impact of PUE on several relevant proteases and signaling pathways .", "entity": [], "task": "NER"}
{"text": "This study demonstrates that PUE , at a range of concentrations ( from 0 to 100 mu g / ml ) , concentration - dependently inhibited the migration / invasion capacities of Saos - 2 without cytotoxic effects .", "entity": [], "task": "NER"}
{"text": "Zymographic and western blot analyses revealed that PUE inhibited the urokinase - type plasminogen activator ( u - PA ) and matrix metalloproteinase - 2 ( MMP - 2 ) enzyme activity , as well as protein expression .", "entity": [], "task": "NER"}
{"text": "Western blot analysis also showed that PUE inhibits phosphorylation of ERK1 / 2 and Akt .", "entity": [], "task": "NER"}
{"text": "Testing of mRNA level , quantitative real - time PCR , and promoter assays evaluated the inhibitory effects of PUE on u - PA expression in Saos - 2 cells .", "entity": [], "task": "NER"}
{"text": "The chromatin immunoprecipitation ( ChIP ) assay was reactive to the transcription protein SP - 1 , which was inhibited by PUE .", "entity": [], "task": "NER"}
{"text": "In conclusion , PUE suppresses human osteosarcoma Saos - 2 cell invasion and migration by transcriptionally inhibiting u - PA via ERK and Akt signaling pathways .", "entity": [], "task": "NER"}
{"text": "Therefore , PUE produces anti - metastatic activity in Saos - 2 cells .", "entity": [], "task": "NER"}
{"text": "Chronic exposure to paclobutrazol causes hepatic steatosis in male rockfish Sebastiscus marmoratus and the mechanism involved .", "entity": [{"entity": "paclobutrazol", "entity_type": "Chemical", "pos": [20, 33]}], "task": "NER"}
{"text": "Paclobutrazol ( PBZ ) is a triazole - containing fungicide which is widely used in agriculture .", "entity": [{"entity": "Paclobutrazol", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "PBZ", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "triazole", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "Acute toxicity can follow its extensive use but it is generally weaker than traditional pesticides such as organochlorine and organophosphorus .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [107, 121]}, {"entity": "organophosphorus", "entity_type": "Chemical", "pos": [126, 142]}], "task": "NER"}
{"text": "However , its adverse effects on aquatic organisms need to be investigated .", "entity": [], "task": "NER"}
{"text": "This study was conducted to investigate the effect of PBZ exposure on the hepatic lipid metabolism of Sebastiscus marmoratus .", "entity": [{"entity": "PBZ", "entity_type": "Chemical", "pos": [54, 57]}], "task": "NER"}
{"text": "After PBZ exposure for 50 days , hepatic lipid droplets were enlarged and the hepatic total lipid , triglyceride , total cholesterol and free fatty acid content had increased in a dose dependent manner compared to the control .", "entity": [{"entity": "PBZ", "entity_type": "Chemical", "pos": [6, 9]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [100, 112]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [121, 132]}, {"entity": "free fatty acid", "entity_type": "Chemical", "pos": [137, 152]}], "task": "NER"}
{"text": "The mRNA expression of lipid metabolism associated genes such as peroxisome proliferator - activated receptors ( PPARs ) , androgen receptor , acetyl - CoA carboxylase 1 , fatty acid synthesis , fatty acid bing protein 4 , liver X receptor alpha ( LXR alpha ) and stearoyl - CoA desaturase were up - regulated by PBZ exposure .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [123, 131]}, {"entity": "acetyl - CoA", "entity_type": "Chemical", "pos": [143, 155]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [172, 182]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [195, 205]}, {"entity": "stearoyl - CoA", "entity_type": "Chemical", "pos": [264, 278]}, {"entity": "PBZ", "entity_type": "Chemical", "pos": [313, 316]}], "task": "NER"}
{"text": "These results indicated that triazole - containing fungicides might affect the metabolism and health of fish via the multi - signal pathways of nuclear receptors such as PPARs and LXR .", "entity": [{"entity": "triazole", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Hierarchical assembly of ultrathin hexagonal SnS2 nanosheets onto electrospun TiO2 nanofibers : enhanced photocatalytic activity based on photoinduced interfacial charge transfer .", "entity": [{"entity": "SnS2", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [78, 82]}], "task": "NER"}
{"text": "Well - designed hierarchical nanostructures with one dimensional ( 1D ) TiO ( 2 ) nanofibers ( 120 - 350 nm in diameter and several micrometers in length ) and ultrathin hexagonal SnS ( 2 ) nanosheets ( 40 - 70 nm in lateral size and 4 - 8 nm in thickness ) were successfully synthesized by combining the electrospinning technique ( for TiO ( 2 ) nanofibers ) and a hydrothermal growth method ( for SnS ( 2 ) nanosheets ) .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [180, 189]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [337, 346]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [399, 408]}], "task": "NER"}
{"text": "The single - crystalline SnS ( 2 ) nanosheets with a 2D layered structure were uniformly grown onto the electrospun TiO ( 2 ) nanofibers consisted of either anatase ( A ) phase or anatase - rutile ( AR ) mixed phase TiO ( 2 ) nanoparticles .", "entity": [{"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [25, 34]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [116, 125]}, {"entity": "anatase", "entity_type": "Chemical", "pos": [157, 164]}, {"entity": "anatase", "entity_type": "Chemical", "pos": [180, 187]}, {"entity": "rutile", "entity_type": "Chemical", "pos": [190, 196]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [216, 225]}], "task": "NER"}
{"text": "The definite heterojunction interface between SnS ( 2 ) nanosheets and TiO ( 2 ) ( A or R ) nanoparticles were investigated by high resolution transmission electron microscopy ( HRTEM ) and X - ray photoelectron spectroscopy ( XPS ) .", "entity": [{"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [46, 55]}, {"entity": "TiO ( 2 ) ( A or R )", "entity_type": "Chemical", "pos": [71, 91]}], "task": "NER"}
{"text": "Moreover , the as - prepared SnS ( 2 ) / TiO ( 2 ) hierarchical nanostructures as nanoheterojunction photocatalysts exhibited excellent UV and visible light photocatalytic activities for the degradation of organic dyes ( rhodamine B and methyl orange ) and phenols ( 4 - nitrophenol ) , remarkably superior to the TiO ( 2 ) nanofibers and the SnS ( 2 ) nanosheets , mainly owing to the photoinduced interfacial charge transfer based on the photosynergistic effect of the SnS ( 2 ) / TiO ( 2 ) heterojunction .", "entity": [{"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [41, 50]}, {"entity": "rhodamine B", "entity_type": "Chemical", "pos": [221, 232]}, {"entity": "methyl orange", "entity_type": "Chemical", "pos": [237, 250]}, {"entity": "phenols", "entity_type": "Chemical", "pos": [257, 264]}, {"entity": "4 - nitrophenol", "entity_type": "Chemical", "pos": [267, 282]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [314, 323]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [343, 352]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [471, 480]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [483, 492]}], "task": "NER"}
{"text": "Significantly , the SnS ( 2 ) / TiO ( 2 ) ( AR ) hierarchical nanostructures as the tricomponent heterojunction system possessed stronger photocatalytic activity than the bicomponent heterojunction system of SnS ( 2 ) / TiO ( 2 ) ( A ) hierarchical nanostructures or TiO ( 2 ) ( AR ) nanofibers , which was discussed in terms of the three - way photosynergistic effect between SnS ( 2 ) , TiO ( 2 ) ( A ) and TiO ( 2 ) ( R ) component in the SnS ( 2 ) / TiO ( 2 ) ( AR ) heterojunction resulting in the high separation efficiency of photoinduced electron - hole pairs , as evidenced by photoluminescence ( PL ) and surface photovoltage spectra ( SPS ) .", "entity": [{"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [20, 29]}, {"entity": "TiO ( 2 ) ( AR )", "entity_type": "Chemical", "pos": [32, 48]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [208, 217]}, {"entity": "TiO ( 2 ) ( A )", "entity_type": "Chemical", "pos": [220, 235]}, {"entity": "TiO ( 2 ) ( AR )", "entity_type": "Chemical", "pos": [267, 283]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [377, 386]}, {"entity": "TiO ( 2 ) ( A )", "entity_type": "Chemical", "pos": [389, 404]}, {"entity": "TiO ( 2 ) ( R )", "entity_type": "Chemical", "pos": [409, 424]}, {"entity": "SnS ( 2 )", "entity_type": "Chemical", "pos": [442, 451]}, {"entity": "TiO ( 2 ) ( AR )", "entity_type": "Chemical", "pos": [454, 470]}], "task": "NER"}
{"text": "Chronic arsenic exposure in nanomolar concentrations compromises wound response and intercellular signaling in airway epithelial cells .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [8, 15]}], "task": "NER"}
{"text": "Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions , including mucociliary clearance , bactericide production , and as an initiating signal in wound repair .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "We evaluated the effects of chronic low - dose arsenic relevant to U . S . drinking water standards ( i . e . , 10 ppb [ 130nM ] ) on airway epithelial cells .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [47, 54]}], "task": "NER"}
{"text": "Immortalized human bronchial epithelial cells ( 16HBE14o - ) were exposed to 0 , 130 , or 330nM arsenic ( as Na - arsenite ) for 4 - 5 weeks and examined for wound repair efficiency and ATP - mediated Ca ( 2 + ) signaling .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [96, 103]}, {"entity": "Na - arsenite", "entity_type": "Chemical", "pos": [109, 122]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [186, 189]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [201, 211]}], "task": "NER"}
{"text": "We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP - mediated Ca ( 2 + ) signaling .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "We further show that arsenic compromises ATP - mediated Ca ( 2 + ) signaling by altering both Ca ( 2 + ) release from intracellular stores ( via metabotropic P2Y receptors ) and Ca ( 2 + ) influx mechanisms ( via ionotropic P2X receptors ) .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [21, 28]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [178, 188]}], "task": "NER"}
{"text": "To better model the effects of arsenic on ATP - mediated Ca ( 2 + ) signaling under conditions of natural exposure , we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na - arsenite supplemented drinking water for 4 weeks .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "Na - arsenite", "entity_type": "Chemical", "pos": [203, 216]}], "task": "NER"}
{"text": "Tracheal epithelial cells from arsenic - exposed mice displayed reduced ATP - mediated Ca ( 2 + ) signaling dynamics similar to our in vitro chronic exposure .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [87, 97]}], "task": "NER"}
{"text": "Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water ( i . e . , 10 - 50 ppb ) alters cellular mechanisms critical to airway innate immunity .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [38, 45]}], "task": "NER"}
{"text": "Identification of ginkgolic acid ( 15 : 1 ) metabolites in rats following oral administration by high - performance liquid chromatography coupled to tandem mass spectrometry .", "entity": [{"entity": "ginkgolic acid ( 15 : 1 )", "entity_type": "Chemical", "pos": [18, 43]}], "task": "NER"}
{"text": "1 . In this article , metabolites of ginkgolic acid ( GA ) ( 15 : 1 ) in rats plasma , bile , urine and faeces after oral administration have been investigated for the first time by high - performance liquid chromatography coupled to tandem mass spectrometry ( HPLC - MS / MS ) with the aid of on - line hydrogen / deuterium ( H / D ) exchange technique and beta - glucuronidase hydrolysis experiments .", "entity": [{"entity": "ginkgolic acid", "entity_type": "Chemical", "pos": [37, 51]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [304, 312]}, {"entity": "deuterium", "entity_type": "Chemical", "pos": [315, 324]}, {"entity": "H", "entity_type": "Chemical", "pos": [327, 328]}, {"entity": "D", "entity_type": "Chemical", "pos": [331, 332]}], "task": "NER"}
{"text": "2 . After oral administration of GA ( 15 : 1 , M0 ) to rats at a dose of 10 mg / kg , it was found that metabolites M1 - M5 together with parent compound ( M0 ) existed in rat plasma ; parent compound ( M0 ) and metabolites M2 - M5 were observed in rat bile , and parent compound ( M0 ) with metabolites M1 and M2 were discovered in rat faeces , and there was no parent compound and metabolite detectable in rat urine .", "entity": [], "task": "NER"}
{"text": "3 . Two oxidative metabolites of GA ( 15 : 1 , M0 ) were identified as 2 - hydroxy - 6 - ( pentadec - 8 - enyl - 10 - hydroxy ) benzoic acid ( M1 ) and 2 - hydroxy - 6 - ( pentadec - 8 - enyl - 11 - hydroxy - 13 - carbonyl ) benzoic acid ( M2 ) , respectively .", "entity": [{"entity": "2 - hydroxy - 6 - ( pentadec - 8 - enyl - 10 - hydroxy ) benzoic acid", "entity_type": "Chemical", "pos": [71, 140]}, {"entity": "2 - hydroxy - 6 - ( pentadec - 8 - enyl - 11 - hydroxy - 13 - carbonyl ) benzoic acid", "entity_type": "Chemical", "pos": [152, 237]}], "task": "NER"}
{"text": "Metabolites M3 , M4 and M5 were identified as the mono - glucuronic acid conjugates of parent compound ( M0 ) , M1 and M2 , respectively .", "entity": [{"entity": "mono - glucuronic acid", "entity_type": "Chemical", "pos": [50, 72]}], "task": "NER"}
{"text": "4 . The results indicated that M1 and M2 with parent compound ( M0 ) were mainly eliminated in faeces and three glucuronide metabolites ( M3 , M4 and M5 ) excreted in bile as the predominant forms after oral administration of GA ( 15 : 1 ) to rats .", "entity": [{"entity": "glucuronide", "entity_type": "Chemical", "pos": [112, 123]}, {"entity": "GA ( 15 : 1 )", "entity_type": "Chemical", "pos": [226, 239]}], "task": "NER"}
{"text": "Shear modulus property characterization of nanorods .", "entity": [], "task": "NER"}
{"text": "We demonstrate an innovative technique for the direct measurement on the shear modulus of an individual nanorod .", "entity": [], "task": "NER"}
{"text": "This measurement is based on atomic force microscopy ( AFM ) and microfabrication techniques .", "entity": [], "task": "NER"}
{"text": "A nanorod is first aligned along the edge of a small trench in a silicon substrate , and then one end of the nanorod is fixed on the substrate .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [65, 72]}], "task": "NER"}
{"text": "When an AFM tip scans over the nanorod in contact mode , the nanorod will be twisted by the comprehensive action from the force of the AFM tip , confinement from the trench edge and the fixing end .", "entity": [], "task": "NER"}
{"text": "The shear deformation and the corresponding force that caused the deformation can be retrieved from topography and lateral force image , respectively .", "entity": [], "task": "NER"}
{"text": "By small - angle approximation , the shear modulus of the ZnO NR , which has a radius of 166 nm and a length of 4 mu m , is measured to be 8 . 1 +/- 1 . 9 GPa .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "This method can be applied directly to characterize the shear modulus of any nanowire / nanorod that possesses a polygon cross section .", "entity": [], "task": "NER"}
{"text": "From an atypical wake - promoting agent to potent histamine - 3 receptor inverse agonists .", "entity": [{"entity": "histamine", "entity_type": "Chemical", "pos": [50, 59]}], "task": "NER"}
{"text": "Utilizing atypical wake - promoting agent modafinil ( inactive in both rH ( 3 ) and hH ( 3 ) binding assays ) as a launching pad , a series of sulfinyl - and sulfone - derived H ( 3 ) receptor inverse agonists were developed .", "entity": [{"entity": "modafinil", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "sulfinyl", "entity_type": "Chemical", "pos": [143, 151]}, {"entity": "sulfone", "entity_type": "Chemical", "pos": [158, 165]}], "task": "NER"}
{"text": "Brain - permeable compound 27 , a potent member of the series displayed excellent selectivity against related family members ( H ( 1 ) , H ( 2 ) , and H ( 4 ) receptors ) .", "entity": [], "task": "NER"}
{"text": "YopK controls both rate and fidelity of Yop translocation .", "entity": [], "task": "NER"}
{"text": "Yersinia pestis , the causative agent of plague , utilizes a type III secretion system ( T3SS ) to intoxicate host cells .", "entity": [], "task": "NER"}
{"text": "The injection of T3SS substrates must be carefully controlled , and dysregulation leads to altered infection kinetics and early clearance of Y . pestis .", "entity": [], "task": "NER"}
{"text": "While the sequence of events leading up to cell contact and initiation of translocation has received much attention , the regulatory events that take place after effector translocation is less understood .", "entity": [], "task": "NER"}
{"text": "Here we show that the regulator YopK is required to maintain fidelity of substrate specificity , in addition to controlling translocation rate .", "entity": [], "task": "NER"}
{"text": "YopK was found to interact with YopD within targeted cells during Y . pestis infection , suggesting that YopK ' s regulatory mechanism involves a direct interaction with the translocation pore .", "entity": [], "task": "NER"}
{"text": "In addition , we identified a single amino acid in YopK that is essential for translocation rate regulation but is dispensable for maintaining fidelity of translocation .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [37, 47]}], "task": "NER"}
{"text": "Furthermore , we found that expression of YopK within host cells was sufficient to downregulate translocation rate , but it did not affect translocation fidelity .", "entity": [], "task": "NER"}
{"text": "Together , our data support a model in which YopK is a bifunctional protein whose activities are genetically and spatially distinct such that fidelity control occurs within bacteria and rate control occurs within host cells .", "entity": [], "task": "NER"}
{"text": "Highly efficient preparation of multiscaled quantum dot barcodes for multiplexed hepatitis B detection .", "entity": [], "task": "NER"}
{"text": "Both disease diagnosis and therapeutic treatments require real - time information from assays capable of identifying multiple targets .", "entity": [], "task": "NER"}
{"text": "Among various multiplexed biochips , multiplexed suspension assays of quantum dot ( QD ) - encoded microspheres are highly advantageous .", "entity": [], "task": "NER"}
{"text": "This arises from the excellent fluorescent properties of the QDs incorporated into these microspheres , thus allowing them to serve as \" QD barcodes \" .", "entity": [], "task": "NER"}
{"text": "QD barcodes can be prepared through various approaches .", "entity": [], "task": "NER"}
{"text": "However , the formulation of improved synthetic techniques that may allow more efficient preparation of QD barcodes with better encoding accuracy still remains a challenge .", "entity": [], "task": "NER"}
{"text": "In this report , we describe a combined membrane emulsification - solvent evaporation ( MESE ) approach for the efficient preparation of QD barcodes .", "entity": [], "task": "NER"}
{"text": "By combining the advantages of the MESE approach in controlling the barcode sizes with accurate encoding , a three - dimensional barcode library that integrates the signals of the forward scattering , fluorescence 1 , and fluorescence 4 channels was established via flow cytometry .", "entity": [], "task": "NER"}
{"text": "The five indexes of hepatitis B viruses were chosen as diagnostic targets to examine the feasibility of the QD barcodes in high - throughput diagnosis .", "entity": [], "task": "NER"}
{"text": "On the basis of showing that singleplex detection is feasible , we demonstrate the ability of these QD barcodes to simultaneously and selectively detect a multitude of diverse biomolecular targets .", "entity": [], "task": "NER"}
{"text": "Identification of a novel benzimidazole derivative as a highly potent NPY Y5 receptor antagonist with an anti - obesity profile .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [26, 39]}], "task": "NER"}
{"text": "Optimization of HTS hit 1 for NPY Y5 receptor binding affinity , CYP450 inhibition , solubility and metabolic stability led to the identification of some orally available oxygen - linker derivatives for in vivo study .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [171, 177]}], "task": "NER"}
{"text": "Among them , derivative 4i inhibited food intake induced by the NPY Y5 selective agonist , and chronic oral administration of 4i in DIO mice caused a dose - dependent reduction of body weight gain .", "entity": [], "task": "NER"}
{"text": "Testosterone positively associated with both male mating effort and paternal behavior in savanna baboons ( Papio cynocephalus ) .", "entity": [{"entity": "Testosterone", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Testosterone ( T ) is often positively associated with male sexual behavior and negatively associated with paternal care .", "entity": [{"entity": "Testosterone", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "These associations have primarily been demonstrated in species where investment in paternal care begins well after mating activity is complete , when offspring are hatched or born .", "entity": [], "task": "NER"}
{"text": "Different patterns may emerge in studies of species where investment in mating and paternal care overlap temporally , for instance in non - seasonal breeders in which males mate with multiple females sequentially and may simultaneously have multiple offspring of different ages .", "entity": [], "task": "NER"}
{"text": "In a 9 - year data set on levels of T in male baboons , fecal concentrations of T ( fT ) were positively associated with both mate guarding ( \" consortship \" ) - a measure of current reproductive activity - and with the number of immature offspring a male had in his social group - a measure of past reproductive activity and an indicator of likely paternal behavior .", "entity": [], "task": "NER"}
{"text": "To further examine the relationship between T and potential paternal behavior , we next drew on an intensive 8 - month study of male behavior , and found that fathers were more likely to be in close proximity to their offspring than expected by chance .", "entity": [], "task": "NER"}
{"text": "Because male baboons are known to provide paternal care , and because time in proximity to offspring would facilitate such care , this suggests that T concentrations in wild male baboons may be associated with both current reproductive activity and with current paternal behavior .", "entity": [], "task": "NER"}
{"text": "These results are consistent with the predicted positive association between T and mating effort but not with a negative association between T and paternal care ; in male baboons , high levels of T occur in males that are differentially associating with their offspring .", "entity": [], "task": "NER"}
{"text": "Silexan , an essential oil from flowers of Lavandula angustifolia , is not recognized as benzodiazepine - like in rats trained to discriminate a diazepam cue .", "entity": [{"entity": "benzodiazepine", "entity_type": "Chemical", "pos": [89, 103]}, {"entity": "diazepam", "entity_type": "Chemical", "pos": [145, 153]}], "task": "NER"}
{"text": "Recently , an essential oil of selected quality produced from the flowering tops of Lavandula angustifolia Mill . by steam distillation ( Silexan ) has been approved in Germany for the treatment of restlessness in case of anxious mood .", "entity": [], "task": "NER"}
{"text": "Based on the observed clinical effects , it has been speculated that lavender oil may exert benzodiazepine - like action including the known dependence and abuse potential of this class of drugs .", "entity": [{"entity": "benzodiazepine", "entity_type": "Chemical", "pos": [92, 106]}], "task": "NER"}
{"text": "Although no evidence for such an activity was generated during the long - standing medicinal use of lavender oil , further preclinical investigations were now conducted to evaluate this potential side effect in more detail .", "entity": [], "task": "NER"}
{"text": "Twelve adult , male , Sprague - Dawley rats were trained to discriminate the benzodiazepine drug diazepam ( 2 mg / kg i . p . ) from saline using a two - lever operant procedure .", "entity": [{"entity": "benzodiazepine", "entity_type": "Chemical", "pos": [77, 91]}, {"entity": "diazepam", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "After approximately 40 training sessions the majority of rats learned the discrimination and pre - treatment with ascending doses of diazepam ( 0 . 3 - 2 mg / kg i . p . ) produced a dose related generalization to the diazepam cue .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [133, 141]}, {"entity": "diazepam", "entity_type": "Chemical", "pos": [218, 226]}], "task": "NER"}
{"text": "In these same animals Silexan was administered to see if animals recognized the drug as \" diazepam - like \" i . e . generalized to diazepam or \" saline - like \" .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [90, 98]}, {"entity": "diazepam", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "Silexan tested at doses 3 - 30 mg / kg i . p . produced almost exclusively ( > 90 % ) saline - like responding .", "entity": [], "task": "NER"}
{"text": "Also there was no effect of Silexan on response rate , i . e . rate of lever pressing , at any dose suggesting that the test article is well tolerated and does not exert a sedating effect .", "entity": [], "task": "NER"}
{"text": "In sum , Silexan has no diazepam - like interoceptive property in adult , male rats .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [24, 32]}], "task": "NER"}
{"text": "This suggests that Silexan does not share the potential of benzodiazepines to induce the development of tolerance , dependence and addiction .", "entity": [{"entity": "benzodiazepines", "entity_type": "Chemical", "pos": [59, 74]}], "task": "NER"}
{"text": "Combination of phenylpropanoids with 5 - fluorouracil as anti - cancer agents against human cervical cancer ( HeLa ) cell line .", "entity": [{"entity": "phenylpropanoids", "entity_type": "Chemical", "pos": [15, 31]}, {"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [37, 53]}], "task": "NER"}
{"text": "Combination therapy is the most effective treatment strategy in cancer to overcome drug toxicity and drug induced resistance .", "entity": [], "task": "NER"}
{"text": "The effect of eight phenylpropanoids in combination with 5 - fluorouracil against the cervical cancer cells ( HeLa ) is reported here .", "entity": [{"entity": "phenylpropanoids", "entity_type": "Chemical", "pos": [20, 36]}, {"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [57, 73]}], "task": "NER"}
{"text": "The cytotoxic activity of these phenylpropanoids against HeLa cells is in the order of eugenol > ferulic > cinnamic > caffeic > chlorogenic > p - coumaric > 3 , 4 - dimethoxycinnamic > 2 , 4 , 5 - trimethoxycinnamic acids .", "entity": [{"entity": "phenylpropanoids", "entity_type": "Chemical", "pos": [32, 48]}, {"entity": "eugenol", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "ferulic", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "cinnamic", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "caffeic", "entity_type": "Chemical", "pos": [118, 125]}, {"entity": "chlorogenic", "entity_type": "Chemical", "pos": [128, 139]}, {"entity": "p - coumaric", "entity_type": "Chemical", "pos": [142, 154]}, {"entity": "3 , 4 - dimethoxycinnamic", "entity_type": "Chemical", "pos": [157, 182]}, {"entity": "2 , 4 , 5 - trimethoxycinnamic acids", "entity_type": "Chemical", "pos": [185, 221]}], "task": "NER"}
{"text": "Eugenol , ferulic and caffeic acids interacted synergistically with the drug , in bringing about a reduction in the amount of the latter .", "entity": [{"entity": "Eugenol", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "ferulic and caffeic acids", "entity_type": "Chemical", "pos": [10, 35]}], "task": "NER"}
{"text": "Flow cytometry results indicated that the combination of eugenol and 5 - fluorouracil increased the number of cells in the S and G2 / M phases when compared to treatment with the individual compounds alone .", "entity": [{"entity": "eugenol", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [69, 85]}], "task": "NER"}
{"text": "This indicates that they possess different cell cycle targets and induce apoptosis in the cancer cells .", "entity": [], "task": "NER"}
{"text": "In vitro hemolytic activity of phenylpropanoids on human erythrocytes showed that the compounds possessed minimum amount of hemolytic activity , indicating that they can be used as drugs without causing adverse toxicity .", "entity": [{"entity": "phenylpropanoids", "entity_type": "Chemical", "pos": [31, 47]}], "task": "NER"}
{"text": "3D - quantitative structure activity relationship studies indicate the importance of electrostatic region near the substitutions present in the benzene ring and near the double bond of the compounds for anticancer and hemolytic activities , respectively .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [144, 151]}], "task": "NER"}
{"text": "The models derived had good statistical predictive capability .", "entity": [], "task": "NER"}
{"text": "Understanding the interactions between metabolites isolated from Achyrocline satureioides in relation to its antibacterial activity .", "entity": [], "task": "NER"}
{"text": "As part of our ongoing research on the antibacterial activity of Achyrocline satureioides , this study seeks to better understand the interactions between the metabolites isolated from this plant .", "entity": [], "task": "NER"}
{"text": "For this purpose , the combined effect of 23 - methyl - 6 - O - desmethylauricepyrone ( 1 ) , quercetin ( 2 ) and 3 - O - methylquercetin ( 3 ) , obtained through bioguided fractionation from A . satureioides ethanol extract , was evaluated against Staphylococcus aureus and Escherichia coli .", "entity": [{"entity": "23 - methyl - 6 - O - desmethylauricepyrone", "entity_type": "Chemical", "pos": [42, 85]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [94, 103]}, {"entity": "3 - O - methylquercetin", "entity_type": "Chemical", "pos": [114, 137]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [209, 216]}], "task": "NER"}
{"text": "In first place , the antibacterial effect of the combination of flavonols 2 and 3 was assessed , as these showed individual effectiveness lower than or equal to that of the fraction from which they were obtained .", "entity": [{"entity": "flavonols", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "When the flavonols were applied together at concentrations below their minimum inhibitory concentration ( MIC ) values , a synergistic effect ( FICI < 0 . 30 ) against S . aureus was observed .", "entity": [{"entity": "flavonols", "entity_type": "Chemical", "pos": [9, 18]}], "task": "NER"}
{"text": "In addition , compounds 2 and 3 in combination reduced 1000 times the MIC of compound 1 , showing a clear synergistic interaction ( FICI < 0 . 15 ) in treatments against the Gram ( + ) bacterium .", "entity": [], "task": "NER"}
{"text": "The most active combination against E . coli showed an additive interaction ( FICI < 0 . 62 ) between the three assayed compounds 1 - 3 .", "entity": [], "task": "NER"}
{"text": "These results indicated the existence of concerted action between these metabolites , evidence of the importance of the synergistic interactions between the components of plant - derived extracts for the control of pathogenic bacteria .", "entity": [], "task": "NER"}
{"text": "pH - responsive composite microspheres based on magnetic mesoporous silica nanoparticle for drug delivery .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [68, 74]}], "task": "NER"}
{"text": "pH - responsive composite microspheres , consisting of a core of Fe3O4 nanoparticle , a sandwiched layer of mesoporous silica and a shell of crosslinked poly ( methacrylic acid ) ( PMAA ) , were successfully synthesized via distillation precipitation polymerization .", "entity": [{"entity": "Fe3O4", "entity_type": "Chemical", "pos": [65, 70]}, {"entity": "silica", "entity_type": "Chemical", "pos": [119, 125]}, {"entity": "poly ( methacrylic acid )", "entity_type": "Chemical", "pos": [153, 178]}, {"entity": "PMAA", "entity_type": "Chemical", "pos": [181, 185]}], "task": "NER"}
{"text": "The pKa of the composite microsphere increased with the increase in the crosslinking density .", "entity": [], "task": "NER"}
{"text": "Doxorubicin hydrochloride ( DOX ) was applied as a model drug , and the behavior of drug storage / release was investigated .", "entity": [{"entity": "Doxorubicin hydrochloride", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "The cumulative release of DOX - loaded composite microsphere in vitro showed that the drug release rate was much faster below its pKa than that of above its pKa .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [26, 29]}], "task": "NER"}
{"text": "Because pH of most tumor tissues was lower than that of normal tissues , the pH - responsive composite microspheres are promising drug delivery system especially for cancer therapy .", "entity": [], "task": "NER"}
{"text": "Expression of antagonists of WNT and BMP signaling after non - rigid fixation of osteotomies .", "entity": [], "task": "NER"}
{"text": "Delayed fracture healing and non - unions represent rare but severe complications in orthopedic surgery .", "entity": [], "task": "NER"}
{"text": "Further knowledge on the mechanisms of the bone repair process and of the development of a pseudoarthrosis is essential to predict and prevent impaired healing of fractures .", "entity": [], "task": "NER"}
{"text": "The present study aimed at elucidating differences in gene expression during the repair of rigidly and non - rigidly fixed osteotomies .", "entity": [], "task": "NER"}
{"text": "For this purpose , the MouseFix (TM) and the FlexiPlate (TM) systems ( AO Development Institute , Davos , CH ) , allowing the creation of well defined osteotomies in mouse femora , were employed .", "entity": [], "task": "NER"}
{"text": "A time course following the healing process of the osteotomy was performed and bones and periimplant tissues were analyzed by high - resolution X - ray , MicroCT and by histology .", "entity": [], "task": "NER"}
{"text": "For the assessment of gene expression , Low Density Arrays ( LDA ) were done .", "entity": [], "task": "NER"}
{"text": "In animals with rigid fixation , X - ray and MicroCT revealed healing of the osteotomy within 3 weeks .", "entity": [], "task": "NER"}
{"text": "Using the FlexiPlate (TM) system , the osteotomy was still visible by X - ray after 3 weeks and a stabilizing cartilaginous callus was formed .", "entity": [], "task": "NER"}
{"text": "After 4 . 5 weeks , the callus was remodeled and the osteotomy was , on a histological level , healed .", "entity": [], "task": "NER"}
{"text": "Gene expression studies revealed levels of transcripts encoding proteins associated with inflammatory processes not to be altered in tissues from bones with rigid and non - rigid fixation , respectively .", "entity": [], "task": "NER"}
{"text": "Levels of transcripts encoding proteins of the extracellular matrix and essential for bone cell functions were not increased in the rigidly fixed group when compared to controls without osteotomy .", "entity": [], "task": "NER"}
{"text": "In the FlexiPlate (TM) group , levels of transcripts encoding the same set of genes were significantly increased 3 weeks after surgery .", "entity": [], "task": "NER"}
{"text": "Expression of transcripts encoding BMPs and BMP antagonists was increased after 3 weeks in repair tissues from bones fixed with FlexiPlate (TM) , as were inhibitors of the WNT signaling pathways .", "entity": [], "task": "NER"}
{"text": "Little changes only were detected in transcript levels of tissues from rigidly fixed bones .", "entity": [], "task": "NER"}
{"text": "The data of the present study suggest that rigid fixation enables accelerated healing of an experimental osteotomy as compared to non - rigid fixation .", "entity": [], "task": "NER"}
{"text": "The changes in the healing process after non - rigid fixation are accompanied by an increase in the levels of transcripts encoding inhibitors of osteogenic pathways and , probably as a consequence , by temporal changes in bone matrix synthesis .", "entity": [], "task": "NER"}
{"text": "Microstructured , functional PVA hydrogels through bioconjugation with oligopeptides under physiological conditions .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [29, 32]}], "task": "NER"}
{"text": "In this work , bioconjugation techniques are developed to achieve peptide functionalization of poly ( vinyl alcohol ) , PVA , as both a polymer in solution and within microstructured physical hydrogels , in both cases under physiological conditions .", "entity": [{"entity": "poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [95, 117]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [120, 123]}], "task": "NER"}
{"text": "PVA is unique in that it is one of very few polymers with excellent biocompatibility and safety and has FDA approval for clinical uses in humans .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "However , decades of development have documented only scant opportunities in bioconjugation with PVA .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "As such , materials derived thereof fail to answer the call for functional biomaterials for advanced cell culture and tissue engineering applications .", "entity": [], "task": "NER"}
{"text": "To address these limitations , PVA is synthesized with terminal thiol groups and conjugated with thiolated peptides using PVA in solution .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [64, 69]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "Further , microstructured , surface - adhered PVA physical hydrogels are assembled , the available conjugation sites within the hydrogels are quantified , and quantitative kinetic data are collected on peptide conjugation to the hydrogels .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "The success of bioconjugation in the gel phase is quantified through the use of a cell - adhesive peptide and visualization of cell adhesion on PVA hydrogels as cell culture substrates .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "Taken together , the presented data establish a novel paradigm in bioconjugation and functionalization of PVA physical hydrogels .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "Coupled with an excellent safety profile of PVA , these results deliver a superior biomaterial for diverse biomedical applications .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [44, 47]}], "task": "NER"}
{"text": "Novel Three - Dimensional Nanoporous Alumina as a Template for Hierarchical TiO2 Nanotube Arrays .", "entity": [{"entity": "Alumina", "entity_type": "Chemical", "pos": [37, 44]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "Hierarchical micro - / nano - structures made easy .", "entity": [], "task": "NER"}
{"text": "By using extremely rough , chemically etched microstructured aluminium foils , anodization in phosphoric acid under very harsh conditions , e . g . , 10 wt % phosphoric acid and room temperature , can be repeatedly accomplished without suffering from breakdown .", "entity": [{"entity": "aluminium", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "phosphoric acid", "entity_type": "Chemical", "pos": [94, 109]}, {"entity": "phosphoric acid", "entity_type": "Chemical", "pos": [158, 173]}], "task": "NER"}
{"text": "As a result , an alumina membrane with a three - dimensionally distributed nanopore structure is formed , which can be used as a general template to fabricate hierarchical micro - / nano - structures .", "entity": [{"entity": "alumina", "entity_type": "Chemical", "pos": [17, 24]}], "task": "NER"}
{"text": "Application of hybrid approach based on empirical and physiological concept for predicting pharmacokinetics in humans - - usefulness of exponent on prospective evaluation of predictability .", "entity": [], "task": "NER"}
{"text": "We developed a hybrid method for predicting plasma concentration - time curves in humans by integrating species differences in in vitro intrinsic clearance ( CL ( int ) ) into the Dedrick approach based on the allometry concept .", "entity": [], "task": "NER"}
{"text": "With prediction of clearance ( CL ) by allometric scaling , taking in vitro CL ( int ) into consideration improved the accuracy and reduced the average fold error from 2 . 72 to 1 . 99 .", "entity": [], "task": "NER"}
{"text": "With the hybrid approach of applying the same concept to the Dedrick approach , the predictability of plasma concentration profiles was compared with the results of the conventional Dedrick approach and the physiologically based pharmacokinetic model using 15 compounds with widely ranging physicochemical and pharmacokinetic profiles .", "entity": [], "task": "NER"}
{"text": "The hybrid approach showed the highest predictability among the examined methods .", "entity": [], "task": "NER"}
{"text": "For CL and the apparent volume of distribution at the steady state ( V ( ss ) ) , the relationship between the exponent of allometric equation and fold error was also evaluated with the hybrid approach .", "entity": [], "task": "NER"}
{"text": "The relationship appeared to be a horseshoe curve .", "entity": [], "task": "NER"}
{"text": "Six compounds with exponents ranging from 0 . 7 to 1 . 1 for both CL and V ( ss ) [ antipyrine , caffeine , epiroprim , propafenone , theophylline , and verapamil ] displayed higher predictability .", "entity": [{"entity": "antipyrine", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [97, 105]}, {"entity": "epiroprim", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "propafenone", "entity_type": "Chemical", "pos": [120, 131]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [134, 146]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [153, 162]}], "task": "NER"}
{"text": "Three compounds with an exponent ranging from 0 . 7 to 1 . 1 for CL showed better predictability for CL , and the other four compounds appeared to display similar relationship between the exponent and predictability for V ( ss ) .", "entity": [], "task": "NER"}
{"text": "These findings indicated that the exponent becomes a preliminary index to speculate on predictability .", "entity": [], "task": "NER"}
{"text": "Combination of the hybrid approach and exponent allows us to prospectively draw human plasma concentration - time curves , with the implication of possible prediction accuracy prior to clinical studies .", "entity": [], "task": "NER"}
{"text": "The potential of Sutherlandia frutescens for herb - drug interaction .", "entity": [], "task": "NER"}
{"text": "In Africa , Sutherlandia frutescens is a popular medicinal herb widely consumed by people living with human immunodeficiency virus / AIDS .", "entity": [], "task": "NER"}
{"text": "Concomitant use with antiretroviral drugs has generated concerns of herb - drug interaction ( HDI ) .", "entity": [], "task": "NER"}
{"text": "This study investigated the inhibitory effects of the crude extracts of S . frutescens on the major cytochrome P450 isozymes with the use of pooled human liver microsomes .", "entity": [], "task": "NER"}
{"text": "Its effect on the metabolic clearance of midazolam using cryopreserved hepatocytes was also monitored .", "entity": [{"entity": "midazolam", "entity_type": "Chemical", "pos": [41, 50]}], "task": "NER"}
{"text": "The potential of S . frutescens to inhibit human ATP - binding cassette transporters ( P - gp and BCRP ) and the human organic anion transporting polypeptide ( OATP1B1 and OATP1B3 ) activity was assessed using cell lines overexpressing the transporter proteins .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [49, 52]}], "task": "NER"}
{"text": "S . frutescens showed inhibitory potency for CYP1A2 ( IC ( 50 ) = 41 . 0 micro g / ml ) , CYP2A6 ( IC ( 50 ) = 160 micro g / ml ) , CYP2B6 ( IC ( 50 ) = 20 . 0 micro g / ml ) , CYP2C8 ( IC ( 50 ) = 22 . 4 micro g / ml ) , CYP2C9 ( IC ( 50 ) = 23 . 0 micro g / ml ) , CYP2C19 ( IC ( 50 ) = 35 . 9 micro g / ml ) , and CYP3A4 / 5 ( IC ( 50 ) = 17 . 5 micro g / ml [ with midazolam1 ' - hydroxylation ] ; IC ( 50 ) = 28 . 3 micro g / ml [ with testosterone 6 beta - hydroxylation ] ) .", "entity": [{"entity": "midazolam1", "entity_type": "Chemical", "pos": [369, 379]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [441, 453]}], "task": "NER"}
{"text": "Time - dependent ( irreversible ) inhibition by S . frutescens was observed for CYP3A4 / 5 ( K ( I ) = 296 micro g / ml , k ( inact ) = 0 . 063 min ( - 1 ) ) under the conditions of this study .", "entity": [], "task": "NER"}
{"text": "S . frutescens also delays the production of midazolam metabolites in the hepatocytes , decreasing its clearance by 40 % .", "entity": [{"entity": "midazolam", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "Furthermore , S . frutescens inhibited P - gp ( IC ( 50 ) = 324 . 8 micro g / ml ) , OATP1B1 ( IC ( 50 ) = 10 . 4 micro g / ml ) , and OATP1B3 ( IC ( 50 ) = 6 . 6 micro g / ml ) .", "entity": [], "task": "NER"}
{"text": "The result indicates the potential for HDI between S . frutescens and the substrates of the affected enzymes , if sufficient in vivo concentration of the extract is attained .", "entity": [], "task": "NER"}
{"text": "Burial of the polymorphic residue 129 in amyloid fibrils of prion stop mutants .", "entity": [], "task": "NER"}
{"text": "Misfolding of the natively alpha - helical prion protein into a beta - sheet rich isoform is related to various human diseases such as Creutzfeldt - Jakob disease and Gerstmann - Str a ussler - Scheinker syndrome .", "entity": [], "task": "NER"}
{"text": "In humans , the disease phenotype is modified by a methionine / valine polymorphism at codon 129 of the prion protein gene .", "entity": [{"entity": "methionine", "entity_type": "Chemical", "pos": [51, 61]}, {"entity": "valine", "entity_type": "Chemical", "pos": [64, 70]}], "task": "NER"}
{"text": "Using a combination of hydrogen / deuterium exchange coupled to NMR spectroscopy , hydroxyl radical probing detected by mass spectrometry , and site - directed mutagenesis , we demonstrate that stop mutants of the human prion protein have a conserved amyloid core .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "deuterium", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "The 129 residue is deeply buried in the amyloid core structure , and its mutation strongly impacts aggregation .", "entity": [], "task": "NER"}
{"text": "Taken together the data support a critical role of the polymorphic residue 129 of the human prion protein in aggregation and disease .", "entity": [], "task": "NER"}
{"text": "Bioresorbable surface - adhered enzymatic microreactors based on physical hydrogels of poly ( vinyl alcohol ) .", "entity": [{"entity": "poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [87, 109]}], "task": "NER"}
{"text": "Hydrogel biomaterials based on poly ( vinyl alcohol ) , PVA , have an extensive history of biomedical applications , yet in their current form suffer from significant shortcomings , such as a lack of mechanism of biodegradation and poor opportunities in controlled drug release .", "entity": [{"entity": "poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [31, 53]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "We investigate physical hydrogels of PVA as surface - adhered materials and present biodegradable matrices equipped with innovative tools in substrate - mediated drug release .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [37, 40]}], "task": "NER"}
{"text": "Toward the final goal , PVA chains with narrow polydispersities ( 1 . 1 - 1 . 2 ) and molecular weights of 5 , 10 , and 28 kDa are synthesized via controlled radical polymerization ( RAFT ) .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [24, 27]}], "task": "NER"}
{"text": "These molecular weights are shown to be suitably high to afford robust hydrogel matrices and at the same time suitably low to allow gradual erosion of the hydrogels with kinetics of degradation controlled via polymer macromolecular characteristics .", "entity": [], "task": "NER"}
{"text": "For opportunities in controlled drug release , hydrogels are equipped with enzymatic cargo to achieve an in situ conversion of externally added prodrug into a final product , thus giving rise to surface - adhered enzymatic microreactors .", "entity": [], "task": "NER"}
{"text": "Hydrogel - mediated enzymatic activity was investigated as a function of polymer molecular weight and concentration of solution taken for assembly of hydrogels .", "entity": [], "task": "NER"}
{"text": "Taken together , we present , to the best of our knowledge , the first example of bioresorbable physical hydrogel based on PVA with engineered opportunities in substrate - mediated enzymatic activity and envisioned utility in surface - mediated drug delivery and tissue engineering .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "Catechol - initiated polyethers : multifunctional hydrophilic ligands for PEGylation and functionalization of metal oxide nanoparticles .", "entity": [{"entity": "Catechol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "polyethers", "entity_type": "Chemical", "pos": [21, 31]}, {"entity": "metal oxide", "entity_type": "Chemical", "pos": [110, 121]}], "task": "NER"}
{"text": "Bifunctional CA - PEG ( catechol - poly ( ethylene glycol ) ) and multifunctional CA - PEG - PGA / PEVGE ( poly ( glycidyl amine ) / poly ( ethylene glycol vinyl glycidyl ether ) ) ligands for the functionalization and solubilization of nanoparticles are introduced .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "catechol", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [35, 59]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "PGA", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "PEVGE", "entity_type": "Chemical", "pos": [99, 104]}, {"entity": "poly ( glycidyl amine )", "entity_type": "Chemical", "pos": [107, 130]}, {"entity": "poly ( ethylene glycol vinyl glycidyl ether )", "entity_type": "Chemical", "pos": [133, 178]}], "task": "NER"}
{"text": "Tunable polymers with polydispersities < 1 . 25 and molecular weights in the range 500 - 7700 g mol ( - 1 ) containing a catechol moiety for conjugation to metal oxide nanoparticles were prepared .", "entity": [{"entity": "catechol", "entity_type": "Chemical", "pos": [121, 129]}, {"entity": "metal oxide", "entity_type": "Chemical", "pos": [156, 167]}], "task": "NER"}
{"text": "The functional PEG ligands were synthesized starting from the acetonide - protected catechol initiator 2 , 2 - dimethyl - 1 , 3 - benzodioxole - 5 - propanol ( CA - OH ) for oxyanionic polymerization .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "acetonide", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "catechol", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "2 , 2 - dimethyl - 1 , 3 - benzodioxole - 5 - propanol", "entity_type": "Chemical", "pos": [103, 157]}, {"entity": "OH", "entity_type": "Chemical", "pos": [165, 167]}], "task": "NER"}
{"text": "CA - OH was used both for homopolymerization of ethylene oxide ( EO ) as well as copolymerization with functional epoxides N , N - diallyl glycidyl amine ( DAGA ) , releasing primary amino groups and ethylene glycol vinyl glycidyl ether ( EVGE ) , exhibiting a double bond for click - type reactions , to generate CA - PEG and CA - PEG - PGA / PEVGE .", "entity": [{"entity": "OH", "entity_type": "Chemical", "pos": [5, 7]}, {"entity": "ethylene oxide", "entity_type": "Chemical", "pos": [48, 62]}, {"entity": "epoxides", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "N , N - diallyl glycidyl amine", "entity_type": "Chemical", "pos": [123, 153]}, {"entity": "DAGA", "entity_type": "Chemical", "pos": [156, 160]}, {"entity": "primary amino", "entity_type": "Chemical", "pos": [175, 188]}, {"entity": "ethylene glycol vinyl glycidyl ether", "entity_type": "Chemical", "pos": [200, 236]}, {"entity": "EVGE", "entity_type": "Chemical", "pos": [239, 243]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [319, 322]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [332, 335]}, {"entity": "PGA", "entity_type": "Chemical", "pos": [338, 341]}, {"entity": "PEVGE", "entity_type": "Chemical", "pos": [344, 349]}], "task": "NER"}
{"text": "We demonstrate the potential of the functional ligands by binding to MnO nanoparticles , rendering the PEGylated nanoparticles highly stable in aqueous environment .", "entity": [{"entity": "MnO", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "Furthermore , addressability of the functional groups has been proven , for example , by coupling with fluoresceine isothiocyanate ( FITC ) , to allow for optical monitoring of the nanoparticle fate in biological systems .", "entity": [{"entity": "fluoresceine isothiocyanate", "entity_type": "Chemical", "pos": [103, 130]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "New chemotherapeutic strategies against malaria , leishmaniasis and trypanosomiases .", "entity": [], "task": "NER"}
{"text": "Due to the persistent lack of suitable vaccines , chemotherapy remains the only option for the treatment of patients infected by protozoan parasites .", "entity": [], "task": "NER"}
{"text": "However , most available antiparasitic drugs have serious disadvantages , ranging from high cost and poor compliance to high toxicity and rapid induction of resistance .", "entity": [], "task": "NER"}
{"text": "In recent decades basic research laboratories identified a considerable number of promising new molecules , but their development has not been pursued in depth by pharmaceutical firms because of poor prospects of economic return .", "entity": [], "task": "NER"}
{"text": "The establishment of adequately funded public - private partnerships is currently reversing the trend .", "entity": [], "task": "NER"}
{"text": "This review deals with new drugs against Plasmodium , Leishmania and Trypanosoma parasites , focusing on the molecules that are in the most advanced stage of development .", "entity": [], "task": "NER"}
{"text": "The purpose of this article is to provide the reader with a panoramic view of the updated literature on the challenges and strategies of contemporary antiprotozoal drug research , paying the due attention to the already published reviews .", "entity": [], "task": "NER"}
{"text": "New molecular and cellular targets for chemoprevention and treatment of skin tumors by plant polyphenols : a critical review .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "As the incidence of skin tumors has been steadily growing , there is an urgent need for the preventive measures as well as the improved therapeutic approaches .", "entity": [], "task": "NER"}
{"text": "In the last two decades , natural plant derived polyphenols ( PPs , resveratrol , silibinin , green tea polyphenols , flavonoids , anthocyanins , etc . ) have been drawing particular interest as emerging active substances in dermatological / cosmeceutical compositions for the prevention , slowing , or reversion of skin tumorigenesis ( chemoprevention ) .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [68, 79]}, {"entity": "silibinin", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [104, 115]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [118, 128]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [131, 143]}], "task": "NER"}
{"text": "When chronically applied to the skin , they supposedly would not damage normal skin cells or negatively affect their functions while they would suppress tumorigenic cell transformation , inhibit tumor cell proliferation , and activate tumor cell apoptosis .", "entity": [], "task": "NER"}
{"text": "PPs are also reported to synergize with conventional anti - cancer therapies .", "entity": [], "task": "NER"}
{"text": "The major aim of this critical review is to provide recent updates on the molecular and cellular targets for the prevention and therapy of skin tumors with a special focus on the crossroad between inflammation and carcinogenesis as the most promising approach to chemoprevention .", "entity": [], "task": "NER"}
{"text": "Novel therapeutic targets as different as epidermal stem cells , cellular senescence , epigenetic enzymes involved in carcinogenesis , epidermal growth factor and aryl hydrocarbon receptors , and metabolic CYP1 subfamily enzymes are highlighted .", "entity": [{"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [163, 179]}], "task": "NER"}
{"text": "The mechanisms of PPs interaction with these molecular and cellular targets are reviewed .", "entity": [], "task": "NER"}
{"text": "The feasibility of PPs to prevent / cure specific cutaneous toxicity connected to anti - EGFR therapy and to reduce multidrug resistance of skin tumors is also discussed .", "entity": [], "task": "NER"}
{"text": "Colchicine semisynthetics : chemotherapeutics for cancer ?", "entity": [{"entity": "Colchicine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Nitrogen - containing bioactive alkaloids of plant origin play a significant role in human health and medicine .", "entity": [{"entity": "Nitrogen", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Several semisynthetic antimitotic alkaloids are successful in anticancer drug development .", "entity": [], "task": "NER"}
{"text": "Gloriosa superba biosynthesizes substantial quantities of colchicine , a bioactive molecule for gout treatment .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "Colchicine also has antimitotic activity , preventing growth of cancer cells by interacting with microtubules , which could lead to the design of better cancer therapeutics .", "entity": [{"entity": "Colchicine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Further , several colchicine semisynthetics are less toxic than colchicine .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "colchicine", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "Research is being conducted on effective , less toxic colchicine semisynthetic formulations with potential drug delivery strategies directly targeting multiple solid cancers .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [54, 64]}], "task": "NER"}
{"text": "This article reviews the dynamic state of anticancer drug development from colchicine semisynthetics and natural colchicine production and briefly discusses colchicine biosynthesis .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [75, 85]}, {"entity": "colchicine", "entity_type": "Chemical", "pos": [113, 123]}, {"entity": "colchicine", "entity_type": "Chemical", "pos": [157, 167]}], "task": "NER"}
{"text": "Antimicrobial plant metabolites : structural diversity and mechanism of action .", "entity": [], "task": "NER"}
{"text": "Microbial infectious diseases continue to be one of the leading causes of morbidity and mortality .", "entity": [], "task": "NER"}
{"text": "It has been estimated that microbial species comprise about 60 % of the Earth ' s biomass .", "entity": [], "task": "NER"}
{"text": "This , together with the fact that their genetic , metabolic and physiological diversity is extraordinary , makes them a major threat to the health and development of populations across the world .", "entity": [], "task": "NER"}
{"text": "Widespread antibiotic resistance , the emergence of new pathogens in addition to the resurgence of old ones , and the lack of effective new therapeutics exacerbate the problems .", "entity": [], "task": "NER"}
{"text": "Thus , the need to discover and develop new antimicrobial agents is critical to improve mankind ' s future health .", "entity": [], "task": "NER"}
{"text": "Plant secondary metabolites ( PSMs ) offer particular promise in this sense .", "entity": [], "task": "NER"}
{"text": "Plant Kingdom could be considered a rich source of the most diverse structures ( e . g . there are more than 12 , 000 known alkaloids , more than 8 , 000 phenolic compounds and over 25 , 000 different terpenoids ) , many of which were proven to possess strong antimicrobial properties ( e . g . thymol , eurabienol , etc . ) .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [154, 162]}, {"entity": "terpenoids", "entity_type": "Chemical", "pos": [201, 211]}, {"entity": "thymol", "entity_type": "Chemical", "pos": [295, 301]}, {"entity": "eurabienol", "entity_type": "Chemical", "pos": [304, 314]}], "task": "NER"}
{"text": "In many instances , PSMs can be easily isolated from the plant matrix , either in pure state or in the form of mixtures of chemically related compounds .", "entity": [], "task": "NER"}
{"text": "What is also important is that the development of bacterial resistance toward natural plant products ( that are generally regarded as eco - friendly ) has been thus far documented in a very limited number of cases ( e . g . for reserpine ) .", "entity": [{"entity": "reserpine", "entity_type": "Chemical", "pos": [228, 237]}], "task": "NER"}
{"text": "Having all of the mentioned advantages of PSMs as potential antimicrobials in mind , a major question arises : why is it that there are still no commercially available or commonly used antibiotics of plant origin ?", "entity": [], "task": "NER"}
{"text": "This review tries to give a critical answer to this question by considering potential mechanisms of antimicrobial action of PSMs ( inhibition of cell wall or protein synthesis , inducing leakage from the cells by tampering with the function of the membranes , interfering with intermediary metabolisms or DNA / RNA synthesis / function ) , as well as their physical and chemical properties ( e . g . hydrophilicity / lipophilicity , chemical stability ) .", "entity": [], "task": "NER"}
{"text": "To address the possible synergistic / antagonistic effects between PSMs and with standard antibiotics , special attention has been given to the antimicrobial activity of PSM - mixtures ( e . g . essential oils , plant extracts ) .", "entity": [], "task": "NER"}
{"text": "Moreover , possible ways of overcoming some of PSMs molecular limitations in respect to their usage as potential antibiotics were also discussed ( e . g . derivatization that would enable fine tuning of certain molecular characteristics ) .", "entity": [], "task": "NER"}
{"text": "From traditional European medicine to discovery of new drug candidates for the treatment of dementia and Alzheimer ' s disease : acetylcholinesterase inhibitors .", "entity": [], "task": "NER"}
{"text": "The leading Alzheimer ' s disease ( AD ) therapeutics to date involves inhibitors of acetylcholinesterase ( AChE ) , which should , in principle , elevate cholinergic signaling and limit inflammation .", "entity": [], "task": "NER"}
{"text": "In spite of the effectiveness in 20 % - 30 % of AD patients , more attention has been paid to find new anti - AChE agents from medicinal plants .", "entity": [], "task": "NER"}
{"text": "Galanthamine , contained in the bulbs and flowers of Galanthus and related genera like Narcissus , represents a good example .", "entity": [{"entity": "Galanthamine", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "The aim of this study is to review the role of possible AChE inhibitors ( AChEI ) present in plants traditionally used in European medicine for improving memory .", "entity": [], "task": "NER"}
{"text": "Starting from Galanthamine , properties of Melissa species , Salvia officinalis , Arnica chamissonis and Ruta graveolens are discussed to point to the role of these plants as potential sources for the development of therapeutic agents for AD .", "entity": [{"entity": "Galanthamine", "entity_type": "Chemical", "pos": [14, 26]}], "task": "NER"}
{"text": "Preclinical profile of bacopasides from Bacopa monnieri ( BM ) as an emerging class of therapeutics for management of chronic pains .", "entity": [{"entity": "bacopasides", "entity_type": "Chemical", "pos": [23, 34]}], "task": "NER"}
{"text": "Chronic pains management costs billions of dollars in medical exchequer to the world population .", "entity": [], "task": "NER"}
{"text": "Additionally , 77 % of people with chronic pains also have a degree of medically treatable depression .", "entity": [], "task": "NER"}
{"text": "Opioids have a narrower safety index due to their side effects associated with its tolerance , hyperalgesia and subsequent dependence .", "entity": [], "task": "NER"}
{"text": "Likewise , non steroidal anti - inflammatory drugs and anticonvulsants , also have limited safety and tolerability profile in the management of chronic pains .", "entity": [{"entity": "steroidal", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "Bacopa monnieri , a renowned ayurvedic medicine has a strong antidepressant effect and significant antinociceptive effect , which is comparable to the effect of morphine via adenosinergic , opioidergic , and adrenergic mechanisms .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [161, 169]}], "task": "NER"}
{"text": "BM has been also reported to be effective in neuropathic pains .", "entity": [], "task": "NER"}
{"text": "Additionally , it has a strong anti - inflammatory effect mediated via COX - 2 inhibitory mechanism .", "entity": [], "task": "NER"}
{"text": "Apart from its effect of augmenting morphine analgesia , BM also inhibits opioid - withdrawal induced hyperalgesia , and acquisition and expression of morphine tolerance .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "BM is reported to have a strong protective effect against toxic effects of opiates on major organs like brain , kidneys and heart .", "entity": [], "task": "NER"}
{"text": "BM is well documented to be safe and well tolerated herbal therapy in multiple clinical trials including various age groups .", "entity": [], "task": "NER"}
{"text": "This minireview evaluated the preclinical data that highlights potential of BM as a future candidate for clinical management of chronic pains .", "entity": [], "task": "NER"}
{"text": "Cantharidin as an antitumor agent : a retrospective review .", "entity": [{"entity": "Cantharidin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "This review summarizes the progress that has been made recently in the medicinal chemistry of cantharidin , a potent antitumor agent from traditional Chinese medicine .", "entity": [{"entity": "cantharidin", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "Thousands of analogs have been synthesized on the basis of cantharidin , a part of which shows excellent properties , in particular , norcantharidin and norcantharimide .", "entity": [{"entity": "cantharidin", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "norcantharidin", "entity_type": "Chemical", "pos": [134, 148]}, {"entity": "norcantharimide", "entity_type": "Chemical", "pos": [153, 168]}], "task": "NER"}
{"text": "Despite the enormous efforts made , the intriguing bioactivities , mechanism , indications , and their interplay are still ill - defined .", "entity": [], "task": "NER"}
{"text": "This review provides our up - to - date understanding in connection with the therapeutic use , mechanism , structure - activity relationship ( SAR ) and interesting properties of cantharidin analogs .", "entity": [{"entity": "cantharidin", "entity_type": "Chemical", "pos": [179, 190]}], "task": "NER"}
{"text": "Considerable development in the design of cantharidin analogs , in combination with mechanistic studies , has laid a foundation for transforming novel antitumor drugs into the clinic .", "entity": [{"entity": "cantharidin", "entity_type": "Chemical", "pos": [42, 53]}], "task": "NER"}
{"text": "Metabolomics analysis for biomarker discovery : advances and challenges .", "entity": [], "task": "NER"}
{"text": "Over the last decades there has been a change in biomedical research with the search for single genes , transcripts , proteins , or metabolites being substituted by the coverage of the entire genome , transcriptome , proteome , and metabolome with the \" omics \" approaches .", "entity": [], "task": "NER"}
{"text": "The emergence of metabolomics , defined as the comprehensive analysis of all metabolites in a system , is still recent compared to other \" omics \" fields , but its particular features and the improvement of both analytical techniques and pattern recognition methods has contributed greatly to its increasingly use .", "entity": [], "task": "NER"}
{"text": "The feasibility of metabolomics for biomarker discovery is supported by the assumption that metabolites are important players in biological systems and that diseases cause disruption of biochemical pathways , which are not new concepts .", "entity": [], "task": "NER"}
{"text": "In fact , metabolomics , meaning the parallel assessment of multiple metabolites , has been shown to have benefits in various clinical areas .", "entity": [], "task": "NER"}
{"text": "Compared to classical diagnostic approaches and conventional clinical biomarkers , metabolomics offers potential advantages in sensitivity and specificity .", "entity": [], "task": "NER"}
{"text": "Despite its potential , metabolomics still retains several intrinsic limitations which have a great impact on its widespread implementation - these limitations in biological and experimental measurements .", "entity": [], "task": "NER"}
{"text": "This review will provide an insight to the characteristics , strengths , limitations , and recent advances in metabolomics , always keeping in mind its potential application in clinical / health areas as a biomarker discovery tool .", "entity": [], "task": "NER"}
{"text": "Confined synthesis and integration of functional materials in sub - nanoliter volumes .", "entity": [], "task": "NER"}
{"text": "We present a novel microchip - based approach to combine the synthesis , characterization , and utilization of different functional materials on a single platform .", "entity": [], "task": "NER"}
{"text": "A two - layer microfluidic device comprising 10 parallel actuated reaction chambers with volumes of a few hundred picoliters is used to localize and confine the synthesis , while the surfaces of the reaction chambers comprise an electrode array for direct integration and further characterization of the created crystalline assemblies without the need for further manipulation or positioning devices .", "entity": [], "task": "NER"}
{"text": "First we visualized and evaluated the dynamics of our method by monitoring the formation of a fluorescent metal - organic complex ( Zn ( bix ) ) .", "entity": [{"entity": "Zn ( bix )", "entity_type": "Chemical", "pos": [132, 142]}], "task": "NER"}
{"text": "Next , we induced the site - specific growth of two types of organic conductive crystals , AuTTF and AgTCNQ , directly onto the electrode arrays in one - and two - step reactions , respectively .", "entity": [{"entity": "AuTTF", "entity_type": "Chemical", "pos": [91, 96]}, {"entity": "AgTCNQ", "entity_type": "Chemical", "pos": [101, 107]}], "task": "NER"}
{"text": "The performance of the created AgTCNQ crystals as memory elements was thoroughly examined .", "entity": [{"entity": "AgTCNQ", "entity_type": "Chemical", "pos": [31, 37]}], "task": "NER"}
{"text": "Moreover , we proved for first time that AuTTF composites can be used as label - free sensing elements .", "entity": [{"entity": "AuTTF", "entity_type": "Chemical", "pos": [41, 46]}], "task": "NER"}
{"text": "Pharmacological characterization of 1 - nitrosocyclohexyl acetate , a long - acting nitroxyl donor that shows vasorelaxant and antiaggregatory effects .", "entity": [{"entity": "1 - nitrosocyclohexyl acetate", "entity_type": "Chemical", "pos": [36, 65]}, {"entity": "nitroxyl", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "Nitroxyl ( HNO ) donors have potential benefit in the treatment of heart failure and other cardiovascular diseases .", "entity": [{"entity": "Nitroxyl", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "HNO", "entity_type": "Chemical", "pos": [11, 14]}], "task": "NER"}
{"text": "1 - Nitrosocyclohexyl acetate ( NCA ) , a new HNO donor , in contrast to the classic HNO donors Angeli ' s salt and isopropylamine NONOate , predominantly releases HNO and has a longer half - life .", "entity": [{"entity": "1 - Nitrosocyclohexyl acetate", "entity_type": "Chemical", "pos": [0, 29]}, {"entity": "NCA", "entity_type": "Chemical", "pos": [32, 35]}, {"entity": "HNO", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "HNO", "entity_type": "Chemical", "pos": [85, 88]}, {"entity": "Angeli ' s salt", "entity_type": "Chemical", "pos": [96, 111]}, {"entity": "isopropylamine NONOate", "entity_type": "Chemical", "pos": [116, 138]}, {"entity": "HNO", "entity_type": "Chemical", "pos": [164, 167]}], "task": "NER"}
{"text": "This study investigated the vasodilatative properties of NCA in isolated aortic rings and human platelets and its mechanism of action .", "entity": [{"entity": "NCA", "entity_type": "Chemical", "pos": [57, 60]}], "task": "NER"}
{"text": "NCA was applied on aortic rings isolated from wild - type mice and apolipoprotein E - deficient mice and in endothelial - denuded aortae .", "entity": [{"entity": "NCA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The mechanism of action of HNO was examined by applying NCA in the absence and presence of the HNO scavenger glutathione ( GSH ) and inhibitors of soluble guanylyl cyclase ( sGC ) , adenylyl cyclase ( AC ) , calcitonin gene - related peptide receptor ( CGRP ) , and K ( + ) channels .", "entity": [{"entity": "HNO", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "NCA", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "HNO", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [123, 126]}, {"entity": "guanylyl", "entity_type": "Chemical", "pos": [155, 163]}, {"entity": "adenylyl", "entity_type": "Chemical", "pos": [182, 190]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [266, 273]}], "task": "NER"}
{"text": "NCA induced a concentration - dependent relaxation ( EC ( 50 ) , 4 . 4 micro M ) .", "entity": [{"entity": "NCA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "This response did not differ between all groups , indicating an endothelium - independent relaxation effect .", "entity": [], "task": "NER"}
{"text": "The concentration - response was markedly decreased in the presence of excess GSH ; the nitric oxide scavenger 2 - ( 4 - carboxyphenyl ) - 4 , 4 , 5 , 5 - tetramethylimidazoline - 1 - oxyl - 3 - oxide had no effect .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [88, 100]}, {"entity": "2 - ( 4 - carboxyphenyl ) - 4 , 4 , 5 , 5 - tetramethylimidazoline - 1 - oxyl - 3 - oxide", "entity_type": "Chemical", "pos": [111, 200]}], "task": "NER"}
{"text": "Inhibitors of sGC , CGRP , and voltage - dependent K ( + ) channels each significantly impaired the vasodilator response to NCA .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [51, 58]}, {"entity": "NCA", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "In contrast , inhibitors of AC , ATP - sensitive K ( + ) channels , or high - conductance Ca ( 2 + ) - activated K ( + ) channels did not change the effects of NCA .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [90, 100]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [113, 120]}, {"entity": "NCA", "entity_type": "Chemical", "pos": [160, 163]}], "task": "NER"}
{"text": "NCA significantly reduced contractile response and platelet aggregation mediated by the thromboxane A ( 2 ) mimetic 9 , 11 - dideoxy - 11 alpha , 9 alpha - epoxymethanoprostaglandin F ( 2 ) ( alpha ) in a cGMP - dependent manner .", "entity": [{"entity": "NCA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "thromboxane A ( 2 )", "entity_type": "Chemical", "pos": [88, 107]}, {"entity": "9 , 11 - dideoxy - 11 alpha , 9 alpha - epoxymethanoprostaglandin F ( 2 ) ( alpha )", "entity_type": "Chemical", "pos": [116, 199]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [205, 209]}], "task": "NER"}
{"text": "In summary , NCA shows vasoprotective effects and may have a promising profile as a therapeutic agent in vascular dysfunction , warranting further evaluation .", "entity": [{"entity": "NCA", "entity_type": "Chemical", "pos": [13, 16]}], "task": "NER"}
{"text": "Liver X Receptors and female reproduction : when cholesterol meets fertility !", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "The role of cholesterol in female reproductive physiology has been suspected for a long time , while the molecular bases were unknown .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Cholesterol is the precursor of ovarian steroid biosynthesis and is also essential for fertility .", "entity": [{"entity": "Cholesterol", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [40, 47]}], "task": "NER"}
{"text": "In the uterus , cholesterol is essential to achieve correct contractions at term , but an excessive uterine cholesterol concentration has been associated with contractility defects .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [108, 119]}], "task": "NER"}
{"text": "Liver X Receptor ( LXR ) alpha and LXR beta are nuclear receptors activated by oxysterols , oxidized derivatives of cholesterol .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [116, 127]}], "task": "NER"}
{"text": "Since their discovery , the role of LXR in the control of cholesterol homeostasis has been widely described .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "Beyond their cholesterol - lowering role , more recent data have linked these nuclear receptors to various physiological processes .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [13, 24]}], "task": "NER"}
{"text": "In particular , they control ovarian endocrine and exocrine functions , as well as uterine contractility .", "entity": [], "task": "NER"}
{"text": "Their contribution to female reproductive cancers will also be discussed .", "entity": [], "task": "NER"}
{"text": "This review will try to enlighten on the LXR as a molecular link between dietary cholesterol and reproductive diseases in women .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [81, 92]}], "task": "NER"}
{"text": "In the future , a better comprehension of the various physiological processes regulated by the LXR will help to develop new ligands to prevent or to cure these pathologies in women .", "entity": [], "task": "NER"}
{"text": "Studies on the bioactivity of aqueous extract of pu - erh tea and its fractions : in vitro antioxidant activity and alpha - glycosidase inhibitory property , and their effect on postprandial hyperglycemia in diabetic mice .", "entity": [], "task": "NER"}
{"text": "Despite abundant research that has been carried out on the potential health benefits of pu - erh tea , no consensus till now , has been reached on which constituent is mainly responsible for its bioactivity .", "entity": [], "task": "NER"}
{"text": "In this work , the aqueous extract ( AE ) and its fraction enriched with active constituents were prepared from pu - erh tea , and their bioactivities were investigated .", "entity": [], "task": "NER"}
{"text": "It was found that tea polyphenols ( TP ) , tea polysaccharides ( TPS ) , caffeine ( Caf ) , protein ( Pro ) , amino acids ( AA ) were accumulated in several fractions after solvent extraction despite not being separated completely .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [22, 33]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [73, 81]}, {"entity": "Caf", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [110, 121]}], "task": "NER"}
{"text": "Meanwhile , 95 % ethanol precipitate ( EP ) and ethyl acetate fraction ( EF ) possessed remarkable antioxidant activity and potent inhibitory effects against alpha - glycosidase in vitro .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [48, 61]}], "task": "NER"}
{"text": "Furthermore , all the extracts ( 50 mg / kg BW ) showed a significant ( p < 0 . 05 ) effect on postprandial hyperglycemia in diabetic mice as compared with a model group , and the suppression of EP was not significantly ( p > 0 . 05 ) different from that of acarbose at the same dosage ( 50 mg / kg BW ) , which indicate that these fractions could be developed as potential anti - diabetic agents .", "entity": [{"entity": "acarbose", "entity_type": "Chemical", "pos": [258, 266]}], "task": "NER"}
{"text": "beta - catenin regulates GnRH - induced FSH beta gene expression .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [25, 29]}], "task": "NER"}
{"text": "The regulation of gonadotropin synthesis by GnRH plays an essential role in the neuroendocrine control of reproduction .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "The known signaling mechanisms involved in gonadotropin synthesis have been expanding .", "entity": [], "task": "NER"}
{"text": "For example , involvement of beta - catenin in LH beta induction by GnRH has been discovered .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "We examined the role of beta - catenin in FSH beta gene expression in L beta T2 gonadotrope cells .", "entity": [], "task": "NER"}
{"text": "GnRH caused a sustained increase in nuclear beta - catenin levels , which was significantly reduced by c - Jun N - terminal kinase ( JNK ) inhibition .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "N", "entity_type": "Chemical", "pos": [111, 112]}], "task": "NER"}
{"text": "Small interfering RNA - mediated knockdown of beta - catenin mRNA demonstrated that induction of FSH beta mRNA by GnRH depended on beta - catenin and that regulation of FSH beta by beta - catenin occurred independently of the JNK - c - jun pathway .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [114, 118]}], "task": "NER"}
{"text": "beta - Catenin depletion had no impact on FSH beta mRNA stability .", "entity": [], "task": "NER"}
{"text": "In L beta T2 cells transfected with FSH beta promoter luciferase fusion constructs , GnRH responsiveness was conferred by the proximal promoter ( - 944 / - 1 ) and was markedly decreased by beta - catenin knockdown .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [85, 89]}], "task": "NER"}
{"text": "However , none of the T - cell factor / lymphoid enhancer factor binding sites in that region were required for promoter activation by GnRH .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "Chromatin immunoprecipitation further corroborated the absence of direct interaction between beta - catenin and the 1 . 8 - kb FSH beta promoter .", "entity": [], "task": "NER"}
{"text": "To elucidate the mechanism for the beta - catenin effect , we analyzed approximately 1 billion reads of next - generation RNA sequencing beta - catenin knockdown assays and selected the nuclear cofactor breast cancer metastasis - suppressor 1 - like ( Brms1L ) as one candidate for further study .", "entity": [], "task": "NER"}
{"text": "Subsequent experiments confirmed that Brms1L mRNA expression was decreased by beta - catenin knockdown as well as by JNK inhibition .", "entity": [], "task": "NER"}
{"text": "Furthermore , knockdown of Brms1L significantly attenuated GnRH - induced FSH beta expression .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [59, 63]}], "task": "NER"}
{"text": "Thus , our findings indicate that the expression of Brms1L depends on beta - catenin activity and contributes to FSH beta induction by GnRH .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "GATA2 - induced silencing and LIM - homeodomain protein - induced activation are mediated by a bi - functional response element in the rat GnRH receptor gene .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "GATA2 transcription factor and LIM homeodomain proteins Islet1 ( ISL1 ) and LIM homeobox 3 ( LHX3 ) are suspected to be involved in gonadotrope cell fate and maintenance .", "entity": [], "task": "NER"}
{"text": "The GnRH receptor gene ( Gnrhr ) , crucial for gonadotrope function , is expressed in the pituitary gland from embryonic day 13 . 5 onward , well before LH and FSH beta - subunits .", "entity": [{"entity": "GnRH", "entity_type": "Chemical", "pos": [4, 8]}], "task": "NER"}
{"text": "This expression pattern together with the presence of WGATAR and TAAT motifs in Gnrhr promoter sequences suggests the involvement of early transcription factors in promoter activation .", "entity": [], "task": "NER"}
{"text": "In this study , using a well - characterized transgenic mouse model , GATA2 was found colocalized with Gnrhr promoter activity in the pituitary .", "entity": [], "task": "NER"}
{"text": "Transient transfection of Gnrhr promoter luciferase fusion constructs together with either GATA2 expression vectors or small interfering RNA in gonadotrope cell lines indicated that GATA2 , which typically acts as a trans - activator , unexpectedly repressed Gnrhr promoter activity .", "entity": [], "task": "NER"}
{"text": "Using DNA chromatography affinity and EMSA , we demonstrated that GATA2 operates via a response element containing a peculiar palindromic GATA motif that overlaps a critical TAAT motif involved in LHX3 / ISL1 trans - activation .", "entity": [], "task": "NER"}
{"text": "Indeed , despite the inhibitory action of GATA2 , this element displayed a clear - cut enhancer activity in gonadotrope cells .", "entity": [], "task": "NER"}
{"text": "Chromatin immunoprecipitation assays indicated that GATA2 , LHX3 , and ISL1 interact with a Gnrhr promoter fragment encompassing this element .", "entity": [], "task": "NER"}
{"text": "The trans - repressive action of GATA2 on Gnrhr promoter activity is likely balanced or even hindered by trans - activating effects of LIM homeodomain proteins via this novel bifunctional LIM / GATA response element .", "entity": [], "task": "NER"}
{"text": "Such a hierarchical interplay may contribute to finely adjust Gnrhr gene expression in gonadotrope cell lineage during pituitary development as well as in the adult animal .", "entity": [], "task": "NER"}
{"text": "Halting metastasis through CXCR4 inhibition .", "entity": [], "task": "NER"}
{"text": "Metastasis occurs when cancer cells leave the primary tumor site and migrate to distant parts of the body .", "entity": [], "task": "NER"}
{"text": "The CXCR4 - SDF - 1 pathway facilitates this migration , and its expression has become the hallmark of several metastatic cancers .", "entity": [], "task": "NER"}
{"text": "Targeted approaches are currently being developed to inhibit this pathway , and several candidates are now in clinical trials .", "entity": [], "task": "NER"}
{"text": "Continued exploration of CXCR4 inhibitors will generate compounds that have improved activity over current candidates .", "entity": [], "task": "NER"}
{"text": "l - DOPA modifies the antidepressant - like effects of reboxetine and fluoxetine in rats .", "entity": [{"entity": "l - DOPA", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "reboxetine", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "fluoxetine", "entity_type": "Chemical", "pos": [70, 80]}], "task": "NER"}
{"text": "Nowadays the most widely used antidepressants are selective serotonin reuptake inhibitors ( SSRI ) or noradrenaline reuptake inhibitors ( NRI ) , however , these take four to eight weeks to exert their effects and each drug is efficacious only in 60 - 70 % of patients .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "noradrenaline", "entity_type": "Chemical", "pos": [102, 115]}], "task": "NER"}
{"text": "In an attempt to improve the efficacy of antidepressants , new drugs that also modify dopamine levels are being developed .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [86, 94]}], "task": "NER"}
{"text": "The aim of this study was to investigate the impact of l - DOPA administration on the effect elicited by antidepressants on serotonergic and noradrenergic neurotransmission .", "entity": [{"entity": "l - DOPA", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "To this end , single - unit extracellular recordings of the noradrenergic nucleus , locus coeruleus ( LC ) , and the serotonergic nucleus , dorsal raphe ( DRN ) combined with behavioural approaches were performed .", "entity": [], "task": "NER"}
{"text": "l - DOPA did not modify the basal neuronal activity in either the LC or the DRN or induce any change in the modified forced swimming test .", "entity": [{"entity": "l - DOPA", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "However , l - DOPA enhanced the neuronal response to reboxetine in the LC and increased its antidepressant - like effects but counteracted the effect of fluoxetine on neurons in the LC and decreased its antidepressant - like effect .", "entity": [{"entity": "l - DOPA", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "reboxetine", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "fluoxetine", "entity_type": "Chemical", "pos": [153, 163]}], "task": "NER"}
{"text": "The sensitivity of neurons in the DRN to reboxetine and fluoxetine was not altered by the administration of l - DOPA .", "entity": [{"entity": "reboxetine", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "fluoxetine", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "l - DOPA", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "Taken together , these results indicate that l - DOPA modifies the effect of SSRI and NRI antidepressants in opposing ways .", "entity": [{"entity": "l - DOPA", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "Prospects for treatment of latent HIV .", "entity": [], "task": "NER"}
{"text": "Recent advances in antiretroviral therapy ( ART ) have drastically improved the quality of life for people with HIV infection .", "entity": [], "task": "NER"}
{"text": "However , owing to the persistence of latent HIV in the presence of therapy , patients must remain on therapy indefinitely .", "entity": [], "task": "NER"}
{"text": "Currently , the solution to the HIV pandemic rests on the prevention of new infections and many decades of ART for the steadily expanding number of people infected worldwide .", "entity": [], "task": "NER"}
{"text": "ART is costly , requires ongoing medical care , and can have side effects , thereby preventing its universal availability .", "entity": [], "task": "NER"}
{"text": "Therefore , to escape the ironic burdens of therapy , efforts have begun to develop treatments for latent HIV infection .", "entity": [], "task": "NER"}
{"text": "Current approaches propose either complete eradication of infection or induction of a state of stringent control over viral replication without ART .", "entity": [], "task": "NER"}
{"text": "This review will discuss these strategies in detail and their potential for clinical development .", "entity": [], "task": "NER"}
{"text": "Emerging target - based paradigms to prevent and treat migraine .", "entity": [], "task": "NER"}
{"text": "Migraine is a primary brain disorder resulting from altered modulation of normal sensory stimuli and trigeminal nerve dysfunction .", "entity": [], "task": "NER"}
{"text": "The second edition of the International Classification of Headache Disorders ( ICHD - 2 ) defines seven subtypes of migraine .", "entity": [], "task": "NER"}
{"text": "Migraine treatment can be acute or preventive .", "entity": [], "task": "NER"}
{"text": "New targeted therapies include 5 - HT ( 1F ) receptor agonists , calcitonin gene - related peptide ( CGRP ) antagonists , nitric oxide synthetase inhibitors , and ion channel antagonists .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [122, 134]}], "task": "NER"}
{"text": "A recent development is the creation of antibodies to CGRP and its receptor for migraine prevention .", "entity": [], "task": "NER"}
{"text": "Evolving approaches of hematopoietic stem cell - based therapies to induce tolerance to organ transplants : the long road to tolerance .", "entity": [], "task": "NER"}
{"text": "The immunoregulatory properties of hematopoietic stem cells ( HSCs ) have been recognized for more than 60 years , beginning in 1945 , when Owen reported that genetically disparate freemartin cattle sharing a common placenta were red blood cell chimeras .", "entity": [], "task": "NER"}
{"text": "In 1953 , Billingham , Brent , and Medawar demonstrated that murine neonatal chimeras prepared by infusion of donor - derived hematopoietic cells exhibited donor - specific tolerance to skin allografts .", "entity": [], "task": "NER"}
{"text": "Various approaches using HSCs in organ transplantation have gradually brought closer to reality the dream of inducing donor - specific tolerance in organ transplant recipients .", "entity": [], "task": "NER"}
{"text": "Several hurdles needed to be overcome , especially the risk of graft - versus - host disease ( GVHD ) , the toxicity of ablative conditioning , and the need for close donor - recipient matching .", "entity": [], "task": "NER"}
{"text": "For wide acceptance , HSC therapy must be safe and reproducible in mismatched donor - recipient combinations .", "entity": [], "task": "NER"}
{"text": "Discoveries in other disciplines have often unexpectedly and synergistically contributed to progress in this area .", "entity": [], "task": "NER"}
{"text": "This review presents a historic perspective of the quest for tolerance in organ transplantation , highlighting current clinical approaches .", "entity": [], "task": "NER"}
{"text": "Impairment of novel object recognition in adulthood after neonatal exposure to diazinon .", "entity": [{"entity": "diazinon", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "Diazinon is an organophosphate pesticide that is still heavily used in agriculture , home gardening , and indoor pest control in Japan .", "entity": [{"entity": "Diazinon", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "organophosphate", "entity_type": "Chemical", "pos": [15, 30]}], "task": "NER"}
{"text": "The present study investigated the effect of neonatal exposure to diazinon on hippocampus - dependent novel object recognition test performance and the expression of the N - methyl - D - aspartate ( NMDA ) receptor and its signal transduction pathway - related genes in the hippocampi of young adult and adult mice .", "entity": [{"entity": "diazinon", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [170, 196]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [199, 203]}], "task": "NER"}
{"text": "Male offspring of C3H / HeN mice were subcutaneously treated with 0 , 0 . 5 , or 5 mg / kg of diazinon for 4 consecutive days beginning on postnatal day ( PND ) 8 .", "entity": [{"entity": "diazinon", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "Beginning on PND 46 or PND 81 , a novel object recognition test was performed on 4 consecutive days .", "entity": [], "task": "NER"}
{"text": "The hippocampi were collected on PND 50 or PND 85 after the completion of the novel object recognition test , and the expression levels of neurotrophins and the NMDA receptor and its signal transduction pathway - related genes were examined using real - time RT - PCR .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [161, 165]}], "task": "NER"}
{"text": "Diazinon - injected mice exhibited a poor ability to discriminate between novel and familiar objects during both the PND 49 and the PND 84 tests .", "entity": [{"entity": "Diazinon", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The NMDA receptor subunits NR1 and NR2B and the related protein kinase calcium / calmodulin - dependent protein kinase ( CaMK ) - IV and the transcription factor cyclic AMP responsive element binding protein ( CREB ) - 1 mRNA levels were reduced in the PND 50 mice .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [4, 8]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [71, 78]}, {"entity": "cyclic AMP", "entity_type": "Chemical", "pos": [162, 172]}], "task": "NER"}
{"text": "However , no significant changes in the expressions of the NMDA subunits and their signal transduction molecules were observed in the hippocampi of the PND 85 mice .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [59, 63]}], "task": "NER"}
{"text": "The expression level of nerve growth factor mRNA was significantly reduced in the PND 50 or 85 mice .", "entity": [], "task": "NER"}
{"text": "These results indicate that neonatal diazinon exposure impaired the hippocampus - dependent novel object recognition ability , accompanied by a modulation in the expressions of the NMDA receptor and neurotrophin in young adult and adult mice .", "entity": [{"entity": "diazinon", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [181, 185]}], "task": "NER"}
{"text": "The role of native salinity regime on grass shrimp ( Palaemonetes pugio ) sensitivity to cadmium .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "In euryhaline crustaceans , sensitivity to toxic trace metals may be linked to osmoregulation and salinity conditions .", "entity": [], "task": "NER"}
{"text": "This study investigated if grass shrimp ( Palaemonetes pugio ) populations from different salinity regimes differed in sensitivity to cadmium ( Cd ) .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [134, 141]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [144, 146]}], "task": "NER"}
{"text": "Grass shrimp were collected in May 2011 from two marsh sites with average salinities of ~ 3 . 0 ppt and 24 . 0 ppt .", "entity": [], "task": "NER"}
{"text": "Groups were acclimated for 3 - 32 weeks in either their respective native salinity ( 3 . 0 ppt --> 3 . 0 ppt and 24 . 0 ppt --> 24 . 0 ppt ) , or the average of the salinities of the two collection sites ( 3 . 0 ppt --> 13 . 5 ppt and 24 . 0 ppt --> 13 . 5 ppt ) .", "entity": [], "task": "NER"}
{"text": "After acclimation , groups were exposed to equivalent free - ion Cd concentration ( 4 . 8 +/- 0 . 3 mg / L , Cd ( 2 + ) ) in their respective acclimated salinity to compare survival among salinity treatments .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [65, 67]}, {"entity": "Cd ( 2 + )", "entity_type": "Chemical", "pos": [109, 119]}], "task": "NER"}
{"text": "Results of Kaplan - Meier survival analysis indicated that 3 . 0 ppt --> 3 . 0 ppt shrimp were more sensitive to Cd ( 2 + ) than any other group ( p < 0 . 0001 ) .", "entity": [{"entity": "Cd ( 2 + )", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "Additionally , 3 . 0 ppt --> 13 . 5 ppt shrimp were less sensitive to Cd ( 2 + ) than were 24 . 0 ppt --> 13 . 5 ppt shrimp ( p = 0 . 0013 ) .", "entity": [{"entity": "Cd ( 2 + )", "entity_type": "Chemical", "pos": [70, 80]}], "task": "NER"}
{"text": "These results suggest that sensitivity of grass shrimp to Cd is dependent upon the salinity during exposure , and the salinity regime from which the tested population originated .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [58, 60]}], "task": "NER"}
{"text": "The implication is that toxicity studies and risk assessments using euryhaline crustaceans should consider the salinity of test population collection sites when interpreting and comparing results .", "entity": [], "task": "NER"}
{"text": "Enhancement of hepatic 4 - hydroxylation of 25 - hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo : Implications for drug - induced osteomalacia .", "entity": [{"entity": "25 - hydroxyvitamin D3", "entity_type": "Chemical", "pos": [44, 66]}], "task": "NER"}
{"text": "Long - term therapy with certain drugs , especially cytochrome P450 ( P450 ; CYP ) - inducing agents , confers an increased risk of osteomalacia that is attributed to vitamin D deficiency .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [167, 176]}], "task": "NER"}
{"text": "Human CYP24A1 , CYP3A4 , and CYP27B1 catalyze the inactivation and activation of vitamin D and have been implicated in the adverse drug response .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "In this study , the inducibility of these enzymes and monohydroxylation of 25 - hydroxyvitamin D3 ( 25OHD3 ) were evaluated after exposure to P450 - inducing drugs .", "entity": [{"entity": "25 - hydroxyvitamin D3", "entity_type": "Chemical", "pos": [75, 97]}, {"entity": "25OHD3", "entity_type": "Chemical", "pos": [100, 106]}], "task": "NER"}
{"text": "With human hepatocytes , treatment with phenobarbital , hyperforin , carbamazepine , and rifampin significantly increased the levels of CYP3A4 , but not CYP24A1 or CYP27B1 mRNA .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [40, 53]}, {"entity": "hyperforin", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "carbamazepine", "entity_type": "Chemical", "pos": [69, 82]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [89, 97]}], "task": "NER"}
{"text": "In addition , rifampin pretreatment resulted in an 8 - fold increase in formation of the major metabolite of 25OHD3 , 4 beta , 25 ( OH ) 2 D3 .", "entity": [{"entity": "rifampin", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "25OHD3", "entity_type": "Chemical", "pos": [109, 115]}, {"entity": "4 beta , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [118, 141]}], "task": "NER"}
{"text": "This inductive effect was blocked by the addition of 6 ' , 7 ' - dihydroxybergamottin , a selective CYP3A4 inhibitor .", "entity": [{"entity": "6 ' , 7 ' - dihydroxybergamottin", "entity_type": "Chemical", "pos": [53, 85]}], "task": "NER"}
{"text": "With human renal proximal tubular HK - 2 cells , treatment with the same inducers did not alter CYP3A4 , CYP24A1 , or CYP27B1 expression .", "entity": [], "task": "NER"}
{"text": "24R , 25 ( OH ) 2 D3 was the predominant monohydroxy metabolite produced from 25OHD3 , but its formation was unaffected by the inducers .", "entity": [{"entity": "24R , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "monohydroxy", "entity_type": "Chemical", "pos": [41, 52]}, {"entity": "25OHD3", "entity_type": "Chemical", "pos": [78, 84]}], "task": "NER"}
{"text": "With healthy volunteers , the mean plasma concentration of 4 beta , 25 ( OH ) 2 D3 was increased 60 % ( p < 0 . 01 ) after short - term rifampin administration .", "entity": [{"entity": "4 beta , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [59, 82]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "This was accompanied by a statistically significant reduction in plasma 1 alpha , 25 ( OH ) 2 D3 ( - 10 % ; p = 0 . 03 ) , and a nonsignificant change in 24R , 25 ( OH ) 2 D3 ( - 8 % ; p = 0 . 09 ) levels .", "entity": [{"entity": "1 alpha , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [72, 96]}, {"entity": "24R , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [154, 174]}], "task": "NER"}
{"text": "Further analysis revealed a negative correlation between the increase in 4 beta , 25 ( OH ) 2 D3 and decrease in 1 alpha , 25 ( OH ) 2 D3 levels .", "entity": [{"entity": "4 beta , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [73, 96]}, {"entity": "1 alpha , 25 ( OH ) 2 D3", "entity_type": "Chemical", "pos": [113, 137]}], "task": "NER"}
{"text": "Examination of the plasma monohydroxy metabolite / 25OHD3 ratios indicated selective induction of the CYP3A4 - dependent 4 beta - hydroxylation pathway of 25OHD3 elimination .", "entity": [{"entity": "monohydroxy", "entity_type": "Chemical", "pos": [26, 37]}, {"entity": "25OHD3", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "25OHD3", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "These results suggest that induction of hepatic CYP3A4 may be important in the etiology of drug - induced osteomalacia .", "entity": [], "task": "NER"}
{"text": "Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations .", "entity": [], "task": "NER"}
{"text": "Large - scale analysis of balanced chromosomal translocation breakpoints has shown nonhomologous end joining and microhomology - mediated repair to be the main drivers of interchromosomal structural aberrations .", "entity": [], "task": "NER"}
{"text": "Breakpoint sequences of de novo unbalanced translocations have not yet been investigated systematically .", "entity": [], "task": "NER"}
{"text": "We analyzed 12 de novo unbalanced translocations and mapped the breakpoints in nine .", "entity": [], "task": "NER"}
{"text": "Surprisingly , in contrast to balanced translocations , we identify nonallelic homologous recombination ( NAHR ) between ( retro ) transposable elements and especially long interspersed elements ( LINEs ) as the main mutational mechanism .", "entity": [], "task": "NER"}
{"text": "This finding shows yet another involvement of ( retro ) transposons in genomic rearrangements and exposes a profoundly different mutational mechanism compared with balanced chromosomal translocations .", "entity": [], "task": "NER"}
{"text": "Furthermore , we show the existence of compound maternal / paternal derivative chromosomes , reinforcing the hypothesis that human cleavage stage embryogenesis is a cradle of chromosomal rearrangements .", "entity": [], "task": "NER"}
{"text": "Bioengineered chimeric spider silk - uranium binding proteins .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [37, 44]}], "task": "NER"}
{"text": "Heavy metals constitute a source of environmental pollution .", "entity": [], "task": "NER"}
{"text": "Here , novel functional hybrid biomaterials for specific interactions with heavy metals are designed by bioengineering consensus sequence repeats from spider silk of Nephila clavipes with repeats of a uranium peptide recognition motif from a mutated 33 - residue of calmodulin protein from Paramecium tetraurelia .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [201, 208]}], "task": "NER"}
{"text": "The self - assembly features of the silk to control nanoscale organic / inorganic material interfaces provides new biomaterials for uranium recovery .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "With subsequent enzymatic digestion of the silk to concentrate the sequestered metals , options can be envisaged to use these new chimeric protein systems in environmental engineering , including to remediate environments contaminated by uranium .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [238, 245]}], "task": "NER"}
{"text": "Interparticle dispersion , membrane curvature , and penetration induced by single - walled carbon nanotubes wrapped with lipids and PEGylated lipids .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [91, 97]}], "task": "NER"}
{"text": "Single - walled carbon nanotubes ( SWNTs ) wrapped with different types of lipids and polyethylene glycol ( PEG ) - grafted lipids were simulated with lipid bilayers .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [86, 105]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Simulations were carried out with the previously parametrized coarse - grained ( CG ) SWNT and PEG force fields that had captured the experimentally observed conformations of self - assembled SWNT - lipid complexes and phase behavior of PEG - grafted lipids .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [237, 240]}], "task": "NER"}
{"text": "Simulations of multiple copies of the SWNT in water show that all pure SWNTs aggregate , lipid - wrapped SWNTs partially aggregate , but those wrapped with lipids grafted to PEG ( M ( w ) = 550 ) completely disperse , indicating the effect of short PEG chains on interparticle aggregation , in agreement with experiment .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [174, 177]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [249, 252]}], "task": "NER"}
{"text": "Starting with initial SWNT orientation parallel to the bilayer surface , SWNTs wrapped with lysophospholipids and PEG ( M ( w ) = 550 ) - grafted lipids insert into the hydrophobic region of the bilayer , while SWNTs wrapped with phospholipids and longer PEG ( M ( w ) = 2000 ) - grafted lipids do not .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [114, 117]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [255, 258]}], "task": "NER"}
{"text": "These indicate that SWNTs insert because of the hydrophobic interaction with the bilayer tails , but the tight wrapping of charged lipid headgroups and long hydrophilic PEG chains can weaken the hydrophobic interaction and inhibit SWNT insertion .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [169, 172]}], "task": "NER"}
{"text": "The inserted SWNTs contact the entire tails of neighboring lipids in one leaflet of the bilayer , which disorders the lipid bilayer and induces positive curvature .", "entity": [], "task": "NER"}
{"text": "Our findings indicate that interparticle aggregation , SWNT penetration , and membrane curvature can be modulated by the SWNT - lipid structure and the PEG length .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [152, 155]}], "task": "NER"}
{"text": "Radiosynthesis and evaluation of [ (1) (1) C - carbonyl ] - labeled carbamates as fatty acid amide hydrolase radiotracers for positron emission tomography .", "entity": [{"entity": "(1) (1) C - carbonyl", "entity_type": "Chemical", "pos": [35, 55]}, {"entity": "carbamates", "entity_type": "Chemical", "pos": [68, 78]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [82, 92]}, {"entity": "amide", "entity_type": "Chemical", "pos": [93, 98]}], "task": "NER"}
{"text": "Fatty acid amide hydrolase ( FAAH ) plays a key role in regulating the tone of the endocannabinoid system .", "entity": [{"entity": "Fatty acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "amide", "entity_type": "Chemical", "pos": [11, 16]}], "task": "NER"}
{"text": "Radiotracers are required to image and quantify FAAH activity in vivo .", "entity": [], "task": "NER"}
{"text": "We have synthesized a series of potent FAAH inhibitors encompassing two classes of N - alkyl - O - arylcarbamates and radiolabeled eight of them with carbon - 11 .", "entity": [{"entity": "N - alkyl - O - arylcarbamates", "entity_type": "Chemical", "pos": [83, 113]}, {"entity": "carbon - 11", "entity_type": "Chemical", "pos": [150, 161]}], "task": "NER"}
{"text": "The [ (1) (1) C - carbonyl ] - radiotracers were evaluated in vitro and ex vivo in rats as potential FAAH imaging agents for positron emission tomography ( PET ) .", "entity": [{"entity": "(1) (1) C - carbonyl", "entity_type": "Chemical", "pos": [6, 26]}], "task": "NER"}
{"text": "Both sets of [ (1) (1) C ] O - arylcarbamates showed good to excellent brain penetration and an appropriate regional distribution .", "entity": [{"entity": "[ (1) (1) C ] O - arylcarbamates", "entity_type": "Chemical", "pos": [13, 45]}], "task": "NER"}
{"text": "Pretreatments with a FAAH inhibitor demonstrated that 80 - 95 % of brain uptake of radioactivity constituted binding of the radiotracers to FAAH .", "entity": [], "task": "NER"}
{"text": "Brain extraction measurements showed that binding to FAAH was irreversible and kinetically different for the two classes of carbamates .", "entity": [{"entity": "carbamates", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "These promising results are discussed in terms of the requirements of a suitable radiotracer for the in vivo imaging of FAAH using PET .", "entity": [], "task": "NER"}
{"text": "Foams stabilized by multilamellar polyglycerol ester self - assemblies .", "entity": [{"entity": "polyglycerol ester", "entity_type": "Chemical", "pos": [34, 52]}], "task": "NER"}
{"text": "The importance of surfactant self - assemblies in foam stabilization is well - known .", "entity": [], "task": "NER"}
{"text": "The aim of the current study was to investigate the self - assemblies of the nonionic surfactant polyglycerol ester ( PGE ) in bulk solutions , at the interface and within foams , using a combined approach of small - angle neutron scattering , neutron reflectivity , and electron microscopy .", "entity": [{"entity": "polyglycerol ester", "entity_type": "Chemical", "pos": [97, 115]}, {"entity": "PGE", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "PGE bulk solutions contain vesicles as well as open lamellar structures .", "entity": [{"entity": "PGE", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Upon heating of the solutions the lamellar spacing increases , with significant differences in the presence of NaCl or CaCl ( 2 ) as compared to the standard solution .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [111, 115]}, {"entity": "CaCl ( 2 )", "entity_type": "Chemical", "pos": [119, 129]}], "task": "NER"}
{"text": "The adsorption of the multilamellar structures present in the bulk solutions lead to a multilayered film at the air - water interface .", "entity": [], "task": "NER"}
{"text": "The ordering within this film was increased as a result of a 20 % area compression mimicking a coalescence event .", "entity": [], "task": "NER"}
{"text": "Finally , PGE foams were shown to be stabilized not only by strong interfacial films but also by agglomerated self - assemblies within the interstitial areas of the foams .", "entity": [{"entity": "PGE", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "Analysis of 15N - 1H NMR relaxation in proteins by a combined experimental and molecular dynamics simulation approach : picosecond - nanosecond dynamics of the Rho GTPase binding domain of plexin - B1 in the dimeric state indicates allosteric pathways .", "entity": [{"entity": "15N", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "1H", "entity_type": "Chemical", "pos": [18, 20]}], "task": "NER"}
{"text": "We investigate picosecond - nanosecond dynamics of the Rho - GTPase Binding Domain ( RBD ) of plexin - B1 , which plays a key role in plexin - mediated cell signaling .", "entity": [], "task": "NER"}
{"text": "Backbone 15N relaxation data of the dimeric RBD are analyzed with the model - free ( MF ) method , and with the slowly relaxing local structure / molecular dynamics ( SRLS - MD ) approach .", "entity": [{"entity": "15N", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "Independent analysis of the MD trajectories , based on the MF paradigm , is also carried out .", "entity": [], "task": "NER"}
{"text": "MF is a widely popular and simple method , SRLS is a general approach , and SRLS - MD is an integrated approach we developed recently .", "entity": [], "task": "NER"}
{"text": "Corresponding parameters from the RBD dimer , a previously studied RBD monomer mutant , and the previously studied complex of the latter with the GTPase Rac1 , are compared .", "entity": [], "task": "NER"}
{"text": "The L2 , L3 , and L4 loops of the plexin - B1 RBD are involved in interactions with other plexin domains , GTPase binding , and RBD dimerization , respectively .", "entity": [], "task": "NER"}
{"text": "Peptide groups in the loops of both the monomeric and dimeric RBD are found to experience weak and moderately asymmetric local ordering centered approximately at the C ( i - 1 ) ( alpha ) - C ( i ) ( alpha ) axes , and nanosecond backbone motion .", "entity": [], "task": "NER"}
{"text": "Peptide groups in the alpha - helices and the beta - strands of the dimer ( the beta - strands of the monomer ) experience strong and highly asymmetric local ordering centered approximately at the C ( i - 1 ) ( alpha ) - C ( i ) ( alpha ) axes ( N - H bonds ) .", "entity": [{"entity": "N - H", "entity_type": "Chemical", "pos": [246, 251]}], "task": "NER"}
{"text": "N - H fluctuations occur on the picosecond time scale .", "entity": [{"entity": "N - H", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "An allosteric pathway for GTPase binding , providing new insights into plexin function , is delineated .", "entity": [], "task": "NER"}
{"text": "Surface - scribed transparency - based microplates .", "entity": [], "task": "NER"}
{"text": "Transparency sheets , which are normally associated with use on overhead projectors , offer lowered costs and high amenability for optical diagnostics in microplate instrumentation .", "entity": [], "task": "NER"}
{"text": "An alternative microplate design in which circles are scribed on the surface of the transparency to create the boundaries to hold the drop in place is investigated here .", "entity": [], "task": "NER"}
{"text": "The 3D profile of the scribed regions obtained optically showed strong likelihood of affecting three - phase contact line interactions .", "entity": [], "task": "NER"}
{"text": "During dispensation , the contact angle ( =~ 95 degrees ) was larger than the drop advancing state ( =~ 80 degrees ) due to a period of nonadhesion , where the contact angle later reduced to the drop advancing state followed by increase in the liquid area coverage on the substrate .", "entity": [], "task": "NER"}
{"text": "It was established that 50 mu L was needed to fill the well fully , and the maximum volume retainable before breaching was 190 mu L .", "entity": [], "task": "NER"}
{"text": "While the tilt angle needed for displacement reduced significantly from 50 to 95 mu L , this was markedly better than nonscribed surfaces , where tilt angles always had to be kept to within 30 degrees .", "entity": [], "task": "NER"}
{"text": "It was found that there was greater ability to fill the well with smaller volumes with dispensation at the center .", "entity": [], "task": "NER"}
{"text": "This was attributed to the growing contact line not meeting the scribed edge in parallel if liquid was dispensed closer to it , wherein pinning reduction in some directions permitted liquid travel along the scribed edge to undergo contact angle hysteresis .", "entity": [], "task": "NER"}
{"text": "Fluorescence measurements conducted showed no performance compromise when using scribed transparency microplates over standard microplates .", "entity": [], "task": "NER"}
{"text": "Amplified fluorescent sensing of DNA using graphene oxide and a conjugated cationic polymer .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [43, 57]}], "task": "NER"}
{"text": "We explore the interactions between a fluorescein ( FAM ) - labeled single - stranded DNA ( P ) , graphene oxide ( GO ) , and a cationic conjugated polymer , poly [ ( 9 , 9 - bis ( 6 ' - N , N , N - trimethylammonium ) hexyl ) - fluorenylene phenylene dibromide ] ( PFP ) .", "entity": [{"entity": "fluorescein", "entity_type": "Chemical", "pos": [38, 49]}, {"entity": "FAM", "entity_type": "Chemical", "pos": [52, 55]}, {"entity": "graphene oxide", "entity_type": "Chemical", "pos": [98, 112]}, {"entity": "poly [ ( 9 , 9 - bis ( 6 ' - N , N , N - trimethylammonium ) hexyl ) - fluorenylene phenylene dibromide ]", "entity_type": "Chemical", "pos": [158, 263]}, {"entity": "PFP", "entity_type": "Chemical", "pos": [266, 269]}], "task": "NER"}
{"text": "It is found that the fluorescence change of P - GO - PFP system is dependent on the addition order of P and PFP .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [53, 56]}, {"entity": "PFP", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "When adding PFP into P / GO complex , the fluorescence resonance energy transfer ( FRET ) from PFP to P is inefficient .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "PFP", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "If P is added to PFP / GO complex , efficient FRET is obtained .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [17, 20]}], "task": "NER"}
{"text": "This may be attributed to the equal binding ability for P and PFP to GO .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [62, 65]}], "task": "NER"}
{"text": "The results of time - resolved fluorescence and fluorescence anisotropy support the different fluorescent response under different addition order of P and PFP to GO .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [155, 158]}], "task": "NER"}
{"text": "Based on the above phenomenon , we demonstrate a method to reduce the high background signal of a traditional PFP - based DNA sensor by introducing GO .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "In comparison to the use of single PFP , the combination of PFP with GO - based method shows enhanced sensitivity with a detection limit as low as 40 pM for target DNA detection .", "entity": [{"entity": "PFP", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "PFP", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "Alpha - heteroatom derivatized analogues of 3 - ( acetylhydroxyamino ) propyl phosphonic acid ( FR900098 ) as antimalarials .", "entity": [{"entity": "3 - ( acetylhydroxyamino ) propyl phosphonic acid", "entity_type": "Chemical", "pos": [44, 93]}, {"entity": "FR900098", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "To explore the hitherto successful derivatization of the alpha - carbon of fosmidomycin , a series of new alpha - substituted analogues was prepared .", "entity": [{"entity": "alpha - carbon", "entity_type": "Chemical", "pos": [57, 71]}, {"entity": "fosmidomycin", "entity_type": "Chemical", "pos": [75, 87]}], "task": "NER"}
{"text": "This was done by introduction of a heteroatom ( N or O ) in alpha - position to the phosphonate and using the resultant OH and NH 2 groups as a handle for appending a variety of substituents by means of several functional groups such as ether , amide , urea , and 1 , 4 - triazole .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [48, 49]}, {"entity": "O", "entity_type": "Chemical", "pos": [53, 54]}, {"entity": "phosphonate", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "OH", "entity_type": "Chemical", "pos": [120, 122]}, {"entity": "NH 2", "entity_type": "Chemical", "pos": [127, 131]}, {"entity": "ether", "entity_type": "Chemical", "pos": [237, 242]}, {"entity": "amide", "entity_type": "Chemical", "pos": [245, 250]}, {"entity": "urea", "entity_type": "Chemical", "pos": [253, 257]}, {"entity": "1 , 4 - triazole", "entity_type": "Chemical", "pos": [264, 280]}], "task": "NER"}
{"text": "The synthesized molecules , as a racemic mixture , were assayed for their EcDXR inhibitory potency .", "entity": [], "task": "NER"}
{"text": "Both the alpha - azido - analogue and the alpha - hydroxylated analogue proved most promising , and docking experiments were performed .", "entity": [{"entity": "alpha - azido", "entity_type": "Chemical", "pos": [9, 22]}], "task": "NER"}
{"text": "Although several compounds showed high potency when assayed against Plasmodium falciparum K1 in human erythrocytes , a clear correlation between the enzyme inhibition constants and P . falciparum inhibition concentrations could not be found .", "entity": [], "task": "NER"}
{"text": "Super - resolution mapping of reactive sites on titania - based nanoparticles with water - soluble fluorogenic probes .", "entity": [{"entity": "titania", "entity_type": "Chemical", "pos": [48, 55]}], "task": "NER"}
{"text": "Interfacial charge transfer at the heterogeneous surface of semiconductor nanoparticles is a fundamental process that is relevant to many important applications , such as photocatalysis , solar cells , and sensors .", "entity": [], "task": "NER"}
{"text": "In this study , we developed new water - soluble fluorogenic probes for interfacial electron transfer reactions on semiconductor nanoparticles .", "entity": [], "task": "NER"}
{"text": "The synthesized boron - dipyrromethene - based fluorescence dyes have one or two sulfonate groups , which confer solubility in aqueous media , and a dinitrophenyl group as a redox reaction site .", "entity": [{"entity": "boron - dipyrromethene", "entity_type": "Chemical", "pos": [16, 38]}, {"entity": "sulfonate", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "dinitrophenyl", "entity_type": "Chemical", "pos": [149, 162]}], "task": "NER"}
{"text": "These probes produce the corresponding fluorescent products via multiple interfacial electron transfer processes , allowing us to investigate the photoinduced redox reactions over individual pristine and Au - nanoparticle - deposited TiO ( 2 ) nanoparticles at the single - particle , single - molecule levels .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [204, 206]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [234, 243]}], "task": "NER"}
{"text": "The minimum probe concentration to detect single - product molecules on a single TiO ( 2 ) nanoparticle was found to be in the nanomolar range ( < 10 nM ) in acidic solution .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "Furthermore , super - resolution mapping of the reaction sites revealed that visible - light - induced reduction reactions preferentially occurred on the TiO ( 2 ) surface within a distance of a few tens of nanometers around the deposited Au nanoparticles .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [154, 163]}, {"entity": "Au", "entity_type": "Chemical", "pos": [239, 241]}], "task": "NER"}
{"text": "This result was qualitatively interpreted on the basis of plasmon - induced electron and / or energy transfer mechanisms .", "entity": [], "task": "NER"}
{"text": "Overall , this study provides a great deal of valuable information related to solar - energy - conversion processes that is impossible or difficult to obtain from ensemble - averaged experiments .", "entity": [], "task": "NER"}
{"text": "Self - assembled pH - sensitive cholesteryl pullulan nanogel as a protein delivery vehicle .", "entity": [{"entity": "cholesteryl", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "A self - assembled nanogel , derived from an acid - labile cholesteryl - modified pullulan ( acL - CHP ) , was prepared by grafting vinyl ether - cholesterol substituents onto a 100 kD pullulan main chain polymer backbone .", "entity": [{"entity": "cholesteryl", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "vinyl ether", "entity_type": "Chemical", "pos": [132, 143]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [146, 157]}], "task": "NER"}
{"text": "Stable nanogels are formed by acL - CHP self - assemblies at neutral pH .", "entity": [], "task": "NER"}
{"text": "The hydrodynamic radius of the nanogels , observed to be 26 . 5 +/- 5 . 1 nm at pH 7 . 0 , increased by ~ 135 % upon acidification of the solution to pH 4 . 0 .", "entity": [], "task": "NER"}
{"text": "SEC analysis of the acL - CHP nanogel at pH 4 . 0 showed that the grafts were nearly 80 % degraded after 24 h , whereas little or no degradation was observed over the same time period for a pH stable analog ( acS - CHP ) at pH 4 . 0 or the acL - CHP at pH 7 . 0 .", "entity": [], "task": "NER"}
{"text": "Complexation of BSA with the acL - CHP nanogel was observed at pH 7 . 0 with subsequent release of the protein upon acidification .", "entity": [], "task": "NER"}
{"text": "These findings suggest that stimuli - responsive , self - assembled nanogels can release protein cargo in a manner that is controlled by the degradation rate of the cholesterol - pullulan grafting moiety .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [165, 176]}], "task": "NER"}
{"text": "An ultrastrong nanofibrillar biomaterial : the strength of single cellulose nanofibrils revealed via sonication - induced fragmentation .", "entity": [], "task": "NER"}
{"text": "We report the mechanical strength of native cellulose nanofibrils .", "entity": [], "task": "NER"}
{"text": "Native cellulose nanofibrils , purified from wood and sea tunicate , were fully dispersed in water via a topochemical modification of cellulose nanofibrils using 2 , 2 , 6 , 6 - tetramethylpiperidinyl - 1 - oxyl ( TEMPO ) as a catalyst .", "entity": [{"entity": "2 , 2 , 6 , 6 - tetramethylpiperidinyl - 1 - oxyl", "entity_type": "Chemical", "pos": [162, 211]}, {"entity": "TEMPO", "entity_type": "Chemical", "pos": [214, 219]}], "task": "NER"}
{"text": "The strength of individual nanofibrils was estimated based on a model for the sonication - induced fragmentation of filamentous nanostructures .", "entity": [], "task": "NER"}
{"text": "The resulting strength parameters were then analyzed based on fracture statistics .", "entity": [], "task": "NER"}
{"text": "The mean strength of the wood cellulose nanofibrils ranged from 1 . 6 to 3 GPa , depending on the method used to measure the nanofibril width .", "entity": [], "task": "NER"}
{"text": "The highly crystalline , thick tunicate cellulose nanofibrils exhibited higher mean strength of 3 - 6 GPa .", "entity": [], "task": "NER"}
{"text": "The strength values estimated for the cellulose nanofibrils in the present study are comparable with those of commercially available multiwalled carbon nanotubes .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [145, 151]}], "task": "NER"}
{"text": "Synergistic activity and mechanism of action of ceftazidime and apigenin combination against ceftazidime - resistant Enterobacter cloacae .", "entity": [{"entity": "ceftazidime", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "The purpose of this investigation was to examine the antibacterial and synergistic effect of naturally occurring flavonoids , apigenin , quercetin , naringenin and ceftazidime when use singly and in combination against ceftazidime - resistant Enterobacter cloacae strains by minimum inhibitory concentration ( MIC ) , checkerboard and viable count methods .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [113, 123]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [126, 134]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [137, 146]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [149, 159]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [164, 175]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [219, 230]}], "task": "NER"}
{"text": "The mode of actions were also studied by electronmicoscopy , enzyme assay , outer and inner membrane permeabilisation .", "entity": [], "task": "NER"}
{"text": "The results showed that these strains were positive in the ESBL - ampC genes combination by multiplex PCR .", "entity": [], "task": "NER"}
{"text": "These findings were confirmed by MICs that these strains were resistant to ceftazidime , cefepime and flomoxef at > 1024 , 16 - 24 , > 256 mu g / ml respectively , while susceptible to imipenem at 1 - 2 mu g / ml .", "entity": [{"entity": "ceftazidime", "entity_type": "Chemical", "pos": [75, 86]}, {"entity": "cefepime", "entity_type": "Chemical", "pos": [89, 97]}, {"entity": "flomoxef", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "imipenem", "entity_type": "Chemical", "pos": [185, 193]}], "task": "NER"}
{"text": "The synergistic activity was observed at ceftazidime plus either apigenin or naringenin combinations with FIC indixes between < 0 . 01 and < 0 . 27 against these strains , whereas ceftazidime plus clavulanic acid or quercetin did not exhibit synergy .", "entity": [{"entity": "ceftazidime", "entity_type": "Chemical", "pos": [41, 52]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [65, 73]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [77, 87]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [180, 191]}, {"entity": "clavulanic acid", "entity_type": "Chemical", "pos": [197, 212]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [216, 225]}], "task": "NER"}
{"text": "The modulation of ceftazidime - resistance by apigenin or narigenin significantly enhanced the activities of ceftazidime .", "entity": [{"entity": "ceftazidime", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "narigenin", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [109, 120]}], "task": "NER"}
{"text": "The 5 , 7 - OH group of A ring and one 4 ' - OH group of the B ring in apigenin and naringenin are important for synergistic activity .", "entity": [{"entity": "5 , 7 - OH", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "4 ' - OH", "entity_type": "Chemical", "pos": [39, 47]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "Viable counts showed that the killing of ceftazidime - resistant E . cloacae DMST 21394 ( CREC ) cells by 3 mu g / ml ceftazidime was potentiated by 3 mu g / ml apigenin to low levels ( 10 ( 3 ) cfu / ml ) over 6h .", "entity": [{"entity": "ceftazidime", "entity_type": "Chemical", "pos": [41, 52]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [118, 129]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [161, 169]}], "task": "NER"}
{"text": "Electronmicroscopy clearly showed that ceftazidime 3 mu g / ml in combination with 3 mu g / ml of apigenin also caused marked morphological damage of cell wall , cell shape and plasma membrane of this strain .", "entity": [{"entity": "ceftazidime", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [98, 106]}], "task": "NER"}
{"text": "Enzymes assays indicated that apigenin showed marked inhibitory activity against penicillinase type IV from E . cloacae .", "entity": [{"entity": "apigenin", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "The results for outer membrane ( OM ) permeabilization in both nitrocefin ( NCF ) assay and crystal violet uptake showed that the combination of ceftazidime plus apigenin significantly altered OM permeabilisation of CREC compared to control or single treatment of these agents .", "entity": [{"entity": "nitrocefin", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "NCF", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "crystal violet", "entity_type": "Chemical", "pos": [92, 106]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [145, 156]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [162, 170]}], "task": "NER"}
{"text": "Both o - nitrophenyl - beta - D - galactoside ( ONPG ) uptake and release of UV - absorbing material concentrations results exhibited that ceftazidime and apigenin combination damaged CREC cytoplasmic membrane ( CM ) and caused subsequent leakage of intracellular constituents .", "entity": [{"entity": "o - nitrophenyl - beta - D - galactoside", "entity_type": "Chemical", "pos": [5, 45]}, {"entity": "ONPG", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [139, 150]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [155, 163]}], "task": "NER"}
{"text": "From the results , it can be concluded that apigenin and naringenin have the synergistic effect with ceftazidime to reverse bacterial resistance to this cephalosporin against CREC .", "entity": [{"entity": "apigenin", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [101, 112]}, {"entity": "cephalosporin", "entity_type": "Chemical", "pos": [153, 166]}], "task": "NER"}
{"text": "This activity may be involved three mechanisms of action by apigenin .", "entity": [{"entity": "apigenin", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "The first is on the peptidoglycan synthesis inhibition .", "entity": [], "task": "NER"}
{"text": "The second mechanism is inhibition the activity of certain beta - lactamase enzymes .", "entity": [], "task": "NER"}
{"text": "The third mode of action is alteration of OM and CM permeabilization .", "entity": [], "task": "NER"}
{"text": "Apigenin and naringenin have a sufficient margin of safety for therapeutic use .", "entity": [{"entity": "Apigenin", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [13, 23]}], "task": "NER"}
{"text": "For this reason , apigenin and naringenin offer for the development of a valuable adjunct to ceftazidime against CREC , which currently almost cephalosporins resistance .", "entity": [{"entity": "apigenin", "entity_type": "Chemical", "pos": [18, 26]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [31, 41]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [93, 104]}, {"entity": "cephalosporins", "entity_type": "Chemical", "pos": [143, 157]}], "task": "NER"}
{"text": "Fragment - based discovery of novel and selective mPGES - 1 inhibitors Part 1 : identification of sulfonamido - 1 , 2 , 3 - triazole - 4 , 5 - dicarboxylic acid .", "entity": [{"entity": "sulfonamido - 1 , 2 , 3 - triazole - 4 , 5 - dicarboxylic acid", "entity_type": "Chemical", "pos": [98, 160]}], "task": "NER"}
{"text": "Microsomal prostaglandin E synthase - 1 ( mPGES - 1 ) is an inducible prostaglandin E synthase that catalyzes the conversion of prostaglandin PGH ( 2 ) to PGE ( 2 ) and represents a novel target for therapeutic treatment of inflammatory disorders .", "entity": [{"entity": "prostaglandin E", "entity_type": "Chemical", "pos": [11, 26]}, {"entity": "prostaglandin E", "entity_type": "Chemical", "pos": [70, 85]}, {"entity": "prostaglandin", "entity_type": "Chemical", "pos": [128, 141]}, {"entity": "PGH ( 2 )", "entity_type": "Chemical", "pos": [142, 151]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [155, 164]}], "task": "NER"}
{"text": "It is essential to identify mPGES - 1 inhibitor with novel scaffold as new hit or lead compound for the purpose of the next - generation anti - inflammatory drugs .", "entity": [], "task": "NER"}
{"text": "Herein we report the discovery of sulfonamido - 1 , 2 , 3 - triazole - 4 , 5 - dicarboxylic derivatives as a novel class of mPGES - 1 inhibitors identified through fragment - based virtual screening and in vitro assays on the inhibitory activity of the actual compounds .", "entity": [{"entity": "sulfonamido - 1 , 2 , 3 - triazole - 4 , 5 - dicarboxylic", "entity_type": "Chemical", "pos": [34, 91]}], "task": "NER"}
{"text": "1 - [ 2 - ( N - Phenylbenzenesulfonamido ) ethyl ] - 1H - 1 , 2 , 3 - triazole - 4 , 5 - dicarboxylic acid ( 6f ) inhibits human mPGES - 1 ( IC ( 50 ) of 1 . 1 mu M ) with high selectivity ( ca . 1000 - fold ) over both COX - 1 and COX - 2 in a cell - free assay .", "entity": [{"entity": "1 - [ 2 - ( N - Phenylbenzenesulfonamido ) ethyl ] - 1H - 1 , 2 , 3 - triazole - 4 , 5 - dicarboxylic acid", "entity_type": "Chemical", "pos": [0, 106]}], "task": "NER"}
{"text": "In addition , the activity of compound 6f was again tested at 10 mu M concentration in presence of 0 . 1 % Triton X - 100 and found to be reduced to 1 / 4 of its original activity without this detergent .", "entity": [{"entity": "Triton X - 100", "entity_type": "Chemical", "pos": [107, 121]}], "task": "NER"}
{"text": "Compared to the complete loss of activity of nuisance inhibitor with the detergent , therefore , compound 6f would be regarded as a partial nuisance inhibitor of mPGES - 1 with a novel scaffold for the optimal design of more potent mPGES - 1 inhibitors .", "entity": [], "task": "NER"}
{"text": "The discovery of potent and selective 4 - aminothienopyridines as B - Raf kinase inhibitors .", "entity": [{"entity": "4 - aminothienopyridines", "entity_type": "Chemical", "pos": [38, 62]}], "task": "NER"}
{"text": "A series of novel , potent 4 - aminothienopyridine B - Raf kinase inhibitors was designed and synthesized using knowledge - based design .", "entity": [{"entity": "4 - aminothienopyridine", "entity_type": "Chemical", "pos": [27, 50]}], "task": "NER"}
{"text": "Compounds 5f , and 6k exhibited not only excellent potency in both enzyme assay ( IC ( 50 ) = 5 . 1 , 16 . 6 nM ) and cellular assay ( IC ( 50 ) = 0 . 2 , 0 . 2 mu M ) , but also had an outstanding selectivity profile against other kinases .", "entity": [], "task": "NER"}
{"text": "Mutational consequences of dNTP pool imbalances in E . coli .", "entity": [], "task": "NER"}
{"text": "The accuracy of DNA synthesis depends on the accuracy of the polymerase as well as the quality and concentration ( s ) of the available 5 ' - deoxynucleoside - triphosphate DNA precursors ( dNTPs ) .", "entity": [{"entity": "5 ' - deoxynucleoside - triphosphate", "entity_type": "Chemical", "pos": [136, 172]}, {"entity": "dNTPs", "entity_type": "Chemical", "pos": [190, 195]}], "task": "NER"}
{"text": "The relationships between dNTPs and error rates have been studied in vitro , but only limited insights exist into these correlations during in vivo replication .", "entity": [{"entity": "dNTPs", "entity_type": "Chemical", "pos": [26, 31]}], "task": "NER"}
{"text": "We have investigated this issue in the bacterium Escherichia coli by analyzing the mutational properties of dcd and ndk strains .", "entity": [], "task": "NER"}
{"text": "These strains , defective in dCTP deaminase and nucleoside diphosphate kinase , respectively , are characterized by both disturbances of dNTP pools and a mutator phenotype . ndk strains have been studied before , but were included in this study , as controversies exist regarding the source of its mutator phenotype .", "entity": [{"entity": "dCTP", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "nucleoside diphosphate", "entity_type": "Chemical", "pos": [48, 70]}, {"entity": "dNTP", "entity_type": "Chemical", "pos": [137, 141]}], "task": "NER"}
{"text": "We show that dcd strains suffer from increased intracellular levels of dCTP ( 4 - fold ) and reduced levels of dGTP ( 2 - fold ) , while displaying , as measured using a set of lacZ reversion markers in a mismatch - repair defective ( mutL ) background , a strong mutator effect for G . C --> T . A and A . T --> T . A transversions ( 27 - and 42 - fold enhancement , respectively ) .", "entity": [{"entity": "dCTP", "entity_type": "Chemical", "pos": [71, 75]}, {"entity": "dGTP", "entity_type": "Chemical", "pos": [111, 115]}], "task": "NER"}
{"text": "In contrast , ndk strains possess a lowered dATP level ( 4 - fold ) and modestly enhanced dCTP level ( 2 - fold ) , while its mutator effect is specific for just the A . T --> T . A transversions .", "entity": [{"entity": "dATP", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "dCTP", "entity_type": "Chemical", "pos": [90, 94]}], "task": "NER"}
{"text": "The two strains also display differential mutability for rifampicin - resistant mutants .", "entity": [{"entity": "rifampicin", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "Overall , our analysis reveals for both strains a satisfactory correlation between dNTP pool alterations and the replication error rates , and also suggests that a minimal explanation for the ndk mutator does not require assumptions beyond the predicted effect of the dNTP pools .", "entity": [{"entity": "dNTP", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "dNTP", "entity_type": "Chemical", "pos": [268, 272]}], "task": "NER"}
{"text": "Parametrisation of the free energy of ATP binding to wild - type and mutant Kir6 . 2 potassium channels .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [38, 41]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [85, 94]}], "task": "NER"}
{"text": "ATP - sensitive K ( + ) ( K ( ATP ) ) channels , comprised of pore - forming Kir6 . x and regulatory SURx subunits , play important roles in many cellular functions ; because of their sensitivity to inhibition by intracellular ATP , K ( ATP ) channels provide a link between cell metabolism and membrane electrical activity .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "K", "entity_type": "Chemical", "pos": [26, 27]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [227, 230]}, {"entity": "K", "entity_type": "Chemical", "pos": [233, 234]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [237, 240]}], "task": "NER"}
{"text": "We constructed structural homology models of Kir6 . 2 and a series of Kir6 . 2 channels carrying mutations within the putative ATP - binding site .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [127, 130]}], "task": "NER"}
{"text": "Computational docking was carried out to determine the conformation of ATP in its binding site .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [71, 74]}], "task": "NER"}
{"text": "The Linear Interaction Energy ( LIE ) method was used to estimate the free - energy of ATP binding to wild - type and mutant Kir6 . 2 channels .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "Comparisons of the theoretical binding free energies for ATP with those determined from mutational experiments enabled the identification of the most probable conformation of ATP bound to the Kir6 . 2 channel .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [57, 60]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [175, 178]}], "task": "NER"}
{"text": "A set of LIE parameters was defined that may enable prediction of the effects of additional Kir6 . 2 mutations within the ATP binding site on the affinity for ATP .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [122, 125]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [159, 162]}], "task": "NER"}
{"text": "Achyrofuran is an antibacterial agent capable of killing methicillin - resistant vancomycin - intermediate Staphylococcus aureus in the nanomolar range .", "entity": [{"entity": "Achyrofuran", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "methicillin", "entity_type": "Chemical", "pos": [57, 68]}, {"entity": "vancomycin", "entity_type": "Chemical", "pos": [81, 91]}], "task": "NER"}
{"text": "Currently , there is a pressing need for novel antibacterial agents against drug - resistant bacteria , especially those which have been common in our communities and hospitals , such as methicillin - resistant Staphylococcus aureus ( MRSA ) .", "entity": [{"entity": "methicillin", "entity_type": "Chemical", "pos": [187, 198]}], "task": "NER"}
{"text": "The South American plant Achyrocline satureioides ( \" Marcela \" ) has been widely used in traditional medicine for a number of diseases , including infections .", "entity": [], "task": "NER"}
{"text": "Several crude extracts from this plant have shown good antimicrobial activities in vitro .", "entity": [], "task": "NER"}
{"text": "In the search for the active principle ( s ) that confers these antimicrobial activities , we have processed the dichloromethane extract from the aerial parts of the plant .", "entity": [{"entity": "dichloromethane", "entity_type": "Chemical", "pos": [113, 128]}], "task": "NER"}
{"text": "One of the isolated compounds showed extraordinary antibacterial activities against a set of clinically relevant Gram - positive strains that widely differ in their antibiogram profiles .", "entity": [], "task": "NER"}
{"text": "This compound was identified as achyrofuran on the basis of its spectroscopic and physical data .", "entity": [{"entity": "achyrofuran", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "We determined the MIC to be around 0 . 1 mu M ( 0 . 07 mu g / ml ) for the reference methicillin - resistant and vancomycin - intermediate S . aureus strain NRS402 .", "entity": [{"entity": "methicillin", "entity_type": "Chemical", "pos": [85, 96]}, {"entity": "vancomycin", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "Moreover , nanomolar concentrations of achyrofuran killed 10 ( 6 ) bacteria within 12 h .", "entity": [{"entity": "achyrofuran", "entity_type": "Chemical", "pos": [39, 50]}], "task": "NER"}
{"text": "Based on the presence of the 2 , 2 ' - biphenol core , we further studied whether achyrofuran killed bacteria through a mechanism of action similar to that reported for the naturally occurring antibiotic MC21 - A .", "entity": [{"entity": "2 , 2 ' - biphenol", "entity_type": "Chemical", "pos": [29, 47]}, {"entity": "achyrofuran", "entity_type": "Chemical", "pos": [82, 93]}, {"entity": "MC21 - A", "entity_type": "Chemical", "pos": [204, 212]}], "task": "NER"}
{"text": "Indeed , we found that achyrofuran was not bacteriolytic by itself although it greatly compromised membrane impermeability as determined by increased SYTOX Green uptake .", "entity": [{"entity": "achyrofuran", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "SYTOX Green", "entity_type": "Chemical", "pos": [150, 161]}], "task": "NER"}
{"text": "Anti - tumor and anti - metastatic actions of wogonin isolated from Scutellaria baicalensis roots through anti - lymphangiogenesis .", "entity": [{"entity": "wogonin", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Tumor growth and metastasis are associated with angiogenesis and lymphangiogenesis through the production of vascular endothelial growth factor ( VEGF ) or VEGF - C in tumors , and the phosphorylation of VEGF receptor ( VEGFR ) - 2 or VEGFR - 3 in vascular endothelial cells or lymphatic endothelial cells ( LECs ) .", "entity": [], "task": "NER"}
{"text": "Tumor - associated macrophages ( TAMs ) play an important role in tumor lymphangiogenesis , and consequently stimulate metastasis through the lymphatic system to lymph nodes .", "entity": [], "task": "NER"}
{"text": "We examined the effects of wogonin isolated from Scutellaria baicalensis roots on tumor growth and metastasis using a highly metastatic model in osteosarcoma LM8 - bearing mice .", "entity": [{"entity": "wogonin", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "Wogonin ( 25 and 50 mg / kg , twice daily ) reduced tumor growth and metastasis to the lung , liver and kidney , angiogenesis ( CD31 - positive cells ) , lymphangiogenesis ( LYVE - 1 - positive cells ) , and TAM ( F4 / 80 - positive cell ) numbers in the tumors of LM8 - bearing mice .", "entity": [{"entity": "Wogonin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Wogonin ( 10 - 100 mu M ) also inhibited increases in IL - 1 beta production and cyclooxygenase ( COX ) - 2 expression induced by lipopolysaccharide in THP - 1 macrophages .", "entity": [{"entity": "Wogonin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Wogonin had no effect on VEGF - C production in LM8 cells , or VEGFR - 3 expression in human lymphatic endothelial cells ( HLECs ) , however , it inhibited VEGF - C - induced VEGFR - 3 phosphorylation in HLECs .", "entity": [{"entity": "Wogonin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "The anti - tumor and anti - metastatic actions of wogonin may be associated with the inhibition of VEGF - C - induced lymphangiogenesis through a reduction in VEGF - C - induced VEGFR - 3 phosphorylation by the inhibition of COX - 2 expression and IL - 1 beta production in TAMs .", "entity": [{"entity": "wogonin", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "Ginkgo biloba leaves extract ( EGb 761 ) attenuates lipopolysaccharide - induced acute lung injury via inhibition of oxidative stress and NF - kappa B - dependent matrix metalloproteinase - 9 pathway .", "entity": [], "task": "NER"}
{"text": "Acute lung injury ( ALI ) presents high mortality and morbidity clinically and by far no effective preventive strategy has been established .", "entity": [], "task": "NER"}
{"text": "Extract of Ginkgo biloba leaves , EGb 761 , is a complex mixture that possesses several clinical beneficial effects such as anti - oxidation , anti - inflammation , anti - tumor , and cardioprotective property .", "entity": [], "task": "NER"}
{"text": "With EGb 761 pretreatment , both lipopolysaccharide ( LPS ) - induced protein leakage and neutrophil infiltration , and LPS - induced inflammatory responses including increased myeloperoxidase ( MPO ) activity , lipid peroxidation , and metalloproteinase ( MMP ) - 9 activity , were inhibited ; LPS - suppressed activation of antioxidative enzymes ( AOE ) were reversed ; and not only the phosphorylation of NF - kappa B but also the degradation of its inhibitor , I kappa B , were suppressed .", "entity": [], "task": "NER"}
{"text": "These results suggested that the protection mechanism of EGb 761 is by inhibition of NF kappa B activation , possibly via the up - regulation of antioxidative enzymes .", "entity": [], "task": "NER"}
{"text": "More studies are needed to further evaluate whether EGb 761 is a suitable candidate as an effective dietary strategy to reduce the incidence of endotoxin - induced ALI .", "entity": [], "task": "NER"}
{"text": "The discovery , engineering and characterisation of a highly potent anti - human IL - 13 fab fragment designed for administration by inhalation .", "entity": [], "task": "NER"}
{"text": "We describe the discovery , engineering and characterisation of a highly potent anti - human interleukin ( IL ) - 13 Fab fragment designed for administration by inhalation .", "entity": [], "task": "NER"}
{"text": "The lead candidate molecule was generated via a novel antibody discovery process , and the selected IgG variable region genes were successfully humanised and reformatted as a human IgG gamma 1 Fab fragment .", "entity": [], "task": "NER"}
{"text": "Evaluation of the biophysical properties of a selection of humanised Fab fragments in a number of assays allowed us to select the molecule with the optimal stability profile .", "entity": [], "task": "NER"}
{"text": "The resulting lead candidate , CA652 . g2 Fab , was shown to have comparable activity to the parental IgG molecule in a range of in vitro assays and was highly stable .", "entity": [], "task": "NER"}
{"text": "Following nebulisation using a mesh nebuliser , CA652 . g2 Fab retained full binding affinity , functional neutralisation potency and structural integrity .", "entity": [], "task": "NER"}
{"text": "Epitope mapping using solution nuclear magnetic resonance confirmed that the antibody bound to the region of human IL - 13 implicated in the interaction with IL - 13R alpha 1 and IL - 13R alpha 2 .", "entity": [], "task": "NER"}
{"text": "The work described here resulted in the discovery and design of CA652 . g2 human gamma 1 Fab , a highly stable and potent anti - IL - 13 molecule suitable for delivery via inhalation .", "entity": [], "task": "NER"}
{"text": "beta - phenylethyl isothiocyanate reverses platinum resistance by a GSH - dependent mechanism in cancer cells with epithelial - mesenchymal transition phenotype .", "entity": [{"entity": "beta - phenylethyl isothiocyanate", "entity_type": "Chemical", "pos": [0, 33]}, {"entity": "platinum", "entity_type": "Chemical", "pos": [43, 51]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [68, 71]}], "task": "NER"}
{"text": "Platinum ( Pt ) - based chemotherapy is an important regimen in the clinical treatment of cancer , but development of drug resistance presents a major challenge .", "entity": [{"entity": "Platinum", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [11, 13]}], "task": "NER"}
{"text": "One key mechanism involved in resistance to Pt drugs is the decrease of intracellular Pt due to the drug efflux through the glutathione ( GSH ) - mediated export , and this is particularly significant in cancer cells with stem - cell like properties .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [86, 88]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [124, 135]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [138, 141]}], "task": "NER"}
{"text": "In the present study , we showed that two Pt - resistant human cancer cell lines exhibited stem - cell like EMT properties , had high cellular GSH and accumulated significantly less cellular Pt compared to their parental cells , and failed to undergo apoptosis when exposed to Pt at the drug concentrations toxic to the parental cells .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [143, 146]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [191, 193]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [277, 279]}], "task": "NER"}
{"text": "Importantly , we found that the natural compound beta - phenylethyl isothiocyanate ( PEITC ) was able to effectively abolish this drug resistant mechanism by effective depletion of cellular GSH , leading to a significant increase in cellular Pt as well as DNA - bound Pt .", "entity": [{"entity": "beta - phenylethyl isothiocyanate", "entity_type": "Chemical", "pos": [49, 82]}, {"entity": "PEITC", "entity_type": "Chemical", "pos": [85, 90]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [190, 193]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [242, 244]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [268, 270]}], "task": "NER"}
{"text": "A combination of PEITC and Pt showed a striking synergistic anticancer activity both in vitro and in vivo , as evidenced by an increase in drug - induced apoptosis , a loss of colony formation capacity , and significant suppression of tumor growth in mice .", "entity": [{"entity": "PEITC", "entity_type": "Chemical", "pos": [17, 22]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [27, 29]}], "task": "NER"}
{"text": "Taken together , our study shows a promising therapeutic strategy to overcome drug resistance to platinum - based chemotherapy and may potentially have broad implications in clinical treatment of cancer .", "entity": [{"entity": "platinum", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "Analysis by substituted cysteine scanning mutagenesis of the fourth transmembrane domain of the CXCR4 receptor in its inactive and active state .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [24, 32]}], "task": "NER"}
{"text": "The chemokine SDF - 1 ( CXCL12 ) selectively binds to CXCR4 , a member of the G protein - coupled receptor ( GPCR ) superfamily .", "entity": [], "task": "NER"}
{"text": "In this study , we used the substituted - cysteine accessibility method ( SCAM ) to identify specific residues of the fourth transmembrane domain ( TM4 ) that contribute to the formation of the binding pocket of CXCR4 in its inactive and active state .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "We successively substituted each residue from E179 ( ( 4 . 68 ) ) to K154 ( ( 4 . 43 ) ) with cysteine and expressed the mutants in COS - 7 cells .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "Mutant receptors were then alkylated with methanethiosulfonate - ethylammonium ( MTSEA ) , and binding inhibition was monitored using the CXCR4 antagonist FC131 [ cyclo ( - D - Tyr ( 1 ) - Arg ( 2 ) - Arg ( 3 ) - Nal ( 4 ) - Gly ( 5 ) - ) ] , which displays anti - HIV activity .", "entity": [{"entity": "methanethiosulfonate - ethylammonium", "entity_type": "Chemical", "pos": [42, 78]}, {"entity": "MTSEA", "entity_type": "Chemical", "pos": [81, 86]}, {"entity": "FC131", "entity_type": "Chemical", "pos": [155, 160]}, {"entity": "cyclo ( - D - Tyr ( 1 ) - Arg ( 2 ) - Arg ( 3 ) - Nal ( 4 ) - Gly ( 5 ) - )", "entity_type": "Chemical", "pos": [163, 238]}], "task": "NER"}
{"text": "MTSEA treatment resulted in a significant reduction of FC131 binding to D171C ( ( 4 . 60 ) ) and P170C ( ( 4 . 59 ) ) .", "entity": [{"entity": "MTSEA", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "FC131", "entity_type": "Chemical", "pos": [55, 60]}], "task": "NER"}
{"text": "To assess TM4 accessibility in an active state of CXCR4 , TM4 cysteine mutants were transposed within the constitutively active mutant N119S ( ( 3 . 35 ) ) .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "MTSEA treatment of TM4 mutants N119S - S178C ( ( 4 . 67 ) ) , N119S - V177C ( ( 4 . 66 ) ) and N119S - I173C ( ( 4 . 62 ) ) resulted in a significant reduction in FC131 binding .", "entity": [{"entity": "MTSEA", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "FC131", "entity_type": "Chemical", "pos": [163, 168]}], "task": "NER"}
{"text": "Protection assays using FC131 prior to MTSEA treatment significantly reduced the alkylation of all MTSEA - sensitive mutants .", "entity": [{"entity": "FC131", "entity_type": "Chemical", "pos": [24, 29]}, {"entity": "MTSEA", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "MTSEA", "entity_type": "Chemical", "pos": [99, 104]}], "task": "NER"}
{"text": "The accessibility of the D171C ( ( 4 . 60 ) ) and P170C ( ( 4 . 59 ) ) residues suggests that they are oriented towards a water - accessible area of the binding pocket of CXCR4 .", "entity": [], "task": "NER"}
{"text": "S178C ( ( 4 . 67 ) ) , V177C ( ( 4 . 66 ) ) and I173C ( ( 4 . 62 ) ) showed binding inhibition only in an N119S ( ( 3 . 35 ) ) background .", "entity": [], "task": "NER"}
{"text": "Taken together our results suggest that TM4 and ECL2 undergo conformational changes during CXCR4 activation and also demonstrate how TM4 is an important feature for the binding of anti - HIV compounds .", "entity": [], "task": "NER"}
{"text": "Discovery of alkenylboronic acids as neuroprotective agents affecting multiple biological targets involved in Alzheimer ' s disease .", "entity": [{"entity": "alkenylboronic acids", "entity_type": "Chemical", "pos": [13, 33]}], "task": "NER"}
{"text": "Alkenylboronic acids have shown important biological activities that contribute to neuroprotection .", "entity": [{"entity": "Alkenylboronic acids", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "We have determined their influence on the beta - amyloid ( beta A ) aggregation process , beta - secretase and acethylcholinesterase activities on cell - free systems , on the redox and lipid peroxidation status , and on the vulnerability to apoptotic death in an APPswe neuroblastoma cell line , before and after hydrogen peroxide treatment .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [314, 331]}], "task": "NER"}
{"text": "We have discovered that 2 - arylvinylboronic acids and some of their esters possess a set of properties which makes them highly useful as neuroprotective agents affecting multiple biological targets involved in AD .", "entity": [{"entity": "2 - arylvinylboronic acids", "entity_type": "Chemical", "pos": [24, 50]}, {"entity": "esters", "entity_type": "Chemical", "pos": [69, 75]}], "task": "NER"}
{"text": "These properties are not paralleled by the related 2 - arylboronic acids .", "entity": [{"entity": "2 - arylboronic acids", "entity_type": "Chemical", "pos": [51, 72]}], "task": "NER"}
{"text": "Studies on percutaneous penetration of chemicals - Impact of storage conditions for excised human skin .", "entity": [], "task": "NER"}
{"text": "According to international guidelines skin penetration experiments can be carried out using freshly excised or frozen stored skin .", "entity": [], "task": "NER"}
{"text": "However , this recommendation refers to data obtained in experiments with human cadaver skin .", "entity": [], "task": "NER"}
{"text": "In our study , the percutaneous penetration of the occupationally relevant chemicals anisole , cyclohexanone and 1 , 4 - dioxane was investigated for freshly excised as well as for 4 and 30 days at - 20 degrees C stored human skin using the diffusion cell technique .", "entity": [{"entity": "anisole", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "cyclohexanone", "entity_type": "Chemical", "pos": [95, 108]}, {"entity": "1 , 4 - dioxane", "entity_type": "Chemical", "pos": [113, 128]}], "task": "NER"}
{"text": "As indicator for the impairment of skin barrier by freezing cholesterol dissolution was determined in the solvents in exposure chambers of diffusion cells .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [60, 71]}], "task": "NER"}
{"text": "Considering the percutaneously penetrated amounts , the following ranking was determined : 1 , 4 - dioxane > anisole > cyclohexanone ( decline to a factor of 5 . 9 ) .", "entity": [{"entity": "1 , 4 - dioxane", "entity_type": "Chemical", "pos": [91, 106]}, {"entity": "anisole", "entity_type": "Chemical", "pos": [109, 116]}, {"entity": "cyclohexanone", "entity_type": "Chemical", "pos": [119, 132]}], "task": "NER"}
{"text": "The differences of fluxes between freshly excised and frozen stored skin ( 4 and 30 days ) were not significant ( p > 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Cholesterol dissolved from the skin indicates no significant differences between freshly excised and frozen stored skin .", "entity": [{"entity": "Cholesterol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "This study shows that freezing of human skin for up to 30 days does not alter the skin barrier function and the permeability of chemicals .", "entity": [], "task": "NER"}
{"text": "Off - target effects of thrombolytic drugs : apolipoprotein A - I proteolysis by alteplase and tenecteplase .", "entity": [], "task": "NER"}
{"text": "The administration of thrombolytic drugs is of proven benefit in a variety of clinical conditions requiring acute revascularization , including acute myocardial infarction ( AMI ) , ischemic stroke , pulmonary embolism , and venous thrombosis .", "entity": [], "task": "NER"}
{"text": "Generated plasmin can degrade non - target proteins , including apolipoprotein A - I ( apoA - I ) , the major protein constituent of high - density lipoproteins ( HDL ) .", "entity": [], "task": "NER"}
{"text": "Aim of the present study was to compare the extent of apoA - I proteolytic degradation in AMI patients treated with two thrombolytic drugs , alteplase and the genetically engineered t - PA variant tenecteplase .", "entity": [], "task": "NER"}
{"text": "ApoA - I degradation was evaluated in sera from 38 AMI patients treated with alteplase or tenecteplase .", "entity": [], "task": "NER"}
{"text": "In vitro , apoA - I degradation was tested by incubating control sera or purified HDL with alteplase or tenecteplase at different concentrations ( 5 - 100 mu g / ml ) .", "entity": [], "task": "NER"}
{"text": "Treatment with alteplase and tenecteplase results in apoA - I proteolysis ; the extent of apoA - I degradation was more pronounced in alteplase - treated patients than in tenecteplase - treated patients .", "entity": [], "task": "NER"}
{"text": "In vitro , the extent of apoA - I proteolysis was higher in alteplase - treated sera than in tenecteplase - treated sera , in the whole drug concentration range .", "entity": [], "task": "NER"}
{"text": "No direct effect of the two thrombolytic agents on apoA - I degradation was observed .", "entity": [], "task": "NER"}
{"text": "In addition to apoA - I , apoA - IV was also degraded by the two thrombolytic agents and again proteolytic degradation was higher with alteplase than tenecteplase .", "entity": [], "task": "NER"}
{"text": "In conclusion , this study indicates that both alteplase and tenecteplase cause plasmin - mediated proteolysis of apoA - I , with alteplase resulting in a greater apoA - I degradation than tenecteplase , potentially causing a transient impairment of HDL atheroprotective functions .", "entity": [], "task": "NER"}
{"text": "Structural determinants of substrate specificity in aldehyde dehydrogenases .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Within the aldehyde dehydrogenase ( ALDH ) superfamily , proteins belonging to the ALDH9 , ALDH10 , ALDH25 , ALDH26 and ALDH27 families display activity as omega - aminoaldehyde dehydrogenases ( AMADHs ) .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "omega - aminoaldehyde", "entity_type": "Chemical", "pos": [156, 177]}], "task": "NER"}
{"text": "These enzymes participate in polyamine , choline and arginine catabolism , as well as in synthesis of several osmoprotectants and carnitine .", "entity": [{"entity": "polyamine", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "choline", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "carnitine", "entity_type": "Chemical", "pos": [130, 139]}], "task": "NER"}
{"text": "Active site aromatic and acidic residues are involved in binding the omega - aminoaldehydes in plant ALDH10 enzymes .", "entity": [{"entity": "omega - aminoaldehydes", "entity_type": "Chemical", "pos": [69, 91]}], "task": "NER"}
{"text": "In order to ascertain the degree of conservation of these residues among AMADHs and to evaluate their possible relevance in determining the aminoaldehyde specificity , we compared the known amino acid sequences of every ALDH family that have at least one member with known crystal structure , as well as the electrostatic potential surface of the aldehyde binding sites of these structures .", "entity": [{"entity": "aminoaldehyde", "entity_type": "Chemical", "pos": [140, 153]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [190, 200]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [347, 355]}], "task": "NER"}
{"text": "Our analyses showed that four or three aromatic residues form a similar \" aromatic box \" in the active site of the AMADH enzymes , being the equivalents to Phe170 and Trp177 ( human ALDH2 numbering ) strictly conserved in all of them , which supports their relevance in binding the aminoaldehyde by cation - pi interactions .", "entity": [{"entity": "Phe170", "entity_type": "Chemical", "pos": [156, 162]}, {"entity": "Trp177", "entity_type": "Chemical", "pos": [167, 173]}, {"entity": "aminoaldehyde", "entity_type": "Chemical", "pos": [282, 295]}], "task": "NER"}
{"text": "In addition , all AMADHs exhibit a negative electrostatic potential surface in the aldehyde - entrance tunnel , due to side - chain carboxyl and hydroxyl groups or main - chain carbonyl groups .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [83, 91]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [132, 140]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [145, 153]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "In contrast , ALDHs that have non - polar or negatively charged substrates exhibit neutral or positive electrostatic potential surfaces , respectively .", "entity": [], "task": "NER"}
{"text": "Finally , our comparative sequence analyses revealed that the residues equivalent to Asp121 and Phe170 are highly conserved in many ALDH families irrespective of their substrate specificity - suggesting that they perform a role in catalysis additional or different to binding of the substrate - and that the positions Met124 , Cys301 , and Cys303 are hot spots changed during evolution to confer aldehyde specificity to several ALDH families .", "entity": [{"entity": "Asp121", "entity_type": "Chemical", "pos": [85, 91]}, {"entity": "Phe170", "entity_type": "Chemical", "pos": [96, 102]}, {"entity": "Met124", "entity_type": "Chemical", "pos": [318, 324]}, {"entity": "Cys301", "entity_type": "Chemical", "pos": [327, 333]}, {"entity": "Cys303", "entity_type": "Chemical", "pos": [340, 346]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [396, 404]}], "task": "NER"}
{"text": "Micelles of zinc protoporphyrin conjugated to N - ( 2 - hydroxypropyl ) methacrylamide ( HPMA ) copolymer for imaging and light - induced antitumor effects in vivo .", "entity": [{"entity": "zinc protoporphyrin", "entity_type": "Chemical", "pos": [12, 31]}, {"entity": "N - ( 2 - hydroxypropyl ) methacrylamide", "entity_type": "Chemical", "pos": [46, 86]}, {"entity": "HPMA", "entity_type": "Chemical", "pos": [89, 93]}], "task": "NER"}
{"text": "We synthesized N - ( 2 - hydroxypropyl ) methacrylamide polymer conjugated with zinc protoporphyrin ( HPMA - ZnPP ) and evaluated its application for tumor detection by imaging and treatment by light exposure using in mouse sarcoma model .", "entity": [{"entity": "N - ( 2 - hydroxypropyl ) methacrylamide", "entity_type": "Chemical", "pos": [15, 55]}, {"entity": "zinc protoporphyrin", "entity_type": "Chemical", "pos": [80, 99]}, {"entity": "HPMA", "entity_type": "Chemical", "pos": [102, 106]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [109, 113]}], "task": "NER"}
{"text": "To characterize HPMA - ZnPP micelle , we measured its micellar size , surface charge , stability , photochemical , biochemical properties and tissue distribution .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [16, 20]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [23, 27]}], "task": "NER"}
{"text": "In vivo anti - tumor effect and fluorescence imaging were carried out to validate the tumor selective accumulation and therapeutic effect by inducing singlet oxygen by light exposure .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [158, 164]}], "task": "NER"}
{"text": "HPMA - ZnPP was highly water soluble and formed micelles spontaneously having hydrophobic clustered head group of ZnPP , in aqueous solution , with a hydrodynamic diameter of 82 . 8 +/- 41 . 8 nm and zeta - potential of + 1 . 12 mV .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [7, 11]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [114, 118]}], "task": "NER"}
{"text": "HPMA - ZnPP had a long plasma half - life and effectively and selectively accumulated in tumors .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [7, 11]}], "task": "NER"}
{"text": "Although HPMA - ZnPP alone had no toxicity in S - 180 tumor - bearing mice , light - irradiation significantly suppressed tumor growth in vivo , similar to the cytotoxicity to HeLa cells in vitro upon endoscopic light - irradiation .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [9, 13]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [16, 20]}], "task": "NER"}
{"text": "HPMA - ZnPP can visualize tumors by fluorescence after i . v . injection , which suggests that this micelle may be useful for both tumor imaging and therapy .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "ZnPP", "entity_type": "Chemical", "pos": [7, 11]}], "task": "NER"}
{"text": "Here we describe preparation of a new fluorescence nanoprobe that is useful for simultaneous tumor imaging and treatment , and application to fluorescence endoscopy is now at visible distance .", "entity": [], "task": "NER"}
{"text": "In vivo biocompatibility , sustained - release and stability of triptorelin formulations based on a liquid , degradable polymer .", "entity": [{"entity": "triptorelin", "entity_type": "Chemical", "pos": [64, 75]}], "task": "NER"}
{"text": "Hexylsubstituted poly ( lactic acid ) ( hexPLA ) is a viscous polymer , which degrades in the presence of water similar to the structure related poly ( lactic acid ) .", "entity": [{"entity": "Hexylsubstituted poly ( lactic acid )", "entity_type": "Chemical", "pos": [0, 37]}, {"entity": "hexPLA", "entity_type": "Chemical", "pos": [40, 46]}, {"entity": "poly ( lactic acid )", "entity_type": "Chemical", "pos": [145, 165]}], "task": "NER"}
{"text": "With hydrophilic active compounds , like Triptorelin acetate , the lipophilic polymer was formulated in form of parenterally injectable suspensions .", "entity": [{"entity": "Triptorelin acetate", "entity_type": "Chemical", "pos": [41, 60]}], "task": "NER"}
{"text": "This first in vivo study toward the biocompatibility of hexPLA implants in rats over 3 months in comparison to in situ forming poly ( lactic - co - glycolic acid ) ( PLGA ) formulations is presented here .", "entity": [{"entity": "hexPLA", "entity_type": "Chemical", "pos": [56, 62]}, {"entity": "poly ( lactic - co - glycolic acid )", "entity_type": "Chemical", "pos": [127, 163]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [166, 170]}], "task": "NER"}
{"text": "The hexPLA implants showed only a mild acute inflammation at the injection site after application , which continuously regressed .", "entity": [{"entity": "hexPLA", "entity_type": "Chemical", "pos": [4, 10]}], "task": "NER"}
{"text": "In contrast to the PLGA formulations , hexPLA did not provoke an encapsulation of the implant with extracellular matrix .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "hexPLA", "entity_type": "Chemical", "pos": [39, 45]}], "task": "NER"}
{"text": "Prior to the formulation application , the stability of Triptorelin inside the hexPLA matrix was assessed under different storage conditions and in the presence of buffer to simulate a peptide degrading environment .", "entity": [{"entity": "Triptorelin", "entity_type": "Chemical", "pos": [56, 67]}, {"entity": "hexPLA", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "At 5 degrees C Triptorelin showed a stability of 98 % inside the polymer for at least 6 months .", "entity": [{"entity": "Triptorelin", "entity_type": "Chemical", "pos": [15, 26]}], "task": "NER"}
{"text": "The stability was still 78 % at an elevated temperature of 40 degrees C .", "entity": [], "task": "NER"}
{"text": "HexPLA protected the incorporated peptide from the surrounding aqueous environment , which resulted in 20 % less degradation inside the polymer compared to the solution .", "entity": [{"entity": "HexPLA", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "This protection effect supports the use of Triptorelin - hexPLA formulations for parenteral sustained - release formulations .", "entity": [{"entity": "Triptorelin", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "hexPLA", "entity_type": "Chemical", "pos": [57, 63]}], "task": "NER"}
{"text": "In a second in vivo evaluation in Wistar Hannover rats , formulations containing 5 % and 10 % Triptorelin in the polymeric matrix released the active compound continuously for 6 months .", "entity": [{"entity": "Triptorelin", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "The formulations showed a higher release during the initial 7 days , which is necessary for the clinical use to down - regulate all GnRH - receptors .", "entity": [], "task": "NER"}
{"text": "Afterwards , a zero order drug release was observed over the first 3 months .", "entity": [], "task": "NER"}
{"text": "After 3 months , the plasma levels decreased slowly but remained at effective concentrations for the total of 6 months .", "entity": [], "task": "NER"}
{"text": "Furthermore , a qualitative in vitro - in vivo correlation was observed , possibly facilitating future optimization of the Triptorelin - hexPLA sustained - release formulations .", "entity": [{"entity": "Triptorelin", "entity_type": "Chemical", "pos": [123, 134]}, {"entity": "hexPLA", "entity_type": "Chemical", "pos": [137, 143]}], "task": "NER"}
{"text": "Nanogel vaccines targeting dendritic cells : contributions of the surface decoration and vaccine cargo on cell targeting and activation .", "entity": [], "task": "NER"}
{"text": "Dendritic cells ( DCs ) play crucial roles in initiating and promoting immune defences , providing a pivotal target for vaccines .", "entity": [], "task": "NER"}
{"text": "Although nanoparticle / nanogel - based delivery vehicles are showing potential for delivering vaccines to the immune system , there is little information on their characteristics of interaction with DCs .", "entity": [], "task": "NER"}
{"text": "While particle uptake by DCs has been shown , the mechanism of cell targeting has not been studied .", "entity": [], "task": "NER"}
{"text": "Moreover , it is still unclear how particle surface decoration influences the handling of such vaccines by DCs .", "entity": [], "task": "NER"}
{"text": "Accordingly , chitosan nanogels carrying a model antigen , ovalbumin ( ova ) , were analysed for interaction with and processing by DCs .", "entity": [], "task": "NER"}
{"text": "Nanogel surfaces decorated with alginate ( alg ) or mannosylated alginate ( alg - man ) , were used for targeting particular DC receptors .", "entity": [{"entity": "man", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "DC uptake of particles was observed , being dependent on endosomal - based processes .", "entity": [], "task": "NER"}
{"text": "Inhibiting PI3 - kinase or lipid raft activities impaired the uptake , which was only reduced , indicating the involvement of more than one endocytic pathway ; notably , this was observed with both nanogel - delivered or free ova .", "entity": [], "task": "NER"}
{"text": "Importantly , surface decoration of particles was less influential on particle uptake , contrasting with the ova cargo which played the major role .", "entity": [], "task": "NER"}
{"text": "Such influence of the vaccine cargo has to date been largely ignored .", "entity": [], "task": "NER"}
{"text": "When receptors interacting directly with ova were blocked , this altered the uptake of alg - nanogels and alg - man - nanogels carrying ova .", "entity": [{"entity": "man", "entity_type": "Chemical", "pos": [112, 115]}], "task": "NER"}
{"text": "The nanogels did have an influential role , in that modulation of DC functional activity owed more to the nanogel structure .", "entity": [], "task": "NER"}
{"text": "Using an in vitro restimulation assay with ova - specific lymphocytes , nanogel - delivered and free ova were similarly effective at inducing specific antibody .", "entity": [], "task": "NER"}
{"text": "Nanogel - delivered ova with mannose surface decoration was superior to free ova for inducing interferon - gamma production by T - lymphocytes .", "entity": [{"entity": "mannose", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "Together , the data demonstrates that particle - based vaccine delivery should consider the influences of both the surface decoration and the vaccine cargo ; each can influence different aspects of the interaction with DCs .", "entity": [], "task": "NER"}
{"text": "Such combined influences are likely to impinge on the characteristics of the immune response induced .", "entity": [], "task": "NER"}
{"text": "Treating epilepsy in Italy between XIX and XX century .", "entity": [], "task": "NER"}
{"text": "Epilepsy is a neurological disorder which has been recognized since antiquity .", "entity": [], "task": "NER"}
{"text": "This paper evaluates the prophylactic and therapeutic remedies used by folk medicine to cure epilepsy in Italy .", "entity": [], "task": "NER"}
{"text": "The data has been collected by reviewing written sources of physicians , ethnographers , folklorists between the late nineteenth and mid twentieth century .", "entity": [], "task": "NER"}
{"text": "This approach leads to unearthing of 78 heterogeneous healing methods that have been divided into 16 ( 20 % ) magical , 20 ( 26 % ) religious and 42 ( 54 % ) natural remedies .", "entity": [], "task": "NER"}
{"text": "The latter has been subdivided into 18 ( 43 % ) animal remedies , 17 ( 40 % ) plant remedies and 7 ( 17 % ) other remedies .", "entity": [], "task": "NER"}
{"text": "Religious and magical remedies were used with the conviction that they would be able to provide recovery from epilepsy and to ward off evil spirits which had taken possession of the sick .", "entity": [], "task": "NER"}
{"text": "Interestingly , the herbal remedies highlighted 12 ( 70 % ) plants that play or might play an important role with respect to the mechanisms that generate the epileptic seizures .", "entity": [], "task": "NER"}
{"text": "This leads us to reconsider the historical significance of folk medicine , too often it is underestimated owing to its use of ineffective remedies , born of incompetence and superstition .", "entity": [], "task": "NER"}
{"text": "Food reward - sensitive interaction of ghrelin and opioid receptor pathways in mesolimbic dopamine system .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "Ghrelin is a stomach - derived orexigenic peptide .", "entity": [], "task": "NER"}
{"text": "The goal of the study was to investigate the roles of mu and kappa opioid receptors in systemic ghrelin - mediated regulation of the mesolimbic dopamine system .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [144, 152]}], "task": "NER"}
{"text": "To evaluate the interaction of systemic ghrelin with values of food reward , rats were exposed to food removal , regular food or palatable food after systemic ghrelin administration .", "entity": [], "task": "NER"}
{"text": "Extracellular dopamine levels were quantified in the nucleus accumbens ( NAc ) and receptor - specific compounds were infused into the ventral tegmental area ( VTA ) using dual - probe microdialysis .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [14, 22]}], "task": "NER"}
{"text": "Consumption of regular or palatable food without systemic ghrelin administration induced an increase in dopamine levels in the NAc via activation of mu opioid receptors in the VTA .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Systemic ghrelin administration ( 3 nmol , i . v . ) followed by no food induced a decrease in dopamine levels via activation of kappa opioid receptors in the VTA .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "Systemic ghrelin administration followed by consumption of regular food induced an increase in dopamine levels via preferential activation of mu opioid receptors , whereas systemic ghrelin administration followed by consumption of palatable food suppressed the increase in dopamine levels via preferential activation of kappa opioid receptors .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [273, 281]}], "task": "NER"}
{"text": "Thus , natural food reward and systemic ghrelin activate mu and kappa opioid receptor pathways in the VTA , respectively , resulting in opposite influences on dopamine release in the NAc .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [159, 167]}], "task": "NER"}
{"text": "Furthermore , systemic ghrelin induces switching of the dominant opioid receptor pathway for highly rewarding food from mu to kappa , resulting in suppression of the mesolimbic dopamine system .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "These novel findings might provide insights into the neural pathways involved in eating disorders .", "entity": [], "task": "NER"}
{"text": "Characterisation of an mGlu8 receptor - selective agonist and antagonist in the lateral and medial perforant path inputs to the dentate gyrus .", "entity": [], "task": "NER"}
{"text": "Since its characterisation in 2001 , the mGlu8 - selective agonist DCPG has been widely used to explore the potential functional role of this group III mGlu receptor within the central nervous system .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "This research has implicated mGlu8 receptors in a number of disease states and conditions such as epilepsy and anxiety , suggesting that mGlu8 - selective ligands may hold important therapeutic potential .", "entity": [], "task": "NER"}
{"text": "However , there is evidence that DCPG exerts off - target effects at higher concentrations , limiting its use as an mGlu8 - selective agonist .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "Here , we have used field recordings in rat hippocampal slices to investigate the effects of DCPG in the lateral perforant path ( LPP ) , a pathway known to express high levels of mGlu8 .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [93, 97]}], "task": "NER"}
{"text": "We show that DCPG does inhibit excitatory transmission in this pathway , but produces a biphasic concentration - response curve suggesting activation of two distinct receptor types .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [13, 17]}], "task": "NER"}
{"text": "The putative mGlu8 - selective antagonist MDCPG antagonises the high , but not the low , potency component of this concentration - response curve .", "entity": [{"entity": "MDCPG", "entity_type": "Chemical", "pos": [42, 47]}], "task": "NER"}
{"text": "In addition , higher concentrations of DCPG also depress excitatory transmission in the medial perforant path ( MPP ) , a pathway expressing very low levels of mGlu8 receptors .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "Experiments in slices from mice lacking mGlu8 receptors indicate that concentrations of DCPG > 1 mu M produce large non - selective effects in both the LPP and MPP .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [88, 92]}], "task": "NER"}
{"text": "Further experiments in slices from mGlu2 , 4 and 7 knock - out mice , as well as in an mGlu2 - deficient substrain of Wistar rat , reveal that these non - selective effects are mediated primarily by mGlu2 receptors .", "entity": [], "task": "NER"}
{"text": "Taken together , our results confirm the mGlu8 - selectivity of DCPG at submicromolar concentrations , but suggest that care must be taken when employing higher concentrations of the agonist , which may additionally activate mGlu2 receptors , especially at synapses where their expression is high .", "entity": [{"entity": "DCPG", "entity_type": "Chemical", "pos": [64, 68]}], "task": "NER"}
{"text": "MDCPG may be a useful tool in determining whether observable DCPG effects are attributable to mGlu8 , versus mGlu2 , receptor activation .", "entity": [{"entity": "MDCPG", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "DCPG", "entity_type": "Chemical", "pos": [61, 65]}], "task": "NER"}
{"text": "Organochlorines and metals induce changes in the mitochondria - rich cells of fish gills : an integrative field study involving chemical , biochemical and morphological analyses .", "entity": [{"entity": "Organochlorines", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Through integrating chemical , biochemical and morphological analyses , this study investigated the effects of multiple pollutants on the gill mitochondria - rich cells ( MRCs ) in two fish species , Astyanax fasciatus and Pimelodus maculatus , collected from five sites ( FU10 , FU20 , FU30 , FU40 and FU50 ) in the Furnas Hydroelectric Power Station reservoir .", "entity": [], "task": "NER"}
{"text": "Water analyses revealed aluminum , iron and zinc as well as organochlorine ( aldrin / dieldrin , endosulfan , heptachlor / heptachlor epoxide and metolachlor ) contamination at all of the sites , with the exception of FU10 .", "entity": [{"entity": "aluminum", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "iron", "entity_type": "Chemical", "pos": [35, 39]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [60, 74]}, {"entity": "aldrin", "entity_type": "Chemical", "pos": [77, 83]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [86, 94]}, {"entity": "endosulfan", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "heptachlor", "entity_type": "Chemical", "pos": [110, 120]}, {"entity": "heptachlor epoxide", "entity_type": "Chemical", "pos": [123, 141]}, {"entity": "metolachlor", "entity_type": "Chemical", "pos": [146, 157]}], "task": "NER"}
{"text": "Copper , chrome , iron and zinc were detected in the gills of both species , and aldrin / dieldrin , endosulfan and heptachlor / heptachlor epoxide were detected in the gills of fish from all of the sites , with the exception of FU10 .", "entity": [{"entity": "Copper", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "chrome", "entity_type": "Chemical", "pos": [9, 15]}, {"entity": "iron", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "aldrin", "entity_type": "Chemical", "pos": [81, 87]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [90, 98]}, {"entity": "endosulfan", "entity_type": "Chemical", "pos": [101, 111]}, {"entity": "heptachlor", "entity_type": "Chemical", "pos": [116, 126]}, {"entity": "heptachlor epoxide", "entity_type": "Chemical", "pos": [129, 147]}], "task": "NER"}
{"text": "Fish collected at FU20 , FU30 and FU50 exhibited numerous alterations in the surface architecture of their pavement cells and MRCs .", "entity": [], "task": "NER"}
{"text": "The surface MRC density and MRC fractional area were lower in fish from FU20 , FU30 , FU40 and FU50 than in those from the reference site ( FU10 ) in the winter , and some variability between the sites was observed in the summer .", "entity": [], "task": "NER"}
{"text": "The organochlorine contamination at FU20 and FU50 was associated with variable changes in the MRCs and inhibition of Na ( + ) / K ( + ) - ATPase ( NKA ) activity , especially in P . maculatus .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [4, 18]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [117, 125]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [128, 135]}], "task": "NER"}
{"text": "At FU30 , the alterations in the MRCs were associated with the contaminants present , especially metals .", "entity": [], "task": "NER"}
{"text": "A multivariate analysis demonstrated a positive association between the biological responses of both species and environmental contamination , indicating that under realistic conditions , a mixture of organochlorines and metals affected the MRCs by inhibiting NKA activity and inducing morphological changes , which may cause an ionic imbalance .", "entity": [{"entity": "organochlorines", "entity_type": "Chemical", "pos": [201, 216]}], "task": "NER"}
{"text": "Identification and discrimination of snake venoms from Egyptian elapids .", "entity": [], "task": "NER"}
{"text": "The avidity to the corresponding antigens is often higher than to the cross - reactive antigens .", "entity": [], "task": "NER"}
{"text": "This was demonstrated with the highly cross - reactive elapid Egyptian snake venoms Naja haje ( Nh ) , Naja nigricollis ( Nn ) and Walterinnesia aegyptia ( Wa ) , and used for the differentiation among the three species in a simple ELISA - based assay .", "entity": [], "task": "NER"}
{"text": "A three - step immuno - affinity protocol was followed and the titer and avidity of the different antibody ( Ab ) preparations were assessed and evaluated .", "entity": [], "task": "NER"}
{"text": "The advantages offered by the avidity power of the venom specific antibodies ( VS - Abs ) obtained after one step purification , outweigh the specificity of the species - specific antibodies ( SS - Abs ) obtained after further purification .", "entity": [], "task": "NER"}
{"text": "The efficiency of the VS - Abs as special immunodiagnostics was validated using 16 venom samples collected from individual snakes of different size and age at different time intervals .", "entity": [], "task": "NER"}
{"text": "The avidities of the VS - Abs to the homologous venoms were 2 . 53 +/- 0 . 4 , 2 . 66 +/- 0 . 31 and 2 . 8 +/- 0 . 06 for Nh , Nn and Wa venoms respectively ; whereas the avidity of the same Abs to the heterologous venoms could hardly exceed 1 .", "entity": [], "task": "NER"}
{"text": "Venom concentrations in the range between 10 - 1250 ng / well were detected with almost the same efficiency , an extra advantage that could be added to the assay to assure equal sensitivity allover the mentioned venom concentration range .", "entity": [], "task": "NER"}
{"text": "Effects of the natural endocrine disruptor equol on the pituitary function in adult male rats .", "entity": [{"entity": "equol", "entity_type": "Chemical", "pos": [43, 48]}], "task": "NER"}
{"text": "Equol ( EQ ) , a potent biologically active metabolite of the soy isoflavone daidzein , interacts with estrogen receptors ( ERs ) , however , as suggested recently , EQ may also exert anti - androgenic actions in androgen regulated tissues like prostate and seminal vesicles in adult male rats .", "entity": [{"entity": "Equol", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "isoflavone", "entity_type": "Chemical", "pos": [66, 76]}, {"entity": "daidzein", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [103, 111]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [191, 199]}], "task": "NER"}
{"text": "However , data regarding a putative anti - androgenic activity of EQ on pituitary function in male individuals are still lacking .", "entity": [], "task": "NER"}
{"text": "Therefore , we investigated the effects of EQ on androgen - and estrogen - regulated gene expressions in the pituitary and circulating luteinizing hormone ( LH ) and prolactin ( PRL ) levels in adult male rats .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [49, 57]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "3 - Month - old male Sprague - Dawley rats ( n = 12 per group ) were treated by gavage for 5 days with either EQ ( 100 and 250 mg / kg BW / day ) or vehicle olive oil ( 1 ml / rat / day ) .", "entity": [], "task": "NER"}
{"text": "As reference compound , the pure anti - androgenic drug flutamide ( FLUT ) was employed at a dose of 100 mg / kg BW / day .", "entity": [{"entity": "flutamide", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "FLUT", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "At day 5 , animals were sacrificed .", "entity": [], "task": "NER"}
{"text": "Levels of pituitary hormones and gene expression were measured by radioimmunoassays and quantitative TaqMan ( (R) ) real - time reverse transcription polymerase chain reaction , respectively .", "entity": [], "task": "NER"}
{"text": "The present findings revealed that the pituitary mechanisms involved in the effects of EQ and FLUT were different due to the opposite changes in the mRNA expression levels of estrogen receptor subtype alpha ( ER alpha ) - , truncated estrogen receptor product - 1 ( TERP - 1 ) - and - 2 ( TERP - 2 ) - , gonadotropin releasing hormone receptor ( GnRH receptor ) - , beta - subunit of LH ( LH beta ) - , and gonadotropin alpha subunit ( alpha - subunit ) genes .", "entity": [{"entity": "FLUT", "entity_type": "Chemical", "pos": [94, 98]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [175, 183]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [234, 242]}, {"entity": "gonadotropin releasing hormone", "entity_type": "Chemical", "pos": [304, 334]}, {"entity": "GnRH", "entity_type": "Chemical", "pos": [346, 350]}], "task": "NER"}
{"text": "EQ displayed typical ER - agonistic actions as shown by the significant increases in ER alpha - , TERP - 1 / - 2 mRNA expressions and serum PRL levels along with the significant reduction in serum LH levels , whereas FLUT exerted opposite effects on gonadotropin secretion and expression .", "entity": [{"entity": "FLUT", "entity_type": "Chemical", "pos": [217, 221]}], "task": "NER"}
{"text": "Taken together , our findings are the first in vivo data that upon sub - acute oral exposure of EQ show an estrogenic effect on reproductive endocrine activity of the pituitary in adult male rats .", "entity": [], "task": "NER"}
{"text": "However , EQ did not exert anti - androgenic effects on male rat pituitary function as observed at the levels of mRNA expression of androgen - and estrogen - regulated genes and circulating pituitary hormones .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [34, 42]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [147, 155]}], "task": "NER"}
{"text": "Retinoic acid biosynthesis catalyzed by retinal dehydrogenases relies on a rate - limiting conformational transition associated with substrate recognition .", "entity": [{"entity": "Retinoic acid", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [40, 47]}], "task": "NER"}
{"text": "Retinoic acid ( RA ) , a metabolite of vitamin A , exerts pleiotropic effects throughout life in vertebrate organisms .", "entity": [{"entity": "Retinoic acid", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "vitamin A", "entity_type": "Chemical", "pos": [39, 48]}], "task": "NER"}
{"text": "Thus , RA action must be tightly regulated through the coordinated action of biosynthetic and degrading enzymes .", "entity": [], "task": "NER"}
{"text": "The last step of retinoic acid biosynthesis is irreversibly catalyzed by the NAD - dependent retinal dehydrogenases ( RALDH ) , which are members of the aldehyde dehydrogenase ( ALDH ) superfamily .", "entity": [{"entity": "retinoic acid", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "NAD", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [93, 100]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [153, 161]}], "task": "NER"}
{"text": "Low intracellular retinal concentrations imply efficient substrate molecular recognition to ensure high affinity and specificity of RALDHs for retinal .", "entity": [{"entity": "retinal", "entity_type": "Chemical", "pos": [18, 25]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [143, 150]}], "task": "NER"}
{"text": "This study addresses the molecular basis of retinal recognition in human ALDH1A1 ( or RALDH1 ) and rat ALDH1A2 ( or RALDH2 ) , through the comparison of the catalytic behavior of retinal analogs and use of the fluorescence properties of retinol .", "entity": [{"entity": "retinal", "entity_type": "Chemical", "pos": [44, 51]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [179, 186]}, {"entity": "retinol", "entity_type": "Chemical", "pos": [237, 244]}], "task": "NER"}
{"text": "We show that , in contrast to long chain unsaturated substrates , the rate - limiting step of retinal oxidation by RALDHs is associated with acylation .", "entity": [{"entity": "retinal", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Use of the fluorescence resonance energy transfer upon retinol interaction with RALDHs provides evidence that retinal recognition occurs in two steps : binding into the substrate access channel , and a slower structural reorganization with a rate constant of the same magnitude as the kcat for retinal oxidation : 0 . 18 vs . 0 . 07 and 0 . 25 vs . 0 . 1 s ( - 1 ) for ALDH1A1 and ALDH1A2 , respectively .", "entity": [{"entity": "retinol", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [110, 117]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [294, 301]}], "task": "NER"}
{"text": "This suggests that the conformational transition of the RALDH - retinal complex significantly contributes to the rate - limiting step that controls the kinetics of retinal oxidation , as a prerequisite for the formation of a catalytically competent Michaelis complex .", "entity": [{"entity": "retinal", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "retinal", "entity_type": "Chemical", "pos": [164, 171]}], "task": "NER"}
{"text": "This conclusion is consistent with the general notion that structural flexibility within the active site of ALDH enzymes has been shown to be an integral component of catalysis .", "entity": [], "task": "NER"}
{"text": "Inhibition of human alcohol and aldehyde dehydrogenases by cimetidine and assessment of its effects on ethanol metabolism .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [32, 40]}, {"entity": "cimetidine", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "Previous studies have reported that cimetidine , an H2 - receptor antagonist used to treat gastric and duodenal ulcers , can inhibit alcohol dehydrogenases ( ADHs ) and ethanol metabolism .", "entity": [{"entity": "cimetidine", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [133, 140]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [169, 176]}], "task": "NER"}
{"text": "Human alcohol dehydrogenases and aldehyde dehydrogenases ( ALDHs ) , the principal enzymes responsible for metabolism of ethanol , are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [6, 13]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [121, 128]}], "task": "NER"}
{"text": "We investigated the inhibition by cimetidine of alcohol oxidation by recombinant human ADH1A , ADH1B1 , ADH1B2 , ADH1B3 , ADH1C1 , ADH1C2 , ADH2 , and ADH4 , and aldehyde oxidation by ALDH1A1 and ALDH2 at pH 7 . 5 and a cytosolic NAD ( + ) concentration .", "entity": [{"entity": "cimetidine", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [162, 170]}, {"entity": "NAD ( + )", "entity_type": "Chemical", "pos": [230, 239]}], "task": "NER"}
{"text": "Cimetidine acted as competitive or noncompetitive inhibitors for the ADH and ALDH isozymes / allozymes with near mM inhibition constants .", "entity": [{"entity": "Cimetidine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The metabolic interactions between cimetidine and ethanol / acetaldehyde were assessed by computer simulation using the inhibition equations and the determined kinetic constants .", "entity": [{"entity": "cimetidine", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [50, 57]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [60, 72]}], "task": "NER"}
{"text": "At therapeutic drug levels ( 0 . 015 mM ) and physiologically relevant concentrations of ethanol ( 10 mM ) and acetaldehyde ( 10 mu M ) in target tissues , cimetidine could weakly inhibit ( < 5 % ) the activities of ADH1B2 and ADH1B3 in liver , ADH2 in liver and small intestine , ADH4 in stomach , and ALDH1A1 in the three tissues , but not significantly affect ADH1A , ADH1B1 , ADH1C1 / 2 , or ALDH2 .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [111, 123]}, {"entity": "cimetidine", "entity_type": "Chemical", "pos": [156, 166]}], "task": "NER"}
{"text": "At higher drug levels , which may accumulate in cells ( 0 . 2 mM ) , the activities of the weakly - inhibited enzymes may be decreased more significantly .", "entity": [], "task": "NER"}
{"text": "The quantitative effects of cimetidine on metabolism of ethanol and other physiological substrates of ADHs need further investigation .", "entity": [{"entity": "cimetidine", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "Anti - inflammatory properties of fruit juices enriched with pine bark extract in an in vitro model of inflamed human intestinal epithelium : the effect of gastrointestinal digestion .", "entity": [], "task": "NER"}
{"text": "Enrichment of fruit juices with pine bark extract ( PBE ) could be a strategy to compensate for phenolic losses during the gastrointestinal digestion .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "A coculture system with Caco - 2 cells and RAW 264 . 7 macrophages was established as an in vitro model of inflamed human intestinal epithelium for evaluating the anti - inflammatory capacity of fruit juices enriched with PBE ( 0 . 5 g L ( - 1 ) ) before and after in vitro digestion .", "entity": [], "task": "NER"}
{"text": "The digestion of both PBE - enriched pineapple and red fruit juice led to significant changes in most of the analysed phenolic compounds .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [118, 126]}], "task": "NER"}
{"text": "The in vitro inflammatory state showed cell barrier dysfunction and overproduction of IL - 8 , nitric oxide ( NO ) and reactive oxygen species ( ROS ) .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [95, 107]}, {"entity": "NO", "entity_type": "Chemical", "pos": [110, 112]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [128, 134]}], "task": "NER"}
{"text": "In the inflamed cells , incubation with nondigested samples reduced ( P < 0 . 05 ) the production of IL - 8 and NO compared with digested samples .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [112, 114]}], "task": "NER"}
{"text": "ROS production increased in the inflamed cells exposed to digested commercial red fruit juice ( 86 . 8 +/- 1 . 3 % ) compared with fresh juice ( 77 . 4 +/- 0 . 8 % ) and increased in the inflamed cells exposed to digested enriched red fruit juice ( 82 . 6 +/- 1 . 6 % ) compared with the fresh enriched juice ( 55 . 8 +/- 6 % ) .", "entity": [], "task": "NER"}
{"text": "The anti - inflammatory properties of PBE - enriched fruit juices decreased after digestion ; further research on the bioavailability of the assayed compounds is needed to properly assess their usefulness for the treatment of gut inflammation .", "entity": [], "task": "NER"}
{"text": "New mycotoxins from marine - derived fungus Aspergillus sp .", "entity": [], "task": "NER"}
{"text": "SCSGAF0093 .", "entity": [], "task": "NER"}
{"text": "Nine mycotoxins including six aspergillic acid group toxins , aluminiumneoaspergillin ( 1 ) , zirconiumneoaspergillin ( 2 ) , aspergilliamide ( 3 ) , ferrineoaspergillin ( 5 ) , flavacol ( 6 ) , neoaspergillic acid ( 7 ) , and three ochratoxins , ochratoxin A n - butyl ester ( 4 ) , ochratoxin A ( 8 ) , ochratoxin A methyl ester ( 9 ) , were isolated from the fermentation broth of marine gorgonian derived fungus Aspergillus sp .", "entity": [{"entity": "aspergillic acid", "entity_type": "Chemical", "pos": [30, 46]}, {"entity": "aluminiumneoaspergillin", "entity_type": "Chemical", "pos": [62, 85]}, {"entity": "zirconiumneoaspergillin", "entity_type": "Chemical", "pos": [94, 117]}, {"entity": "aspergilliamide", "entity_type": "Chemical", "pos": [126, 141]}, {"entity": "ferrineoaspergillin", "entity_type": "Chemical", "pos": [150, 169]}, {"entity": "flavacol", "entity_type": "Chemical", "pos": [178, 186]}, {"entity": "neoaspergillic acid", "entity_type": "Chemical", "pos": [195, 214]}, {"entity": "ochratoxins", "entity_type": "Chemical", "pos": [233, 244]}, {"entity": "ochratoxin A n - butyl ester", "entity_type": "Chemical", "pos": [247, 275]}, {"entity": "ochratoxin A", "entity_type": "Chemical", "pos": [284, 296]}, {"entity": "ochratoxin A methyl ester", "entity_type": "Chemical", "pos": [305, 330]}], "task": "NER"}
{"text": "Four of them ( 1 - 4 ) were new mycotoxins , and their structures were elucidated on the basis of spectroscopic analysis and chemical evidence .", "entity": [], "task": "NER"}
{"text": "The bio - toxicity of compounds 1 - 9 were determined by brine shrimp lethality bioassay with median lethal concentration ( LC ( 50 ) ) values of 2 . 59 - 205 . 67 mu M .", "entity": [], "task": "NER"}
{"text": "This was the first report about zirconium complex obtained from nature and ochratoxins isolated from marine environment .", "entity": [{"entity": "zirconium", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "ochratoxins", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "The selective SYK inhibitor P505 - 15 ( PRT062607 ) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia .", "entity": [{"entity": "P505 - 15", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "PRT062607", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "fludarabine", "entity_type": "Chemical", "pos": [141, 152]}], "task": "NER"}
{"text": "B - cell receptor ( BCR ) associated kinases including spleen tyrosine kinase ( SYK ) contribute to the pathogenesis of B - cell malignancies .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "SYK is persistently phosphorylated in a subset of non - Hodgkin lymphoma ( NHL ) and chronic lymphocytic leukemia ( CLL ) , and SYK inhibition results in abrogation of downstream kinase activity and apoptosis .", "entity": [], "task": "NER"}
{"text": "P505 - 15 ( also known as PRT062607 ) is a novel , highly selective , and orally bioavailable small molecule SYK inhibitor ( SYK IC ( 50 ) = 1 nM ) with anti - SYK activity that is at least 80 - fold greater than its affinity for other kinases .", "entity": [{"entity": "P505 - 15", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "PRT062607", "entity_type": "Chemical", "pos": [26, 35]}], "task": "NER"}
{"text": "We evaluated the preclinical characteristics of P505 - 15 in models of NHL and CLL .", "entity": [{"entity": "P505 - 15", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "P505 - 15 successfully inhibited SYK - mediated B - cell receptor signaling and decreased cell viability in NHL and CLL .", "entity": [{"entity": "P505 - 15", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Oral dosing in mice prevented BCR - mediated splenomegaly and significantly inhibited NHL tumor growth in a xenograft model .", "entity": [], "task": "NER"}
{"text": "In addition , combination treatment of primary CLL cells with P505 - 15 plus fludarabine produced synergistic enhancement of activity at nanomolar concentrations .", "entity": [{"entity": "P505 - 15", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "fludarabine", "entity_type": "Chemical", "pos": [77, 88]}], "task": "NER"}
{"text": "Our findings support the ongoing development of P505 - 15 as a therapeutic agent for B - cell malignancies .", "entity": [{"entity": "P505 - 15", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "A dose finding study in healthy volunteers has been completed .", "entity": [], "task": "NER"}
{"text": "Ticlopidine , a cholestatic liver injury - inducible drug , causes dysfunction of bile formation via diminished biliary secretion of phospholipids : involvement of biliary - excreted glutathione - conjugated ticlopidine metabolites .", "entity": [{"entity": "Ticlopidine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [183, 194]}, {"entity": "ticlopidine", "entity_type": "Chemical", "pos": [208, 219]}], "task": "NER"}
{"text": "The antiplatelet drug , ticlopidine ( TIC ) , reportedly causes cholestatic liver injuries .", "entity": [{"entity": "ticlopidine", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "TIC", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "The present study analyzed the effect of TIC on bile formation , revealing that the biliary secretion of phospholipids was significantly decreased in TIC - administered Sprague Dawley ( SD ) rats .", "entity": [{"entity": "TIC", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "TIC", "entity_type": "Chemical", "pos": [150, 153]}], "task": "NER"}
{"text": "However , the effect of TIC on biliary phospholipids was not observed in SD rats pretreated with diethylaminoethyl diphenylpropylacetate that inhibits cytochrome P450s ( P450 ) , or in Eisai hyperbilirubinemic rats ( EHBR ) lacking functional multidrug resistance - associated protein 2 ( MRP2 / ABCC2 ) .", "entity": [{"entity": "TIC", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "diethylaminoethyl diphenylpropylacetate", "entity_type": "Chemical", "pos": [97, 136]}], "task": "NER"}
{"text": "These results suggest that glutathione - conjugated TIC metabolites ( TIC - SGs ) , which were formed in the liver after P450s - mediated metabolism and were excreted extensively into bile by MRP2 , mediated the observed alterations of the bile composition .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "TIC", "entity_type": "Chemical", "pos": [52, 55]}, {"entity": "TIC", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "Administration of TIC caused significant liver injuries in SD rats , with decreased biliary phospholipids , but not in EHBR , consistent with the in vitro observation that phospholipid - bile acid - mixed micelles moderated the cytotoxic effects of bile acids .", "entity": [{"entity": "TIC", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [187, 196]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [249, 259]}], "task": "NER"}
{"text": "Further analyses revealed that TIC - SGs did not directly inhibit multidrug resistance 3 P - glycoprotein ( MDR3 / ABCB4 ) - mediated phosphatidylcholine efflux in vitro .", "entity": [{"entity": "TIC", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [134, 153]}], "task": "NER"}
{"text": "Because the diminished biliary secretion of phospholipids with TIC administration was restored by taurocholate infusion in SD rats , the decreased biliary concentration of bile acids , due to the stimulation of bile acid - independent bile flow driven by TIC - SGs , might have indirectly attenuated phospholipid secretion .", "entity": [{"entity": "TIC", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "taurocholate", "entity_type": "Chemical", "pos": [98, 110]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [172, 182]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [211, 220]}, {"entity": "TIC", "entity_type": "Chemical", "pos": [255, 258]}], "task": "NER"}
{"text": "In conclusion , extensive biliary excretion of TIC - SGs decreased the biliary secretion of phospholipids , which might have increased the risk of TIC - induced cholestatic liver injury .", "entity": [{"entity": "TIC", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "TIC", "entity_type": "Chemical", "pos": [147, 150]}], "task": "NER"}
{"text": "Apomorphine is a bimodal modulator of TRPA1 channels .", "entity": [{"entity": "Apomorphine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Apomorphine is a non - narcotic derivative of morphine , which acts as a dopamine agonist and is clinically used to treat \" off - states \" in patients suffering from Parkinson ' s disease .", "entity": [{"entity": "Apomorphine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "Adverse effects of apomorphine treatment include severe emesis and nausea , and ulceration and pain at the injection site .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [19, 30]}], "task": "NER"}
{"text": "We wanted to test whether sensory transient receptor potential ( TRP ) channels are a molecular target for apomorphine .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [107, 118]}], "task": "NER"}
{"text": "Here , we show that rTRPV1 , rTRPV2 , rTRPV3 , and mTRPV4 , as well as hTRPM8 , and rTRPM3 , which are expressed in dorsal root ganglion neurons , are insensitive toward apomorphine treatment .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [170, 181]}], "task": "NER"}
{"text": "This also applied to the cellular redox sensor hTRPM2 .", "entity": [], "task": "NER"}
{"text": "On the contrary , human TRPA1 could be concentration - dependently modulated by apomorphine .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "Whereas the addition of apomorphine in the low micromolar range produced an irreversible activation of the channel , application of higher concentrations caused a reversible voltage - dependent inhibition of heterologously expressed TRPA1 channels , resulting from a reduction of single - channel open times .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "In addition , we provide evidence that apomorphine also acts on endogenous TRPA1 in cultured dorsal root ganglion neurons from rats and in the enterochromaffin model cell line QGP - 1 , from which serotonin is released upon activation of TRPA1 .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [197, 206]}], "task": "NER"}
{"text": "Our study shows that human TRPA1 is a target for apomorphine , suggesting that an activation of TRPA1 might contribute to adverse side effects such as nausea and painful injections , which can occur during treatment with apomorphine .", "entity": [{"entity": "apomorphine", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "apomorphine", "entity_type": "Chemical", "pos": [221, 232]}], "task": "NER"}
{"text": "Human stearoyl - CoA desaturase 1 ( SCD - 1 ) gene expression is negatively regulated by thyroid hormone without direct binding of thyroid hormone receptor to the gene promoter .", "entity": [{"entity": "stearoyl - CoA", "entity_type": "Chemical", "pos": [6, 20]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [89, 104]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [131, 146]}], "task": "NER"}
{"text": "Stearoyl - CoA desaturase - 1 ( SCD - 1 ) plays a pivotal role in an increase of triglyceride by an excess of dietary carbohydrate intake .", "entity": [{"entity": "Stearoyl - CoA", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [118, 130]}], "task": "NER"}
{"text": "Dietary carbohydrates increase SCD - 1 gene expression in liver by sterol response element binding protein ( SREBP ) - 1c - dependent and SREBP - 1c - independent pathways .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [67, 73]}], "task": "NER"}
{"text": "Previous report demonstrated that thyroid hormone ( TH ) negatively regulates mouse SCD - 1 gene promoter before SREBP - 1c was revealed .", "entity": [{"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [34, 49]}], "task": "NER"}
{"text": "We reported that TH negatively regulates SREBP - 1c recently .", "entity": [], "task": "NER"}
{"text": "Therefore , in the current study , we examined whether and how TH regulates human SCD - 1 gene expression and evaluated SREBP - 1c effect on the negative regulation .", "entity": [], "task": "NER"}
{"text": "Luciferase assays revealed that TH suppresses both mouse and human SCD - 1 gene promoter activity .", "entity": [], "task": "NER"}
{"text": "In SREBP - 1 knockdown HepG2 cells , TH still suppresses SCD - 1 gene promoter activity , and it also exerted the negative regulation under cotransfection of a small amount of SREBP - 1c .", "entity": [], "task": "NER"}
{"text": "These data indicated that SREBP - 1c does not play the decisive role for the negative regulation by TH .", "entity": [], "task": "NER"}
{"text": "The responsible region for the negative regulation in human SCD - 1 gene promoter turned out to be between - 124 and - 92 bp , referred to as site A .", "entity": [], "task": "NER"}
{"text": "Chromatin immunoprecipitation assays demonstrated that TH receptor - beta is recruited to the region upon T ( 3 ) administration , although TR - beta does not bind directly to site A .", "entity": [], "task": "NER"}
{"text": "In conclusion , TH negatively regulates human SCD - 1 gene expression in without direct binding of the TH receptor to the SCD - 1 gene promoter .", "entity": [], "task": "NER"}
{"text": "An in vitro network of intermolecular interactions between viral RNA segments of an avian H5N2 influenza A virus : comparison with a human H3N2 virus .", "entity": [], "task": "NER"}
{"text": "The genome of influenza A viruses ( IAV ) is split into eight viral RNAs ( vRNAs ) that are encapsidated as viral ribonucleoproteins .", "entity": [], "task": "NER"}
{"text": "The existence of a segment - specific packaging mechanism is well established , but the molecular basis of this mechanism remains to be deciphered .", "entity": [], "task": "NER"}
{"text": "Selective packaging could be mediated by direct interaction between the vRNA packaging regions , but such interactions have never been demonstrated in virions .", "entity": [], "task": "NER"}
{"text": "Recently , we showed that the eight vRNAs of a human H3N2 IAV form a single interaction network in vitro that involves regions of the vRNAs known to contain packaging signals in the case of H1N1 IAV strains .", "entity": [], "task": "NER"}
{"text": "Here , we show that the eight vRNAs of an avian H5N2 IAV also form a single network of interactions in vitro , but , interestingly , the interactions and the regions of the vRNAs they involve differ from those described for the human H3N2 virus .", "entity": [], "task": "NER"}
{"text": "We identified the vRNA sequences involved in five of these interactions at the nucleotide level , and in two cases , we validated the existence of the interaction using compensatory mutations in the interacting sequences .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [79, 89]}], "task": "NER"}
{"text": "Electron tomography also revealed significant differences in the interactions taking place between viral ribonucleoproteins in H5N2 and H3N2 virions , despite their canonical ' 7 + 1 ' arrangement .", "entity": [], "task": "NER"}
{"text": "Chromatin - dependent and - independent regulation of DNA replication origin activation in budding yeast .", "entity": [], "task": "NER"}
{"text": "To elucidate the role of the chromatin environment in the regulation of replication origin activation , autonomously replicating sequences were inserted into identical locations in the budding yeast genome and their activation times in S phase determined .", "entity": [], "task": "NER"}
{"text": "Chromatin - dependent origins adopt to the firing time of the surrounding locus .", "entity": [], "task": "NER"}
{"text": "In contrast , the origins containing two binding sites for Forkhead transcription factors are activated early in the S phase regardless of their location in the genome .", "entity": [], "task": "NER"}
{"text": "Our results also show that genuinely late - replicating parts of the genome can be converted into early - replicating loci by insertion of a chromatin - independent early replication origin , ARS607 , whereas insertion of two Forkhead - binding sites is not sufficient for conversion .", "entity": [], "task": "NER"}
{"text": "HLA - DO acts as a substrate mimic to inhibit HLA - DM by a competitive mechanism .", "entity": [], "task": "NER"}
{"text": "Mammalian class II major histocompatibility ( MHCII ) proteins bind peptide antigens in endosomal compartments of antigen - presenting cells .", "entity": [], "task": "NER"}
{"text": "The nonclassical MHCII protein HLA - DM chaperones peptide - free MHCII , protecting it against inactivation , and catalyzes peptide exchange on loaded MHCII .", "entity": [], "task": "NER"}
{"text": "Another nonclassical MHCII protein , HLA - DO , binds HLA - DM and influences the repertoire of peptides presented by MHCII proteins .", "entity": [], "task": "NER"}
{"text": "However , the mechanism by which HLA - DO functions is unclear .", "entity": [], "task": "NER"}
{"text": "Here we have used X - ray crystallography , enzyme kinetics and mutagenesis approaches to investigate human HLA - DO structure and function .", "entity": [], "task": "NER"}
{"text": "In complex with HLA - DM , HLA - DO adopts a classical MHCII structure , with alterations near the alpha subunit ' s 3 1 0 helix .", "entity": [], "task": "NER"}
{"text": "HLA - DO binds to HLA - DM at the same sites implicated in MHCII interaction , and kinetic analysis showed that HLA - DO acts as a competitive inhibitor .", "entity": [], "task": "NER"}
{"text": "These results show that HLA - DO inhibits HLA - DM function by acting as a substrate mimic , and the findings also limit the possible functional roles for HLA - DO in antigen presentation .", "entity": [], "task": "NER"}
{"text": "DAXX - dependent supply of soluble ( H3 . 3 - H4 ) dimers to PML bodies pending deposition into chromatin .", "entity": [], "task": "NER"}
{"text": "Replication - independent chromatin deposition of histone variant H3 . 3 is mediated by several chaperones .", "entity": [], "task": "NER"}
{"text": "We report a multistep targeting of newly synthesized epitope - tagged H3 . 3 to chromatin via PML bodies .", "entity": [], "task": "NER"}
{"text": "H3 . 3 is recruited to PML bodies in a DAXX - dependent manner , a process facilitated by ASF1A .", "entity": [], "task": "NER"}
{"text": "DAXX is required for enrichment of ATRX , but not ASF1A or HIRA , with PML .", "entity": [], "task": "NER"}
{"text": "Nonetheless , the chaperones colocalize with H3 . 3 at PML bodies and are found in one or more complexes with PML .", "entity": [], "task": "NER"}
{"text": "Both DAXX and PML are necessary to prevent accumulation of a soluble , nonincorporated pool of H3 . 3 .", "entity": [], "task": "NER"}
{"text": "H3 . 3 targeting to PML is enhanced with an ( H3 . 3 - H4 ) 2 tetramerization mutant of H3 . 3 , suggesting H3 . 3 recruitment to PML as an ( H3 . 3 - H4 ) dimer rather than as a tetramer .", "entity": [], "task": "NER"}
{"text": "Our data support a model of DAXX - mediated recruitment of ( H3 . 3 - H4 ) dimers to PML bodies , which may function as triage centers for H3 . 3 deposition into chromatin by distinct chaperones .", "entity": [], "task": "NER"}
{"text": "Cell - based screening identifies paroxetine as an inhibitor of diabetic endothelial dysfunction .", "entity": [{"entity": "paroxetine", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "We have conducted a phenotypic screening in endothelial cells exposed to elevated extracellular glucose ( an in vitro model of hyperglycemia ) to identify compounds that prevent hyperglycemia - induced reactive oxygen species ( ROS ) formation without adversely affecting cell viability .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [96, 103]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [211, 217]}], "task": "NER"}
{"text": "From a focused library of > 6 , 000 clinically used drug - like and pharmacologically active compounds , several classes of active compounds emerged , with a confirmed hit rate of < 0 . 5 % .", "entity": [], "task": "NER"}
{"text": "Follow - up studies focused on paroxetine , a clinically used antidepressant compound that has not been previously implicated in the context of hyperglycemia or diabetes .", "entity": [{"entity": "paroxetine", "entity_type": "Chemical", "pos": [31, 41]}], "task": "NER"}
{"text": "Paroxetine reduced hyperglycemia - induced mitochondrial ROS formation , mitochondrial protein oxidation , and mitochondrial and nuclear DNA damage , without interfering with mitochondrial electron transport or cellular bioenergetics .", "entity": [{"entity": "Paroxetine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The ability of paroxetine to improve hyperglycemic endothelial cell injury was unique among serotonin reuptake blockers and can be attributed to its antioxidant effect , which primarily resides within its sesamol moiety .", "entity": [{"entity": "paroxetine", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [92, 101]}, {"entity": "sesamol", "entity_type": "Chemical", "pos": [205, 212]}], "task": "NER"}
{"text": "Paroxetine maintained the ability of vascular rings to respond to the endothelium - dependent relaxant acetylcholine , both during in vitro hyperglycemia and ex vivo , in a rat model of streptozotocin - induced diabetes .", "entity": [{"entity": "Paroxetine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [103, 116]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [186, 200]}], "task": "NER"}
{"text": "Thus , the current work identifies a novel pharmacological action of paroxetine as a protector of endothelial cells against hyperglycemic injury and raises the potential of repurposing of this drug for the experimental therapy of diabetic cardiovascular complications .", "entity": [{"entity": "paroxetine", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "Gamma - radiolysis - assisted cobalt oxide nanoparticle formation .", "entity": [{"entity": "cobalt oxide", "entity_type": "Chemical", "pos": [30, 42]}], "task": "NER"}
{"text": "The formation of Co ( 3 ) O ( 4 ) nano - scale colloid particles by gamma irradiation of CoSO ( 4 ) solutions was investigated .", "entity": [{"entity": "Co ( 3 ) O ( 4 )", "entity_type": "Chemical", "pos": [17, 33]}, {"entity": "CoSO ( 4 )", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "Solutions of 0 . 2 - 0 . 3 mM CoSO ( 4 ) at pH 6 . 0 and 10 . 6 ( air - saturated and Ar - purged ) were irradiated at an absorbed dose rate of 5 . 5 kGy h ( - 1 ) .", "entity": [{"entity": "CoSO ( 4 )", "entity_type": "Chemical", "pos": [30, 40]}], "task": "NER"}
{"text": "The resulting concentrations of H ( 2 ) , H ( 2 ) O ( 2 ) , Co ( II ) and Co ( III ) species in solution and the chemical composition and sizes of particles that were formed were measured as a function of irradiation time .", "entity": [{"entity": "H ( 2 )", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [42, 57]}, {"entity": "Co ( II )", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "Co ( III )", "entity_type": "Chemical", "pos": [74, 84]}], "task": "NER"}
{"text": "Particle formation was observed only for initially air - saturated CoSO ( 4 ) solutions at pH 10 . 6 .", "entity": [{"entity": "CoSO ( 4 )", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Analysis of the particle formation as a function of irradiation time shows that the particles evolve from Co ( OH ) ( 2 ) to CoOOH and then to Co ( 3 ) O ( 4 ) .", "entity": [{"entity": "Co ( OH ) ( 2 )", "entity_type": "Chemical", "pos": [106, 121]}, {"entity": "CoOOH", "entity_type": "Chemical", "pos": [125, 130]}, {"entity": "Co ( 3 ) O ( 4 )", "entity_type": "Chemical", "pos": [143, 159]}], "task": "NER"}
{"text": "The radiolytic oxidation of Co ( II ) to Co ( III ) was completed in 100 min and the chemical composition of the final particles was identified as Co ( 3 ) O ( 4 ) by XPS , Raman and UV - Vis spectroscopy .", "entity": [{"entity": "Co ( II )", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "Co ( III )", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "Co ( 3 ) O ( 4 )", "entity_type": "Chemical", "pos": [147, 163]}], "task": "NER"}
{"text": "Transmission electron microscopy ( TEM ) images show the final particles are approximately uniform in size , ranging from 8 to 20 nm .", "entity": [], "task": "NER"}
{"text": "A mechanism is proposed to explain the particle formation .", "entity": [], "task": "NER"}
{"text": "A key factor is the low solubility of Co ( OH ) ( 2 ) in air - saturated solutions at high pH .", "entity": [{"entity": "Co ( OH ) ( 2 )", "entity_type": "Chemical", "pos": [38, 53]}], "task": "NER"}
{"text": "This mechanism for particle formation is compared with the mechanism previously reported for the radiolytic formation of gamma - FeOOH nanoparticles .", "entity": [{"entity": "gamma - FeOOH", "entity_type": "Chemical", "pos": [121, 134]}], "task": "NER"}
{"text": "Plasma electrochemistry : voltammetry in a flame plasma electrolyte .", "entity": [], "task": "NER"}
{"text": "In this paper we present detailed dynamic electrochemical measurements in a flame plasma electrolyte in the presence of tungsten oxide salts .", "entity": [{"entity": "tungsten oxide salts", "entity_type": "Chemical", "pos": [120, 140]}], "task": "NER"}
{"text": "Defined reproducible redox processes are measured using conventional cyclic voltammetry in an operational potential window between 1 and - 9 V .", "entity": [], "task": "NER"}
{"text": "This wide potential window is possible due to the absence of solvent and its associated limits due to solvent electrolysis at high over potentials .", "entity": [], "task": "NER"}
{"text": "The measurements were enabled through the development of a new reference electrode , composed of yttria stabilised zirconia ( YSZ ) which maintains a stable potential at 1100 K .", "entity": [{"entity": "yttria", "entity_type": "Chemical", "pos": [97, 103]}, {"entity": "zirconia", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "In this paper we focus on developing a phenomenological understanding of electron transfer at the solid - gas interface , using cyclic voltammetry .", "entity": [], "task": "NER"}
{"text": "The effect of working electrode surface area and material , as well as potential scan rate on the voltammetric redox features is presented .", "entity": [], "task": "NER"}
{"text": "We discuss the physical origin of the observed Faradaic current peaks measured in a flame plasma electrolyte , and propose a simple model to describe the redox processes occurring .", "entity": [], "task": "NER"}
{"text": "We conclude that redox processes at the solid - gas interface are actually similar to the analogous processes at the solid - liquid interface described by conventional electrochemical theory ; the departures are mainly due to the mass transport processes that dominate in the gas phase .", "entity": [], "task": "NER"}
{"text": "We associate migration effects with the total absence of any oxidation processes .", "entity": [], "task": "NER"}
{"text": "Parenteral nutrition - associated hyperglycemia in non - critically ill inpatients increases the risk of in - hospital mortality ( multicenter study ) .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE Hyperglycemia may increase mortality in patients who receive total parenteral nutrition ( TPN ) .", "entity": [], "task": "NER"}
{"text": "However , this has not been well studied in noncritically ill patients ( i . e . , patients in the nonintensive care unit setting ) .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine whether mean blood glucose level during TPN infusion is associated with increased mortality in noncritically ill hospitalized patients .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "RESEARCH DESIGN AND METHODS This prospective multicenter study involved 19 Spanish hospitals .", "entity": [], "task": "NER"}
{"text": "Noncritically ill patients who were prescribed TPN were included prospectively , and data were collected on demographic , clinical , and laboratory variables as well as on in - hospital mortality .", "entity": [], "task": "NER"}
{"text": "RESULTS The study included 605 patients ( mean age 63 . 2 +/- 15 . 7 years ) .", "entity": [], "task": "NER"}
{"text": "The daily mean TPN values were 1 . 630 +/- 323 kcal , 3 . 2 +/- 0 . 7 g carbohydrates / kg , 1 . 26 +/- 0 . 3 g amino acids / kg , and 0 . 9 +/- 0 . 2 g lipids / kg .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [72, 85]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [112, 123]}], "task": "NER"}
{"text": "Multiple logistic regression analysis showed that the patients who had mean blood glucose levels > 180 mg / dL during the TPN infusion had a risk of mortality that was 5 . 6 times greater than those with mean blood glucose levels < 140 mg / dL ( 95 % CI 1 . 47 - 21 . 4 mg / dL ) after adjusting for age , sex , nutritional state , presence of diabetes or hyperglycemia before starting TPN , diagnosis , prior comorbidity , carbohydrates infused , use of steroid therapy , SD of blood glucose level , insulin units supplied , infectious complications , albumin , C - reactive protein , and HbA1c levels .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [82, 89]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [215, 222]}, {"entity": "carbohydrates", "entity_type": "Chemical", "pos": [424, 437]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [455, 462]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [485, 492]}], "task": "NER"}
{"text": "CONCLUSIONS Hyperglycemia ( mean blood glucose level > 180 mg / dL ) in noncritically ill patients who receive TPN is associated with a higher risk of in - hospital mortality .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "Effect of nuclear vibrations , temperature , co - adsorbed water , and dye orientation on light absorption , charge injection and recombination conditions in organic dyes on TiO2 .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [174, 178]}], "task": "NER"}
{"text": "We study the effect of nuclear motions at different temperatures , including the effect of a dye molecule ' s orientation with respect to the oxide surface , on factors determining the performance of dye sensitized solar cells : light absorption , electron injection , and back - donation .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [142, 147]}], "task": "NER"}
{"text": "We perform ab initio molecular dynamics simulations of aminophenyl acid dyes NK1 and NK7 , differing by the electron donating group , in a vacuum and adsorbed in mono - and bi - dentate modes on a dry and a water - covered anatase ( 101 ) surface of TiO ( 2 ) , at 300 and 350 K .", "entity": [{"entity": "aminophenyl acid", "entity_type": "Chemical", "pos": [55, 71]}, {"entity": "NK1", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "NK7", "entity_type": "Chemical", "pos": [85, 88]}, {"entity": "anatase ( 101 )", "entity_type": "Chemical", "pos": [223, 238]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [250, 259]}], "task": "NER"}
{"text": "Nuclear vibrations and an increase of temperature cause a red shift in the absorption spectra of free dyes .", "entity": [], "task": "NER"}
{"text": "This effect is preserved in dyes on dry TiO ( 2 ) but largely disappears in the presence of water .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "Averaged over nuclear vibrations , the driving force to injection , Delta G , differs from the static estimate .", "entity": [], "task": "NER"}
{"text": "It depends on the adsorption mode and the presence of H ( 2 ) O but is almost the same for 300 and 350 K .", "entity": [{"entity": "H ( 2 ) O", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "Recombination to the dye cation is expected to be much enhanced by the approach of the dye oxidation equivalent hole to the surface during dye wagging around TiO ( 2 ) .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [158, 167]}], "task": "NER"}
{"text": "This effect is somewhat mitigated by the co - adsorbed water .", "entity": [], "task": "NER"}
{"text": "The dynamics of Delta G ( t ) are explained by uncorrelated evolution of the energies of the dye excited state and the conduction band minimum of the oxide due to their respective vibrations , and are almost independent of dye orientation .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [150, 155]}], "task": "NER"}
{"text": "It may therefore be possible to independently control the conditions of recombination and of injection .", "entity": [], "task": "NER"}
{"text": "Loss of LARGE2 disrupts functional glycosylation of alpha - dystroglycan in prostate cancer .", "entity": [], "task": "NER"}
{"text": "Dystroglycan ( DG ) is a cell surface receptor for extracellular matrix proteins and is involved in cell polarity , matrix organization , and mechanical stability of tissues .", "entity": [], "task": "NER"}
{"text": "Previous studies documented loss of DG protein expression and glycosylation in a variety of cancer types , but the underlying mechanisms and the functional consequences with respect to cancer progression remain unclear .", "entity": [], "task": "NER"}
{"text": "Here , we show that the level of expression of the beta DG subunit as well as the glycosylation status of the alpha DG subunit inversely correlate with the Gleason scores of prostate cancers ; furthermore , we show that the functional glycosylation of alpha DG is substantially reduced in prostate cancer metastases .", "entity": [], "task": "NER"}
{"text": "Additionally , we demonstrate that LARGE2 ( GYLTL1B ) , a gene not previously implicated in cancer , regulates functional alpha DG glycosylation in prostate cancer cell lines ; knockdown of LARGE2 resulted in hypoglycosylation of alpha DG and loss of its ability to bind laminin - 111 while overexpression restored ligand binding and diminished growth and migration of an aggressive prostate cancer cell line .", "entity": [], "task": "NER"}
{"text": "Finally , our analysis of LARGE2 expression in human cancer specimens reveals that LARGE2 is significantly down - regulated in the context of prostate cancer , and that its reduction correlates with disease progression .", "entity": [], "task": "NER"}
{"text": "Our results describe a novel molecular mechanism to account for the commonly observed hypoglycosylation of alpha DG in prostate cancer .", "entity": [], "task": "NER"}
{"text": "Prolyl 4 - hydroxlase activity is essential for development and cuticle formation in the human infective parasitic nematode Brugia malayi .", "entity": [], "task": "NER"}
{"text": "Collagen prolyl 4 - hydroxylases ( C - P4H ) are required for formation of extracellular matrices in higher eukaryotes .", "entity": [], "task": "NER"}
{"text": "These enzymes convert proline residues within the repeat regions of collagen polypeptides to 4 - hydroxyproline , a modification essential for the stability of the final triple helix .", "entity": [{"entity": "proline", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "4 - hydroxyproline", "entity_type": "Chemical", "pos": [93, 111]}], "task": "NER"}
{"text": "C - P4H are most often oligomeric complexes , with enzymatic activity contributed by the alpha subunits , and the beta subunits formed by protein disulfide isomerase ( PDI ) .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [146, 155]}], "task": "NER"}
{"text": "Here , we characterize this enzyme class in the important human parasitic nematode Brugia malayi .", "entity": [], "task": "NER"}
{"text": "All potential C - P4H subunits were identified by detailed bioinformatic analysis of sequence databases , function was investigated both by RNAi in the parasite and heterologous expression in Caenorhabditis elegans , whereas biochemical activity and complex formation were examined via co - expression in insect cells .", "entity": [], "task": "NER"}
{"text": "Simultaneous RNAi of two B . malayi C - P4H alpha subunit - like genes resulted in a striking , highly penetrant body morphology phenotype in parasite larvae .", "entity": [], "task": "NER"}
{"text": "This was replicated by single RNAi of a B . malayi C - P4H beta subunit - like PDI .", "entity": [], "task": "NER"}
{"text": "Surprisingly , however , the B . malayi proteins were not capable of rescuing a C . elegans alpha subunit mutant , whereas the human enzymes could .", "entity": [], "task": "NER"}
{"text": "In contrast , the B . malayi PDI did functionally complement the lethal phenotype of a C . elegans beta subunit mutant .", "entity": [], "task": "NER"}
{"text": "Comparison of recombinant and parasite derived material indicates that enzymatic activity may be dependent on a non - reducible covalent link , present only in the parasite .", "entity": [], "task": "NER"}
{"text": "We therefore demonstrate that C - P4H activity is essential for development of B . malayi and uncover a novel parasite - specific feature of these collagen biosynthetic enzymes that may be exploited in future parasite control .", "entity": [], "task": "NER"}
{"text": "Alteration of the expression of pesticide - metabolizing enzymes in pregnant mice : potential role in the increased vulnerability of the developing brain .", "entity": [], "task": "NER"}
{"text": "Studies on therapeutic drug disposition in humans have shown significant alterations as the result of pregnancy .", "entity": [], "task": "NER"}
{"text": "However , it is not known whether pesticide metabolic capacity changes throughout pregnancy , which could affect exposure of the developing brain .", "entity": [], "task": "NER"}
{"text": "We sought to determine the effect of pregnancy on the expression of hepatic enzymes involved in the metabolism of pesticides .", "entity": [], "task": "NER"}
{"text": "Livers were collected from virgin and pregnant C57BL / 6 mice at gestational days ( GD ) 7 , GD11 , GD14 , GD17 , and postpartum days ( PD ) 1 , PD15 , and PD30 .", "entity": [], "task": "NER"}
{"text": "Relative mRNA expression of several enzymes involved in the metabolism of pesticides , including hepatic cytochromes ( Cyp ) P450s , carboxylesterases ( Ces ) , and paraoxonase 1 ( Pon1 ) , were assessed in mice during gestation and the postpartum period .", "entity": [], "task": "NER"}
{"text": "Compared with virgin mice , alterations in the expression occurred at multiple time points , with the largest changes observed on GD14 .", "entity": [], "task": "NER"}
{"text": "At this time point , the expression of most of the Cyps involved in pesticide metabolism in the liver ( Cyp1a2 , Cyp2d22 , Cyp2c37 , Cyp2c50 , Cyp2c54 , and Cyp3a11 ) were downregulated by 30 % or more .", "entity": [], "task": "NER"}
{"text": "Expression of various Ces isoforms and Pon1 were also decreased along with Pon1 activity .", "entity": [], "task": "NER"}
{"text": "These data demonstrate significant alterations in the expression of key enzymes that detoxify pesticides during pregnancy , which could alter exposure of developing animals to these chemicals .", "entity": [], "task": "NER"}
{"text": "Altered UDP - glucuronosyltransferase and sulfotransferase expression and function during progressive stages of human nonalcoholic fatty liver disease .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [8, 11]}], "task": "NER"}
{"text": "The UDP - glucuronosyltransferases ( UGTs ) and sulfotransferases ( SULTs ) represent major phase II drug - metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics .", "entity": [], "task": "NER"}
{"text": "Nonalcoholic fatty liver disease ( NAFLD ) represents a spectrum of liver damage ranging from steatosis to nonalcoholic steatohepatitis ( NASH ) and cirrhosis .", "entity": [], "task": "NER"}
{"text": "Because the liver plays a central role in the metabolism of xenobiotics , the purpose of the current study was to determine the effect of human NAFLD progression on the expression and function of UGTs and SULTs in normal , steatosis , NASH ( fatty ) , and NASH ( not fatty / cirrhosis ) samples .", "entity": [], "task": "NER"}
{"text": "We identified upregulation of UGT1A9 , 2B10 , and 3A1 and SULT1C4 mRNA in both stages of NASH , whereas UGT2A3 , 2B15 , and 2B28 and SULT1A1 , 2B1 , and 4A1 as well as 3 ' - phosphoadenosine - 5 ' - phosphosulfate synthase 1 were increased in NASH ( not fatty / cirrhosis ) only .", "entity": [{"entity": "3 ' - phosphoadenosine - 5 ' - phosphosulfate", "entity_type": "Chemical", "pos": [168, 213]}], "task": "NER"}
{"text": "UGT1A9 and 1A6 and SULT1A1 and 2A1 protein levels were decreased in NASH ; however , SULT1C4 was increased .", "entity": [], "task": "NER"}
{"text": "Measurement of the glucuronidation and sulfonation of acetaminophen ( APAP ) revealed no alterations in glucuronidation ; however , SULT activity was increased in steatosis compared with normal samples , but then decreased in NASH compared with steatosis .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [54, 67]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "In conclusion , the expression of specific UGT and SULT isoforms appears to be differentially regulated , whereas sulfonation of APAP is disrupted during progression of NAFLD .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [129, 133]}], "task": "NER"}
{"text": "SERS performance of gold nanotubes obtained by sputtering onto polycarbonate track - etched membranes .", "entity": [{"entity": "polycarbonate", "entity_type": "Chemical", "pos": [63, 76]}], "task": "NER"}
{"text": "Surface - enhanced Raman scattering ( SERS ) is a powerful and versatile tool for studying molecules on metallic surfaces with great impact on areas such as electrochemistry , catalysis and related subjects .", "entity": [], "task": "NER"}
{"text": "The search for new SERS - active substrates with high performance , namely high enhancement factors and reproducibility , is currently the main focus of several research groups .", "entity": [], "task": "NER"}
{"text": "Here is shown an alternative easy and inexpensive synthetic approach to a SERS - substrate comprised of gold nanotubes obtained by the sputtering onto polycarbonate track - etched membranes used as template .", "entity": [{"entity": "polycarbonate", "entity_type": "Chemical", "pos": [151, 164]}], "task": "NER"}
{"text": "Its SERS performance was evaluated by mapping ( 10 x 10 ) mu m ( 2 ) areas and resulted in average enhancement factors that span from 2 . 3 x 10 ( 3 ) to 1 . 2 x 10 ( 5 ) with a maximum enhancement factor of 2 . 5 x 10 ( 5 ) .", "entity": [], "task": "NER"}
{"text": "The enhancement depended strongly on the template pore diameter , with the best performance obtained when membranes with pore diameters of 400 nm were used as template .", "entity": [], "task": "NER"}
{"text": "Further analysis showed that the larger enhancements came from coalesced gold nanotubes and detection of the dye rhodamine 6G at concentrations as low as 0 . 1 nM was possible .", "entity": [{"entity": "rhodamine 6G", "entity_type": "Chemical", "pos": [113, 125]}], "task": "NER"}
{"text": "These results put this substrate as a valuable and easy - to - fabricate tool for studying and detecting molecules on surfaces .", "entity": [], "task": "NER"}
{"text": "The proposed methodology could be easily adapted to other metals , such as silver and copper .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "copper", "entity_type": "Chemical", "pos": [86, 92]}], "task": "NER"}
{"text": "Advanced gecko - foot - mimetic dry adhesives based on carbon nanotubes .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [55, 61]}], "task": "NER"}
{"text": "Geckos can run freely on vertical walls and even ceilings .", "entity": [], "task": "NER"}
{"text": "Recent studies have discovered that gecko ' s extraordinary climbing ability comes from a remarkable design of nature with nanoscale beta - keratin elastic hairs on their feet and toes , which collectively generate sufficiently strong van der Waals force to hold the animal onto an opposing surface while at the same time disengaging at will .", "entity": [], "task": "NER"}
{"text": "Vertically aligned carbon nanotube ( VA - CNT ) arrays , resembling gecko ' s adhesive foot hairs with additional superior mechanical , chemical and electrical properties , have been demonstrated to be a promising candidate for advanced fibrillar dry adhesives .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [19, 25]}], "task": "NER"}
{"text": "The VA - CNT arrays with tailor - made hierarchical structures can be patterned and / or transferred onto various flexible substrates , including responsive polymers .", "entity": [], "task": "NER"}
{"text": "This , together with recent advances in nanofabrication techniques , could offer ' smart ' dry adhesives for various potential applications , even where traditional adhesives cannot be used .", "entity": [], "task": "NER"}
{"text": "A detailed understanding of the underlying mechanisms governing the material properties and adhesion performances is critical to the design and fabrication of gecko inspired CNT dry adhesives of practical significance .", "entity": [], "task": "NER"}
{"text": "In this feature article , we present an overview of recent progress in both fundamental and applied frontiers for the development of CNT - based adhesives by summarizing important studies in this exciting field , including our own work .", "entity": [], "task": "NER"}
{"text": "Factors limiting device efficiency in organic photovoltaics .", "entity": [], "task": "NER"}
{"text": "The power conversion efficiency of the most efficient organic photovoltaic ( OPV ) cells has recently increased to over 10 % .", "entity": [], "task": "NER"}
{"text": "To enable further increases , the factors limiting the device efficiency in OPV must be identified .", "entity": [], "task": "NER"}
{"text": "In this review , the operational mechanism of OPV cells is explained and the detailed balance limit to photovoltaic energy conversion , as developed by Shockley and Queisser , is outlined .", "entity": [], "task": "NER"}
{"text": "The various approaches that have been developed to estimate the maximum practically achievable efficiency in OPV are then discussed , based on empirical knowledge of organic semiconductor materials .", "entity": [], "task": "NER"}
{"text": "Subsequently , approaches made to adapt the detailed balance theory to incorporate some of the fundamentally different processes in organic solar cells that originate from using a combination of two complementary , donor and acceptor , organic semiconductors using thermodynamic and kinetic approaches are described .", "entity": [], "task": "NER"}
{"text": "The more empirical formulations to the efficiency limits provide estimates of 10 - 12 % , but the more fundamental descriptions suggest limits of 20 - 24 % to be reachable in single junctions , similar to the highest efficiencies obtained for crystalline silicon p - n junction solar cells .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [255, 262]}], "task": "NER"}
{"text": "Closing this gap sets the stage for future materials research and development of OPV .", "entity": [], "task": "NER"}
{"text": "Exploring the polyamine regulatory site of the NMDA receptor : a parallel synthesis approach .", "entity": [{"entity": "polyamine", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [47, 51]}], "task": "NER"}
{"text": "The elongated structures of polyamine inverse agonists such as 1 , 12 - diaminododecane ( N12N ) and 5 - ( 4 - aminobutyl ) - 2 - thiopheneoctanamine ( N4T8N ) lend themselves to a combinatorial chemistry approach to explore a potential polyamine pharmacophore at the NMDA receptor .", "entity": [{"entity": "polyamine", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "1 , 12 - diaminododecane", "entity_type": "Chemical", "pos": [63, 87]}, {"entity": "N12N", "entity_type": "Chemical", "pos": [90, 94]}, {"entity": "5 - ( 4 - aminobutyl ) - 2 - thiopheneoctanamine", "entity_type": "Chemical", "pos": [101, 149]}, {"entity": "N4T8N", "entity_type": "Chemical", "pos": [152, 157]}, {"entity": "polyamine", "entity_type": "Chemical", "pos": [237, 246]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [268, 272]}], "task": "NER"}
{"text": "Herein we describe more than 100 new analogues of N4T8N obtained by breaking up the long octanamine arm into a dipeptide chain of equivalent length .", "entity": [{"entity": "N4T8N", "entity_type": "Chemical", "pos": [50, 55]}, {"entity": "octanamine", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "Solid - phase parallel synthesis based on cross - linked polystyrene and a Wang anchor allowed the low - scale preparation of four small libraries based on the combination of two amino acid residues ( out of Gly , Leu , Phe , Lys , phenylglycine , Tyr , Trp , His , and Arg ) .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [57, 68]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [179, 189]}, {"entity": "Gly", "entity_type": "Chemical", "pos": [208, 211]}, {"entity": "Leu", "entity_type": "Chemical", "pos": [214, 217]}, {"entity": "Phe", "entity_type": "Chemical", "pos": [220, 223]}, {"entity": "Lys", "entity_type": "Chemical", "pos": [226, 229]}, {"entity": "phenylglycine", "entity_type": "Chemical", "pos": [232, 245]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [248, 251]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [254, 257]}, {"entity": "His", "entity_type": "Chemical", "pos": [260, 263]}, {"entity": "Arg", "entity_type": "Chemical", "pos": [270, 273]}], "task": "NER"}
{"text": "The obtained compounds were tested as modulators of [ ( 3 ) H ] MK - 801 binding to rat brain membranes and of NMDA - induced currents in cultured rat hippocampal neurons .", "entity": [{"entity": "[ ( 3 ) H ] MK - 801", "entity_type": "Chemical", "pos": [52, 72]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [111, 115]}], "task": "NER"}
{"text": "Compounds with two aromatic residues acted as binding inhibitors ( inverse agonists ) .", "entity": [], "task": "NER"}
{"text": "Compounds with two Lys residues acted as binding stimulators ( agonists ) and had stimulatory and inhibitory effects on NMDA - induced currents , depending on the holding potential .", "entity": [{"entity": "Lys", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [120, 124]}], "task": "NER"}
{"text": "High sensitivity of binding inhibition to spermine was conferred by a Tyr residue , whereas a His residue favored high potency at acidic pH .", "entity": [{"entity": "spermine", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [70, 73]}, {"entity": "His", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "Design strategies and applications of tissue bioadhesives .", "entity": [], "task": "NER"}
{"text": "In the past two decades tissue adhesives and sealants have revolutionized bleeding control and wound healing .", "entity": [], "task": "NER"}
{"text": "This paper focuses on existing tissue adhesive design , their structure , functioning mechanism , and their pros and cons in wound management .", "entity": [], "task": "NER"}
{"text": "It also includes the latest advances in the development of new tissue adhesives as well as the emerging applications in regenerative medicine .", "entity": [], "task": "NER"}
{"text": "We expect that this paper will provide insightful discussion on tissue bioadhesive design and lead to innovations for the development of the next generation of tissue bioadhesives and their related biomedical applications .", "entity": [], "task": "NER"}
{"text": "Microbial transformation of asiatic acid .", "entity": [{"entity": "asiatic acid", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "Asiatic acid ( 1 ) , a major pentacyclic triterpene of Centella asiatica , was subjected to transformation by Penicillium lilacinum ACCC 31890 , Fusarium equiseti CGMCC 3 . 3658 , and Streptomyces griseus CGMCC 4 . 18 strains .", "entity": [{"entity": "Asiatic acid", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "pentacyclic triterpene", "entity_type": "Chemical", "pos": [29, 51]}], "task": "NER"}
{"text": "Incubation of asiatic acid with P . lilacinum ACCC 31890 and F . equiseti CGMCC 3 . 3658 gave an identical product : 2 alpha , 3 beta , 15 alpha , 23 - tetrahydroxyurs - 12 - en - 28 - oic acid ( 2 ) .", "entity": [{"entity": "asiatic acid", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "2 alpha , 3 beta , 15 alpha , 23 - tetrahydroxyurs - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [117, 193]}], "task": "NER"}
{"text": "Biotransformation of asiatic acid by S . griseus CGMCC 4 . 18 resulted in three derivatives : 2 alpha , 3 beta , 21 beta , 23 - tetrahydroxyurs - 12 - en - 28 - oic acid ( 3 ) , 2 alpha , 3 beta , 23 - trihydroxyurs - 12 - en - 28 , 30 - dioic acid ( 4 ) , and 2 alpha , 3 beta , 23 , 30 - tetrahydroxyurs - 12 - en - 28 - oic acid ( 5 ) .", "entity": [{"entity": "asiatic acid", "entity_type": "Chemical", "pos": [21, 33]}, {"entity": "2 alpha , 3 beta , 21 beta , 23 - tetrahydroxyurs - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [94, 169]}, {"entity": "2 alpha , 3 beta , 23 - trihydroxyurs - 12 - en - 28 , 30 - dioic acid", "entity_type": "Chemical", "pos": [178, 248]}, {"entity": "2 alpha , 3 beta , 23 , 30 - tetrahydroxyurs - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [261, 331]}], "task": "NER"}
{"text": "The structures of those derivatives were deduced from their spectral data .", "entity": [], "task": "NER"}
{"text": "Products ( 2 ) , ( 3 ) , and ( 4 ) were new compounds .", "entity": [], "task": "NER"}
{"text": "In addition , the in vitro cytotoxicities of those derivatives along with 1 were evaluated with several human cancer cell lines .", "entity": [], "task": "NER"}
{"text": "Predicting dislocations and grain boundaries in two - dimensional metal - disulfides from the first principles .", "entity": [{"entity": "metal - disulfides", "entity_type": "Chemical", "pos": [66, 84]}], "task": "NER"}
{"text": "Guided by the principles of dislocation theory , we use the first - principles calculations to determine the structure and properties of dislocations and grain boundaries ( GB ) in single - layer transition metal disulfides MS ( 2 ) ( M = Mo or W ) .", "entity": [{"entity": "transition metal disulfides", "entity_type": "Chemical", "pos": [196, 223]}, {"entity": "MS ( 2 )", "entity_type": "Chemical", "pos": [224, 232]}, {"entity": "Mo", "entity_type": "Chemical", "pos": [239, 241]}, {"entity": "W", "entity_type": "Chemical", "pos": [245, 246]}], "task": "NER"}
{"text": "In sharp contrast to other two - dimensional materials ( truly planar graphene and h - BN ) , here the edge dislocations extend in third dimension , forming concave dreidel - shaped polyhedra .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [70, 78]}, {"entity": "h - BN", "entity_type": "Chemical", "pos": [83, 89]}], "task": "NER"}
{"text": "They include different number of homoelemental bonds and , by reacting with vacancies , interstitials , and atom substitutions , yield families of the derivative cores for each Burgers vector .", "entity": [], "task": "NER"}
{"text": "The overall structures of GB are controlled by both local - chemical and far - field mechanical energies and display different combinations of dislocation cores .", "entity": [], "task": "NER"}
{"text": "Further , we find two distinct electronic behaviors of GB .", "entity": [], "task": "NER"}
{"text": "Typically , their localized deep - level states act as sinks for carriers but at large 60 degrees - tilt the GB become metallic .", "entity": [], "task": "NER"}
{"text": "The analysis shows how the versatile GB in MS ( 2 ) ( if carefully engineered ) should enable new developments for electronic and opto - electronic applications .", "entity": [{"entity": "MS ( 2 )", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "Terpenoids from Incarvillea arguta .", "entity": [{"entity": "Terpenoids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "One new monoterpenoid , ( + ) - argutoid A ( 1 ) , three new iridoids , ( - ) - incarvoid A ( 2 ) , ( + ) - incarvoid B ( 3 ) , and incarvoid C ( 4 ) , and five known compounds were isolated from Incarvillea arguta .", "entity": [{"entity": "monoterpenoid", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "( + ) - argutoid A", "entity_type": "Chemical", "pos": [24, 42]}, {"entity": "iridoids", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "( - ) - incarvoid A", "entity_type": "Chemical", "pos": [72, 91]}, {"entity": "( + ) - incarvoid B", "entity_type": "Chemical", "pos": [100, 119]}, {"entity": "incarvoid C", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "Their structures were characterized by means of spectroscopic methods .", "entity": [], "task": "NER"}
{"text": "Amino acid - based zwitterionic poly ( serine methacrylate ) as an antifouling material .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "zwitterionic poly ( serine methacrylate )", "entity_type": "Chemical", "pos": [19, 60]}], "task": "NER"}
{"text": "A serine - based zwitterionic poly ( serine methacrylate ) ( pSerMA ) was developed in this work to be used as a potential antifouling material .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [2, 8]}, {"entity": "zwitterionic poly ( serine methacrylate )", "entity_type": "Chemical", "pos": [17, 58]}, {"entity": "pSerMA", "entity_type": "Chemical", "pos": [61, 67]}], "task": "NER"}
{"text": "A surface - initiated photoiniferter - mediated polymerization ( SI - PIMP ) method was used to graft polymer brushes on gold surfaces .", "entity": [], "task": "NER"}
{"text": "The pSerMA - grafted samples with different polymer film thicknesses were readily prepared by varying the UV - irradiation time .", "entity": [{"entity": "pSerMA", "entity_type": "Chemical", "pos": [4, 10]}], "task": "NER"}
{"text": "With the optimal film thickness , the adsorptions from bovine serum albumin , human serum , and human plasma onto the pSerMA - grafted surfaces , as evaluated by a surface plasmon resonance ( SPR ) biosensor , were 1 . 8 , 9 . 2 , and 12 . 9 ng / cm ( 2 ) , respectively , comparable to the traditional antifouling material such as poly ( ethylene glycol ) .", "entity": [{"entity": "pSerMA", "entity_type": "Chemical", "pos": [118, 124]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [332, 356]}], "task": "NER"}
{"text": "The pSerMA - grafted surfaces also strongly resisted adhesion from bovine aortic endothelial cells .", "entity": [{"entity": "pSerMA", "entity_type": "Chemical", "pos": [4, 10]}], "task": "NER"}
{"text": "This is the first work to develop an amino acid - based zwitterionic polymer as an antifouling material , demonstrating that pSerMA is a promising alternative to the traditional ethylene glycol - based antifouling materials .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "pSerMA", "entity_type": "Chemical", "pos": [125, 131]}, {"entity": "ethylene glycol", "entity_type": "Chemical", "pos": [178, 193]}], "task": "NER"}
{"text": "Discriminating the endogenous and exogenous urinary estrogens in human by isotopic ratio mass spectrometry and its potential clinical value .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "Estrogens were prohibited in the food producing animals by European Union ( 96 / 22 / EC directive ) and added to the Report on Carcinogens in United States since 2002 .", "entity": [{"entity": "Estrogens", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Due to very low concentration in serum or urine ( ~ pg / mL ) , the method of control its abuse had not been fully developed .", "entity": [], "task": "NER"}
{"text": "The endogenous estrogens were separated from urines of 18 adult men and women .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "The exogenous estrogens were chemical reference standards and over the counter preparations .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Two patients of dysfunctional uterine bleeding ( DUB ) administered exogenous estradiol and the urines were collected for 72 h .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [78, 87]}], "task": "NER"}
{"text": "The urinary estrogens were separated by high - performance liquid chromatography ( HPLC ) and confirmed .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [12, 21]}], "task": "NER"}
{"text": "The exogenous and exogenous estrogens were analyzed by gas chromatography combustion isotope ratio mass spectrometry ( GC - C - IRMS ) to determine the ( 13 ) C / ( 12 ) C ratio ( delta ( 13 ) C /1000 ) .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [152, 160]}, {"entity": "( 12 ) C", "entity_type": "Chemical", "pos": [163, 171]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [186, 194]}], "task": "NER"}
{"text": "The delta ( 13 ) C /1000 values of reference standard of E1 , E2 , and E3 were - 29 . 36 +/- 0 . 72 , - 27 . 98 +/- 0 . 35 , - 27 . 62 +/- 0 . 51 , respectively .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "The delta ( 13 ) C /1000 values of the endogenous E1 , E2 , and E3 were - 21 . 62 +/- 1 . 07 , - 22 . 14 +/- 0 . 98 , and - 21 . 88 +/- 1 . 16 , with P < 0 . 01 ( t - test ) .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "Two DUB patients ' urinary estradiol delta ( 13 ) C /1000 values was depleted to - 28 . 02 +/- 0 . 33 after the administration .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "The progesterone , 17 alpha - hydroxyprogesterone , pregnanediol , as well as desogestrel and ethinylestradiol from contraceptives were also determined .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "17 alpha - hydroxyprogesterone", "entity_type": "Chemical", "pos": [19, 49]}, {"entity": "pregnanediol", "entity_type": "Chemical", "pos": [52, 64]}, {"entity": "desogestrel", "entity_type": "Chemical", "pos": [78, 89]}, {"entity": "ethinylestradiol", "entity_type": "Chemical", "pos": [94, 110]}], "task": "NER"}
{"text": "Stable carbon isotope analysis can distinguish the endogenous and exogenous urinary estrogen in human .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [7, 13]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "Identification and characterization of MIP - 1 alpha / CCL3 isoform 2 from bovine serum as a potent monocyte / dendritic cell chemoattractant .", "entity": [], "task": "NER"}
{"text": "Bovine serum is a rich source of cytokines and growth factors supporting in vitro cell culture .", "entity": [], "task": "NER"}
{"text": "Here , a novel bovine monocyte chemotactic factor ( boMCF - 1 ) was isolated from commercial bovine serum by a four step purification procedure including adsorption to silicic acid , heparin affinity and cation - exchange chromatography and reversed phase HPLC .", "entity": [{"entity": "silicic acid", "entity_type": "Chemical", "pos": [168, 180]}], "task": "NER"}
{"text": "Homogeneous boMCF - 1 was characterized as a 7717Da protein by mass spectrometry and identified by Edman degradation as the predicted product of bovine macrophage inflammatory protein - 1 alpha gene ( boMIP - 1 alpha / CCL3 ) isoform 2 ( lacking three NH 2 - terminal amino acids ) , belonging to the MIP subfamily of CC chemokines .", "entity": [{"entity": "NH 2", "entity_type": "Chemical", "pos": [252, 256]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [268, 279]}], "task": "NER"}
{"text": "Monocyte chemotactic activity of boCCL3 isoform 2 was completely desensitized by human CCL3 and CCL5 , partially by CCL7 and not by CCL2 .", "entity": [], "task": "NER"}
{"text": "Its activity was better inhibited by CCR1 than by CCR5 blockade .", "entity": [], "task": "NER"}
{"text": "BoCCL3 isoform 2 , present in bovine serum at about 10 ng / ml , functioned as a most potent chemoattractant for immature ( but not mature ) dendritic cells with a minimal effective concentration of 0 . 03 ng / ml and a maximal chemotactic index of 30 at 0 . 3 ng / ml .", "entity": [], "task": "NER"}
{"text": "Its chemotactic activity on immature dendritic cells was significantly desensitized by human CCL3 , CCL5 and CCL7 .", "entity": [], "task": "NER"}
{"text": "Blockade of CCR5 rather than CCR1 partially prevented chemotactic activity , whereas blockade of both further enhanced this inhibition .", "entity": [], "task": "NER"}
{"text": "BoCCL3 isoform 2 was not chemokinetic but , like human CCL3 , synergized with CXCL12 in monocytic cell chemotaxis .", "entity": [], "task": "NER"}
{"text": "Since it cannot be deduced which is the exact human homolog of boCCL3 isoform 2 , further research is required to study the biology of other boCCL3 family members .", "entity": [], "task": "NER"}
{"text": "A naonoporous cell - therapy device with controllable biodegradation for long - term drug release .", "entity": [], "task": "NER"}
{"text": "Herein we describe the development and implementation of a nanoporous cell - therapy device with controllable biodegradation .", "entity": [], "task": "NER"}
{"text": "Dopamine - secreting PC12 cells were housed within newly formulated alginate - glutamine degradable polylysine ( A - GD - PLL ) microcapsules .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "polylysine", "entity_type": "Chemical", "pos": [100, 110]}, {"entity": "PLL", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "The A - GD - PLL microcapsules provided a 3 - D microenvironment for good spatial cell growth , viability and proliferation .", "entity": [{"entity": "PLL", "entity_type": "Chemical", "pos": [13, 16]}], "task": "NER"}
{"text": "The microcapsules were subsequently placed within a poly ( ethylene glycol ) ( PEG ) - coated poly ( epsilon - caprolactone ) ( PCL ) chamber covered with a PEG - grafted PCL nanoporous membrane formed by phase inversion .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [52, 76]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "poly ( epsilon - caprolactone )", "entity_type": "Chemical", "pos": [94, 125]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "PEG - grafted PCL", "entity_type": "Chemical", "pos": [157, 174]}], "task": "NER"}
{"text": "To enhance PC12 cell growth and to assist in controlled degradation of both the PC12 cells and the device construct , small PCL capsules containing neural growth factor ( PCL - NGF ) and a poly ( lactic - co - glycolic acid ) pellet containing glutamine ( PLGA - GLN ) were also placed within the PCL chamber .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [171, 174]}, {"entity": "poly ( lactic - co - glycolic acid )", "entity_type": "Chemical", "pos": [189, 225]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [244, 253]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [256, 260]}, {"entity": "GLN", "entity_type": "Chemical", "pos": [263, 266]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [297, 300]}], "task": "NER"}
{"text": "Release of NGF from the PCL - NGF capsules facilitated cell proliferation and viability , while the controlled release of GLN from the PLGA - GLN pellet resulted in A - GD - PLL microcapsule degradation and eventual PC12 cell death following a pre - specified period of time ( 4 weeks in this study ) .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "GLN", "entity_type": "Chemical", "pos": [122, 125]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [135, 139]}, {"entity": "GLN", "entity_type": "Chemical", "pos": [142, 145]}, {"entity": "PLL", "entity_type": "Chemical", "pos": [174, 177]}], "task": "NER"}
{"text": "In vivo , our device was found to be well tolerated and we successfully demonstrated the controlled release of dopamine over a period of four weeks .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "This integrated biodegradable device holds great promise for the future treatment of a variety of diseases .", "entity": [], "task": "NER"}
{"text": "Metals loads into the Mediterranean Sea : estimate of Sarno River inputs and ecological risk .", "entity": [], "task": "NER"}
{"text": "The metals pollution in the Sarno River and its environmental impact on the Gulf of Naples ( Tyrrhenian Sea , Central Mediterranean Sea ) were estimated .", "entity": [], "task": "NER"}
{"text": "Eight selected metals ( As , Hg , Cd , Cr , Cu , Ni , Pb and Zn ) were determined in the water dissolved phase ( DP ) , suspended particulate matter ( SPM ) and sediment samples .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [24, 26]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [34, 36]}, {"entity": "Cr", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [49, 51]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [61, 63]}], "task": "NER"}
{"text": "Selected metals concentrations ranged from 0 . 32 to 1 , 680 . 39 mu g l ( - 1 ) in water DP , from 103 . 6 to 7 , 734 . 6 mu g l ( - 1 ) in SPM and from 90 . 7 to 2 , 470 . 3 mg kg ( - 1 ) in sediment samples .", "entity": [], "task": "NER"}
{"text": "Contaminant discharges of selected metals into the sea were calculated in about 13 , 977 . 6 kg year ( - 1 ) showing that this river should account as one of the main contribution sources of metals to the Tyrrhenian Sea .", "entity": [], "task": "NER"}
{"text": "Dynamic bioavailability of copper in soil estimated by uptake and elimination kinetics in the springtail Folsomia candida .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [27, 33]}], "task": "NER"}
{"text": "This study aimed to assess the bioavailability of copper in soil , by measuring its uptake kinetics into a representative soil invertebrate , the collembolan Folsomia candida .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [50, 56]}], "task": "NER"}
{"text": "The animals were exposed to 25 or 100 mu g Cu g ( - 1 ) dry LUFA 2 . 2 soil at nominal pH ( CaCl2 ) 4 . 5 , 5 . 5 , or 6 . 5 during 14 days after which they were transferred to clean soil for 14 days elimination .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [43, 45]}, {"entity": "CaCl2", "entity_type": "Chemical", "pos": [92, 97]}], "task": "NER"}
{"text": "Uptake and elimination rate constants were calculated based on total and extractable soil concentrations and porewater concentrations using one - compartment first - order kinetics modelling .", "entity": [], "task": "NER"}
{"text": "Copper was present in the animals at a basal physiological level of 40 - 90 mu g g ( - 1 ) dry weight , on top of this uptake and elimination kinetics were observed .", "entity": [{"entity": "Copper", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Uptake rates constants varied between 0 . 02 and 0 . 17 g ( soil ) g ( animal ) ( - 1 ) day ( - 1 ) , being higher at lower exposure level , but did not differ significantly between different soil pH levels .", "entity": [], "task": "NER"}
{"text": "Elimination rate constants ranged between 0 . 04 and 0 . 20 day ( - 1 ) and were negligible ( k ( 2 ) < 0 . 001 day ( - 1 ) ) at pH 4 . 5 and 6 . 5 .", "entity": [], "task": "NER"}
{"text": "Multiple linear regressions showed that the pH effect on copper uptake was only significant when taking into account cation exchange capacity , or calcium and dissolved organic carbon levels in the pore water .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [57, 63]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [147, 154]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [177, 183]}], "task": "NER"}
{"text": "Copper concentrations in the animals however , never were higher than 185 mu g g ( - 1 ) dry weight , independent of exposure level and pH , suggesting homeostatic regulation .", "entity": [{"entity": "Copper", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "These results show that the chemical composition of the pore water does affect bioavailability of copper in soil , but that copper uptake in collembolans is dominated by homeostatic regulation rather than by soil properties like pH .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [98, 104]}, {"entity": "copper", "entity_type": "Chemical", "pos": [124, 130]}], "task": "NER"}
{"text": "A photoinduced charge transfer composite of graphene oxide and ferrocene .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [44, 58]}, {"entity": "ferrocene", "entity_type": "Chemical", "pos": [63, 72]}], "task": "NER"}
{"text": "We demonstrate the formation of a photoinduced charge transfer composite with graphene oxide ( GO ) and ferrocene ( Fc ) molecules .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [78, 92]}, {"entity": "ferrocene", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "Derived insulating GO was partially reduced to improve the conductivity and modified with the Fc molecules .", "entity": [], "task": "NER"}
{"text": "Transmission electron microscopy ( TEM ) , elemental mapping , X - ray photoelectron and UV - visible spectroscopy studies confirm that the Fc molecules were well grafted to the surface of a GO sheet .", "entity": [], "task": "NER"}
{"text": "Photoresponsivity of the prepared GO - Fc composite was investigated by fabricating a metal / GO - Fc / metal device .", "entity": [{"entity": "GO - Fc", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "GO - Fc", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "The fabricated device shows enhanced current density under light illumination , suggesting a photo - induced charge transfer process in the developed GO - Fc composite .", "entity": [{"entity": "GO - Fc", "entity_type": "Chemical", "pos": [150, 157]}], "task": "NER"}
{"text": "Phase transition - induced elasticity of alpha - helical bioelastomeric fibres and networks .", "entity": [], "task": "NER"}
{"text": "Natural elastomeric fibres play central structural and functional roles in a variety of tissues produced by many organisms from diverse Phyla .", "entity": [], "task": "NER"}
{"text": "Most of these fibres feature amorphous structure and their long - range elastic response is well described within the framework of entropic ( rubber - like ) elasticity .", "entity": [], "task": "NER"}
{"text": "Recently , it has been recognized that long - range reversible deformation can also occur in biomacromolecular fibres or networks that feature significant secondary structure and long - range order .", "entity": [], "task": "NER"}
{"text": "Their elastomeric response is then associated with conformational changes of the backbone of the constitutive protein - based polymers .", "entity": [], "task": "NER"}
{"text": "Under axially imposed loads , several groups of proteins whose structure is dominated by alpha - helical coiled - coil structures can undergo unfolding transitions and secondary structure transformations , for example from coiled - coil alpha - helices to beta - sheet strands .", "entity": [], "task": "NER"}
{"text": "In contrast to rubber - like biopolymers , the retractive elastic force in these biomacromolecular materials is not dominated by a return to a maximum entropic state , but is mostly the result of variations in internal energy associated with the conformational changes .", "entity": [], "task": "NER"}
{"text": "Here , a review of alpha - helix based elastomeric materials is presented that encompasses examples and experimental evidence across multiple length scales , from the molecular to the macroscopic scale .", "entity": [], "task": "NER"}
{"text": "We begin by summarizing the basic thermodynamic formalism of thermoelasticity .", "entity": [], "task": "NER"}
{"text": "While this formalism is well established for amorphous ( entropically - dominated ) fibres under tensile loading , its extension towards conformational ( internal energy - dominated ) elasticity is less known .", "entity": [], "task": "NER"}
{"text": "Recent experimental evidence as well as corroborating computer simulations are then reviewed and discussed in the light of secondary structure and nano - scale features of these biopolymers .", "entity": [], "task": "NER"}
{"text": "Comparisons are also drawn with physiologically important structural fibres that share common characteristics at the molecular and the nano - scale , including intermediate filament ( IF ) proteins from the cell cytoskeleton , myosins from motor proteins , and fibrin from blood clot .", "entity": [], "task": "NER"}
{"text": "We conclude with a discussion on future directions and opportunities for these materials from a biomimetics engineering perspective .", "entity": [], "task": "NER"}
{"text": "Regions on adenylyl cyclase VII required for selective regulation by the G13 pathway .", "entity": [{"entity": "adenylyl", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "Regulation of multiple adenylyl cyclases ( AC ) provides unique inputs to mediate the synthesis of cAMP , a ubiquitous second messenger that controls many aspects of cellular function .", "entity": [{"entity": "adenylyl", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [99, 103]}], "task": "NER"}
{"text": "On stimulation by G ( s ) , the activities of ACs can be further selectively modulated by other pathways to ensure precise control of intracellular cAMP responses to specific stimuli .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [148, 152]}], "task": "NER"}
{"text": "Recently , we reported that one of the AC isoforms , AC7 , is uniquely regulated by the G ( 13 ) pathway .", "entity": [], "task": "NER"}
{"text": "To understand more fully the molecular mechanism of this regulation , we compared the regulation of AC7 with that of AC2 in bone marrow - derived macrophages devoid of AC7 .", "entity": [], "task": "NER"}
{"text": "Although both enzymes could fully restore regulation of cAMP by G beta gamma , activation of the G ( 13 ) pathway preferentially synergized with AC7 .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "Exchange of domains between the two isoforms indicates that the C1b domain and the N - terminus of the C1a domain are important for directing selective regulation of AC7 by the G ( 13 ) pathway .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [83, 84]}], "task": "NER"}
{"text": "A mutagenesis screen identified more specific regions of AC7 that differentially mediate its regulation by distinct pathways .", "entity": [], "task": "NER"}
{"text": "Vitamin K2 covalently binds to Bak and induces Bak - mediated apoptosis .", "entity": [{"entity": "Vitamin K2", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Vitamin K2 ( VK2 , menaquinone ) is known to have anticancer activity in vitro and in vivo .", "entity": [{"entity": "Vitamin K2", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "VK2", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "menaquinone", "entity_type": "Chemical", "pos": [19, 30]}], "task": "NER"}
{"text": "Although its effect is thought to be mediated , at least in part , by the induction of apoptosis , the underlying molecular mechanism remains elusive .", "entity": [], "task": "NER"}
{"text": "Here , we identified Bcl - 2 antagonist killer 1 ( Bak ) as a molecular target of VK2 - induced apoptosis .", "entity": [{"entity": "VK2", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "VK2 directly interacts with Bak and induces mitochondrial - mediated apoptosis .", "entity": [{"entity": "VK2", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Although Bak and Bcl - 2 - associated X protein ( Bax ) , another member of the Bcl - 2 family , are generally thought to be functionally redundant , only Bak is necessary and sufficient for VK2 - induced cytochrome c ( cyt c ) release and cell death .", "entity": [{"entity": "VK2", "entity_type": "Chemical", "pos": [191, 194]}], "task": "NER"}
{"text": "Moreover , VK2 - 2 , 3 epoxide , an intracellular metabolite of VK2 , was shown to covalently bind to the cysteine - 166 residue of Bak .", "entity": [{"entity": "VK2 - 2 , 3 epoxide", "entity_type": "Chemical", "pos": [11, 30]}, {"entity": "VK2", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "Several lines of evidence suggested that the covalent attachment of VK2 is critical for apoptosis induction .", "entity": [{"entity": "VK2", "entity_type": "Chemical", "pos": [68, 71]}], "task": "NER"}
{"text": "Thus this study reveals a specific role for Bak in mitochondria - mediated apoptosis .", "entity": [], "task": "NER"}
{"text": "This study also provides insight into the anticancer effects of VK2 and suggests that Bak may be a potential target of cancer therapy .", "entity": [{"entity": "VK2", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Relative oral bioavailability of 3 - MCPD from 3 - MCPD fatty acid esters in rats .", "entity": [{"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "3 - MCPD fatty acid esters", "entity_type": "Chemical", "pos": [47, 73]}], "task": "NER"}
{"text": "In order to quantify the relative oral bioavailability of 3 - chloropropane - 1 , 2 - diol ( 3 - MCPD ) from 3 - MCPD fatty acid diesters in vivo , 1 , 2 - dipalmitoyl - 3 - chloropropane - 1 , 2 - diol ( 3 - MCPD diester ) and 3 - MCPD were orally applied to rats in equimolar doses .", "entity": [{"entity": "3 - chloropropane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [58, 90]}, {"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [93, 101]}, {"entity": "3 - MCPD fatty acid diesters", "entity_type": "Chemical", "pos": [109, 137]}, {"entity": "1 , 2 - dipalmitoyl - 3 - chloropropane - 1 , 2 - diol", "entity_type": "Chemical", "pos": [148, 202]}, {"entity": "3 - MCPD diester", "entity_type": "Chemical", "pos": [205, 221]}, {"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [228, 236]}], "task": "NER"}
{"text": "In both cases , the time courses of 3 - MCPD concentrations were measured in blood , various organs , tissues and intestinal luminal contents .", "entity": [{"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "The results show that 3 - MCPD is released by enzymatic hydrolysis from the 3 - MCPD diester in the gastrointestinal tract and distributed to blood , organs and tissues .", "entity": [{"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "3 - MCPD diester", "entity_type": "Chemical", "pos": [76, 92]}], "task": "NER"}
{"text": "Based on the measurements in blood , the areas under the curve ( AUC ) for 3 - MCPD were calculated .", "entity": [{"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "By comparing both AUC , the relative amount of 3 - MCPD bioavailable from the 3 - MCPD diester was calculated to be 86 % on average of the amount bioavailable following administration of 3 - MCPD .", "entity": [{"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [47, 55]}, {"entity": "3 - MCPD diester", "entity_type": "Chemical", "pos": [78, 94]}, {"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [187, 195]}], "task": "NER"}
{"text": "In view of limited experimental data , it is justified for the purpose of risk assessment to assume complete hydrolysis of the diesters in the gastro - intestinal tract .", "entity": [], "task": "NER"}
{"text": "Therefore , assessment of the extent of exposure to 3 - MCPD released from its fatty acid esters should be performed in the same way as exposure to the same molar quantity of 3 - MCPD .", "entity": [{"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "fatty acid esters", "entity_type": "Chemical", "pos": [79, 96]}, {"entity": "3 - MCPD", "entity_type": "Chemical", "pos": [175, 183]}], "task": "NER"}
{"text": "Enantioresolution of chiral derivatives of xanthones on ( S , S ) - Whelk - O1 and L - phenylglycine stationary phases and chiral recognition mechanism by docking approach for ( S , S ) - Whelk - O1 .", "entity": [{"entity": "xanthones", "entity_type": "Chemical", "pos": [43, 52]}, {"entity": "L - phenylglycine", "entity_type": "Chemical", "pos": [83, 100]}], "task": "NER"}
{"text": "The resolution of seven enantiomeric pairs of chiral derivatives of xanthones ( CDXs ) on ( S , S ) - Whelk - O1 and L - phenylglycine chiral stationary phases ( CSPs ) was systematically investigated using multimodal elution conditions ( normal - phase , polar - organic , and reversed - phase ) .", "entity": [{"entity": "xanthones", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "L - phenylglycine", "entity_type": "Chemical", "pos": [117, 134]}], "task": "NER"}
{"text": "The ( S , S ) - Whelk - O1 CSP , under polar - organic conditions , demonstrated a very good power of resolution for the CDXs possessing an aromatic moiety linked to the stereogenic center with separation factor and resolution factor ranging from 1 . 91 to 7 . 55 and from 6 . 71 to 24 . 16 , respectively .", "entity": [], "task": "NER"}
{"text": "The chiral recognition mechanisms were also investigated for ( S , S ) - Whelk - O1 CSP by molecular docking technique .", "entity": [], "task": "NER"}
{"text": "Data regarding the CSP - CDX molecular conformations and interactions were retrieved .", "entity": [], "task": "NER"}
{"text": "These results were in accordance with the experimental chromatographic parameters regarding enantioselectivity and enantiomer elution order .", "entity": [], "task": "NER"}
{"text": "The results of the present study fulfilled the initial objectives of enantioselective studies of CDXs and elucidation of intermolecular CSP - CDX interactions .", "entity": [], "task": "NER"}
{"text": "The Midregional Fragment of Pro - A - Type Natriuretic Peptide , Blood Pressure , and Mortality in a Prospective Cohort Study of Patients With Type 2 Diabetes ( ZODIAC - 25 ) .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE Evidence that midregional fragment of pro - A - type natriuretic peptide ( MR - proANP ) is a marker of mortality in patients with type 2 diabetes is limited .", "entity": [], "task": "NER"}
{"text": "Therefore , we aimed to investigate the capabilities of MR - proANP in predicting mortality .", "entity": [], "task": "NER"}
{"text": "We also investigated whether MR - proANP influences the relationship between blood pressure and mortality in old age .", "entity": [], "task": "NER"}
{"text": "RESEARCH DESIGN AND METHODS In 1998 , 1 , 143 primary care patients with type 2 diabetes participated in the ZODIAC study .", "entity": [], "task": "NER"}
{"text": "Because blood was drawn for 867 patients ( 76 % ) and confounders were missing for 19 patients , the final study sample comprised 848 patients .", "entity": [], "task": "NER"}
{"text": "After a follow - up time of 10 years , we used Cox proportional hazard models to evaluate the relationship between MR - proANP and ( cardiovascular ) mortality .", "entity": [], "task": "NER"}
{"text": "Harrell C statistic was used to compare models with and without MR - proANP .", "entity": [], "task": "NER"}
{"text": "The regression analyses were repeated without MR - proANP for patients aged older than 75 years .", "entity": [], "task": "NER"}
{"text": "RESULTS Median MR - proANP in the total study sample was 75 pmol / L ( interquartile range , 48 - 124 pmol / L ) .", "entity": [], "task": "NER"}
{"text": "During follow - up , 354 ( 42 % ) out of 848 patients had died , of whom 152 ( 43 % ) deaths were attributable to cardiovascular factors .", "entity": [], "task": "NER"}
{"text": "MR - proANP was independently associated with all - cause and cardiovascular mortality , irrespective of age .", "entity": [], "task": "NER"}
{"text": "During old age , there was a significant inverse relationship between blood pressure and mortality .", "entity": [], "task": "NER"}
{"text": "This relationship did not change after adjustment for MR - proANP .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS MR - proANP is independently associated with mortality in patients with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "MR - proANP did not influence the inverse relationship between blood pressure and mortality in elderly patients .", "entity": [], "task": "NER"}
{"text": "Involvement of UDP - glucuronosyltransferases UGT1A9 and UGT2B7 in ethanol glucuronidation , and interactions with common drugs of abuse .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [67, 74]}], "task": "NER"}
{"text": "Ethyl glucuronide ( EtG ) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption .", "entity": [{"entity": "Ethyl glucuronide", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "EtG", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [109, 116]}], "task": "NER"}
{"text": "The enzymes involved in EtG production , as well as potential interactions with common drugs of abuse , have not been extensively studied .", "entity": [{"entity": "EtG", "entity_type": "Chemical", "pos": [24, 27]}], "task": "NER"}
{"text": "Activities of human liver ( HLM ) , kidney ( HKM ) , and intestinal ( HIM ) microsomes , as well as of 12 major human recombinant UDP - glucuronosyltransferases ( UGTs ) , toward ethanol ( 50 and 500 mM ) were evaluated in vitro using liquid chromatography - tandem mass spectrometry .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [130, 133]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity .", "entity": [], "task": "NER"}
{"text": "Individual contributions of UGTs were estimated using the relative activity factor approach , proposed for scaling activities obtained with cDNA - expressed enzymes to HLM .", "entity": [], "task": "NER"}
{"text": "Interaction of morphine , codeine , lorazepam , oxazepam , nicotine , cotinine , cannabinol , and cannabidiol ( 5 , 10 , 15 mg / l ) with ethanol ( 1 . 15 , 4 . 6 , 11 . 5 g / l ; i . e . , 25 , 100 , 250 mM ) glucuronidation was assessed using pooled HLM .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [26, 33]}, {"entity": "lorazepam", "entity_type": "Chemical", "pos": [36, 45]}, {"entity": "oxazepam", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [59, 67]}, {"entity": "cotinine", "entity_type": "Chemical", "pos": [70, 78]}, {"entity": "cannabinol", "entity_type": "Chemical", "pos": [81, 91]}, {"entity": "cannabidiol", "entity_type": "Chemical", "pos": [98, 109]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "Ethanol glucuronidation intrinsic clearance ( Cl ( int ) ) was 4 and 12 . 7 times higher for HLM than for HKM and HIM , respectively .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "All recombinant UGTs , except UGT1A1 , 1A6 , and 1A10 , produced EtG in detectable amounts .", "entity": [{"entity": "EtG", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "UGT1A9 and 2B7 were the most active enzymes , each accounting for 17 and 33 % of HLM Cl ( int ) , respectively .", "entity": [], "task": "NER"}
{"text": "Only cannabinol and cannabidiol significantly affected ethanol glucuronidation .", "entity": [{"entity": "cannabinol", "entity_type": "Chemical", "pos": [5, 15]}, {"entity": "cannabidiol", "entity_type": "Chemical", "pos": [20, 31]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "Cannabinol increased ethanol glucuronidation in a concentration - dependent manner , whereas cannabidiol significantly inhibited EtG formation in a noncompetitive manner ( IC ( 50 ) = 1 . 17 mg / l ; inhibition constant ( K ( i ) ) = 3 . 1 mg / l ) .", "entity": [{"entity": "Cannabinol", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [21, 28]}, {"entity": "cannabidiol", "entity_type": "Chemical", "pos": [93, 104]}, {"entity": "EtG", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [48, 55]}], "task": "NER"}
{"text": "In addition , our results suggest that cannabinol and cannabidiol could significantly alter ethanol glucuronidation .", "entity": [{"entity": "cannabinol", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "cannabidiol", "entity_type": "Chemical", "pos": [54, 65]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "Mutation of a zinc - binding residue in the glycine receptor alpha 1 subunit changes ethanol sensitivity in vitro and alcohol consumption in vivo .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [44, 51]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "Ethanol is a widely used drug , yet an understanding of its sites and mechanisms of action remains incomplete .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Among the protein targets of ethanol are glycine receptors ( GlyRs ) , which are potentiated by millimolar concentrations of ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [29, 36]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "In addition , zinc ions also modulate GlyR function , and recent evidence suggests that physiologic concentrations of zinc enhance ethanol potentiation of GlyRs .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [118, 122]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [131, 138]}], "task": "NER"}
{"text": "Here , we first built a homology model of a zinc - bound GlyR using the D80 position as a coordination site for a zinc ion .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [114, 118]}], "task": "NER"}
{"text": "Next , we investigated in vitro the effects of zinc on ethanol action at recombinant wild - type ( WT ) and mutant alpha 1 GlyRs containing the D80A substitution , which eliminates zinc potentiation .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [47, 51]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [181, 185]}], "task": "NER"}
{"text": "At D80A GlyRs , the effects of 50 and 200 mM ethanol were reduced as compared with WT receptors .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "Also , in contrast to what was seen with WT GlyRs , neither adding nor chelating zinc changed the magnitude of ethanol enhancement of mutant D80A receptors .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [81, 85]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [111, 118]}], "task": "NER"}
{"text": "Next , we evaluated the in vivo effects of the D80A substitution by using heterozygous Glra1 ( D80A ) knock - in ( KI ) mice .", "entity": [], "task": "NER"}
{"text": "The KI mice showed decreased ethanol consumption and preference , and they displayed increased startle responses compared with their WT littermates .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "Other behavioral tests , including ethanol - induced motor incoordination and strychnine - induced convulsions , revealed no differences between the KI and WT mice .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "strychnine", "entity_type": "Chemical", "pos": [78, 88]}], "task": "NER"}
{"text": "Together , our findings indicate that zinc is critical in determining the effects of ethanol at GlyRs and suggest that zinc binding at the D80 position may be important for mediating some of the behavioral effects of ethanol action at GlyRs .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [38, 42]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [119, 123]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [217, 224]}], "task": "NER"}
{"text": "Expression and activity of nitric oxide synthase isoforms in methamphetamine - induced striatal dopamine toxicity .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [61, 76]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "Nitric oxide is implicated in methamphetamine ( METH ) - induced neurotoxicity ; however , the source of the nitric oxide has not been identified .", "entity": [{"entity": "Nitric oxide", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [30, 45]}, {"entity": "METH", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [109, 121]}], "task": "NER"}
{"text": "Previous work has also revealed that animals with partial dopamine loss induced by a neurotoxic regimen of methamphetamine fail to exhibit further decreases in striatal dopamine when re - exposed to methamphetamine 7 - 30 days later .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [58, 66]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [107, 122]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [169, 177]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [199, 214]}], "task": "NER"}
{"text": "The current study examined nitric oxide synthase expression and activity and protein nitration in striata of animals administered saline or neurotoxic regimens of methamphetamine at postnatal days 60 and / or 90 , resulting in four treatment groups : Saline : Saline , METH : Saline , Saline : METH , and METH : METH .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [163, 178]}, {"entity": "METH", "entity_type": "Chemical", "pos": [269, 273]}, {"entity": "METH", "entity_type": "Chemical", "pos": [294, 298]}, {"entity": "METH", "entity_type": "Chemical", "pos": [305, 309]}, {"entity": "METH", "entity_type": "Chemical", "pos": [312, 316]}], "task": "NER"}
{"text": "Acute administration of methamphetamine on postnatal day 90 ( Saline : METH and METH : METH ) increased nitric oxide production , as evidenced by increased protein nitration .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [24, 39]}, {"entity": "METH", "entity_type": "Chemical", "pos": [71, 75]}, {"entity": "METH", "entity_type": "Chemical", "pos": [80, 84]}, {"entity": "METH", "entity_type": "Chemical", "pos": [87, 91]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [104, 116]}], "task": "NER"}
{"text": "Methamphetamine did not , however , change the expression of endothelial or inducible isoforms of nitric oxide synthase , nor did it change the number of cells positive for neuronal nitric oxide synthase mRNA expression or the amount of neuronal nitric oxide synthase mRNA per cell .", "entity": [{"entity": "Methamphetamine", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [98, 110]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [182, 194]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [246, 258]}], "task": "NER"}
{"text": "However , nitric oxide synthase activity in striatal interneurons was increased in the Saline : METH and METH : METH animals .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [10, 22]}, {"entity": "METH", "entity_type": "Chemical", "pos": [96, 100]}, {"entity": "METH", "entity_type": "Chemical", "pos": [105, 109]}, {"entity": "METH", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "These data suggest that increased nitric oxide production after a neurotoxic regimen of methamphetamine results from increased nitric oxide synthase activity , rather than an induction of mRNA , and that constitutively expressed neuronal nitric oxide synthase is the most likely source of nitric oxide after methamphetamine administration .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [34, 46]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [88, 103]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [127, 139]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [238, 250]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [289, 301]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [308, 323]}], "task": "NER"}
{"text": "Of interest , animals rendered resistant to further methamphetamine - induced dopamine depletions still show equivalent degrees of methamphetamine - induced nitric oxide production , suggesting that nitric oxide production alone in response to methamphetamine is not sufficient to induce acute neurotoxic injury .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [52, 67]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [78, 86]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [131, 146]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [157, 169]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [199, 211]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [244, 259]}], "task": "NER"}
{"text": "The yeast cap binding complex modulates transcription factor recruitment and establishes proper histone H3K36 trimethylation during active transcription .", "entity": [], "task": "NER"}
{"text": "Recent studies have revealed a close relationship between transcription , histone modification , and RNA processing .", "entity": [], "task": "NER"}
{"text": "In fact , genome - wide analyses that correlate histone marks with RNA processing signals raise the possibility that specific RNA processing factors may modulate transcription and help to \" write \" chromatin marks .", "entity": [], "task": "NER"}
{"text": "Here we show that the nuclear cap binding complex ( CBC ) directs recruitment of transcription elongation factors and establishes proper histone marks during active transcription .", "entity": [], "task": "NER"}
{"text": "A directed genetic screen revealed that deletion of either subunit of the CBC confers a synthetic growth defect when combined with deletion of genes encoding either Ctk2 or Bur2 , a component of the Saccharomyces cerevisiae ortholog of P - TEFb .", "entity": [], "task": "NER"}
{"text": "The CBC physically associates with these complexes to recruit them during transcription and mediates phosphorylation at Ser - 2 of the C - terminal domain ( CTD ) of RNA polymerase II .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [120, 123]}, {"entity": "C", "entity_type": "Chemical", "pos": [135, 136]}], "task": "NER"}
{"text": "To understand how these interactions influence downstream events , histone H3K36me3 was examined , and we demonstrate that CBC Delta affects proper Set2 - dependent H3K36me3 .", "entity": [], "task": "NER"}
{"text": "Consistent with this , the CBC and Set2 have similar effects on the ability to rapidly induce and sustain activated gene expression , and these effects are distinct from other histone methyltransferases .", "entity": [], "task": "NER"}
{"text": "This work provides evidence for an emerging model that RNA processing factors can modulate the recruitment of transcription factors and influence histone modification during elongation .", "entity": [], "task": "NER"}
{"text": "Continuum - and particle - based modeling of shapes and dynamics of red blood cells in health and disease .", "entity": [], "task": "NER"}
{"text": "We review recent advances in multiscale modeling of the mechanics of healthy and diseased red blood cells ( RBCs ) , and blood flow in the microcirculation .", "entity": [], "task": "NER"}
{"text": "We cover the traditional continuum - based methods but also particle - based methods used to model both the RBCs and the blood plasma .", "entity": [], "task": "NER"}
{"text": "We highlight examples of successful simulations of blood flow including malaria and sickle cell anemia .", "entity": [], "task": "NER"}
{"text": "Surfactant - free microemulsion composed of oleic acid , n - propanol , and H2O .", "entity": [{"entity": "oleic acid", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "n - propanol", "entity_type": "Chemical", "pos": [57, 69]}, {"entity": "H2O", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "Generally , a microemulsion consists of oil , water , surfactant , and sometimes cosurfactant .", "entity": [], "task": "NER"}
{"text": "Herein , we report a surfactant - free microemulsion ( denoted as SFME ) , consisting of oleic acid ( oil phase ) , water , and n - propanol without the amphiphilic molecular structure of a traditional surfactant .", "entity": [{"entity": "oleic acid", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "n - propanol", "entity_type": "Chemical", "pos": [128, 140]}], "task": "NER"}
{"text": "The phase behavior of the ternary system was investigated , showing that there were a single - phase microemulsion region and a multiphase region in the ternary phase diagram .", "entity": [], "task": "NER"}
{"text": "The electrical conductivity measurement was employed to investigate the microregions of the single - phase microemulsion region , and three different microregions , that is , water - in - oleic acid ( W / O ) , a bicontinuous ( B . C . ) region , and oleic acid - in - water ( O / W ) , were identified , which were further confirmed by freeze - fracture and cryogenic transmission electron microscopy ( FF - TEM and Cryo - TEM ) observations .", "entity": [{"entity": "oleic acid", "entity_type": "Chemical", "pos": [188, 198]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [251, 261]}], "task": "NER"}
{"text": "The polarity and the salt solubility of water domains in the W / O SFME were investigated by UV - visible spectroscopy using methyl orange and potassium ferricyanide as probes , respectively .", "entity": [{"entity": "methyl orange", "entity_type": "Chemical", "pos": [125, 138]}, {"entity": "potassium ferricyanide", "entity_type": "Chemical", "pos": [143, 165]}], "task": "NER"}
{"text": "Experimental results showed that the water domains in the W / O microemulsion had a lower polarity than bulk water and a normal solubility for salt species , indicating that the SFMEs have much significance in the preparation of various nanomaterials .", "entity": [], "task": "NER"}
{"text": "An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity .", "entity": [], "task": "NER"}
{"text": "Homologous recombination ( HR ) is an essential process in cells that provides repair of DNA double - strand breaks and lesions that block DNA replication .", "entity": [], "task": "NER"}
{"text": "RAD51 is an evolutionarily conserved protein that is central to HR .", "entity": [], "task": "NER"}
{"text": "Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology .", "entity": [], "task": "NER"}
{"text": "We previously described a chemical inhibitor of RAD51 , called RI - 1 ( referred to as compound 1 in this report ) .", "entity": [{"entity": "RI - 1", "entity_type": "Chemical", "pos": [63, 69]}], "task": "NER"}
{"text": "The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51 , using a conjugate addition - elimination mechanism .", "entity": [{"entity": "chloromaleimide", "entity_type": "Chemical", "pos": [4, 19]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [102, 107]}], "task": "NER"}
{"text": "In order to reduce the likelihood of off - target effects and to improve compound stability in biological systems , we developed an analogue of compound 1 that lacks maleimide - based reactivity but retains RAD51 inhibitory activity .", "entity": [{"entity": "maleimide", "entity_type": "Chemical", "pos": [166, 175]}], "task": "NER"}
{"text": "This compound , 1 - ( 3 , 4 - dichlorophenyl ) - 3 - ( 4 - methoxyphenyl ) - 4 - morpholino - 1H - pyrrole - 2 , 5 - dione , named RI - 2 ( referred to as compound 7a in this report ) , appears to bind reversibly to the same site on the RAD51 protein as does compound 1 .", "entity": [{"entity": "1 - ( 3 , 4 - dichlorophenyl ) - 3 - ( 4 - methoxyphenyl ) - 4 - morpholino - 1H - pyrrole - 2 , 5 - dione", "entity_type": "Chemical", "pos": [16, 122]}, {"entity": "RI - 2", "entity_type": "Chemical", "pos": [131, 137]}], "task": "NER"}
{"text": "Like compound 1 , compound 7a specifically inhibits HR repair in human cells .", "entity": [], "task": "NER"}
{"text": "Tilting the balance between canonical and noncanonical conformations for the H1 hypervariable loop of a llama VHH through point mutations .", "entity": [], "task": "NER"}
{"text": "Nanobodies are single - domain antibodies found in camelids .", "entity": [], "task": "NER"}
{"text": "These are the smallest naturally occurring binding domains and derive functionality via three hypervariable loops ( H1 - H3 ) that form the binding surface .", "entity": [], "task": "NER"}
{"text": "They are excellent candidates for antibody engineering because of their favorable characteristics like small size , high solubility , and stability .", "entity": [], "task": "NER"}
{"text": "To rationally engineer antibodies with affinity for a specific target , the hypervariable loops can be tailored to obtain the desired binding surface .", "entity": [], "task": "NER"}
{"text": "As a first step toward such a goal , we consider the design of loops with a desired conformation .", "entity": [], "task": "NER"}
{"text": "In this study , we focus on the H1 loop of the anti - hCG llama nanobody that exhibits a noncanonical conformation .", "entity": [], "task": "NER"}
{"text": "We aim to \" tilt \" the stability of the H1 loop structure from a noncanonical conformation to a ( humanized ) type 1 canonical conformation by studying the effect of selected mutations to the amino acid sequence of the H1 , H2 , and proximal residues .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [192, 202]}], "task": "NER"}
{"text": "We use all - atomistic , explicit - solvent , biased molecular dynamic simulations to simulate the wild - type and mutant loops in a prefolded framework .", "entity": [], "task": "NER"}
{"text": "We thus find mutants with increasing propensity to form a stable type 1 canonical conformation of the H1 loop .", "entity": [], "task": "NER"}
{"text": "Free energy landscapes reveal the existence of conformational isomers of the canonical conformation that may play a role in binding different antigenic surfaces .", "entity": [], "task": "NER"}
{"text": "We also elucidate the approximate mechanism and kinetics of transitions between such conformational isomers by using a Markovian model .", "entity": [], "task": "NER"}
{"text": "We find that a particular three - point mutant has the strongest thermodynamic propensity to form the H1 type 1 canonical structure but also to exhibit transitions between conformational isomers , while a different , more rigid three - point mutant has the strongest propensity to be kinetically trapped in such a canonical structure .", "entity": [], "task": "NER"}
{"text": "Peptidyl - prolyl cis / trans - isomerase A1 ( Pin1 ) is a target for modification by lipid electrophiles .", "entity": [{"entity": "prolyl", "entity_type": "Chemical", "pos": [11, 17]}], "task": "NER"}
{"text": "Oxidation of membrane phospholipids is associated with inflammation , neurodegenerative disease , and cancer .", "entity": [], "task": "NER"}
{"text": "Oxyradical damage to phospholipids results in the production of reactive aldehydes that adduct proteins and modulate their function .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "4 - Hydroxynonenal ( HNE ) , a common product of oxidative damage to lipids , adducts proteins at exposed Cys , His , or Lys residues .", "entity": [{"entity": "4 - Hydroxynonenal", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "HNE", "entity_type": "Chemical", "pos": [21, 24]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [106, 109]}, {"entity": "His", "entity_type": "Chemical", "pos": [112, 115]}, {"entity": "Lys", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "Here , we demonstrate that peptidyl - prolyl cis / trans - isomerase A1 ( Pin1 ) , an enzyme that catalyzes the conversion of the peptide bond of pSer / pThr - Pro moieties in signaling proteins from cis to trans , is highly susceptible to HNE modification .", "entity": [{"entity": "prolyl", "entity_type": "Chemical", "pos": [38, 44]}, {"entity": "pSer", "entity_type": "Chemical", "pos": [146, 150]}, {"entity": "pThr", "entity_type": "Chemical", "pos": [153, 157]}, {"entity": "Pro", "entity_type": "Chemical", "pos": [160, 163]}, {"entity": "HNE", "entity_type": "Chemical", "pos": [240, 243]}], "task": "NER"}
{"text": "Incubation of purified Pin1 with HNE followed by MALDI - TOF / TOF mass spectrometry resulted in detection of Michael adducts at the active site residues His - 157 and Cys - 113 .", "entity": [{"entity": "HNE", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "His", "entity_type": "Chemical", "pos": [154, 157]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [168, 171]}], "task": "NER"}
{"text": "Time and concentration dependencies indicate that Cys - 113 is the primary site of HNE modification .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "HNE", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Pin1 was adducted in MDA - MB - 231 breast cancer cells treated with 8 - alkynyl - HNE as judged by click chemistry conjugation with biotin followed by streptavidin - based pulldown and Western blotting with anti - Pin1 antibody .", "entity": [{"entity": "8 - alkynyl - HNE", "entity_type": "Chemical", "pos": [69, 86]}, {"entity": "biotin", "entity_type": "Chemical", "pos": [133, 139]}], "task": "NER"}
{"text": "Furthermore , orbitrap MS data support the adduction of Cys - 113 in the Pin1 active site upon HNE treatment of MDA - MB - 231 cells .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "HNE", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "siRNA knockdown of Pin1 in MDA - MB - 231 cells partially protected the cells from HNE - induced toxicity .", "entity": [{"entity": "HNE", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Recent studies indicate that Pin1 is an important molecular target for the chemopreventive effects of green tea polyphenols .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [112, 123]}], "task": "NER"}
{"text": "The present study establishes that it is also a target for electrophilic modification by products of lipid peroxidation .", "entity": [], "task": "NER"}
{"text": "New iridoid glycoside and triterpenoid glycoside from Premna fulva .", "entity": [{"entity": "iridoid glycoside", "entity_type": "Chemical", "pos": [4, 21]}, {"entity": "triterpenoid glycoside", "entity_type": "Chemical", "pos": [26, 48]}], "task": "NER"}
{"text": "Liquid chromatography - photodiode array detector - mass spectrometry - based chemical investigation of the leaves and stems of Premna fulva yielded one new iridoid glycoside ( 1 ) , one new triterpenoid glycoside ( 2 ) along with six known compounds isolated for the first time from the genus .", "entity": [{"entity": "iridoid glycoside", "entity_type": "Chemical", "pos": [157, 174]}, {"entity": "triterpenoid glycoside", "entity_type": "Chemical", "pos": [191, 213]}], "task": "NER"}
{"text": "Their structures were established on the basis of extensive spectroscopic data analyses and chemical methods .", "entity": [], "task": "NER"}
{"text": "Acetazolamide impairs fear memory consolidation in rodents .", "entity": [{"entity": "Acetazolamide", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Acetazolamide ( AZ ) is an carbonic anhydrase inhibitor , which has been used in the treatment of seizures , mountain sickness and glaucoma .", "entity": [{"entity": "Acetazolamide", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Memory impairment by AZ has been reported in patient interviews ; however , the related mechanism is unclear .", "entity": [], "task": "NER"}
{"text": "We applied two fear conditioning paradigms , shuttle avoidance and passive avoidance , in both rats and mice to investigate this clinical anecdote .", "entity": [], "task": "NER"}
{"text": "Adult Wistar rats receiving AZ 1 h before the shuttle avoidance test showed decreased avoidance rates , especially at high dosage .", "entity": [], "task": "NER"}
{"text": "Adult ICR mice receiving AZ both before and after acquisition trials showed the decreased step - through latencies during the passive avoidance test .", "entity": [], "task": "NER"}
{"text": "This impairment of fear memory was corroborated with decreased LTP by AZ in the amygdala .", "entity": [], "task": "NER"}
{"text": "AZ only inhibited fear conditioning - induced ERK phosphorylation and had no effect on Akt phosphorylation .", "entity": [], "task": "NER"}
{"text": "In conclusion , our study confirmed the adverse cognitive effect of AZ in animal and electrophysiological studies .", "entity": [], "task": "NER"}
{"text": "In clinical practice , clinicians should be aware of this side effect in patients taking AZ .", "entity": [], "task": "NER"}
{"text": "In addition , this inhibition of fear memory by AZ could potentially be applied to patients with posttraumatic stress disorder .", "entity": [], "task": "NER"}
{"text": "Structure - based optimization of angiostatic agent 6DBF7 , an allosteric antagonist of galectin - 1 .", "entity": [{"entity": "6DBF7", "entity_type": "Chemical", "pos": [52, 57]}], "task": "NER"}
{"text": "Galectin - 1 ( gal - 1 ) , which binds beta - galactoside groups on various cell surface receptors , is crucial to cell adhesion and migration , and is found to be elevated in several cancers .", "entity": [], "task": "NER"}
{"text": "Previously , we reported on 6DBF7 , a dibenzofuran ( DBF ) - based peptidomimetic of the gal - 1 antagonist anginex .", "entity": [{"entity": "6DBF7", "entity_type": "Chemical", "pos": [28, 33]}, {"entity": "dibenzofuran", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "DBF", "entity_type": "Chemical", "pos": [53, 56]}], "task": "NER"}
{"text": "In the present study , we used a structure - based approach to optimize 6DBF7 .", "entity": [{"entity": "6DBF7", "entity_type": "Chemical", "pos": [72, 77]}], "task": "NER"}
{"text": "Initial NMR studies showed that 6DBF7 binds to gal - 1 on one side of the beta - sandwich away from the lectin ' s carbohydrate binding site .", "entity": [{"entity": "6DBF7", "entity_type": "Chemical", "pos": [32, 37]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [115, 127]}], "task": "NER"}
{"text": "Although an alanine scan of 6DBF7 showed that the two cationic groups ( lysines ) in the partial peptide are crucial to its angiostatic activity , it is the hydrophobic face of the amphipath that appears to interact directly with the surface of gal - 1 .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "6DBF7", "entity_type": "Chemical", "pos": [28, 33]}, {"entity": "lysines", "entity_type": "Chemical", "pos": [72, 79]}], "task": "NER"}
{"text": "Based on this structural information , we designed and tested additional DBF analogs .", "entity": [{"entity": "DBF", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "In particular , substitution of the C - terminal Asp for alanine and branched alkyl side chains ( Val , Leu , Ile ) for linear ones ( Nle , Nva ) rendered the greatest improvements in activity .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [36, 37]}, {"entity": "Asp", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [78, 83]}, {"entity": "Val", "entity_type": "Chemical", "pos": [98, 101]}, {"entity": "Leu", "entity_type": "Chemical", "pos": [104, 107]}, {"entity": "Ile", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "Nle", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "Nva", "entity_type": "Chemical", "pos": [140, 143]}], "task": "NER"}
{"text": "Flow cytometry with gal - 1 ( - / - ) splenocytes showed that 6DBF7 and two of its more potent analogs ( DB16 and DB21 ) can fully inhibit fluorescein isothiocyanate - gal - 1 binding .", "entity": [{"entity": "6DBF7", "entity_type": "Chemical", "pos": [62, 67]}, {"entity": "DB16", "entity_type": "Chemical", "pos": [105, 109]}, {"entity": "DB21", "entity_type": "Chemical", "pos": [114, 118]}, {"entity": "fluorescein isothiocyanate", "entity_type": "Chemical", "pos": [139, 165]}], "task": "NER"}
{"text": "Moreover , heteronuclear single - quantum coherence NMR titrations showed that the presence of DB16 decreases gal - 1 affinity for lactose , indicating that the peptidomimetic targets gal - 1 as a noncompetitive , allosteric inhibitor of glycan binding .", "entity": [{"entity": "DB16", "entity_type": "Chemical", "pos": [95, 99]}, {"entity": "lactose", "entity_type": "Chemical", "pos": [131, 138]}], "task": "NER"}
{"text": "Using tumor mouse models ( B16F10 melanoma , LS174 lung , and MA148 ovarian ) , we found that DB21 inhibits tumor angiogenesis and tumor growth significantly better than 6DBF7 , DB16 , or anginex .", "entity": [{"entity": "DB21", "entity_type": "Chemical", "pos": [94, 98]}, {"entity": "6DBF7", "entity_type": "Chemical", "pos": [170, 175]}, {"entity": "DB16", "entity_type": "Chemical", "pos": [178, 182]}], "task": "NER"}
{"text": "DB21 is currently being developed further and holds promise for the management of human cancer in the clinic .", "entity": [{"entity": "DB21", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "An integrated assessment of sediment remediation in a midwestern U . S . stream using sediment chemistry , water quality , bioassessment , and fish biomarkers .", "entity": [], "task": "NER"}
{"text": "A comprehensive biological , sediment , and water quality study of the lower Little Scioto River near Marion , Ohio , USA , was undertaken to evaluate the changes or improvements in biotic measurements following the removal of creosote - contaminated sediment .", "entity": [], "task": "NER"}
{"text": "The study area covered 7 . 5 river miles ( RMs ) , including a remediated section between RMs 6 . 0 and 6 . 8 .", "entity": [], "task": "NER"}
{"text": "Fish and macroinvertebrate assemblages , fish biomarkers ( i . e . , polycyclic aromatic hydrocarbon [ PAH ] metabolite levels in white sucker [ Castostomus commersoni ] and common carp [ Cyprinus carpio ] bile and DNA damage ) , sediment chemistry , and water quality were assessed at five locations relative to the primary source of historical PAH contamination - upstream ( RM 9 . 2 ) , adjacent ( RM 6 . 5 ) , and downstream ( RMs 5 . 7 , 4 . 4 , and 2 . 7 ) .", "entity": [{"entity": "polycyclic aromatic hydrocarbon", "entity_type": "Chemical", "pos": [69, 100]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [346, 349]}], "task": "NER"}
{"text": "Overall , the biomarker results were consistent with the sediment PAH results , showing a pattern of low levels of PAH bile metabolites and DNA damage at the upstream ( reference or background location ) , as well as the remediated section , high levels at the two immediate downstream sites , and somewhat lower levels at the furthest downstream site .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "Results show that remediation was effective in reducing sediment contaminant concentrations and exposure of fish to PAHs and in improving fish assemblages ( 60 % increase in index of biotic integrity scores ) in remediated river sections .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [116, 120]}], "task": "NER"}
{"text": "Additional remedial investigation and potentially further remediation is needed to improve the downstream benthic fish community , which is still heavily exposed to PAH contaminants .", "entity": [{"entity": "PAH", "entity_type": "Chemical", "pos": [165, 168]}], "task": "NER"}
{"text": "A maternal \" junk - food \" diet reduces sensitivity to the opioid antagonist naloxone in offspring postweaning .", "entity": [{"entity": "naloxone", "entity_type": "Chemical", "pos": [77, 85]}], "task": "NER"}
{"text": "Perinatal exposure to a maternal \" junk - food \" diet has been demonstrated to increase the preference for palatable diets in adult offspring .", "entity": [], "task": "NER"}
{"text": "We aimed to determine whether this increased preference could be attributed to changes in mu - opioid receptor expression within the mesolimbic reward pathway .", "entity": [], "task": "NER"}
{"text": "We report here that mRNA expression of the mu - opioid receptor in the ventral tegmental area ( VTA ) at weaning was 1 . 4 - fold ( males ) and 1 . 9 - fold ( females ) lower in offspring of junk - food ( JF ) - fed rat dams than in offspring of dams fed a standard rodent diet ( control ) ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Administration of the opioid antagonist naloxone to offspring given a palatable diet postweaning significantly reduced fat intake in control offspring ( males : 7 . 7 +/- 0 . 7 vs . 5 . 4 +/- 0 . 6 g / kg / d ; females : 6 . 9 +/- 0 . 3 vs . 3 . 9 +/- 0 . 5 g / kg / d ; P < 0 . 05 ) , but not in male JF offspring ( 8 . 6 +/- 0 . 6 vs . 7 . 1 +/- 0 . 5 g / kg / d ) and was less effective at reducing fat intake in JF females ( 42 . 2 +/- 6 . 0 vs . 23 . 1 +/- 4 . 1 % reduction , P < 0 . 05 ) .", "entity": [{"entity": "naloxone", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "Similar findings were observed for total energy intake .", "entity": [], "task": "NER"}
{"text": "Naloxone treatment did not affect intake of standard rodent feed in control or JF offspring .", "entity": [{"entity": "Naloxone", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "These findings suggest that exposure to a maternal junk - food diet results in early desensitization of the opioid system which may explain the increased preference for junk food in these offspring .", "entity": [], "task": "NER"}
{"text": "Short - peptide fusion inhibitors with high potency against wild - type and enfuvirtide - resistant HIV - 1 .", "entity": [], "task": "NER"}
{"text": "Peptides derived from the C - terminal heptad repeat ( C peptides ) of HIV - 1 gp41 are potent inhibitors against virus entry .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [26, 27]}], "task": "NER"}
{"text": "However , development of a short C peptide possessing high anti - HIV potency is considered a daunting challenge .", "entity": [], "task": "NER"}
{"text": "We recently discovered that the residues Met626 and Thr627 preceding the pocket - binding domain of the C peptide adopt a unique M - T hook structure that is crucial for the design of HIV - 1 fusion inhibitors .", "entity": [{"entity": "Met626", "entity_type": "Chemical", "pos": [41, 47]}, {"entity": "Thr627", "entity_type": "Chemical", "pos": [52, 58]}], "task": "NER"}
{"text": "In this study , we first presented a proof - of - concept prototype that the M - T hook residues can dramatically improve the antiviral activity and thermostability of a short C peptide .", "entity": [], "task": "NER"}
{"text": "We then generated a 24 - mer peptide termed MT - SC22EK by incorporating the M - T hook structure to the N terminus of the poorly active short C peptide SC22EK .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [105, 106]}], "task": "NER"}
{"text": "Amazingly , MT - SC22EK inhibited HIV - 1 - mediated cell fusion and infection at a level comparable to C34 , T1249 , SC29EK , and sifuvirtide , and it was highly active against diverse HIV - 1 subtypes and variants , including those T20 ( enfuvirtide ) and SC29EK - resistant viruses .", "entity": [], "task": "NER"}
{"text": "The high - resolution crystal structure of MT - SC22EK reveals the N - terminal M - T hook conformation folded by incorporated Met626 and Thr627 and identifies the C - terminal boundary critical for the anti - HIV activity .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [67, 68]}, {"entity": "Met626", "entity_type": "Chemical", "pos": [127, 133]}, {"entity": "Thr627", "entity_type": "Chemical", "pos": [138, 144]}, {"entity": "C", "entity_type": "Chemical", "pos": [164, 165]}], "task": "NER"}
{"text": "Collectively , our studies provide new insights into the mechanisms of HIV - 1 fusion and its inhibition .", "entity": [], "task": "NER"}
{"text": "Design and assessment of a microfluidic network system for oxygen transport in engineered tissue .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [59, 65]}], "task": "NER"}
{"text": "Oxygen and nutrients cannot be delivered to cells residing in the interior of large - volume scaffolds via diffusion alone .", "entity": [{"entity": "Oxygen", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Several efforts have been made to meet the metabolic needs of cells in a scaffold by constructing mass transport channels , particularly in the form of bifurcated networks .", "entity": [], "task": "NER"}
{"text": "In contrast to progress in fabrication technologies , however , an approach to designing an optimal network based on experimental evaluation has not been actively reported .", "entity": [], "task": "NER"}
{"text": "The main objective of this study was to establish a procedure for designing an effective microfluidic network system for a cell - seeded scaffold and to develop an experimental model to evaluate the design .", "entity": [], "task": "NER"}
{"text": "We proposed a process to design a microfluidic network by combining an oxygen transport simulation with biomimetic principles governing biological vascular trees .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [71, 77]}], "task": "NER"}
{"text": "The simulation was performed with the effective diffusion coefficient ( D ( e , s ) ) , which was experimentally measured in our previous study .", "entity": [], "task": "NER"}
{"text": "Porous scaffolds containing an embedded microfluidic network were fabricated using the lost mold shape - forming process and salt leaching method .", "entity": [], "task": "NER"}
{"text": "The reliability of the procedure was demonstrated by experiments using the scaffolds .", "entity": [], "task": "NER"}
{"text": "This approach established a practical basis for designing an effective microfluidic network in a cell - seeded scaffold .", "entity": [], "task": "NER"}
{"text": "Mapping the ion current distribution in nanopore / electrode devices .", "entity": [], "task": "NER"}
{"text": "Solid - state nanopores with integrated electrodes have interesting prospects in next - generation single - molecule biosensing and sequencing .", "entity": [], "task": "NER"}
{"text": "These include \" gated \" nanopores with a single electrode integrated into the membrane , as well as two - electrode designs , such as a transversal tunneling junction .", "entity": [], "task": "NER"}
{"text": "Here we report the first comprehensive analysis of current flow in a three - electrode device as a model for this class of sensors .", "entity": [], "task": "NER"}
{"text": "As a new feature , we observe apparent rectification in the pore current that is rooted in the current distribution of the cell , rather than the geometry or electrostatics of the pore .", "entity": [], "task": "NER"}
{"text": "We benchmark our results against a recently developed theoretical model and define operational parameters for nanopore / electrode structures .", "entity": [], "task": "NER"}
{"text": "Our findings thus facilitate the rational design of such sensor devices .", "entity": [], "task": "NER"}
{"text": "Novobiocin analogues with second - generation noviose surrogates .", "entity": [{"entity": "Novobiocin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "noviose", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Hsp90 is a promising therapeutic target for the treatment of cancer .", "entity": [], "task": "NER"}
{"text": "Novobiocin is the first Hsp90 C - terminal inhibitor ever identified and recent structure - activity relationship studies on the noviose sugar identified several commercially available amines as suitable surrogates .", "entity": [{"entity": "Novobiocin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "noviose", "entity_type": "Chemical", "pos": [129, 136]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [137, 142]}, {"entity": "amines", "entity_type": "Chemical", "pos": [185, 191]}], "task": "NER"}
{"text": "In an effort to further understand this region of the molecule , analogues containing various N ' - amino substituents were prepared and evaluated against two breast cancer cell lines for determination of their efficacy .", "entity": [{"entity": "N ' - amino", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "Compound 37j manifested the most potent anti - proliferative activity from these studies and induced Hsp90 - dependent client protein degradation at mid nano - molar concentrations .", "entity": [], "task": "NER"}
{"text": "Enhancement of electrical and thermomechanical properties of silver nanowire composites by the introduction of nonconductive nanoparticles : experiment and simulation .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [61, 67]}], "task": "NER"}
{"text": "Electrically conductive polymer nanocomposites have been applied extensively in many fields to develop the next generation of devices .", "entity": [], "task": "NER"}
{"text": "Large amounts of conductive nanofillers in polymer matrices are , however , often required for a sufficiently high electrical conductivity , which in turn deteriorates the desired thermomechanical properties .", "entity": [], "task": "NER"}
{"text": "We illustrate a novel but facile strategy to improve the electrical conductivity and the thermomechanical property of silver nanowire / polymer nanocomposites .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [118, 124]}], "task": "NER"}
{"text": "We find that one may increase the electrical conductivity of silver nanowire / polymer nanocomposites by up to about 8 orders of magnitude by introducing silica nanoparticles with nanocomposites .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [61, 67]}, {"entity": "silica", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "The electrical percolation threshold volume fraction of silver nanowires decreases from 0 . 12 to 0 . 02 .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [56, 62]}], "task": "NER"}
{"text": "Thermomechanical properties also improve as silica nanoparticles are introduced .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [44, 50]}], "task": "NER"}
{"text": "We carry out extensive Monte Carlo simulations to elucidate the effects of silica nanoparticles at a molecular level and find that van der Waals attractive interaction between silica nanoparticles and silver nanowires dominates over the depletion - induced interaction between silver nanowires , thus improving the dispersion of silver nanowires .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "silica", "entity_type": "Chemical", "pos": [176, 182]}, {"entity": "silver", "entity_type": "Chemical", "pos": [201, 207]}, {"entity": "silver", "entity_type": "Chemical", "pos": [277, 283]}, {"entity": "silver", "entity_type": "Chemical", "pos": [329, 335]}], "task": "NER"}
{"text": "Without silica nanoparticles , silver nanowires tend to aggregate , which is why additional silver nanowires are required for a desired electrical conductivity .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [8, 14]}, {"entity": "silver", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "silver", "entity_type": "Chemical", "pos": [92, 98]}], "task": "NER"}
{"text": "On the other hand , with silica nanoparticles mixed , the electrical percolating network is likely to form at a smaller volume fraction of silver nanowires .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [25, 31]}, {"entity": "silver", "entity_type": "Chemical", "pos": [139, 145]}], "task": "NER"}
{"text": "Impact of the redox - cycling herbicide diquat on transcript expression and antioxidant enzymatic activities of the freshwater snail Lymnaea stagnalis .", "entity": [{"entity": "diquat", "entity_type": "Chemical", "pos": [40, 46]}], "task": "NER"}
{"text": "The presence of pesticides in the environment results in potential unwanted effects on non - target species .", "entity": [], "task": "NER"}
{"text": "Freshwater organisms inhabiting water bodies adjacent to agricultural areas , such as ditches , ponds and marshes , are good models to test such effects as various pesticides may reach these habitats through several ways , including aerial drift , run - off , and drainage .", "entity": [], "task": "NER"}
{"text": "Diquat is a non - selective herbicide used for crop protection or for weed control in such water bodies .", "entity": [{"entity": "Diquat", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "In this study , we investigated the effects of diquat on a widely spread aquatic invertebrate , the holarctic freshwater snail Lymnaea stagnalis .", "entity": [{"entity": "diquat", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "Due to the known redox - cycling properties of diquat , we studied transcript expression and enzymatic activities relative to oxidative and general stress in the haemolymph and gonado - digestive complex ( GDC ) .", "entity": [{"entity": "diquat", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "As diquat is not persistent , snails were exposed for short times ( 5 , 24 , and 48 h ) to ecologically relevant concentrations ( 22 . 2 , 44 . 4 , and 222 . 2 mu g l ( - 1 ) ) of diquat dibromide .", "entity": [{"entity": "diquat", "entity_type": "Chemical", "pos": [3, 9]}, {"entity": "diquat dibromide", "entity_type": "Chemical", "pos": [180, 196]}], "task": "NER"}
{"text": "RT - qPCR was used to quantify the transcription of genes encoding catalase ( cat ) , a cytosolic superoxide dismutase ( Cu / Zn - sod ) , a selenium - dependent glutathione peroxidase ( gpx ) , a glutathione reductase ( gred ) , the retinoid X receptor ( rxr ) , two heat shock proteins ( hsp40 and hsp70 ) , cortactin ( cor ) and the two ribosomal genes r18S and r28s .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [121, 123]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [126, 128]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [141, 149]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [162, 173]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [197, 208]}, {"entity": "retinoid", "entity_type": "Chemical", "pos": [234, 242]}], "task": "NER"}
{"text": "Enzymatic activities of SOD , Gpx , Gred and glutathione S - transferase ( GST ) were investigated in the GDC using spectrophoto / fluorometric methods .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "S", "entity_type": "Chemical", "pos": [57, 58]}], "task": "NER"}
{"text": "Opposite trends were obtained in the haemolymph depending on the herbicide concentration .", "entity": [], "task": "NER"}
{"text": "At the lowest concentration , effects were mainly observed after 24 h of exposure , with over - transcription of cor , hsp40 , rxr , and sod , whereas higher concentrations down - regulated the expression of most of the studied transcripts , especially after 48 h of exposure .", "entity": [], "task": "NER"}
{"text": "In the GDC , earlier responses were observed and the fold - change magnitude was generally much higher : transcription of all target genes increased significantly ( or non - significantly for cat ) after 5 h of exposure , and went back to control levels afterwards , suggesting the onset of an early response to oxidative stress associated to the unbalance of reactive oxygen species ( ROS ) in hepatocytes .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [369, 375]}], "task": "NER"}
{"text": "Although increases obtained for Gred and SOD activities were globally consistent with their respective transcript expressions , up - regulation of transcription was not always correlated with increase of enzymatic activity , indicating that diquat might affect steps downstream of transcription .", "entity": [{"entity": "diquat", "entity_type": "Chemical", "pos": [241, 247]}], "task": "NER"}
{"text": "However , constitutive levels of enzymatic activities were at least maintained .", "entity": [], "task": "NER"}
{"text": "In conclusion , diquat was shown to affect expression of the whole set of studied transcripts , reflecting their suitability as markers of early response to oxidative stress in L . stagnalis .", "entity": [{"entity": "diquat", "entity_type": "Chemical", "pos": [16, 22]}], "task": "NER"}
{"text": "Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists .", "entity": [{"entity": "aminothiazole", "entity_type": "Chemical", "pos": [21, 34]}, {"entity": "benzazepines", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "Dopamine ( D ( 2 ) ) partial agonists ( D2PAs ) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D ( 2 ) partial agonists .", "entity": [{"entity": "aminothiazole", "entity_type": "Chemical", "pos": [54, 67]}, {"entity": "benzazepines", "entity_type": "Chemical", "pos": [74, 86]}], "task": "NER"}
{"text": "These compounds have good selectivity , CNS drug - like properties and tunable D ( 2 ) partial agonism .", "entity": [], "task": "NER"}
{"text": "One of the key compounds , 8h , has good in vitro / in vivo ADME characteristics , and is active in a rat amphetamine - induced locomotor activity model .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [106, 117]}], "task": "NER"}
{"text": "Synthesis and antimycobacterial evaluation of pyrazinamide derivatives with benzylamino substitution .", "entity": [{"entity": "pyrazinamide", "entity_type": "Chemical", "pos": [46, 58]}, {"entity": "benzylamino", "entity_type": "Chemical", "pos": [76, 87]}], "task": "NER"}
{"text": "A series of 19 new compounds related to pyrazinamide were synthesized , characterized with analytical data and screened for in vitro whole cell antimycobacterial activity against Mycobacterium tuberculosis H37Rv , Mycobacterium kansasii and two types of Mycobacterium avium .", "entity": [{"entity": "pyrazinamide", "entity_type": "Chemical", "pos": [40, 52]}], "task": "NER"}
{"text": "The series consisted of 3 - ( benzylamino ) - 5 - cyanopyrazine - 2 - carboxamides and 3 - ( benzylamino ) pyrazine - 2 , 5 - dicarbonitriles with various substituents on the phenyl ring .", "entity": [{"entity": "3 - ( benzylamino ) - 5 - cyanopyrazine - 2 - carboxamides", "entity_type": "Chemical", "pos": [24, 82]}, {"entity": "3 - ( benzylamino ) pyrazine - 2 , 5 - dicarbonitriles", "entity_type": "Chemical", "pos": [87, 141]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [175, 181]}], "task": "NER"}
{"text": "RP - HPLC method was used to determine the lipophilicity of the prepared compounds .", "entity": [], "task": "NER"}
{"text": "Nine compounds exerted similar or better activity against Mycobacterium tuberculosis compared to pyrazinamide ( MIC = 6 . 25 - 12 . 5 mu g / mL ) .", "entity": [{"entity": "pyrazinamide", "entity_type": "Chemical", "pos": [97, 109]}], "task": "NER"}
{"text": "3 - ( Benzylamino ) pyrazine - 2 , 5 - dicarbonitrile inhibited all of the tested mycobacterial strains with MIC within the range 12 . 5 - 25 mu g / mL .", "entity": [{"entity": "3 - ( Benzylamino ) pyrazine - 2 , 5 - dicarbonitrile", "entity_type": "Chemical", "pos": [0, 53]}], "task": "NER"}
{"text": "Although not the most active , 4 - NH ( 2 ) substituted compounds possessed the lowest in vitro cytotoxicity ( hepatotoxicity ) , leading to selectivity index SI = 5 . 5 and SI > 21 .", "entity": [{"entity": "4 - NH ( 2 )", "entity_type": "Chemical", "pos": [31, 43]}], "task": "NER"}
{"text": "2 ' - Fluoro - 6 ' - methylene - carbocyclic adenosine phosphoramidate ( FMCAP ) prodrug : in vitro anti - HBV activity against the lamivudine - entecavir resistant triple mutant and its mechanism of action .", "entity": [{"entity": "2 ' - Fluoro - 6 ' - methylene - carbocyclic adenosine phosphoramidate", "entity_type": "Chemical", "pos": [0, 70]}, {"entity": "FMCAP", "entity_type": "Chemical", "pos": [73, 78]}, {"entity": "lamivudine", "entity_type": "Chemical", "pos": [132, 142]}, {"entity": "entecavir", "entity_type": "Chemical", "pos": [145, 154]}], "task": "NER"}
{"text": "Novel 2 ' - fluoro - 6 ' - methylene - carbocyclic adenosine ( FMCA ) monophosphate prodrug ( FMCAP ) was synthesized and evaluated for its in vitro anti - HBV potency against a lamivudine - entecavir resistant clone ( L180M + M204V + S202G ) .", "entity": [{"entity": "2 ' - fluoro - 6 ' - methylene - carbocyclic adenosine", "entity_type": "Chemical", "pos": [6, 60]}, {"entity": "FMCA", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "monophosphate", "entity_type": "Chemical", "pos": [70, 83]}, {"entity": "FMCAP", "entity_type": "Chemical", "pos": [94, 99]}, {"entity": "lamivudine", "entity_type": "Chemical", "pos": [178, 188]}, {"entity": "entecavir", "entity_type": "Chemical", "pos": [191, 200]}], "task": "NER"}
{"text": "FMCA demonstrated significant antiviral activity against wild - type as well as lamivudine - entecavir resistant triple mutant ( L180M + M204V + S202G ) .", "entity": [{"entity": "FMCA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "lamivudine", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "entecavir", "entity_type": "Chemical", "pos": [93, 102]}], "task": "NER"}
{"text": "The monophosphate prodrug ( FMCAP ) demonstrated greater than 12 - fold ( 12 x ) increase in anti - HBV activity without increased cellular toxicity .", "entity": [{"entity": "monophosphate", "entity_type": "Chemical", "pos": [4, 17]}, {"entity": "FMCAP", "entity_type": "Chemical", "pos": [28, 33]}], "task": "NER"}
{"text": "Mitochondrial and cellular toxicity studies of FMCA indicated that there is no significant toxicity up to 100 mu M .", "entity": [{"entity": "FMCA", "entity_type": "Chemical", "pos": [47, 51]}], "task": "NER"}
{"text": "Mode of action studies by molecular modeling indicate that the 2 ' - fluoro moiety by hydrogen bond as well as the Van der Waals interaction of the carbocyclic ring with the phenylalanine moiety of the polymerase promote the positive binding , even in the drug - resistant mutants .", "entity": [{"entity": "2 ' - fluoro", "entity_type": "Chemical", "pos": [63, 75]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [86, 94]}, {"entity": "carbocyclic", "entity_type": "Chemical", "pos": [148, 159]}, {"entity": "phenylalanine", "entity_type": "Chemical", "pos": [174, 187]}], "task": "NER"}
{"text": "Osteocyte apoptosis .", "entity": [], "task": "NER"}
{"text": "Apoptotic death of osteocytes was recognized over 15years ago , but its significance for bone homeostasis has remained elusive .", "entity": [], "task": "NER"}
{"text": "A new paradigm has emerged that invokes osteocyte apoptosis as a critical event in the recruitment of osteoclasts to a specific site in response to skeletal unloading , fatigue damage , estrogen deficiency and perhaps in other states where bone must be removed .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [186, 194]}], "task": "NER"}
{"text": "This is accomplished by yet to be defined signals emanating from dying osteocytes , which stimulate neighboring viable osteocytes to produce osteoclastogenic cytokines .", "entity": [], "task": "NER"}
{"text": "The osteocyte apoptosis caused by chronic glucocorticoid administration does not increase osteoclasts ; however , it does negatively impact maintenance of bone hydration , vascularity , and strength .", "entity": [], "task": "NER"}
{"text": "Bisphenol A interferes with thyroid specific gene expression .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is an endocrine - disrupting chemical that leads to low - dose human exposure due to its ability to leach from chemically derived products , as polycarbonate plastics and epoxy resin .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "polycarbonate", "entity_type": "Chemical", "pos": [164, 177]}, {"entity": "epoxy", "entity_type": "Chemical", "pos": [191, 196]}], "task": "NER"}
{"text": "In addition to its known xeno - endocrine action , BPA exerts a wide range of metabolic effects .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "Despite the documented BPA exposure outcomes on synthesis of thyroid hormones , there are not any data available on its actions on the thyroid follicular cells , site of synthesis of the thyroid hormones .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "thyroid hormones", "entity_type": "Chemical", "pos": [61, 77]}, {"entity": "thyroid hormones", "entity_type": "Chemical", "pos": [187, 203]}], "task": "NER"}
{"text": "Recently , it has been shown that several environmental pollutants , as BPA , can exert a thyroid disrupting activity .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [72, 75]}], "task": "NER"}
{"text": "In this study , we employed in vitro and in vivo ( zebrafish ) models to examine the effects of BPA in regulating the expression of genes involved in the thyroid hormone synthesis and of their transcriptional regulators at BPA doses as low as 10 ( - 9 ) M , a dose that is environmentally pertinent and far below the one detected in infants plasma .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [96, 99]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [154, 169]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [223, 226]}], "task": "NER"}
{"text": "In both systems we could detect an altered expression of the genes involved in thyroid hormones synthesis and of thyroid specific transcriptional factors in BPA dose and time dependent manner .", "entity": [{"entity": "thyroid hormones", "entity_type": "Chemical", "pos": [79, 95]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [157, 160]}], "task": "NER"}
{"text": "Our results suggest that BPA exerts a direct effect on thyroid follicular cell .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [25, 28]}], "task": "NER"}
{"text": "We show that these cells can \" sense \" very low amount of BPA .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "Thus they , potentially , represent an ideal in vitro system to develop assays to detect BPA and other pollutants with thyroid disrupting activity at level far below the ones considered to be environmental relevant .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Moreover , this report may provide new insight into the mode of BPA - induced deregulation of physiological processes as well as on the extensively debated molecular pathways underlying its biological activities .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "A re - evaluation of fifteen years of European risk assessment using effect models .", "entity": [], "task": "NER"}
{"text": "Ecological risk assessments of chemicals can be informed by a suite of effect models , including population and food web models .", "entity": [], "task": "NER"}
{"text": "In the risk assessments conducted under EU regulation 793 / 93 / EC , however , applications of such effect models are extremely scarce and toxicity - extrapolation approaches are often used instead .", "entity": [], "task": "NER"}
{"text": "The objective of the present study was to re - evaluate these risk assessments using two types of effect models : species sensitivity distributions ( SSDs , non - mechanistic ) , and food web models ( mechanistic ) .", "entity": [], "task": "NER"}
{"text": "Species sensitivity distributions significantly fitted the available toxicity data for up to 35 % of the chemicals , depending on the trophic levels included and the amount of data available .", "entity": [], "task": "NER"}
{"text": "Median hazardous concentrations for 5 % of the species ( HC5 - 50 ) estimated by the SSDs were less accurate predictors of measured community - level no observed effect concentration than food web model - derived HC5 - 50s , albeit data were available for seven chemicals only .", "entity": [], "task": "NER"}
{"text": "For datasets with more than 10 data points , the 90 % confidence interval of the estimated HC5s was narrower for the food web modeling approach than for the SSD approach .", "entity": [], "task": "NER"}
{"text": "The HC5 - 50s predicted by the two approaches were two to five times ( metals ) and 10 to 100 times ( organic chemicals ) higher than the predicted no effect concentrations ( PNECs ) for the aquatic environment listed in the risk assessment reports .", "entity": [], "task": "NER"}
{"text": "This suggests that the derived PNECs are protective for aquatic ecosystems .", "entity": [], "task": "NER"}
{"text": "Threshold collision - induced dissociation of hydrated magnesium : experimental and theoretical investigation of the binding energies for Mg ( 2 + ) ( H2O ) x complexes ( x = 2 - 10 ) .", "entity": [{"entity": "hydrated magnesium", "entity_type": "Chemical", "pos": [46, 64]}, {"entity": "Mg ( 2 + ) ( H2O ) x", "entity_type": "Chemical", "pos": [138, 158]}], "task": "NER"}
{"text": "The sequential bond energies of Mg ( 2 + ) ( H2O ) x complexes , in which x = 2 - 10 , are measured by threshold collision - induced dissociation in a guided ion beam tandem mass spectrometer .", "entity": [{"entity": "Mg ( 2 + ) ( H2O ) x", "entity_type": "Chemical", "pos": [32, 52]}], "task": "NER"}
{"text": "From an electrospray ionization source that produces an initial distribution of Mg ( 2 + ) ( H2O ) x complexes in which x = 7 - 10 , complexes down to x = 3 are formed by using an in - source fragmentation technique .", "entity": [{"entity": "Mg ( 2 + ) ( H2O ) x", "entity_type": "Chemical", "pos": [80, 100]}], "task": "NER"}
{"text": "Complexes smaller than Mg ( 2 + ) ( H2O ) 3 cannot be formed in this source because charge separation into MgOH ( + ) ( H2O ) and H3O ( + ) is a lower - energy pathway than simple water loss from Mg ( 2 + ) ( H2O ) 3 .", "entity": [{"entity": "Mg ( 2 + ) ( H2O ) 3", "entity_type": "Chemical", "pos": [23, 43]}, {"entity": "MgOH ( + ) ( H2O )", "entity_type": "Chemical", "pos": [107, 125]}, {"entity": "H3O ( + )", "entity_type": "Chemical", "pos": [130, 139]}, {"entity": "Mg ( 2 + ) ( H2O ) 3", "entity_type": "Chemical", "pos": [196, 216]}], "task": "NER"}
{"text": "The kinetic energy dependent cross sections for dissociation of Mg ( 2 + ) ( H2O ) x complexes , in which x = 3 - 10 , are examined over a wide energy range to monitor all dissociation products and are modeled to obtain 0 and 298 K binding energies .", "entity": [{"entity": "Mg ( 2 + ) ( H2O ) x", "entity_type": "Chemical", "pos": [64, 84]}], "task": "NER"}
{"text": "Analysis of both primary and secondary water molecule losses from each sized complex provides thermochemistry for the sequential hydration energies of Mg ( 2 + ) for x = 2 - 10 and the first experimental values for x = 2 - 4 .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [151, 161]}], "task": "NER"}
{"text": "Additionally , the thermodynamic onsets leading to the charge - separation products from Mg ( 2 + ) ( H2O ) 3 and Mg ( 2 + ) ( H2O ) 4 are determined for the first time .", "entity": [{"entity": "Mg ( 2 + ) ( H2O ) 3", "entity_type": "Chemical", "pos": [89, 109]}, {"entity": "Mg ( 2 + ) ( H2O ) 4", "entity_type": "Chemical", "pos": [114, 134]}], "task": "NER"}
{"text": "Our experimental results for x = 3 - 7 agree well with quantum chemical calculations performed here and previously calculated binding enthalpies , as well as previous measurements for x = 6 .", "entity": [], "task": "NER"}
{"text": "The present values for x = 7 - 10 are slightly lower than previous experimental results and theory , but within experimental uncertainties .", "entity": [], "task": "NER"}
{"text": "Boron - based inhibitors of acyl protein thioesterases 1 and 2 .", "entity": [{"entity": "Boron", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "acyl", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "Ras proteins are of importance in cell proliferation , and hence their mutated forms play causative roles in many kinds of cancer in different tissues .", "entity": [], "task": "NER"}
{"text": "Inhibition of the Ras - depalmitoylating enzyme acyl protein thioesterases APT1 and - 2 is a new approach to modulating the Ras cycle .", "entity": [{"entity": "acyl", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors .", "entity": [{"entity": "boronic", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "borinic acid", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and - 2 in a competitive mode .", "entity": [], "task": "NER"}
{"text": "Furthermore , one of the molecules was demonstrated to inhibit Erk1 / 2 phosphorylation significantly .", "entity": [], "task": "NER"}
{"text": "Three - Dimensional CdS - Titanate Composite Nanomaterials for Enhanced Visible - Light - Driven Hydrogen Evolution .", "entity": [{"entity": "CdS", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "Titanate", "entity_type": "Chemical", "pos": [26, 34]}, {"entity": "Hydrogen", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "3D Hierarchical echinus - like titanate spheres ( HETSs ) , serving as the supporting material for CdS nanoparticles , are synthesized via a fast one - step hydrothermal method .", "entity": [{"entity": "titanate", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [99, 102]}], "task": "NER"}
{"text": "The obtained 3D CdS - HETS composite materials show enhanced H2 generation under visible light irradiation .", "entity": [{"entity": "CdS", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "H2", "entity_type": "Chemical", "pos": [61, 63]}], "task": "NER"}
{"text": "Enzyme - catalyzed crosslinking in a partly frozen state : a new way to produce supermacroporous protein structures .", "entity": [], "task": "NER"}
{"text": "In this study a new way to produce supermacroporous protein structures was investigated .", "entity": [], "task": "NER"}
{"text": "Enzyme - mediated crosslinking of gelatin or casein was performed in a partly frozen state , which yielded stable , protein - based cryogels .", "entity": [], "task": "NER"}
{"text": "The reaction kinetics for the formation of cryogels were found to be fairly slow , most likely due to the low temperature ( - 12 degrees C ) used or due to an increased viscosity owing to the cryo - concentration taking place .", "entity": [], "task": "NER"}
{"text": "The produced cryogels were characterized with regards to their physical properties and in vitro degradation .", "entity": [], "task": "NER"}
{"text": "Furthermore , cryogels produced from gelatin and casein were evaluated as potential scaffolds by fibroblast cultivation to confirm their in vitro biocompatibility .", "entity": [], "task": "NER"}
{"text": "Gelatin - and casein - based scaffolds both supported cell proliferation and migration through the scaffold .", "entity": [], "task": "NER"}
{"text": "Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi ( COG ) complex and the golgin TATA element modulatory factor ( TMF ) .", "entity": [], "task": "NER"}
{"text": "Protein sorting between eukaryotic compartments requires vesicular transport , wherein tethering provides the first contact between vesicle and target membranes .", "entity": [], "task": "NER"}
{"text": "Here we map and start to functionally analyze the interaction network of the conserved oligomeric Golgi ( COG ) complex that mediates retrograde tethering at the Golgi .", "entity": [], "task": "NER"}
{"text": "The interactions of COG subunits with members of transport factor families assign the individual subunits as specific interaction hubs .", "entity": [], "task": "NER"}
{"text": "Functional analysis of selected interactions suggests a mechanistic tethering model .", "entity": [], "task": "NER"}
{"text": "We find that the COG complex interacts with two different Rabs in addition to each end of the golgin \" TATA element modulatory factor \" ( TMF ) .", "entity": [], "task": "NER"}
{"text": "This allows COG to potentially bridge the distance between the distal end of the golgin and the target membrane thereby promoting tighter docking .", "entity": [], "task": "NER"}
{"text": "Concurrently we show that the central portion of TMF can bind to Golgi membranes that are liberated of their COPI cover .", "entity": [], "task": "NER"}
{"text": "This latter interaction could serve to bring vesicle and target membranes into close apposition prior to fusion .", "entity": [], "task": "NER"}
{"text": "A target selection mechanism , in which a hetero - oligomeric tethering factor organizes Rabs and coiled transport factors to enable protein sorting specificity , could be applicable to vesicle targeting throughout eukaryotic cells .", "entity": [], "task": "NER"}
{"text": "FINDSITE ( comb ) : a threading / structure - based , proteomic - scale virtual ligand screening approach .", "entity": [], "task": "NER"}
{"text": "Virtual ligand screening is an integral part of the modern drug discovery process .", "entity": [], "task": "NER"}
{"text": "Traditional ligand - based , virtual screening approaches are fast but require a set of structurally diverse ligands known to bind to the target .", "entity": [], "task": "NER"}
{"text": "Traditional structure - based approaches require high - resolution target protein structures and are computationally demanding .", "entity": [], "task": "NER"}
{"text": "In contrast , the recently developed threading / structure - based FINDSITE - based approaches have the advantage that they are as fast as traditional ligand - based approaches and yet overcome the limitations of traditional ligand - or structure - based approaches .", "entity": [], "task": "NER"}
{"text": "These new methods can use predicted low - resolution structures and infer the likelihood of a ligand binding to a target by utilizing ligand information excised from the target ' s remote or close homologous proteins and / or libraries of ligand binding databases .", "entity": [], "task": "NER"}
{"text": "Here , we develop an improved version of FINDSITE , FINDSITE ( filt ) , that filters out false positive ligands in threading identified templates by a better binding site detection procedure that includes information about the binding site amino acid similarity .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [240, 250]}], "task": "NER"}
{"text": "We then combine FINDSITE ( filt ) with FINDSITE ( X ) that uses publicly available binding databases ChEMBL and DrugBank for virtual ligand screening .", "entity": [], "task": "NER"}
{"text": "The combined approach , FINDSITE ( comb ) , is compared to two traditional docking methods , AUTODOCK Vina and DOCK 6 , on the DUD benchmark set .", "entity": [], "task": "NER"}
{"text": "It is shown to be significantly better in terms of enrichment factor , dependence on target structure quality , and speed .", "entity": [], "task": "NER"}
{"text": "FINDSITE ( comb ) is then tested for virtual ligand screening on a large set of 3576 generic targets from the DrugBank database as well as a set of 168 Human GPCRs .", "entity": [], "task": "NER"}
{"text": "Excluding close homologues , FINDSITE ( comb ) gives an average enrichment factor of 52 . 1 for generic targets and 22 . 3 for GPCRs within the top 1 % of the screened compound library .", "entity": [], "task": "NER"}
{"text": "Around 65 % of the targets have better than random enrichment factors .", "entity": [], "task": "NER"}
{"text": "The performance is insensitive to target structure quality , as long as it has a TM - score >= 0 . 4 to native .", "entity": [], "task": "NER"}
{"text": "Thus , FINDSITE ( comb ) makes the screening of millions of compounds across entire proteomes feasible .", "entity": [], "task": "NER"}
{"text": "The FINDSITE ( comb ) web service is freely available for academic users at http : / / cssb . biology . gatech . edu / skolnick / webservice / FINDSITE - COMB / index . html .", "entity": [], "task": "NER"}
{"text": "Optimization of brush - like cationic copolymers for nonviral gene delivery .", "entity": [], "task": "NER"}
{"text": "Polyethylenimine ( PEI ) is one of the most broadly used polycations for gene delivery due to its high transfection efficiency and commercial availability but materials are cytotoxic and often polydisperse .", "entity": [{"entity": "Polyethylenimine", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [19, 22]}], "task": "NER"}
{"text": "The goal of current work is to develop an alternative family of polycations based on controlled living radical polymerization ( CLRP ) and to optimize the polymer structure for efficient gene delivery .", "entity": [], "task": "NER"}
{"text": "In this study , well - defined poly ( glycidyl methacrylate ) ( P ( GMA ) ) homopolymers were synthesized using reversible addition - fragmentation chain transfer ( RAFT ) polymerization followed by decoration using three different types of oligoamines , i . e . , tetraethylenepentamine ( TEPA ) , pentaethylenehexamine ( PEHA ) , and tris ( 2 - aminoethyl ) amine ( TREN ) , respectively , to generate various P ( GMA - oligoamine ) homopolycations .", "entity": [{"entity": "poly ( glycidyl methacrylate )", "entity_type": "Chemical", "pos": [31, 61]}, {"entity": "P ( GMA )", "entity_type": "Chemical", "pos": [64, 73]}, {"entity": "oligoamines", "entity_type": "Chemical", "pos": [241, 252]}, {"entity": "tetraethylenepentamine", "entity_type": "Chemical", "pos": [265, 287]}, {"entity": "TEPA", "entity_type": "Chemical", "pos": [290, 294]}, {"entity": "pentaethylenehexamine", "entity_type": "Chemical", "pos": [299, 320]}, {"entity": "PEHA", "entity_type": "Chemical", "pos": [323, 327]}, {"entity": "tris ( 2 - aminoethyl ) amine", "entity_type": "Chemical", "pos": [336, 365]}, {"entity": "TREN", "entity_type": "Chemical", "pos": [368, 372]}, {"entity": "P ( GMA - oligoamine )", "entity_type": "Chemical", "pos": [412, 434]}], "task": "NER"}
{"text": "The effect of P ( GMA ) backbone length and structure of oligoamine on gene transfer efficiency was then determined .", "entity": [{"entity": "P ( GMA )", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "oligoamine", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "The optimal polymer , P ( GMA - TEPA ) ( 50 ) , provided comparable transfection efficiency but lower cytotoxicity than PEI .", "entity": [{"entity": "P ( GMA - TEPA ) ( 50 )", "entity_type": "Chemical", "pos": [22, 45]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [120, 123]}], "task": "NER"}
{"text": "P ( GMA - TEPA ) ( 50 ) was then used as the cationic block in diblock copolymers containing hydrophilic N - ( 2 - hydroxypropyl ) methacrylamide ( HPMA ) and oligo ( ethylene glycol ) monomethyl ether methacrylate ( OEGMA ) .", "entity": [{"entity": "P ( GMA - TEPA ) ( 50 )", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "N - ( 2 - hydroxypropyl ) methacrylamide", "entity_type": "Chemical", "pos": [105, 145]}, {"entity": "HPMA", "entity_type": "Chemical", "pos": [148, 152]}, {"entity": "oligo ( ethylene glycol ) monomethyl ether methacrylate", "entity_type": "Chemical", "pos": [159, 214]}, {"entity": "OEGMA", "entity_type": "Chemical", "pos": [217, 222]}], "task": "NER"}
{"text": "Polyplexes of block copolymers were stable against aggregation in physiological salt condition and in Opti - MEM due to the shielding effect of P ( HPMA ) and P ( OEGMA ) .", "entity": [{"entity": "P ( HPMA )", "entity_type": "Chemical", "pos": [144, 154]}, {"entity": "P ( OEGMA )", "entity_type": "Chemical", "pos": [159, 170]}], "task": "NER"}
{"text": "However , the presence of the HPMA / OEGMA block significantly decreased the transfection efficacy of P ( GMA - TEPA ) ( 50 ) homopolycation .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [30, 34]}, {"entity": "OEGMA", "entity_type": "Chemical", "pos": [37, 42]}, {"entity": "P ( GMA - TEPA ) ( 50 )", "entity_type": "Chemical", "pos": [102, 125]}], "task": "NER"}
{"text": "To compensate for reduced cell uptake caused by the hydrophilic shell of polyplex , the integrin - binding peptide , RGD , was conjugated to the hydrophilic chain end of P ( OEGMA ) ( 15 ) - b - P ( GMA - TEPA ) ( 50 ) copolymer by Michael - type addition reaction .", "entity": [{"entity": "P ( OEGMA ) ( 15 ) - b - P ( GMA - TEPA ) ( 50 )", "entity_type": "Chemical", "pos": [170, 218]}], "task": "NER"}
{"text": "At low polymer to DNA ratios , the RGD - functionalized polymer showed increased gene delivery efficiency to HeLa cells compared to analogous polymers lacking RGD .", "entity": [], "task": "NER"}
{"text": "Optomechanical Shutter Modulated Broad - Band Cavity - Enhanced Absorption Spectroscopy of Molecular Transients of Astrophysical Interest .", "entity": [], "task": "NER"}
{"text": "We describe a sensitive spectroscopic instrument capable of measuring broad - band absorption spectra through supersonically expanding planar plasma pulses .", "entity": [], "task": "NER"}
{"text": "The instrument utilizes incoherent broad - band cavity - enhanced absorption spectroscopy ( IBBCEAS ) and incorporates an optomechanical shutter to modulate light from a continuous incoherent light source , enabling measurements of durations as low as ~ 400 mu s .", "entity": [], "task": "NER"}
{"text": "The plasma expansion is used to mimic conditions in translucent interstellar clouds .", "entity": [], "task": "NER"}
{"text": "The new setup is particularly applicable to test proposed carriers of the diffuse interstellar bands , as it permits swift measurements over a broad spectral range with a resolution comparable to astronomical observations .", "entity": [], "task": "NER"}
{"text": "The sensitivity is estimated to be better than 10 ppm / pass , measured with an effective exposure time of only 1 s .", "entity": [], "task": "NER"}
{"text": "Acid - degradable cationic poly ( ketal amidoamine ) for enhanced RNA interference in vitro and in vivo .", "entity": [{"entity": "poly ( ketal amidoamine )", "entity_type": "Chemical", "pos": [27, 52]}], "task": "NER"}
{"text": "Efficient delivery of small interfering RNA ( siRNA ) is one of major challenges in the successful applications of siRNA in clinic .", "entity": [], "task": "NER"}
{"text": "In the present study , we report a new acid - degradable poly ( ketal amidoamine ) ( PKAA ) as a siRNA carrier , which has high delivery efficiency and low cytotoxicity .", "entity": [{"entity": "poly ( ketal amidoamine )", "entity_type": "Chemical", "pos": [57, 82]}, {"entity": "PKAA", "entity_type": "Chemical", "pos": [85, 89]}], "task": "NER"}
{"text": "PKAA was designed to have acid - cleavable ketal linkages in the backbone of cationic biodegradable poly ( amidoamine ) .", "entity": [{"entity": "PKAA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "poly ( amidoamine )", "entity_type": "Chemical", "pos": [100, 119]}], "task": "NER"}
{"text": "PKAA efficiently self - assembled with siRNA to form nanocomplexes with a diameter of ~ 200 nm and slightly positive charges , which are stable under physiological conditions , but rapidly release siRNA at acidic pH .", "entity": [{"entity": "PKAA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "PKAA exhibited sufficient buffering capability and endosomolytic activity due mainly to the presence of secondary amine groups in its backbone and rapid degradation in acidic endosomes , leading to the enhanced release of siRNA to cytoplasm .", "entity": [{"entity": "PKAA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "secondary amine", "entity_type": "Chemical", "pos": [104, 119]}], "task": "NER"}
{"text": "Cell culture studies demonstrated that PKAA is capable of delivering anti - TNF ( tumor necrosis factor ) - alpha siRNA to lipopolysaccharide ( LPS ) - stimulated macrophages and significantly inhibits the expression of TNF - alpha .", "entity": [{"entity": "PKAA", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "A mouse model of acetaminophen ( APAP ) - induced acute liver failure was used to evaluate in vivo siRNA delivery efficacy of PKAA .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [33, 37]}, {"entity": "PKAA", "entity_type": "Chemical", "pos": [126, 130]}], "task": "NER"}
{"text": "PKAA / anti - TNF - alpha siRNA nanocomplexes significantly reduced the ALT ( alanine transaminase ) and the hepatic cellular damages in APAP - intoxicated mice .", "entity": [{"entity": "PKAA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [137, 141]}], "task": "NER"}
{"text": "We anticipate that acid - degradable PKAA has great potential as siRNA carriers based on its excellent biocompatibility , pH sensitivity , potential endosomolytic activity , and high delivery efficiency .", "entity": [{"entity": "PKAA", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "Lysozyme hydration in concentrated aqueous solutions .", "entity": [], "task": "NER"}
{"text": "Effect of an equilibrium cluster phase .", "entity": [], "task": "NER"}
{"text": "Water close to proteins plays a key role in determining their structural and functional properties .", "entity": [], "task": "NER"}
{"text": "Despite being a subject of considerable interest , the characterization of hydration water , as far as its total amount is concerned , is still controversial and its influence on protein structure and folding is not yet fully understood .", "entity": [], "task": "NER"}
{"text": "In this work , we have investigated the dielectric properties of lysozyme aqueous solutions over the frequency range where the orientational polarization relaxation of the aqueous phase occurs ( from 500 MHz to 50 GHz ) .", "entity": [], "task": "NER"}
{"text": "Measurements extend over a wide concentration range , up to 300 mg / mL , corresponding to a volume fraction of the order of 0 . 4 .", "entity": [], "task": "NER"}
{"text": "The analysis of the dielectric spectra , based on the decrease of the dielectric increment of the gamma - dispersion as a function of protein concentration , allows us to estimate the total amount of hydration water ( both bound water and loosely bound water ) present in the system investigated .", "entity": [], "task": "NER"}
{"text": "We observe a decrease of the hydration number as a function of the protein concentration .", "entity": [], "task": "NER"}
{"text": "This behavior is well accounted for by considering the formation of small equilibrium clusters with aggregation number of some units , as recently reported by Stradner et al .", "entity": [], "task": "NER"}
{"text": "( 1 ) on the basis of small - angle X - ray and neutron scattering measurements .", "entity": [], "task": "NER"}
{"text": "5 - Benzylglycinyl - amiloride kills proliferating and nonproliferating malignant glioma cells through caspase - independent necroptosis mediated by apoptosis - inducing factor .", "entity": [{"entity": "5 - Benzylglycinyl - amiloride", "entity_type": "Chemical", "pos": [0, 30]}], "task": "NER"}
{"text": "5 ' - Beta enzylglycinyl - amiloride ( UCD38B ) and glycinyl - amiloride ( UCD74A ) are cell - permeant and cell - impermeant derivatives of amiloride , respectively , and used here to identify the cellular mechanisms of action underlying their antiglioma effects .", "entity": [{"entity": "5 ' - Beta enzylglycinyl - amiloride", "entity_type": "Chemical", "pos": [0, 36]}, {"entity": "UCD38B", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "glycinyl - amiloride", "entity_type": "Chemical", "pos": [52, 72]}, {"entity": "UCD74A", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "amiloride", "entity_type": "Chemical", "pos": [141, 150]}], "task": "NER"}
{"text": "UCD38B comparably kills proliferating and nonproliferating gliomas cells when cell cycle progression is arrested either by cyclin D1 siRNA or by acidification .", "entity": [{"entity": "UCD38B", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Cell impermeant UCD74A inhibits plasmalemmal urokinase plasminogen activator ( uPA ) and the type 1 sodium - proton exchanger with potencies analogous to UCD38B , but is cytostatic .", "entity": [{"entity": "UCD74A", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [100, 106]}, {"entity": "UCD38B", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "In contrast , UCD38B targets intracellular uPA causing mistrafficking of uPA into perinuclear mitochondria , reducing the mitochondrial membrane potential , and followed by the release of apoptotic inducible factor ( AIF ) .", "entity": [{"entity": "UCD38B", "entity_type": "Chemical", "pos": [14, 20]}], "task": "NER"}
{"text": "AIF nuclear translocation is followed by a caspase - independent necroptotic cell death .", "entity": [], "task": "NER"}
{"text": "Reduction in AIF expression by siRNA reduces the antiglioma cytotoxic effects of UCD38B , while not activating the caspase pathway .", "entity": [{"entity": "UCD38B", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "Ultrastructural changes shortly following treatment with UCD38B demonstrate dilation of endoplasmic reticulum ( ER ) and mitochondrial swelling followed by nuclear condensation within hours consistent with a necroptotic cell death differing from apoptosis and from autophagy .", "entity": [{"entity": "UCD38B", "entity_type": "Chemical", "pos": [57, 63]}], "task": "NER"}
{"text": "These drug mechanism of action studies demonstrate that UCD38B induces a cell cycle - independent , caspase - independent necroptotic glioma cell death that is mediated by AIF and independent of poly ( ADP - ribose ) polymerase and H2AX activation .", "entity": [{"entity": "UCD38B", "entity_type": "Chemical", "pos": [56, 62]}, {"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [195, 216]}], "task": "NER"}
{"text": "Polyazamacrocycles as potential antitumor agents for human prostate cancer cells .", "entity": [{"entity": "Polyazamacrocycles", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "Polyazamacrocycles are currently being studied and used in a variety of applications beyond their traditional place in supramolecular and co - ordination chemistry .", "entity": [{"entity": "Polyazamacrocycles", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "This study suggests additional applications of these compounds with particular emphasis on their use as antiproliferative agents that could be potentially used to treat cancer .", "entity": [], "task": "NER"}
{"text": "Four polyazamacrocycles were tested in human prostate cancer LNCaP and prostate epithelial PNTA1 cells to analyze changes in cell proliferation and cell death capabilities .", "entity": [{"entity": "polyazamacrocycles", "entity_type": "Chemical", "pos": [5, 23]}], "task": "NER"}
{"text": "Their intracellular localization was also evaluated by confocal microscopy .", "entity": [], "task": "NER"}
{"text": "The results show a decrease in proliferation rate and cell viability of LNCaP and PNTA1 , after treatment with these compounds .", "entity": [], "task": "NER"}
{"text": "The decrease in the number of viable cells is similar for the majority of the compounds studied , and at higher concentration , the proliferation efficiency decreased significantly in the cell lines studied .", "entity": [], "task": "NER"}
{"text": "Also , our results suggest that L and L2 induce early apoptosis in PNTA1 cells and late apoptosis / necrosis in LNCaP cells .", "entity": [], "task": "NER"}
{"text": "The compounds did not induce a significant increase in necrosis of both cell types .", "entity": [], "task": "NER"}
{"text": "Although the compounds did not localize in a unique organelle , all of them have as main target the Golgi apparatus and other localization profiles differed depending on the cell line .", "entity": [], "task": "NER"}
{"text": "PreCisIon : PREdiction of CIS - regulatory elements improved by gene ' s positION .", "entity": [], "task": "NER"}
{"text": "Conventional approaches to predict transcriptional regulatory interactions usually rely on the definition of a shared motif sequence on the target genes of a transcription factor ( TF ) .", "entity": [], "task": "NER"}
{"text": "These efforts have been frustrated by the limited availability and accuracy of TF binding site motifs , usually represented as position - specific scoring matrices , which may match large numbers of sites and produce an unreliable list of target genes .", "entity": [], "task": "NER"}
{"text": "To improve the prediction of binding sites , we propose to additionally use the unrelated knowledge of the genome layout .", "entity": [], "task": "NER"}
{"text": "Indeed , it has been shown that co - regulated genes tend to be either neighbors or periodically spaced along the whole chromosome .", "entity": [], "task": "NER"}
{"text": "This study demonstrates that respective gene positioning carries significant information .", "entity": [], "task": "NER"}
{"text": "This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon .", "entity": [], "task": "NER"}
{"text": "To optimize this combination , PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position .", "entity": [], "task": "NER"}
{"text": "This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence , genome layout or on novel criteria .", "entity": [], "task": "NER"}
{"text": "With the current state of the art , PreCisIon consistently improves methods based on sequence information only .", "entity": [], "task": "NER"}
{"text": "This is shown by implementing a cross - validation analysis of the 20 major TFs from two phylogenetically remote model organisms .", "entity": [], "task": "NER"}
{"text": "For Bacillus subtilis and Escherichia coli , respectively , PreCisIon achieves on average an area under the receiver operating characteristic curve of 70 and 60 % , a sensitivity of 80 and 70 % and a specificity of 60 and 56 % .", "entity": [], "task": "NER"}
{"text": "The newly predicted gene targets are demonstrated to be functionally consistent with previously known targets , as assessed by analysis of Gene Ontology enrichment or of the relevant literature and databases .", "entity": [], "task": "NER"}
{"text": "Primary hepatocyte cultures for pharmaco - toxicological studies : at the busy crossroad of various anti - dedifferentiation strategies .", "entity": [], "task": "NER"}
{"text": "Continuously increasing understanding of the molecular triggers responsible for the onset of diseases , paralleled by an equally dynamic evolution of chemical synthesis and screening methods , offers an abundance of pharmacological agents with a potential to become new successful drugs .", "entity": [], "task": "NER"}
{"text": "However , before patients can benefit of newly developed pharmaceuticals , stringent safety filters need to be applied to weed out unfavourable drug candidates .", "entity": [], "task": "NER"}
{"text": "Cost effectiveness and the need to identify compound liabilities , without exposing humans to unnecessary risks , has stimulated the shift of the safety studies to the earliest stages of drug discovery and development .", "entity": [], "task": "NER"}
{"text": "In this regard , in vivo relevant organotypic in vitro models have high potential to revolutionize the preclinical safety testing .", "entity": [], "task": "NER"}
{"text": "They can enable automation of the process , to match the requirements of high - throughput screening approaches , while satisfying ethical considerations .", "entity": [], "task": "NER"}
{"text": "Cultures of primary hepatocytes became already an inherent part of the preclinical pharmaco - toxicological testing battery , yet their routine use , particularly for long - term assays , is limited by the progressive deterioration of liver - specific features .", "entity": [], "task": "NER"}
{"text": "The availability of suitable hepatic and other organ - specific in vitro models is , however , of paramount importance in the light of changing European legal regulations in the field of chemical compounds of different origin , which gradually restrict the use of animal studies for safety assessment , as currently witnessed in cosmetic industry .", "entity": [], "task": "NER"}
{"text": "Fortunately , research groups worldwide spare no effort to establish hepatic in vitro systems .", "entity": [], "task": "NER"}
{"text": "In the present review , both classical and innovative methodologies to stabilize the in vivo - like hepatocyte phenotype in culture of primary hepatocytes are presented and discussed .", "entity": [], "task": "NER"}
{"text": "Profiling genome - wide chromatin methylation with engineered posttranslation apparatus within living cells .", "entity": [], "task": "NER"}
{"text": "Protein methyltransferases ( PMTs ) have emerged as important epigenetic regulators in myriad biological processes in both normal physiology and disease conditions .", "entity": [], "task": "NER"}
{"text": "However , elucidating PMT - regulated epigenetic processes has been hampered by ambiguous knowledge about in vivo activities of individual PMTs particularly because of their overlapping but nonredundant functions .", "entity": [], "task": "NER"}
{"text": "To address limitations of conventional approaches in mapping chromatin modification of specific PMTs , we have engineered the chromatin - modifying apparatus and formulated a novel technology , termed clickable chromatin enrichment with parallel DNA sequencing ( CliEn - seq ) , to probe genome - wide chromatin modification within living cells .", "entity": [], "task": "NER"}
{"text": "The three - step approach of CliEn - seq involves in vivo synthesis of S - adenosyl - L - methionine ( SAM ) analogues from cell - permeable methionine analogues by engineered SAM synthetase ( methionine adenosyltransferase or MAT ) , in situ chromatin modification by engineered PMTs , subsequent enrichment and sequencing of the uniquely modified chromatins .", "entity": [{"entity": "S - adenosyl - L - methionine", "entity_type": "Chemical", "pos": [71, 100]}, {"entity": "SAM", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "methionine", "entity_type": "Chemical", "pos": [141, 151]}, {"entity": "SAM", "entity_type": "Chemical", "pos": [176, 179]}, {"entity": "methionine", "entity_type": "Chemical", "pos": [193, 203]}], "task": "NER"}
{"text": "Given critical roles of the chromatin - modifying enzymes in epigenetics and structural similarity among many PMTs , we envision that the CliEn - seq technology is generally applicable in deciphering chromatin methylation events of individual PMTs in diverse biological settings .", "entity": [], "task": "NER"}
{"text": "Self - assembly of segmented anisotropic particles : tuning compositional anisotropy to form vertical or horizontal arrays .", "entity": [], "task": "NER"}
{"text": "Columnar arrays of anisotropic nano - and microparticles , in which the long axes of the particles are oriented perpendicular to the substrate , are of interest for photovoltaics and other applications .", "entity": [], "task": "NER"}
{"text": "Array assembly typically requires applied electric or magnetic fields and / or controlled drying , which are challenging over large areas .", "entity": [], "task": "NER"}
{"text": "Here , we describe a scalable approach to self - assemble multicomponent nanowires into columnar arrays .", "entity": [], "task": "NER"}
{"text": "Self - assembly of partially etched nanowires ( PENs ) occurred spontaneously during sedimentation from suspension , without drying or applied fields .", "entity": [], "task": "NER"}
{"text": "PENs , which have segments that are either gold or \" empty \" ( solvent - filled ) surrounded by a silica shell , were produced from striped metal nanowires by first coating with silica and then removing sacrificial segments by acid etching .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [98, 104]}, {"entity": "silica", "entity_type": "Chemical", "pos": [178, 184]}], "task": "NER"}
{"text": "Electrostatic repulsion between the particles was necessary for array assembly ; however , details of PEN surface chemistry were relatively unimportant .", "entity": [], "task": "NER"}
{"text": "The aspect ratio and relative center of mass ( COM ) of the PENs were important for determining whether the PEN long axes were vertically or horizontally aligned with respect to the underlying substrate .", "entity": [], "task": "NER"}
{"text": "Arrays with predominantly vertically aligned particles were achieved for PENs with a large offset in COM relative to the geometric center , while other types of PENs formed horizontal arrays .", "entity": [], "task": "NER"}
{"text": "Assemblies were formed over > 10 cm ( 2 ) areas , with over 60 % of particles standing .", "entity": [], "task": "NER"}
{"text": "We assessed array uniformity and reproducibility by imaging many positions within each sample and performing multiple assemblies of differently segmented PENs .", "entity": [], "task": "NER"}
{"text": "This work demonstrates the versatility of gravity - driven PEN array assembly and provides a framework for designing other anisotropic particle systems that self - assemble into columnar arrays .", "entity": [], "task": "NER"}
{"text": "Xyloglucan - derivatized films for the culture of adherent cells and their thermocontrolled detachment : a promising alternative to cells sensitive to protease treatment .", "entity": [], "task": "NER"}
{"text": "By taking advantage of a natural and abundant polymer as well as a straightforward film formation technique , this paper focuses on the conception and use of a new alternative tool for thermo - controlled cell detachment .", "entity": [], "task": "NER"}
{"text": "Thermoresponsive xyloglucan was produced after partial galactose removal by a 24 h reaction with beta - galactosidase .", "entity": [{"entity": "galactose", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "The obtained polymer ( T24 ) was then activated by reaction with 4 - nitrophenyl chloroformate ( NPC ) in order to graft a cyclic peptide presenting an arginine - glycine - aspartic acid ( RGD ) motif .", "entity": [{"entity": "4 - nitrophenyl chloroformate", "entity_type": "Chemical", "pos": [65, 94]}, {"entity": "NPC", "entity_type": "Chemical", "pos": [97, 100]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [152, 160]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [163, 170]}, {"entity": "aspartic acid", "entity_type": "Chemical", "pos": [173, 186]}], "task": "NER"}
{"text": "The effect of RGD grafting on the sol - gel transition temperature of T24 is evaluated by rheological measurements .", "entity": [], "task": "NER"}
{"text": "Solvent - casted films of T24 - RGD successfully promoted cell adhesion , proliferation , and thermo - controlled detachment .", "entity": [], "task": "NER"}
{"text": "The presented approach is a new alternative for cells sensitive to the proteolytic treatment routinely used for cell detachment .", "entity": [], "task": "NER"}
{"text": "Because the RGD sequence used herein is widely recognized by different cell types , this protocol may be extended to other cells .", "entity": [], "task": "NER"}
{"text": "Besides , the presented chemical route can be applied to different peptide sequences .", "entity": [], "task": "NER"}
{"text": "Anion - pi interactions : generality , binding strength , and structure .", "entity": [], "task": "NER"}
{"text": "Anion - pi interactions have been systematically studied using tetraoxacalix [ 2 ] arene [ 2 ] triazine 1 , an electron - deficient and cavity self - tunable macrocyclic host , as an electron - neutral molecular probe .", "entity": [{"entity": "tetraoxacalix [ 2 ] arene [ 2 ] triazine", "entity_type": "Chemical", "pos": [63, 103]}], "task": "NER"}
{"text": "As revealed by electrospray ionization mass spectrometry ( ESI - MS ) , fluorescence titration and X - ray crystallography , tetraoxacalix [ 2 ] arene [ 2 ] triazine has been found to form 1 : 1 complexes with four typical polyatomic anions of different geometries and shapes in the gaseous phase , in solution , and in the solid state .", "entity": [{"entity": "tetraoxacalix [ 2 ] arene [ 2 ] triazine", "entity_type": "Chemical", "pos": [125, 165]}], "task": "NER"}
{"text": "The association constants for the formation of anion - pi complexes in acetonitrile are in the range of 239 to 16950 M ( - 1 ) , following the order of 1 . NO ( 3 ) ( - ) > 1 . BF ( 4 ) ( - ) > 1 . PF ( 6 ) ( - ) > 1 . SCN ( - ) .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [71, 83]}, {"entity": "NO ( 3 ) ( - )", "entity_type": "Chemical", "pos": [156, 170]}, {"entity": "BF ( 4 ) ( - )", "entity_type": "Chemical", "pos": [177, 191]}, {"entity": "PF ( 6 ) ( - )", "entity_type": "Chemical", "pos": [198, 212]}, {"entity": "SCN ( - )", "entity_type": "Chemical", "pos": [219, 228]}], "task": "NER"}
{"text": "X - ray molecular structures of the complexes showed that two opposing triazine rings of tetraoxacalix [ 2 ] arene [ 2 ] triazine act as a pair of tweezers to interact with the included anions through cooperative anion - pi and lone - pair electron - pi interactions .", "entity": [{"entity": "triazine", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "tetraoxacalix [ 2 ] arene [ 2 ] triazine", "entity_type": "Chemical", "pos": [89, 129]}], "task": "NER"}
{"text": "The generality of anion - pi interactions and diverse anion - pi interaction motifs can provide a new dimension in the study of molecular recognition and self - assembly .", "entity": [], "task": "NER"}
{"text": "Moreover , this study potentiates the effect of anion - pi interactions in chemical and biological systems , especially those involving anion and electron - deficient aromatic species .", "entity": [], "task": "NER"}
{"text": "Effects and mechanism of organ protection by cardiotrophin - 1 .", "entity": [], "task": "NER"}
{"text": "Cardiotrophin - 1 ( CT - 1 ) , a member of the interleukin ( IL ) - 6 family , is reported to exhibit a plethora of pleiotropic effects in the heart such as cytoprotective , pro - proliferative and pro - fibrotic ones .", "entity": [], "task": "NER"}
{"text": "An extensive research has been devoted on proliferative and profibrotic effects of CT - 1 on the heart .", "entity": [], "task": "NER"}
{"text": "Thus the present review has been aimed to critically define the cytoprotective effects of CT - 1 and the cellular and molecular mechanisms involved in them .", "entity": [], "task": "NER"}
{"text": "Although many effects of CT - 1 have been described on the heart , CT - 1 has now also been reported to exhibit important protective effects in other organs such as liver , kidney or nervous system .", "entity": [], "task": "NER"}
{"text": "CT - 1 produces its effects through a unique receptor system comprising LIF receptor ( LIFR beta ) and a common signal transducer , the glycoprotein 130 ( gp130 ) .", "entity": [], "task": "NER"}
{"text": "The signaling pathway downstream from gp130 is based on at least , three distinct pathways : 1 ) the janus kinase / signal transducer and activator of transcription ( JAK / STAT ) pathway , 2 ) the p42 / 44 mitogen - activated protein kinase ( p42 / 44 MAPK ) pathway , also known as the extracellular receptor kinase - 1 / 2 ( ERK1 / 2 ) pathway , and 3 ) the phosphatidylinositol 3 - OH kinase ( PI3K ) / Akt pathway .", "entity": [{"entity": "phosphatidylinositol 3 - OH", "entity_type": "Chemical", "pos": [361, 388]}], "task": "NER"}
{"text": "Since CT - 1 easily achieves its cytoprotective effects via a combination of the above three signaling pathways , it becomes quite necessary to determine which pathway ( s ) is involved in each particular effect of CT - 1 .", "entity": [], "task": "NER"}
{"text": "In each of its target organs , CT - 1 may also display differential mechanisms of cytoprotection , and thus it is relevant to understand how these mechanisms are locally regulated .", "entity": [], "task": "NER"}
{"text": "Assessment of the antineoplastic potential of chalcones in animal models .", "entity": [{"entity": "chalcones", "entity_type": "Chemical", "pos": [46, 55]}], "task": "NER"}
{"text": "One part of chemical space that is endowed with interesting biological properties is the area of the chalcones .", "entity": [{"entity": "chalcones", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "With this review , we provide a comprehensive overview of the numerous in vivo animal studies on the antineoplastic potential of both natural and synthetic members of this flavonoid subclass ( covering : up to mid - 2011 ) .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [172, 181]}], "task": "NER"}
{"text": "The thus far identified modes of action of these compounds are also discussed .", "entity": [], "task": "NER"}
{"text": "We hope that this overview may stimulate deeper investigations into the biochemical mechanisms by which chalcones exert their antineoplastic action .", "entity": [{"entity": "chalcones", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "As a result , in the foreseeable future , chalcones may prove suitable lead molecules or early drug candidates for the prevention or treatment of various neoplastic diseases .", "entity": [{"entity": "chalcones", "entity_type": "Chemical", "pos": [42, 51]}], "task": "NER"}
{"text": "Band gap engineering via controlling donor - acceptor compositions in conjugated copolymers .", "entity": [], "task": "NER"}
{"text": "Varying composition of pi - donor / acceptor moieties has been considered as an effective strategy for fine - tuning of the electronic properties of D - A conjugated copolymers .", "entity": [], "task": "NER"}
{"text": "In this study , the change of optoelectronic properties with the change of donor / acceptor ratios is investigated on the basis of first - principles density functional calculations .", "entity": [], "task": "NER"}
{"text": "Copolymers containing moieties of similar pi - electron donating and / or accepting capabilities , e . g . , thiophene ( T ) - methoxythiophene ( OT ) , exhibit a linear dependence of electronic properties ( especially , HOMO / LUMO , band gap , and bandwidth ) on the D / A content .", "entity": [{"entity": "thiophene", "entity_type": "Chemical", "pos": [109, 118]}, {"entity": "methoxythiophene", "entity_type": "Chemical", "pos": [127, 143]}], "task": "NER"}
{"text": "In contrast , for strong D / A contrast systems , e . g . , thiophene ( T ) - thienopyrazine ( TP ) , the electronic properties vary nonlinearly with D / A compositions .", "entity": [{"entity": "thiophene", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "thienopyrazine", "entity_type": "Chemical", "pos": [78, 92]}], "task": "NER"}
{"text": "However , when the block size of one parent monomer in a strong D / A contrast system is fixed , the variation of electronic properties shows a remarkable linear correlation against D / A compositions .", "entity": [], "task": "NER"}
{"text": "We found that the deviation of electronic properties from a linear composition dependence is dominated by the strength of orbital interactions between D and A .", "entity": [], "task": "NER"}
{"text": "Weak orbital interactions between D and A moieties tend to lead to a nonlinear composition dependence .", "entity": [], "task": "NER"}
{"text": "Our results provide useful insights for band gap tuning through the adjustment of D / A compositions in D - A conjugated copolymers .", "entity": [], "task": "NER"}
{"text": "Microarray analysis of isolated human islet transcriptome in type 2 diabetes and the role of the ubiquitin - proteasome system in pancreatic beta cell dysfunction .", "entity": [], "task": "NER"}
{"text": "To shed light on islet cell molecular phenotype in human type 2 diabetes ( T2D ) , we studied the transcriptome of non - diabetic ( ND ) and T2D islets to then focus on the ubiquitin - proteasome system ( UPS ) , the major protein degradation pathway .", "entity": [], "task": "NER"}
{"text": "We assessed gene expression , amount of ubiquitinated proteins , proteasome activity , and the effects of proteasome inhibition and prolonged exposure to palmitate .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [154, 163]}], "task": "NER"}
{"text": "Microarray analysis identified more than one thousand genes differently expressed in T2D islets , involved in many structures and functions , with consistent alterations of the UPS .", "entity": [], "task": "NER"}
{"text": "Quantitative RT - PCR demonstrated downregulation of selected UPS genes in T2D islets and beta cell fractions , with greater ubiquitin accumulation and reduced proteasome activity .", "entity": [], "task": "NER"}
{"text": "Chemically induced reduction of proteasome activity was associated with lower glucose - stimulated insulin secretion , which was partly reproduced by palmitate exposure .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [150, 159]}], "task": "NER"}
{"text": "These results show the presence of many changes in islet transcriptome in T2D islets and underline the importance of the association between UPS alterations and beta cell dysfunction in human T2D .", "entity": [], "task": "NER"}
{"text": "Dual action spirobicycloimidazolidine - 2 , 4 - diones : antidiabetic agents and inhibitors of aldose reductase - an enzyme involved in diabetic complications .", "entity": [{"entity": "spirobicycloimidazolidine - 2 , 4 - diones", "entity_type": "Chemical", "pos": [12, 54]}, {"entity": "aldose", "entity_type": "Chemical", "pos": [95, 101]}], "task": "NER"}
{"text": "The desired 3 - ( arylsulfonyl ) spiroimidazolidine - 2 , 4 - diones were synthesized by reacting spiroiminoimidazolidine - 2 , 4 - dione with arylsulfonyl chlorides .", "entity": [{"entity": "3 - ( arylsulfonyl ) spiroimidazolidine - 2 , 4 - diones", "entity_type": "Chemical", "pos": [12, 68]}, {"entity": "spiroiminoimidazolidine - 2 , 4 - dione", "entity_type": "Chemical", "pos": [98, 137]}, {"entity": "arylsulfonyl chlorides", "entity_type": "Chemical", "pos": [143, 165]}], "task": "NER"}
{"text": "Spiroimidazolidine - 2 , 4 - dione was in turn synthesized from norcamphor .", "entity": [{"entity": "Spiroimidazolidine - 2 , 4 - dione", "entity_type": "Chemical", "pos": [0, 34]}, {"entity": "norcamphor", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "Structures of the synthesized molecules were established by modern spectroscopic techniques .", "entity": [], "task": "NER"}
{"text": "The synthesized compounds were screened for in vivo antidiabetic activity and aldose reductase inhibition .", "entity": [{"entity": "aldose", "entity_type": "Chemical", "pos": [78, 84]}], "task": "NER"}
{"text": "Compounds 2a , 2b and 2g exhibited excellent dual activity , compound 2a being most prominent .", "entity": [], "task": "NER"}
{"text": "These results reveal that the synthesized compounds may serve as the molecule of choice to treat diabetes and diabetic complications using a single medication .", "entity": [], "task": "NER"}
{"text": "A SWI / SNF chromatin - remodeling complex acts in noncoding RNA - mediated transcriptional silencing .", "entity": [], "task": "NER"}
{"text": "RNA - mediated transcriptional silencing prevents deleterious effects of transposon activity and controls the expression of protein - coding genes .", "entity": [], "task": "NER"}
{"text": "It involves long noncoding RNAs ( lncRNAs ) .", "entity": [], "task": "NER"}
{"text": "In Arabidopsis thaliana , some of those lncRNAs are produced by a specialized RNA Polymerase V ( Pol V ) .", "entity": [], "task": "NER"}
{"text": "The mechanism by which lncRNAs affect chromatin structure and mRNA production remains mostly unknown .", "entity": [], "task": "NER"}
{"text": "Here we identify the SWI / SNF ATP - dependent nucleosome - remodeling complex as a component of the RNA - mediated transcriptional silencing pathway .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [31, 34]}], "task": "NER"}
{"text": "We found that SWI3B , an essential subunit of the SWI / SNF complex , physically interacts with a lncRNA - binding protein , IDN2 .", "entity": [], "task": "NER"}
{"text": "SWI / SNF subunits contribute to lncRNA - mediated transcriptional silencing .", "entity": [], "task": "NER"}
{"text": "Moreover , Pol V mediates stabilization of nucleosomes on silenced regions .", "entity": [], "task": "NER"}
{"text": "We propose that Pol V - produced lncRNAs mediate transcriptional silencing by guiding the SWI / SNF complex and establishing positioned nucleosomes on specific genomic loci .", "entity": [], "task": "NER"}
{"text": "We further propose that guiding ATP - dependent chromatin - remodeling complexes may be a more general function of lncRNAs .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Dendritic cell activation by polysaccharide isolated from Angelica dahurica .", "entity": [], "task": "NER"}
{"text": "Angelica dahurica is used in functional foods for the prevention and treatment of various diseases , such as inflammation and cancer .", "entity": [], "task": "NER"}
{"text": "In the present study , we examined the effect of A . dahurica polysaccharide ( ADP ) on dendritic cell ( DC ) maturation .", "entity": [], "task": "NER"}
{"text": "ADP increased the expressions of CD86 and MHC - II molecules , the production of IL - 12 , IL - 1 beta , and TNF - alpha , and allogeneic T cell activation ability of DCs , and reduced DC endocytosis .", "entity": [], "task": "NER"}
{"text": "As a mechanism of action , the knockdown of TLR4 with small interfering RNA decreased the ADP - induced production of nitric oxide and IL - 12 by DCs , suggesting the membrane receptor candidate of ADP .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [118, 130]}], "task": "NER"}
{"text": "After binding to TLR4 , ADP increased the phosphorylation of ERK , JNK , and p38 MAPKs , and the nuclear translocation of NF - kappa B p50 / p65 .", "entity": [], "task": "NER"}
{"text": "These results indicate that ADP activates DCs through TLR4 and downstream signalings .", "entity": [], "task": "NER"}
{"text": "Poly ( ethylene glycol ) - block - poly ( epsilon - caprolactone ) micelles for combination drug delivery : evaluation of paclitaxel , cyclopamine and gossypol in intraperitoneal xenograft models of ovarian cancer .", "entity": [{"entity": "Poly ( ethylene glycol ) - block - poly ( epsilon - caprolactone )", "entity_type": "Chemical", "pos": [0, 66]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [122, 132]}, {"entity": "cyclopamine", "entity_type": "Chemical", "pos": [135, 146]}, {"entity": "gossypol", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "Ovarian cancer is the most lethal gynecological malignancy , characterized by a high rate of chemoresistance .", "entity": [], "task": "NER"}
{"text": "Current treatment strategies for ovarian cancer focus on novel drug combinations of cytotoxic agents and molecular targeted agents or novel drug delivery strategies that often involve intraperitoneal ( IP ) injection .", "entity": [], "task": "NER"}
{"text": "Poly ( ethylene glycol ) - block - poly ( epsilon - caprolactone ) ( PEG - b - PCL ) micelles were loaded with paclitaxel ( cytotoxic agent ) , cyclopamine ( hedgehog inhibitor ) , and gossypol ( Bcl - 2 inhibitor ) .", "entity": [{"entity": "Poly ( ethylene glycol ) - block - poly ( epsilon - caprolactone )", "entity_type": "Chemical", "pos": [0, 66]}, {"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [69, 82]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [111, 121]}, {"entity": "cyclopamine", "entity_type": "Chemical", "pos": [144, 155]}, {"entity": "gossypol", "entity_type": "Chemical", "pos": [185, 193]}], "task": "NER"}
{"text": "After physicochemical studies focusing on combination drug solubilization , 3 - drug PEG - b - PCL micelles were evaluated in vitro in 2 - D and 3 - D cell culture and in vivo in xenograft models of ovarian cancer , tracking bioluminescence signals from ES - 2 and SKOV3 human ovarian cancer cell lines after IP injection .", "entity": [{"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [85, 98]}], "task": "NER"}
{"text": "3 - Drug PEG - b - PCL micelles were not significantly more potent in 2 - D cell culture in comparison to paclitaxel ; however , they disaggregated ES - 2 tumor spheroids , whereas single drugs or 2 - drug combinations only slowed growth of ES - 2 tumor spheroids or had no noticeable effects .", "entity": [{"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [9, 22]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [106, 116]}], "task": "NER"}
{"text": "In ES - 2 and SKOV3 xenograft models , 3 - drug PEG - b - PCL micelles had significantly less tumor burden than paclitaxel based on bioluminescence imaging , 3 ' - deoxy - 3 ' - ( 18 ) F - fluorothymidine ( ( 18 ) F - FLT ) PET imaging , and overall survival .", "entity": [{"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [48, 61]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [112, 122]}, {"entity": "3 ' - deoxy - 3 ' - ( 18 ) F - fluorothymidine", "entity_type": "Chemical", "pos": [158, 204]}, {"entity": "( 18 ) F - FLT", "entity_type": "Chemical", "pos": [207, 221]}], "task": "NER"}
{"text": "( 18 ) F - FLT - PET images clearly showed that 3 - drug PEG - b - PCL micelles dramatically reduce tumor volumes over paclitaxel and vehicle controls .", "entity": [{"entity": "( 18 ) F - FLT", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [57, 70]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [119, 129]}], "task": "NER"}
{"text": "In summary , PEG - b - PCL micelles enable the IP combination drug delivery of paclitaxel , cyclopamine and gossypol , resulting in tumor growth inhibition and prolonged survival over paclitaxel alone .", "entity": [{"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [13, 26]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "cyclopamine", "entity_type": "Chemical", "pos": [92, 103]}, {"entity": "gossypol", "entity_type": "Chemical", "pos": [108, 116]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [184, 194]}], "task": "NER"}
{"text": "These results validate a novel treatment strategy for ovarian cancer based on drug combinations of cytotoxic agents and molecular targeted agents , delivered concurrently by a nanoscale drug delivery system , e . g . PEG - b - PCL micelles .", "entity": [{"entity": "PEG - b - PCL", "entity_type": "Chemical", "pos": [217, 230]}], "task": "NER"}
{"text": "Torching the Haystack : modelling fast - fail strategies in drug development .", "entity": [], "task": "NER"}
{"text": "By quickly clearing the development pipeline of failing or marginal products , fast - fail strategies release resources to focus on more promising molecules .", "entity": [], "task": "NER"}
{"text": "The Quick - Kill model of drug development demonstrates that fast - fail strategies will : ( 1 ) reduce the expected time to market ; ( 2 ) reduce expected R & D costs ; and ( 3 ) increase R & D productivity .", "entity": [], "task": "NER"}
{"text": "This paper outlines the model and demonstrates the impact of fast - fail strategies .", "entity": [], "task": "NER"}
{"text": "The model is illustrated with costs and risks data from pharmaceutical and biopharmaceutical companies .", "entity": [], "task": "NER"}
{"text": "Mechanisms underlying induction of LTP - associated changes in short - term dynamics of transmission at immature synapses .", "entity": [], "task": "NER"}
{"text": "While the activity - dependent mechanisms guiding functional maturation of synaptic transmission postsynaptically are well characterized , less is known about the corresponding presynaptic mechanisms .", "entity": [], "task": "NER"}
{"text": "Here we show that during the first postnatal week , a subset of CA3 - CA1 synapses express postsynaptically induced LTP that is tightly associated with a robust decrease in synaptic facilitation , consistent with an increase in release probability ( P ( r ) ) .", "entity": [], "task": "NER"}
{"text": "The loss of facilitation is readily induced by physiologically relevant pairing protocols at immature synapses and is dependent on activation of NMDA - receptors but not L - type calcium channels .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [145, 149]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "The putative pre - and postsynaptic components of neonatal LTP were distinguished in their downstream signaling requirements , PKC activity being selectively needed for the decrease in facilitation but not for synaptic potentiation per se .", "entity": [], "task": "NER"}
{"text": "These data suggest that maturation of glutamatergic synapses involves a critical period during which presynaptic function is highly susceptible to activity - dependent regulation via a PKC - dependent mechanism .", "entity": [], "task": "NER"}
{"text": "In vitro neurotoxic effects of Pseudechis spp . venoms : A comparison of avian and murine skeletal muscle preparations .", "entity": [], "task": "NER"}
{"text": "Two common in vitro skeletal muscle preparations used for the study of venom neurotoxicity are the indirectly stimulated chick isolated biventer cervicis nerve - muscle preparation and the rat isolated phrenic nerve - diaphragm preparation .", "entity": [], "task": "NER"}
{"text": "The aim of the current study was to compare the in vitro neurotoxicity of six Pseudechis spp .", "entity": [], "task": "NER"}
{"text": "( Black snakes ) venoms in both avian ( chicken ) and mammalian ( rat ) skeletal muscle preparations to determine differences in sensitivity .", "entity": [], "task": "NER"}
{"text": "All Pseudechis spp . venoms significantly inhibited indirect twitches , in both preparations , indicating the presence of post synaptic neurotoxins .", "entity": [], "task": "NER"}
{"text": "The inhibitory effects of all venoms were more rapid in the avian preparation , except for Pseudechis colletti venom where no significant difference was seen between the murine and avian muscles .", "entity": [], "task": "NER"}
{"text": "Time taken to produce 50 % reduction in stimulated twitches ( i . e . t ( 50 ) ) was markedly shorter in the avian preparation .", "entity": [], "task": "NER"}
{"text": "We have shown that the avian in vitro preparation is more sensitive to the neurotoxic activity of Pseudechis spp . than the murine preparation .", "entity": [], "task": "NER"}
{"text": "This difference is likely to be due to species differences in the interaction between the neurotoxins and the nicotinic receptor binding sites as well as differences in the ' safety factor ' between the preparations .", "entity": [], "task": "NER"}
{"text": "Development and evaluation of colloidal modified nanolipid carrier : Application to topical delivery of tacrolimus , Part II - In vivo assessment , drug targeting , efficacy , and safety in treatment for atopic dermatitis .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "In atopic dermatitis ( AD ) , topical anti - inflammatory therapy with skin barrier restoration to prevent repeated inflammatory episodes leads to long - term therapeutic success .", "entity": [], "task": "NER"}
{"text": "Tacrolimus , although effective against AD , is a challenging molecule due to low solubility , low - penetration , poor - bioavailability , and toxicity .", "entity": [{"entity": "Tacrolimus", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Part I of this paper , reported novel modified nanolipid carrier system for topical delivery of tacrolimus ( T - MNLC ) , offering great opportunity to load low - solubility drug with improved entrapment efficiency , enhanced stability and improved skin deposition .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [96, 106]}], "task": "NER"}
{"text": "Present investigation focused on restoration of skin barrier , site - specific delivery , therapeutic effectiveness , and safety of novel T - MNLC .", "entity": [], "task": "NER"}
{"text": "T - MNLC greatly enhanced occlusive properties , skin hydration potential and reduced transepidermal water loss .", "entity": [], "task": "NER"}
{"text": "This might help to reduce the number of flares and better control the disease .", "entity": [], "task": "NER"}
{"text": "Cutaneous uptake and drug deposition in albino rats by HPLC and confocal laser scanning microscopy revealed prominently elevated drug levels in all skin strata with T - MNLC as compared to reference .", "entity": [], "task": "NER"}
{"text": "T - MNLC demonstrated efficient suppression of inflammatory responses in BALB / c mice model of AD .", "entity": [], "task": "NER"}
{"text": "Safety assessment by acute and repeated - dose dermal toxicity demonstrated mild keratosis and collagenous mass infiltration at the treatment area with repeated application of reference .", "entity": [], "task": "NER"}
{"text": "Interestingly , T - MNLC showed no evident toxicity exhibiting safe drug delivery .", "entity": [], "task": "NER"}
{"text": "Thus , novel T - MNLC would be a safe , effective , and esthetically appealing alternative to conventional vehicles for treatment for AD .", "entity": [], "task": "NER"}
{"text": "Size - dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts .", "entity": [], "task": "NER"}
{"text": "Gold nanoparticles ( AuNPs ) are currently used in several fields including biomedical applications , although no conclusive information on their cytotoxicity is available .", "entity": [], "task": "NER"}
{"text": "For this reason this work has investigated the effects of AuNPs in vitro on Balb / 3T3 mouse fibroblasts .", "entity": [], "task": "NER"}
{"text": "Results obtained exposing cells for 72 h to AuNPs 5 and 15 nm citrate stabilized , revealed cytotoxic effects only for AuNPs 5 nm at concentration >= 50 mu M if measured by colony forming efficiency ( CFE ) .", "entity": [{"entity": "citrate", "entity_type": "Chemical", "pos": [62, 69]}], "task": "NER"}
{"text": "To understand the differences in cytotoxicity observed for the two AuNPs sizes , we investigated the uptake and the intracellular distribution of the nanoparticles .", "entity": [], "task": "NER"}
{"text": "By TEM it was observed that 5 and 15 nm AuNPs are internalized by Balb / 3T3 cells and located within intracellular endosomal compartments .", "entity": [], "task": "NER"}
{"text": "Quantification of the uptake by ICP - MS showed that AuNPs internalization enhanced even up to 72 h .", "entity": [], "task": "NER"}
{"text": "Disruption of the actin cytoskeleton was evident , with cell footprints narrow and contracted ; effects more remarkable in cells exposed to 5 nm AuNP .", "entity": [], "task": "NER"}
{"text": "The mechanism of NPs cell internalization was investigated using immunocytochemistry and western blot .", "entity": [], "task": "NER"}
{"text": "No significant effect was observed in the expression level of caveolin , while reduction of the expression and degradation of the clathrin heavy chain was observed in cells exposed for 72 h to AuNPs .", "entity": [], "task": "NER"}
{"text": "Failure to generate bone marrow adipocytes does not protect mice from ovariectomy - induced osteopenia .", "entity": [], "task": "NER"}
{"text": "A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents , suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance .", "entity": [], "task": "NER"}
{"text": "Mice with loss of function mutations in kit receptor ( kit ( W / W - v ) ) have no bone marrow adipocytes in tibia or lumbar vertebra .", "entity": [], "task": "NER"}
{"text": "We therefore tested the hypothesis that marrow fat contributes to the development of osteopenia by comparing the skeletal response to ovariectomy ( ovx ) in growing wild type ( WT ) and bone marrow adipocyte - deficient kit ( W / W - v ) mice .", "entity": [], "task": "NER"}
{"text": "Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post - surgery .", "entity": [], "task": "NER"}
{"text": "Body composition was measured at necropsy by dual - energy X - ray absorptiometry .", "entity": [], "task": "NER"}
{"text": "Cortical ( tibia ) and cancellous ( tibia and lumbar vertebra ) bone architecture were evaluated by microcomputed tomography .", "entity": [], "task": "NER"}
{"text": "Bone marrow adipocyte size and density , osteoblast - and osteoclast - lined bone perimeters , and bone formation were determined by histomorphometry .", "entity": [], "task": "NER"}
{"text": "Ovx resulted in an increase in total body fat mass at 10 weeks post - ovx in both genotypes , but the response was attenuated in the in kit ( W / W - v ) mice .", "entity": [], "task": "NER"}
{"text": "Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx .", "entity": [], "task": "NER"}
{"text": "In contrast , marrow adipocytes were not detected in either intact or ovx kit ( W / W - v ) mice .", "entity": [], "task": "NER"}
{"text": "However , ovx in WT and kit ( W / W - v ) mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass , cortical and cancellous bone formation rate , and cancellous osteoblast and osteoclast - lined bone perimeters .", "entity": [], "task": "NER"}
{"text": "In conclusion , our findings do not support a causal role for increased bone marrow fat as a mediator of ovx - induced osteopenia in mice .", "entity": [], "task": "NER"}
{"text": "Ameliorating effects of extracellular polymeric substances excreted by Thalassiosira pseudonana on algal toxicity of CdSe quantum dots .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [117, 121]}], "task": "NER"}
{"text": "Quantum dots ( QDs ) are engineered nanoparticles ( ENs ) that have found increasing applications and shown great potential in drug delivery , biological imaging and industrial products .", "entity": [], "task": "NER"}
{"text": "Knowledge of their stability , fate and transport in the aquatic environment is still lacking , including details of how these nanomaterials interact with marine phytoplankton .", "entity": [], "task": "NER"}
{"text": "Here , we examined the toxicity of functionalized CdSe / ZnS QDs ( amine - and carboxyl - ) by exposing them for five days to Thalassiosira pseudonana ( marine diatom ) grown under different nutrient - conditions ( enriched versus nitrogen - limited media ) .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "ZnS", "entity_type": "Chemical", "pos": [57, 60]}, {"entity": "amine", "entity_type": "Chemical", "pos": [67, 72]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [231, 239]}], "task": "NER"}
{"text": "The released polysaccharides and proteins , the major components of extracellular polymeric substances ( EPS ) , were measured to assess their potential effects on the interactions between QDs and T . pseudonana .", "entity": [], "task": "NER"}
{"text": "The partitioning of QDs was analyzed by monitoring the concentration of Cd in different size fractions of the cultures ( i . e . , filtrate , < 0 . 22 mu m and permeate , < 3 kDa ) .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [72, 74]}], "task": "NER"}
{"text": "We found that the Cd release of QDs in the T . pseudonana culture was dependent on the nutrient conditions and nature of QDs ' surface coating .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [18, 20]}], "task": "NER"}
{"text": "Both amine - and carboxyl - functionalized QDs exhibited higher rates of Cd release in N - limited cultures than in nutrient enriched cultures .", "entity": [{"entity": "amine", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [73, 75]}], "task": "NER"}
{"text": "The results also showed that amine - functionalized QDs aggregate with minimal Cd release , independent of nutrient conditions .", "entity": [{"entity": "amine", "entity_type": "Chemical", "pos": [29, 34]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [79, 81]}], "task": "NER"}
{"text": "Laser scanning confocal microscopy images confirmed that aggregates are composed of QDs and the culture matrix ( EPS ) .", "entity": [], "task": "NER"}
{"text": "In addition , both types of QDs showed limited toxicity to T . pseudonana .", "entity": [], "task": "NER"}
{"text": "The increasing production of proteins induced by QDs suggests that extracellular proteins might be involved in the detoxification of QDs to T . pseudonana via the Cd release of QDs .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [163, 165]}], "task": "NER"}
{"text": "Our results here demonstrated that EPS can play an ameliorating role in QD toxicity , fate and transport in the aquatic environment .", "entity": [], "task": "NER"}
{"text": "17 beta estradiol regulation of connexin 43 - based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte - like MLO - Y4 cells .", "entity": [{"entity": "17 beta estradiol", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "Connexin 43 ( Cx43 ) plays an essential role in osteocyte mechanotransduction .", "entity": [], "task": "NER"}
{"text": "Although estrogen involves in the adaptive responses of bone cells to mechanical loadings , its effects on osteocytic Cx43 - based gap junction intercellular communication ( GJIC ) remain obscure .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [9, 17]}], "task": "NER"}
{"text": "We found that 17 beta estradiol ( E2 ) up - regulated Cx43 , and enhanced GJIC in osteocyte - like MLO - Y4 cells in fluorescence recovery after photobleaching ( FRAP ) assay .", "entity": [{"entity": "17 beta estradiol", "entity_type": "Chemical", "pos": [14, 31]}], "task": "NER"}
{"text": "Combination of E2 pre - treatment and oscillating fluid flow ( OFF ) further enhanced Cx43 expression and mitogen - activated protein kinase ( MAPK ) phosphorylation , comparing to E2 or OFF treatment alone .", "entity": [], "task": "NER"}
{"text": "Both blocking of classical estrogen receptors ( ER alpha / beta ) by fulvestrant and ER alpha knockdown by small interfering RNA inhibited E2 - mediated Cx43 increase , while a GPR30 - specific agonist G - 1 failed to promote Cx43 expression .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "Our results suggest that the presence of E2 enhanced Cx43 - based GJIC mainly via ER alpha / beta pathway , and sensitized osteocytes to mechanical loading .", "entity": [], "task": "NER"}
{"text": "Phase separation as a key to a thermoelectric high efficiency .", "entity": [], "task": "NER"}
{"text": "This work elucidates the possible reasons for the outstanding , but never reproduced thermoelectric properties of the doped Ti ( 0 . 5 ) Zr ( 0 . 25 ) Hf ( 0 . 25 ) NiSn Heusler compounds .", "entity": [{"entity": "Ti ( 0 . 5 ) Zr ( 0 . 25 ) Hf ( 0 . 25 ) NiSn", "entity_type": "Chemical", "pos": [124, 169]}], "task": "NER"}
{"text": "The structural investigations done via synchrotron X - ray diffraction measurements and scanning electron microscope measurements , which clearly show that the microstructure consists of three temperature stable C1 ( b ) phases with possible semi - coherent interfaces , are presented .", "entity": [], "task": "NER"}
{"text": "The exceptional thermoelectric properties are due to this intrinsic phase separation .", "entity": [], "task": "NER"}
{"text": "It is possible to reproduce the high Figure of Merit values with ZT = 1 . 2 at 830 K .", "entity": [], "task": "NER"}
{"text": "Furthermore , the influence of doping different elements on the Sn position in this Heusler material system is investigated .", "entity": [{"entity": "Sn", "entity_type": "Chemical", "pos": [64, 66]}], "task": "NER"}
{"text": "Halogen - bonding - triggered supramolecular gel formation .", "entity": [{"entity": "Halogen", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Supramolecular gels are topical soft materials involving the reversible formation of fibrous aggregates using non - covalent interactions .", "entity": [], "task": "NER"}
{"text": "There is significant interest in controlling the properties of such materials by the formation of multicomponent systems , which exhibit non - additive properties emerging from interaction of the components .", "entity": [], "task": "NER"}
{"text": "The use of hydrogen bonding to assemble supramolecular gels in organic solvents is well established .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "In contrast , the use of halogen bonding to trigger supramolecular gel formation in a two - component gel ( ' co - gel ' ) is essentially unexplored , and forms the basis for this study .", "entity": [{"entity": "halogen", "entity_type": "Chemical", "pos": [25, 32]}], "task": "NER"}
{"text": "Here , we show that halogen bonding between a pyridyl substituent in a bis ( pyridyl urea ) and 1 , 4 - diiodotetrafluorobenzene brings about gelation , even in polar media such as aqueous methanol and aqueous dimethylsulfoxide .", "entity": [{"entity": "halogen", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "pyridyl", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "bis ( pyridyl urea )", "entity_type": "Chemical", "pos": [71, 91]}, {"entity": "1 , 4 - diiodotetrafluorobenzene", "entity_type": "Chemical", "pos": [96, 128]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [189, 197]}, {"entity": "dimethylsulfoxide", "entity_type": "Chemical", "pos": [210, 227]}], "task": "NER"}
{"text": "This demonstrates that halogen bonding is sufficiently strong to interfere with competing gel - inhibitory interactions and create a ' tipping point ' in gel assembly .", "entity": [{"entity": "halogen", "entity_type": "Chemical", "pos": [23, 30]}], "task": "NER"}
{"text": "Using this concept , we have prepared a halogen bond donor bis ( urea ) gelator that forms co - gels with halogen bond acceptors .", "entity": [{"entity": "halogen", "entity_type": "Chemical", "pos": [40, 47]}, {"entity": "bis ( urea )", "entity_type": "Chemical", "pos": [59, 71]}, {"entity": "halogen", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "Translational research : the changing landscape of drug discovery .", "entity": [], "task": "NER"}
{"text": "Drug discovery represents the first step in the creation of new drugs , and takes place in academic institutions , biotech companies , and large pharmaceutical corporations .", "entity": [], "task": "NER"}
{"text": "Until recently , these sectors have each operated independently with little collaboration between those at the forefront of discovery research and those with experience in developing drugs .", "entity": [], "task": "NER"}
{"text": "With the rise of translational research these relationships are shifting and new hubs are emerging , as key players seek to pool the expertise necessary to generate new therapies by linking laboratory discoveries directly to unmet clinical needs .", "entity": [], "task": "NER"}
{"text": "In this article I discuss how the increasing adoption of translational research is leading to novel integrated discovery nexuses that may change the landscape of drug discovery .", "entity": [], "task": "NER"}
{"text": "Drug - drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of OATP1B1 .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [33, 45]}], "task": "NER"}
{"text": "Organic anion - transporting polypeptide 1B1 ( OATP1B1 ) is an important hepatic uptake transporter , of which the polymorphic variant OATP1B1 * 15 ( Asn130Asp and Val174Ala ) has been associated with decreased transport activity .", "entity": [], "task": "NER"}
{"text": "Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with oral antidiabetics in the clinic .", "entity": [{"entity": "Rosuvastatin", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "The aim of this study was to investigate possible drug - drug interactions between these drugs at the level of OATP1B1 and OATP1B1 * 15 .", "entity": [], "task": "NER"}
{"text": "We generated human embryonic kidney ( HEK ) 293 cells stably overexpressing OATP1B1 or OATP1B1 * 15 that showed similar protein expression levels of OATP1B1 and OATP1B1 * 15 at the cell membrane as measured by liquid chromatography - tandem mass spectrometry .", "entity": [], "task": "NER"}
{"text": "In HEK - OATP1B1 * 15 cells , the V ( max ) for OATP1B1 - mediated transport of E ( 2 ) 17 beta - G ( estradiol 17 beta - d - glucuronide ) was decreased > 60 % , whereas K ( m ) values ( Michaelis constant ) were comparable .", "entity": [{"entity": "estradiol 17 beta - d - glucuronide", "entity_type": "Chemical", "pos": [102, 137]}], "task": "NER"}
{"text": "Uptake of rosuvastatin in HEK - OATP1B1 cells ( K ( m ) 13 . 1 +/- 0 . 43 mu M ) was nearly absent in HEK - OATP1B1 * 15 cells .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [10, 22]}], "task": "NER"}
{"text": "Interestingly , several oral antidiabetics ( glyburide , glimepiride , troglitazone , pioglitazone , glipizide , gliclazide , and tolbutamide ) , but not metformin , were identified as significant inhibitors of the OATP1B1 - mediated transport of rosuvastatin .", "entity": [{"entity": "glyburide", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "glimepiride", "entity_type": "Chemical", "pos": [57, 68]}, {"entity": "troglitazone", "entity_type": "Chemical", "pos": [71, 83]}, {"entity": "pioglitazone", "entity_type": "Chemical", "pos": [86, 98]}, {"entity": "glipizide", "entity_type": "Chemical", "pos": [101, 110]}, {"entity": "gliclazide", "entity_type": "Chemical", "pos": [113, 123]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [130, 141]}, {"entity": "metformin", "entity_type": "Chemical", "pos": [154, 163]}, {"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [247, 259]}], "task": "NER"}
{"text": "The IC ( 50 ) values for inhibition of E ( 2 ) 17 beta - G uptake were similar between OATP1B1 and OATP1B1 * 15 .", "entity": [{"entity": "E ( 2 ) 17 beta - G", "entity_type": "Chemical", "pos": [39, 58]}], "task": "NER"}
{"text": "In conclusion , these studies indicate that several oral antidiabetic drugs affect the OATP1B1 - mediated uptake of rosuvastatin in vitro .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [116, 128]}], "task": "NER"}
{"text": "The next step will be to translate these data to the clinical situation , as it remains to be established whether the studied oral antidiabetics indeed affect the clinical pharmacokinetic profile of rosuvastatin in patients .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [199, 211]}], "task": "NER"}
{"text": "Optical and electrical detection of single - molecule translocation through carbon nanotubes .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [76, 82]}], "task": "NER"}
{"text": "Ion current through a single - walled carbon nanotube ( SWCNT ) was monitored at the same time as fluorescence was recorded from charged dye molecules translocating through the SWCNT .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [38, 44]}], "task": "NER"}
{"text": "Fluorescence bursts generally follow ion current peaks with a delay time consistent with diffusion from the end of the SWCNT to the fluorescence collection point .", "entity": [], "task": "NER"}
{"text": "The fluorescence amplitude distribution of the bursts is consistent with single - molecule signals .", "entity": [], "task": "NER"}
{"text": "Thus each peak in the ion current flowing through the SWCNT is associated with the translocation of a single molecule .", "entity": [], "task": "NER"}
{"text": "Ion current peaks ( as opposed to blockades ) were produced by both positively ( Rhodamine 6G ) and negatively ( Alexa 546 ) charged molecules , showing that the charge filtering responsible for the current bursts is caused by the molecules themselves .", "entity": [{"entity": "Rhodamine 6G", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "Alexa 546", "entity_type": "Chemical", "pos": [113, 122]}], "task": "NER"}
{"text": "Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [94, 103]}, {"entity": "hydrocodone", "entity_type": "Chemical", "pos": [108, 119]}], "task": "NER"}
{"text": "Prescription opioids abuse and associated deaths are an emerging concern in the USA .", "entity": [], "task": "NER"}
{"text": "Vaccination against prescription opioids may provide an alternative to pharmacotherapy .", "entity": [], "task": "NER"}
{"text": "An oxycodone hapten containing a tetraglycine linker at the C6 position ( 6OXY ( Gly ) ( 4 ) OH ) conjugated to keyhole limpet hemocyanin ( KLH ) has shown early proof - of - efficacy in rodents as a candidate immunogen ( 6OXY ( Gly ) ( 4 ) - KLH ) for the treatment of oxycodone abuse .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [3, 12]}, {"entity": "tetraglycine", "entity_type": "Chemical", "pos": [33, 45]}, {"entity": "6OXY ( Gly ) ( 4 ) OH", "entity_type": "Chemical", "pos": [74, 95]}, {"entity": "6OXY ( Gly ) ( 4 )", "entity_type": "Chemical", "pos": [222, 240]}, {"entity": "oxycodone", "entity_type": "Chemical", "pos": [270, 279]}], "task": "NER"}
{"text": "In this study , oxycodone - based and hydrocodone - based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "hydrocodone", "entity_type": "Chemical", "pos": [38, 49]}, {"entity": "oxycodone", "entity_type": "Chemical", "pos": [138, 147]}, {"entity": "hydrocodone", "entity_type": "Chemical", "pos": [152, 163]}], "task": "NER"}
{"text": "Vaccination with 6OXY ( Gly ) ( 4 ) - KLH increased drug binding in serum , reduced drug distribution to brain , and blunted analgesia for both oxycodone and hydrocodone .", "entity": [{"entity": "6OXY ( Gly ) ( 4 )", "entity_type": "Chemical", "pos": [17, 35]}, {"entity": "oxycodone", "entity_type": "Chemical", "pos": [144, 153]}, {"entity": "hydrocodone", "entity_type": "Chemical", "pos": [158, 169]}], "task": "NER"}
{"text": "An analogous C6 - linked hydrocodone vaccine blocked hydrocodone effects but less so than 6OXY ( Gly ) ( 4 ) - KLH .", "entity": [{"entity": "hydrocodone", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "hydrocodone", "entity_type": "Chemical", "pos": [53, 64]}, {"entity": "6OXY ( Gly ) ( 4 )", "entity_type": "Chemical", "pos": [90, 108]}], "task": "NER"}
{"text": "C8 - Linked hydrocodone immunogens had only limited efficacy .", "entity": [{"entity": "hydrocodone", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH ( mKLH ) .", "entity": [{"entity": "Amide", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "thioether", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "maleimide", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "The 6OXY ( Gly ) ( 4 ) - KLH vaccine may be used for treatment of prescription opioid abuse .", "entity": [{"entity": "6OXY ( Gly ) ( 4 )", "entity_type": "Chemical", "pos": [4, 22]}], "task": "NER"}
{"text": "Interactions of NO2 with Zr - based MOF : effects of the size of organic linkers on NO2 adsorption at ambient conditions .", "entity": [{"entity": "NO2", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "Zr", "entity_type": "Chemical", "pos": [25, 27]}, {"entity": "NO2", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Zirconium - based metal organic framework ( Zr - MOF ) , UiO - 66 and UiO - 67 , were synthesized and used as adsorbents of NO ( 2 ) at ambient temperatures in either dry or moist conditions .", "entity": [{"entity": "Zirconium", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Zr", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "UiO - 66", "entity_type": "Chemical", "pos": [57, 65]}, {"entity": "UiO - 67", "entity_type": "Chemical", "pos": [70, 78]}, {"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "The samples were characterized before and after exposure to NO ( 2 ) by X - ray diffraction , scanning electron microscopy , N ( 2 ) - adsorption at 77 K , thermal analysis , and infrared spectroscopy .", "entity": [{"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "N ( 2 )", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "The results indicate the important effect of a ligand size on the adsorption of NO ( 2 ) on Zr - MOF materials .", "entity": [{"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [80, 88]}, {"entity": "Zr", "entity_type": "Chemical", "pos": [92, 94]}], "task": "NER"}
{"text": "While the large size of the 4 , 4 - benzenebiphenyldicarboxylic acid ( BDPC ) ligand has a positive impact on the adsorption of NO ( 2 ) on UiO - 67 in moist conditions , the opposite effect is found in dry conditions .", "entity": [{"entity": "4 , 4 - benzenebiphenyldicarboxylic acid", "entity_type": "Chemical", "pos": [28, 68]}, {"entity": "BDPC", "entity_type": "Chemical", "pos": [71, 75]}, {"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "UiO - 67", "entity_type": "Chemical", "pos": [140, 148]}], "task": "NER"}
{"text": "The large pore volume of UiO - 67 enhances the adsorption of moisture and formation of nitric and nitrous acids .", "entity": [{"entity": "UiO - 67", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "nitric and nitrous acids", "entity_type": "Chemical", "pos": [87, 111]}], "task": "NER"}
{"text": "The small pore sizes of UiO - 66 favor the NO ( 2 ) removal in dry conditions via dispersive forces .", "entity": [{"entity": "UiO - 66", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "Upon interaction of NO ( 2 ) molecules with the Zr - MOF in dry conditions , the bond between the organic linker and metallic oxide center is broken , leading to the formation of nitrate and nitrite species .", "entity": [{"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "Zr", "entity_type": "Chemical", "pos": [48, 50]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [126, 131]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [179, 186]}, {"entity": "nitrite", "entity_type": "Chemical", "pos": [191, 198]}], "task": "NER"}
{"text": "Moreover , organic ligands also contribute to the NO ( 2 ) reactive adsorption via nitration reaction .", "entity": [{"entity": "NO ( 2 )", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Potent microRNA suppression by RNA Pol II - transcribed ' Tough Decoy ' inhibitors .", "entity": [], "task": "NER"}
{"text": "MicroRNAs ( miRNAs ) are key regulators of gene expression and modulators of diverse biological pathways .", "entity": [], "task": "NER"}
{"text": "Analyses of miRNA function as well as therapeutic managing of miRNAs rely on cellular administration of miRNA inhibitors which may be achieved by the use of viral vehicles .", "entity": [], "task": "NER"}
{"text": "This study explores the miRNA - suppressive capacity of inhibitors expressed intracellularly from lentivirus - derived gene vectors .", "entity": [], "task": "NER"}
{"text": "Superior activity of two decoy - type inhibitors , a \" Bulged Sponge \" with eight miRNA recognition sites and a hairpin - shaped \" Tough Decoy \" containing two miRNA recognition sites , is demonstrated in a side - by - side comparison of seven types of miRNA inhibitors transcribed as short RNAs from an RNA Pol III promoter .", "entity": [], "task": "NER"}
{"text": "We find that lentiviral vectors expressing Tough Decoy inhibitors are less vulnerable than Bulged Sponge - encoding vectors to targeting by the cognate miRNA and less prone , therefore , to reductions in transfer efficiency .", "entity": [], "task": "NER"}
{"text": "Importantly , it is demonstrated that Tough Decoy inhibitors retain their miRNA suppression capacity in the context of longer RNA transcripts expressed from an RNA Pol II promoter .", "entity": [], "task": "NER"}
{"text": "Such RNA Pol II - transcribed Tough Decoy inhibitors are new tools in managing of miRNAs and may have potential for temporal and spatial regulation of miRNA activity as well as for therapeutic targeting of miRNAs that are aberrantly expressed in human disease .", "entity": [], "task": "NER"}
{"text": "Androgens promote prostate cancer cell growth through induction of autophagy .", "entity": [{"entity": "Androgens", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Androgens regulate both the physiological development of the prostate and the pathology of prostatic diseases .", "entity": [{"entity": "Androgens", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "However , the mechanisms by which androgens exert their regulatory activities on these processes are poorly understood .", "entity": [{"entity": "androgens", "entity_type": "Chemical", "pos": [34, 43]}], "task": "NER"}
{"text": "In this study , we have determined that androgens regulate overall cell metabolism and cell growth , in part , by increasing autophagy in prostate cancer cells .", "entity": [{"entity": "androgens", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "Importantly , inhibition of autophagy using either pharmacological or molecular inhibitors significantly abrogated androgen - induced prostate cancer cell growth .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "Mechanistically , androgen - mediated autophagy appears to promote cell growth by augmenting intracellular lipid accumulation , an effect previously demonstrated to be necessary for prostate cancer cell growth .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "Further , autophagy and subsequent cell growth is potentiated , in part , by androgen - mediated increases in reactive oxygen species .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [119, 125]}], "task": "NER"}
{"text": "These findings demonstrate a role for increased fat metabolism and autophagy in prostatic neoplasias and highlight the potential of targeting underexplored metabolic pathways for the development of novel therapeutics .", "entity": [], "task": "NER"}
{"text": "Regulation of H2O2 stress - responsive genes through a novel transcription factor in the protozoan pathogen Entamoeba histolytica .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "Outcome of infection depends upon complex interactions between the invading pathogen and the host .", "entity": [], "task": "NER"}
{"text": "As part of the host ' s innate immune response , the release of reactive oxygen and nitrogen species by phagocytes represents a major obstacle to the establishment of infection .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [73, 79]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "The ability of the human parasite Entamoeba histolytica to survive reactive oxygen and nitrogen species is central to its pathogenic potential and contributes to disease outcome .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [76, 82]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "In order to define the transcriptional network associated with oxidative stress , we utilized the MEME and MAST programs to analyze the promoter regions of 57 amoebic genes that had increased expression specifically in response to H ( 2 ) O ( 2 ) exposure .", "entity": [{"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [231, 246]}], "task": "NER"}
{"text": "We functionally characterized an H ( 2 ) O ( 2 ) - regulatory motif ( HRM ) ( ( 1 ) AAACCTCAATGAAGA ( 15 ) ) , which was enriched in these promoters and specifically bound amoebic nuclear protein ( s ) .", "entity": [{"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [33, 48]}], "task": "NER"}
{"text": "Assays with promoter - luciferase fusions established the importance of key residues and that the HRM motif directly impacted the ability of H ( 2 ) O ( 2 ) - responsive promoters to drive gene expression .", "entity": [{"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [141, 156]}], "task": "NER"}
{"text": "DNA affinity chromatography and mass spectrometry identified EHI _ 108720 as an HRM DNA - binding protein .", "entity": [], "task": "NER"}
{"text": "Overexpression and down - regulation of EHI _ 108720 demonstrated the specificity of EHI _ 108720 protein binding to the HRM , and overexpression increased basal expression from an H ( 2 ) O ( 2 ) - responsive wild - type promoter but not from its mutant counterpart .", "entity": [{"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [181, 196]}], "task": "NER"}
{"text": "Thus , EHI _ 108720 , or HRM - binding protein , represents a new stress - responsive transcription factor in E . histolytica that controls a transcriptional regulatory network associated with oxidative stress .", "entity": [], "task": "NER"}
{"text": "Overexpression of EHI _ 108720 increased parasite virulence .", "entity": [], "task": "NER"}
{"text": "Insight into how E . histolytica responds to oxidative stress increases our understanding of how this important human pathogen establishes invasive disease .", "entity": [], "task": "NER"}
{"text": "Palmitate and lipopolysaccharide trigger synergistic ceramide production in primary macrophages .", "entity": [{"entity": "Palmitate", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ceramide", "entity_type": "Chemical", "pos": [53, 61]}], "task": "NER"}
{"text": "Macrophages play a key role in host defense and in tissue repair after injury .", "entity": [], "task": "NER"}
{"text": "Emerging evidence suggests that macrophage dysfunction in states of lipid excess can contribute to the development of insulin resistance and may underlie inflammatory complications of diabetes .", "entity": [], "task": "NER"}
{"text": "Ceramides are sphingolipids that modulate a variety of cellular responses including cell death , autophagy , insulin signaling , and inflammation .", "entity": [{"entity": "Ceramides", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "sphingolipids", "entity_type": "Chemical", "pos": [14, 27]}], "task": "NER"}
{"text": "In this study we investigated the intersection between TLR4 - mediated inflammatory signaling and saturated fatty acids with regard to ceramide generation .", "entity": [{"entity": "saturated fatty acids", "entity_type": "Chemical", "pos": [98, 119]}, {"entity": "ceramide", "entity_type": "Chemical", "pos": [135, 143]}], "task": "NER"}
{"text": "Primary macrophages treated with lipopolysaccharide ( LPS ) did not produce C16 ceramide , whereas palmitate exposure led to a modest increase in this sphingolipid .", "entity": [{"entity": "C16 ceramide", "entity_type": "Chemical", "pos": [76, 88]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [99, 108]}, {"entity": "sphingolipid", "entity_type": "Chemical", "pos": [151, 163]}], "task": "NER"}
{"text": "Strikingly , the combination of LPS and palmitate led to a synergistic increase in C16 ceramide .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "C16 ceramide", "entity_type": "Chemical", "pos": [83, 95]}], "task": "NER"}
{"text": "This response occurred via cross - talk at the level of de novo ceramide synthesis in the ER .", "entity": [{"entity": "ceramide", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "The synergistic response required TLR4 signaling via MyD88 and TIR - domain - containing adaptor - inducing interferon beta ( TRIF ) , whereas palmitate - induced ceramide production occurred independent of these inflammatory molecules .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [143, 152]}, {"entity": "ceramide", "entity_type": "Chemical", "pos": [163, 171]}], "task": "NER"}
{"text": "This ceramide response augmented IL - 1 beta and TNF alpha release , a process that may contribute to the enhanced inflammatory response in metabolic diseases characterized by dyslipidemia .", "entity": [{"entity": "ceramide", "entity_type": "Chemical", "pos": [5, 13]}], "task": "NER"}
{"text": "Substituent effect in 2 - benzoylmethylenequinoline difluoroborates exhibiting through - space couplings .", "entity": [{"entity": "2 - benzoylmethylenequinoline difluoroborates", "entity_type": "Chemical", "pos": [22, 67]}], "task": "NER"}
{"text": "Multinuclear magnetic resonance , X - ray diffraction , and computational study .", "entity": [], "task": "NER"}
{"text": "The series of nine 2 - benzoylmethylenequinoline difluoroborates have been synthesized and characterized by multinuclear magnetic resonance , X - ray diffraction ( XRD ) , and computational methods .", "entity": [{"entity": "2 - benzoylmethylenequinoline difluoroborates", "entity_type": "Chemical", "pos": [19, 64]}], "task": "NER"}
{"text": "The through - space spin - spin couplings between ( 19 ) F and ( 1 ) H / ( 13 ) C nuclei have been observed in solution .", "entity": [{"entity": "( 19 ) F", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [63, 70]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "The NMR chemical shifts have been correlated to the Hammett substituent constants .", "entity": [], "task": "NER"}
{"text": "The crystal structures of six compounds have been solved by XRD .", "entity": [], "task": "NER"}
{"text": "For two derivatives the X - ray wave function refinement was performed to evaluate the character of bonds in the NBF ( 2 ) O moiety by topological and integrated bond descriptors .", "entity": [{"entity": "NBF ( 2 ) O", "entity_type": "Chemical", "pos": [113, 124]}], "task": "NER"}
{"text": "Dynamic or nondynamic ?", "entity": [], "task": "NER"}
{"text": "Helical trajectory in hexabenzocoronene nanotubes biased by a detachable chiral auxiliary .", "entity": [{"entity": "hexabenzocoronene", "entity_type": "Chemical", "pos": [22, 39]}], "task": "NER"}
{"text": "When ether vapor was allowed to diffuse into a CH ( 2 ) Cl ( 2 ) solution of an enantiomer of a hexa - peri - hexabenzocoronene ( HBC ) derivative carrying a chiral ( BINAP ) Pt ( II ) - appended coordination metallacycle ( HBC ( Py ) ( [ ( R ) - Pt ] ) or HBC ( Py ) ( [ ( S ) - Pt ] ) ) , screw - sense - selective assembly took place to give optically active nanotubes ( NT ( Py ) ( [ ( R ) - Pt ] ) or NT ( Py ) ( [ ( S ) - Pt ] ) ) with helical chirality , which were enriched in either left - handed ( M ) - NT ( Py ) ( [ ( R ) - Pt ] ) or right - handed ( P ) - NT ( Py ) ( [ ( S ) - Pt ] ) , depending on the absolute configuration of the ( BINAP ) Pt ( II ) pendant .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "CH ( 2 ) Cl ( 2 )", "entity_type": "Chemical", "pos": [47, 64]}, {"entity": "hexa - peri - hexabenzocoronene", "entity_type": "Chemical", "pos": [96, 127]}, {"entity": "HBC", "entity_type": "Chemical", "pos": [130, 133]}, {"entity": "( BINAP ) Pt ( II )", "entity_type": "Chemical", "pos": [165, 184]}, {"entity": "HBC ( Py ) ( [ ( R ) - Pt ]", "entity_type": "Chemical", "pos": [224, 251]}, {"entity": "HBC ( Py ) ( [ ( S ) - Pt ] )", "entity_type": "Chemical", "pos": [257, 286]}, {"entity": "Py", "entity_type": "Chemical", "pos": [379, 381]}, {"entity": "[ ( R ) - Pt ]", "entity_type": "Chemical", "pos": [386, 400]}, {"entity": "Py", "entity_type": "Chemical", "pos": [411, 413]}, {"entity": "[ ( S ) - Pt ]", "entity_type": "Chemical", "pos": [418, 432]}, {"entity": "Py", "entity_type": "Chemical", "pos": [519, 521]}, {"entity": "[ ( R ) - Pt ]", "entity_type": "Chemical", "pos": [526, 540]}, {"entity": "Py", "entity_type": "Chemical", "pos": [574, 576]}, {"entity": "[ ( S ) - Pt ]", "entity_type": "Chemical", "pos": [581, 595]}, {"entity": "( BINAP ) Pt ( II )", "entity_type": "Chemical", "pos": [647, 666]}], "task": "NER"}
{"text": "When MeOH was used instead of ether for the vapor - diffusion - induced assembly , nanocoils formed along with the nanotubes .", "entity": [{"entity": "MeOH", "entity_type": "Chemical", "pos": [5, 9]}], "task": "NER"}
{"text": "As determined by scanning electron microscopy , the diastereomeric excess of the nanocoils was 60 % ( 80 : 20 diastereomeric ratio ) .", "entity": [], "task": "NER"}
{"text": "Removal of the ( BINAP ) Pt ( II ) pendants from NT ( Py ) ( [ ( R ) - Pt ] ) or NT ( Py ) ( [ ( S ) - Pt ] ) with ethylenediamine yielded metal - free nanotubes ( NT ( Py ) ) that remained optically active even upon heating without any change in the circular dichroism spectral profile .", "entity": [{"entity": "( BINAP ) Pt ( II )", "entity_type": "Chemical", "pos": [15, 34]}, {"entity": "Py", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "[ ( R ) - Pt ]", "entity_type": "Chemical", "pos": [61, 75]}, {"entity": "Py", "entity_type": "Chemical", "pos": [86, 88]}, {"entity": "[ ( S ) - Pt ]", "entity_type": "Chemical", "pos": [93, 107]}, {"entity": "ethylenediamine", "entity_type": "Chemical", "pos": [115, 130]}, {"entity": "Py", "entity_type": "Chemical", "pos": [169, 171]}], "task": "NER"}
{"text": "No helical inversion took place when NT ( Py ) derived from HBC ( Py ) ( [ ( R ) - Pt ] ) or HBC ( Py ) ( [ ( S ) - Pt ] ) was allowed to complex with ( BINAP ) Pt ( II ) with an absolute configuration opposite to the original one .", "entity": [{"entity": "Py", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "HBC ( Py ) ( [ ( R ) - Pt ] )", "entity_type": "Chemical", "pos": [60, 89]}, {"entity": "HBC ( Py ) ( [ ( S ) - Pt ] )", "entity_type": "Chemical", "pos": [93, 122]}, {"entity": "( BINAP ) Pt ( II )", "entity_type": "Chemical", "pos": [151, 170]}], "task": "NER"}
{"text": "Cooperative effects of drug - resistance mutations in the flap region of HIV - 1 protease .", "entity": [], "task": "NER"}
{"text": "Understanding the interdependence of multiple mutations in conferring drug resistance is crucial to the development of novel and robust inhibitors .", "entity": [], "task": "NER"}
{"text": "As HIV - 1 protease continues to adapt and evade inhibitors while still maintaining the ability to specifically recognize and efficiently cleave its substrates , the problem of drug resistance has become more complicated .", "entity": [], "task": "NER"}
{"text": "Under the selective pressure of therapy , correlated mutations accumulate throughout the enzyme to compromise inhibitor binding , but characterizing their energetic interdependency is not straightforward .", "entity": [], "task": "NER"}
{"text": "A particular drug resistant variant ( L10I / G48V / I54V / V82A ) displays extreme entropy - enthalpy compensation relative to wild - type enzyme but a similar variant ( L10I / G48V / I54A / V82A ) does not .", "entity": [], "task": "NER"}
{"text": "Individual mutations of sites in the flaps ( residues 48 and 54 ) of the enzyme reveal that the thermodynamic effects are not additive .", "entity": [], "task": "NER"}
{"text": "Rather , the thermodynamic profile of the variants is interdependent on the cooperative effects exerted by a particular combination of mutations simultaneously present .", "entity": [], "task": "NER"}
{"text": "Exploring the sequence - structure relationship for amyloid peptides .", "entity": [], "task": "NER"}
{"text": "Amyloid fibril formation is associated with misfolding diseases , as well as fulfilling a functional role .", "entity": [], "task": "NER"}
{"text": "The cross - beta molecular architecture has been reported in increasing numbers of amyloid - like fibrillar systems .", "entity": [], "task": "NER"}
{"text": "The Waltz algorithm is able to predict ordered self - assembly of amyloidogenic peptides by taking into account the residue type and position .", "entity": [], "task": "NER"}
{"text": "This algorithm has expanded the amyloid sequence space , and in the present study we characterize the structures of amyloid - like fibrils formed by three peptides identified by Waltz that form fibrils but not crystals .", "entity": [], "task": "NER"}
{"text": "The structural challenge is met by combining electron microscopy , linear dichroism , CD and X - ray fibre diffraction .", "entity": [], "task": "NER"}
{"text": "We propose structures that reveal a cross - beta conformation with ' steric - zipper ' features , giving insights into the role for side chains in peptide packing and stability within fibrils .", "entity": [], "task": "NER"}
{"text": "The amenity of these peptides to structural characterization makes them compelling model systems to use for understanding the relationship between sequence , self - assembly , stability and structure of amyloid fibrils .", "entity": [], "task": "NER"}
{"text": "Chemical Modification of Lysozyme , Glucose 6 - Phosphate Dehydrogenase , and Bovine Eye Lens Proteins Induced by Peroxyl Radicals : Role of Oxidizable Amino Acid Residues .", "entity": [{"entity": "Glucose 6 - Phosphate", "entity_type": "Chemical", "pos": [36, 57]}, {"entity": "Peroxyl", "entity_type": "Chemical", "pos": [114, 121]}, {"entity": "Amino Acid", "entity_type": "Chemical", "pos": [152, 162]}], "task": "NER"}
{"text": "Chemical and structural alterations to lysozyme ( LYSO ) , glucose 6 - phosphate dehydrogenase ( G6PD ) , and bovine eye lens proteins ( BLP ) promoted by peroxyl radicals generated by the thermal decomposition of 2 , 2 ' - azobis ( 2 - amidinopropane ) hydrochloride ( AAPH ) under aerobic conditions were investigated .", "entity": [{"entity": "glucose 6 - phosphate", "entity_type": "Chemical", "pos": [59, 80]}, {"entity": "peroxyl", "entity_type": "Chemical", "pos": [155, 162]}, {"entity": "2 , 2 ' - azobis ( 2 - amidinopropane ) hydrochloride", "entity_type": "Chemical", "pos": [214, 267]}, {"entity": "AAPH", "entity_type": "Chemical", "pos": [270, 274]}], "task": "NER"}
{"text": "SDS - PAGE analysis of the AAPH - treated proteins revealed the occurrence of protein aggregation , cross - linking , and fragmentation ; BLP , which are naturally organized in globular assemblies , were the most affected proteins .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "AAPH", "entity_type": "Chemical", "pos": [27, 31]}], "task": "NER"}
{"text": "Transmission electron microscopy ( TEM ) analysis of BLP shows the formation of complex protein aggregates after treatment with AAPH .", "entity": [{"entity": "AAPH", "entity_type": "Chemical", "pos": [128, 132]}], "task": "NER"}
{"text": "These structural modifications were accompanied by the formation of protein carbonyl groups and protein hydroperoxides .", "entity": [{"entity": "carbonyl", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "hydroperoxides", "entity_type": "Chemical", "pos": [104, 118]}], "task": "NER"}
{"text": "The yield of carbonyls was lower than that for protein hydroperoxide generation and was unrelated to protein fragmentation .", "entity": [{"entity": "carbonyls", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "hydroperoxide", "entity_type": "Chemical", "pos": [55, 68]}], "task": "NER"}
{"text": "The oxidized proteins were also characterized by significant oxidation of Met , Trp , and Tyr ( but not other ) residues , and low levels of dityrosine .", "entity": [{"entity": "Met", "entity_type": "Chemical", "pos": [74, 77]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [80, 83]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [90, 93]}, {"entity": "dityrosine", "entity_type": "Chemical", "pos": [141, 151]}], "task": "NER"}
{"text": "As the dityrosine yield is too low to account for the observed cross - linking , we propose that aggregation is associated with tryptophan oxidation and Trp - derived cross - links .", "entity": [{"entity": "dityrosine", "entity_type": "Chemical", "pos": [7, 17]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [128, 138]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "It is also proposed that Trp oxidation products play a fundamental role in nonrandom fragmentation and carbonyl group formation particularly for LYSO and G6PD .", "entity": [{"entity": "Trp", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "These data point to a complex mechanism of peroxyl - radical mediated modification of proteins with monomeric ( LYSO ) , dimeric ( G6PD ) , and multimeric ( BLP ) structural organization , which not only results in oxidation of protein side chains but also gives rise to radical - mediated protein cross - links and fragmentation , with Trp species being critical intermediates .", "entity": [{"entity": "peroxyl", "entity_type": "Chemical", "pos": [43, 50]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [337, 340]}], "task": "NER"}
{"text": "Comparative structural and functional studies of 4 - ( thiazol - 5 - yl ) - 2 - ( phenylamino ) pyrimidine - 5 - carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity .", "entity": [{"entity": "4 - ( thiazol - 5 - yl ) - 2 - ( phenylamino ) pyrimidine - 5 - carbonitrile", "entity_type": "Chemical", "pos": [49, 125]}], "task": "NER"}
{"text": "Cyclin - dependent kinase 9 / cyclin T , the protein kinase heterodimer that constitutes positive transcription elongation factor b , is a well - validated target for treatment of several diseases , including cancer and cardiac hypertrophy .", "entity": [], "task": "NER"}
{"text": "In order to aid inhibitor design and rationalize the basis for CDK9 selectivity , we have studied the CDK - binding properties of six different members of a 4 - ( thiazol - 5 - yl ) - 2 - ( phenylamino ) pyrimidine - 5 - carbonitrile series that bind to both CDK9 / cyclin T and CDK2 / cyclin A .", "entity": [{"entity": "4 - ( thiazol - 5 - yl ) - 2 - ( phenylamino ) pyrimidine - 5 - carbonitrile", "entity_type": "Chemical", "pos": [157, 233]}], "task": "NER"}
{"text": "We find that for a given CDK , the melting temperature of a CDK / cyclin / inhibitor complex correlates well with inhibitor potency , suggesting that differential scanning fluorimetry ( DSF ) is a useful orthogonal measure of inhibitory activity for this series .", "entity": [], "task": "NER"}
{"text": "We have used DSF to demonstrate that the binding of these compounds is independent of the presence or absence of the C - terminal tail region of CDK9 , unlike the binding of the CDK9 - selective inhibitor 5 , 6 - dichlorobenzimidazone - 1 - beta - d - ribofuranoside ( DRB ) .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [117, 118]}, {"entity": "5 , 6 - dichlorobenzimidazone - 1 - beta - d - ribofuranoside", "entity_type": "Chemical", "pos": [205, 266]}, {"entity": "DRB", "entity_type": "Chemical", "pos": [269, 272]}], "task": "NER"}
{"text": "Finally , on the basis of 11 cocrystal structures bound to CDK9 / cyclin T or CDK2 / cyclin A , we conclude that selective inhibition of CDK9 / cyclin T by members of the 4 - ( thiazol - 5 - yl ) - 2 - ( phenylamino ) pyrimidine - 5 - carbonitrile series results from the relative malleability of the CDK9 active site rather than from the formation of specific polar contacts .", "entity": [{"entity": "4 - ( thiazol - 5 - yl ) - 2 - ( phenylamino ) pyrimidine - 5 - carbonitrile", "entity_type": "Chemical", "pos": [171, 247]}], "task": "NER"}
{"text": "Development of new cathepsin B inhibitors : combining bioisosteric replacements and structure - based design to explore the structure - activity relationships of nitroxoline derivatives .", "entity": [{"entity": "nitroxoline", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "Human cathepsin B has many house - keeping functions , such as protein turnover in lysosomes .", "entity": [], "task": "NER"}
{"text": "However , dysregulation of its activity is associated with numerous diseases , including cancers .", "entity": [], "task": "NER"}
{"text": "We present here the structure - based design and synthesis of new cathepsin B inhibitors using the cocrystal structure of 5 - nitro - 8 - hydroxyquinoline in the cathepsin B active site .", "entity": [{"entity": "5 - nitro - 8 - hydroxyquinoline", "entity_type": "Chemical", "pos": [122, 154]}], "task": "NER"}
{"text": "A focused library of over 50 compounds was prepared by modifying positions 5 , 7 , and 8 of the parent compound nitroxoline .", "entity": [{"entity": "nitroxoline", "entity_type": "Chemical", "pos": [112, 123]}], "task": "NER"}
{"text": "The kinetic parameters and modes of inhibition were characterized , and the selectivities of the most promising inhibitors were determined .", "entity": [], "task": "NER"}
{"text": "The best performing inhibitor 17 was effective in cell - based in vitro models of tumor invasion , where it significantly abrogated invasion of MCF - 10A neoT cells .", "entity": [], "task": "NER"}
{"text": "These data show that we have successfully explored the structure - activity relationships of nitroxoline derivatives to provide new inhibitors that could eventually lead to compounds with clinical usefulness against the deleterious effects of cathepsin B in cancer progression .", "entity": [{"entity": "nitroxoline", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "Adverse events associated with mTOR inhibitors .", "entity": [], "task": "NER"}
{"text": "INTRODUCTION : The mTOR ( mechanistic target of rapamycin , formerly known as mammalian target of rapamycin ) kinase is centrally involved in the regulation of cell growth and metabolism in response to intra - and extracellular energetic stimuli and growth factors .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "The importance of mTOR in health and diseases has fueled the development of molecules that inhibit mTOR signaling , including rapalogs ( sirolimus , temsirolimus , everolimus and deforolimus ) , which complex with FK506 - binding protein 12 ( FK - BP12 ) to inhibit mTOR complex 1 ( MTORC1 ) activity in an allosteric manner , or the more recent ATP - competitive mTOR inhibitors ( mTORi ) , which target the catalytic site of the enzyme .", "entity": [{"entity": "sirolimus", "entity_type": "Chemical", "pos": [137, 146]}, {"entity": "temsirolimus", "entity_type": "Chemical", "pos": [149, 161]}, {"entity": "everolimus", "entity_type": "Chemical", "pos": [164, 174]}, {"entity": "deforolimus", "entity_type": "Chemical", "pos": [179, 190]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [346, 349]}], "task": "NER"}
{"text": "However , clinical development of these mTORi has revealed that these drugs produced numerous side effects that could be serious and / or debilitating .", "entity": [], "task": "NER"}
{"text": "Despite pharmacological efforts to develop drugs with an improved safety profile , these side effects are often unpredictable and may frequently preclude the efficiency of mTORi .", "entity": [], "task": "NER"}
{"text": "AREAS COVERED : The objective of this review is to perform a comprehensive survey of the safety profiles of various rapalog - based therapies from the available clinical literature .", "entity": [], "task": "NER"}
{"text": "The authors will discuss the potential mechanisms of these therapies , taking into account the knowledge of the biological pathways regulated by mTOR .", "entity": [], "task": "NER"}
{"text": "EXPERT OPINION : A better prevention and management of mTORi - related side effects requires the identification of alterations in related biological pathways that will help to delineate therapeutic targets .", "entity": [], "task": "NER"}
{"text": "Dependence of QSAR models on the selection of trial descriptor sets : a demonstration using nanotoxicity endpoints of decorated nanotubes .", "entity": [], "task": "NER"}
{"text": "Little attention has been given to the selection of trial descriptor sets when designing a QSAR analysis even though a great number of descriptor classes , and often a greater number of descriptors within a given class , are now available .", "entity": [], "task": "NER"}
{"text": "This paper reports an effort to explore interrelationships between QSAR models and descriptor sets .", "entity": [], "task": "NER"}
{"text": "Zhou and co - workers ( Zhou et al . , Nano Lett . 2008 , 8 ( 3 ) , 859 - 865 ) designed , synthesized , and tested a combinatorial library of 80 surface modified , that is decorated , multi - walled carbon nanotubes for their composite nanotoxicity using six endpoints all based on a common 0 to 100 activity scale .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [200, 206]}], "task": "NER"}
{"text": "Each of the six endpoints for the 29 most nanotoxic decorated nanotubes were incorporated as the training set for this study .", "entity": [], "task": "NER"}
{"text": "The study reported here includes trial descriptor sets for all possible combinations of MOE , VolSurf , and 4D - fingerprints ( FP ) descriptor classes , as well as including and excluding explicit spatial contributions from the nanotube .", "entity": [], "task": "NER"}
{"text": "Optimized QSAR models were constructed from these multiple trial descriptor sets .", "entity": [], "task": "NER"}
{"text": "It was found that ( a ) both the form and quality of the best QSAR models for each of the endpoints are distinct and ( b ) some endpoints are quite dependent upon 4D - FP descriptors of the entire nanotube - decorator complex .", "entity": [], "task": "NER"}
{"text": "However , other endpoints yielded equally good models only using decorator descriptors with and without the decorator - only 4D - FP descriptors .", "entity": [], "task": "NER"}
{"text": "Lastly , and most importantly , the quality , significance , and interpretation of a QSAR model were found to be critically dependent on the trial descriptor sets used within a given QSAR endpoint study .", "entity": [], "task": "NER"}
{"text": "Towards a balanced value business model for personalized medicine : an outlook .", "entity": [], "task": "NER"}
{"text": "Novel targeted drugs , mainly in oncology , have commanded substantial price premiums in the recent past .", "entity": [], "task": "NER"}
{"text": "Consequently , the attention of pharmaceutical companies has shifted away from the traditional low - price and high - volume blockbuster business model to drugs that command high , and sometimes extremely high , prices in limited markets defined by targeted patient populations .", "entity": [], "task": "NER"}
{"text": "This model may have already passed its zenith , as the impact of more and more high - priced drugs coming to market substantially increases their combined burden on payors and public health finances .", "entity": [], "task": "NER"}
{"text": "This article introduces a new ' balanced value ' business model for personalized medicine , leveraging the emerging opportunities to reduce drug development cost and time for targeted therapies .", "entity": [], "task": "NER"}
{"text": "This model allows pharmaceutical companies to charge prices for targeted therapy below the likely future thresholds for payors ' willingness to pay , at the same time preserving attractive margins for the drug developers .", "entity": [], "task": "NER"}
{"text": "Improving clinical trial sampling for future research - an international approach : outcomes and next steps from the DIA future use sampling workshop 2011 .", "entity": [], "task": "NER"}
{"text": "Clinical trial samples collected for pharmacogenomic and future research are vital resources for the development of safe and effective drugs , yet collecting adequate , representative sample sets in global trials is challenging .", "entity": [], "task": "NER"}
{"text": "The Drug Information Association ( DIA ) sponsored a workshop on future use sampling in September 2011 , bringing together experts from regulatory agencies , academia and industry to discuss challenges to future use sample collection and identify actions to improve collection .", "entity": [], "task": "NER"}
{"text": "Several common themes and associated action items emerged , including the need for international guidance on the collection of samples for future research ; additional discussion related to coding , scope of research , and return of research results ; and additional education about pharmacogenomic / future research and the importance of long - term storage of specimens .", "entity": [], "task": "NER"}
{"text": "Expanding the number of ' druggable ' targets : non - enzymes and protein - protein interactions .", "entity": [], "task": "NER"}
{"text": "Following sequencing and assembly of the human genome , the preferred methods for identification of new drug targets have changed dramatically .", "entity": [], "task": "NER"}
{"text": "Modern tactics such as genome - wide association studies ( GWAS ) and deep sequencing are fundamentally different from the pharmacology - guided approaches used previously , in which knowledge of small molecule ligands acting at their cellular targets was the primary discovery engine .", "entity": [], "task": "NER"}
{"text": "A consequence of the ' target - first , pharmacology - second ' strategy is that many predicted drug targets are non - enzymes , such as scaffolding , regulatory or structural proteins , and their activities are often dependent on protein - protein interactions ( PPIs ) .", "entity": [], "task": "NER"}
{"text": "These types of targets create unique challenges to drug discovery efforts because enzymatic turnover cannot be used as a convenient surrogate for compound potency .", "entity": [], "task": "NER"}
{"text": "Moreover , it is often challenging to predict how ligand binding to non - enzymes might affect changes in protein function and / or pathobiology .", "entity": [], "task": "NER"}
{"text": "Thus , in the postgenomic era , targets might be strongly implicated by molecular biology - based methods , yet they often later earn the designation of ' undruggable ' .", "entity": [], "task": "NER"}
{"text": "Can the scope of available targets be widened to include these promising , but challenging , non - enzymes ?", "entity": [], "task": "NER"}
{"text": "In this review , we discuss advances in high - throughput screening ( HTS ) technology and chemical library design that are emerging to deal with these challenges .", "entity": [], "task": "NER"}
{"text": "Antibody - drug conjugates for the treatment of cancer .", "entity": [], "task": "NER"}
{"text": "With over 20 antibody - drug conjugates in clinical trials as well as a recently FDA - approved drug , it is clear that this is becoming an important and viable approach for selectively delivering highly cytotoxic agents to tumor cells while sparing normal tissue .", "entity": [], "task": "NER"}
{"text": "This review discusses the critical aspects for this approach with an emphasis on the properties of the linker between the antibody and the cytotoxic payload that are required for an effective antibody - drug conjugate .", "entity": [], "task": "NER"}
{"text": "Different linkers are illustrated with attention focused on ( i ) the specifics of attachment to the antibody , ( ii ) the polarity of the linker , ( iii ) the trigger on the linker that initiates cleavage from the drug , and ( iv ) the self - immolative spacer that liberates the active payload .", "entity": [], "task": "NER"}
{"text": "Future directions in the field are proposed .", "entity": [], "task": "NER"}
{"text": "Peptide scanning for studying structure - activity relationships in drug discovery .", "entity": [], "task": "NER"}
{"text": "Peptide - based therapeutics have grown in importance over the last few decades .", "entity": [], "task": "NER"}
{"text": "Furthermore , peptides have been extensively used as lead compounds in the drug discovery process to investigate the nature of chemical space required for molecular recognition and activity at a variety of targets .", "entity": [], "task": "NER"}
{"text": "This critical commentary reviews scanning techniques , which employ natural and non - proteinogenic amino acids to facilitate understanding of structural requirements for peptide biological activity .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "The value of sequence analysis by such methods is highlighted by examples , in which the elements for peptide affinity and activity have been elucidated and employed to prepare peptidomimetic leads for drug development .", "entity": [], "task": "NER"}
{"text": "Neurochemical control of rapid stress - induced changes in brain aromatase activity .", "entity": [], "task": "NER"}
{"text": "In the male brain , the medial preoptic nucleus ( POM ) is known to be a critical relay for the activation of sexual behaviour , with the aromatisation of testosterone into 17 beta - oestradiol ( E2 ) playing a key role .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [155, 167]}, {"entity": "17 beta - oestradiol", "entity_type": "Chemical", "pos": [173, 193]}], "task": "NER"}
{"text": "Acute stress has been shown to differentially modulate the aromatase enzyme in this and other brain nuclei in a sex - specific manner .", "entity": [], "task": "NER"}
{"text": "In POM specifically , stress induces increases in aromatase activity ( AA ) that are both rapid and reversible .", "entity": [], "task": "NER"}
{"text": "How the physiological processes initiated during an acute stress response mediate sex - and nuclei - specific changes in AA and which stress response hormones are involved remains to be determined .", "entity": [], "task": "NER"}
{"text": "By examining the relative effects of corticosterone ( CORT ) , arginine vasotocin ( AVT , the avian homologue to arginine vasopressin ) and corticotrophin - releasing factor ( CRF ) , the present study aimed to define the hormone profile regulating stress - induced increases in AA in the POM .", "entity": [{"entity": "corticosterone", "entity_type": "Chemical", "pos": [37, 51]}, {"entity": "CORT", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "arginine vasotocin", "entity_type": "Chemical", "pos": [63, 81]}, {"entity": "AVT", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "arginine vasopressin", "entity_type": "Chemical", "pos": [113, 133]}], "task": "NER"}
{"text": "We found that CORT , AVT and CRF all appear to play some role in these changes in the male brain .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "AVT", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "In addition , these effects occur in a targeted manner , such that modulation of the enzyme by these hormones only occurs in the POM rather than in all aromatase - expressing nuclei .", "entity": [], "task": "NER"}
{"text": "Similarly , in the female brain , the experimental effects were restricted to the POM but only CRF was capable of inducing the stress - like increases in AA .", "entity": [], "task": "NER"}
{"text": "These data further demonstrate the high degree of specificity ( nuclei - , sex - and hormone - specific effects ) in this system , highlighting the complexity of the stress - aromatase link and suggesting modes through which the nongenomic modulation of this enzyme can result in targeted , rapid changes in local oestrogen concentrations .", "entity": [{"entity": "oestrogen", "entity_type": "Chemical", "pos": [314, 323]}], "task": "NER"}
{"text": "Assessment of the usefulness of the murine cytotoxic T cell line CTLL - 2 for immunotoxicity screening by transcriptomics .", "entity": [], "task": "NER"}
{"text": "A toxicogenomics approach was applied to assess the usefulness of the mouse cytotoxic T cell line CTLL - 2 for in vitro immunotoxicity testing .", "entity": [], "task": "NER"}
{"text": "CTLL - 2 cells were exposed for 6 h to two model immunotoxic compounds : ( 1 ) the mycotoxin deoxynivalenol ( DON , 1 and 2 mu M ) , a ribotoxic stress inducer , and ( 2 ) the organotin compound tributyltin oxide ( TBTO , 100 and 200 nM ) , an endoplasmic reticulum ( ER ) stress inducer .", "entity": [{"entity": "deoxynivalenol", "entity_type": "Chemical", "pos": [93, 107]}, {"entity": "DON", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "organotin", "entity_type": "Chemical", "pos": [176, 185]}, {"entity": "tributyltin oxide", "entity_type": "Chemical", "pos": [195, 212]}, {"entity": "TBTO", "entity_type": "Chemical", "pos": [215, 219]}], "task": "NER"}
{"text": "Effects on whole - genome mRNA expression were assessed by microarray analysis .", "entity": [], "task": "NER"}
{"text": "The biological interpretation of the microarray data indicated that TBTO ( 200 nM ) induced genes involved in T cell activation , ER stress , NF kappa B activation and apoptosis , which agreed very well with results obtained before on TBTO exposed Jurkat cells and mouse primary thymocytes .", "entity": [{"entity": "TBTO", "entity_type": "Chemical", "pos": [68, 72]}, {"entity": "TBTO", "entity_type": "Chemical", "pos": [235, 239]}], "task": "NER"}
{"text": "Remarkably , DON ( 2 mu M ) downregulated genes involved in T cell activation , ER stress and apoptosis , which is opposite to results obtained before for DON - exposed Jurkat cells and mouse primary thymocytes .", "entity": [{"entity": "DON", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "DON", "entity_type": "Chemical", "pos": [155, 158]}], "task": "NER"}
{"text": "Furthermore , the results for DON in CTLL - 2 cells are also opposite to the results obtained for TBTO in CTLL - 2 cells .", "entity": [{"entity": "DON", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "TBTO", "entity_type": "Chemical", "pos": [98, 102]}], "task": "NER"}
{"text": "In agreement with the lack of induction of ER stress and apoptosis , viability assays showed that CTLL - 2 cells are much more resistant to the toxicity of DON than Jurkat cells and primary thymocytes .", "entity": [{"entity": "DON", "entity_type": "Chemical", "pos": [156, 159]}], "task": "NER"}
{"text": "We propose that CTLL - 2 cells lack the signal transduction that induces ER stress and apoptosis in response to ribotoxic stress .", "entity": [], "task": "NER"}
{"text": "Based on the results for TBTO and DON , the CTLL - 2 cell line does not yield an added value for immunotoxicity compared to the human Jurkat T cell line .", "entity": [{"entity": "TBTO", "entity_type": "Chemical", "pos": [25, 29]}, {"entity": "DON", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "Effect of lactation on postpartum cardiac function of pregnancy - associated hypertensive mice .", "entity": [], "task": "NER"}
{"text": "Preeclampsia is a serious complication during pregnancy , and recent epidemiological studies indicate the association between preeclampsia and cardiac morbidity and mortality during the postpartum period .", "entity": [], "task": "NER"}
{"text": "Although the risk of cardiovascular diseases in the postpartum period is affected by lactation , its role in maternal heart with a history of preeclampsia remains unclear .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated postpartum change in cardiac remodeling and function of pregnancy - associated hypertensive ( PAH ) mice with and without lactation .", "entity": [], "task": "NER"}
{"text": "The systolic blood pressure was increased in PAH mice at day 19 of gestation ( E19 ) and was reduced to normal levels in both lactating and nonlactating ( NL ) groups in the postpartum period .", "entity": [], "task": "NER"}
{"text": "Histological analyses revealed that cardiac hypertrophy and macrophage infiltration in PAH mice at E19 were improved in both lactating and NL groups at 4 weeks postpartum ( 4W - PP ) , while marked fibrosis remained .", "entity": [], "task": "NER"}
{"text": "Increased mRNA expression of profibrotic genes and proinflammatory cytokines in PAH mice at E19 was significantly reduced in both lactating and NL groups at 4W - PP .", "entity": [], "task": "NER"}
{"text": "Echocardiographic analysis found no significant differences in fractional shortening between PAH mice and C57BL / 6J mice at E19 .", "entity": [], "task": "NER"}
{"text": "On the other hand , at 4W - PP , NL PAH mice showed normal fractional shortening , but lactating PAH mice exhibited significant decreases in cardiac contractility compared with NL PAH mice .", "entity": [], "task": "NER"}
{"text": "These results show that cardiac remodeling induced by hypertension during pregnancy are improved in the postpartum period except fibrosis , whereas lactation induces cardiac contractile dysfunction in mice with a history of pregnancy - associated hypertension .", "entity": [], "task": "NER"}
{"text": "Focal adhesion size uniquely predicts cell migration .", "entity": [], "task": "NER"}
{"text": "Focal adhesions are large protein complexes organized at the basal surface of cells , which physically connect the extracellular matrix to the cytoskeleton and have long been speculated to mediate cell migration .", "entity": [], "task": "NER"}
{"text": "However , whether clustering of these molecular components into focal adhesions is actually required for these proteins to regulate cell motility is unclear .", "entity": [], "task": "NER"}
{"text": "Here we use quantitative microscopy to characterize descriptors of focal adhesion and cell motility for mouse embryonic fibroblasts and human fibrosarcoma cells , across a wide range of matrix compliance and following genetic manipulations of focal adhesion proteins ( vinculin , talin , zyxin , FAK , and paxilin ) .", "entity": [], "task": "NER"}
{"text": "This analysis reveals a tight , biphasic gaussian relationship between mean size of focal adhesions ( not their number , surface density , or shape ) and cell speed .", "entity": [], "task": "NER"}
{"text": "The predictive power of this relationship is comprehensively validated by disrupting nonfocal adhesion proteins ( alpha - actinin , F - actin , and myosin II ) and subcellular organelles ( mitochondria , nuclear DNA , etc . ) not known to affect either focal adhesions or cell migration .", "entity": [], "task": "NER"}
{"text": "This study suggests that the mean size of focal adhesions robustly and precisely predicts cell speed independently of focal adhesion surface density and molecular composition . - Kim , D . - H . , Wirtz , D .", "entity": [], "task": "NER"}
{"text": "Formation and infrared absorption of protonated naphthalenes ( 1 - C10H9 + and 2 - C10H9 + ) and their neutral counterparts in solid para - hydrogen .", "entity": [{"entity": "protonated naphthalenes", "entity_type": "Chemical", "pos": [37, 60]}, {"entity": "1 - C10H9 +", "entity_type": "Chemical", "pos": [63, 74]}, {"entity": "2 - C10H9 +", "entity_type": "Chemical", "pos": [79, 90]}, {"entity": "para - hydrogen", "entity_type": "Chemical", "pos": [133, 148]}], "task": "NER"}
{"text": "Protonated naphthalene ( C ( 10 ) H ( 9 ) ( + ) ) and its neutral counterparts ( hydronaphthyl radicals , C ( 10 ) H ( 9 ) ) are important intermediates in the reactions of aromatic compounds and in understanding the unidentified infrared ( IR ) emissions from interstellar media .", "entity": [{"entity": "Protonated naphthalene", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [25, 47]}, {"entity": "hydronaphthyl", "entity_type": "Chemical", "pos": [81, 94]}, {"entity": "C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [106, 122]}], "task": "NER"}
{"text": "We report the IR spectra of 1 - C ( 10 ) H ( 9 ) ( + ) , 2 - C ( 10 ) H ( 9 ) ( + ) , 1 - C ( 10 ) H ( 9 ) , and 2 - C ( 10 ) H ( 9 ) trapped in solid para - hydrogen ( p - H ( 2 ) ) ; the latter three are new .", "entity": [{"entity": "1 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [28, 54]}, {"entity": "2 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [57, 83]}, {"entity": "1 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [86, 106]}, {"entity": "2 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [113, 133]}, {"entity": "para - hydrogen", "entity_type": "Chemical", "pos": [151, 166]}, {"entity": "p - H ( 2 )", "entity_type": "Chemical", "pos": [169, 180]}], "task": "NER"}
{"text": "These species were produced upon electron bombardment of a mixture of naphthalene ( C ( 10 ) H ( 8 ) ) and p - H ( 2 ) during matrix deposition .", "entity": [{"entity": "naphthalene", "entity_type": "Chemical", "pos": [70, 81]}, {"entity": "C ( 10 ) H ( 8 )", "entity_type": "Chemical", "pos": [84, 100]}, {"entity": "p - H ( 2 )", "entity_type": "Chemical", "pos": [107, 118]}], "task": "NER"}
{"text": "The intensities of IR features of 1 - C ( 10 ) H ( 9 ) ( + ) decreased after the matrix was maintained in darkness for 19 h , whereas those of 1 - C ( 10 ) H ( 9 ) and 2 - C ( 10 ) H ( 9 ) increased .", "entity": [{"entity": "1 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [34, 60]}, {"entity": "1 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [143, 163]}, {"entity": "2 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [168, 188]}], "task": "NER"}
{"text": "Irradiation of this matrix sample with light at 365 nm diminished lines of 1 - C ( 10 ) H ( 9 ) ( + ) and 2 - C ( 10 ) H ( 9 ) and enhanced lines of 1 - C ( 10 ) H ( 9 ) and 2 - C ( 10 ) H ( 9 ) ( + ) ; the latter species was unstable and converted to 1 - C ( 10 ) H ( 9 ) ( + ) in less than 30 min and 2 - C ( 10 ) H ( 9 ) was converted to 1 - C ( 10 ) H ( 9 ) at 365 nm .", "entity": [{"entity": "1 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [75, 101]}, {"entity": "2 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [106, 126]}, {"entity": "1 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [149, 169]}, {"entity": "2 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [174, 200]}, {"entity": "1 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [252, 278]}, {"entity": "2 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [303, 323]}, {"entity": "1 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [341, 361]}], "task": "NER"}
{"text": "Observed wavenumbers and relative intensities of these species agree satisfactorily with the anharmonic vibrational wavenumbers and IR intensities predicted with the B3PW91 / 6 - 311 + + G ( 2d , 2p ) method .", "entity": [], "task": "NER"}
{"text": "Compared with spectra recorded previously with IR photodissociation of Ar - tagged C ( 10 ) H ( 9 ) ( + ) or IR multiphoton dissociation of C ( 10 ) H ( 9 ) ( + ) , our method has the advantages of producing high - resolution IR spectra with a wide spectral coverage , true IR intensity and excellent ratio of signal to noise ; both protonated species and their neutral counterparts are produced with little interference from other fragments .", "entity": [{"entity": "Ar", "entity_type": "Chemical", "pos": [71, 73]}, {"entity": "C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [83, 105]}, {"entity": "C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [140, 162]}], "task": "NER"}
{"text": "With these advantages , the IR spectra of 1 - C ( 10 ) H ( 9 ) ( + ) , 2 - C ( 10 ) H ( 9 ) ( + ) , 1 - C ( 10 ) H ( 9 ) , and 2 - C ( 10 ) H ( 9 ) are here clearly characterized .", "entity": [{"entity": "1 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [42, 68]}, {"entity": "2 - C ( 10 ) H ( 9 ) ( + )", "entity_type": "Chemical", "pos": [71, 97]}, {"entity": "1 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [100, 120]}, {"entity": "2 - C ( 10 ) H ( 9 )", "entity_type": "Chemical", "pos": [127, 147]}], "task": "NER"}
{"text": "Identification of multiple binding sites for substrate transport in bovine organic anion transporting polypeptide 1a2 .", "entity": [], "task": "NER"}
{"text": "Organic anion transporting polypeptides ( OATP ) have been extensively recognized as key determinants of absorption , distribution , metabolism , and excretion of various drugs because of their broad substrate specificity , wide tissue distribution , and the involvement of drug - drug interaction .", "entity": [], "task": "NER"}
{"text": "As the first cloned human OATP , OATP1A2 has been found to transport a wide spectrum of endogenous and exogenous compounds .", "entity": [], "task": "NER"}
{"text": "Bovine Oapt1a2 shared high homology with the human transporter and is considered as its functional ortholog .", "entity": [], "task": "NER"}
{"text": "In the present study , we expressed bovine Oatp1a2 in human embryonic kidney 293 cells and found that , unlike human OATP1A2 , the transport of estrone - 3 - sulfate ( E - 3 - S ) exhibited biphasic saturation kinetics .", "entity": [{"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [144, 165]}, {"entity": "E - 3 - S", "entity_type": "Chemical", "pos": [168, 177]}], "task": "NER"}
{"text": "The K ( m ) values are 0 . 25 +/- 0 . 08 and 46 . 6 +/- 18 . 5 micro M , and V ( max ) values were 24 . 5 +/- 4 . 4 and 375 +/- 142 pmol / mg protein / min for high - and low - affinity sites , respectively , suggesting the presence of multiple binding sites .", "entity": [], "task": "NER"}
{"text": "Further study on other Oatp1a2 substrates showed that the high affinity component for E - 3 - S is responsible for the interaction with taurocholate , bromsulphthalein , and rifampicin and is sensitive to proton concentration change , whereas the low affinity binding site is only involved in the binding of the antitumor drug methotrexate and had no response to change of pH .", "entity": [{"entity": "E - 3 - S", "entity_type": "Chemical", "pos": [86, 95]}, {"entity": "taurocholate", "entity_type": "Chemical", "pos": [136, 148]}, {"entity": "bromsulphthalein", "entity_type": "Chemical", "pos": [151, 167]}, {"entity": "rifampicin", "entity_type": "Chemical", "pos": [174, 184]}, {"entity": "methotrexate", "entity_type": "Chemical", "pos": [327, 339]}], "task": "NER"}
{"text": "Bamboo salt has in vitro anticancer activity in HCT - 116 cells and exerts anti - metastatic effects in vivo .", "entity": [], "task": "NER"}
{"text": "Bamboo salt is a traditional food widely used in Korea .", "entity": [], "task": "NER"}
{"text": "The in vitro anticancer effects of this salt were evaluated in HCT - 116 human colon cancer cells using a 3 - ( 4 , 5 - dimethyl - 2 - thiazolyl ) - 2 , 5 - diphenyltetrazolium bromide ( MTT ) assay .", "entity": [{"entity": "3 - ( 4 , 5 - dimethyl - 2 - thiazolyl ) - 2 , 5 - diphenyltetrazolium bromide", "entity_type": "Chemical", "pos": [106, 184]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [187, 190]}], "task": "NER"}
{"text": "A 1 % salt concentration of bamboo salt baked nine times ( 9 x ) inhibited the growth of HCT - 116 cells by 53 % , which was higher than salt baked three times ( 3 x ) or once ( 1 x ; 44 % and 41 % , respectively ) and much higher than solar sea salt ( Korean sea salt ) and purified salt ( 22 % and 18 % , respectively ) .", "entity": [], "task": "NER"}
{"text": "To elucidate the inhibitory mechanisms underlying the anticancer effect of the salt samples in cancer cells , expression of genes associated with apoptosis , inflammation , and metastasis was measured with reverse transcription - polymerase chain reaction and Western blotting .", "entity": [], "task": "NER"}
{"text": "Bamboo salt ( 9 x ) significantly induced apoptosis in cancer cells ( P < . 05 ) by upregulating Bax , caspase - 9 , and caspase - 3 , and downregulating Bcl - 2 .", "entity": [], "task": "NER"}
{"text": "The expression of genes associated with inflammation ( NF - kappa B , iNOS , and COX - 2 ) was significantly downregulated ( P < . 05 ) by 9 x bamboo salt , demonstrating its anti - inflammatory properties .", "entity": [], "task": "NER"}
{"text": "The 9 x bamboo salt also exerted a greater anti - metastatic effect on cancer cells than the other salts as demonstrated by decreased mRNA expression of MMP genes and increased expression of tissue inhibitors of metalloproteinases , which was confirmed by the inhibition of tumor metastasis induced in colon 26 - M3 . 1 cells in BALB / c mice .", "entity": [], "task": "NER"}
{"text": "In contrast , purified and solar salts increased metastasis in the mice .", "entity": [{"entity": "solar salts", "entity_type": "Chemical", "pos": [27, 38]}], "task": "NER"}
{"text": "Our results demonstrated that 9 x bamboo salt had the most potent in vitro anticancer effect , induced apoptosis , had anti - inflammatory activities , and exerted in vivo anti - metastatic effects .", "entity": [], "task": "NER"}
{"text": "Additionally , the anticancer , anti - inflammatory , and anti - metastatic effects of the 1 x and 3 x bamboo salts were stronger than those of the purified and solar salts .", "entity": [{"entity": "solar salts", "entity_type": "Chemical", "pos": [161, 172]}], "task": "NER"}
{"text": "Iodine - 129 microdosing for protein and peptide drug development : erythropoietin as a case study .", "entity": [{"entity": "Iodine - 129", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "BACKGROUND : Microdosing is a technique for studying the behavior of compounds in vivo at 1 / 100th of the dose of a test substance calculated , based on animal data , to yield a pharmacologic effect .", "entity": [], "task": "NER"}
{"text": "In microdosing , use is made of accelerator MS ( AMS ) .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated whether ( 129 ) I - labeling of proteins with subsequent AMS measurements is a suitable method to perform microdose studies with therapeutic proteins .", "entity": [{"entity": "( 129 ) I", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "We used erythropoietin ( EPO ) as a case study .", "entity": [], "task": "NER"}
{"text": "RESULTS : In an animal study with ( 129 ) I - labeled EPO in Han - Wistar rats , an increase of ( 129 ) I - EPO is observed after dose administration .", "entity": [{"entity": "( 129 ) I", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "( 129 ) I", "entity_type": "Chemical", "pos": [96, 105]}], "task": "NER"}
{"text": "The half - life was found to be 2 and 5 . 5 h for two different EPOs .", "entity": [], "task": "NER"}
{"text": "These results are in accordance with expected values .", "entity": [], "task": "NER"}
{"text": "CoNCLUSION : Although further research is required , ( 129 ) I - labeling of proteins seems a feasible method for AMS microdose studies with peptide and protein drugs , such as biosimilars .", "entity": [{"entity": "( 129 ) I", "entity_type": "Chemical", "pos": [53, 62]}], "task": "NER"}
{"text": "Structural - Functional Studies of Burkholderia cenocepaciad - Glycero - beta - d - manno - heptose 7 - Phosphate Kinase ( HldA ) and Characterization of Inhibitors with Antibiotic Adjuvant and Antivirulence Properties .", "entity": [{"entity": "Glycero - beta - d - manno - heptose 7 - Phosphate", "entity_type": "Chemical", "pos": [63, 113]}], "task": "NER"}
{"text": "As an essential constituent of the outer membrane of Gram - negative bacteria , lipopolysaccharide contributes significantly to virulence and antibiotic resistance .", "entity": [], "task": "NER"}
{"text": "The lipopolysaccharide biosynthetic pathway therefore serves as a promising therapeutic target for antivirulence drugs and antibiotic adjuvants .", "entity": [], "task": "NER"}
{"text": "Here we report the structural - functional studies of d - glycero - beta - d - manno - heptose 7 - phosphate kinase ( HldA ) , an absolutely conserved enzyme in this pathway , from Burkholderia cenocepacia .", "entity": [{"entity": "d - glycero - beta - d - manno - heptose 7 - phosphate", "entity_type": "Chemical", "pos": [54, 108]}], "task": "NER"}
{"text": "HldA is structurally similar to members of the PfkB carbohydrate kinase family and appears to catalyze heptose phosphorylation via an in - line mechanism mediated mainly by a conserved aspartate , Asp270 .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [52, 64]}, {"entity": "heptose", "entity_type": "Chemical", "pos": [103, 110]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [185, 194]}, {"entity": "Asp270", "entity_type": "Chemical", "pos": [197, 203]}], "task": "NER"}
{"text": "Moreover , we report the structures of HldA in complex with two potent inhibitors in which both inhibitors adopt a folded conformation and occupy the nucleotide - binding sites .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [150, 160]}], "task": "NER"}
{"text": "Together , these results provide important insight into the mechanism of HldA - catalyzed heptose phosphorylation and necessary information for further development of HldA inhibitors .", "entity": [{"entity": "heptose", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "Application of a liquid chromatography - electrospray mass spectrometry ( LC / MS ) method to the biodistribution and excretion studies of novel 5 ' - chloro - 2 , 3 - didehydroindolo ( 2 ' , 3 ' : 2 , 3 ) betulinic acid ( DRF - 4012 ) in tumour - bearing mice .", "entity": [{"entity": "5 ' - chloro - 2 , 3 - didehydroindolo ( 2 ' , 3 ' : 2 , 3 ) betulinic acid", "entity_type": "Chemical", "pos": [145, 220]}, {"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [223, 233]}], "task": "NER"}
{"text": "Novel betulinic acid derivative 5 ' - chloro - 2 , 3 - didehydroindolo [ 2 ' , 3 ' : 2 , 3 ] betulinic acid ( DRF - 4012 ) is a new effective lupane type triterpenes with greater anticancer activity and efficacy than betulinic acid and currently under advanced preclinical investigation phase .", "entity": [{"entity": "betulinic acid", "entity_type": "Chemical", "pos": [6, 20]}, {"entity": "5 ' - chloro - 2 , 3 - didehydroindolo [ 2 ' , 3 ' : 2 , 3 ] betulinic acid", "entity_type": "Chemical", "pos": [32, 107]}, {"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [110, 120]}, {"entity": "lupane", "entity_type": "Chemical", "pos": [142, 148]}, {"entity": "triterpenes", "entity_type": "Chemical", "pos": [154, 165]}, {"entity": "betulinic acid", "entity_type": "Chemical", "pos": [217, 231]}], "task": "NER"}
{"text": "In this study , a sensitive and rapid liquid chromatography - electrospray mass spectrometric ( LC / MS ) method has been developed for the determination of DRF - 4012 in tumour - bearing mice plasma , urine , feces and tissues ( liver , brain , lungs , heart , spleen , stomach , thigh muscle , kidneys , urinary bladder , small intestine and tumour ) .", "entity": [{"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [157, 167]}], "task": "NER"}
{"text": "Biodistribution and excretion studies were performed for DRF - 4012 nanoparticle ( 30 mg / kg body weight ) after intravenous ( i . v . ) injection in tumour - bearing mice .", "entity": [{"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "DRF - 4012 rapidly distributed throughout the body .", "entity": [{"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "After 0 . 5 h , tumour showed the second highest concentration , which was nearly half of the liver .", "entity": [], "task": "NER"}
{"text": "After 4 and 24 h , the highest concentration of DRF - 4012 was found in tumour indicating its retention in tumour site for a longer time .", "entity": [{"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [48, 58]}], "task": "NER"}
{"text": "Excretion studies revealed that very low amount of unchanged DRF - 4012 was observed in urine and primarily excreted through fecal route .", "entity": [{"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [61, 71]}], "task": "NER"}
{"text": "This study may be useful to explain the manner in which DRF - 4012 can inhibit tumour growth without apparent toxicity and preclinical / clinical evaluation of this potential antitumour agent .", "entity": [{"entity": "DRF - 4012", "entity_type": "Chemical", "pos": [56, 66]}], "task": "NER"}
{"text": "Characterization of in vitro metabolites of luotonin A in human liver microsomes using electrospray / tandem mass spectrometry .", "entity": [{"entity": "luotonin A", "entity_type": "Chemical", "pos": [44, 54]}], "task": "NER"}
{"text": "The pharmacological activity of luotonin A varies , depending on the type of functional group and the site of derivatization .", "entity": [{"entity": "luotonin A", "entity_type": "Chemical", "pos": [32, 42]}], "task": "NER"}
{"text": "To understand the in vivo efficacy of luotonin A , the in vitro metabolism of luotonin A was investigated in human liver microsomes and recombinant cDNA - expressed cytochromeP450 ( CYP ) .", "entity": [{"entity": "luotonin A", "entity_type": "Chemical", "pos": [38, 48]}, {"entity": "luotonin A", "entity_type": "Chemical", "pos": [78, 88]}], "task": "NER"}
{"text": "Incubation of luotonin A with pooled human liver microsomes in the presence of NADPH - generating system resulted in the formation of four metabolites and the structures of each metabolite were tentatively characterized on the basis of electrospray tandem mass spectra .", "entity": [{"entity": "luotonin A", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [79, 84]}], "task": "NER"}
{"text": "The main metabolic pathway of luotonin A in human liver microsomes was hydroxylation , resulting in the generation of two mono - hydroxyl metabolites ( M1 and M2 ) and two di - hydroxyl metabolites ( M3 and M4 ) .", "entity": [{"entity": "luotonin A", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "mono - hydroxyl", "entity_type": "Chemical", "pos": [122, 137]}, {"entity": "di - hydroxyl", "entity_type": "Chemical", "pos": [172, 185]}], "task": "NER"}
{"text": "CYP1A2 was primarily involved in hydroxylation of the quinolone moiety ( M1 andM3 ) , while CYP3A4 was mainly responsible for hydroxylation of the quinazoline moiety of luotonin A ( M2 and M4 ) in human liver microsomes .", "entity": [{"entity": "quinolone", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [147, 158]}, {"entity": "luotonin A", "entity_type": "Chemical", "pos": [169, 179]}], "task": "NER"}
{"text": "Evaluation of low background liquid scintillation counter for non - clinical ADME studies .", "entity": [], "task": "NER"}
{"text": "1 . The performance of low background ( BG ) liquid scintillation counter ( LSC ) was evaluated for practical purposes of non - clinical drug absorption , distribution , metabolism and excretion ( ADME ) studies .", "entity": [], "task": "NER"}
{"text": "The measurement conditions for the radioactivity for low BG LSC were investigated and metabolite profiling in rat plasma after single oral administration of ( 14 ) C - labeled compounds was performed .", "entity": [{"entity": "( 14 ) C", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "Metabolite profiling was also conducted using conventional LSC and accelerator mass spectrometer ( AMS ) , and the performances of these measuring instruments were compared .", "entity": [], "task": "NER"}
{"text": "2 . The established measurement conditions showed good linearity of the calibration curve over the concentration range from 3 to 300 dpm / vial .", "entity": [], "task": "NER"}
{"text": "Metabolite profiling using low BG LSC for the plasma samples diluted to 5 - 55 times was comparable to that using conventional LSC for the undiluted plasma samples .", "entity": [], "task": "NER"}
{"text": "Meanwhile , metabolite profiling using AMS for the plasma samples diluted to 250 - 2000 times was comparable to that using conventional LSC .", "entity": [], "task": "NER"}
{"text": "3 . These results suggest that the application of low BG LSC is one of the useful tools for non - clinical ADME studies and that it is possible to select conventional LSC , low BG LSC or AMS for radioactivity measurement by considering the specific radioactivity of the compounds and the predicted concentrations of radioactivity in biological samples in ADME studies .", "entity": [], "task": "NER"}
{"text": "The effects of kisspeptin in human reproductive function - therapeutic implications .", "entity": [], "task": "NER"}
{"text": "Kisspeptin is a 54 - amino acid peptide which is encoded by the KiSS - 1 gene and activates the G protein - coupled receptor GPR54 .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "Evidence suggests that this system is a key regulator of mammalian and human reproduction .", "entity": [], "task": "NER"}
{"text": "Animal studies have shown that GPR54 - deficient mice have abnormal sexual development .", "entity": [], "task": "NER"}
{"text": "Central and peripheral administration of kisspeptin stimulates the hypothalamic - pituitary - gonadal ( HPG ) axis whilst pre - administration of a gonadotrophin releasing hormone ( GnRH ) antagonist abolishes this effect .", "entity": [{"entity": "gonadotrophin releasing hormone", "entity_type": "Chemical", "pos": [148, 179]}, {"entity": "GnRH", "entity_type": "Chemical", "pos": [182, 186]}], "task": "NER"}
{"text": "In humans , inactivating GPR54 mutations cause normosmic hypogonadotrophic hypogonadism whilst activation of GPR54 signalling is associated with premature puberty .", "entity": [], "task": "NER"}
{"text": "In healthy human volunteers , the acute intravenous administration of kisspeptin potently increases plasma luteinising hormone ( LH ) levels and significantly increases plasma follicle stimulating hormone ( FSH ) and testosterone without side effects in both males and in females particularly in the preovulatatory phase of the menstrual cycle .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [217, 229]}], "task": "NER"}
{"text": "In infertility due to hypothalamic amenorrhoea acute administration of kisspeptin results in stimulation of reproductive hormones .", "entity": [], "task": "NER"}
{"text": "The kisspeptin / GPR54 system therefore appears to play an important role in the regulation of reproduction in humans .", "entity": [], "task": "NER"}
{"text": "Hence kisspeptin has potential as a novel tool for the manipulation of the HPG axis and treatment of infertility in humans .", "entity": [], "task": "NER"}
{"text": "This review discusses the evidence highlighting kisspeptin ' s key role in human reproduction .", "entity": [], "task": "NER"}
{"text": "Construction and Characterization of Molecular Nonwoven Fabrics Consisting of Cross - Linked Poly ( gamma - methyl - l - glutamate ) .", "entity": [{"entity": "Poly ( gamma - methyl - l - glutamate )", "entity_type": "Chemical", "pos": [93, 132]}], "task": "NER"}
{"text": "Molecular nonwoven fabrics in the form of ultrathin layer - by - layer ( LbL ) helical polymer films with covalent cross - linking were assembled on substrates by an alternate ester - amide exchange reaction between poly ( gamma - methyl l - glutamate ) ( PMLG ) and cross - linking agent ethylene diamine or 4 , 4 ' - diamino azobenzene .", "entity": [{"entity": "ester", "entity_type": "Chemical", "pos": [176, 181]}, {"entity": "amide", "entity_type": "Chemical", "pos": [184, 189]}, {"entity": "poly ( gamma - methyl l - glutamate )", "entity_type": "Chemical", "pos": [216, 253]}, {"entity": "PMLG", "entity_type": "Chemical", "pos": [256, 260]}, {"entity": "ethylene diamine", "entity_type": "Chemical", "pos": [289, 305]}, {"entity": "4 , 4 ' - diamino azobenzene", "entity_type": "Chemical", "pos": [309, 337]}], "task": "NER"}
{"text": "The regular growth of helical monolayers without excessive adsorption and the formation of amide bonds were confirmed by ultraviolet - visible ( UV - vis ) spectrophotometry , quartz crystal microbalance ( QCM ) , ellipsometry , and infrared reflection - absorption spectroscopy ( IR - RAS ) measurements .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [91, 96]}, {"entity": "quartz", "entity_type": "Chemical", "pos": [176, 182]}], "task": "NER"}
{"text": "Nanostructures with high uniformity and ultrathin films with few defects formed by helical rod segments of PMLG were characterized by atomic force microscopy ( AFM ) and Kelvin probe force microscopy ( KFM ) .", "entity": [{"entity": "PMLG", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "Dating an impressive Neotropical radiation : Molecular time estimates for the Sigmodontinae ( Rodentia ) provide insights into its historical biogeography .", "entity": [], "task": "NER"}
{"text": "With about 400 living species and 82 genera , rodents of the subfamily Sigmodontinae comprise one of the most diverse and more broadly distributed Neotropical mammalian clades .", "entity": [], "task": "NER"}
{"text": "There has been much debate on the origin of the lineage or the lineages of sigmodontines that entered South America , the timing of entrance and different aspects of further diversification within South America .", "entity": [], "task": "NER"}
{"text": "The ages of divergence of the main lineages and the crown age of the subfamily were estimated by using sequences of the interphotoreceptor retinoid binding protein and cytochrome b genes for a dense sigmodontine and muroid sampling .", "entity": [{"entity": "retinoid", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "Bayesian inference using three fossil calibration points and a relaxed molecular clock estimated a middle Miocene origin for Sigmodontinae ( ~ 12Ma ) , with most tribes diversifying throughout the Late Miocene ( 6 . 9 - 9 . 4Ma ) .", "entity": [], "task": "NER"}
{"text": "These estimates together results of analyses of ancestral area reconstructions suggest a distribution for the most recent common ancestor of Sigmodontinae in Central - South America and a South American distribution for the most recent common ancestor of Oryzomyalia .", "entity": [], "task": "NER"}
{"text": "Fragile X syndrome : from targets to treatments .", "entity": [], "task": "NER"}
{"text": "Fragile X syndrome ( FXS ) is one of the most prevalent and well - studied monogenetic causes of intellectual disability and autism and , although rare , its high penetrance makes it a desirable model for the study of neurodevelopmental disorders more generally .", "entity": [], "task": "NER"}
{"text": "Indeed recent studies suggest that there is functional convergence of a number of genes that are implicated in intellectual disability and autism indicating that an understanding of the cellular and biochemical dysfunction that occurs in monogenic forms of these disorders are likely to reveal common targets for therapeutic intervention .", "entity": [], "task": "NER"}
{"text": "Fundamental research into FXS has provided a wealth of information about how the loss of function of the fragile X mental retardation protein results in biochemical , anatomical and physiological dysfunction leading to the discovery of interventions that correct many of the core pathological phenotypes associated with animal models of FXS .", "entity": [], "task": "NER"}
{"text": "Most promisingly such strategies have led to development of drugs that are now in clinical trials .", "entity": [], "task": "NER"}
{"text": "This review highlights how progress in understanding disorders such as FXS has led to a new era in which targeted molecular treatment towards neurodevelopmental disorders is becoming a reality .", "entity": [], "task": "NER"}
{"text": "Genipin stimulates glucose transport in C2C12 myotubes via an IRS - 1 and calcium - dependent mechanism .", "entity": [{"entity": "Genipin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "Genipin , a compound derived from Gardenia jasminoides Ellis fruits , has been used over the years in traditional Chinese medicine to treat symptoms of type 2 diabetes .", "entity": [{"entity": "Genipin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "However , the molecular basis for its antidiabetic effect has not been fully revealed .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated the effects of genipin on glucose uptake and signaling pathways in C ( 2 ) C ( 12 ) myotubes .", "entity": [{"entity": "genipin", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "Our study demonstrates that genipin stimulated glucose uptake in a time - and dose - dependent manner .", "entity": [{"entity": "genipin", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [47, 54]}], "task": "NER"}
{"text": "The maximal effect was achieved at 2 h with a concentration of 10 mu M .", "entity": [], "task": "NER"}
{"text": "In myotubes , genipin promoted glucose transporter 4 ( GLUT4 ) translocation to the cell surface , which was observed by analyzing their distribution in subcellular membrane fraction , and increased the phosphorylation of insulin receptor substrate - 1 ( IRS - 1 ) , AKT , and GSK3 beta .", "entity": [{"entity": "genipin", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [31, 38]}], "task": "NER"}
{"text": "Meanwhile , genipin increased ATP levels , closed K ( ATP ) channels , and then increased the concentration of calcium in the cytoplasm in C ( 2 ) C ( 12 ) myotubes .", "entity": [{"entity": "genipin", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "K", "entity_type": "Chemical", "pos": [50, 51]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [111, 118]}], "task": "NER"}
{"text": "Genipin - stimulated glucose uptake could be blocked by both the PI3 - K inhibitor wortmannin and calcium chelator EGTA .", "entity": [{"entity": "Genipin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [21, 28]}, {"entity": "wortmannin", "entity_type": "Chemical", "pos": [83, 93]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [98, 105]}, {"entity": "EGTA", "entity_type": "Chemical", "pos": [115, 119]}], "task": "NER"}
{"text": "Moreover , genipin increases the level of reactive oxygen species and ATP in C ( 2 ) C ( 12 ) myotubes .", "entity": [{"entity": "genipin", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "These results suggest that genipin activates IRS - 1 , PI3 - K , and downstream signaling pathway and increases concentrations of calcium , resulting in GLUT4 translocation and glucose uptake increase in C ( 2 ) C ( 12 ) myotubes .", "entity": [{"entity": "genipin", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [177, 184]}], "task": "NER"}
{"text": "Electrophoresis of randomly and vertically embedded graphene nanosheets in activated carbon film as a counter electrode for dye - sensitized solar cells .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [85, 91]}], "task": "NER"}
{"text": "A new approach has been developed to randomly and vertically embed the graphene nanosheets ( GNs ) in the activated carbon ( AC ) film in an applied electric field .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [116, 122]}], "task": "NER"}
{"text": "The activated carbon ( AC ) nanoparticles in suspension during electrophoresis play an important role in supporting the GNs perpendicular to the FTO ( fluorine - doped tin oxide ) glass .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "FTO", "entity_type": "Chemical", "pos": [145, 148]}, {"entity": "fluorine - doped tin oxide", "entity_type": "Chemical", "pos": [151, 177]}], "task": "NER"}
{"text": "Insufficient amount of AC nanoparticles might result in a deposition of GNs parallel to the FTO glass , leading to incomplete utilization of the surface area accessible to electrolyte ions .", "entity": [{"entity": "FTO", "entity_type": "Chemical", "pos": [92, 95]}], "task": "NER"}
{"text": "An AC cathode with randomly and vertically embedded GNs facilitated electrolyte penetration and electron conduction .", "entity": [], "task": "NER"}
{"text": "The photoelectron conversion efficiency of the cell was increased to 7 . 50 % by employing the AC cathode with randomly and vertically embedded GNs .", "entity": [], "task": "NER"}
{"text": "Heterogeneous oxidation of a phosphocholine on synthetic sea salt by ozone at room temperature .", "entity": [{"entity": "phosphocholine", "entity_type": "Chemical", "pos": [29, 43]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [69, 74]}], "task": "NER"}
{"text": "The ozonolysis of 1 - palmitoyl - 2 - oleoyl - sn - glycero - 3 - phosphocholine ( POPC ) adsorbed on salt mixtures as models for sea - salt particles was studied in real time using diffuse reflection infrared Fourier transform spectrometry ( DRIFTS ) at room temperature with and without added water vapor .", "entity": [{"entity": "1 - palmitoyl - 2 - oleoyl - sn - glycero - 3 - phosphocholine", "entity_type": "Chemical", "pos": [18, 80]}, {"entity": "POPC", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "The salt substrates were a mixture of MgCl ( 2 ) . 6H ( 2 ) O with NaCl or a commercially available synthetic sea salt .", "entity": [{"entity": "MgCl ( 2 ) . 6H ( 2 ) O", "entity_type": "Chemical", "pos": [38, 61]}, {"entity": "NaCl", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "Ozone concentrations ranged from ( 0 . 25 to 3 . 9 ) x 10 ( 13 ) molecules cm ( - 3 ) ( 0 . 1 - 1 . 6 ppm ) .", "entity": [{"entity": "Ozone", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "The major products identified by FTIR and confirmed using matrix - assisted laser desorption / ionization ( MALDI ) mass spectrometry were the secondary ozonide ( SOZ ) and a phospholipid aldehyde and carboxylic acid formed by scission of the double bond .", "entity": [{"entity": "secondary ozonide", "entity_type": "Chemical", "pos": [143, 160]}, {"entity": "SOZ", "entity_type": "Chemical", "pos": [163, 166]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [188, 196]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [201, 216]}], "task": "NER"}
{"text": "The reaction probabilities for the two substrates were similar , gamma = ( 6 - 7 ) x 10 ( - 7 ) , with an estimated overall uncertainty of a factor of two .", "entity": [], "task": "NER"}
{"text": "The presence of water vapor decreased the yield of SOZ relative to the products formed by C [ double bond , length as m - dash ] C scission , but also increased the availability of the double bond for reaction , particularly on the less hygroscopic commercial sea - salt substrate .", "entity": [{"entity": "SOZ", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "C", "entity_type": "Chemical", "pos": [90, 91]}, {"entity": "C", "entity_type": "Chemical", "pos": [129, 130]}], "task": "NER"}
{"text": "Thus , water not only affects the mechanisms and products , but also the structure of the phospholipid on the salt in a manner that affects its reactivity .", "entity": [], "task": "NER"}
{"text": "The results of these studies suggest that the reactivity and products of oxidation of unsaturated phospholipids on sea - salt particles in air will be very sensitive to the nature and phase of the substrate , the amount of water present , and whether there is phase separation between the organics and the inorganic salt mixture .", "entity": [], "task": "NER"}
{"text": "Prediction of ( TiO2 ) x ( Cu2O ) y alloys for efficient photoelectrochemical water splitting .", "entity": [{"entity": "( TiO2 ) x ( Cu2O ) y", "entity_type": "Chemical", "pos": [14, 35]}], "task": "NER"}
{"text": "The formation of ( TiO ( 2 ) ) ( x ) ( Cu ( 2 ) O ) ( y ) solid - solutions is investigated using a global optimization evolutionary algorithm .", "entity": [{"entity": "( TiO ( 2 ) ) ( x ) ( Cu ( 2 ) O ) ( y )", "entity_type": "Chemical", "pos": [17, 57]}], "task": "NER"}
{"text": "First - principles calculations based on density functional theory are then used to gain insight into the electronic properties of these alloys .", "entity": [], "task": "NER"}
{"text": "We find that : ( i ) Ti and Cu in ( TiO ( 2 ) ) ( x ) ( Cu ( 2 ) O ) ( y ) alloys have similar local environments as in bulk TiO ( 2 ) and Cu ( 2 ) O except for ( TiO ( 2 ) ) ( Cu ( 2 ) O ) which has some trigonal - planar Cu ions .", "entity": [{"entity": "Ti", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [28, 30]}, {"entity": "( TiO ( 2 ) ) ( x ) ( Cu ( 2 ) O ) ( y )", "entity_type": "Chemical", "pos": [34, 74]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [125, 134]}, {"entity": "Cu ( 2 ) O", "entity_type": "Chemical", "pos": [139, 149]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [163, 172]}, {"entity": "Cu ( 2 ) O", "entity_type": "Chemical", "pos": [177, 187]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [223, 225]}], "task": "NER"}
{"text": "( ii ) The predicted optical band gaps are around 2 . 1 eV ( 590 nm ) , thus having much better performance in the absorption of visible light compared with both binary oxides .", "entity": [{"entity": "oxides", "entity_type": "Chemical", "pos": [169, 175]}], "task": "NER"}
{"text": "( iii ) ( TiO ( 2 ) ) ( 2 ) ( Cu ( 2 ) O ) has the lowest formation energy amongst all studied alloys and the positions of its band edges are found to be suitable for solar - driven water splitting applications .", "entity": [{"entity": "( TiO ( 2 ) ) ( 2 ) ( Cu ( 2 ) O )", "entity_type": "Chemical", "pos": [8, 42]}], "task": "NER"}
{"text": "pH tuning of DNA translocation time through organically functionalized nanopores .", "entity": [], "task": "NER"}
{"text": "Controlling DNA translocation speed is critically important for nanopore sequencing as free electrophoretic threading is far too rapid to resolve individual bases .", "entity": [], "task": "NER"}
{"text": "A number of promising strategies have been explored in recent years , largely driven by the demands of next - generation sequencing .", "entity": [], "task": "NER"}
{"text": "Engineering DNA - nanopore interactions ( known to dominate translocation dynamics ) with organic coatings is an attractive method as it does not require sample modification , processive enzymes , or complicated and expensive fabrication steps .", "entity": [], "task": "NER"}
{"text": "In this work , we show for the first time 4 - fold tuning of unfolded , single - file translocation time through small , amine - functionalized solid - state nanopores by varying the solution pH in situ .", "entity": [{"entity": "amine", "entity_type": "Chemical", "pos": [121, 126]}], "task": "NER"}
{"text": "Additionally , we develop a simple analytical model based on electrostatic interactions to explain this effect which will be a useful tool in designing future devices and experiments .", "entity": [], "task": "NER"}
{"text": "Visualization and virtual screening of the chemical universe database GDB - 17 .", "entity": [], "task": "NER"}
{"text": "The chemical universe database GDB - 17 contains 166 . 4 billion molecules of up to 17 atoms of C , N , O , S , and halogens obeying rules for chemical stability , synthetic feasibility , and medicinal chemistry .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [96, 97]}, {"entity": "N", "entity_type": "Chemical", "pos": [100, 101]}, {"entity": "O", "entity_type": "Chemical", "pos": [104, 105]}, {"entity": "S", "entity_type": "Chemical", "pos": [108, 109]}, {"entity": "halogens", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "GDB - 17 was analyzed using 42 integer value descriptors of molecular structure which we term \" Molecular Quantum Numbers \" ( MQN ) .", "entity": [], "task": "NER"}
{"text": "Principal component analysis and representation of the ( PC1 , PC2 ) - plane provided a graphical overview of the GDB - 17 chemical space .", "entity": [], "task": "NER"}
{"text": "Rapid ligand - based virtual screening ( LBVS ) of GDB - 17 using the city - block distance CBD ( MQN ) as a similarity search measure was enabled by a hashed MQN - fingerprint .", "entity": [], "task": "NER"}
{"text": "LBVS of the entire GDB - 17 and of selected subsets identified shape similar , scaffold hopping analogs ( ROCS > 1 . 6 and T ( SF ) < 0 . 5 ) of 15 drugs .", "entity": [], "task": "NER"}
{"text": "Over 97 % of these analogs occurred within CBD ( MQN ) <= 12 from each drug , a constraint which might help focus advanced virtual screening .", "entity": [], "task": "NER"}
{"text": "An MQN - searchable 50 million subset of GDB - 17 is publicly available at www . gdb . unibe . ch .", "entity": [], "task": "NER"}
{"text": "Tailorable cell culture platforms from enzymatically cross - linked multifunctional poly ( ethylene glycol ) - based hydrogels .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [84, 108]}], "task": "NER"}
{"text": "As stem - cell - based therapies rapidly advance toward clinical applications , there is a need for cheap , easily manufactured , injectable gels that can be tailored to carry stem cells and impart function to such cells .", "entity": [], "task": "NER"}
{"text": "Herein we describe a process for making hydrogels composed of hydroxyphenyl propionic acid ( HPA ) conjugated , branched poly ( ethylene glycol ) ( PEG ) via an enzyme mediated , oxidative cross - linking method .", "entity": [{"entity": "hydroxyphenyl propionic acid", "entity_type": "Chemical", "pos": [62, 90]}, {"entity": "HPA", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [121, 145]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "Functionalization of the branched PEG with HPA at varying degrees of substitution was confirmed via attenuated total reflectance Fourier transform infrared spectroscopy ( ATR - FTIR ) and ( 1 ) H NMR .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "HPA", "entity_type": "Chemical", "pos": [43, 46]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [188, 195]}], "task": "NER"}
{"text": "The versatility of this hydrogel system was exemplified through variations in the degree of HPA substitution , polymer concentration , and the concentration of cross - linking reagents ( horseradish peroxidase and H ( 2 ) O ( 2 ) ) , which resulted in a range of mechanical properties and gelation kinetics for these gels .", "entity": [{"entity": "HPA", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [214, 229]}], "task": "NER"}
{"text": "Cross - linking of the PEG - HPA conjugate with a recombinantly produced Fibronectin fragment ( Type III domains 7 - 10 ) encouraged attachment and spreading of human mesenchymal stem cells ( hMSCs ) when assessed in both two - dimensional and three - dimensional formats .", "entity": [{"entity": "PEG - HPA", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "Interestingly , when encapsulated in both nonfunctionalized and functionalized cross - linked PEG - HPA gels , MSCs showed good viability over all time periods assessed .", "entity": [{"entity": "PEG - HPA", "entity_type": "Chemical", "pos": [94, 103]}], "task": "NER"}
{"text": "With tunable gelation kinetics and mechanical properties , these hydrogels provide a flexible in vitro cell culture platform that will likely have significant utility in tissue engineering as an injectable delivery platform for cells to sites of tissue damage .", "entity": [], "task": "NER"}
{"text": "Discovery of a new series of [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] quinoxalines as dual phosphodiesterase 2 / phosphodiesterase 10 ( PDE2 / PDE10 ) inhibitors .", "entity": [{"entity": "[ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] quinoxalines", "entity_type": "Chemical", "pos": [29, 78]}], "task": "NER"}
{"text": "The synthesis , preliminary evaluation and structure - activity relationship ( SAR ) of a series of 1 - aryl - 4 - methyl [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] quinoxalines as dual phosphodiesterase 2 / phosphodiesterase 10 ( PDE2 / PDE10 ) inhibitors are described .", "entity": [{"entity": "1 - aryl - 4 - methyl [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] quinoxalines", "entity_type": "Chemical", "pos": [100, 171]}], "task": "NER"}
{"text": "From this investigation compound 31 was identified , showing good combined potency , acceptable brain uptake and high selectivity for both PDE2 and PDE10 enzymes .", "entity": [], "task": "NER"}
{"text": "Compound 31 was subjected to a microdosing experiment in rats , showing preferential distribution in brain areas where both PDE2 and PDE10 are highly expressed .", "entity": [], "task": "NER"}
{"text": "These promising results may drive the further development of highly potent combined PDE2 / PDE10 inhibitors , or even of selective inhibitors of PDE2 and / or PDE10 .", "entity": [], "task": "NER"}
{"text": "Discovering gene - environment interactions in Glioblastoma through a comprehensive data integration bioinformatics method .", "entity": [], "task": "NER"}
{"text": "Glioblastoma multiforme ( GBM ) is the most common and aggressive type of human brain tumor .", "entity": [], "task": "NER"}
{"text": "Although considerable efforts to delineate the underlying pathophysiological pathways have been made during the last decades , only very limited progress on treatment have been achieved because molecular pathways that drive the aggressive nature of GBM are largely unknown .", "entity": [], "task": "NER"}
{"text": "Recent studies have emphasized the importance of environmental factors and the role of gene - environment interactions ( GEI ) in the development of GBM .", "entity": [], "task": "NER"}
{"text": "Factors such as small sample sizes and study costs have limited the conduct of GEI studies in brain tumors however .", "entity": [], "task": "NER"}
{"text": "Additionally , advances in high - throughput microarrays have produced a wealth of information concerning molecular biology of glioma .", "entity": [], "task": "NER"}
{"text": "In particular , microarrays have been used to obtain genetic and epigenetic changes between normal non - tumor tissue and glioma tissue .", "entity": [], "task": "NER"}
{"text": "Due to the relative rarity of gliomas , microarray data for these tumors is often the product of small studies , and thus pooling this data becomes desirable .", "entity": [], "task": "NER"}
{"text": "To address the challenge of small sample sizes and GEI study difficulties , we introduce a comprehensive bioinformatics method using genetic variations ( copy number variations and small - scale variations ) and environmental data integration that links with Glioblastoma ( GEG ) to identify : ( 1 ) genes that interact with chemicals and have genetic variants linked to the development of GBM , ( 2 ) important pathways that may be influenced by environmental exposures ( or endogenous chemicals ) , and ( 3 ) genes with variants in GBM that have been understudied in relation to GBM development .", "entity": [], "task": "NER"}
{"text": "The first step in our GEG method identified genes responsive to environmental exposures using the Environmental Genome Project , Comparative Toxicology , and Seattle SNPs databases .", "entity": [], "task": "NER"}
{"text": "These environmentally responsive genes were then compared to a curated list of genes containing copy number variation and / or mutations in GBM .", "entity": [], "task": "NER"}
{"text": "This comparison produced a list of genes responsive to the environment and important to GBM that was then further analyzed using gene networking tools such as RSpider , Cytoscape , and DAVID .", "entity": [], "task": "NER"}
{"text": "Using this GEG bioinformatics method we were able to identify 173 genes with the potential to be involved in GEI that may be important to the development of GBM .", "entity": [], "task": "NER"}
{"text": "Sixty five of these environmentally responsive genes have not been reported as important to GBM development , despite several of them having substantial potential for response to chemicals and subsequent disease related actions .", "entity": [], "task": "NER"}
{"text": "The main biological functions of these 173 genes include signaling by Nerve Growth Factor , DNA Repair , Integrin Cell Surface Interactions , Biological Oxidations , Apoptosis , Synaptic Transmission , Cell Cycle Checkpoints , and Arachidonic Acid Metabolism .", "entity": [{"entity": "Arachidonic Acid", "entity_type": "Chemical", "pos": [231, 247]}], "task": "NER"}
{"text": "Importantly , some of these functions have been implicated in the development of several cancers , including glioma .", "entity": [], "task": "NER"}
{"text": "In summary , our GEG bioinformatics approach revealed potential gene - environment interactions , and generated new data for hypothesis generation , in GBM .", "entity": [], "task": "NER"}
{"text": "Central nervous system damage due to acute paraquat poisoning : an experimental study with rat model .", "entity": [{"entity": "paraquat", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "Paraquat ( PQ ) is a common herbicide and PQ poisoning is a major medical problem in Asia .", "entity": [{"entity": "Paraquat", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "However , few studies have focused on the acute neurotoxic changes caused by PQ .", "entity": [], "task": "NER"}
{"text": "Here we report the acute neurotoxicological findings of rats treated with lethal dose of PQ .", "entity": [], "task": "NER"}
{"text": "In substantia nigra ( SN ) and striatum we found obvious microglia ( labeled by Iba - 1 ) activation within one week .", "entity": [], "task": "NER"}
{"text": "In SN and hippocampus , we detected increased oxidative stress in the neurons based on NeuN / 8 - OHdG immunofluorescence double labeling and laser cofocal microscopy .", "entity": [{"entity": "8 - OHdG", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "Moreover , we provided ultrastructural evidences of astrocyte edema and neurons apoptosis in rat brain by electron microscopy .", "entity": [], "task": "NER"}
{"text": "Further studies will be needed with non - lethal dose of PQ to confirm these results and demonstrate the direct CNS toxicity of PQ .", "entity": [], "task": "NER"}
{"text": "The uptake and distribution of selenium in three aquatic plants grown in Se ( IV ) solution .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "Se ( IV )", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "The uptake of Se ( IV ) by Myriophyllum spicatum , Ceratophyllum demersum and Potamogeton perfoliatus , and the effects of Se ( IV ) on their physiological and biochemical characteristics were studied .", "entity": [{"entity": "Se ( IV )", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "Se ( IV )", "entity_type": "Chemical", "pos": [123, 132]}], "task": "NER"}
{"text": "Plants were cultivated outdoors under semi - controlled conditions in water solution containing Na selenite ( 20 mu g Se L ( - 1 ) and 10 mg Se L ( - 1 ) ) .", "entity": [{"entity": "Na selenite", "entity_type": "Chemical", "pos": [96, 107]}, {"entity": "Se", "entity_type": "Chemical", "pos": [118, 120]}, {"entity": "Se", "entity_type": "Chemical", "pos": [141, 143]}], "task": "NER"}
{"text": "The higher concentration of Se lowered the photochemical efficiency of PSII in all species studied , while the lower concentration had no effect on any species .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [28, 30]}], "task": "NER"}
{"text": "The higher concentration of Se lowered respiratory potential in M . spicatum .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [28, 30]}], "task": "NER"}
{"text": "The response of M . spicatum and C . demersum to Se ( IV ) regarding chlorophylls was variable , however in the majority of cases , there was a trend of increasing the amount of chlorophylls , while in P . perfoliatus the amount of chlorophyll a decreased .", "entity": [{"entity": "Se ( IV )", "entity_type": "Chemical", "pos": [49, 58]}, {"entity": "chlorophylls", "entity_type": "Chemical", "pos": [69, 81]}, {"entity": "chlorophylls", "entity_type": "Chemical", "pos": [178, 190]}, {"entity": "chlorophyll a", "entity_type": "Chemical", "pos": [232, 245]}], "task": "NER"}
{"text": "The concentration of Se in plants cultured in 10 mg Se ( IV ) L ( - 1 ) ranged from 436 to 839 mu g Se g ( - 1 ) DM in M . spicatum , 319 to 988 mu g Se g ( - 1 ) DM in C . demersum and 310 to 661 mu g Se g ( - 1 ) DM in P . perfoliatus .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Se ( IV )", "entity_type": "Chemical", "pos": [52, 61]}, {"entity": "Se", "entity_type": "Chemical", "pos": [100, 102]}, {"entity": "Se", "entity_type": "Chemical", "pos": [150, 152]}, {"entity": "Se", "entity_type": "Chemical", "pos": [202, 204]}], "task": "NER"}
{"text": "The amount of soluble Se compounds in enzyme extracts of high Se treatment was 27 % in M . spicatum , 41 % in C . demersum and 35 % in P . perfoliatus .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "Se", "entity_type": "Chemical", "pos": [62, 64]}], "task": "NER"}
{"text": "Se compounds were determined using HPLC - ICP - MS .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "It was observed that the applied Se ( IV ) was mainly transformed to insoluble Se .", "entity": [{"entity": "Se ( IV )", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "Se", "entity_type": "Chemical", "pos": [79, 81]}], "task": "NER"}
{"text": "Qalibra : a general model for food risk - benefit assessment that quantifies variability and uncertainty .", "entity": [], "task": "NER"}
{"text": "The EU project BRAFO proposed a framework for risk - benefit assessment of foods , or changes in diet , that present both potential risks and potential benefits to consumers ( Hoekstra et al . , 2012a ) .", "entity": [], "task": "NER"}
{"text": "In higher tiers of the BRAFO framework , risks and benefits are integrated quantitatively to estimate net health impact measured in DALYs or QALYs ( disability - or quality - adjusted life years ) .", "entity": [], "task": "NER"}
{"text": "This paper describes a general model that was developed by a second EU project , Qalibra , to assist users in conducting these assessments .", "entity": [], "task": "NER"}
{"text": "Its flexible design makes it applicable to a wide range of dietary questions involving different nutrients , contaminants and health effects .", "entity": [], "task": "NER"}
{"text": "Account can be taken of variation between consumers in their diets and also other characteristics relevant to the estimation of risk and benefit , such as body weight , gender and age .", "entity": [], "task": "NER"}
{"text": "Uncertainty in any input parameter may be quantified probabilistically , using probability distributions , or deterministically by repeating the assessment with alternative assumptions .", "entity": [], "task": "NER"}
{"text": "Uncertainties that are not quantified should be evaluated qualitatively .", "entity": [], "task": "NER"}
{"text": "Outputs produced by the model are illustrated using results from a simple assessment of fish consumption .", "entity": [], "task": "NER"}
{"text": "More detailed case studies on oily fish and phytosterols are presented in companion papers .", "entity": [{"entity": "phytosterols", "entity_type": "Chemical", "pos": [44, 56]}], "task": "NER"}
{"text": "The model can be accessed as web - based software at www . qalibra . eu .", "entity": [], "task": "NER"}
{"text": "Shikonin induces programmed necrosis - like cell death through the formation of receptor interacting protein 1 and 3 complex .", "entity": [{"entity": "Shikonin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "An alternative cell demise programmed necrosis has also been proposed when apoptotic machinery is impaired or blocked during tumor necrosis factor alpha ( TNF alpha ) stimulation .", "entity": [], "task": "NER"}
{"text": "Shikonin ( SKN ) , an herbal extract from the Chinese plant , has been reported to induce either apoptosis or necrosis depending on cell types or its concentrations .", "entity": [{"entity": "Shikonin", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "SKN", "entity_type": "Chemical", "pos": [11, 14]}], "task": "NER"}
{"text": "In this presentation , SKN caused cell death of NIH3T3 in a dose - dependent manner .", "entity": [{"entity": "SKN", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "Intriguingly , SKN - mediated cell death was in part protected by necrostatin - 1 ( Nec - 1 ) , a specific inhibitor of programmed necrosis , but not zVAD a pan - caspase inhibitor .", "entity": [{"entity": "SKN", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "necrostatin - 1", "entity_type": "Chemical", "pos": [66, 81]}, {"entity": "Nec - 1", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "SKN directly mediated cell death via receptor interacting protein1 and 3 ( RIP1 - RIP3 ) complex formation , which is required for TNF alpha - mediated programmed necrosis .", "entity": [{"entity": "SKN", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Additionally , SKN - caused cell death was reversed by a reactive oxygen species ( ROS ) scavenger N - acetylcysteine ( NAC ) whereas TNF alpha - mediated necrosis was successfully protected by butylated hydroxyanisole ( BHA ) , implying that ROS may be differentially derived from death inducing agents .", "entity": [{"entity": "SKN", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [99, 117]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [120, 123]}, {"entity": "butylated hydroxyanisole", "entity_type": "Chemical", "pos": [194, 218]}, {"entity": "BHA", "entity_type": "Chemical", "pos": [221, 224]}], "task": "NER"}
{"text": "Concurrently with the protective effect of the ROS scavenger or Nec - 1 on TNF alpha or SKN , the RIP1 - RIP3 complex was significantly affected in the presence of those agents .", "entity": [{"entity": "Nec - 1", "entity_type": "Chemical", "pos": [64, 71]}], "task": "NER"}
{"text": "Here , it is highlighted that SKN as well as TNF alpha can directly mediate cell death via a pronecrotic complex , but ROS were generated via different routes depending on cell death - inducing agents .", "entity": [{"entity": "SKN", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster .", "entity": [], "task": "NER"}
{"text": "Nucleoside reverse - transcriptase inhibitor ( NRTI ) drugs are a major component of highly - active antiretroviral therapy ( HAART ) .", "entity": [{"entity": "Nucleoside", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count , thereby showing clear clinical benefits .", "entity": [], "task": "NER"}
{"text": "Therefore , the secondary effects caused by the combination of two NRTIs , mainly those related to amplification of genotoxic effects , due to increased risk of DNA damage caused by these drugs , should be carefully examined .", "entity": [], "task": "NER"}
{"text": "We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT + ddI , AZT + 3TC and AZT + d4T .", "entity": [{"entity": "AZT", "entity_type": "Chemical", "pos": [164, 167]}, {"entity": "ddI", "entity_type": "Chemical", "pos": [170, 173]}, {"entity": "AZT", "entity_type": "Chemical", "pos": [176, 179]}, {"entity": "3TC", "entity_type": "Chemical", "pos": [182, 185]}, {"entity": "AZT", "entity_type": "Chemical", "pos": [190, 193]}, {"entity": "d4T", "entity_type": "Chemical", "pos": [196, 199]}], "task": "NER"}
{"text": "Our results showed that all combinations increased the frequencies of induction of mutant spots .", "entity": [], "task": "NER"}
{"text": "The combinations AZT + ddI and AZT + 3TC were shown to induce recombination rates ranging from 86 . 38 % to 98 . 36 % while AZT + d4T showed a large discrepancy between recombination and mutation percentages .", "entity": [{"entity": "AZT", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "ddI", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "AZT", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "3TC", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "AZT", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "d4T", "entity_type": "Chemical", "pos": [130, 133]}], "task": "NER"}
{"text": "The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT .", "entity": [{"entity": "3TC", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "d4T", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "ddI", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "AZT", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "New enzymatic assay for the AKR1C enzymes .", "entity": [], "task": "NER"}
{"text": "The imbalance in expression of the human aldo - keto reductases AKR1C1 - AKR1C3 is related to different hormone dependent and independent cancers and some other diseases .", "entity": [], "task": "NER"}
{"text": "The AKR1C1 - 3 enzymes thus represent emerging targets for the development of new drugs .", "entity": [], "task": "NER"}
{"text": "Currently , various enzymatic assays are used in the search for AKR1C inhibitors , and consequently the results of different research groups are not necessarily comparable .", "entity": [], "task": "NER"}
{"text": "During our recent search for AKR1C inhibitors , we found a cyclopentanol derivative ( 2 - ( 4 - chlorobenzylidene ) cyclopentanol , CBCP - ol ) and its respective cyclopentanone counterpart ( 2 - ( 4 - chlorobenzylidene ) cyclopentanone , CBCP - one ) that acted as AKR1C substrates .", "entity": [{"entity": "cyclopentanol", "entity_type": "Chemical", "pos": [59, 72]}, {"entity": "2 - ( 4 - chlorobenzylidene ) cyclopentanol", "entity_type": "Chemical", "pos": [86, 129]}, {"entity": "CBCP - ol", "entity_type": "Chemical", "pos": [132, 141]}, {"entity": "cyclopentanone", "entity_type": "Chemical", "pos": [163, 177]}, {"entity": "2 - ( 4 - chlorobenzylidene ) cyclopentanone", "entity_type": "Chemical", "pos": [192, 236]}, {"entity": "CBCP - one", "entity_type": "Chemical", "pos": [239, 249]}], "task": "NER"}
{"text": "We determined the kinetic parameters KM , kcat and kcat / KM for oxidation of CBCP - ol and reduction of CBCP - one by AKR1C enzymes in the presence of NAD ( + ) / NADP ( + ) and NADH / NADPH , respectively .", "entity": [{"entity": "CBCP - ol", "entity_type": "Chemical", "pos": [78, 87]}, {"entity": "CBCP - one", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "NAD ( + )", "entity_type": "Chemical", "pos": [152, 161]}, {"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [164, 174]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [179, 183]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [186, 191]}], "task": "NER"}
{"text": "The catalytic efficiencies for the oxidation of CBCP - ol in the presence of NAD ( + ) or NADP ( + ) were in general higher when compared to the catalytic efficiencies for reduction of CBCP - one in the presence of NADH or NADPH .", "entity": [{"entity": "CBCP - ol", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "NAD ( + )", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [90, 100]}, {"entity": "CBCP - one", "entity_type": "Chemical", "pos": [185, 195]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [215, 219]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [223, 228]}], "task": "NER"}
{"text": "When NADPH was used , as compared to NADH , the reductions of CBCP - one by AKR1C1 , AKR1C2 and AKR1C3 were 14 - , 51 - and 31 - fold more efficient , respectively .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [37, 41]}, {"entity": "CBCP - one", "entity_type": "Chemical", "pos": [62, 72]}], "task": "NER"}
{"text": "When comparing to oxidations of the well - known artificial substrates , 1 - acenaphthenol and S - tetralol , we observed similar catalytic efficiencies as for CBCP - ol oxidation with NAD ( + ) and NADP ( + ) .", "entity": [{"entity": "1 - acenaphthenol", "entity_type": "Chemical", "pos": [73, 90]}, {"entity": "S - tetralol", "entity_type": "Chemical", "pos": [95, 107]}, {"entity": "CBCP - ol", "entity_type": "Chemical", "pos": [160, 169]}, {"entity": "NAD ( + )", "entity_type": "Chemical", "pos": [185, 194]}, {"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [199, 209]}], "task": "NER"}
{"text": "The comparison of CBCP - one reduction with NADPH to reductions of physiological substrates revealed in general higher efficiencies , except for reduction of 9 - cis - retinaldehyde by AKR1C3 .", "entity": [{"entity": "CBCP - one", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [44, 49]}, {"entity": "9 - cis - retinaldehyde", "entity_type": "Chemical", "pos": [158, 181]}], "task": "NER"}
{"text": "This NADPH - dependent reduction of CBCP - one was then used to re - evaluate inhibitory potencies of the known inhibitors of the target AKR1C3 and the anti - target AKR1C2 , medroxyprogesterone acetate and ursodeoxycholic acid , respectively , showing Ki constants similar to the reported values .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "CBCP - one", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "medroxyprogesterone acetate", "entity_type": "Chemical", "pos": [175, 202]}, {"entity": "ursodeoxycholic acid", "entity_type": "Chemical", "pos": [207, 227]}], "task": "NER"}
{"text": "Our data thus confirm that the new enzymatic assays with two cyclopentane substrates CBP - ol and CBP - one , and especially reduction of CBCP - one with NADPH , are appropriate for the evaluation of AKR1C inhibitors .", "entity": [{"entity": "cyclopentane", "entity_type": "Chemical", "pos": [61, 73]}, {"entity": "CBP - ol", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "CBP - one", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "CBCP - one", "entity_type": "Chemical", "pos": [138, 148]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [154, 159]}], "task": "NER"}
{"text": "Effects of p53 knockout on ochratoxin A - induced genotoxicity in p53 - deficient gpt delta mice .", "entity": [{"entity": "ochratoxin A", "entity_type": "Chemical", "pos": [27, 39]}], "task": "NER"}
{"text": "Ochratoxin A ( OTA ) is a mycotoxin produced by fungal species and is carcinogenic targeting the S3 segment of the renal proximal tubules in rodents .", "entity": [{"entity": "Ochratoxin A", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [15, 18]}], "task": "NER"}
{"text": "We previously reported that exposure of gpt delta rats to OTA induced both mutations in the red / gam gene ( Spi ( - ) ) , suggesting large deletion mutations , and fluctuations in genes transcribed by p53 in the kidneys , which were associated with DNA double - strand break ( DSB ) repair , particularly homologous recombination ( HR ) repair .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "In the present study , to investigate the effects of p53 knockout on OTA - induced mutagenicity , apoptosis , and karyomegaly in renal tubular cells , p53 - proficient and p53 - deficient gpt delta mice were given 1 and 5mg / kg of OTA for 4 weeks .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [232, 235]}], "task": "NER"}
{"text": "Significant increases in Spi ( - ) mutant frequencies ( MFs ) were observed in the kidneys of p53 - deficient gpt delta mice given 5 mg / kg of OTA , but not in the kidneys of p53 - proficient gpt delta mice given the same dose .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "There were no changes in gpt MFs in both genotypes of mice treated with OTA .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [72, 75]}], "task": "NER"}
{"text": "Western blotting analysis demonstrated that p53 protein levels in the kidneys of p53 - proficient mice given OTA were significantly increased compared with the control .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [109, 112]}], "task": "NER"}
{"text": "Incidences of apoptosis and karyomegaly in not only the outer stripe of outer medulla but also the cortex were significantly higher in p53 - deficient at 5mg / kg than in p53 - proficient gpt delta mice at same dose , which had no change in the cortex , the inner stripe of outer stripe , and the inner medulla .", "entity": [], "task": "NER"}
{"text": "Given that p53 regulates HR repair in DSBs , these results suggest that OTA may promote large deletion mutations in the process of HR repair for DSBs .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [72, 75]}], "task": "NER"}
{"text": "Additionally , the lower incidence of karyomegaly and apoptosis found in the p53 - proficient gpt delta mice suggests that these phenomena may arise from OTA - induced DNA damage .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [154, 157]}], "task": "NER"}
{"text": "Sex hormones and mental rotation : an intensive longitudinal investigation .", "entity": [], "task": "NER"}
{"text": "The present study used an intensive longitudinal design to examine whether mental rotation performance varies according to a monthly cycle in both males and females and whether these variations are related to variations in progesterone , estradiol , and testosterone levels .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [223, 235]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [238, 247]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [254, 266]}], "task": "NER"}
{"text": "We collected reaction time and accuracy data for 10 males and seven females each workday over eight weeks using 136 pairs of mental rotation stimuli / day , and measured sexual hormones concentrations in the saliva twice a week .", "entity": [], "task": "NER"}
{"text": "A mixed linear model statistical analysis revealed that all females and seven males showed significant cycle effects in mental rotation performance .", "entity": [], "task": "NER"}
{"text": "The female cycle showed an amplitude that was twice as large compared with the amplitude found in males .", "entity": [], "task": "NER"}
{"text": "For males and females , estradiol and testosterone were significantly linearly and quadratically related to interindividual variation in performance at the beginning of the study ( progesterone was linearly related to performance for females ) .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [181, 193]}], "task": "NER"}
{"text": "The association between testosterone and performance differed across sexes : for males , it had an inverse U - shape , for females it was U - shaped .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [24, 36]}], "task": "NER"}
{"text": "Towards the end of the study , none of the hormones were significantly related to performance anymore .", "entity": [], "task": "NER"}
{"text": "Thus , the relationship between hormones and mental rotation performance disappeared with repeated testing .", "entity": [], "task": "NER"}
{"text": "Only estradiol levels were significantly elevated at the lowest point of the cycle in mental rotation performance in females .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [5, 14]}], "task": "NER"}
{"text": "In conclusion , in this intensive longitudinal study spanning two months , a monthly cycle in mental rotation performance was found among both males and females , with a larger cycle ' s amplitude for females .", "entity": [], "task": "NER"}
{"text": "Effects of oxygen and glucose deprivation on synaptic transmission in rat dentate gyrus : role of A ( 2A ) adenosine receptors .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [11, 17]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [107, 116]}], "task": "NER"}
{"text": "The hippocampus is comprised of two distinct subfields that show different responses to hypoxic - ischemic brain injury : the CA1 region is particularly susceptible whereas the dentate gyrus ( DG ) is quite resistant .", "entity": [], "task": "NER"}
{"text": "Our aim was to determine the synaptic and proliferative response of the DG to severe oxygen and glucose deprivation ( OGD ) in acute rat hippocampal slices and to investigate the contribution of A ( 2A ) adenosine receptor antagonism to recovery of synaptic activity after OGD .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [85, 91]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [96, 103]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [204, 213]}], "task": "NER"}
{"text": "Extracellular recordings of field excitatory post - synaptic potentials ( fEPSPs ) in granule cells of the DG in brain slices prepared from male Wistar rats were used .", "entity": [], "task": "NER"}
{"text": "A 9 - min OGD is needed in the DG to always induce the appearance of anoxic depolarization ( AD ) and the irreversible block of synaptic activity , as recorded up to 24 h from the end of the insult , whereas only 7 - min OGD is required in the CA1 region .", "entity": [], "task": "NER"}
{"text": "Selective antagonism of A ( 2A ) adenosine receptors by ZM241385 significantly prevents or delays the appearance of AD and protects from the irreversible block of neurotransmission induced by 9 - min OGD in the DG .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "ZM241385", "entity_type": "Chemical", "pos": [56, 64]}], "task": "NER"}
{"text": "The effects of 9 - min OGD on proliferation and maturation of cells localized in the subgranular zone of DG in slices prepared from 5 - bromo - 2 ' - deoxyuridine ( BrdU ) treated rats was investigated .", "entity": [{"entity": "5 - bromo - 2 ' - deoxyuridine", "entity_type": "Chemical", "pos": [132, 162]}, {"entity": "BrdU", "entity_type": "Chemical", "pos": [165, 169]}], "task": "NER"}
{"text": "Slices were further incubated with an immature neuronal marker , doublecortin ( DCX ) .", "entity": [], "task": "NER"}
{"text": "The number of BrdU ( + ) cells was significantly decreased 6 h after 9 - min OGD and this effect was antagonized by ZM241385 .", "entity": [{"entity": "BrdU ( + )", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "ZM241385", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "After 24 h from the end of 9 - min OGD , the number of BrdU ( + ) cells returned to that found before OGD and increased arborization of tertiary dendrites of DCX ( + ) cells was observed .", "entity": [{"entity": "BrdU ( + )", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "The adenosine A ( 2A ) antagonist ZM241385 protects from synaptic failure and from decreased proliferation of immature neuronal cells at a precocious time after OGD .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "ZM241385", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "Psychostimulant pharmacological profile of paraxanthine , the main metabolite of caffeine in humans .", "entity": [{"entity": "paraxanthine", "entity_type": "Chemical", "pos": [43, 55]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [81, 89]}], "task": "NER"}
{"text": "Caffeine induces locomotor activation by its ability to block adenosine receptors .", "entity": [{"entity": "Caffeine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "Caffeine is metabolized to several methylxanthines , with paraxanthine being the main metabolite in humans .", "entity": [{"entity": "Caffeine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "methylxanthines", "entity_type": "Chemical", "pos": [35, 50]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [58, 70]}], "task": "NER"}
{"text": "In this study we show that in rats paraxanthine has a stronger locomotor activating effect than caffeine or the two other main metabolites of caffeine , theophylline and theobromine .", "entity": [{"entity": "paraxanthine", "entity_type": "Chemical", "pos": [35, 47]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [96, 104]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [142, 150]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [153, 165]}, {"entity": "theobromine", "entity_type": "Chemical", "pos": [170, 181]}], "task": "NER"}
{"text": "As previously described for caffeine , the locomotor activating doses of paraxanthine more efficiently counteract the locomotor depressant effects of an adenosine A ( 1 ) than an adenosine A ( 2A ) receptor agonist .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [73, 85]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [153, 162]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [179, 188]}], "task": "NER"}
{"text": "In drug discrimination experiments in rats trained to discriminate a maximal locomotor activating dose of caffeine , paraxanthine , unlike theophylline , generalized poorly to caffeine suggesting the existence of additional mechanisms other than adenosine antagonism in the behavioral effects of paraxanthine .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [106, 114]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [117, 129]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [139, 151]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [176, 184]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [246, 255]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [296, 308]}], "task": "NER"}
{"text": "Pretreatment with the nitric oxide inhibitor N ( G ) - nitro - l - arginine methyl ester ( l - NAME ) reduced the locomotor activating effects of paraxanthine , but not caffeine .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [22, 34]}, {"entity": "N ( G ) - nitro - l - arginine methyl ester", "entity_type": "Chemical", "pos": [45, 88]}, {"entity": "l - NAME", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [146, 158]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [169, 177]}], "task": "NER"}
{"text": "On the other hand , pretreatment with the selective cGMP - preferring phosphodiesterase PDE9 inhibitor BAY 73 - 6691 , increased locomotor activity induced by caffeine , but not paraxanthine .", "entity": [{"entity": "cGMP", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "BAY 73 - 6691", "entity_type": "Chemical", "pos": [103, 116]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [159, 167]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [178, 190]}], "task": "NER"}
{"text": "Ex vivo experiments demonstrated that paraxanthine , but not caffeine , can induce cGMP accumulation in the rat striatum .", "entity": [{"entity": "paraxanthine", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "Finally , in vivo microdialysis experiments showed that paraxanthine , but not caffeine , significantly increases extracellular levels of dopamine in the dorsolateral striatum , which was blocked by l - NAME .", "entity": [{"entity": "paraxanthine", "entity_type": "Chemical", "pos": [56, 68]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [138, 146]}, {"entity": "l - NAME", "entity_type": "Chemical", "pos": [199, 207]}], "task": "NER"}
{"text": "These findings indicate that inhibition of cGMP - preferring PDE is involved in the locomotor activating effects of the acute administration of paraxanthine .", "entity": [{"entity": "cGMP", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "paraxanthine", "entity_type": "Chemical", "pos": [144, 156]}], "task": "NER"}
{"text": "The present results demonstrate a unique psychostimulant profile of paraxanthine , which might contribute to the reinforcing effects of caffeine in humans .", "entity": [{"entity": "paraxanthine", "entity_type": "Chemical", "pos": [68, 80]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Site - specific modulation of brain glucocorticoid receptor and corticotropin - releasing hormone expression using lentiviral vectors .", "entity": [], "task": "NER"}
{"text": "The glucocorticoid receptor ( GR ) and corticotropin - releasing hormone ( CRH ) are important molecular regulators of an individual ' s ability to respond to stressful stimuli in an adaptive manner .", "entity": [], "task": "NER"}
{"text": "Impaired signaling of both GR and CRH often leads to dysfunction of the hypothalamic - pituitary - adrenal axis , which underlies the etiology of many affective disorders such as anxiety and depression .", "entity": [], "task": "NER"}
{"text": "Studies focusing on how GR and CRH influence the stress response are limited as they generalize to broad brain regions , thus hindering identification of how specific CNS nuclei contribute to maladaptive stress responses .", "entity": [], "task": "NER"}
{"text": "Our objective is to distinguish the site - specific involvement of GR and CRH in limbic regions involved in the stress response .", "entity": [], "task": "NER"}
{"text": "With that intent , we use lentiviral ( LV ) vectors in combination with transgenic mouse lines , enabling us to modify expression of GR or CRH in a very localized manner .", "entity": [], "task": "NER"}
{"text": "This paper describes the generation of several distinct LV vectors and transgenic mice models that will help further elucidate the site - specific actions of GR and CRH .", "entity": [], "task": "NER"}
{"text": "The molecular mystique of tetrodotoxin .", "entity": [{"entity": "tetrodotoxin", "entity_type": "Chemical", "pos": [26, 38]}], "task": "NER"}
{"text": "In many respects tetrodotoxin ( TTX ) is the quintessential natural toxin .", "entity": [{"entity": "tetrodotoxin", "entity_type": "Chemical", "pos": [17, 29]}, {"entity": "TTX", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "It is unequivocally toxic to mammals with LD ( 50 ) values for mice in the range of 10 mu g / kg ( intraperitoneal ) , 16 mu g / kg ( subcutaneous ) , and 332 mu g / kg ( oral ) ( Kao , 1966 ) .", "entity": [], "task": "NER"}
{"text": "Its biothreat status is recognized by its listing as a \" Select Agent \" by the US Department of Health and Human Services which includes regulated agents \" determined to have the potential to pose a severe threat to both human and animal health \" ( http : / / www . selectagents . gov / ) .", "entity": [], "task": "NER"}
{"text": "It has a well - defined cellular target ( i . e . , NaV channels ) and pharmacological mode of action ( i . e . , block of nerve and muscle action potentials ) , and it is an indispensable chemical tool in neuroscience .", "entity": [], "task": "NER"}
{"text": "It is widely distributed in marine and terrestrial ecosystems where it plays a role in the chemical ecology of predator - prey relationships and drives evolutionary selection of TTX - resistance ( Hanifin , 2010 ; Williams , 2010 ; Zimmer and Ferrer , 2007 ) .", "entity": [{"entity": "TTX", "entity_type": "Chemical", "pos": [178, 181]}], "task": "NER"}
{"text": "Lastly , TTX has acquired a certain mystique in scientific lore attributable to many fascinating aspects of its natural history and molecular interactions as presented in selected summary below .", "entity": [{"entity": "TTX", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "Additional information may be found in other excellent reviews ( Fozzard and Lipkind , 2010 ; Kao , 1966 ; Lee and Ruben , 2008 ; Narahashi , 2001 , 2008 ) .", "entity": [], "task": "NER"}
{"text": "Glast - expressing progenitor cells contribute to heterotopic ossification .", "entity": [], "task": "NER"}
{"text": "Heterotopic ossification ( HO ) , acquired or hereditary , is the formation of true bone outside the normal skeleton .", "entity": [], "task": "NER"}
{"text": "Although the lineages of cells contributing to bone formation during normal development are well defined , the precise lineages of cells that contribute to HO are not clear .", "entity": [], "task": "NER"}
{"text": "This study utilized Cre - lox based genetic lineage tracing to examine the contribution to HO of cells that expressed either FoxD1 or Glast .", "entity": [], "task": "NER"}
{"text": "Both lineages contributed broadly to different normal tissues , and FoxD1 - cre labeled cells contributed to normal bone formation .", "entity": [], "task": "NER"}
{"text": "Despite the similarity in labeling patterns of normal tissues , and the significant contribution of FoxD1 - cre labeled cells to normal bone , only Glast - creERT labeled progenitors contributed significantly to HO at all stages , suggesting that the cell populations that normally contribute to physiological bone formation , such as the Foxd1 - cre labeled cells , may not participate in pathological HO .", "entity": [], "task": "NER"}
{"text": "Further , identification of Glast - expressing cells as precursors that give rise to HO should help with the molecular targeting of this population both for the prevention and for the treatment of HO .", "entity": [], "task": "NER"}
{"text": "Anti - tumor efficacy of chitosan - g - poly ( ethylene glycol ) nanocapsules containing docetaxel : anti - TMEFF - 2 functionalized nanocapsules vs . non - functionalized nanocapsules .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [40, 64]}, {"entity": "docetaxel", "entity_type": "Chemical", "pos": [89, 98]}], "task": "NER"}
{"text": "The development and evaluation of PEGylated chitosan ( CS ) nanocapsules ( NCs ) conjugated to a monoclonal antibody anti - TMEFF - 2 ( CS - PEG - anti - TMEFF - 2 mAb NCs ) for targeted delivery of docetaxel ( DCX ) is presented .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "docetaxel", "entity_type": "Chemical", "pos": [199, 208]}, {"entity": "DCX", "entity_type": "Chemical", "pos": [211, 214]}], "task": "NER"}
{"text": "CS - PEG - Biotin NCs , displaying biotin tags at their surface , were obtained and efficiently functionalized with an anti - TMEFF - 2 mAb through a convenient avidin - biotin approach .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [5, 8]}, {"entity": "Biotin", "entity_type": "Chemical", "pos": [11, 17]}, {"entity": "biotin", "entity_type": "Chemical", "pos": [35, 41]}, {"entity": "biotin", "entity_type": "Chemical", "pos": [170, 176]}], "task": "NER"}
{"text": "Cell cycle analysis after treatment with different DCX - loaded CS - PEG NC formulations indicated that the encapsulated drug remained fully active , showing a similar functional behavior to free DCX .", "entity": [{"entity": "DCX", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "DCX", "entity_type": "Chemical", "pos": [196, 199]}], "task": "NER"}
{"text": "In vivo efficacy studies using a non - small cell lung carcinoma xenograft revealed that CS - PEG - anti - TMEFF - 2 NCs resulted as effective as free DCX ( Taxotere (R) ) .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [94, 97]}, {"entity": "DCX", "entity_type": "Chemical", "pos": [151, 154]}, {"entity": "Taxotere", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "Interestingly , differences on the pharmacodynamic behavior among the different DCX formulations were observed .", "entity": [{"entity": "DCX", "entity_type": "Chemical", "pos": [80, 83]}], "task": "NER"}
{"text": "Thus , while free DCX exhibited a fast and short effect on tumor volume reduction , CS - PEG - anti - TMEFF - 2 mAb NCs showed a delayed and prolonged action , with no significant side effects of treatments .", "entity": [{"entity": "DCX", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Phenylethanoid glycosides from the stems of Callicarpa peii ( hemostatic drug ) .", "entity": [{"entity": "Phenylethanoid glycosides", "entity_type": "Chemical", "pos": [0, 25]}], "task": "NER"}
{"text": "Two new trisaccharide intermediates of phenylethanoid glycosides , peiioside A ( 1 ) / A ( 2 ) ( 1a / 1b ) and peiioside B ( 2 ) , were isolated from the n - BuOH fraction of MeOH extract of the stems of Callicarpa peii H . T .", "entity": [{"entity": "trisaccharide", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "phenylethanoid glycosides", "entity_type": "Chemical", "pos": [39, 64]}, {"entity": "peiioside A ( 1 ) / A ( 2 )", "entity_type": "Chemical", "pos": [67, 94]}, {"entity": "peiioside B", "entity_type": "Chemical", "pos": [111, 122]}, {"entity": "n - BuOH", "entity_type": "Chemical", "pos": [154, 162]}, {"entity": "MeOH", "entity_type": "Chemical", "pos": [175, 179]}], "task": "NER"}
{"text": "Chang , together with five biogenetic relevant known compounds 3 - 7 .", "entity": [], "task": "NER"}
{"text": "The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods ( especially 2D - NMR techniques ) and acid - catalyzed hydrolysis as O - alpha - l - rhamnopyranosyl - ( 1 '' --> 3 ' ) - O - [ beta - d - apiofuranosyl - ( 1 ''' --> 6 ' ) ] - 4 ' - O - [ ( E ) - caffeoyl ] - d - glucopyranoside ] ( 1a / 1b ) , 3 , 4 - dihydroxy - beta - phenylethoxy - O - [ beta - d - apiofuranosyl - ( 1 ''' --> 6 ' ) - alpha - l - rhamnopyranosyl - ( 1 '' --> 3 ' ) - O - beta - d - glucopyranoside ] ( 2 ) , respectively .", "entity": [{"entity": "O - alpha - l - rhamnopyranosyl - ( 1 '' --> 3 ' ) - O - [ beta - d - apiofuranosyl - ( 1 ''' --> 6 ' ) ] - 4 ' - O - [ ( E ) - caffeoyl ] - d - glucopyranoside ]", "entity_type": "Chemical", "pos": [157, 319]}, {"entity": "3 , 4 - dihydroxy - beta - phenylethoxy - O - [ beta - d - apiofuranosyl - ( 1 ''' --> 6 ' ) - alpha - l - rhamnopyranosyl - ( 1 '' --> 3 ' ) - O - beta - d - glucopyranoside ]", "entity_type": "Chemical", "pos": [334, 510]}], "task": "NER"}
{"text": "On the basis of the isolated compounds , a presumable biogenetic pathway of the biologically interesting phenylethanoid glycosides about forsythoside B ( 3 ) and acteoside ( 4 ) isolated from this species was proposed .", "entity": [{"entity": "phenylethanoid glycosides", "entity_type": "Chemical", "pos": [105, 130]}, {"entity": "forsythoside B", "entity_type": "Chemical", "pos": [137, 151]}, {"entity": "acteoside", "entity_type": "Chemical", "pos": [162, 171]}], "task": "NER"}
{"text": "Isolation of five related intermediates ( 1 - 2 , 5 - 7 ) provided further support for the biogenetic path .", "entity": [], "task": "NER"}
{"text": "This is the first report about phytochemical research on C . peii and the biogenetic hypothesis of forsythoside B and acteoside .", "entity": [{"entity": "forsythoside B", "entity_type": "Chemical", "pos": [99, 113]}, {"entity": "acteoside", "entity_type": "Chemical", "pos": [118, 127]}], "task": "NER"}
{"text": "Reducing effect of an extract of Phaseolus vulgaris on food intake in mice - - focus on highly palatable foods .", "entity": [], "task": "NER"}
{"text": "Different lines of experimental evidence indicate that treatment with extracts from and derivatives of Phaseolus vulgaris reduces intake of food , including highly palatable foods and beverages , in rats .", "entity": [], "task": "NER"}
{"text": "The present study was designed to extend to mice these lines of evidence .", "entity": [], "task": "NER"}
{"text": "To this end , CD1 mice were treated acutely with a standardized extract of P . vulgaris and then exposed to unlimited access to regular food pellets ( Experiment 1 ) or 1 - hour limited access to three different palatable foods / beverages , such as butter cookies ( Experiment 2 ) , a condensed - milk beverage ( Experiment 3 ) , and a chocolate - flavored beverage ( Experiment 4 ) .", "entity": [], "task": "NER"}
{"text": "Treatment with P . vulgaris extract resulted in a significant reduction in the intake of regular food pellets , that was still evident 24h later , as well as of the three palatable nourishments .", "entity": [], "task": "NER"}
{"text": "Together , these results ( a ) extend to mice several previous findings on the capacity of P . vulgaris extracts to suppress food intake in rats , ( b ) suggest that P . vulgaris extracts may interfere with the central mechanisms regulating appetite , food intake , palatability , and / or the rewarding and hedonic properties of food , and ( c ) P . vulgaris extracts may represent a potentially effective therapy for overeating , obesity , and food craving .", "entity": [], "task": "NER"}
{"text": "Characterization of tyrosinase inhibitors in the twigs of Cudrania tricuspidata and their structure - activity relationship study .", "entity": [], "task": "NER"}
{"text": "The twigs of Cudrania tricuspidata were found to show strong tyrosinase inhibitory activity , and further detailed component analysis resulted in the isolation of a new flavanol glucoside , ( 2S , 3S ) - 2 , 3 - trans - dihydromorin - 7 - O - beta - d - glucoside ( 1 ) , plus twenty - seven known compounds ( 2 - 28 ) .", "entity": [{"entity": "flavanol glucoside", "entity_type": "Chemical", "pos": [169, 187]}, {"entity": "( 2S , 3S ) - 2 , 3 - trans - dihydromorin - 7 - O - beta - d - glucoside", "entity_type": "Chemical", "pos": [190, 263]}], "task": "NER"}
{"text": "Their structures were elucidated on the basis of ESI - MS and NMR spectral data .", "entity": [], "task": "NER"}
{"text": "Among the isolated compounds , trans - dihydromorin ( 8 ) , oxyresveratrol ( 9 ) , and steppogenin ( 12 ) were found to exhibit significant tyrosinase inhibition activities .", "entity": [{"entity": "trans - dihydromorin", "entity_type": "Chemical", "pos": [31, 51]}, {"entity": "oxyresveratrol", "entity_type": "Chemical", "pos": [60, 74]}, {"entity": "steppogenin", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Moreover , the structure - activity relationship of these isolated compounds was also discussed .", "entity": [], "task": "NER"}
{"text": "Design , synthesis , inhibition studies , and molecular modeling of pepstatin analogues addressing different secreted aspartic proteinases of Candida albicans .", "entity": [{"entity": "pepstatin", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "The family of secreted aspartic proteinases is known as an important virulence factor of yeast infections by Candida albicans in particular , which is the most common fungal pathogen for humans with respect to systemic disease .", "entity": [], "task": "NER"}
{"text": "Due to the continuing increase of drug resistant strains , these proteinases are currently considered as promising drug target candidates .", "entity": [], "task": "NER"}
{"text": "Based on the known Sap2 - substrate specificity data and X - ray analyses of Sap / inhibitor complexes , three libraries of inhibitors were designed and synthesized by modifying the structure of pepstatin A , a common non - selective aspartic proteinase inhibitor , at the P3 , P2 , or P2 ' position .", "entity": [{"entity": "pepstatin A", "entity_type": "Chemical", "pos": [195, 206]}], "task": "NER"}
{"text": "These novel inhibitors showed high inhibitory potencies for the isoenzymes Sap1 , Sap3 , Sap5 and Sap6 .", "entity": [], "task": "NER"}
{"text": "Then , the affinity and selectivity of the peptide ligands were investigated by molecular modeling , highlighting new key structural information for the design of potent and selective anti - virulence agents targeting Candida albicans .", "entity": [], "task": "NER"}
{"text": "FluidFM as a lithography tool in liquid : spatially controlled deposition of fluorescent nanoparticles .", "entity": [], "task": "NER"}
{"text": "The atomic force microscope ( AFM ) is a powerful instrument for nanolithography , which is well characterized in air where the deposition process is steered by capillary action .", "entity": [], "task": "NER"}
{"text": "In contrast , AFM patterning has been seldom achieved in liquid , mostly via electrochemical deposition .", "entity": [], "task": "NER"}
{"text": "This study investigates the pressure - controlled local deposition of nanoparticles in a liquid environment using a FluidFM .", "entity": [], "task": "NER"}
{"text": "Fluorescent 25 nm polystyrene nanospheres were chosen as nanoobjects to be dispensed because they enable both the in situ monitoring of the process by optical microscopy and the ex situ high - resolution characterization of the pattern by e . g . scanning electron microscopy .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [18, 29]}], "task": "NER"}
{"text": "The FluidFM microchannel was filled with an aqueous solution of negatively charged nanoparticles to be delivered onto a glass surface coated with a polycation .", "entity": [], "task": "NER"}
{"text": "An overpressure in the internal fluidic circuit leads to the deposition of nanoparticle dots and lines under the tip , while the force control regulates the contact between the probe and the surface .", "entity": [], "task": "NER"}
{"text": "The nanoparticle adsorption process depends both on applied pressure and contact time ( respectively tip velocity ) and can be described using the Langmuir approximation for the random sequential adsorption model .", "entity": [], "task": "NER"}
{"text": "Moreover , we observed that the force setpoint , which does not influence the capillary - driven mechanism in air , indeed affects the hydrodynamic resistance at the tip aperture and therefore the volumetric flow .", "entity": [], "task": "NER"}
{"text": "The described method demonstrates the potential of FluidFM in depositing nano - sized objects in liquid with nanometre precision .", "entity": [], "task": "NER"}
{"text": "Both CpG methylation and activation - induced deaminase are required for the fragility of the human bcl - 2 major breakpoint region : implications for the timing of the breaks in the t ( 14 ; 18 ) translocation .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [5, 8]}], "task": "NER"}
{"text": "The t ( 14 ; 18 ) chromosomal translocation typically involves breakage at the bcl - 2 major breakpoint region ( MBR ) to cause human follicular lymphoma .", "entity": [], "task": "NER"}
{"text": "A theory to explain the striking propensity of the MBR breaks at three CpG clusters within the 175 - bp MBR region invoked activation - induced deaminase ( AID ) .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [71, 74]}], "task": "NER"}
{"text": "In a test of that theory , we used here minichromosomal substrates in human pre - B cell lines .", "entity": [], "task": "NER"}
{"text": "Consistent with the essential elements of the theory , we found that the MBR breakage process is indeed highly dependent on DNA methylation at the CpG sites and highly dependent on the AID enzyme to create lesions at peak locations within the MBR .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [147, 150]}], "task": "NER"}
{"text": "Interestingly , breakage of the phosphodiester bonds at the AID - initiated MBR lesions is RAG dependent , but , unexpectedly , most are also dependent on Artemis .", "entity": [{"entity": "phosphodiester", "entity_type": "Chemical", "pos": [32, 46]}], "task": "NER"}
{"text": "We found that Artemis is capable of nicking small heteroduplex structures and is even able to nick single - base mismatches .", "entity": [], "task": "NER"}
{"text": "This raises the possibility that activated Artemis , derived from the unjoined D to J ( H ) DNA ends at the IgH locus on chromosome 14 , nicks AID - generated TG mismatches at methyl CpG sites , and this would explain why the breaks at the chromosome 18 MBR occur within the same time window as those on chromosome 14 .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [183, 186]}], "task": "NER"}
{"text": "Quantitative analysis of chromosome condensation in fission yeast .", "entity": [], "task": "NER"}
{"text": "Chromosomes undergo extensive conformational rearrangements in preparation for their segregation during cell divisions .", "entity": [], "task": "NER"}
{"text": "Insights into the molecular mechanisms behind this still poorly understood condensation process require the development of new approaches to quantitatively assess chromosome formation in vivo .", "entity": [], "task": "NER"}
{"text": "In this study , we present a live - cell microscopy - based chromosome condensation assay in the fission yeast Schizosaccharomyces pombe .", "entity": [], "task": "NER"}
{"text": "By automatically tracking the three - dimensional distance changes between fluorescently marked chromosome loci at high temporal and spatial resolution , we analyze chromosome condensation during mitosis and meiosis and deduct defined parameters to describe condensation dynamics .", "entity": [], "task": "NER"}
{"text": "We demonstrate that this method can determine the contributions of condensin , topoisomerase II , and Aurora kinase to mitotic chromosome condensation .", "entity": [], "task": "NER"}
{"text": "We furthermore show that the assay can identify proteins required for mitotic chromosome formation de novo by isolating mutants in condensin , DNA polymerase epsilon , and F - box DNA helicase I that are specifically defective in pro - / metaphase condensation .", "entity": [], "task": "NER"}
{"text": "Thus , the chromosome condensation assay provides a direct and sensitive system for the discovery and characterization of components of the chromosome condensation machinery in a genetically tractable eukaryote .", "entity": [], "task": "NER"}
{"text": "The conserved PHD1 - PHD2 domain of ZFP - 1 / AF10 is a discrete functional module essential for viability in Caenorhabditis elegans .", "entity": [], "task": "NER"}
{"text": "Plant homeodomain ( PHD ) - type zinc fingers play an important role in recognizing chromatin modifications and recruiting regulatory proteins to specific genes .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "A specific module containing a conventional PHD finger followed by an extended PHD finger exists in the mammalian AF10 protein , among a few others .", "entity": [], "task": "NER"}
{"text": "AF10 has mostly been studied in the context of the leukemic MLL - AF10 fusion protein , which lacks the N - terminal PHD fingers of AF10 .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [104, 105]}], "task": "NER"}
{"text": "Although this domain of AF10 is the most conserved region of the protein , its biological significance has not been elucidated .", "entity": [], "task": "NER"}
{"text": "In this study , we used genetic and biochemical approaches to examine the PHD1 - PHD2 region of the Caenorhabditis elegans ortholog of AF10 , zinc finger protein 1 ( ZFP - 1 ) .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [142, 146]}], "task": "NER"}
{"text": "We demonstrate that the PHD1 - PHD2 region is essential for viability and that the first PHD finger contributes to the preferred binding of PHD1 - PHD2 to lysine 4 - methylated histone H3 tails .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "Moreover , we show that ZFP - 1 localization peaks overlap with H3K4 methylation - enriched promoters of actively expressed genes genomewide and that H3K4 methylation is important for ZFP - 1 localization to promoters in the embryo .", "entity": [], "task": "NER"}
{"text": "We predict that the essential biological role of the PHD1 - PHD2 module of ZFP - 1 / AF10 is connected to the regulation of actively expressed genes during early development .", "entity": [], "task": "NER"}
{"text": "Interferon beta and glatiramer acetate therapy .", "entity": [{"entity": "glatiramer acetate", "entity_type": "Chemical", "pos": [20, 38]}], "task": "NER"}
{"text": "Interferon beta and glatiramer acetate have been mainstays of treatment in relapsingremitting multiple sclerosis for two decades .", "entity": [{"entity": "glatiramer acetate", "entity_type": "Chemical", "pos": [20, 38]}], "task": "NER"}
{"text": "Remarkable advances in our understanding of immune function and dysfunction as well as increasingly sophisticated clinical trial design have stemmed from efforts to better understand these drugs .", "entity": [], "task": "NER"}
{"text": "In this chapter , we review the history of their development and elaborate on known and theorized mechanisms of action .", "entity": [], "task": "NER"}
{"text": "We describe the pivotal clinical trials that have led to their widespread use .", "entity": [], "task": "NER"}
{"text": "We evaluate the clinical use of the drugs including tolerability , side effects , and efficacy measures .", "entity": [], "task": "NER"}
{"text": "Finally , we look to the future of interferon beta and glatiramer acetate in the context of an ever growing armamentarium of treatments for relapsing remitting multiple sclerosis .", "entity": [{"entity": "glatiramer acetate", "entity_type": "Chemical", "pos": [55, 73]}], "task": "NER"}
{"text": "Long - lasting inhibitory effect of apple and orange juices , but not grapefruit juice , on OATP2B1 - mediated drug absorption .", "entity": [], "task": "NER"}
{"text": "Enzyme - based grapefruit juice ( GFJ ) - drug interactions are mainly due to mechanism - based irreversible inhibition of metabolizing enzyme CYP3A4 by GFJ components , but the transporter organic anion transporting polypeptide ( OATP ) 2B1 is also a putative site of interaction between drugs and fruit juices ( FJ ) in the absorption process .", "entity": [], "task": "NER"}
{"text": "Here we aimed to investigate the effect of preincubation with FJ on OATP2B1 - mediated transport of drugs in vitro .", "entity": [], "task": "NER"}
{"text": "When OATP2B1 - expressing Xenopus oocytes were preincubated with GFJ , orange juice ( OJ ) , or apple juice ( AJ ) , AJ induced a remarkable decrease in OATP2B1 - mediated estrone - 3 - sulfate uptake in a concentration - dependent manner ( IC ( 50 ) = 1 . 5 % ) .", "entity": [{"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [172, 193]}], "task": "NER"}
{"text": "A similar but less potent effect was observed with OJ ( IC ( 50 ) = 21 % ) , whereas GFJ had no effect .", "entity": [], "task": "NER"}
{"text": "Similar results were obtained in preincubation studies using fexofenadine .", "entity": [{"entity": "fexofenadine", "entity_type": "Chemical", "pos": [61, 73]}], "task": "NER"}
{"text": "Preincubation with OJ and AJ resulted in time - dependent inhibition of OATP2B1 .", "entity": [], "task": "NER"}
{"text": "Again , AJ had the more potent effect ; its action lasted for at least 240 minutes , suggesting that AJ irreversibly inhibits OATP2B1 - mediated drug uptake .", "entity": [], "task": "NER"}
{"text": "Kinetic analysis revealed that coincubation and preincubation with AJ reduced OATP2B1 - mediated estrone - 3 - sulfate uptake via competitive and noncompetitive mechanisms , respectively .", "entity": [{"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [97, 118]}], "task": "NER"}
{"text": "Thus , OATP2B1 is functionally impaired through both competitive and long - lasting inhibition mechanisms by AJ and OJ , but not GFJ .", "entity": [], "task": "NER"}
{"text": "Interestingly , although GFJ but not AJ is able to irreversibly inhibit CYP3A4 , in the case of OATP2B1 , AJ but not GFJ has a long - lasting inhibitory effect .", "entity": [], "task": "NER"}
{"text": "Accordingly , complex FJ - drug interactions may occur in vivo , and their clinical significance should be examined .", "entity": [], "task": "NER"}
{"text": "Vicilin and the basic subunit of legumin are putative chickpea allergens .", "entity": [], "task": "NER"}
{"text": "IgE - mediated reactions to food allergens constitute a major health problem in industrialized countries .", "entity": [], "task": "NER"}
{"text": "Chickpea is consumed in Mediterranean countries , and reportedly associated with IgE - mediated hypersensitivity reactions .", "entity": [], "task": "NER"}
{"text": "However , the nature of allergic reactions to chickpea has not been characterized .", "entity": [], "task": "NER"}
{"text": "A serum pool from paediatric patients allergic to chickpeas was used to detect IgE - binding proteins from chickpea seeds by immunoassay and immunoblot inhibition assay .", "entity": [], "task": "NER"}
{"text": "Protein samples enriched in chickpea legumin and vicilin were obtained by anion exchange chromatography , and were identified by mass spectrometric analysis .", "entity": [], "task": "NER"}
{"text": "IgE - immunoassays of globulin fractions from chickpeas revealed that vicilin ( 50 kDa ) and the basic subunit of legumin ( 20 kDa ) were bound by IgE from patient sera .", "entity": [], "task": "NER"}
{"text": "Pea and lentil protein extracts strongly inhibited the IgE binding to chickpea globulin .", "entity": [], "task": "NER"}
{"text": "We speculate that vicilin and the basic subunit of legumin are major chickpea allergens .", "entity": [], "task": "NER"}
{"text": "Also , the globulin fraction of chickpea likely cross - reacts with the allergenic proteins of pea and lentil .", "entity": [], "task": "NER"}
{"text": "Antioxidant and immunomodulatory activity of selenium exopolysaccharide produced by Lactococcus lactis subsp . lactis .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "Exopolysaccharide ( EPS ) was isolated and purified from Lactococcus lactis subsp .", "entity": [], "task": "NER"}
{"text": "Lactis culture broth .", "entity": [], "task": "NER"}
{"text": "Selenium chloride oxide ( SeCl ( 2 ) O ) was added to the EPS to synthesize selenium - exopolysaccharide ( Se - EPS ) .", "entity": [{"entity": "Selenium chloride oxide", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "SeCl ( 2 ) O", "entity_type": "Chemical", "pos": [26, 38]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "Se", "entity_type": "Chemical", "pos": [107, 109]}], "task": "NER"}
{"text": "The in vitro and in vivo antioxidant and in vivo immunomodulatory activity of EPS and Se - EPS were compared .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [86, 88]}], "task": "NER"}
{"text": "EPS and Se - EPS scavenged superoxide anions and hydroxyl radicals .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [8, 10]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [27, 37]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "They also increased catalase ( CAT ) , superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH - Px ) activity , while decreasing malondialdehyde ( MDA ) levels in serum and in the livers of mice .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [72, 83]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [97, 100]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [136, 151]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [154, 157]}], "task": "NER"}
{"text": "Se - EPS showed stronger in vitro and in vivo antioxidant activity than were shown by EPS .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "The in vivo immunoenhancement activity of EPS and Se - EPS induced by cyclophosphamide ( CY ) treatment in immunosuppressed mice was researched .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [50, 52]}, {"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [70, 86]}], "task": "NER"}
{"text": "EPS and Se - EPS treatments increased macrophage phagocytosis , spleen and thymus indices and haemolytic complement activity ( HC ( 50 ) ) .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [8, 10]}], "task": "NER"}
{"text": "Se - EPS showed stronger immunomodulatory activity than did EPS .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Apoptosis during postmortem conditioning and its relationship to duck meat quality .", "entity": [], "task": "NER"}
{"text": "The aim of this work was to examine the relationship of skeletal muscle apoptosis and postmortem development of meat quality .", "entity": [], "task": "NER"}
{"text": "Colour , cooking loss , myofibril fragmentation index ( MFI ) and shear force of duck breast and thigh meat postmortem were measured , and changes of positive nuclei were assessed with Terminal deoxynucleotidyl transferase - mediated deoxyuridine triphosphophate nick end - labelling method ( TUNEL ) .", "entity": [{"entity": "deoxynucleotidyl", "entity_type": "Chemical", "pos": [194, 210]}, {"entity": "deoxyuridine triphosphophate", "entity_type": "Chemical", "pos": [234, 262]}], "task": "NER"}
{"text": "Correlation analysis revealed that apoptosis were positively correlated with colour ( L ( * ) , a ( * ) and b ( * ) ) , cooking loss and MFI ( P < 0 . 05 ) , while it is negatively correlated with shear force ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Our results indicate the growing level of duck skeletal muscle cell apoptosis was associated with the postmortem development of meat quality traits such as meat colour , water holding capacity and tenderness .", "entity": [], "task": "NER"}
{"text": "Biochemical characterisation of Alaska pollock , Pacific whiting , and threadfin bream surimi as affected by comminution conditions .", "entity": [], "task": "NER"}
{"text": "Salt - soluble protein , surface reactive sulfhydryl content , and surface hydrophobicity of Alaska pollock , Pacific whiting , and threadfin bream surimi were characterised , as affected by various comminution conditions .", "entity": [{"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [42, 52]}], "task": "NER"}
{"text": "Chopping time / temperatures were explored in consideration of their habitat temperatures .", "entity": [], "task": "NER"}
{"text": "Salt - soluble protein ( SSP ) significantly decreased when chopping time was extended .", "entity": [], "task": "NER"}
{"text": "Corresponding to our follow - up study , no relationship between SSP and gel texture was found .", "entity": [], "task": "NER"}
{"text": "Surface hydrophobicity was inversely proportional to SSP concentration , indicating the unfolding of protein upon comminution .", "entity": [], "task": "NER"}
{"text": "Alaska pollock surimi demonstrated aggregation during chopping at 10 and 20 degrees C , based on the surface hydrophobicity .", "entity": [], "task": "NER"}
{"text": "Surface reactive sulfhydryl ( SRSH ) contents of the three fish species behaved differently .", "entity": [{"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "The SH groups were oxidized to disulphide bonds when higher chopping temperature was applied .", "entity": [{"entity": "SH", "entity_type": "Chemical", "pos": [4, 6]}, {"entity": "disulphide", "entity_type": "Chemical", "pos": [31, 41]}], "task": "NER"}
{"text": "As a result , increased SRSH content was not observed in Alaska pollock ( 10 and 20 degrees C chopping ) and threadfin bream paste ( 25 and 30 degrees C chopping ) .", "entity": [], "task": "NER"}
{"text": "Characterization of modified high - amylose maize starch - alpha - naphthol complexes and their influence on rheological properties of wheat starch .", "entity": [{"entity": "alpha - naphthol", "entity_type": "Chemical", "pos": [59, 75]}], "task": "NER"}
{"text": "Amylose can form inclusion complexes with diverse small molecules .", "entity": [], "task": "NER"}
{"text": "Modified starch has different and unique properties compared with its native counterpart .", "entity": [], "task": "NER"}
{"text": "In this study , chemically / enzymatically modified high - amylose maize starches were used to make inclusion complexes with alpha - naphthol , and the physical properties of complexes and their influences on the rheology of wheat starch were characterized .", "entity": [{"entity": "alpha - naphthol", "entity_type": "Chemical", "pos": [125, 141]}], "task": "NER"}
{"text": "The results showed that modification of starch had little influence on the wide angle X - ray diffraction pattern of complex ( eightfold single helix ) , but did so on the complexation index and precipitation yield .", "entity": [], "task": "NER"}
{"text": "Inclusion complexes with chemically modified starch showed a lower range of thermostability and recrystallization temperatures .", "entity": [], "task": "NER"}
{"text": "Addition of complex considerably influenced the rheological properties of wheat starch , and the effect was dependent on the type of modified starch used .", "entity": [], "task": "NER"}
{"text": "It may be concluded that starch inclusion complexes , with a range of properties and potential food applications , may be feasibly prepared by using diverse modified high - amylose maize starches .", "entity": [], "task": "NER"}
{"text": "Retention of aroma compounds from Mentha piperita essential oil by cyclodextrins and crosslinked cyclodextrin polymers .", "entity": [], "task": "NER"}
{"text": "In this paper , the controlled release of aroma compounds from cyclodextrins ( CDs ) and CD polymers was studied by multiple headspace extraction ( MHE ) experiments .", "entity": [], "task": "NER"}
{"text": "Mentha piperita essential oil was obtained by Soxhlet extraction and identification of the major compounds was performed by GC - MS analysis .", "entity": [], "task": "NER"}
{"text": "Menthol , menthone , pulegone and eucalyptol were identified as the major components .", "entity": [{"entity": "Menthol", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "menthone", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "pulegone", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "eucalyptol", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "Retention of standard compounds in the presence of different CDs and CD polymers has been realised by static headspace gas chromatography ( SH - GC ) at 25 degrees C in the aqueous or gaseous phase .", "entity": [], "task": "NER"}
{"text": "Stability constants for standard compounds and for compounds in essential oil have been also determined with monomeric CD derivatives .", "entity": [], "task": "NER"}
{"text": "The obtained results indicated the formation of a 1 : 1 inclusion complex for all the studied compounds .", "entity": [], "task": "NER"}
{"text": "Molecular modelling was used to investigate the complementarities between host and guest .", "entity": [], "task": "NER"}
{"text": "This study showed that beta - CDs were the most versatile CDs and that beta - CD polymers could perform the controlled release of aroma compounds .", "entity": [{"entity": "beta - CDs", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "beta - CD", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "Effects of ozone microbubble treatment on removal of residual pesticides and quality of persimmon leaves .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [11, 16]}], "task": "NER"}
{"text": "This study investigated the effects of ozone microbubble ( OMCB ) treatment on the removal of residual fenitrothion ( FT ) and benomyl pesticides from red and green persimmon leaves , and also the treatment effect on the leaf colours , physical properties and flavour .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "fenitrothion", "entity_type": "Chemical", "pos": [103, 115]}, {"entity": "benomyl", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "The continuous bubbling OMCB treatment was more effective than the non - bubbling OMCB treatments at reducing the FT and benomyl agricultural pesticide residues from both the red and green persimmon leaves .", "entity": [{"entity": "benomyl", "entity_type": "Chemical", "pos": [121, 128]}], "task": "NER"}
{"text": "Moreover , the bubbling OMCB treatment had no effect on the colour and pulling strength of the leaves .", "entity": [], "task": "NER"}
{"text": "These results indicate that the treatment by bubbling OMCB is an extremely effective method for removing the residues of FT and benomyl in persimmon leaves and has relatively little effect on leaf quality characteristics .", "entity": [{"entity": "benomyl", "entity_type": "Chemical", "pos": [128, 135]}], "task": "NER"}
{"text": "The influence of pectolytic enzyme addition and prefermentative mash heating during the winemaking process on the phenolic composition of Okuzgozu red wine .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [114, 122]}], "task": "NER"}
{"text": "The effects of pectolytic enzyme addition and mash heating prior to fermentation on the phenolic component of Okuzgozu red wine during the winemaking and ageing processes were investigated .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "In general , the highest concentration of total phenolics was found in the mash - heated wines , whereas the total flavan - 3 - ol and total anthocyanin contents in all of the wines , decreased notably during the winemaking and ageing processes .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "flavan - 3 - ol", "entity_type": "Chemical", "pos": [115, 130]}, {"entity": "anthocyanin", "entity_type": "Chemical", "pos": [141, 152]}], "task": "NER"}
{"text": "As determined by HPLC , hydroxycinnamic acids were the major phenolic acids in the red wines .", "entity": [{"entity": "hydroxycinnamic acids", "entity_type": "Chemical", "pos": [24, 45]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [61, 75]}], "task": "NER"}
{"text": "After 6 months in the bottle , the enzyme - treated wines had lower phenolic acid concentrations than had the control and mash - heated wines , but no significant ( p < 0 . 05 ) differences were found in the concentration of total phenolic acids between the control and mash - heated wines .", "entity": [{"entity": "phenolic acid", "entity_type": "Chemical", "pos": [68, 81]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [231, 245]}], "task": "NER"}
{"text": "All of the phenolic acid levels decreased with the winemaking and ageing processes whereas only gallic acid increased .", "entity": [{"entity": "phenolic acid", "entity_type": "Chemical", "pos": [11, 24]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [96, 107]}], "task": "NER"}
{"text": "The wines treated by the pectolytic enzyme addition had a lower monomeric flavan - 3 - ol content than had the other wines , and the amount of monomeric anthocyanins extracted did not increase with the addition of enzymes .", "entity": [{"entity": "flavan - 3 - ol", "entity_type": "Chemical", "pos": [74, 89]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [153, 165]}], "task": "NER"}
{"text": "Identification of xyloglucan endotransglucosylase / hydrolase genes ( XTHs ) and their expression in persimmon fruit as influenced by 1 - methylcyclopropene and gibberellic acid during storage at ambient temperature .", "entity": [{"entity": "1 - methylcyclopropene", "entity_type": "Chemical", "pos": [134, 156]}, {"entity": "gibberellic acid", "entity_type": "Chemical", "pos": [161, 177]}], "task": "NER"}
{"text": "Xyloglucan endotransglucosylase / hydrolase ( XTH ) is thought to contribute to fruit softening by degrading xyloglucan that is a predominant hemicellulose in the cell wall .", "entity": [], "task": "NER"}
{"text": "In this study , two full - length XTH genes ( DKXTH1 and DKXTH2 ) were identified from ' Fupingjianshi ' persimmon fruit , and the expression level of both XTH genes was investigated during softening for 18 - 24 d using RT - qPCR .", "entity": [], "task": "NER"}
{"text": "Sequence analysis showed that DKXTH1 and DKXTH2 contained a putative open reading frame of 861 and 876 bp encoding polypeptides of 287 and 292 amino acid residues , respectively , which contained the conserved DEIDFEFLG motif of XTH , a potential N - linked glycosylation signal site .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [143, 153]}], "task": "NER"}
{"text": "RT - qPCR analysis showed that DKXTH1 and DKXTH2 in untreated fruit had different expression patterns during fruit softening , in which maximum expression occurred on days 3 and 12 of ripening , respectively .", "entity": [], "task": "NER"}
{"text": "1 - Methylcyclopropene ( 1 - MCP ) and gibberellic acid ( GA ( 3 ) ) treatments delayed the softening and ethylene peak of persimmon fruit , as well as suppressed the expression of both XTH genes , especially DKXTH1 .", "entity": [{"entity": "1 - Methylcyclopropene", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "1 - MCP", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "gibberellic acid", "entity_type": "Chemical", "pos": [39, 55]}, {"entity": "GA ( 3 )", "entity_type": "Chemical", "pos": [58, 66]}, {"entity": "ethylene", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "These results indicated that the expression of both XTH genes might be ethylene dependent action , and closely related to softening of persimmon in the early ( DKXTH1 ) and later ( DKXTH2 ) ripening stages .", "entity": [{"entity": "ethylene", "entity_type": "Chemical", "pos": [71, 79]}], "task": "NER"}
{"text": "Production of the alpha - glycosidase inhibitor 1 - deoxynojirimycin from Bacillus species .", "entity": [{"entity": "1 - deoxynojirimycin", "entity_type": "Chemical", "pos": [48, 68]}], "task": "NER"}
{"text": "1 - Deoxynojirimycin ( DNJ ) , a potent alpha - glycosidase inhibitor , has therapeutic applications in treatments of HIV , Gaucher ' s disease , and diabetes .", "entity": [{"entity": "1 - Deoxynojirimycin", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "DNJ has been extracted from natural sources ( mulberry leaves ) for therapeutic purposes ; however , DNJ ingredients are in limited supply and are costly to obtain on a large scale .", "entity": [{"entity": "DNJ", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Since certain strains of Bacillus and Streptomyces species reportedly produce DNJ , they may serve as potential sources for high - yield DNJ production .", "entity": [{"entity": "DNJ", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [137, 140]}], "task": "NER"}
{"text": "In this study , we obtained evidence for a DNJ production in Bacillus subtilis DSM704 by hydrophilic interaction chromatography - tandem mass spectrometry .", "entity": [{"entity": "DNJ", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "In addition , from a screen of 750 microorganisms , we identified additional Bacillus strains ( Bacillus amyloliquefaciens AS385 and Bacillus subtilis B4 ) that produce DNJ in large quantities .", "entity": [{"entity": "DNJ", "entity_type": "Chemical", "pos": [169, 172]}], "task": "NER"}
{"text": "Investigation of the effect of various culture conditions , using Bacillus subtilis DSM704 and the DNJ high - production Bacillus strains , provided evidence for the importance of sorbitol supplementation on the yield of the DNJ precursor , 2 - amino - 2 - deoxy - D - mannitol , thereby increasing DNJ production .", "entity": [{"entity": "DNJ", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "sorbitol", "entity_type": "Chemical", "pos": [180, 188]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [225, 228]}, {"entity": "2 - amino - 2 - deoxy - D - mannitol", "entity_type": "Chemical", "pos": [241, 277]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [299, 302]}], "task": "NER"}
{"text": "The role of sorbitol in increased DNJ production was supported by an observed increase in mRNA expression of the biosynthetic gene , gabT1 .", "entity": [{"entity": "sorbitol", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "When Bacillus amyloliquefaciens AS385 was cultured in medium supplemented with sorbitol , extracellular DNJ concentration reached a maximum of 460 mg / l of medium ( equivalent to 9 . 20mg / g of freeze - dried medium ) , indicating that this strain can serve as a source for food - and drug - grade products .", "entity": [{"entity": "sorbitol", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [104, 107]}], "task": "NER"}
{"text": "These findings not only lead to a further understanding of the DNJ biosynthetic pathway , but also suggest a method for microbial mass production of DNJ for therapeutic applications .", "entity": [{"entity": "DNJ", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "DNJ", "entity_type": "Chemical", "pos": [149, 152]}], "task": "NER"}
{"text": "Grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta - cells .", "entity": [{"entity": "procyanidin", "entity_type": "Chemical", "pos": [11, 22]}], "task": "NER"}
{"text": "Grape seed procyanidin extract ( GSPE ) modulates glucose homeostasis and insulinemia in several animal models .", "entity": [{"entity": "procyanidin", "entity_type": "Chemical", "pos": [11, 22]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "Under pathological conditions , insulin levels are dependent on pancreatic beta - cell functionality , as well as on the beta - cell mass expansion or apoptosis in the pancreas .", "entity": [], "task": "NER"}
{"text": "In this study , we analysed the effects of GSPE on modulating apoptosis and proliferation in beta - cells .", "entity": [], "task": "NER"}
{"text": "We tested the effects of GSPE in the INS - 1E pancreatic beta - cell line , either under basal or altered conditions with high glucose , insulin or palmitate levels .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [148, 157]}], "task": "NER"}
{"text": "GSPE enhanced the pro - apoptotic effect of high glucose and showed clear antiproliferative effects under high glucose , insulin and palmitate conditions .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [111, 118]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [133, 142]}], "task": "NER"}
{"text": "These antiproliferative effects are likely due to high molecular weight compounds contained in the extract .", "entity": [], "task": "NER"}
{"text": "GSPE also modulated pro - and anti - apoptotic markers in the pancreas of rats fed a cafeteria diet , with the effect depending on the dose of GSPE and duration of treatment .", "entity": [], "task": "NER"}
{"text": "Thus , GSPE is able to modulate apoptosis and proliferation of beta - cells under altered , but not basal , conditions .", "entity": [], "task": "NER"}
{"text": "Physicochemical properties of lard - based diacylglycerols in blends with lard .", "entity": [{"entity": "diacylglycerols", "entity_type": "Chemical", "pos": [43, 58]}], "task": "NER"}
{"text": "The objective of the study was to investigate how blending of triacylglycerols and diacylglycerols affected the melting and crystallisation properties in a solid fat system .", "entity": [{"entity": "triacylglycerols", "entity_type": "Chemical", "pos": [62, 78]}, {"entity": "diacylglycerols", "entity_type": "Chemical", "pos": [83, 98]}], "task": "NER"}
{"text": "Lard - based diacylglycerols ( DAGs ) were blended with lard in various concentrations ( 0 % , 1 % , 5 % , 10 % , 20 % , 50 % , 60 % , 70 % , 80 % , 90 % , and 100 % ) .", "entity": [{"entity": "diacylglycerols", "entity_type": "Chemical", "pos": [13, 28]}, {"entity": "DAGs", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "The melting and crystallisation properties were investigated by the determination of dropping point ( DP ) , solid fat content ( SFC ) , differential scanning calorimetry ( DSC ) and X - ray diffraction ( XRD ) .", "entity": [], "task": "NER"}
{"text": "In general , the effects of DAGs were found to be dependent on concentration .", "entity": [{"entity": "DAGs", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "The DP was significantly ( P < 0 . 0001 ) decreased when DAGs were added to the lard from 5 - 50 % , whereas the DP was increased ( P < 0 . 0001 ) when the blends contained more than 60 % DAGs .", "entity": [{"entity": "DAGs", "entity_type": "Chemical", "pos": [57, 61]}, {"entity": "DAGs", "entity_type": "Chemical", "pos": [188, 192]}], "task": "NER"}
{"text": "The DSC thermograms showed that DAGs changed the melting and crystallisation profiles of lard .", "entity": [{"entity": "DAGs", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "The crystallisation onset point increased ( P < 0 . 05 ) with increasing the DAG concentrations ( 10 - 100 % ) .", "entity": [{"entity": "DAG", "entity_type": "Chemical", "pos": [77, 80]}], "task": "NER"}
{"text": "The melting peaks and off - set points generally shifted slightly towards higher temperatures as the content of DAGs increased above 50 % .", "entity": [{"entity": "DAGs", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "DAG content of 5 % and 10 % resulted in lowering of the off - set point .", "entity": [{"entity": "DAG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The lard contained both beta and beta ' crystals .", "entity": [], "task": "NER"}
{"text": "The beta form was more pronounced in the blends with high concentrations of DAGs .", "entity": [{"entity": "DAGs", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "Blending of TAGs and DAGs may serve as a solution to achieve specific functional properties in products containing solid fats .", "entity": [{"entity": "TAGs", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "DAGs", "entity_type": "Chemical", "pos": [21, 25]}], "task": "NER"}
{"text": "Reduction of acrylamide formation by vanadium salt in potato French fries and chips .", "entity": [{"entity": "acrylamide", "entity_type": "Chemical", "pos": [13, 23]}, {"entity": "vanadium", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "The effects of vanadyl sulphate on the formation of acrylamide have been studied in fried potato products , such as French fries and chips .", "entity": [{"entity": "vanadyl sulphate", "entity_type": "Chemical", "pos": [15, 31]}, {"entity": "acrylamide", "entity_type": "Chemical", "pos": [52, 62]}], "task": "NER"}
{"text": "Acrylamide formation was inhibited by 30 . 3 % , 53 . 3 % and 89 . 3 % when the sliced potato strips were soaked in 0 . 001 , 0 . 01 and 0 . 1 M vanadyl sulphate ( VOSO ( 4 ) ) solutions , respectively , for 60 min before frying .", "entity": [{"entity": "Acrylamide", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "vanadyl sulphate", "entity_type": "Chemical", "pos": [145, 161]}, {"entity": "VOSO ( 4 )", "entity_type": "Chemical", "pos": [164, 174]}], "task": "NER"}
{"text": "Moreover , 57 . 7 % , 71 . 4 % and 92 . 5 % inhibition of acrylamide formation was observed when chips were soaked in the respective vanadyl sulphate solution before frying .", "entity": [{"entity": "acrylamide", "entity_type": "Chemical", "pos": [58, 68]}, {"entity": "vanadyl sulphate", "entity_type": "Chemical", "pos": [133, 149]}], "task": "NER"}
{"text": "In a separate model reaction , a solution containing an equimolar concentration of L - asparagine and D - glucose showed a significant inhibition of acrylamide formation when heated at 150 degrees C for 30 min in the presence of vanadyl sulphate ( VOSO ( 4 ) ) .", "entity": [{"entity": "L - asparagine", "entity_type": "Chemical", "pos": [83, 97]}, {"entity": "D - glucose", "entity_type": "Chemical", "pos": [102, 113]}, {"entity": "acrylamide", "entity_type": "Chemical", "pos": [149, 159]}, {"entity": "vanadyl sulphate", "entity_type": "Chemical", "pos": [229, 245]}, {"entity": "VOSO ( 4 )", "entity_type": "Chemical", "pos": [248, 258]}], "task": "NER"}
{"text": "The results indicate that the binding of VO ( 2 + ) to asparagine and the decrease in the pH of the potato samples resulted in a significant reduction of acrylamide formation in fried potato products .", "entity": [{"entity": "VO ( 2 + )", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "asparagine", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "acrylamide", "entity_type": "Chemical", "pos": [154, 164]}], "task": "NER"}
{"text": "Determination of fluorine in milk samples via calcium - monofluoride by electrothermal molecular absorption spectrometry .", "entity": [{"entity": "fluorine", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "calcium - monofluoride", "entity_type": "Chemical", "pos": [46, 68]}], "task": "NER"}
{"text": "The determination of fluorine in milk samples via the molecular absorption of calcium mono - fluoride ( CaF ) was performed using a HR - CS - ETAAS .", "entity": [{"entity": "fluorine", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "calcium mono - fluoride", "entity_type": "Chemical", "pos": [78, 101]}, {"entity": "CaF", "entity_type": "Chemical", "pos": [104, 107]}], "task": "NER"}
{"text": "For this purpose , calcium was pipetted to graphite furnace together with samples .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "The amount of Ca and the graphite furnace program were optimised .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [14, 16]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "Fluorine was determined in pyrolytically coated platforms at 606 . 440 nm applying a pyrolysis temperature of 700 degrees C and a molecule forming temperature of 2250 degrees C .", "entity": [{"entity": "Fluorine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Finally , applying standard addition technique , F contents of several milk samples were determined .", "entity": [{"entity": "F", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "The results obtained by linear calibration and standard addition techniques were significantly different which can be attributed to non - spectral interferences in milk due to matrix concomitants .", "entity": [], "task": "NER"}
{"text": "Therefore , in order to tolerate the errors , the F contents of several milk samples were determined applying standard addition technique .", "entity": [{"entity": "F", "entity_type": "Chemical", "pos": [50, 51]}], "task": "NER"}
{"text": "However , since the ingredients of milk samples change for different kinds , the F in each sample was determined from its own standard addition curve .", "entity": [{"entity": "F", "entity_type": "Chemical", "pos": [81, 82]}], "task": "NER"}
{"text": "The range of F content for the milk samples were 0 . 027 - 0 . 543 mu g mL ( - 1 ) .", "entity": [{"entity": "F", "entity_type": "Chemical", "pos": [13, 14]}], "task": "NER"}
{"text": "The limit of detection and characteristic mass of the method were 0 . 26 and 0 . 13 ng of F , respectively .", "entity": [{"entity": "F", "entity_type": "Chemical", "pos": [90, 91]}], "task": "NER"}
{"text": "Characterising protein , salt and water interactions with combined vibrational spectroscopic techniques .", "entity": [], "task": "NER"}
{"text": "In this paper a combination of NIR spectroscopy and FTIR and Raman microspectroscopy was used to elucidate the effects of different salts ( NaCl , KCl and MgSO ( 4 ) ) on structural proteins and their hydration in muscle tissue .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [140, 144]}, {"entity": "KCl", "entity_type": "Chemical", "pos": [147, 150]}, {"entity": "MgSO ( 4 )", "entity_type": "Chemical", "pos": [155, 165]}], "task": "NER"}
{"text": "Multivariate multi - block technique Consensus Principal Component Analysis enabled integration of different vibrational spectroscopic techniques : macroscopic information obtained by NIR spectroscopy is directly related to microscopic information obtained by FTIR and Raman microspectroscopy .", "entity": [], "task": "NER"}
{"text": "Changes in protein secondary structure observed at different concentrations of salts were linked to changes in protein hydration affinity .", "entity": [], "task": "NER"}
{"text": "The evidence for this was given by connecting the underlying FTIR bands of the amide I region ( 1700 - 1600 cm ( - 1 ) ) and the water region ( 3500 - 3000 cm ( - 1 ) ) with water vibrations obtained by NIR spectroscopy .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [79, 84]}], "task": "NER"}
{"text": "In addition , Raman microspectroscopy demonstrated that different cations affected structures of aromatic amino acid residues differently , which indicates that cation - pi interactions play an important role in determination of the final structure of protein molecules .", "entity": [{"entity": "aromatic amino acid", "entity_type": "Chemical", "pos": [97, 116]}], "task": "NER"}
{"text": "Influence of nitrogen supply on the production of higher alcohols / esters and expression of flavour - related genes in cacha c a fermentation .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [13, 21]}, {"entity": "alcohols", "entity_type": "Chemical", "pos": [57, 65]}, {"entity": "esters", "entity_type": "Chemical", "pos": [68, 74]}], "task": "NER"}
{"text": "This study provides the first attempt to analyse the influence of ammonium supplements on sugar - cane juice fermentation and the flavour profile in a cacha c a industrial process .", "entity": [{"entity": "ammonium", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [90, 95]}], "task": "NER"}
{"text": "The objective was to find a relationship between higher alcohol / ester content and the transcription levels of the main genes involved in production of these compounds under cacha c a fermentation .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "ester", "entity_type": "Chemical", "pos": [66, 71]}], "task": "NER"}
{"text": "Sugar - cane juice with a low amount of assimilable nitrogen ( 81 mg N / L ) , was further supplemented with mid - range or high concentrations of ammonium sulfate .", "entity": [{"entity": "Sugar", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "ammonium sulfate", "entity_type": "Chemical", "pos": [147, 163]}], "task": "NER"}
{"text": "Overall , higher alcohol production was reduced by ammonium supplementation , and this can be correlated with a general downregulation of genes encoding decarboxylases and dehydrogenases of the Ehrlich pathway .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [51, 59]}], "task": "NER"}
{"text": "The production of acetate esters was enhanced by mid - range ammonium supplementation and the production of acyl esters by high ammonium supplementation .", "entity": [{"entity": "acetate esters", "entity_type": "Chemical", "pos": [18, 32]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "acyl esters", "entity_type": "Chemical", "pos": [108, 119]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "The acyl esters could be correlated with expression of alcohol acyl - transferase EEB1 and the acyl esterase IAH1 .", "entity": [{"entity": "acyl esters", "entity_type": "Chemical", "pos": [4, 15]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "acyl", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "acyl", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Near native binding of a fluorescent serotonin conjugate to serotonin type 3 receptors .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "Described is the synthesis of 5 - hydroxytryptamine - tetramethylrhodamine ( 5HT * ) ; an indole nitrogen linked fluorescent conjugate of serotonin .", "entity": [{"entity": "5 - hydroxytryptamine - tetramethylrhodamine", "entity_type": "Chemical", "pos": [30, 74]}, {"entity": "5HT", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "indole nitrogen", "entity_type": "Chemical", "pos": [90, 105]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [138, 147]}], "task": "NER"}
{"text": "Through a series fluorescence quenching experiments and experiments in the presence of a known competitive antagonist ( Granisetron ) , it was shown that 5HT * specifically binds to purified homo - pentameric type - 3 human serotonin receptors ( 5HT ( 3A ) ) .", "entity": [{"entity": "Granisetron", "entity_type": "Chemical", "pos": [120, 131]}, {"entity": "5HT", "entity_type": "Chemical", "pos": [154, 157]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [224, 233]}, {"entity": "5HT", "entity_type": "Chemical", "pos": [246, 249]}], "task": "NER"}
{"text": "The measured dissociation constant and Hill coefficient are K ( d ) = 83 +/- 3 nM and n = 3 . 1 +/- 0 . 3 , respectively which is indicative of multi - ligand binding and cooperativity similar to that of unconjugated serotonin .", "entity": [], "task": "NER"}
{"text": "Design and synthesis of tricyclic cores for kinase inhibition .", "entity": [], "task": "NER"}
{"text": "Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology .", "entity": [], "task": "NER"}
{"text": "To date , ATP - mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine .", "entity": [{"entity": "pyrrolopyridine", "entity_type": "Chemical", "pos": [162, 177]}, {"entity": "pyrrolopyrazine", "entity_type": "Chemical", "pos": [182, 197]}], "task": "NER"}
{"text": "Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest .", "entity": [], "task": "NER"}
{"text": "3 ' - Modified oligodeoxyribonucleotides for the study of 2 - deoxyribose damage in DNA .", "entity": [{"entity": "2 - deoxyribose", "entity_type": "Chemical", "pos": [58, 73]}], "task": "NER"}
{"text": "Well - defined substrates for the study of oxidative processes are important for the elucidation of the role of DNA damage in the etiology of diseases such as cancer .", "entity": [], "task": "NER"}
{"text": "We have synthesized 3 ' - modified oligodeoxyribonucleotides ( ODNs ) using 5 ' --> 3 ' ' reverse ' DNA synthesis for the study of 2 - deoxyribose oxidative damage to DNA .", "entity": [{"entity": "2 - deoxyribose", "entity_type": "Chemical", "pos": [131, 146]}], "task": "NER"}
{"text": "The modified monomers designed for these studies all share a common feature , they lack the naturally occurring 3 ' - hydroxyl group found in 2 - deoxyribonucleosides .", "entity": [{"entity": "3 ' - hydroxyl", "entity_type": "Chemical", "pos": [112, 126]}, {"entity": "2 - deoxyribonucleosides", "entity_type": "Chemical", "pos": [142, 166]}], "task": "NER"}
{"text": "Modified H - phosphonates containing 3 ' - phenyl selenides as well as saturated and unsaturated sugars were obtained and incorporated in ODNs .", "entity": [{"entity": "H - phosphonates", "entity_type": "Chemical", "pos": [9, 25]}, {"entity": "3 ' - phenyl selenides", "entity_type": "Chemical", "pos": [37, 59]}, {"entity": "saturated and unsaturated sugars", "entity_type": "Chemical", "pos": [71, 103]}, {"entity": "ODNs", "entity_type": "Chemical", "pos": [138, 142]}], "task": "NER"}
{"text": "These ODNs were used to investigate the fate of C3 ' - dideoxyribonucleotide radicals in DNA .", "entity": [{"entity": "ODNs", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "C3 ' - dideoxyribonucleotide", "entity_type": "Chemical", "pos": [48, 76]}], "task": "NER"}
{"text": "Discovery of nosokophic acid , a predicted intermediate of moenomycins , from nosokomycin - producing Streptomyces sp .", "entity": [{"entity": "nosokophic acid", "entity_type": "Chemical", "pos": [13, 28]}, {"entity": "moenomycins", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "nosokomycin", "entity_type": "Chemical", "pos": [78, 89]}], "task": "NER"}
{"text": "K04 - 0144 .", "entity": [], "task": "NER"}
{"text": "A new actinomycete metabolite designated nosokophic acid was isolated from the culture broth of nosokomycin - producing Streptomyces sp .", "entity": [{"entity": "nosokophic acid", "entity_type": "Chemical", "pos": [41, 56]}, {"entity": "nosokomycin", "entity_type": "Chemical", "pos": [96, 107]}], "task": "NER"}
{"text": "K04 - 0144 , and the structure was elucidated by various NMR experiments .", "entity": [], "task": "NER"}
{"text": "Nosokophic acid was found to be 3 - phosphoglycosyl - 2 - sesquiterpenyl dihydroxypropionic acid , a predicted biosynthetic intermediate of nosokomycin - related moenomycins .", "entity": [{"entity": "Nosokophic acid", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "3 - phosphoglycosyl - 2 - sesquiterpenyl dihydroxypropionic acid", "entity_type": "Chemical", "pos": [32, 96]}, {"entity": "nosokomycin", "entity_type": "Chemical", "pos": [140, 151]}, {"entity": "moenomycins", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "The compound showed no activity against MRSA , but potentiated imipenem activity against MRSA by 512 - fold .", "entity": [], "task": "NER"}
{"text": "Synthesis of new N - ( arylcyclopropyl ) acetamides and N - ( arylvinyl ) acetamides as conformationally - restricted ligands for melatonin receptors .", "entity": [{"entity": "N - ( arylcyclopropyl ) acetamides", "entity_type": "Chemical", "pos": [17, 51]}, {"entity": "N - ( arylvinyl ) acetamides", "entity_type": "Chemical", "pos": [56, 84]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [130, 139]}], "task": "NER"}
{"text": "N - ( Arylcyclopropyl ) acetamides and N - ( arylvinyl ) acetamides or methyl ureas have been prepared as constrained analogues of melatonin .", "entity": [{"entity": "N - ( Arylcyclopropyl ) acetamides", "entity_type": "Chemical", "pos": [0, 34]}, {"entity": "N - ( arylvinyl ) acetamides", "entity_type": "Chemical", "pos": [39, 67]}, {"entity": "methyl ureas", "entity_type": "Chemical", "pos": [71, 83]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [131, 140]}], "task": "NER"}
{"text": "The affinity of these new compounds for chicken brain melatonin receptors and recombinant human MT ( 1 ) and MT ( 2 ) receptors was evaluated using 2 - [ ( 125 ) I ] - iodomelatonin as radioligand .", "entity": [{"entity": "melatonin", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "2 - [ ( 125 ) I ] - iodomelatonin", "entity_type": "Chemical", "pos": [148, 181]}], "task": "NER"}
{"text": "Strict ethylenic or cyclopropyl analogues of the commercialized agonist agomelatine ( Valdoxan (R) ) were equipotent to agomelatine in binding bioassays .", "entity": [{"entity": "ethylenic", "entity_type": "Chemical", "pos": [7, 16]}, {"entity": "cyclopropyl", "entity_type": "Chemical", "pos": [20, 31]}, {"entity": "agomelatine", "entity_type": "Chemical", "pos": [72, 83]}, {"entity": "Valdoxan", "entity_type": "Chemical", "pos": [86, 94]}, {"entity": "agomelatine", "entity_type": "Chemical", "pos": [120, 131]}], "task": "NER"}
{"text": "However , the ethylenic analogue was more effective than the cyclopropyl one in the melanophore aggregation bioassay , but was still less potent than the disubstituted 2 , 7 - dimethoxy - naphtalenic compounds .", "entity": [{"entity": "ethylenic", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "cyclopropyl", "entity_type": "Chemical", "pos": [61, 72]}, {"entity": "2 , 7 - dimethoxy - naphtalenic", "entity_type": "Chemical", "pos": [168, 199]}], "task": "NER"}
{"text": "Non - benzimidazole containing inhibitors of respiratory syncytial virus .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [6, 19]}], "task": "NER"}
{"text": "Several non - benzimidazole containing inhibitors of respiratory syncytial virus are described .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [14, 27]}], "task": "NER"}
{"text": "Core template modification , analysis of antiviral activity , physicochemistry and optimisation of properties led to the thiazole - imidazole 13 , that showed a good potency and pharmacokinetic profile in the rat .", "entity": [{"entity": "thiazole", "entity_type": "Chemical", "pos": [121, 129]}, {"entity": "imidazole", "entity_type": "Chemical", "pos": [132, 141]}], "task": "NER"}
{"text": "Design and synthesis of novel 2 - methyl - 4 , 5 - substitutedbenzo [ f ] - 3 , 3a , 4 , 5 - tetrahydro - pyrazolo [ 1 , 5 - d ] [ 1 , 4 ] oxazepin - 8 ( 7H ) - one derivatives as telomerase inhibitors .", "entity": [{"entity": "2 - methyl - 4 , 5 - substitutedbenzo [ f ] - 3 , 3a , 4 , 5 - tetrahydro - pyrazolo [ 1 , 5 - d ] [ 1 , 4 ] oxazepin - 8 ( 7H ) - one", "entity_type": "Chemical", "pos": [30, 164]}], "task": "NER"}
{"text": "Eight novel 4 , 5 - tetrahydropyrazolo [ 1 , 5 - d ] [ 1 , 4 ] oxazepine derivatives have been synthesized and purified to be screened for anticancer activity .", "entity": [{"entity": "4 , 5 - tetrahydropyrazolo [ 1 , 5 - d ] [ 1 , 4 ] oxazepine", "entity_type": "Chemical", "pos": [12, 72]}], "task": "NER"}
{"text": "By a modified TRAP assay , some titled compounds were tested against telomerase , and compound 4a showed the most potent inhibitory activity with IC ( 50 ) value at 0 . 78 +/- 0 . 22 mu M .", "entity": [], "task": "NER"}
{"text": "Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1 , TERT , phospho - AKT and PI3K / AKT pathway .", "entity": [], "task": "NER"}
{"text": "Triazole - based inhibitors of geranylgeranyltransferase II .", "entity": [{"entity": "Triazole", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "A small set of triazole bisphosphonates has been prepared and tested for the ability to inhibit geranylgeranyltransferase II ( GGTase II ) .", "entity": [{"entity": "triazole bisphosphonates", "entity_type": "Chemical", "pos": [15, 39]}], "task": "NER"}
{"text": "The compounds were prepared through use of click chemistry to assemble a central triazole that links a polar head group to a hydrophobic tail .", "entity": [{"entity": "triazole", "entity_type": "Chemical", "pos": [81, 89]}], "task": "NER"}
{"text": "The resulting compounds were tested for their ability to inhibit GGTase II in an in vitro enzyme assay and also were tested for cytotoxic activity in an MTT assay with the human myeloma RPMI - 8226 cell line .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "The most potent enzyme inhibitor was the triazole with a geranylgeranyl tail , which suggests that inhibitors that can access the enzyme region that holds the isoprenoid tail will display greater activity .", "entity": [{"entity": "triazole", "entity_type": "Chemical", "pos": [41, 49]}, {"entity": "geranylgeranyl", "entity_type": "Chemical", "pos": [57, 71]}, {"entity": "isoprenoid", "entity_type": "Chemical", "pos": [159, 169]}], "task": "NER"}
{"text": "Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert - butyl hydroperoxide - induced hepatotoxicity through Nrf2 - mediated antioxidant enzymes .", "entity": [{"entity": "ganodermanondiol", "entity_type": "Chemical", "pos": [21, 37]}, {"entity": "tert - butyl hydroperoxide", "entity_type": "Chemical", "pos": [81, 107]}], "task": "NER"}
{"text": "Ganodermanondiol , a biologically active compound , was isolated from the Lingzhi mushroom ( Ganoderma lucidum ) .", "entity": [{"entity": "Ganodermanondiol", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "The present study examined the protective effects of ganodermanondiol against tert - butyl hydroperoxide ( t - BHP ) - induced hepatotoxicity .", "entity": [{"entity": "ganodermanondiol", "entity_type": "Chemical", "pos": [53, 69]}, {"entity": "tert - butyl hydroperoxide", "entity_type": "Chemical", "pos": [78, 104]}, {"entity": "t - BHP", "entity_type": "Chemical", "pos": [107, 114]}], "task": "NER"}
{"text": "Ganodermanondiol protected human liver - derived HepG2 cells through nuclear factor - E2 - related factor 2 ( Nrf2 ) pathway - dependent heme oxygenase - 1 expressions .", "entity": [{"entity": "Ganodermanondiol", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "heme", "entity_type": "Chemical", "pos": [137, 141]}], "task": "NER"}
{"text": "Moreover , ganodermanondiol increased cellular glutathione levels and the expression of the glutamine - cysteine ligase gene in a dose - dependent manner .", "entity": [{"entity": "ganodermanondiol", "entity_type": "Chemical", "pos": [11, 27]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [92, 101]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Furthermore , ganodermanondiol exposure enhanced the phosphorylation of adenosine monophosphate - activated protein kinase ( AMPK ) and its upstream kinase activators , LKB1 and Ca ( 2 + ) / calmodulin - dependent protein kinase - II ( CaMKII ) .", "entity": [{"entity": "ganodermanondiol", "entity_type": "Chemical", "pos": [14, 30]}, {"entity": "adenosine monophosphate", "entity_type": "Chemical", "pos": [72, 95]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [178, 188]}], "task": "NER"}
{"text": "This study indicates that ganodermanondiol exhibits potent cytoprotective effects on t - BHP - induced hepatotoxicity in human liver - derived HepG2 cells , presumably through Nrf2 - mediated antioxidant enzymes and AMPK .", "entity": [{"entity": "ganodermanondiol", "entity_type": "Chemical", "pos": [26, 42]}, {"entity": "t - BHP", "entity_type": "Chemical", "pos": [85, 92]}], "task": "NER"}
{"text": "Anti - inflammatory effects of trans - 1 , 3 - diphenyl - 2 , 3 - epoxypropane - 1 - one mediated by suppression of inflammatory mediators in LPS - stimulated RAW 264 . 7 macrophages .", "entity": [{"entity": "trans - 1 , 3 - diphenyl - 2 , 3 - epoxypropane - 1 - one", "entity_type": "Chemical", "pos": [31, 88]}], "task": "NER"}
{"text": "To assess the potential therapeutic properties of trans - 1 , 3 - diphenyl - 2 , 3 - epoxypropane - 1 - one ( DPEP ) , its anti - inflammatory effects were investigated in lipopolysaccharide ( LPS ) - stimulated mouse macrophage ( RAW 264 . 7 ) cells .", "entity": [{"entity": "trans - 1 , 3 - diphenyl - 2 , 3 - epoxypropane - 1 - one", "entity_type": "Chemical", "pos": [50, 107]}, {"entity": "DPEP", "entity_type": "Chemical", "pos": [110, 114]}], "task": "NER"}
{"text": "DPEP induced dose - dependent reduction of the protein levels of inducible nitric oxide synthase ( iNOS ) and cyclooxygenase - 2 ( COX - 2 ) and concomitant reduction in the production of NO and prostaglandin E ( 2 ) ( PGE ( 2 ) ) .", "entity": [{"entity": "DPEP", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [75, 87]}, {"entity": "NO", "entity_type": "Chemical", "pos": [100, 102]}, {"entity": "prostaglandin E ( 2 )", "entity_type": "Chemical", "pos": [195, 216]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [219, 228]}], "task": "NER"}
{"text": "Additionally , DPEP suppressed the production of inflammatory cytokines , including tumor necrosis factor - alpha ( TNF - alpha ) , interleukin ( IL ) - 1 beta , and IL - 6 .", "entity": [{"entity": "DPEP", "entity_type": "Chemical", "pos": [15, 19]}], "task": "NER"}
{"text": "We investigated the mechanism by which DPEP inhibits NO and PGE ( 2 ) by examining the level of nuclear factor - kappa B ( NF - kappa B ) activation within the mitogen - activated protein kinase ( MAPK ) pathway , which is an inflammation - induced signaling pathway in RAW 264 . 7 cells .", "entity": [{"entity": "DPEP", "entity_type": "Chemical", "pos": [39, 43]}, {"entity": "NO", "entity_type": "Chemical", "pos": [53, 55]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [60, 69]}], "task": "NER"}
{"text": "DPEP inhibited LPS - induced phosphorylation of ERK , JNK , and p38 .", "entity": [{"entity": "DPEP", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Furthermore , DPEP inhibited the LPS - induced phosphorylation of inhibitor kappa B ( I kappa B ) - alpha and NF - kappa B p50 .", "entity": [{"entity": "DPEP", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "Taken together , the results of this study demonstrate that DPEP inhibits LPS - stimulated inflammation by blocking the NF - kappa B and MAPK pathways in macrophages .", "entity": [{"entity": "DPEP", "entity_type": "Chemical", "pos": [60, 64]}], "task": "NER"}
{"text": "Radioprotection by two phenolic compounds : chlorogenic and quinic acid , on X - ray induced DNA damage in human blood lymphocytes in vitro .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "chlorogenic and quinic acid", "entity_type": "Chemical", "pos": [44, 71]}], "task": "NER"}
{"text": "The present study was designed to determine the radioprotective effect of two phytochemicals , namely , quinic acid and chlorogenic acid , against X - ray irradiation - induced genomic instability in non - tumorigenic human blood lymphocytes .", "entity": [{"entity": "quinic acid", "entity_type": "Chemical", "pos": [104, 115]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [120, 136]}], "task": "NER"}
{"text": "The protective ability of two phenolic acids against radiation - induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [30, 44]}], "task": "NER"}
{"text": "A Siemens Mevatron MD2 ( Siemens AG , USA , 1994 ) linear accelerator was used for irradiation .", "entity": [], "task": "NER"}
{"text": "The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X - ray irradiation and provided a significant radioprotective effect .", "entity": [{"entity": "quinic acid", "entity_type": "Chemical", "pos": [54, 65]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [70, 86]}], "task": "NER"}
{"text": "Quinic acid decreased the presence of irradiation - induced DNA damage by 5 . 99 - 53 . 57 % and chlorogenic acid by 4 . 49 - 48 . 15 % , as determined by the alkaline comet assay .", "entity": [{"entity": "Quinic acid", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [97, 113]}], "task": "NER"}
{"text": "The results show that quinic acid and chlorogenic acid may act as radioprotective compounds .", "entity": [{"entity": "quinic acid", "entity_type": "Chemical", "pos": [22, 33]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [38, 54]}], "task": "NER"}
{"text": "Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [72, 86]}], "task": "NER"}
{"text": "Additive inhibition of human alpha 1 beta 2 gamma 2 GABAA receptors by mixtures of commonly used drugs of abuse .", "entity": [], "task": "NER"}
{"text": "Yearly , exposure to drugs of abuse results in ~ 1 million emergency department visits in the US .", "entity": [], "task": "NER"}
{"text": "In ~ 50 % of the visits , stimulant drugs like cocaine and amphetamine - like substances ( e . g . 3 , 4 - methylenedioxymethamphetamine ( MDMA , the main active ingredient of ecstasy ) ) are involved , whereas in ~ 60 % multiple drugs are involved .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "3 , 4 - methylenedioxymethamphetamine", "entity_type": "Chemical", "pos": [99, 136]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [139, 143]}, {"entity": "ecstasy", "entity_type": "Chemical", "pos": [176, 183]}], "task": "NER"}
{"text": "These drugs induce higher dopamine and serotonin levels resulting in drug - induced toxicity .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [26, 34]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [39, 48]}], "task": "NER"}
{"text": "Since GABA receptors ( GABA - R ) provide the main inhibitory input on dopaminergic and serotonergic neurons , drug - induced inhibition of GABA - R could contribute to higher neurotransmitter levels and thus toxicity .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [23, 27]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "We therefore investigated the effects of combinations of commonly abused stimulant drugs ( cocaine , MDMA , 3 , 4 - methylenedioxyamphetamine ( MDA ) and meta - chlorophenylpiperazine ( mCPP ) ) on the function of the human alpha 1 beta 2 gamma 2 GABAA receptor ( hGABAA - R ) , expressed in Xenopus oocytes , using the two - electrode voltage - clamp technique .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [91, 98]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [101, 105]}, {"entity": "3 , 4 - methylenedioxyamphetamine", "entity_type": "Chemical", "pos": [108, 141]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [144, 147]}, {"entity": "meta - chlorophenylpiperazine", "entity_type": "Chemical", "pos": [154, 183]}, {"entity": "mCPP", "entity_type": "Chemical", "pos": [186, 190]}], "task": "NER"}
{"text": "These drugs concentration - dependently inhibited the GABA - evoked current ( mCPP > cocaine > MDMA > MDA ) .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "mCPP", "entity_type": "Chemical", "pos": [78, 82]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [95, 99]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Most drug combinations decreased the GABA - evoked current stronger than the single drug .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "Additivity was observed during combined exposure to low concentrations of cocaine and mCPP as well as during combined exposure to MDA with cocaine or mCPP .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [74, 81]}, {"entity": "mCPP", "entity_type": "Chemical", "pos": [86, 90]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [130, 133]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [139, 146]}, {"entity": "mCPP", "entity_type": "Chemical", "pos": [150, 154]}], "task": "NER"}
{"text": "However , combinations containing MDMA mainly resulted in sub - additivity or no additivity .", "entity": [{"entity": "MDMA", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "At drug concentrations relevant for clinical toxicology , co - exposure to >= 2 drugs can decrease the GABA - evoked current in an additive manner .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "Thus , in patients exposed to multiple drugs , inhibitory GABA - ergic input is reduced more prominently , likely resulting in higher brain dopamine levels .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [58, 62]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [140, 148]}], "task": "NER"}
{"text": "As this will increase the risk for drug - induced toxicity , treatment of drug - intoxicated patients with drugs that enhance GABA - ergic input should be further optimized .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [126, 130]}], "task": "NER"}
{"text": "A self - assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor .", "entity": [{"entity": "teniposide", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self - assembled nanocarrier for further oral chemotherapy .", "entity": [{"entity": "teniposide", "entity_type": "Chemical", "pos": [56, 66]}], "task": "NER"}
{"text": "The teniposide loaded self - assembled nanocarrier ( TSN ) was spherical nanometric particles with narrow size distribution .", "entity": [{"entity": "teniposide", "entity_type": "Chemical", "pos": [4, 14]}], "task": "NER"}
{"text": "The intestinal absorption of teniposide from TSN was obviously improved 4 . 09 - and 6 . 35 - fold in duodenum and jejunum at 0 . 5h after oral administration , then significantly decreased with the prolongation of time .", "entity": [{"entity": "teniposide", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "The cellular uptake of TSN in Caco - 2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time .", "entity": [], "task": "NER"}
{"text": "Moreover , TSN could be internalized into Caco - 2 cell monolayer through clathrin - mediated endocytosis pathway , and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway .", "entity": [], "task": "NER"}
{"text": "The pharmacokinetic results indicated that the AUC ( 0 - t ) value of TSN in rats was significantly improved 5 . 41 - fold than that of teniposide solution , moreover , the teniposide concentration in tumor from TSN was obviously improved over 7 - fold in tumor bearing mice .", "entity": [{"entity": "teniposide", "entity_type": "Chemical", "pos": [136, 146]}, {"entity": "teniposide", "entity_type": "Chemical", "pos": [173, 183]}], "task": "NER"}
{"text": "The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model .", "entity": [], "task": "NER"}
{"text": "Therefore , the self - assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy .", "entity": [{"entity": "teniposide", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "Combined delivery of BMP - 2 and bFGF from nanostructured colloidal gelatin gels and its effect on bone regeneration in vivo .", "entity": [], "task": "NER"}
{"text": "During the process of bone regeneration , a multitude of morphogenetic signaling factors regulate cellular behavior and ultimately tissue response .", "entity": [], "task": "NER"}
{"text": "These factors are presented to cells under strong spatial and temporal control , which stresses the relevance of controlled delivery of multiple growth factors for bone tissue regeneration .", "entity": [], "task": "NER"}
{"text": "This demand for biomimetic delivery has prompted the development of a novel generation of biomaterials that is capable of delivering multiple growth factors in a controlled manner .", "entity": [], "task": "NER"}
{"text": "Therefore , the current study has exploited the strong capacity of colloidal gels solely made of oppositely charged gelatin nanospheres to obtain controlled release of angiogenic and osteogenic growth factors .", "entity": [], "task": "NER"}
{"text": "The release kinetics of dual delivery of osteogenic bone morphogenetic protein - 2 ( BMP - 2 ) and angiogenic basic fibroblast growth factor ( bFGF ) were investigated in vitro by radiolabeling the respective growth factors and monitoring their release in vitro .", "entity": [], "task": "NER"}
{"text": "Furthermore , the effect of single or dual delivery of BMP - 2 and bFGF on bone regeneration was evaluated in vivo using a rat femoral condyle defect model .", "entity": [], "task": "NER"}
{"text": "The in vitro results confirmed that the delivery kinetics of BMP - 2 and / or bFGF are more dependent on the degree of crosslinking than on the type of gelatin .", "entity": [], "task": "NER"}
{"text": "Sequential release characterized by rapid release of angiogenic bFGF and more sustained release of BMP - 2 was obtained by loading bFGF onto cationic nanospheres of low crosslinking density and BMP - 2 onto anionic nanospheres of high crosslinking density .", "entity": [], "task": "NER"}
{"text": "The in vivo study demonstrated the biocompatibility and biodegradability of bare colloidal gelatin gels , and did not show any adverse effects on the process of bone healing after 4 week of implantation since the volumes of new bone formation were comparable to empty control defects .", "entity": [], "task": "NER"}
{"text": "An obvious stimulatory effect on bone regeneration was observed for the colloidal gels loaded with BMP - 2 , whereas bFGF - loaded colloidal gelatin gels did not influence the rate of bone regeneration .", "entity": [], "task": "NER"}
{"text": "In contrast , the combined delivery of BMP - 2 and bFGF resulted into an inhibitory effect on osteogenesis under the current experimental conditions .", "entity": [], "task": "NER"}
{"text": "Summarizing , the current study proved that nanostructured colloidal gelatin gels are suitable carriers for programmed and sustained release of multiple therapeutic proteins for tissue regeneration .", "entity": [], "task": "NER"}
{"text": "Influence of drying and cooking process on the phytochemical content , antioxidant and hypoglycaemic properties of two bell Capsicum annum L . cultivars .", "entity": [], "task": "NER"}
{"text": "The present study evaluates the influence of drying and cooking processes on the health properties of two bell Capsicum annuum L . cultivars Roggiano and Senise compared with fresh peppers .", "entity": [], "task": "NER"}
{"text": "The content of phytochemicals decreased in the order fresh > dried > dried frying processes .", "entity": [], "task": "NER"}
{"text": "HPLC analysis was applied to quantify five flavonoids from peppers .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "Apigenin was identified as main constituent .", "entity": [{"entity": "Apigenin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Its content was affected by drying and dried frying processes .", "entity": [], "task": "NER"}
{"text": "The antioxidant activity was evaluated by DPPH , ABTS , beta - carotene bleaching test and Fe - chelating activity assay .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [42, 46]}, {"entity": "ABTS", "entity_type": "Chemical", "pos": [49, 53]}, {"entity": "beta - carotene", "entity_type": "Chemical", "pos": [56, 71]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [91, 93]}], "task": "NER"}
{"text": "A comparable radical scavenging activity was observed for both cultivars .", "entity": [], "task": "NER"}
{"text": "Interestingly , frying process did not influenced this property .", "entity": [], "task": "NER"}
{"text": "Roggiano peppers exhibited the highest antioxidant activity using beta - carotene bleaching test with IC ( 50 ) values of 38 . 1 and 24 . 9 mu g / mL for total extract and n - hexane fraction , respectively .", "entity": [{"entity": "beta - carotene", "entity_type": "Chemical", "pos": [66, 81]}, {"entity": "n - hexane", "entity_type": "Chemical", "pos": [172, 182]}], "task": "NER"}
{"text": "GC - MS analysis of lipophilic fraction revealed the presence of fatty acids and vitamin E as major components .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [65, 76]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "In the inhibition of the carbohydrate - hydrolyzing enzymes fresh Senise peppers exerted the strongest activity against alpha - amylase with an IC ( 50 ) value of 55 . 3 mu g / mL .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [25, 37]}], "task": "NER"}
{"text": "Our results indicate that C . annuum cultivars Roggiano and Senise have an interestingly potential health benefits not influenced by processes that are used before consumption .", "entity": [], "task": "NER"}
{"text": "Activation of an apoptotic signal transduction pathway involved in the upregulation of calpain and apoptosis - inducing factor in aldosterone - induced primary cultured cardiomyocytes .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [130, 141]}], "task": "NER"}
{"text": "In this study , aldosterone ( ALD ) - induced apoptosis of cardiomyocyte was evaluated based on the previous studies , and the roles of calpain signaling were clarified .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "ALD", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "Primary cultured rat cardiomyocytes were injured by ALD ( 0 . 01 - 10 mu M ) for varying time periods .", "entity": [{"entity": "ALD", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "Then , the effects of ethylene glycol tetraacetic acid ( EGTA ) ( 0 . 5 mM ) , calpeptin ( 2 . 5 mu M ) , and spironoclactone ( 10 mu M ) were evaluated on cardiomyocytes activated by ALD .", "entity": [{"entity": "ethylene glycol tetraacetic acid", "entity_type": "Chemical", "pos": [22, 54]}, {"entity": "EGTA", "entity_type": "Chemical", "pos": [57, 61]}, {"entity": "calpeptin", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "spironoclactone", "entity_type": "Chemical", "pos": [110, 125]}, {"entity": "ALD", "entity_type": "Chemical", "pos": [184, 187]}], "task": "NER"}
{"text": "Cardiomyocytes that were injured by ALD were assayed by the MTT and LDH leakage ratio .", "entity": [{"entity": "ALD", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "Apoptosis was evaluated by a TUNEL assay , annexin V / PI staining , and caspase - 3 activity .", "entity": [], "task": "NER"}
{"text": "The expression of cleavage of Bid ( tBid ) , calpain and apoptosis - inducing factor ( AIF ) was evaluated by western blot analysis .", "entity": [], "task": "NER"}
{"text": "ALD increased calpain expression and caspase - 3 activity and promoted Bid cleavage .", "entity": [{"entity": "ALD", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "It also induced the release of AIF from mitochondria into the cytosol .", "entity": [], "task": "NER"}
{"text": "The upregulation of calpain , tBid and caspase - 3 activity were further inhibited by treatment with EGTA in the presence of ALD .", "entity": [{"entity": "EGTA", "entity_type": "Chemical", "pos": [101, 105]}, {"entity": "ALD", "entity_type": "Chemical", "pos": [125, 128]}], "task": "NER"}
{"text": "Additionally , AIF levels in the cytosol decreased due to EGTA but not due to calpeptin .", "entity": [{"entity": "EGTA", "entity_type": "Chemical", "pos": [58, 62]}, {"entity": "calpeptin", "entity_type": "Chemical", "pos": [78, 87]}], "task": "NER"}
{"text": "This was also accompanied by a significant decrease in apoptosis .", "entity": [], "task": "NER"}
{"text": "Furthermore , treatment with spironoclactone not only attenuated the pro - apoptotic effect of ALD but reversed the ALD - induced increase of calpain and AIF levels .", "entity": [{"entity": "spironoclactone", "entity_type": "Chemical", "pos": [29, 44]}, {"entity": "ALD", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "ALD", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "DHA supplementation : current implications in pregnancy and childhood .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Dietary supplementation with omega - 3 long chain fatty acids including docosahexaenoic acid ( DHA ) has increased in popularity in recent years and adequate DHA supplementation during pregnancy and early childhood is of clinical importance .", "entity": [{"entity": "omega - 3 long chain fatty acids", "entity_type": "Chemical", "pos": [29, 61]}, {"entity": "docosahexaenoic acid", "entity_type": "Chemical", "pos": [72, 92]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [158, 161]}], "task": "NER"}
{"text": "Some evidence has been built for the neuro - cognitive benefits of supplementation with long chain polyunsaturated fatty acids ( LCPUFA ) such as DHA during pregnancy ; however , recent data indicate that the anti - inflammatory properties may be of at least equal significance .", "entity": [{"entity": "long chain polyunsaturated fatty acids", "entity_type": "Chemical", "pos": [88, 126]}, {"entity": "LCPUFA", "entity_type": "Chemical", "pos": [129, 135]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [146, 149]}], "task": "NER"}
{"text": "Adequate DHA availability in the fetus / infant optimizes brain and retinal maturation in part by influencing neurotransmitter pathways .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "The anti - inflammatory properties of LCPUFA are largely mediated through modulation of signaling either directly through binding to receptors or through changes in lipid raft formation and receptor presentation .", "entity": [{"entity": "LCPUFA", "entity_type": "Chemical", "pos": [38, 44]}], "task": "NER"}
{"text": "Our goal is to review the current findings on DHA supplementation , specifically in pregnancy and infant neurodevelopment , as a pharmacologic agent with both preventative and therapeutic value .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "Given the overall benefits of DHA , maternal and infant supplementation may improve neurological outcomes especially in vulernable populations .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "However , optimal composition of the supplement and dosing and treatment strategies still need to be determined to lend support for routine supplementation .", "entity": [], "task": "NER"}
{"text": "Expression profiles of hippocampal regenerative sprouting - related genes and their regulation by E - 64d in a developmental rat model of penicillin - induced recurrent epilepticus .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [98, 105]}, {"entity": "penicillin", "entity_type": "Chemical", "pos": [138, 148]}], "task": "NER"}
{"text": "E - 64d ( a calpain and autophagy inhibitor ) has previously been shown safe for the treatment of Alzheimer ' s disease in humans .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In the present study , the potential protective mechanism of E - 64d on hippocampal aberrant mossy fiber sprouting was examined in a developmental rat model of penicillin - induced recurrent epilepticus .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "penicillin", "entity_type": "Chemical", "pos": [160, 170]}], "task": "NER"}
{"text": "A seizure was induced by penicillin every other day in Sprague - Dawley rats from postnatal day 21 ( P21 ) .", "entity": [{"entity": "penicillin", "entity_type": "Chemical", "pos": [25, 35]}], "task": "NER"}
{"text": "The rats were randomly assigned into the control group ( CONT1 ) , the control plus E - 64d ( CONT2 ) , the seizure group ( EXP1 ) and the seizure plus E - 64d ( EXP2 ) .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [84, 91]}, {"entity": "E - 64d", "entity_type": "Chemical", "pos": [152, 159]}], "task": "NER"}
{"text": "On P51 , mossy fiber sprouting and related gene expression in hippocampus were assessed by Timm staining and real - time RT - PCR methods , respectively .", "entity": [], "task": "NER"}
{"text": "To validate the RT - PCR results , western blot analysis was performed on selected genes .", "entity": [], "task": "NER"}
{"text": "E - 64d obviously suppressed the aberrant mossy fiber sprouting in the supragranular region of dentate gyrus and CA3 subfield of hippocampus .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Among the total twelve genes , six genes were strongly up - ( MT - 3 , ACAT1 , clusterin and ApoE ) or down - ( ZnT - 1 and PRG - 3 ) regulated by developmental seizures ( EXP1 ) compared with that in the CONT1 .", "entity": [], "task": "NER"}
{"text": "Up - regulation of ApoE and Clusterin was blocked by pretreatment with E - 64d both in mRNA and protein levels .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "Further , E - 64d - pretreated seizure rats ( EXP2 ) showed a significant downregulation of mRNA expression of PRG - 1 , PRG - 3 and PRG - 5 , cathepsin B and ApoE , as well as up - regulated nSMase and ANX7 in hippocampus when compared with EXP1 rats .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [10, 17]}], "task": "NER"}
{"text": "The results of the present study suggest that E - 64d , an elective inhibitor of calpain and autophagy , is potentially useful in the treatment of developmental seizure - induced brain damage both by regulating abnormal zinc signal transduction and through the modulation of altered lipid metabolism via ApoE / clusterin pathway in hippocampus .", "entity": [{"entity": "E - 64d", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [220, 224]}], "task": "NER"}
{"text": "Studies on a rhein - producing endophytic fungus isolated from Rheum palmatum L .", "entity": [{"entity": "rhein", "entity_type": "Chemical", "pos": [13, 18]}], "task": "NER"}
{"text": "Rheum palmatum L .", "entity": [], "task": "NER"}
{"text": "( Chinese rhubarb ) is a highly regarded medicinal plant .", "entity": [], "task": "NER"}
{"text": "Its dominant active constituents are anthraquinones including emodin , aloe - emodin , rhein , etc .", "entity": [{"entity": "anthraquinones", "entity_type": "Chemical", "pos": [37, 51]}, {"entity": "emodin", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "aloe - emodin", "entity_type": "Chemical", "pos": [71, 84]}, {"entity": "rhein", "entity_type": "Chemical", "pos": [87, 92]}], "task": "NER"}
{"text": "Rhein naturally occurs in anthraquinone ( 1 , 3 , 8 - trihydroxy - 6 - methyl anthraquinone ) , which is found in R . palmatum L . and related plants such as rhubarb .", "entity": [{"entity": "Rhein", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "anthraquinone", "entity_type": "Chemical", "pos": [26, 39]}, {"entity": "1 , 3 , 8 - trihydroxy - 6 - methyl anthraquinone", "entity_type": "Chemical", "pos": [42, 91]}], "task": "NER"}
{"text": "It has good antitumor , anti - inflammatory , anticancer , antimicrobial and hemostatic properties .", "entity": [], "task": "NER"}
{"text": "In this study , a total of 14 strains of endophytic fungi were isolated from R . palmatum L .", "entity": [], "task": "NER"}
{"text": "All fungal isolates were fermented in liquid PDA medium and their extracts were preliminarily analyzed by antibacterial reactions , magnesium acetate - methanol reagent and Borntraiger ' s reaction , and the strain reselection was made by thin - layer chromatography ( TLC ) , high - performance liquid chromatography ( HPLC ) and LC - MS to identify the fermentation products of the selected strains and confirmed through a comparison with authentic standards .", "entity": [{"entity": "magnesium acetate", "entity_type": "Chemical", "pos": [132, 149]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "Extract from one strain , R13 , showed positive reactions with both reagents .", "entity": [], "task": "NER"}
{"text": "The strain R13 had a component with the same TLC ( Rf ) value and HPLC , LC - MS retention time as authentic rhein standards .", "entity": [{"entity": "rhein", "entity_type": "Chemical", "pos": [109, 114]}], "task": "NER"}
{"text": "The yield of rhein in R13 can reach 5 . 672mgl ( - 1 ) .", "entity": [{"entity": "rhein", "entity_type": "Chemical", "pos": [13, 18]}], "task": "NER"}
{"text": "The fungi were identified as Fusarium solani by using both ITS rDNA sequencing and spore morphology .", "entity": [], "task": "NER"}
{"text": "Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis .", "entity": [{"entity": "triterpenoids", "entity_type": "Chemical", "pos": [30, 43]}, {"entity": "saponin", "entity_type": "Chemical", "pos": [113, 120]}], "task": "NER"}
{"text": "The tea seed triterpene saponin ( TS ) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin ( TTS ) , hydrolysate of the TTS and tea seed flavonoid glycosides ( TF ) .", "entity": [{"entity": "triterpene saponin", "entity_type": "Chemical", "pos": [13, 31]}, {"entity": "saponin", "entity_type": "Chemical", "pos": [236, 243]}, {"entity": "flavonoid glycosides", "entity_type": "Chemical", "pos": [290, 310]}], "task": "NER"}
{"text": "By bioassay - guided isolation , the TS fraction was separated and seven major components were purified and identified as theasaponin E1 ( 1 ) , theasaponin E2 ( 2 ) , theasaponin C1 ( 3 ) , assamsaponin C ( 4 ) , theasaponin H1 ( 5 ) , theasaponin A9 ( 6 ) , and theasaponin A8 ( 7 ) , among which compounds 4 and 5 were isolated from this genus for the first time .", "entity": [{"entity": "theasaponin E1", "entity_type": "Chemical", "pos": [122, 136]}, {"entity": "theasaponin E2", "entity_type": "Chemical", "pos": [145, 159]}, {"entity": "theasaponin C1", "entity_type": "Chemical", "pos": [168, 182]}, {"entity": "assamsaponin C", "entity_type": "Chemical", "pos": [191, 205]}, {"entity": "theasaponin H1", "entity_type": "Chemical", "pos": [214, 228]}, {"entity": "theasaponin A9", "entity_type": "Chemical", "pos": [237, 251]}, {"entity": "theasaponin A8", "entity_type": "Chemical", "pos": [264, 278]}], "task": "NER"}
{"text": "The antitumor bioassay of the isolated compounds showed that compounds 1 , 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60 .", "entity": [], "task": "NER"}
{"text": "Furthermore , compound 1 ( the major constituent with a mass content of over 1 % ) showed significant QR inducing activity with an IR value of 4 . 2 at 4 mu g / ml .", "entity": [], "task": "NER"}
{"text": "So it can be concluded that tea seed especially the compound 1 ( theasaponin E1 ) could be used as an antitumor agent and a chemoprevention agent of cancer .", "entity": [{"entity": "theasaponin E1", "entity_type": "Chemical", "pos": [65, 79]}], "task": "NER"}
{"text": "The preliminary structure - activity relationship in the anti - tumor activity and QR inducing activity of tea saponins was discussed briefly .", "entity": [{"entity": "saponins", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "On the structure of aspongopusin recently isolated from Aspongopus chinensis .", "entity": [{"entity": "aspongopusin", "entity_type": "Chemical", "pos": [20, 32]}], "task": "NER"}
{"text": "The 2 , 5 - disubstituted oxazole recently proposed for aspongopusin , a natural product isolated from Aspongopus chinensis , was synthesized through an unambiguous route .", "entity": [{"entity": "2 , 5 - disubstituted oxazole", "entity_type": "Chemical", "pos": [4, 33]}, {"entity": "aspongopusin", "entity_type": "Chemical", "pos": [56, 68]}], "task": "NER"}
{"text": "The synthetic sample showed ( 1 ) H and ( 13 ) C NMR entirely different from those in the literature , revealing that the initially assigned structure was incorrect .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "The spectroscopic data for the given structure are thus made available for the first time .", "entity": [], "task": "NER"}
{"text": "DNA polymerase minor groove interactions modulate mutagenic bypass of a templating 8 - oxoguanine lesion .", "entity": [{"entity": "8 - oxoguanine", "entity_type": "Chemical", "pos": [83, 97]}], "task": "NER"}
{"text": "A major base lesion resulting from oxidative stress is 8 - oxo - 7 , 8 - dihydro - 2 ' - deoxyguanosine ( 8 - oxoG ) that has ambiguous coding potential .", "entity": [{"entity": "8 - oxo - 7 , 8 - dihydro - 2 ' - deoxyguanosine", "entity_type": "Chemical", "pos": [55, 103]}, {"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "Error - free DNA synthesis involves 8 - oxoG adopting an anti - conformation to base pair with cytosine whereas mutagenic bypass involves 8 - oxoG adopting a syn - conformation to base pair with adenine .", "entity": [{"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "cytosine", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [138, 146]}, {"entity": "adenine", "entity_type": "Chemical", "pos": [195, 202]}], "task": "NER"}
{"text": "Left unrepaired the syn - 8 - oxoG / dAMP base pair results in a G - C to T - A transversion .", "entity": [{"entity": "syn - 8 - oxoG", "entity_type": "Chemical", "pos": [20, 34]}, {"entity": "dAMP", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "During base excision repair of this mispair , DNA polymerase ( pol ) beta is confronted with gap filling opposite 8 - oxoG .", "entity": [{"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [114, 122]}], "task": "NER"}
{"text": "To determine how pol beta discriminates between anti - and syn - 8 - oxoG , we introduced a point mutation ( R283K ) to alter insertion specificity .", "entity": [{"entity": "anti - and syn - 8 - oxoG", "entity_type": "Chemical", "pos": [48, 73]}], "task": "NER"}
{"text": "Kinetic studies demonstrate that this substitution results in an increased fidelity opposite 8 - oxoG .", "entity": [{"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "Structural studies with R283K pol beta show that the binary DNA complex has 8 - oxoG in equilibrium between anti - and syn - forms .", "entity": [{"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "Ternary complexes with incoming dCTP resemble the wild - type enzyme , with templating anti - 8 - oxoG base pairing with incoming cytosine .", "entity": [{"entity": "dCTP", "entity_type": "Chemical", "pos": [32, 36]}, {"entity": "anti - 8 - oxoG", "entity_type": "Chemical", "pos": [87, 102]}, {"entity": "cytosine", "entity_type": "Chemical", "pos": [130, 138]}], "task": "NER"}
{"text": "In contrast to wild - type pol beta , the ternary complex of the R283K mutant with an incoming dATP - analogue and templating 8 - oxoG resembles a G - A mismatched structure with 8 - oxoG adopting an anti - conformation .", "entity": [{"entity": "dATP", "entity_type": "Chemical", "pos": [95, 99]}, {"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [126, 134]}, {"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [179, 187]}], "task": "NER"}
{"text": "These results demonstrate that the incoming nucleotide is unable to induce a syn - 8 - oxoG conformation without minor groove DNA polymerase interactions that influence templating ( anti - / syn - equilibrium ) of 8 - oxoG while modulating fidelity .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "syn - 8 - oxoG", "entity_type": "Chemical", "pos": [77, 91]}, {"entity": "8 - oxoG", "entity_type": "Chemical", "pos": [214, 222]}], "task": "NER"}
{"text": "Effect of long - term co - administration of Wuzhi tablet ( Schisandra sphenanthera extract ) and prednisone on the pharmacokinetics of tacrolimus .", "entity": [{"entity": "prednisone", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "tacrolimus", "entity_type": "Chemical", "pos": [136, 146]}], "task": "NER"}
{"text": "Tacrolimus ( TAC ) is an immunosuppressant that has been widely used alone or in combination with prednisone ( PRED ) to prevent acute rejection after organ transplantation .", "entity": [{"entity": "Tacrolimus", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "TAC", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "prednisone", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "PRED", "entity_type": "Chemical", "pos": [111, 115]}], "task": "NER"}
{"text": "Wuzhi tablet ( WZ , Schisandra sphenanthera extract ) is often prescribed with TAC to prevent drug - induced hepatitis .", "entity": [{"entity": "TAC", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "We recently reported that WZ could significantly increase TAC blood exposure by inhibiting P - gp - mediated efflux and CYP3A - mediated metabolism of TAC .", "entity": [{"entity": "TAC", "entity_type": "Chemical", "pos": [58, 61]}, {"entity": "TAC", "entity_type": "Chemical", "pos": [151, 154]}], "task": "NER"}
{"text": "PRED is also a substrate of P - gp and is a weak inducer of CYP3A , and drug - drug interactions within this combination therapy might occur .", "entity": [{"entity": "PRED", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Therefore , the purpose of this study was to investigate the effect of long - term treatment of WZ and PRED on the pharmacokinetics of TAC in rats .", "entity": [{"entity": "PRED", "entity_type": "Chemical", "pos": [103, 107]}, {"entity": "TAC", "entity_type": "Chemical", "pos": [135, 138]}], "task": "NER"}
{"text": "After 14 days of co - administration of WZ and PRED , the AUC ( 0 - 24h ) of oral TAC was increased ( from 59 . 6 +/- 37 . 3 to 95 . 3 +/- 39 . 4 ng h / ml , p = 0 . 18 ) and the clearance was decreased ( from 38 . 4 +/- 28 . 4 to 17 . 7 +/- 6 . 4 l / h / kg , p = 0 . 15 ) .", "entity": [{"entity": "PRED", "entity_type": "Chemical", "pos": [47, 51]}, {"entity": "TAC", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "When only co - administered with WZ , AUC ( 0 - 24h ) of TAC was demonstrated a significantly increase ( from 59 . 6 +/- 37 . 3 to 135 . 9 +/- 34 . 8 ng h / ml , p < 0 . 05 ) .", "entity": [{"entity": "TAC", "entity_type": "Chemical", "pos": [57, 60]}], "task": "NER"}
{"text": "The concomitant administration of PRED resulted in a reduction in the systemic exposure of TAC and an increase in its clearance , though neither was statistically significant .", "entity": [{"entity": "PRED", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "TAC", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "Thus , our study suggested that the presence of WZ and PRED still could increase the systemic exposure of TAC in rats .", "entity": [{"entity": "PRED", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "TAC", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "The drug - drug interactions among this combination therapy should still be taken into consideration in clinical practice .", "entity": [], "task": "NER"}
{"text": "Naturally occurring HCA1 missense mutations result in loss of function : potential impact on lipid deposition .", "entity": [], "task": "NER"}
{"text": "The hydroxy - carboxylic acid receptor ( HCA1 ) is a G protein - coupled receptor that is highly expressed on adipocytes and considered a potential target for the treatment of dyslipidemia .", "entity": [{"entity": "hydroxy - carboxylic acid", "entity_type": "Chemical", "pos": [4, 29]}], "task": "NER"}
{"text": "In the current study , we investigated the pharmacological properties of naturally occurring variants in this receptor ( H43Q , A110V , S172L , and D253H ) .", "entity": [], "task": "NER"}
{"text": "After transient expression of these receptors into human embryonic kidney 293 cells , basal and ligand - induced signaling were assessed using luciferase reporter gene assays .", "entity": [], "task": "NER"}
{"text": "The A110V , S172L , and D253 variants showed reduced basal activity ; the S172L mutant displayed a decrease in potency to the endogenous ligand L - lactate .", "entity": [{"entity": "L - lactate", "entity_type": "Chemical", "pos": [144, 155]}], "task": "NER"}
{"text": "Both the S172L and D253H variants also showed impaired cell surface expression , which may in part explain the reduced activity of these receptors .", "entity": [], "task": "NER"}
{"text": "The impact of a loss in HCA1 function on lipid accumulation was investigated in the adipocyte cell line , OP9 .", "entity": [], "task": "NER"}
{"text": "In these cells , endogenous HCA1 transcript levels rapidly increased and reached maximal levels 3 days after the addition of differentiation media .", "entity": [], "task": "NER"}
{"text": "Knockdown of HCA1 using siRNA resulted in an increase in lipid accumulation as assessed by quantification of Nile Red staining and TLC analysis .", "entity": [{"entity": "Nile Red", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "Our data suggest that lipid homeostasis may be altered in carriers of selected HCA1 missense variants .", "entity": [], "task": "NER"}
{"text": "Anti - inflammatory sesquiterpene derivatives from the leaves of Tripterygium wilfordii .", "entity": [{"entity": "sesquiterpene", "entity_type": "Chemical", "pos": [20, 33]}], "task": "NER"}
{"text": "Twelve new dihydroagarofuran sesquiterpene polyol esters , triptersinines A - L ( 1 - 12 ) , and eight known sesquiterpene pyridine alkaloids were isolated from the leaves of Tripterygium wilfordii .", "entity": [{"entity": "dihydroagarofuran sesquiterpene polyol esters", "entity_type": "Chemical", "pos": [11, 56]}, {"entity": "triptersinines A - L", "entity_type": "Chemical", "pos": [59, 79]}, {"entity": "sesquiterpene", "entity_type": "Chemical", "pos": [109, 122]}, {"entity": "pyridine alkaloids", "entity_type": "Chemical", "pos": [123, 141]}], "task": "NER"}
{"text": "Their structures were elucidated on the basis of spectroscopic analyses , including UV , IR , and NMR experiments ( ( 1 ) H - ( 1 ) H COSY , NOESY , HSQC , and HMBC ) .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [116, 123]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Furthermore , in an in vitro bioassay , compounds 1 , 9 , 11 , 13 , 14 , and 18 showed moderate inhibitory effects on nitric oxide production in LPS - induced macrophages at 5 mu M ; all compounds were inactive when tested against five human cancer cell lines ( IC ( 50 ) values > 1 mu M ) .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [118, 130]}], "task": "NER"}
{"text": "Bioassay - guided isolation of proanthocyanidins with antiangiogenic activities .", "entity": [{"entity": "proanthocyanidins", "entity_type": "Chemical", "pos": [31, 48]}], "task": "NER"}
{"text": "The proangiogenic members of the vascular endothelial growth factor ( VEGF ) family and related receptors play a central role in the modulation of pathological angiogenesis .", "entity": [], "task": "NER"}
{"text": "In order to identify plant compounds able to interfere in the VEGFs / VEGFR - 1 ( Flt - 1 ) recognition by VEGF family members , the extracts of the aerial parts of Campsiandra guayanensis and Feretia apodanthera were screened by a competitive ELISA - based assay .", "entity": [], "task": "NER"}
{"text": "By using this bioassay - oriented approach five proanthocyanindins , including the new natural compounds ( 2S ) - 4 ' , 5 , 7 - trihydroxyflavan - ( 4 beta --> 8 ) - afzelechin ( 1 ) and ( 2S ) - 4 ' , 5 , 7 - trihydroxyflavan - ( 4 beta --> 8 ) - epiafzelechin ( 2 ) and the known geranin B ( 3 ) , proanthocyanidin A2 ( 4 ) , and proanthocyanidin A1 ( 5 ) , were isolated .", "entity": [{"entity": "proanthocyanindins", "entity_type": "Chemical", "pos": [48, 66]}, {"entity": "( 2S ) - 4 ' , 5 , 7 - trihydroxyflavan - ( 4 beta --> 8 ) - afzelechin", "entity_type": "Chemical", "pos": [105, 176]}, {"entity": "( 2S ) - 4 ' , 5 , 7 - trihydroxyflavan - ( 4 beta --> 8 ) - epiafzelechin", "entity_type": "Chemical", "pos": [187, 261]}, {"entity": "geranin B", "entity_type": "Chemical", "pos": [282, 291]}, {"entity": "proanthocyanidin A2", "entity_type": "Chemical", "pos": [300, 319]}, {"entity": "proanthocyanidin A1", "entity_type": "Chemical", "pos": [332, 351]}], "task": "NER"}
{"text": "The study of the antiangiogenic activities of compounds 1 - 5 using ELISA and SPR assays showed compound 1 as being the most active .", "entity": [], "task": "NER"}
{"text": "The antiangiogenic activity of 1 was also confirmed in vivo by the chicken chorioallantoic membrane assay .", "entity": [], "task": "NER"}
{"text": "Our results indicated 1 as a new antiangiogenic compound inhibiting the interaction between VEGF - A or PlGF and their receptor VEGRF - 1 .", "entity": [], "task": "NER"}
{"text": "Highly ordered cobalt - phthalocyanine chains on fractional atomic steps : one - dimensionality and electron hybridization .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [15, 21]}, {"entity": "phthalocyanine", "entity_type": "Chemical", "pos": [24, 38]}], "task": "NER"}
{"text": "Precisely controlled fabrication of low - dimensional molecular structures with tailored morphologies and electronic properties is at the heart of the nanotechnology research .", "entity": [], "task": "NER"}
{"text": "Especially , the formation of one - dimensional ( 1D ) structures has been strongly desired due to their expected high performance for information processing in electronic / magnetic devices .", "entity": [], "task": "NER"}
{"text": "So far , however , they have been obtained by tough and slow methods such as manipulation of individual molecules , which are totally unsuited for mass production .", "entity": [], "task": "NER"}
{"text": "Here we show that highly ordered cobalt - phthalocyanine chains can be self - assembled on a metal surface using fractional atomic steps as a template .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [33, 39]}, {"entity": "phthalocyanine", "entity_type": "Chemical", "pos": [42, 56]}], "task": "NER"}
{"text": "We also demonstrate that the substrate surface electrons , which can be confined by cobalt - phthalocyanine molecules , can propagate along the step arrays and can hybridize with the molecular orbitals .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [84, 90]}, {"entity": "phthalocyanine", "entity_type": "Chemical", "pos": [93, 107]}], "task": "NER"}
{"text": "These findings provide a significant step toward readily realization of 1D charge / spin transport , which can be mediated either directly by the molecules or by the surface electrons .", "entity": [], "task": "NER"}
{"text": "Discovery of small molecule vanin inhibitors : new tools to study metabolism and disease .", "entity": [], "task": "NER"}
{"text": "Vanins are enzymes with pantetheinase activity and are presumed to play a role in the recycling of pantothenic acid ( vitamin B5 ) from pantetheine .", "entity": [{"entity": "pantothenic acid", "entity_type": "Chemical", "pos": [99, 115]}, {"entity": "vitamin B5", "entity_type": "Chemical", "pos": [118, 128]}, {"entity": "pantetheine", "entity_type": "Chemical", "pos": [136, 147]}], "task": "NER"}
{"text": "Pantothenic acid is an essential nutrient required to synthesize coenzyme A , a cofactor involved in many biological processes such as fatty acid synthesis and oxidation of pyruvate to fuel the citric acid cycle .", "entity": [{"entity": "Pantothenic acid", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "coenzyme A", "entity_type": "Chemical", "pos": [65, 75]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [135, 145]}, {"entity": "pyruvate", "entity_type": "Chemical", "pos": [173, 181]}, {"entity": "citric acid", "entity_type": "Chemical", "pos": [194, 205]}], "task": "NER"}
{"text": "Hydrolysis of pantetheine also liberates cysteamine , a known antioxidant .", "entity": [{"entity": "pantetheine", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "cysteamine", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "Vanin - 1 is highly expressed in liver and is under transcriptional control of PPAR - alpha and nutritional status , suggesting a role in energy metabolism .", "entity": [], "task": "NER"}
{"text": "The lack of potent and specific inhibitors of vanins has hampered detailed investigation of their function .", "entity": [], "task": "NER"}
{"text": "We hereby report the design , synthesis , and characterization of a novel pantetheine analogue , RR6 , that acts as a selective , reversible , and competitive vanin inhibitor at nanomolar concentration .", "entity": [{"entity": "pantetheine", "entity_type": "Chemical", "pos": [74, 85]}, {"entity": "RR6", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "Oral administration of RR6 in rats completely inhibited plasma vanin activity and caused alterations of plasma lipid concentrations upon fasting , thereby illustrating its potential use in chemical biology research .", "entity": [{"entity": "RR6", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "Theoretical characterization of X - ray absorption , emission , and photoelectron spectra of nitrogen doped along graphene edges .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [93, 101]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [114, 122]}], "task": "NER"}
{"text": "K - edge X - ray absorption ( XAS ) , emission ( XES ) , and photoelectron ( XPS ) spectra of nitrogen doped along graphene edges are systematically investigated by using first - principles methods .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [94, 102]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "In this study we considered pyridinium - like , pyridine - like , cyanide - like , and amine - like nitrogens at armchair and zigzag edges and pyrrole - like nitrogen at armchair edge as well as graphite - like nitrogen at graphene interior site .", "entity": [{"entity": "pyridinium", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "pyridine", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "cyanide", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "amine", "entity_type": "Chemical", "pos": [87, 92]}, {"entity": "nitrogens", "entity_type": "Chemical", "pos": [100, 109]}, {"entity": "pyrrole", "entity_type": "Chemical", "pos": [143, 150]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [158, 166]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [195, 203]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [211, 219]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [223, 231]}], "task": "NER"}
{"text": "Our results indicate that nitrogen configuration and its location ( armchair or zigzag edge ) in nitrogen - doped graphene can be identified via the spectral analysis .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [26, 34]}, {"entity": "nitrogen - doped graphene", "entity_type": "Chemical", "pos": [97, 122]}], "task": "NER"}
{"text": "Furthermore , some controversial spectral features observed in experiment for N - doped graphene - like materials are unambiguously assigned .", "entity": [{"entity": "N - doped graphene", "entity_type": "Chemical", "pos": [78, 96]}], "task": "NER"}
{"text": "The present analysis gives an explanation to the reason why the peak assignment is usually made differently between XPS and XAS .", "entity": [], "task": "NER"}
{"text": "Study of the potential oxidative stress induced by six solvents in the rat brain .", "entity": [], "task": "NER"}
{"text": "The mechanisms of action involved in the neurotoxicity of solvents are poorly understood .", "entity": [], "task": "NER"}
{"text": "In vitro studies have suggested that the effects of some solvents might be due to the formation of reactive oxygen species ( ROS ) .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "This study assesses hydroxyl radical ( OH ) generation and measures malondialdehyde ( MDA ) levels in the cerebral tissue of rats exposed to six solvents ( n - hexane , n - octane , toluene , n - butylbenzene , cyclohexane and 1 , 2 , 4 - trimethylcyclohexane ) .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "OH", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [68, 83]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "n - hexane", "entity_type": "Chemical", "pos": [156, 166]}, {"entity": "n - octane", "entity_type": "Chemical", "pos": [169, 179]}, {"entity": "toluene", "entity_type": "Chemical", "pos": [182, 189]}, {"entity": "n - butylbenzene", "entity_type": "Chemical", "pos": [192, 208]}, {"entity": "cyclohexane", "entity_type": "Chemical", "pos": [211, 222]}, {"entity": "1 , 2 , 4 - trimethylcyclohexane", "entity_type": "Chemical", "pos": [227, 259]}], "task": "NER"}
{"text": "Three of these solvents have been shown to generate ROS in studies carried out in vitro on granular cell cultures from rat cerebellum .", "entity": [], "task": "NER"}
{"text": "We assessed OH production by quantifying the rate of formation of 3 , 4 - dihydroxybenzoic acid using a trapping agent , 4 - hydroxybenzoic acid , infused via the microdialysis probe , into the prefrontal cortex of rats exposed intraperitoneally to the solvents .", "entity": [{"entity": "OH", "entity_type": "Chemical", "pos": [12, 14]}, {"entity": "3 , 4 - dihydroxybenzoic acid", "entity_type": "Chemical", "pos": [66, 95]}, {"entity": "4 - hydroxybenzoic acid", "entity_type": "Chemical", "pos": [121, 144]}], "task": "NER"}
{"text": "Extracellular MDA was quantified in microdialysates collected from the prefrontal cortex of rats exposed , 6h / day for ten days , to 1000ppm of the solvents ( except for n - butylbenzene , generated at 830ppm ) in inhalation chambers .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "n - butylbenzene", "entity_type": "Chemical", "pos": [171, 187]}], "task": "NER"}
{"text": "Tissue levels of free and total MDA were measured in different brain structures for rats acutely ( intraperitoneal route ) and sub - acutely ( inhalation ) exposed to solvents .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "None of the six solvents studied increased the production of hydroxyl radicals in the prefrontal cortex after acute administration .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "Nor did they increase extracellular or tissue levels of MDA after 10 days ' inhalation exposure .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "On the other hand , a decrease in the concentrations of free MDA in brain structures was observed after acute administration of n - hexane , 1 , 2 , 4 - trimethylcyclohexane , toluene and n - butylbenzene .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [61, 64]}, {"entity": "n - hexane", "entity_type": "Chemical", "pos": [128, 138]}, {"entity": "1 , 2 , 4 - trimethylcyclohexane", "entity_type": "Chemical", "pos": [141, 173]}, {"entity": "toluene", "entity_type": "Chemical", "pos": [176, 183]}, {"entity": "n - butylbenzene", "entity_type": "Chemical", "pos": [188, 204]}], "task": "NER"}
{"text": "Therefore , data of this study carried out in vivo did not confirm observations made in vitro on cell cultures .", "entity": [], "task": "NER"}
{"text": "Antivirals : past , present and future .", "entity": [], "task": "NER"}
{"text": "Vaccination is possible to prevent infections with some viruses : hepatitis B virus ( HBV ) , varicella - zoster virus ( VZV ) , influenza A and B viruses , Yellow fever virus and poliovirus ; but not for others : human immunodeficiency virus ( HIV ) , hepatitis C virus ( HCV ) , herpes simplex virus ( HSV ) , cytomegalovirus ( CMV ) , and most hemorrhagic fever viruses ( HFV ) ( except for Yellow fever virus ) .", "entity": [], "task": "NER"}
{"text": "Antiviral therapy is obviously needed to control those infections that are not amenable to prophylaxis by vaccination , but is also highly desirable for those infections where vaccination has not been implemented or did not fulfill its premises for complete protection .", "entity": [], "task": "NER"}
{"text": "The vasorelaxant effects of 1 - nitro - 2 - phenylethane involve stimulation of the soluble guanylate cyclase - cGMP pathway .", "entity": [{"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [28, 56]}, {"entity": "guanylate", "entity_type": "Chemical", "pos": [92, 101]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "1 - Nitro - 2 - phenylethane is the first organic NO 2 - containing molecule isolated from plants .", "entity": [{"entity": "1 - Nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [0, 28]}, {"entity": "NO 2", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "It possesses interesting hypotensive , bradycardic , and vasodilator properties , but the mode by which it induces vasorelaxation is still unknown .", "entity": [], "task": "NER"}
{"text": "The underlying mechanism involved in the vasodilator effect of 1 - nitro - 2 - phenylethane was investigated in rat aorta .", "entity": [{"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [63, 91]}], "task": "NER"}
{"text": "The vasorelaxant effects of 1 - nitro - 2 - phenylethane did not depend on endothelial layer integrity , and the effects were refractory to L - N ( G ) - nitroarginine methyl ester ( L - NAME ) - induced nitric oxide synthase inhibition .", "entity": [{"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [28, 56]}, {"entity": "L - N ( G ) - nitroarginine methyl ester", "entity_type": "Chemical", "pos": [140, 180]}, {"entity": "L - NAME", "entity_type": "Chemical", "pos": [183, 191]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [204, 216]}], "task": "NER"}
{"text": "Vasorelaxation was similarly resistant to treatment with indomethacin , cis - N - ( 2 - phenylcyclopentyl ) - azacyclotridec - 1 - en - 2 - amine hydrochloride ( MDL - 12330A ) , and KT5720 , indicating that neither prostaglandin release nor adenylyl cyclase activation is involved .", "entity": [{"entity": "indomethacin", "entity_type": "Chemical", "pos": [57, 69]}, {"entity": "cis - N - ( 2 - phenylcyclopentyl ) - azacyclotridec - 1 - en - 2 - amine hydrochloride", "entity_type": "Chemical", "pos": [72, 159]}, {"entity": "MDL - 12330A", "entity_type": "Chemical", "pos": [162, 174]}, {"entity": "KT5720", "entity_type": "Chemical", "pos": [183, 189]}, {"entity": "prostaglandin", "entity_type": "Chemical", "pos": [216, 229]}, {"entity": "adenylyl", "entity_type": "Chemical", "pos": [242, 250]}], "task": "NER"}
{"text": "Conversely , methylene blue - and ODQ - induced guanylate cyclase inhibition reduced the vasorelaxation induced by 1 - nitro - 2 - phenylethane .", "entity": [{"entity": "methylene blue", "entity_type": "Chemical", "pos": [13, 27]}, {"entity": "ODQ", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "guanylate", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [115, 143]}], "task": "NER"}
{"text": "The pharmacological blockade of K ( + ) channels with tetraethylammonium , glybenclamide , and 4 - aminopyridine also blunted vasorelaxation induced by 1 - nitro - 2 - phenylethane .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "tetraethylammonium", "entity_type": "Chemical", "pos": [54, 72]}, {"entity": "glybenclamide", "entity_type": "Chemical", "pos": [75, 88]}, {"entity": "4 - aminopyridine", "entity_type": "Chemical", "pos": [95, 112]}, {"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [152, 180]}], "task": "NER"}
{"text": "The effects of 1 - nitro - 2 - phenylethane were reversed by 1H - [ 1 , 2 , 4 ] oxadiazolo [ 4 , 3 - a ] quinoxalin - 1 - one ( ODQ ) and comparable to the effects induced by sodium nitroprusside .", "entity": [{"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [15, 43]}, {"entity": "1H - [ 1 , 2 , 4 ] oxadiazolo [ 4 , 3 - a ] quinoxalin - 1 - one", "entity_type": "Chemical", "pos": [61, 125]}, {"entity": "ODQ", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "sodium nitroprusside", "entity_type": "Chemical", "pos": [175, 195]}], "task": "NER"}
{"text": "In silico analysis using an Ns H - NOX subunit of guanylate cyclase revealed a pocket on the macromolecule surface where 1 - nitro - 2 - phenylethane preferentially docked .", "entity": [{"entity": "guanylate", "entity_type": "Chemical", "pos": [50, 59]}, {"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [121, 149]}], "task": "NER"}
{"text": "In vitro , 1 - nitro - 2 - phenylethane increased cyclic guanosine 3 ' , 5 ' - monophosphate ( cGMP ) levels in rat aortic rings , an effect also reversed by ODQ .", "entity": [{"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [11, 39]}, {"entity": "cyclic guanosine 3 ' , 5 ' - monophosphate", "entity_type": "Chemical", "pos": [50, 92]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [95, 99]}, {"entity": "ODQ", "entity_type": "Chemical", "pos": [158, 161]}], "task": "NER"}
{"text": "In conclusion , 1 - nitro - 2 - phenylethane produces vasodilator effects by stimulating the soluble guanylate cyclase - cGMP pathway .", "entity": [{"entity": "1 - nitro - 2 - phenylethane", "entity_type": "Chemical", "pos": [16, 44]}, {"entity": "guanylate", "entity_type": "Chemical", "pos": [101, 110]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin - induced diabetic rats .", "entity": [{"entity": "secoisolariciresinol diglucoside", "entity_type": "Chemical", "pos": [23, 55]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [59, 73]}], "task": "NER"}
{"text": "Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia .", "entity": [], "task": "NER"}
{"text": "Its complications such as neuropathy , cardiopathy , nephropathy , and micro and macro vascular diseases are believed to be due to the increase in oxidative stress and decrease in the level of antioxidants .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine the antihyperglycemic activity of synthetic Secoisolariciresinol diglucoside ( SDG ) in streptozotocin ( STZ ) - induced diabetic rats .", "entity": [{"entity": "Secoisolariciresinol diglucoside", "entity_type": "Chemical", "pos": [83, 115]}, {"entity": "SDG", "entity_type": "Chemical", "pos": [118, 121]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [127, 141]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "The synthetic SDG in a single - dose ( 20 mg / kg b . w . ) two - day study showed dose - dependent reduction in glucose levels with maximum effect of 64 . 62 % at 48 h post drug treatment ( p < 0 . 05 ) , which is comparable to that of the standard drug tolbutamide ( 20 mg / kg b . w . ) .", "entity": [{"entity": "SDG", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [113, 120]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [255, 266]}], "task": "NER"}
{"text": "In a multi - dose fourteen - day study , lower doses of SDG ( 5 and 10 mg / kg b . w . ) exhibited moderate reduction in glucose levels , lipid profile , restoration of antioxidant enzymes and improvement of the insulin and c - peptide levels which shows the regeneration of beta - cell which secretes insulin .", "entity": [{"entity": "SDG", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [121, 128]}], "task": "NER"}
{"text": "Altered levels of lipids and enzymatic antioxidants were also restored by the SDG to the considerable levels in diabetic rats .", "entity": [{"entity": "SDG", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "Results of the present investigation suggest that diabetes is associated with an increase in oxidative stress as shown by increase in serum malondialdehyde ( MDA ) , decreased levels of catalase ( CAT ) , superoxide dismutase ( SOD ) , and glutathione ( GSH ) .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [140, 155]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [158, 161]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [205, 215]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [240, 251]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [254, 257]}], "task": "NER"}
{"text": "Also , diabetes is associated with an increase in serum total cholesterol as well as triglycerides levels and decrease in insulin and c - peptide levels .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [62, 73]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [85, 98]}], "task": "NER"}
{"text": "SDG is effective in retarding the development of diabetic complications .", "entity": [{"entity": "SDG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "We propose that synthetic SDG exerts anti hyperglycemic effect by preventing the liver from peroxidation damage through inhibition of ROS level mediated increased level of enzymatic and non - enzymatic antioxidants .", "entity": [{"entity": "SDG", "entity_type": "Chemical", "pos": [26, 29]}], "task": "NER"}
{"text": "And , also maintaining tissue function which results in improving the sensitivity and response of target cells in STZ - induced diabetic rats to insulin .", "entity": [{"entity": "STZ", "entity_type": "Chemical", "pos": [114, 117]}], "task": "NER"}
{"text": "Feeding of selenium alone or in combination with glucoraphanin differentially affects intestinal and hepatic antioxidant and phase II enzymes in growing rats .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "glucoraphanin", "entity_type": "Chemical", "pos": [49, 62]}], "task": "NER"}
{"text": "The anti - carcinogenic effects of sulforaphane ( SFN ) are based on the up - regulation of antioxidant enzymes ( AE ) and phase II enzymes ( PIIE ) through the transcription factor Nrf2 .", "entity": [{"entity": "sulforaphane", "entity_type": "Chemical", "pos": [35, 47]}, {"entity": "SFN", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "Current knowledge on the roles of the SFN precursor glucoraphanin ( GRA ) on these processes is limited .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [38, 41]}, {"entity": "glucoraphanin", "entity_type": "Chemical", "pos": [52, 65]}, {"entity": "GRA", "entity_type": "Chemical", "pos": [68, 71]}], "task": "NER"}
{"text": "Anti - carcinogenic effects of Se depending on glutathione peroxidase ( GPx ) activity have also been reported .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [31, 33]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [47, 58]}], "task": "NER"}
{"text": "We studied effects and possible synergisms of Se and GRA on the expression and activity of a broad spectrum of AE and PIIE in jejunum , colon and the liver of rats fed diets differing in Se and GRA concentration .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [46, 48]}, {"entity": "GRA", "entity_type": "Chemical", "pos": [53, 56]}, {"entity": "Se", "entity_type": "Chemical", "pos": [187, 189]}, {"entity": "GRA", "entity_type": "Chemical", "pos": [194, 197]}], "task": "NER"}
{"text": "In all organs , GPx1 mRNA expression was 70 % to 90 % lower in Se deficiency than in Se sufficiency .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [63, 65]}, {"entity": "Se", "entity_type": "Chemical", "pos": [85, 87]}], "task": "NER"}
{"text": "GPx2 expression increased in jejunum and liver under Se deficiency and decreased in the colon .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [53, 55]}], "task": "NER"}
{"text": "Se deficiency increased most colonic AE and PIIE compared to Se adequacy .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Se", "entity_type": "Chemical", "pos": [61, 63]}], "task": "NER"}
{"text": "Adequate and in particular supranutritive Se combined with GRA increased colonic AE and PIIE expression up to 3 . 72 - fold .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "GRA", "entity_type": "Chemical", "pos": [59, 62]}], "task": "NER"}
{"text": "In the liver Se deficiency raised the expression of AE and PIIE up to 4 . 49 - fold .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [13, 15]}], "task": "NER"}
{"text": "GRA attenuated liver AE and PIIE response in Se deficiency .", "entity": [{"entity": "GRA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "Se", "entity_type": "Chemical", "pos": [45, 47]}], "task": "NER"}
{"text": "Expression - and correlation analyses revealed that Keap1 mRNA better reflects AE and PIIE gene expression than Nrf2 mRNA .", "entity": [], "task": "NER"}
{"text": "We conclude that : ( 1 ) GPx1 sensitively indicates Se deficiency ; ( 2 ) the influence of Se and Nrf2 / Keap1 on GPx2 expression depends on the organ ; ( 3 ) GRA combined with supranutritive Se may effectively protect against inflammation and colon cancer ; ( 4 ) future investigations on AE and PIIE expression should consider the role of Keap1 to a higher extent .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "Se", "entity_type": "Chemical", "pos": [91, 93]}, {"entity": "GRA", "entity_type": "Chemical", "pos": [159, 162]}, {"entity": "Se", "entity_type": "Chemical", "pos": [192, 194]}], "task": "NER"}
{"text": "Specific conserved C - terminal amino acids of Caenorhabditis elegans HMP - 1 / alpha - catenin modulate F - actin binding independently of vinculin .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [19, 20]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "Stable intercellular adhesions formed through the cadherin - catenin complex are important determinants of proper tissue architecture and help maintain tissue integrity during morphogenetic movements in developing embryos .", "entity": [], "task": "NER"}
{"text": "A key regulator of this stability is alpha - catenin , which connects the cadherin - catenin complex to the actin cytoskeleton .", "entity": [], "task": "NER"}
{"text": "Although the C - terminal F - actin - binding domain of alpha - catenin has been shown to be crucial for its function , a more detailed in vivo analysis of discrete regions and residues required for actin binding has not been performed .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [13, 14]}], "task": "NER"}
{"text": "Using Caenorhabditis elegans as a model system , we have characterized mutations in hmp - 1 / alpha - catenin that identify HMP - 1 residues 687 - 742 and 826 - 927 , as well as amino acid 802 , as critical to the localization of junctional proximal actin during epidermal morphogenesis .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [178, 188]}], "task": "NER"}
{"text": "We also find that the S823F transition in a hypomorphic allele , hmp - 1 ( fe4 ) , decreases actin binding in vitro .", "entity": [], "task": "NER"}
{"text": "Using hmp - 1 ( fe4 ) animals in a mutagenesis screen , we were then able to identify 11 intragenic suppressors of hmp - 1 ( fe4 ) that revert actin binding to wild - type levels .", "entity": [], "task": "NER"}
{"text": "Using homology modeling , we show that these amino acids are positioned at key conserved sites within predicted alpha - helices in the C terminus .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "C", "entity_type": "Chemical", "pos": [135, 136]}], "task": "NER"}
{"text": "Through the use of transgenic animals , we also demonstrate that HMP - 1 residues 315 - 494 , which correspond to a putative mechanotransduction domain that binds vinculin in vertebrate alpha E - catenin , are not required during epidermal morphogenesis but may aid efficient recruitment of HMP - 1 to the junction .", "entity": [], "task": "NER"}
{"text": "Our studies are the first to identify key conserved amino acids in the C terminus of alpha - catenin that modulate F - actin binding in living embryos of a simple metazoan .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "C", "entity_type": "Chemical", "pos": [71, 72]}], "task": "NER"}
{"text": "Nanoscale stabilization of new phases in the PbTe - Sb2Te3 system : Pb ( m ) Sb ( 2n ) Te ( m + 3n ) nanocrystals .", "entity": [{"entity": "PbTe", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "Sb2Te3", "entity_type": "Chemical", "pos": [52, 58]}, {"entity": "Pb ( m ) Sb ( 2n ) Te ( m + 3n )", "entity_type": "Chemical", "pos": [68, 100]}], "task": "NER"}
{"text": "A series of novel rock - salt - type Pb ( m ) Sb ( 2n ) Te ( m + 3n ) nanocrystals ( m = 2 , 3 , 4 , 6 , 8 , and 10 ; n = 1 and 2 ) were successfully prepared using a colloidal synthesis route .", "entity": [{"entity": "Pb ( m ) Sb ( 2n ) Te ( m + 3n )", "entity_type": "Chemical", "pos": [37, 69]}], "task": "NER"}
{"text": "These materials are stable only on the nanoscale and have no bulk analogues .", "entity": [], "task": "NER"}
{"text": "Elemental compositions were determined using scanning transmission electron microscopy / energy - dispersive X - ray spectroscopy ( STEM / EDS ) and inductively coupled plasma atomic emission spectroscopy ( ICP - AES ) .", "entity": [], "task": "NER"}
{"text": "The nanocrystals exhibit well - defined band energies in the mid - IR region that are nearly independent of their atomic compositions .", "entity": [], "task": "NER"}
{"text": "Pb ( m ) Sb ( 2n ) Te ( m + 3n ) nanocrystals behave as metastable homogeneous solid solutions at room temperature and tend to phase separate into the respective binary PbTe + Sb ( 2 ) Te ( 3 ) at 300 degrees C .", "entity": [{"entity": "Pb ( m ) Sb ( 2n ) Te ( m + 3n )", "entity_type": "Chemical", "pos": [0, 32]}, {"entity": "PbTe", "entity_type": "Chemical", "pos": [169, 173]}, {"entity": "Sb ( 2 ) Te ( 3 )", "entity_type": "Chemical", "pos": [176, 193]}], "task": "NER"}
{"text": "Furthermore , pair distribution function ( PDF ) analysis suggests that the local structure of these Pb ( m ) Sb ( 2n ) Te ( m + 3n ) nanocrystals is distorted with respect to the rock - salt structure .", "entity": [{"entity": "Pb ( m ) Sb ( 2n ) Te ( m + 3n )", "entity_type": "Chemical", "pos": [101, 133]}], "task": "NER"}
{"text": "N - cinnamoylated chloroquine analogues as dual - stage antimalarial leads .", "entity": [{"entity": "N - cinnamoylated chloroquine", "entity_type": "Chemical", "pos": [0, 29]}], "task": "NER"}
{"text": "The control of malaria is challenged by drug resistance , and new antimalarial drugs are needed .", "entity": [], "task": "NER"}
{"text": "New drug discovery efforts include consideration of hybrid compounds as potential multitarget antimalarials .", "entity": [], "task": "NER"}
{"text": "Previous work from our group has demonstrated that hybrid structures resulting from cinnamic acid conjugation with heterocyclic moieties from well - known antimalarials present improved antimalarial activity .", "entity": [{"entity": "cinnamic acid", "entity_type": "Chemical", "pos": [84, 97]}], "task": "NER"}
{"text": "Now , we report the synthesis and SAR analysis of an expanded series of cinnamic acid derivatives displaying remarkably high activities against both blood - and liver - stage malaria parasites .", "entity": [{"entity": "cinnamic acid", "entity_type": "Chemical", "pos": [72, 85]}], "task": "NER"}
{"text": "Two compounds judged most promising , based on their in vitro activity and druglikeness according to the Lipinski rules and Veber filter , were active in vivo against blood - stage rodent malaria parasites .", "entity": [], "task": "NER"}
{"text": "Therefore , the compounds reported represent a new entry as promising dual - stage antimalarial leads .", "entity": [], "task": "NER"}
{"text": "Bistable magnetoresistance switching in exchange - coupled CoFe 2 O 4 - - Fe 3 O 4 binary nanocrystal superlattices by self - assembly and thermal annealing .", "entity": [{"entity": "CoFe 2 O 4", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "Fe 3 O 4", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "Self - assembly of multicomponent nanocrystal superlattices provides a modular approach to the design of metamaterials by choosing constituent nanocrystal building blocks with desired physical properties and engineering the interparticle coupling .", "entity": [], "task": "NER"}
{"text": "In this work , we report the self - assembly of binary nanocrystal superlattices composed of magnetically hard CoFe 2 O 4 nanocrystals and magnetically soft Fe 3 O 4 nanocrystals .", "entity": [{"entity": "CoFe 2 O 4", "entity_type": "Chemical", "pos": [111, 121]}, {"entity": "Fe 3 O 4", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "Both NaZn 1 3 - and MgZn 2 - type CoFe 2 O 4 - - Fe 3 O 4 binary nanocrystal superlattices have been formed by the liquid - air interfacial assembly approach .", "entity": [{"entity": "NaZn 1 3", "entity_type": "Chemical", "pos": [5, 13]}, {"entity": "MgZn 2", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "CoFe 2 O 4", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "Fe 3 O 4", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Exchange coupling is achieved in both types of binary superlattices after thermal annealing under vacuum at 400 degrees C .", "entity": [], "task": "NER"}
{"text": "The exchange - coupled CoFe 2 O 4 - - Fe 3 O 4 binary nanocrystal superlattices show single - phase magnetization switching behavior and magnetoresistance switching behavior below 200 K .", "entity": [{"entity": "CoFe 2 O 4", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "Fe 3 O 4", "entity_type": "Chemical", "pos": [38, 46]}], "task": "NER"}
{"text": "The NaZn 1 3 - type CoFe 2 O 4 - - Fe 3 O 4 binary nanocrystal superlattices annealed at 500 degrees C even exhibit bistable magnetoresistance switching behavior at room temperature constituting a simple nonvolatile memory function .", "entity": [{"entity": "NaZn 1 3", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "CoFe 2 O 4", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "Fe 3 O 4", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "Synthesis , molecular modeling and evaluation of novel N ' - 2 - ( 4 - benzylpiperidin - / piperazin - 1 - yl ) acylhydrazone derivatives as dual inhibitors for cholinesterases and A beta aggregation .", "entity": [{"entity": "N ' - 2 - ( 4 - benzylpiperidin - / piperazin - 1 - yl ) acylhydrazone", "entity_type": "Chemical", "pos": [55, 125]}], "task": "NER"}
{"text": "To develop new drugs for treatment of Alzheimer ' s disease , a group of N ' - 2 - ( 4 - Benzylpiperidin - / piperazin - 1 - yl ) acylhydrazones was designed , synthesized and tested for their ability to inhibit acetylcholinesterase , butyrylcholinesterase and aggregation of amyloid beta peptides ( 1 - 40 , 1 - 42 and 1 - 40 _ 1 - 42 ) .", "entity": [{"entity": "N ' - 2 - ( 4 - Benzylpiperidin - / piperazin - 1 - yl ) acylhydrazones", "entity_type": "Chemical", "pos": [73, 144]}], "task": "NER"}
{"text": "The enzyme inhibition assay results indicated that compounds moderately inhibit both acetylcholinesterase and butyrylcholinesterase .", "entity": [], "task": "NER"}
{"text": "beta - Amyloid aggregation results showed that all compounds exhibited remarkable A beta fibril aggregation inhibition activity with a nearly similar potential as the reference compound rifampicin , which makes them promising anti - Alzheimer drug candidates .", "entity": [{"entity": "rifampicin", "entity_type": "Chemical", "pos": [186, 196]}], "task": "NER"}
{"text": "Docking experiments were carried out with the aim to understand the interactions of the most active compounds with the active site of the cholinesterase enzymes .", "entity": [], "task": "NER"}
{"text": "Synthesis and biological evaluation of analogues of the kinase inhibitor nilotinib as Abl and Kit inhibitors .", "entity": [{"entity": "nilotinib", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "The importance of the trifluoromethyl group in the polypharmacological profile of nilotinib was investigated .", "entity": [{"entity": "trifluoromethyl", "entity_type": "Chemical", "pos": [22, 37]}, {"entity": "nilotinib", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "Molecular editing of nilotinib led to the design , synthesis and biological evaluation of analogues where the trifluoromethyl group was replaced by a proton , fluorine and a methyl group .", "entity": [{"entity": "nilotinib", "entity_type": "Chemical", "pos": [21, 30]}, {"entity": "trifluoromethyl", "entity_type": "Chemical", "pos": [110, 125]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [159, 167]}, {"entity": "methyl", "entity_type": "Chemical", "pos": [174, 180]}], "task": "NER"}
{"text": "While these analogues were less active than nilotinib toward Abl , their activity toward Kit was comparable , with the monofluorinated analogue being the most active .", "entity": [{"entity": "nilotinib", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "Docking of nilotinib and of analogues 2a - c to the binding pocket of Abl and of Kit showed that the lack of shape complementarity in Kit is compensated by the stabilizing effect from its juxtamembrane region .", "entity": [{"entity": "nilotinib", "entity_type": "Chemical", "pos": [11, 20]}], "task": "NER"}
{"text": "HCV NS5A replication complex inhibitors .", "entity": [], "task": "NER"}
{"text": "Part 3 : discovery of potent analogs with distinct core topologies .", "entity": [], "task": "NER"}
{"text": "In a recent disclosure , we described the discovery of dimeric , prolinamide - based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon .", "entity": [{"entity": "prolinamide", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype , and herein is described the SAR uncovered from a complementary effort that focused on the central core region .", "entity": [], "task": "NER"}
{"text": "From this effort , the contribution of the core region to the overall topology of the pharmacophore , primarily vector orientation and planarity , was determined , with a set of analogs exhibiting < 10 nM EC ( 50 ) in a genotype 1b replicon assay .", "entity": [], "task": "NER"}
{"text": "Endophytic fungi from Miquelia dentata Bedd . , produce the anti - cancer alkaloid , camptothecine .", "entity": [{"entity": "camptothecine", "entity_type": "Chemical", "pos": [85, 98]}], "task": "NER"}
{"text": "Camptothecine ( Campothecin , CPT ) , a quinoline alkaloid , is a potent inhibitor of eukaryotic topoisomerase I .", "entity": [{"entity": "Camptothecine", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "Campothecin", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "quinoline alkaloid", "entity_type": "Chemical", "pos": [40, 58]}], "task": "NER"}
{"text": "Several semi - synthetic derivatives of CPT are in clinical use against ovarian , small lung and refractory ovarian cancers .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "While CPT is produced by several plant species belonging to the Asterid clade , in recent years , efforts have been made to isolate endophytic fungi from some of these plants as possible alternative sources of CPT .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [6, 9]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [210, 213]}], "task": "NER"}
{"text": "In this study we report the isolation of three endophytic fungi from fruit and seed regions of Miquelia dentata ( Icacinaceae ) , that produce CPT , 9 - methoxy CPT ( 9 - MeO - CPT ) and 10 - hydroxy CPT ( 10 - OH - CPT ) .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [143, 146]}, {"entity": "9 - methoxy CPT", "entity_type": "Chemical", "pos": [149, 164]}, {"entity": "9 - MeO - CPT", "entity_type": "Chemical", "pos": [167, 180]}, {"entity": "10 - hydroxy CPT", "entity_type": "Chemical", "pos": [187, 203]}, {"entity": "10 - OH - CPT", "entity_type": "Chemical", "pos": [206, 219]}], "task": "NER"}
{"text": "All the three fungi identified as , Fomitopsis sp .", "entity": [], "task": "NER"}
{"text": "P .", "entity": [], "task": "NER"}
{"text": "Karst ( MTCC 10177 ) , Alternaria alternata ( Fr . ) Keissl ( MTCC 5477 ) and Phomposis sp .", "entity": [], "task": "NER"}
{"text": "( Sacc . ) produced CPT , 9 - MeO - CPT and 10 - OH - CPT in mycelial mats in shake flasks containing potato dextrose broth .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "9 - MeO - CPT", "entity_type": "Chemical", "pos": [26, 39]}, {"entity": "10 - OH - CPT", "entity_type": "Chemical", "pos": [44, 57]}], "task": "NER"}
{"text": "Methanolic and ethyl acetate extracts of these fungal species were cytotoxic to colon and breast cancer cell lines .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [15, 28]}], "task": "NER"}
{"text": "We discuss these results in the context of the recent interest in endophytic fungi as possible alternative sources of plant secondary metabolites .", "entity": [], "task": "NER"}
{"text": "A link between the cytoplasmic engulfment protein Elmo1 and the Mediator complex subunit Med31 .", "entity": [], "task": "NER"}
{"text": "The cytoplasmic Elmo1 : Dock180 complex acts as a guanine nucleotide exchange factor ( GEF ) for the small GTPase Rac and functions downstream of the phagocytic receptor BAI1 during apoptotic cell clearance , and in the entry of Salmonella and Shigella into cells .", "entity": [{"entity": "guanine", "entity_type": "Chemical", "pos": [50, 57]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "We discovered an unexpected binding between Elmo1 and the Mediator complex subunit Med31 .", "entity": [], "task": "NER"}
{"text": "The Mediator complex is a regulatory hub for nearly all gene transcription via RNA polymerase II , bridging the general transcription machinery with gene - specific regulatory proteins .", "entity": [], "task": "NER"}
{"text": "Med31 is the smallest and the most evolutionarily conserved Mediator subunit , and knockout of Med31 results in embryonic lethality in mice ; however , Med31 function in specific biological contexts is poorly understood .", "entity": [], "task": "NER"}
{"text": "We observed that in primary macrophages , during Salmonella infection , Elmo1 and Med31 specifically affected expression of the cytokine genes Il10 and Il33 among the > 25 genes monitored .", "entity": [], "task": "NER"}
{"text": "Although endogenous Med31 is predominantly nuclear localized , Elmo1 increased the cytoplasmic localization of Med31 .", "entity": [], "task": "NER"}
{"text": "We identify ubiquitination as a novel posttranslational modification of Med31 , with the cytoplasmic monoubiquitinated form of Med31 being enhanced by Elmo1 .", "entity": [], "task": "NER"}
{"text": "These data identify Elmo1 as a novel regulator of Med31 , revealing a previously unrecognized link between cytoplasmic signaling proteins and the Mediator complex .", "entity": [], "task": "NER"}
{"text": "Jaceosidin , isolated from dietary mugwort ( Artemisia princeps ) , induces G2 / M cell cycle arrest by inactivating cdc25C - cdc2 via ATM - Chk1 / 2 activation .", "entity": [{"entity": "Jaceosidin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Jaceosidin , a flavonoid derived from Artemisia princeps ( Japanese mugwort ) , has been shown to inhibit the growth of several human cancer cells , However , the exact mechanism for the cytotoxic effect of jaceosidin is not completely understood .", "entity": [{"entity": "Jaceosidin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "jaceosidin", "entity_type": "Chemical", "pos": [207, 217]}], "task": "NER"}
{"text": "In this study , we investigated the molecular mechanism involved in the antiproliferative effect of jaceosidin in human endometrial cancer cells .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [100, 110]}], "task": "NER"}
{"text": "We demonstrated that jaceosidin is a more potent inhibitor of cell growth than cisplatin in human endometrial cancer cells .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [21, 31]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [79, 88]}], "task": "NER"}
{"text": "In contrast , jaceosidin - induced cytotoxicity in normal endometrial cells was lower than that observed for cisplatin .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [109, 118]}], "task": "NER"}
{"text": "Jaceosidin induced G2 / M phase cell cycle arrest and modulated the levels of cyclin B and p - Cdc2 in Hec1A cells .", "entity": [{"entity": "Jaceosidin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Knockdown of p21 using specific siRNAs partially abrogated jaceosidin - induced cell growth inhibition .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [59, 69]}], "task": "NER"}
{"text": "Additional mechanistic studies revealed that jaceosidin treatment resulted in an increase in phosphorylation of Cdc25C and ATM - Chk1 / 2 .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [45, 55]}], "task": "NER"}
{"text": "Ku55933 , an ATM inhibitor , reversed jaceosidin - induced cell growth inhibition , in part .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [38, 48]}], "task": "NER"}
{"text": "Moreover , jaceosidin treatment resulted in phosphorylation of ERK , and pretreatment with the ERK inhibitor , PD98059 , attenuated cell growth inhibition by jaceosidin .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [11, 21]}, {"entity": "PD98059", "entity_type": "Chemical", "pos": [111, 118]}, {"entity": "jaceosidin", "entity_type": "Chemical", "pos": [158, 168]}], "task": "NER"}
{"text": "These data suggest that jaceosidin , isolated from Japanese mugwort , modulates the ERK / ATM / Chk1 / 2 pathway , leading to inactivation of the Cdc2 - cyclin B1 complex , followed by G2 / M cell cycle arrest in endometrial cancer cells .", "entity": [{"entity": "jaceosidin", "entity_type": "Chemical", "pos": [24, 34]}], "task": "NER"}
{"text": "AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo .", "entity": [], "task": "NER"}
{"text": "AMPK is a metabolic sensor that helps maintain cellular energy homeostasis .", "entity": [], "task": "NER"}
{"text": "Despite evidence linking AMPK with tumor suppressor functions , the role of AMPK in tumorigenesis and tumor metabolism is unknown .", "entity": [], "task": "NER"}
{"text": "Here we show that AMPK negatively regulates aerobic glycolysis ( the Warburg effect ) in cancer cells and suppresses tumor growth in vivo .", "entity": [], "task": "NER"}
{"text": "Genetic ablation of the alpha 1 catalytic subunit of AMPK accelerates Myc - induced lymphomagenesis .", "entity": [], "task": "NER"}
{"text": "Inactivation of AMPK alpha in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis , increased allocation of glucose carbon into lipids , and biomass accumulation .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [147, 154]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "These metabolic effects require normoxic stabilization of the hypoxia - inducible factor - 1 alpha ( HIF - 1 alpha ) , as silencing HIF - 1 alpha reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPK alpha signaling .", "entity": [], "task": "NER"}
{"text": "Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation .", "entity": [], "task": "NER"}
{"text": "Ptaquiloside reduces NK cell activities by enhancing metallothionein expression , which is prevented by selenium .", "entity": [{"entity": "Ptaquiloside", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Pteridium aquilinum , one of the most important poisonous plants in the world , is known to be carcinogenic to animals and humans .", "entity": [], "task": "NER"}
{"text": "Moreover , our previous studies showed that the immunosuppressive effects of ptaquiloside , its main toxic agent , were prevented by selenium in mouse natural killer ( NK ) cells .", "entity": [{"entity": "ptaquiloside", "entity_type": "Chemical", "pos": [77, 89]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [133, 141]}], "task": "NER"}
{"text": "We also verified that this immunosuppression facilitated development of cancer .", "entity": [], "task": "NER"}
{"text": "Here , we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with ptaquiloside ( 5 . 3 mg / kg ) and / or selenium ( 1 . 3 mg / kg ) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium .", "entity": [{"entity": "ptaquiloside", "entity_type": "Chemical", "pos": [111, 123]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [151, 159]}, {"entity": "ptaquiloside", "entity_type": "Chemical", "pos": [218, 230]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [308, 316]}], "task": "NER"}
{"text": "Transcriptome analysis of ptaquiloside samples revealed that 872 transcripts were expressed differentially ( fold change > 2 and p < 0 . 05 ) , including 77 up - regulated and 795 down - regulated transcripts .", "entity": [{"entity": "ptaquiloside", "entity_type": "Chemical", "pos": [26, 38]}], "task": "NER"}
{"text": "Gene ontology analysis mapped these up - regulated transcripts to three main biological processes ( cellular ion homeostasis , negative regulation of apoptosis and regulation of transcription ) .", "entity": [], "task": "NER"}
{"text": "Considering the immunosuppressive effect of ptaquiloside , we hypothesized that two genes involved in cellular ion homeostasis , metallothionein 1 ( Mt1 ) and metallothionein 2 ( Mt2 ) , could be implicated because Mt1 and Mt2 are responsible for zinc homeostasis , and a reduction of free intracellular zinc impairs NK functions .", "entity": [{"entity": "ptaquiloside", "entity_type": "Chemical", "pos": [44, 56]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [247, 251]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [304, 308]}], "task": "NER"}
{"text": "We confirm these hypotheses and show increased expression of metallothionein in splenic NK cells and reduction in free intracellular zinc following treatment with ptaquiloside that were completely prevented by selenium co - treatment .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [133, 137]}, {"entity": "ptaquiloside", "entity_type": "Chemical", "pos": [163, 175]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [210, 218]}], "task": "NER"}
{"text": "These findings could help avoid the higher susceptibility to cancer that is induced by P . aquilinum - mediated immunosuppressive effects .", "entity": [], "task": "NER"}
{"text": "Interference of a novel indolylmaleimide with microtubules induces mitotic arrest and apoptosis in human progenitor and cancer cells .", "entity": [{"entity": "indolylmaleimide", "entity_type": "Chemical", "pos": [24, 40]}], "task": "NER"}
{"text": "Indolylmaleimides display a broad spectrum of biological activity and offer great opportunity to influence several aspects of cell fate , as proliferation and differentiation .", "entity": [{"entity": "Indolylmaleimides", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "In this study we describe the effect of PDA - 66 , a newly synthesised indolylmaleimide , showing a strong dose dependent anti - proliferative effect on immortalised human progenitor and cancer cells .", "entity": [{"entity": "PDA - 66", "entity_type": "Chemical", "pos": [40, 48]}, {"entity": "indolylmaleimide", "entity_type": "Chemical", "pos": [71, 87]}], "task": "NER"}
{"text": "We demonstrated a highly depolymerizing effect on in vitro tubulin assembly and conclude that PDA - 66 acts as microtubule destabilising agent .", "entity": [{"entity": "PDA - 66", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "In addition we found that PDA - 66 induces mitotic arrest of cells in the G 2 / M phase of the cell cycle .", "entity": [{"entity": "PDA - 66", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "Subsequently cells undergo apoptosis , indicating the major mechanism of the anti - proliferative effect .", "entity": [], "task": "NER"}
{"text": "To prove a potential anti - cancer activity of PDA - 66 we examined the effect of PDA - 66 on human SH - SY5Y neuroblastoma and A - 459 lung cancer cells , showing a significant reduction in cancer cell proliferation in a dose dependent manner .", "entity": [{"entity": "PDA - 66", "entity_type": "Chemical", "pos": [47, 55]}, {"entity": "PDA - 66", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "Thus PDA - 66 is a new anti - mitotic compound with an indole - core with the potential to be used for cancer therapy .", "entity": [{"entity": "PDA - 66", "entity_type": "Chemical", "pos": [5, 13]}, {"entity": "indole", "entity_type": "Chemical", "pos": [55, 61]}], "task": "NER"}
{"text": "alpha - Terpineol induces fatty liver in mice mediated by the AMP - activated kinase and sterol response element binding protein pathway .", "entity": [{"entity": "alpha - Terpineol", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "AMP", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "The use of herbal medicines in disease prevention and treatment is growing rapidly worldwide , without careful consideration of safety issues .", "entity": [], "task": "NER"}
{"text": "alpha - Terpineol is a monoterpene alcoholic component of Melaleuca alternifolia , Salvia officinalis and Carthamus tinctorius that is used widely as a flavor and essential oil in food .", "entity": [{"entity": "alpha - Terpineol", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "monoterpene", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "alcoholic", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "The present study showed that alpha - terpineol induces fatty liver via the AMP - activated protein kinase ( AMPK ) - mTOR - sterol regulatory element - binding protein - 1 ( SREBP - 1 ) pathway .", "entity": [{"entity": "alpha - terpineol", "entity_type": "Chemical", "pos": [30, 47]}, {"entity": "AMP", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [125, 131]}], "task": "NER"}
{"text": "alpha - Terpineol - treated hepatocytes had significantly increased neutral lipid accumulation .", "entity": [{"entity": "alpha - Terpineol", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "alpha - Terpineol suppressed AMPK phosphorylation , and increased p70S6 kinase ( p70S6K ) phosphorylation and SREBP - 1 activation .", "entity": [{"entity": "alpha - Terpineol", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "It also increased luciferase activity in cells transfected with LXRE - tk - Luc and SRE - tk - Luc .", "entity": [], "task": "NER"}
{"text": "Inhibition of mTOR signaling by co - treatment with rapamycin or co - transfection with dominant negative p70S6K blocked completely the effects of alpha - terpineol .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [52, 61]}, {"entity": "alpha - terpineol", "entity_type": "Chemical", "pos": [147, 164]}], "task": "NER"}
{"text": "alpha - Terpineol oral administration to mice for 2weeks led to decreased AMPK phosphorylation and increased SREBP - 1 activation in the liver , followed by hepatic lipid accumulation .", "entity": [{"entity": "alpha - Terpineol", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Conversely , rapamycin co - treatment reversed alpha - terpineol - induced SREBP - 1 activation and fatty liver in mice .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "alpha - terpineol", "entity_type": "Chemical", "pos": [47, 64]}], "task": "NER"}
{"text": "These data provide evidence that alpha - terpineol causes fatty liver , an effect mediated by the AMPK / mTOR / SREBP - 1 pathway .", "entity": [{"entity": "alpha - terpineol", "entity_type": "Chemical", "pos": [33, 50]}], "task": "NER"}
{"text": "Multi - walled carbon nanotube increases the excitability of hippocampal CA1 neurons through inhibition of potassium channels in rat ' s brain slices .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [15, 21]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [107, 116]}], "task": "NER"}
{"text": "This study was to investigate the neurotoxicity of multi - walled carbon nanotube ( MWCNT ) by measuring neuronal excitability in rat hippocampal neurons and exploring the underlying mechanism .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [66, 72]}], "task": "NER"}
{"text": "Whole cell patch - clamp technique was used .", "entity": [], "task": "NER"}
{"text": "Action potential properties and the pattern of repetitive firing rate were assessed .", "entity": [], "task": "NER"}
{"text": "Our data showed that spike half - width and repetitive firing rate were significantly increased in a concentration - dependent manner .", "entity": [], "task": "NER"}
{"text": "Furthermore , voltage - activated potassium currents were recorded .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [34, 43]}], "task": "NER"}
{"text": "It was found that MWCNT produced a concentration - dependent inhibition in amplitudes of I ( A ) and I ( K ) .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [105, 106]}], "task": "NER"}
{"text": "In addition , MWCNT had effect on the activation kinetics of I ( A ) and I ( K ) with V ( h ) being shifted to the negative potential at high concentration , while I ( A ) inactivation curve was considerably shifted to the hyperpolarize potential with V ( h ) being increased .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [77, 78]}], "task": "NER"}
{"text": "However , no effect was found on the recovery from inactivation of I ( A ) .", "entity": [], "task": "NER"}
{"text": "The results suggest that MWCNT increases the excitability of hippocampal CA1 neurons by inhibiting voltage - gated potassium current .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "Bile acids in the colon , from healthy to cytotoxic molecules .", "entity": [{"entity": "Bile acids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Bile acids are natural detergents mainly involved in facilitating the absorption of dietary fat in the intestine .", "entity": [{"entity": "Bile acids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "In addition to this absorptive function , bile acids are also essential in the maintenance of the intestinal epithelium homeostasis .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [42, 52]}], "task": "NER"}
{"text": "To accomplish this regulatory function , bile acids may induce programmed cell death fostering the renewal of the epithelium .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "Here we first discuss on the different molecular pathways of cell death focusing on apoptosis in colon epithelial cells .", "entity": [], "task": "NER"}
{"text": "Bile acids may induce apoptosis in colonocytes through different mechanisms .", "entity": [{"entity": "Bile acids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "In contrast to hepatocytes , the extrinsic apoptotic pathway seems to have a low relevance regarding bile acid cytotoxicity in the colon .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "On the contrary , these molecules mainly trigger apoptosis through direct or indirect mitochondrial perturbations , where oxidative stress plays a key role .", "entity": [], "task": "NER"}
{"text": "In addition , bile acids may also act as regulatory molecules involved in different cell signaling pathways in colon cells .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "On the other hand , there is increasing evidence that the continuous exposure to certain hydrophobic bile acids , due to a fat - rich diet or pathological conditions , may induce oxidative DNA damage that , in turn , may lead to colorectal carcinogenesis as a consequence of the appearance of cell populations resistant to bile acid - induced apoptosis .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [101, 111]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [323, 332]}], "task": "NER"}
{"text": "Finally , some bile acids , such as UDCA , or low concentrations of hydrophobic bile acids , can protect colon cells against apoptosis induced by high concentrations of cytotoxic bile acids , suggesting a dual behavior of these agents as pro - death or pro - survival molecules .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "UDCA", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [179, 189]}], "task": "NER"}
{"text": "In vitro evaluation of cytochrome P450 induction and the inhibition potential of mitragynine , a stimulant alkaloid .", "entity": [{"entity": "mitragynine", "entity_type": "Chemical", "pos": [81, 92]}], "task": "NER"}
{"text": "CYP450 enzymes are key determinants in drug toxicities , reduced pharmacological effect and adverse drug reactions .", "entity": [], "task": "NER"}
{"text": "Mitragynine , an euphoric compound was evaluated for its effects on the expression of mRNAs encoding CYP1A2 , CYP2D6 and CYP3A4 and protein expression and resultant enzymatic activity .", "entity": [{"entity": "Mitragynine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The mRNA and protein expression of CYP450 isoforms were carried out using an optimized multiplex qRT - PCR assay and Western blot analysis .", "entity": [], "task": "NER"}
{"text": "CYP1A2 and CYP3A4 enzyme activities were evaluated using P450 - Glo (TM) assays .", "entity": [], "task": "NER"}
{"text": "The effects of mitragynine on human CYP3A4 protein expression were determined using an optimized hCYP3A4 - HepG2 cell - based assay .", "entity": [{"entity": "mitragynine", "entity_type": "Chemical", "pos": [15, 26]}], "task": "NER"}
{"text": "An in silico computational method to predict the binding conformation of mitragynine to the active site of the CYP3A4 enzyme was performed and further validated using in vitro CYP3A4 inhibition assays .", "entity": [{"entity": "mitragynine", "entity_type": "Chemical", "pos": [73, 84]}], "task": "NER"}
{"text": "Mitragynine was found to induce mRNA and protein expression of CYP1A2 .", "entity": [{"entity": "Mitragynine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "For the highest concentration of 25 mu M , induction of mRNA was approximately 70 % that of the positive control and was consistent with the increased CYP1A2 enzymatic activity .", "entity": [], "task": "NER"}
{"text": "Thus , mitragynine is a significant in vitro CYP1A2 inducer .", "entity": [{"entity": "mitragynine", "entity_type": "Chemical", "pos": [7, 18]}], "task": "NER"}
{"text": "However , it appeared to be a weak CYP3A4 inducer at the transcriptional level and a weak CYP3A4 enzyme inhibitor .", "entity": [], "task": "NER"}
{"text": "It is therefore , unlikely to have any significant clinical effects on CYP3A4 activity .", "entity": [], "task": "NER"}
{"text": "NF - kappa B - associated mechanisms underlying the response of embryonic cells to Doxorubicin .", "entity": [{"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "The involvement of NF - kappa B in the regulation of teratogen - induced apoptosis has not been established yet .", "entity": [], "task": "NER"}
{"text": "Therefore , we tried to assess the involvement of the p65 subunit of NF - kappa B in the embryonic response to the anti - cancer drug Doxorubicin ( DOX ) .", "entity": [{"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [134, 145]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "Thus , exposure of p65 knockout ( p65 ( - / - ) ) or wild type ( WT ) mouse embryonic fibroblasts ( MEFs ) to DOX resulted in a decrease in cell survival , culture density and cell proliferation , which was found to be more prominent in p65 ( - / - ) MEFs .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "Those phenomena were accompanied by a DOX - induced increase in the proportion of apoptotic cells , which was demonstrated only in p65 ( - / - ) cells and a G2 / M arrest , which was found to be more prominent in WT cells .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Furthermore , DOX - treated WT and p65 ( - / - ) MEFs differed in their expression of various apoptosis - associated molecules , when the former demonstrated a decrease in the percentage of p65 - positive and a more prominent decrease in the percentage of p53 - positive cells , while a decreased percentage of I kappa B alpha - positive and a more prominent decrease in the percentage of bcl - 2 - positive cells was detected among the latter .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "The fact that the response of the cells to the teratogen was clearly p65 - dependent implicates this molecule to be involved in the response of the embryonic cells to DOX .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "Chemical constituents from the fibrous root of Ophiopogon japonicus , and their effect on tube formation in human myocardial microvascular endothelial cells .", "entity": [], "task": "NER"}
{"text": "In an effort to identify novel active constituents on the cardiovascular system , a systematic study on macroporous resin adsorption of extracts from the fibrous root of Ophiopogon japonicus was performed in a human myocardial microvascular endothelial cell line ( HMMEC ) based assay .", "entity": [], "task": "NER"}
{"text": "One novel spirostan , named ophiogenin ( 1 ) , together with six known spirostans ( 4 - 8 , 10 ) , and one new sesquiterpene glycoside , named ophioside A ( 2 ) , together with one known monoterpene glycoside ( 9 ) were isolated from the active fractions , and the aglycone of compound 2 that was a new natural compound was obtained from the acid hydrolysis of 2 , named ophiopogonol ( 3 ) .", "entity": [{"entity": "spirostan", "entity_type": "Chemical", "pos": [10, 19]}, {"entity": "ophiogenin", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "spirostans", "entity_type": "Chemical", "pos": [71, 81]}, {"entity": "sesquiterpene glycoside", "entity_type": "Chemical", "pos": [111, 134]}, {"entity": "ophioside A", "entity_type": "Chemical", "pos": [143, 154]}, {"entity": "monoterpene glycoside", "entity_type": "Chemical", "pos": [187, 208]}, {"entity": "ophiopogonol", "entity_type": "Chemical", "pos": [371, 383]}], "task": "NER"}
{"text": "Their structures were determined by spectral and chemical analyses .", "entity": [], "task": "NER"}
{"text": "Furthermore , their effect on HMMEC tube formation was also determined .", "entity": [], "task": "NER"}
{"text": "Our results indicated that compounds 4 and 8 could significantly improve the tube formation and 2 showed moderate increasing effect , while compound 5 exhibited potent inhibitory effect .", "entity": [], "task": "NER"}
{"text": "Fetal PGC - 1 alpha overexpression programs adult pancreatic beta - cell dysfunction .", "entity": [], "task": "NER"}
{"text": "Adult beta - cell dysfunction , a hallmark of type 2 diabetes , can be programmed by adverse fetal environment .", "entity": [], "task": "NER"}
{"text": "We have shown that fetal glucocorticoids ( GCs ) participate in this programming through inhibition of beta - cell development .", "entity": [], "task": "NER"}
{"text": "Here we have investigated the molecular mechanisms underlying this regulation .", "entity": [], "task": "NER"}
{"text": "We showed that GCs stimulate the expression of peroxisome proliferator - activated receptor - gamma coactivator - 1 alpha ( PGC - 1 alpha ) , a coregulator of the GCs receptor ( GR ) , and that the overexpression of PGC - 1 alpha represses genes important for beta - cell development and function .", "entity": [], "task": "NER"}
{"text": "More precisely , PGC - 1 alpha inhibited the expression of the key beta - cell transcription factor pancreatic duodenal homeobox 1 ( Pdx1 ) .", "entity": [], "task": "NER"}
{"text": "This repression required the GR and was mediated through binding of a GR / PGC - 1 alpha complex to the Pdx1 promoter .", "entity": [], "task": "NER"}
{"text": "To explore PGC - 1 alpha function , we generated mice with inducible beta - cell PGC - 1 alpha overexpression .", "entity": [], "task": "NER"}
{"text": "Mice overexpressing PGC - 1 alpha exhibited at adult age impaired glucose tolerance associated with reduced insulin secretion , decreased beta - cell mass , and beta - cell hypotrophy .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [66, 73]}], "task": "NER"}
{"text": "Interestingly , PGC - 1 alpha expression in fetal life only was sufficient to impair adult beta - cell function whereas beta - cell PGC - 1 alpha overexpression from adult age had no consequence on beta - cell function .", "entity": [], "task": "NER"}
{"text": "Altogether , our results demonstrate that the GR and PGC - 1 alpha participate in the fetal programming of adult beta - cell function through inhibition of Pdx1 expression .", "entity": [], "task": "NER"}
{"text": "G6PC2 : A Negative Regulator of Basal Glucose - Stimulated Insulin Secretion .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [38, 45]}], "task": "NER"}
{"text": "Elevated fasting blood glucose ( FBG ) is associated with increased risk for the development of type 2 diabetes and cardiovascular - associated mortality .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [23, 30]}], "task": "NER"}
{"text": "Genome - wide association studies ( GWAS ) have linked polymorphisms in G6PC2 with variations in FBG and body fat , although not insulin sensitivity or glucose tolerance .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [152, 159]}], "task": "NER"}
{"text": "G6PC2 encodes an islet - specific , endoplasmic reticulum - resident glucose - 6 - phosphatase catalytic subunit .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [69, 76]}], "task": "NER"}
{"text": "A combination of in situ perfused pancreas , in vitro isolated islet , and in vivo analyses were used to explore the function of G6pc2 in mice .", "entity": [], "task": "NER"}
{"text": "G6pc2 deletion had little effect on insulin sensitivity and glucose tolerance , whereas body fat was reduced in female G6pc2 knockout ( KO ) mice on both a chow and high - fat diet , observations that are all consistent with human GWAS data .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "G6pc2 deletion resulted in a leftward shift in the dose - response curve for glucose - stimulated insulin secretion ( GSIS ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "As a consequence , under fasting conditions in which plasma insulin levels were identical , blood glucose levels were reduced in G6pc2 KO mice , again consistent with human GWAS data .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [98, 105]}], "task": "NER"}
{"text": "Glucose - 6 - phosphatase activity was reduced , whereas basal cytoplasmic calcium levels were elevated in islets isolated from G6pc2 KO mice .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [75, 82]}], "task": "NER"}
{"text": "These data suggest that G6pc2 represents a novel , negative regulator of basal GSIS that acts by hydrolyzing glucose - 6 - phosphate , thereby reducing glycolytic flux .", "entity": [{"entity": "glucose - 6 - phosphate", "entity_type": "Chemical", "pos": [109, 132]}], "task": "NER"}
{"text": "Congenital Hyperinsulinism Caused by Hexokinase I Expression or Glucokinase - Activating Mutation in a Subset of beta - Cells .", "entity": [], "task": "NER"}
{"text": "Congenital hyperinsulinism causes persistent hypoglycemia in neonates and infants .", "entity": [], "task": "NER"}
{"text": "Most often , uncontrolled insulin secretion ( IS ) results from a lack of functional KATP channels in all beta - cells or only in beta - cells within a resectable focal lesion .", "entity": [{"entity": "KATP", "entity_type": "Chemical", "pos": [85, 89]}], "task": "NER"}
{"text": "In more rare cases , without KATP channel mutations , hyperfunctional islets are confined within few lobules , whereas hypofunctional islets are present throughout the pancreas .", "entity": [{"entity": "KATP", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "They also can be cured by selective partial pancreatectomy ; however , unlike those with a KATP focal lesion , they show clinical sensitivity to diazoxide .", "entity": [{"entity": "KATP", "entity_type": "Chemical", "pos": [91, 95]}, {"entity": "diazoxide", "entity_type": "Chemical", "pos": [145, 154]}], "task": "NER"}
{"text": "Here , we characterized in vitro IS by fragments of pathological and adjacent normal pancreas from six such cases .", "entity": [], "task": "NER"}
{"text": "Responses of normal pancreas were unremarkable .", "entity": [], "task": "NER"}
{"text": "In pathological region , IS was elevated at 1 mmol / L and was further increased by 15 mmol / L glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [96, 103]}], "task": "NER"}
{"text": "Diazoxide suppressed IS and tolbutamide antagonized the inhibition .", "entity": [{"entity": "Diazoxide", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "The most conspicuous anomaly was a large stimulation of IS by 1 mmol / L glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [73, 80]}], "task": "NER"}
{"text": "In five of six cases , immunohistochemistry revealed undue presence of low - Km hexokinase - I in beta - cells of hyperfunctional islets only .", "entity": [], "task": "NER"}
{"text": "In one case , an activating mutation of glucokinase ( I211F ) was found in pathological islets only .", "entity": [], "task": "NER"}
{"text": "Both abnormalities , attributed to somatic genetic events , may account for inappropriate IS at low glucose levels by a subset of beta - cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "They represent a novel cause of focal congenital hyperinsulinism .", "entity": [], "task": "NER"}
{"text": "The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action .", "entity": [{"entity": "diospyrin", "entity_type": "Chemical", "pos": [19, 28]}], "task": "NER"}
{"text": "Tuberculosis and other bacterial diseases represent a significant threat to human health .", "entity": [], "task": "NER"}
{"text": "The DNA topoisomerases are excellent targets for chemotherapy , and DNA gyrase in particular is a well - validated target for antibacterial agents .", "entity": [], "task": "NER"}
{"text": "Naphthoquinones ( e . g . diospyrin and 7 - methyljuglone ) have been shown to have therapeutic potential , particularly against Mycobacterium tuberculosis .", "entity": [{"entity": "Naphthoquinones", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "diospyrin", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "7 - methyljuglone", "entity_type": "Chemical", "pos": [40, 57]}], "task": "NER"}
{"text": "We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M . tuberculosis gyrase and other gyrases .", "entity": [], "task": "NER"}
{"text": "Our evidence strongly suggests that the compounds bind to the N - terminal domain of GyrB , which contains the ATPase active site , but are not competitive inhibitors of the ATPase reaction .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [62, 63]}], "task": "NER"}
{"text": "We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site .", "entity": [{"entity": "naphthoquinones", "entity_type": "Chemical", "pos": [16, 31]}], "task": "NER"}
{"text": "This novel mode of action could be exploited to develop new antibacterial agents .", "entity": [], "task": "NER"}
{"text": "Structure , stability and function of 5 - chlorouracil modified A : U and G : U base pairs .", "entity": [{"entity": "5 - chlorouracil", "entity_type": "Chemical", "pos": [38, 54]}], "task": "NER"}
{"text": "The thymine analog 5 - chlorouridine , first reported in the 1950s as anti - tumor agent , is known as an effective mutagen , clastogen and toxicant as well as an effective inducer of sister - chromatid exchange .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [4, 11]}, {"entity": "5 - chlorouridine", "entity_type": "Chemical", "pos": [19, 36]}], "task": "NER"}
{"text": "Recently , the first microorganism with a chemically different genome was reported ; the selected Escherichia coli strain relies on the four building blocks 5 - chloro - 2 ' - deoxyuridine ( ClU ) , A , C and G instead of the standard T , A , C , G alphabet [ Marli e re , P . , Patrouix , J . , D o ring , V . , Herdewijn , P . , Tricot , S . , Cruveiller , S . , Bouzon , M . and Mutzel , R . ( 2011 ) Chemical evolution of a bacterium ' s genome . Angew . Chem . Int . Ed . , 50 , 7109 - 7114 ] .", "entity": [{"entity": "5 - chloro - 2 ' - deoxyuridine", "entity_type": "Chemical", "pos": [157, 188]}, {"entity": "ClU", "entity_type": "Chemical", "pos": [191, 194]}], "task": "NER"}
{"text": "The residual fraction of T in the DNA of adapted bacteria was < 2 % and the switch from T to ClU was accompanied by a massive number of mutations , including > 1500 A to G or G to A transitions in a culture .", "entity": [{"entity": "ClU", "entity_type": "Chemical", "pos": [93, 96]}], "task": "NER"}
{"text": "The former is most likely due to wobble base pairing between ClU and G , which may be more common for ClU than T .", "entity": [{"entity": "ClU", "entity_type": "Chemical", "pos": [61, 64]}, {"entity": "ClU", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "To identify potential changes in the geometries of base pairs and duplexes as a result of replacement of T by ClU , we determined four crystal structures of a B - form DNA dodecamer duplex containing ClU : A or ClU : G base pairs .", "entity": [{"entity": "ClU", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "ClU", "entity_type": "Chemical", "pos": [200, 203]}, {"entity": "ClU", "entity_type": "Chemical", "pos": [211, 214]}], "task": "NER"}
{"text": "The structures reveal nearly identical geometries of these pairs compared with T : A or T : G , respectively , and no consequences for stability and cleavage by an endonuclease ( EcoRI ) .", "entity": [], "task": "NER"}
{"text": "The lack of significant changes in the geometry of ClU : A and ClU : G base pairs relative to the corresponding native pairs is consistent with the sustained unlimited self - reproduction of E . coli strains with virtually complete T --> ClU genome substitution .", "entity": [{"entity": "ClU", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "ClU", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "ClU", "entity_type": "Chemical", "pos": [238, 241]}], "task": "NER"}
{"text": "Circularized synthetic oligodeoxynucleotides serve as promoterless RNA polymerase III templates for small RNA generation in human cells .", "entity": [], "task": "NER"}
{"text": "Synthetic RNA formulations and viral vectors are the two main approaches for delivering small therapeutic RNA to human cells .", "entity": [], "task": "NER"}
{"text": "Here we report findings supporting an alternative strategy in which an endogenous human RNA polymerase ( RNAP ) is harnessed to make RNA hairpin - containing small RNA from synthetic single - stranded DNA oligonucleotides .", "entity": [], "task": "NER"}
{"text": "We report that circularizing a DNA template strand encoding a pre - microRNA hairpin mimic can trigger its circumtranscription by human RNAP III in vitro and in human cells .", "entity": [], "task": "NER"}
{"text": "Sequence and secondary structure preferences that appear to promote productive transcription are described .", "entity": [], "task": "NER"}
{"text": "The circular topology of the template is required for productive transcription , at least in part , to stabilize the template against exonucleases .", "entity": [], "task": "NER"}
{"text": "In contrast to bacteriophage and Escherichia coli RNAPs , human RNAPs do not carry out rolling circle transcription on circularized templates .", "entity": [], "task": "NER"}
{"text": "While transfected DNA circles distribute between the nucleus and cytosol , their transcripts are found mainly in the cytosol .", "entity": [], "task": "NER"}
{"text": "Circularized oligonucleotides are synthetic , free of the hazards of viral vectors and maintain small RNA information in a stable form that RNAP III can access in a cellular context with , in some cases , near promoter - like precision and biologically relevant efficiency .", "entity": [], "task": "NER"}
{"text": "Melanocortins as innovative drugs for ischemic diseases and neurodegenerative disorders : established data and perspectives .", "entity": [], "task": "NER"}
{"text": "Ischemic insults and neurodegenerative diseases are by far the leading cause of mortality and disability .", "entity": [], "task": "NER"}
{"text": "Whole - body hypoperfusion , as it occurs in polytraumatic and hemorrhagic shock , is alike an increasingly frequent condition , especially due to traffic accidents , wars and acts of terrorism .", "entity": [], "task": "NER"}
{"text": "It is now clearly established that inflammatory processes play a fundamental role in the pathophysiology of both hypoperfusion / ischemia damage ( be it generalized to the whole body , as in the case of shock , or limited to individual organs ) and neurodegenerative diseases ( Alzheimer ' s disease , Parkinson ' s disease , multiple sclerosis , amyotrophic lateral sclerosis ) .", "entity": [], "task": "NER"}
{"text": "On the other hand , concurrent animal and human data show that melanocortin peptides with agonist activity at melanocortin MC3 / MC4 receptors are highly effective in different shock conditions as well as in conditions of ischemia / ischemia - reperfusion of individual organs ( heart , brain , intestine , kidney , etc . ) , and accumulating evidence indicates that such effects of melanocortins are mostly due to quite peculiar antiinflammatory mechanisms .", "entity": [], "task": "NER"}
{"text": "Melanocortins have also long been known ( i ) to exert important neurotrophic effects , not only during fetal development but also in adulthood , in different animal models of brain lesions ; ( ii ) to reduce the morphological correlates of brain aging ; ( iii ) to retard the behavioral deficits that develop during the aging process .", "entity": [], "task": "NER"}
{"text": "Moreover , recent data from different laboratories show that after brain ischemic episodes melanocortins activate the transcription of neurotrophins and their receptors in the cerebral cortex and in the hippocampus , and increase the proliferation of progenitor neuron cells .", "entity": [], "task": "NER"}
{"text": "The above arguments support the view that pharmacokinetically suitable agonists at MC3 / MC4 melanocortin receptors may represent a completely innovative class of drugs for an effective treatment of both ischemic and neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "Histone deacetylase inhibitors : an attractive strategy for cancer therapy .", "entity": [], "task": "NER"}
{"text": "Histone deacetylases are able to catalyze the hydrolysis of N - acetyl lysine residues of histones which package chromosomal DNA .", "entity": [{"entity": "N - acetyl lysine", "entity_type": "Chemical", "pos": [60, 77]}], "task": "NER"}
{"text": "Therefore they play an important role in mediating gene expression and cell proliferation .", "entity": [], "task": "NER"}
{"text": "HDAC inhibitors have not only shown promise as antiparasitic , antineurodegenerative , antirheumatologic agents and immunosuppressant , but as potent anticancer agents by inducing cell cycle arrest , differentiation and apoptosis .", "entity": [], "task": "NER"}
{"text": "This review highlights recent development in design , synthesis and biological evaluation of HDAC inhibitors for cancer therapy .", "entity": [], "task": "NER"}
{"text": "Alkyl substituted 2 ' - benzoylpyridine thiosemicarbazone chelators with potent and selective anti - neoplastic activity : novel ligands that limit methemoglobin formation .", "entity": [{"entity": "Alkyl substituted 2 ' - benzoylpyridine thiosemicarbazone", "entity_type": "Chemical", "pos": [0, 57]}], "task": "NER"}
{"text": "Thiosemicarbazone chelators , including the 2 ' - benzoylpyridine thiosemicarbazones ( BpT ) class , show marked potential as anticancer agents .", "entity": [{"entity": "Thiosemicarbazone", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "2 ' - benzoylpyridine thiosemicarbazones", "entity_type": "Chemical", "pos": [44, 84]}, {"entity": "BpT", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "Importantly , 3 - aminopyridine - 2 - carboxaldehyde thiosemicarbazone ( 3 - AP ) has been investigated in > 20 phase I and II clinical trials .", "entity": [{"entity": "3 - aminopyridine - 2 - carboxaldehyde thiosemicarbazone", "entity_type": "Chemical", "pos": [14, 70]}, {"entity": "3 - AP", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "However , side effects associated with 3 - AP administration include methemoglobinemia .", "entity": [{"entity": "3 - AP", "entity_type": "Chemical", "pos": [39, 45]}], "task": "NER"}
{"text": "Considering this problem , novel BpT analogues were designed bearing hydrophobic , electron - donating substituents at the para position of the phenyl group ( RBpT ) .", "entity": [{"entity": "BpT", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [144, 150]}, {"entity": "RBpT", "entity_type": "Chemical", "pos": [159, 163]}], "task": "NER"}
{"text": "Their Fe ( III / II ) redox potentials were all within the range accessible to cellular oxidants and reductants , suggesting they can redox cycle .", "entity": [{"entity": "Fe ( III / II )", "entity_type": "Chemical", "pos": [6, 21]}], "task": "NER"}
{"text": "These RBpT ligands exhibited potent and selective antiproliferative activity , which was comparable or exceeded their BpT counterparts .", "entity": [{"entity": "RBpT", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "BpT", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "Major findings include that methemoglobin formation mediated by the lipophilic t - BuBpT series was significantly ( p < 0 . 05 - 0 . 001 ) decreased in comparison to 3 - AP in intact red blood cells and were generally comparable to the control .", "entity": [{"entity": "t - BuBpT", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "3 - AP", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "These data indicate the t - BuBpT ligands may minimize methemoglobinemia , which is a marked advantage over 3 - AP and other potent thiosemicarbazones .", "entity": [{"entity": "t - BuBpT", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "3 - AP", "entity_type": "Chemical", "pos": [108, 114]}, {"entity": "thiosemicarbazones", "entity_type": "Chemical", "pos": [132, 150]}], "task": "NER"}
{"text": "Besting vitamin E : sidechain substitution is key to the reactivity of naphthyridinol antioxidants in lipid bilayers .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [8, 17]}, {"entity": "naphthyridinol", "entity_type": "Chemical", "pos": [71, 85]}], "task": "NER"}
{"text": "A series of naphthyridinol analogs of alpha - tocopherol ( alpha - TOH , right ) with varying sidechain substitution was synthesized to determine how systematic changes in the lipophilicity of these potent antioxidants impact their radical - trapping activities in lipid bilayers , regenerability by water - soluble reductants , and binding to human tocopherol transport protein ( TTP ) .", "entity": [{"entity": "naphthyridinol", "entity_type": "Chemical", "pos": [12, 26]}, {"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [38, 56]}, {"entity": "alpha - TOH", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "tocopherol", "entity_type": "Chemical", "pos": [350, 360]}], "task": "NER"}
{"text": "The activities of the naphthyridinols were assayed in phosphatidylcholine unilamellar liposomes using a recently developed high - throughput assay that employs a boron dipyrromethene conjugate of alpha - TOH ( H ( 2 ) B - PMHC ) that undergoes fluorescence enhancement upon oxidation .", "entity": [{"entity": "naphthyridinols", "entity_type": "Chemical", "pos": [22, 37]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [54, 73]}, {"entity": "boron dipyrromethene", "entity_type": "Chemical", "pos": [162, 182]}, {"entity": "alpha - TOH", "entity_type": "Chemical", "pos": [196, 207]}], "task": "NER"}
{"text": "The naphthyridinols afforded a dose - dependent protection of H ( 2 ) B - PMHC consistent with unprecedented peroxyl radical - trapping activity in lipid bilayers .", "entity": [{"entity": "naphthyridinols", "entity_type": "Chemical", "pos": [4, 19]}, {"entity": "peroxyl", "entity_type": "Chemical", "pos": [109, 116]}], "task": "NER"}
{"text": "While sidechain length and / or branching had no effect on their apparent reactivity , it dramatically impacted reaction stoichiometry , with more lipophilic compounds trapping two peroxyl radicals and more hydrophilic compounds trapping significantly less than one .", "entity": [{"entity": "peroxyl", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "It is suggested that the less lipophilic compounds autoxidize rapidly in the aqueous phase and that preferential partitioning of the more lipophilic compounds to the bilayer protects them from autoxidation .", "entity": [], "task": "NER"}
{"text": "The cooperativity of a lipophilic naphthyridinol with water - soluble reducing agents was also studied in liposomes using H ( 2 ) B - PMHC and revealed superior regenerability by each of ascorbate , N - acetylcysteine , and urate when compared to alpha - TOH .", "entity": [{"entity": "naphthyridinol", "entity_type": "Chemical", "pos": [34, 48]}, {"entity": "ascorbate", "entity_type": "Chemical", "pos": [187, 196]}, {"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [199, 217]}, {"entity": "urate", "entity_type": "Chemical", "pos": [224, 229]}, {"entity": "alpha - TOH", "entity_type": "Chemical", "pos": [247, 258]}], "task": "NER"}
{"text": "Binding assays with human TTP , a key determinant of the bioavailability of the tocopherols , reveal that the naphthyiridinols can be very good ligands for the protein .", "entity": [{"entity": "tocopherols", "entity_type": "Chemical", "pos": [80, 91]}, {"entity": "naphthyiridinols", "entity_type": "Chemical", "pos": [110, 126]}], "task": "NER"}
{"text": "In fact , naphthyridinols with sidechains of eight or more carbons had affinities for TTP which were similar to , and in one case 10 - fold better than , alpha - TOH .", "entity": [{"entity": "naphthyridinols", "entity_type": "Chemical", "pos": [10, 25]}, {"entity": "carbons", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "alpha - TOH", "entity_type": "Chemical", "pos": [154, 165]}], "task": "NER"}
{"text": "Potential antipsoriatic effect of chondroitin sulfate through inhibition of NF - kappa B and STAT3 in human keratinocytes .", "entity": [{"entity": "sulfate", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Chondroitin sulfate ( CS ) is a natural glycosaminoglycan , formed by the 1 - 3 linkage of d - glucuronic acid to N - acetylgalactosamine , present in the extracellular matrix .", "entity": [{"entity": "sulfate", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "d - glucuronic acid", "entity_type": "Chemical", "pos": [91, 110]}, {"entity": "N - acetylgalactosamine", "entity_type": "Chemical", "pos": [114, 137]}], "task": "NER"}
{"text": "It is used as a slow acting disease modifying agent in the treatment of osteoarthritis , and part of its beneficial effects are due to its antiinflammatory properties that result from an inhibitory effect on NF - kappa B signaling pathway .", "entity": [], "task": "NER"}
{"text": "This ability raises the hypothesis that CS might be effective in other chronic inflammatory processes such as psoriasis , in which a deregulation of NF - kappa B is a key feature .", "entity": [], "task": "NER"}
{"text": "In addition , psoriasis is characterized by an upregulation of STAT3 signaling pathway that is related to the epidermal hyperplasia .", "entity": [], "task": "NER"}
{"text": "In the present study we report the pharmacological modulation of the NF - kappa B and STAT3 signaling pathways by CS in normal human keratinocytes .", "entity": [], "task": "NER"}
{"text": "CS inhibited NF - kappa B activation and the release of some of the key psoriatic cytokines such as TNF alpha , IL - 8 , IL - 6 and CCL27 .", "entity": [], "task": "NER"}
{"text": "Moreover , it impaired STAT3 translocation to the nucleus and significantly reduced STAT3 transcriptional activity by a mechanism that was independent from STAT3 phosphorylation .", "entity": [], "task": "NER"}
{"text": "Our results confirm the interest of CS as a candidate for future drug research in the therapeutics of psoriasis given the need of more effective and safer oral medications for these patients .", "entity": [], "task": "NER"}
{"text": "Generating thermal stable variants of protein domains through phage display .", "entity": [], "task": "NER"}
{"text": "Often in protein design research , one desires to generate thermally stable variants of a protein or domain .", "entity": [], "task": "NER"}
{"text": "One route to identifying mutations that yield domains that remain folded and active at a higher temperature is through the use of directed evolution .", "entity": [], "task": "NER"}
{"text": "A library of protein domain variants can be generated by mutagenic PCR , expressed on the surface of bacteriophage M13 , and subjected to heat , such that the unfolded forms of the domain , showing reduced or no binding activity , are lost during subsequent affinity selection , whereas variants that still retain binding to their target are selected and enriched with each subsequent round of affinity selection .", "entity": [], "task": "NER"}
{"text": "This approach takes advantage of the fact that bacteriophage M13 particles are heat stable and resistant to many proteases and protein denaturants .", "entity": [], "task": "NER"}
{"text": "We present the application of this general approach to generating thermally stable variants of a eukaryotic peptide - binding domain .", "entity": [], "task": "NER"}
{"text": "The benefits of producing such variants are that they typically express at high levels in Escherichia coli ( 30 - 60mg / L shake flask ) and remain soluble in solution at higher concentrations for longer periods of time than the wild - type form of the domain .", "entity": [], "task": "NER"}
{"text": "The process of library generation and screening generally requires about one month of effort , and yields variants with > 10 degrees C increase in thermal stability , as measured in a simple fluorescence - based thermal shift assay .", "entity": [], "task": "NER"}
{"text": "It is anticipated that thermally stable variants will serve as excellent scaffolds for generating affinity reagents to a variety of targets of interest .", "entity": [], "task": "NER"}
{"text": "Effects of glyphosate - based herbicides on embryo - larval development and metamorphosis in the Pacific oyster , Crassostrea gigas .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [11, 21]}], "task": "NER"}
{"text": "Pesticides may be involved in oyster summer mortality events , not necessarily as a single causative agent but as an additional stressor .", "entity": [], "task": "NER"}
{"text": "In this context , the present study aimed to assess the toxicity of glyphosate , its by - product , aminomethylphosphonic acid ( AMPA ) and two commercial formulations , Roundup Express ( (R) ) ( R ( EX ) ) and Roundup All e es et Terrasses ( (R) ) ( R ( AT ) ) , containing glyphosate as the active ingredient , on the early life stages of the Pacific oyster , Crassostrea gigas .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [68, 78]}, {"entity": "aminomethylphosphonic acid", "entity_type": "Chemical", "pos": [100, 126]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [129, 133]}, {"entity": "glyphosate", "entity_type": "Chemical", "pos": [275, 285]}], "task": "NER"}
{"text": "The embryotoxicity of these chemicals were quantified by considering both the rates of abnormalities and the arrested development or types of abnormalities in D - shaped larvae after 48 h exposure .", "entity": [], "task": "NER"}
{"text": "The success of metamorphosis was examined in pediveliger larvae exposed for 24 h .", "entity": [], "task": "NER"}
{"text": "Experiments involving both endpoints included range finding experiments for herbicide concentrations ranging from 0 . 1 to 100 , 000 mu g L ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "This range was then narrowed down in order to determine precise EC ( 50 ) values .", "entity": [], "task": "NER"}
{"text": "Actual concentrations of the herbicide were determined at the beginning and after 48 h ( embryotoxicity ) and 24 h ( metamorphosis ) to evaluate the potential temporal variation in the concentrations .", "entity": [], "task": "NER"}
{"text": "During embryo - larval development , no mortalities were recorded at any of the concentrations of glyphosate and AMPA , whereas no embryos or D - shaped larvae could be observed after exposure to 10 , 000 mu g L ( - 1 ) of R ( EX ) or R ( AT ) .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [113, 117]}], "task": "NER"}
{"text": "Compared with the controls , no effects on embryo - larval development were recorded between 0 . 1 and 1000 mu g L ( - 1 ) , regardless of the chemical tested .", "entity": [], "task": "NER"}
{"text": "Above a threshold , which varied according to the chemical used , the gradient of herbicide concentrations correlated with a gradient of severity of abnormality ranging from normal larvae to arrested development ( an \" old embryo \" stage ) .", "entity": [], "task": "NER"}
{"text": "The EC ( 50 ) values were 28 , 315 and 40 , 617 mu g L ( - 1 ) for glyphosate and its metabolite , respectively , but much lowered values of 1133 and 1675 mu g L ( - 1 ) for R ( EX ) and R ( AT ) , respectively .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Metamorphosis tests also revealed a significant difference between molecules , as the EC ( 50 ) values exceeded 100 , 000 mu g L ( - 1 ) for glyphosate and AMPA but were as low as 6366 and 6060 mu g L ( - 1 ) for the commercial formulations , which appeared relatively more toxic .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [141, 151]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [156, 160]}], "task": "NER"}
{"text": "Overall , the embryo - larval development of C . gigas was more sensitive to glyphosate - based herbicides compared to various endpoints studied in regulatory model organisms , and embryos and D - shaped larvae were more sensitive compared to pediveliger larvae .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [77, 87]}], "task": "NER"}
{"text": "Ly6C + Ly6G - Myeloid - derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury .", "entity": [], "task": "NER"}
{"text": "Acute inflammation is a prominent feature of central nervous system ( CNS ) insult and is detrimental to the CNS tissue .", "entity": [], "task": "NER"}
{"text": "Although this reaction spontaneously diminishes within a short period of time , the mechanism underlying this inflammatory resolution remains largely unknown .", "entity": [], "task": "NER"}
{"text": "In this study , we demonstrated that an initial infiltration of Ly6C ( + ) Ly6G ( - ) immature monocyte fraction exhibited the same characteristics as myeloid - derived suppressor cells ( MDSCs ) , and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury ( SCI ) model .", "entity": [], "task": "NER"}
{"text": "Complete depletion of Ly6C ( + ) Ly6G ( - ) fraction prior to injury by anti - Gr - 1 antibody ( clone : RB6 - 8C5 ) treatment significantly exacerbated tissue edema , vessel permeability , and hemorrhage , causing impaired neurological outcomes .", "entity": [], "task": "NER"}
{"text": "Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury , suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome .", "entity": [], "task": "NER"}
{"text": "Moreover , intraspinal transplantation of ex vivo - generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration , resulting in better functional recovery .", "entity": [], "task": "NER"}
{"text": "Our findings reveal the crucial role of an Ly6C ( + ) Ly6G ( - ) fraction as MDSCs in regulating inflammation and tissue repair after SCI , and also suggests an MDSC - based strategy that can be applied to acute inflammatory diseases .", "entity": [], "task": "NER"}
{"text": "Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "Abstract 1 .", "entity": [], "task": "NER"}
{"text": "Disposition of tacrolimus and its major metabolites , 13 - O - desmethyl tacrolimus and 15 - O - desmethyl tacrolimus , was evaluated in stable kidney transplant recipients in relation to diabetes mellitus and genetic polymorphism of cytochrome P450 ( CYP ) 3A .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "13 - O - desmethyl tacrolimus", "entity_type": "Chemical", "pos": [54, 83]}, {"entity": "15 - O - desmethyl tacrolimus", "entity_type": "Chemical", "pos": [88, 117]}], "task": "NER"}
{"text": "Steady - state concentration - time profiles were obtained for 12 - hour or 2 - hour post - dose , in 20 ( 11 with diabetes ) and 32 ( 24 with diabetes ) patients , respectively .", "entity": [], "task": "NER"}
{"text": "In addition , single nucleotide polymorphisms of the following genes : CYP3A4 ( CYP3A4 : CYP3A4 * 1B , - 392A > G ) , 3A5 ( CYP3A5 : CYP3A5 * 3 , 6986A > G ) and P - glycoprotein ( ABCB1 : 3435C > T ) were characterized .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "Dose - normalized concentrations of tacrolimus or metabolites were higher in diabetic patients .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [36, 46]}], "task": "NER"}
{"text": "CYP3A4 * 1B carriers and CYP3A5 expressers , independently or when assessed as a combined CYP3A4 - 3A5 genotype , had significantly lower dose - normalized pre - dose ( C ( 0 ) / dose ) and 2 - hour post - dose ( C ( 2 ) / dose ) concentrations of tacrolimus and metabolites .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [248, 258]}], "task": "NER"}
{"text": "Non - diabetic patients with at least one CYP3A4 * 1B and CYP3A5 * 1 allele had lower C ( 0 ) / dose as compared to the rest of the population .", "entity": [], "task": "NER"}
{"text": "Genetic polymorphism of CYP3A5 or CYP3A4 influence tacrolimus or metabolites dose - normalized concentrations but not metabolite to parent concentration ratios .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [51, 61]}], "task": "NER"}
{"text": "The effect of diabetes on tacrolimus metabolism is subject to debate and requires a larger sample size of genetically stratified subjects .", "entity": [{"entity": "tacrolimus", "entity_type": "Chemical", "pos": [26, 36]}], "task": "NER"}
{"text": "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas .", "entity": [], "task": "NER"}
{"text": "Sarcomas of the soft tissue are a heterogeneous , rare and complex group of mesenchymal malignant tumors , accounting for less than 1 % of all adult malignancies and about 10 - 15 % of childhood cancer .", "entity": [], "task": "NER"}
{"text": "Despite local disease control obtained with surgery and pre - or postoperative radiotherapy , roughly one half of patients with high - grade tumors experience metastatic disease .", "entity": [], "task": "NER"}
{"text": "The adjunction of chemotherapy , either before or after resection , is not currently viewed as standard practice due to the lack of reproducible impact on survival .", "entity": [], "task": "NER"}
{"text": "The 1997 SMAC meta - analysis based on individual data from randomized studies confirmed a significant impact of adjuvant chemotherapy on both local and metastatic relapse , without any significant benefit on survival .", "entity": [], "task": "NER"}
{"text": "Further meta - analyses demonstrated a significant benefit also in overall survival .", "entity": [], "task": "NER"}
{"text": "Yet , the latest adjuvant EORTC trial was disappointedly negative .", "entity": [], "task": "NER"}
{"text": "To date , adjuvant chemotherapy may be recommended as a reasonable option for the high - risk individual patient who should be well informed on the possible risks and benefits of treatment .", "entity": [], "task": "NER"}
{"text": "Also the indications for neoadjuvant chemotherapy remain controversial .", "entity": [], "task": "NER"}
{"text": "A local benefit may be gained , facilitating surgery , but data on survival are limited and affected by a strong patient selection bias .", "entity": [], "task": "NER"}
{"text": "In order to improve our knowledge on sarcomas and to offer patients the best of current standards , we strongly recommend that all patients be referred to a sarcoma multidisciplinary group , under whose supervision they could receive the correct combined - modality management as well as have access to new clinical trials appropriately stratified for risk and histological and / or molecular subtypes .", "entity": [], "task": "NER"}
{"text": "Statistical analyses of protein sequence alignments identify structures and mechanisms in signal activation of sensor histidine kinases .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [118, 127]}], "task": "NER"}
{"text": "Statistical analyses of genome sequence - derived protein sequence data can identify amino acid residues that interact between proteins or between domains of a protein .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [85, 95]}], "task": "NER"}
{"text": "These statistical methods are based on evolution - directed amino acid variation responding to structural and functional constraints in proteins .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [60, 70]}], "task": "NER"}
{"text": "The identified residues form a basis for determining structure and folding of proteins as well as inferring mechanisms of protein function .", "entity": [], "task": "NER"}
{"text": "When applied to two - component systems , several research groups have shown they can be used to identify the amino acid interactions between response regulators and histidine kinases and the specificity therein .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [110, 120]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [166, 175]}], "task": "NER"}
{"text": "Recently , statistical studies between the HisKA and HATPase - ATP - binding domains of histidine kinases identified amino acid interactions for both the inactive and the active catalytic states of such kinases .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [88, 97]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [117, 127]}], "task": "NER"}
{"text": "The identified interactions generated a model structure for the domain conformation of the active state .", "entity": [], "task": "NER"}
{"text": "This conformation requires an unwinding of a portion of the C - terminal helix of the HisKA domain that destroys the inactive state residue contacts and suggests how signal - binding determines the equilibrium between the inactive and active states of histidine kinases .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [60, 61]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [252, 261]}], "task": "NER"}
{"text": "The rapidly accumulating protein sequence databases from genome , metagenome and microbiome studies are an important resource for functional and structural understanding of proteins and protein complexes in microbes .", "entity": [], "task": "NER"}
{"text": "Self - trimerization of ExsD limits inhibition of the Pseudomonas aeruginosa transcriptional activator ExsA in vitro .", "entity": [], "task": "NER"}
{"text": "The opportunistic pathogen Pseudomonas aeruginosa ranks among the leading causes of nosocomial infection .", "entity": [], "task": "NER"}
{"text": "The type III secretion system ( T3SS ) aids acute Pseudomonas aeruginosa infection by injecting potent cytotoxins into host cells to suppress the host ' s innate immune response .", "entity": [], "task": "NER"}
{"text": "Expression of all T3SS - related genes is strictly dependent on the transcription factor ExsA .", "entity": [], "task": "NER"}
{"text": "Consequently , ExsA and the biological processes that regulate ExsA function are of great biomedical interest .", "entity": [], "task": "NER"}
{"text": "The present study focused on the ExsA - ExsC - ExsD - ExsE signaling cascade , which ties host cell contact to the upregulation of T3SS gene expression .", "entity": [], "task": "NER"}
{"text": "Prior to T3SS induction , the antiactivator protein ExsD binds to ExsA and blocks ExsA - dependent transcription by interfering with ExsA dimerization and promoter interactions .", "entity": [], "task": "NER"}
{"text": "Upon host cell contact , ExsD is sequestered by the T3SS chaperone ExsC , resulting in the release of ExsA and upregulation of the T3SS .", "entity": [], "task": "NER"}
{"text": "Previous studies have shown that the ExsD - ExsA interactions are not freely reversible .", "entity": [], "task": "NER"}
{"text": "Because independently folded ExsD and ExsA were not found to interact , it has been hypothesized that folding intermediates of the two proteins form the complex .", "entity": [], "task": "NER"}
{"text": "Here , we demonstrate , for the first time , that ExsD alone is sufficient to inhibit ExsA - dependent transcription in vitro and that no other cellular factors are required .", "entity": [], "task": "NER"}
{"text": "More significantly , we show that independently folded ExsD and ExsA are capable of interacting , but only at 37 degrees C and not at 30 degrees C .", "entity": [], "task": "NER"}
{"text": "Guided by the crystal structure of ExsD , we designed a monomeric variant of the protein , and demonstrated that ExsD trimerization prevents ExsD from inhibiting ExsA - dependent transcription at 30 degrees C .", "entity": [], "task": "NER"}
{"text": "We propose that this unique mechanism plays an important role in T3SS regulation .", "entity": [], "task": "NER"}
{"text": "Morin inhibits STAT3 tyrosine 705 phosphorylation in tumor cells through activation of protein tyrosine phosphatase SHP1 .", "entity": [{"entity": "Morin", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "The major goal of cancer drug discovery is to find an agent that is safe and affordable , yet effective against cancer .", "entity": [], "task": "NER"}
{"text": "Here we show that morin ( 3 , 5 , 7 , 2 ' , 4 ' - pentahydroxyflavone ) has potential against cancer cells through suppression of the signal transducer and activator of transcription 3 ( STAT3 ) pathway , which is closely linked to the transformation , survival , proliferation , and metastasis of cancer .", "entity": [{"entity": "morin", "entity_type": "Chemical", "pos": [18, 23]}, {"entity": "3 , 5 , 7 , 2 ' , 4 ' - pentahydroxyflavone", "entity_type": "Chemical", "pos": [26, 69]}], "task": "NER"}
{"text": "We found that morin completely suppressed inducible and constitutively activated STAT3 and blocked the nuclear translocation of STAT3 and its DNA binding in multiple myeloma and head and neck squamous carcinoma cells .", "entity": [{"entity": "morin", "entity_type": "Chemical", "pos": [14, 19]}], "task": "NER"}
{"text": "Morin inhibited activated Src , JAK - 1 , and JAK - 2 , all of which are linked to STAT3 activation , while up - regulating a protein inhibitor of activated STAT3 , PIAS3 .", "entity": [{"entity": "Morin", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Pervanadate reversed the effects of morin on STAT3 phosphorylation , indicating the role of a protein tyrosine phosphatase .", "entity": [{"entity": "morin", "entity_type": "Chemical", "pos": [36, 41]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "Furthermore , morin induced SHP1 expression at both the mRNA and protein levels , and silencing of SHP1 abrogated the effect of morin on STAT3 phosphorylation , indicating that morin mediates its effects on STAT3 through SHP1 .", "entity": [{"entity": "morin", "entity_type": "Chemical", "pos": [14, 19]}, {"entity": "morin", "entity_type": "Chemical", "pos": [128, 133]}, {"entity": "morin", "entity_type": "Chemical", "pos": [177, 182]}], "task": "NER"}
{"text": "Suppression of STAT3 correlated with the down - regulation of various gene products linked to tumor survival , proliferation , and angiogenesis and led to sensitization of tumor cells to thalidomide and bortezomib .", "entity": [{"entity": "thalidomide", "entity_type": "Chemical", "pos": [187, 198]}, {"entity": "bortezomib", "entity_type": "Chemical", "pos": [203, 213]}], "task": "NER"}
{"text": "Comparing the activities of morin with those of four structurally related flavonols demonstrated the importance of hydroxyl groups in the B ring in inhibiting STAT3 activation .", "entity": [{"entity": "morin", "entity_type": "Chemical", "pos": [28, 33]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [74, 83]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "These findings suggest that morin suppresses the STAT3 pathway , leading to the down - regulation of STAT3 - dependent gene expression and chemosensitization of tumor cells .", "entity": [{"entity": "morin", "entity_type": "Chemical", "pos": [28, 33]}], "task": "NER"}
{"text": "Blood pressure and levels of Fe , Ca , Mg , Zn , Cu , Na and K in the hair of young Bantu men from Tanzania .", "entity": [{"entity": "Fe", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [34, 36]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [49, 51]}, {"entity": "Na", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "K", "entity_type": "Chemical", "pos": [61, 62]}], "task": "NER"}
{"text": "Mineral imbalance in the body may significantly contribute to the development and course of hypertension .", "entity": [], "task": "NER"}
{"text": "In this paper , blood pressure figures have been linked to the levels of Fe , Ca , Mg , Zn , Cu , Na and K in hair .", "entity": [{"entity": "Fe", "entity_type": "Chemical", "pos": [73, 75]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [78, 80]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [83, 85]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [88, 90]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [93, 95]}, {"entity": "Na", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "K", "entity_type": "Chemical", "pos": [105, 106]}], "task": "NER"}
{"text": "The research sample was composed of young men ( n = 91 ) aged 13 - 21 , from the town of Mafinga , Iringa District , Tanzania .", "entity": [], "task": "NER"}
{"text": "The data collected included their age , tribal background and weekly diet .", "entity": [], "task": "NER"}
{"text": "Based on body mass index , the participants were categorised into pre - defined subgroups .", "entity": [], "task": "NER"}
{"text": "To examine how the minerals in question affect blood pressure , correlation analysis and multiple ridge regression analysis were performed .", "entity": [], "task": "NER"}
{"text": "Analysis of ridge regression findings for the researched group ( n = 91 ) shows that the minerals under scrutiny account for systolic blood pressure variation in 13 % and in 15 % for diastolic blood pressure variation .", "entity": [], "task": "NER"}
{"text": "After including two additional variables - calendar age and body mass index - in regression analysis , the ultimate coefficient of determination ( R ( 2 ) ) changes for systolic blood pressure and remains the same for diastolic blood pressure ( R ( 2 ) = 0 . 194 and R ( 2 ) = 0 . 156 , respectively ) .", "entity": [], "task": "NER"}
{"text": "Nutritional analysis shows that the students included in the study received insufficient calories per day ( 1 , 500 - 2 , 200 kcal ) .", "entity": [], "task": "NER"}
{"text": "The group of students with abnormal blood pressure were not aware of their poor health .", "entity": [], "task": "NER"}
{"text": "Research findings may result from progressive environmental changes and poor nutrition in terms of food quantity and quality , which had an impact on the subjects ' blood pressure .", "entity": [], "task": "NER"}
{"text": "Hair analysis used to determine mineral content in the body may be an auxiliary tool in identifying the links between factors leading to the development of hypertension .", "entity": [], "task": "NER"}
{"text": "Mussel - inspired adhesive binders for high - performance silicon nanoparticle anodes in lithium - ion batteries .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "Conjugation of mussel - inspired catechol groups to various polymer backbones results in materials suitable as silicon anode binders .", "entity": [{"entity": "catechol", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [111, 118]}], "task": "NER"}
{"text": "The unique wetness - resistant adhesion provided by the catechol groups allows the silicon nanoparticle electrodes to maintain their structure throughout the repeated volume expansion and shrinkage during lithiation cycling , thus facilitating substantially improved specific capacities and cycle lives of lithium - ion batteries .", "entity": [{"entity": "catechol", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [83, 90]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [306, 313]}], "task": "NER"}
{"text": "Revising the absolute configurations of coatlines via density functional theory calculations of electronic circular dichroism spectra .", "entity": [{"entity": "coatlines", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "Coatline A ( 1 ) and alpha - epi - coatline A ( 4 ) co - occur in the trunk extract of Andira coriacea .", "entity": [{"entity": "Coatline A", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "alpha - epi - coatline A", "entity_type": "Chemical", "pos": [21, 45]}], "task": "NER"}
{"text": "Inspection of their chiroptical properties led to intriguing results .", "entity": [], "task": "NER"}
{"text": "After a careful examination of the experimental data used for the previously reported absolute configuration of these compounds , some uncertainties were identified .", "entity": [], "task": "NER"}
{"text": "A combined theoretical approach including conformational analyses and calculation of electronic circular dichroism ( ECD ) spectra , in addition with experimental data obtained for schoepfin A ( 5 ) and the new schoepfin D ( 6 ) isolated from Senna quinquangulata , allowed the revision of the absolute configuration of coatlines A ( 1 ) and B ( 2 ) .", "entity": [{"entity": "schoepfin A", "entity_type": "Chemical", "pos": [181, 192]}, {"entity": "schoepfin D", "entity_type": "Chemical", "pos": [211, 222]}, {"entity": "coatlines", "entity_type": "Chemical", "pos": [320, 329]}], "task": "NER"}
{"text": "Relative importance of direct and trophic uranium exposures in the crayfish Orconectes limosus : Implication for predicting uranium bioaccumulation and its associated toxicity .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "uranium", "entity_type": "Chemical", "pos": [124, 131]}], "task": "NER"}
{"text": "Pollutants that occur at sublethal concentrations in the environment may lead to chronic exposure in aquatic organisms .", "entity": [], "task": "NER"}
{"text": "If these pollutants bioaccumulate , then organisms higher in the food chain may also be at risk .", "entity": [], "task": "NER"}
{"text": "Increased attention has thus been focused on the relative importance of dietary uptake , but additional knowledge of the cellular distribution of metals after dietary exposure is required to assess the potential toxicity .", "entity": [], "task": "NER"}
{"text": "The authors address concerns relating to increasing uranium ( U ) concentrations ( from 12 micro g / L to 2 mg / L ) in the freshwater ecosystem caused by anthropogenic activities .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "U", "entity_type": "Chemical", "pos": [62, 63]}], "task": "NER"}
{"text": "The objective of the present study is to compare uranium bioaccumulation levels in tissues and in the subcellular environment .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [49, 56]}], "task": "NER"}
{"text": "The authors focused on the cytosol fraction and its microlocalization ( TEM - EDX ) in the gills and the hepatopancreas ( HP ) of the crayfish Orconectes limosus after 10 d of direct exposure ( at concentrations of 20 , 100 , and 500 micro g / L ) and five trophic exposure treatments ( at concentrations from 1 to 20 micro g / g ) .", "entity": [], "task": "NER"}
{"text": "Results indicated that adsorption of uranium on the cuticle represents the main contribution of total uranium accumulation to the animal .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [37, 44]}, {"entity": "uranium", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "Accumulation in the gills should be considered only as a marker of waterborne uranium exposure .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [78, 85]}], "task": "NER"}
{"text": "Accumulation in the HP after trophic environmental exposure conditions was higher ( 18 . 9 +/- 3 . 8 micro g / g ) than after direct exposure .", "entity": [], "task": "NER"}
{"text": "Moreover , no significant difference in the subcellular distribution of uranium ( 50 % ) in HP was observed between animals that had been exposed to both types of treatment .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [72, 79]}], "task": "NER"}
{"text": "A potential toxic effect after uranium accumulation could therefore exist after trophic exposure .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [31, 38]}], "task": "NER"}
{"text": "This confirms the need to focus further studies on the metal ( uranium ) risk assessment .", "entity": [{"entity": "uranium", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "Photoactivable amino acid bioisosteres and mass spectrometry : snapshots of in vivo 3D protein structures .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [15, 25]}], "task": "NER"}
{"text": "From folded to crosslinked proteins .", "entity": [], "task": "NER"}
{"text": "A new promising photo - crosslinking / mass spectrometry method for the structural characterisation of folded proteins is highlighted .", "entity": [], "task": "NER"}
{"text": "A reactive photo - leucine can clamp the front residues in beta - turn and beta - hairpin domains , thus allowing us to look into the specific native 3D structure of proteins .", "entity": [{"entity": "leucine", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "Assessment of density functional methods for reaction energetics : iridium - catalyzed water oxidation as case study .", "entity": [{"entity": "iridium", "entity_type": "Chemical", "pos": [67, 74]}], "task": "NER"}
{"text": "We investigate basis set convergence for a series of density functional theory ( DFT ) functionals ( both hybrid and nonhybrid ) and compare to coupled - cluster with single and double excitations and perturbative triples [ CCSD ( T ) ] benchmark calculations .", "entity": [], "task": "NER"}
{"text": "The case studied is the energetics of the water oxidation reaction by an iridium - oxo complex .", "entity": [{"entity": "iridium - oxo", "entity_type": "Chemical", "pos": [73, 86]}], "task": "NER"}
{"text": "Complexation energies for the reactants and products complexes as well as the transition state ( TS ) energy are considered .", "entity": [], "task": "NER"}
{"text": "Contrary to the expectation of relatively weak basis set dependence for DFT , the basis set effects are large , for example , more than 10 kcal mol ( - 1 ) difference from converged basis for the activation energy with \" small \" basis sets ( DZ / 6 - 31G * * for Ir / other atoms , or SVP ) and still more than 6 kcal mol ( - 1 ) for def2 - TZVPP / 6 - 31G * * .", "entity": [{"entity": "Ir", "entity_type": "Chemical", "pos": [263, 265]}], "task": "NER"}
{"text": "Inclusion of the dispersion correction in DFT - D3 schemes affects the energies of reactant complex ( RC ) , TS , and product complex ( PC ) by almost the same amount ; it significantly improves the complexation energy ( the formation of RC ) , but has little effect on the activation energy with respect to RC .", "entity": [], "task": "NER"}
{"text": "With converged basis , some pure GGAs ( PBE - D3 , BP86 - D3 ) as well as the hybrid functional B3LYP - D3 are very accurate compared to benchmark CCSD ( T ) calculations .", "entity": [], "task": "NER"}
{"text": "Effect of molecular crowding on the temperature - pressure stability diagram of ribonuclease A .", "entity": [], "task": "NER"}
{"text": "FT - IR spectroscopic and thermodynamic measurements were designed to explore the effect of a macromolecular crowder , dextran , on the temperature and pressure - dependent phase diagram of the protein Ribonuclease A ( RNase A ) , and we compare the experimental data with approximate theoretical predictions based on configuration entropy .", "entity": [], "task": "NER"}
{"text": "Exploring the crowding effect on the pressure - induced unfolding of proteins provides insight in protein stability and folding under cell - like dense conditions , since pressure is a fundamental thermodynamic variable linked to molecular volume .", "entity": [], "task": "NER"}
{"text": "Moreover , these studies are of relevance for understanding protein stability in deep - sea organisms , which have to cope with pressures in the kbar range .", "entity": [], "task": "NER"}
{"text": "We found that not only temperature - induced equilibrium unfolding of RNase A , but also unfolding induced by pressure is markedly prohibited in the crowded dextran solutions , suggesting that crowded environments such as those found intracellularly , will also oppress high - pressure protein unfolding .", "entity": [], "task": "NER"}
{"text": "The FT - IR spectroscopic measurements revealed a marked increase in unfolding pressure of 2 kbar in the presence of 30 wt % dextran .", "entity": [], "task": "NER"}
{"text": "Whereas the structural changes upon thermal unfolding of the protein are not significantly influenced in the presence of the crowding agent , through stabilization by dextran the pressure - unfolded state of the protein retains more ordered secondary structure elements , which seems to be a manifestation of the entropic destabilization of the unfolded state by crowding .", "entity": [], "task": "NER"}
{"text": "Proteome profiling of peripheral mononuclear cells from human blood .", "entity": [], "task": "NER"}
{"text": "Peripheral blood mononuclear cells ( MNCs ) are accessible through blood collection and represent a useful source for investigations on disease mechanisms and treatment response .", "entity": [], "task": "NER"}
{"text": "Aiming to build a reference proteome database , we generated three proteome data sets from MNCs using a combination of SDS - PAGE and nanoflow LC - MS .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [119, 122]}], "task": "NER"}
{"text": "Experiments were performed in triplicates and 514 unique proteins were identified by at least two non - redundant peptides with 95 % confidence for all replicates .", "entity": [], "task": "NER"}
{"text": "Identified proteins are associated with a range of dermatologic , inflammatory and neurological conditions as well as molecular processes , such as free radical scavenging and cellular growth and proliferation .", "entity": [], "task": "NER"}
{"text": "Mapping the MNC proteome provides a valuable resource for studies on disease pathogenesis and the identification of therapeutic targets .", "entity": [], "task": "NER"}
{"text": "Bifunctional nanoparticles constructed using one - pot encapsulation of a fluorescent polymer and magnetic ( Fe3O4 ) nanoparticles in a silica shell .", "entity": [{"entity": "Fe3O4", "entity_type": "Chemical", "pos": [109, 114]}, {"entity": "silica", "entity_type": "Chemical", "pos": [136, 142]}], "task": "NER"}
{"text": "Integration of biocompatible silica with a fluorescent polymer ( PDDF ) and superparamagnetic iron oxide nanoparticles ( Fe3 O4 ) to form uniform core - shell nanostructures has the great potential to form particles for use in multimodal bioimaging applications .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [29, 35]}, {"entity": "iron oxide", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "Fe3 O4", "entity_type": "Chemical", "pos": [121, 127]}], "task": "NER"}
{"text": "Core - shell nanoparticles ( PDDF / Fe3 O4 @ SiO2 ) exhibit fluorescent and magnetic properties that are favorable for their use in magnetic separation and guiding applications , as well as optical and magnetic resonance ( MR ) imaging capabilities .", "entity": [{"entity": "Fe3 O4", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "With the biological analysis in an in vitro intracellular permeation and cytotoxicity test , chemical conjugation of the surface using folic acid ( FA ) molecules can provide the nanoparticles with cell - targeting properties , localizing the nanoparticles to folate receptors ( FRs ) on target KB cells that over - express the FRs .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [135, 145]}, {"entity": "folate", "entity_type": "Chemical", "pos": [260, 266]}], "task": "NER"}
{"text": "Inclusion of pediatric samples in an opt - out biorepository linking DNA to de - identified medical records : pediatric BioVU .", "entity": [], "task": "NER"}
{"text": "The Vanderbilt DNA repository , BioVU , links DNA from leftover clinical blood samples to de - identified electronic medical records ( EMRs ) .", "entity": [], "task": "NER"}
{"text": "After initiating adult sample collection , pediatric extension required consideration of ethical concerns specific to pediatrics and implementation of specialized DNA extraction methods .", "entity": [], "task": "NER"}
{"text": "In the first year of pediatric sample collection , more than 11 , 000 samples from individuals younger than 18 years were included .", "entity": [], "task": "NER"}
{"text": "We compared data from the pediatric BioVU cohort with those from the overall Vanderbilt University Medical Center pediatric population and found similar demographic characteristics ; however , the BioVU cohort had higher rates of select diseases , medication exposures , and laboratory testing , demonstrating enriched representation of severe or chronic disease .", "entity": [], "task": "NER"}
{"text": "The fact that the sample accumulation is not balanced may accelerate research in some cohorts while limiting the study of relatively benign conditions and the accrual of unaffected and unbiased control samples .", "entity": [], "task": "NER"}
{"text": "BioVU represents a feasible model for pediatric DNA biobanking but involves both ethical and practical considerations specific to the pediatric population .", "entity": [], "task": "NER"}
{"text": "Is this the dose for you ? : the role of modeling .", "entity": [], "task": "NER"}
{"text": "To make an informed benefit - risk evaluation of a drug , a range of doses needs to be evaluated and its dose - response and exposure - response relationships for safety and effectiveness assessed during drug development ( International Conference on Harmonisation E4 ) .", "entity": [], "task": "NER"}
{"text": "Once a safe and effective population dose ( or doses ) has been determined for indicated use ( s ) , the individual patient dose can then be adjusted based on patient - specific factors ( e . g . , age , race , genetics , organ functions , concomitant medications ) .", "entity": [], "task": "NER"}
{"text": "One - pot assembly of a hetero - dimeric DNA origami from chip - derived staples and double - stranded scaffold .", "entity": [], "task": "NER"}
{"text": "Although structural DNA nanotechnology , and especially scaffolded DNA origami , hold great promise for bottom - up fabrication of novel nanoscale materials and devices , concerns about scalability have tempered widespread enthusiasm .", "entity": [], "task": "NER"}
{"text": "Here we report a single - pot reaction where both strands of double - stranded M13 - bacteriophage DNA are simultaneously folded into two distinct shapes that then heterodimerize with high yield .", "entity": [], "task": "NER"}
{"text": "The fully addressable , two - dimensional heterodimer DNA origami , with twice the surface area of standard M13 origami , formed in high yield ( 81 % of the well - formed monomers undergo dimerization ) .", "entity": [], "task": "NER"}
{"text": "We also report the concurrent production of entire sets of staple strands by a unique , nicking strand - displacement amplification ( nSDA ) involving reusable surface - bound template strands that were synthesized in situ using a custom piezoelectric inkjet system .", "entity": [], "task": "NER"}
{"text": "The combination of chip - based staple strand production , double - sized origami , and high - yield one - pot assembly markedly increases the useful scale of DNA origami .", "entity": [], "task": "NER"}
{"text": "In vivo biodistribution of mixed shell micelles with tunable hydrophilic / hydrophobic surface .", "entity": [], "task": "NER"}
{"text": "The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system ( RES ) , leading to inefficient enhanced permeability and retention ( EPR ) effect after intravenous injection ( i . v . ) .", "entity": [], "task": "NER"}
{"text": "Herein , we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen .", "entity": [], "task": "NER"}
{"text": "In this work , we fabricated a series of mixed shell micelles ( MSMs ) with approximately the same size , charge and core composition but with varied hydrophilic / hydrophobic ratios in the shell through spontaneously self - assembly of block copolymers poly ( ethylene glycol ) - block - poly ( l - lysine ) ( PEG - b - PLys ) and poly ( N - isopropylacrylamide ) - block - poly ( aspartic acid ) ( PNIPAM - b - PAsp ) in aqueous medium .", "entity": [{"entity": "poly ( ethylene glycol ) - block - poly ( l - lysine )", "entity_type": "Chemical", "pos": [254, 308]}, {"entity": "PEG - b - PLys", "entity_type": "Chemical", "pos": [311, 325]}, {"entity": "poly ( N - isopropylacrylamide ) - block - poly ( aspartic acid )", "entity_type": "Chemical", "pos": [332, 397]}, {"entity": "PNIPAM - b - PAsp", "entity_type": "Chemical", "pos": [400, 417]}], "task": "NER"}
{"text": "The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the ( 125 ) I - labeled MSMs determined by Gamma counter .", "entity": [{"entity": "( 125 ) I", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "Compared with single PEGylated micelles , some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i . v . .", "entity": [], "task": "NER"}
{"text": "The results provide us a novel strategy for future development of long - circulating nanocarriers for efficient cancer therapy .", "entity": [], "task": "NER"}
{"text": "Tetrahydropyrroloquinolinone type dual inhibitors of aromatase / aldosterone synthase as a novel strategy for breast cancer patients with elevated cardiovascular risks .", "entity": [{"entity": "Tetrahydropyrroloquinolinone", "entity_type": "Chemical", "pos": [0, 28]}, {"entity": "aldosterone", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "The application of aromatase inhibitors to postmenopausal breast cancer patients increases the risk of cardiovascular diseases ( CVD ) , which is believed to be caused by the abnormally high concentrations of aldosterone as a consequence of the estrogen deficiency .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [209, 220]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [245, 253]}], "task": "NER"}
{"text": "Dual inhibitors of aromatase ( CYP19 ) and aldosterone synthase ( CYP11B2 ) are therefore proposed as a novel strategy for the adjuvant therapy to reduce the CVD risk for these patients .", "entity": [{"entity": "aldosterone", "entity_type": "Chemical", "pos": [43, 54]}], "task": "NER"}
{"text": "By combining decisive structural features of CYP11B2 and CYP19 inhibitors into a common template , a series of pyridinylmethyl substituted 1 , 2 , 5 , 6 - tetrahydro - pyrrolo [ 3 , 2 , 1 - ij ] quinolin - 4 - ones were designed and synthesized .", "entity": [{"entity": "pyridinylmethyl substituted 1 , 2 , 5 , 6 - tetrahydro - pyrrolo [ 3 , 2 , 1 - ij ] quinolin - 4 - ones", "entity_type": "Chemical", "pos": [111, 214]}], "task": "NER"}
{"text": "Interestingly , the substituents on the methylene bridge showed strong influences on the inhibitory activities leading to opposite effects , that is , a given substituent showed an increase in inhibition of one enzyme , while it led to a decrease for the other enzyme .", "entity": [{"entity": "methylene", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "The compromise of this conflict led to compounds 3j , 3k , 3n , and 3p as potent and selective dual inhibitors of CYP19 and CYP11B2 , especially compound 3p , which exhibited IC ( 50 ) values of 32 and 41 nM for CYP19 and CYP11B2 , respectively , and a high selectivity toward CYP17 and CYP11B1 .", "entity": [], "task": "NER"}
{"text": "This compound is considered as a candidate for further evaluation in vivo .", "entity": [], "task": "NER"}
{"text": "Absolute configuration and conformational analysis of brevipolides , bioactive 5 , 6 - dihydro - alpha - pyrones from Hyptis brevipes .", "entity": [{"entity": "brevipolides", "entity_type": "Chemical", "pos": [54, 66]}, {"entity": "5 , 6 - dihydro - alpha - pyrones", "entity_type": "Chemical", "pos": [79, 112]}], "task": "NER"}
{"text": "The ( 6 ' S ) - configuration of brevipolides A - J ( 1 - 10 ) , isolated from Hyptis brevipes , was established by X - ray diffraction analysis of 9 in conjunction with Mosher ' s ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations .", "entity": [{"entity": "brevipolides A - J", "entity_type": "Chemical", "pos": [33, 51]}, {"entity": "Mosher ' s ester", "entity_type": "Chemical", "pos": [170, 186]}], "task": "NER"}
{"text": "The structure of the new brevipolide J ( 10 ) was characterized through NMR and MS data as having the same 6 - heptyl - 5 , 6 - dihydro - 2H - pyran - 2 - one framework possessing the cyclopropane moiety of all brevipolides but substituted by an isoferuloyl group instead of the p - methoxycinnamoyl moiety found in 8 and 9 .", "entity": [{"entity": "brevipolide J", "entity_type": "Chemical", "pos": [25, 38]}, {"entity": "6 - heptyl - 5 , 6 - dihydro - 2H - pyran - 2 - one", "entity_type": "Chemical", "pos": [107, 158]}, {"entity": "cyclopropane", "entity_type": "Chemical", "pos": [184, 196]}, {"entity": "brevipolides", "entity_type": "Chemical", "pos": [211, 223]}, {"entity": "isoferuloyl", "entity_type": "Chemical", "pos": [246, 257]}, {"entity": "p - methoxycinnamoyl", "entity_type": "Chemical", "pos": [279, 299]}], "task": "NER"}
{"text": "Conformational analysis of these cytotoxic 6 - heptyl - 5 , 6 - dihydro - alpha - pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT - calculated vicinal ( 1 ) H - ( 1 ) H NMR coupling constants .", "entity": [{"entity": "6 - heptyl - 5 , 6 - dihydro - alpha - pyrones", "entity_type": "Chemical", "pos": [43, 89]}, {"entity": "( 1 ) H - ( 1 ) H", "entity_type": "Chemical", "pos": [219, 236]}], "task": "NER"}
{"text": "Molecular modeling was used to correlate minimum energy conformers and observed electronic circular dichroism transitions for the isomeric series of brevipolides .", "entity": [{"entity": "brevipolides", "entity_type": "Chemical", "pos": [149, 161]}], "task": "NER"}
{"text": "Compounds 7 - 10 exhibited moderate activity ( ED ( 50 ) 0 . 3 - 8 . 0 mu g / mL ) against a variety of tumor cell lines .", "entity": [], "task": "NER"}
{"text": "Treatment and prevention of various therapeutic conditions using OX receptor antagonistic activity ( WO2012081692 ) .", "entity": [{"entity": "WO2012081692", "entity_type": "Chemical", "pos": [101, 113]}], "task": "NER"}
{"text": "Application WO2012081692 from Taisho Pharmaceutical Co .", "entity": [{"entity": "WO2012081692", "entity_type": "Chemical", "pos": [12, 24]}], "task": "NER"}
{"text": "Ltd . claims pyrazole - based antagonists of the orexin - 1 and orexin - 2 receptors .", "entity": [{"entity": "pyrazole", "entity_type": "Chemical", "pos": [13, 21]}], "task": "NER"}
{"text": "Utility in a number of therapeutic areas is claimed , including the treatment of sleep disorders ; the most likely use of the claimed compounds .", "entity": [], "task": "NER"}
{"text": "Data from in vitro functional assays are presented , with the claimed compounds typically being dual orexin receptor antagonists ( DORAs ) or having moderate selectivity for orexin - 1 .", "entity": [], "task": "NER"}
{"text": "Structurally , the claimed compounds represent a variation on established DORA SAR themes and translate features of clinical compounds into a pyrazole - based scaffold .", "entity": [{"entity": "pyrazole", "entity_type": "Chemical", "pos": [142, 150]}], "task": "NER"}
{"text": "Example 52 , the most potent molecule in the application , has similar molecular weight and lipophilicity to suvorexant , the most advanced DORA , with broadly comparable potency in functional assays .", "entity": [{"entity": "suvorexant", "entity_type": "Chemical", "pos": [109, 119]}], "task": "NER"}
{"text": "Highly sensitive fluorescent and colorimetric pH sensor based on polyethylenimine - capped silver nanoclusters .", "entity": [{"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [65, 81]}, {"entity": "silver", "entity_type": "Chemical", "pos": [91, 97]}], "task": "NER"}
{"text": "Silver nanoclusters capped by hyperbranched polyethylenimine ( PEI ) have been developed as a highly sensitive fluorescent and colorimetric pH sensor .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [44, 60]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "The probe responds rapidly to pH fluctuations and has such absorption characteristics that the color changes from the colorless or a nearly colorless state to a colored state with increasing acidity , so PEI - capped Ag nanoclusters could be used as a color indicator for colorimetric pH detection .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [204, 207]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [217, 219]}], "task": "NER"}
{"text": "Quantitatively , the fluorescence intensity of PEI - capped Ag nanoclusters exhibits a linear fashion over the pH range of 5 . 02 - 7 . 96 and increases by around 10 - fold approximately with greater fluorescence at higher pH values .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [60, 62]}], "task": "NER"}
{"text": "The repulsion development and conformational change of PEI with decreasing pH induce the aggregation of Ag nanoclusters , leading to an obvious color change and fluorescence quenching of Ag nanoclusters at low pH values .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [104, 106]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [187, 189]}], "task": "NER"}
{"text": "As expected , the pH probe is also sensitive to the different buffer solutions , except for those containing some anions that could react with Ag nanoclusters .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [143, 145]}], "task": "NER"}
{"text": "Besides , the ionic strength of the buffers has a little influence on the pH - responsive behavior .", "entity": [], "task": "NER"}
{"text": "Our pH sensor with nanoscaled physical dimensions would be a promising candidate in the applications in biological , medical , and pharmaceutical fields .", "entity": [], "task": "NER"}
{"text": "Multicolor fluorescent semiconducting polymer dots with narrow emissions and high brightness .", "entity": [], "task": "NER"}
{"text": "Fluorescent semiconducting polymer dots ( Pdots ) have attracted great interest because of their superior characteristics as fluorescent probes , such as high fluorescence brightness , fast radiative rates , and excellent photostability .", "entity": [], "task": "NER"}
{"text": "However , currently available Pdots generally exhibit broad emission spectra , which significantly limit their usefulness in many biological applications involving multiplex detections .", "entity": [], "task": "NER"}
{"text": "Here , we describe the design and development of multicolor narrow emissive Pdots based on different boron dipyrromethene ( BODIPY ) units .", "entity": [{"entity": "boron dipyrromethene", "entity_type": "Chemical", "pos": [101, 121]}, {"entity": "BODIPY", "entity_type": "Chemical", "pos": [124, 130]}], "task": "NER"}
{"text": "BODIPY - containing semiconducting polymers emitting at multiple wavelengths were synthesized and used as precursors for preparing the Pdots , where intraparticle energy transfer led to highly bright , narrow emissions .", "entity": [{"entity": "BODIPY", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "The emission full width at half - maximum of the resulting Pdots varies from 40 to 55 nm , which is 1 . 5 - 2 times narrower than those of conventional semiconducting polymer dots .", "entity": [], "task": "NER"}
{"text": "BODIPY 520 Pdots were about an order of magnitude brighter than commercial Qdot 525 under identical laser excitation conditions .", "entity": [{"entity": "BODIPY", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Fluorescence imaging and flow cytometry experiments indicate that the narrow emissions from these bright Pdots are promising for multiplexed biological detections .", "entity": [], "task": "NER"}
{"text": "Characterization of arsenic induced cytotoxicity in liver with stress in erythrocytes and its reversibility with Pleurotus florida lectin .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [20, 27]}], "task": "NER"}
{"text": "Arsenic is one of the most hazardous substances in the environment known to cause toxicity in multiple organs .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Cell adhesion , morphological alterations , cell proliferation , terminal deoxyuridine triphosphate nick - end labeling ( TUNEL ) and caspase - 3 / CPP32 fluorometric protease assay were important biomarkers to assess apoptosis in cells .", "entity": [{"entity": "deoxyuridine triphosphate", "entity_type": "Chemical", "pos": [74, 99]}], "task": "NER"}
{"text": "This study aimed to evaluate arsenic - induced apoptosis in the hepatocytes of rat and its protective efficacy with coadministration of ascorbic acid ( AA ) and Pleurotus florida lectin ( PFL ) individually .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [29, 36]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [136, 149]}], "task": "NER"}
{"text": "Results of the present study also showed that arsenic caused cytotoxicity by elevating morphological alterations , TUNEL - positive nuclei , caspase - 3 activity and DNA damage and reducing cell adhesion and cell proliferation in a time - dependent manner .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "The apoptosis in hepatocytes was reverted to normal value after coadministration of mushroom lectin in arsenic - exposed rat .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "The study provided significant evidence that PFL has antiapoptotic property against arsenic - induced toxicity .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "The beneficial effect of PFL was proportional to its duration of exposure .", "entity": [], "task": "NER"}
{"text": "Retard activities of superoxide dismutase and catalase , enhanced lipid peroxidation as well as protein carbonyl in erythrocytes caused by arsenic could also be maintained toward normalcy by supplementation of AA and PFL .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [21, 31]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [104, 112]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "These antioxidative effects were exhibited in a time - dependant manner .", "entity": [], "task": "NER"}
{"text": "In rat , treatment with AA and PFL prevented alteration of plasma enzyme activities caused by arsenic .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "The results concluded that treatment with PFL has significant role in protecting animals from arsenic - induced erythrocytic damage .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources , a global problem especially relevant to millions of people on the Indian subcontinent .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "Control of transcriptional fidelity by active center tuning as derived from RNA polymerase endonuclease reaction .", "entity": [], "task": "NER"}
{"text": "Precise transcription by cellular RNA polymerase requires the efficient removal of noncognate nucleotide residues that are occasionally incorporated .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [94, 104]}], "task": "NER"}
{"text": "Mis - incorporation causes the transcription elongation complex to backtrack , releasing a single strand 3 ' - RNA segment bearing a noncognate residue , which is hydrolyzed by the active center that carries two Mg ( 2 + ) ions .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [212, 222]}], "task": "NER"}
{"text": "However , in most x - ray structures only one Mg ( 2 + ) is present .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "This Mg ( 2 + ) is tightly bound to the active center aspartates , creating an inactive stable state .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [5, 15]}, {"entity": "aspartates", "entity_type": "Chemical", "pos": [54, 64]}], "task": "NER"}
{"text": "The first residue of the single strand RNA segment in the backtracked transcription elongation complex strongly promotes transcript hydrolytic cleavage by establishing a network of interactions that force a shift of stably bound Mg ( 2 + ) to release some of its aspartate coordination valences for binding to the second Mg ( 2 + ) thus enabling catalysis .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [229, 239]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [263, 272]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [321, 331]}], "task": "NER"}
{"text": "Such a rearrangement that we call active center tuning ( ACT ) occurs when all recognition contacts of the active center - bound RNA segment are established and verified by tolerance to stress .", "entity": [], "task": "NER"}
{"text": "Transcription factor Gre builds on the ACT mechanism in the same reaction by increasing the retention of the second Mg ( 2 + ) and by activating the attacking water , causing 3000 - 4000 - fold reaction acceleration and strongly reinforcing proofreading .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [116, 126]}], "task": "NER"}
{"text": "The unified mechanism for RNA synthesis and degradation by RNA polymerase predicts that ACT also executes NTP selection thereby contributing to high transcription fidelity .", "entity": [], "task": "NER"}
{"text": "Discovery of 5 - benzyl - 3 - phenyl - 4 , 5 - dihydroisoxazoles and 5 - benzyl - 3 - phenyl - 1 , 4 , 2 - dioxazoles as potent firefly luciferase inhibitors .", "entity": [{"entity": "5 - benzyl - 3 - phenyl - 4 , 5 - dihydroisoxazoles", "entity_type": "Chemical", "pos": [13, 64]}, {"entity": "5 - benzyl - 3 - phenyl - 1 , 4 , 2 - dioxazoles", "entity_type": "Chemical", "pos": [69, 117]}], "task": "NER"}
{"text": "Luciferase reporter assays are commonly used in high - throughput screening methods .", "entity": [], "task": "NER"}
{"text": "Here , we report new firefly luciferase ( FLuc ) inhibitors based on 5 - benzyl - 3 - phenyl - 4 , 5 - dihydroisoxazoles and 5 - benzyl - 3 - phenyl - 1 , 4 , 2 - dioxazoles , which showed up as \" false positives \" in a luciferase reporter gene - based assay for nuclear receptor antagonists .", "entity": [{"entity": "5 - benzyl - 3 - phenyl - 4 , 5 - dihydroisoxazoles", "entity_type": "Chemical", "pos": [69, 120]}, {"entity": "5 - benzyl - 3 - phenyl - 1 , 4 , 2 - dioxazoles", "entity_type": "Chemical", "pos": [125, 173]}], "task": "NER"}
{"text": "The inhibition was shown to be noncompetitive for both natural enzyme substrates ( d - luciferin and ATP ) and selective to FLuc and proven to arise from a direct interaction between the enzyme and the inhibitor .", "entity": [{"entity": "d - luciferin", "entity_type": "Chemical", "pos": [83, 96]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Of the 63 evaluated compounds , 28 showed significantly better inhibition potency than the well - known inhibitor resveratrol ( IC ( 50 ) = 59 nM ) , with five compounds having distinctly subnanomolar IC ( 50 ) values .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "The most efficient compounds inhibited the luminescence at concentrations lower than ( 1 ) / ( 100 ) in comparison to resveratrol ( lowest IC ( 50 ) = 0 . 26 nM ) and can thus be considered to belong to the most potent FLuc inhibitors reported thus far .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [118, 129]}], "task": "NER"}
{"text": "Overall , the novel inhibitors form a unique molecular library for structure - activity relationship ( SAR ) analyses .", "entity": [], "task": "NER"}
{"text": "Design and implementation of two - dimensional polymer adsorption models : evaluating the stability of Candida antarctica lipase B / solid - support interfaces by QCM - D .", "entity": [], "task": "NER"}
{"text": "A two - dimensional model of a solid - supported enzyme catalyst bead is fabricated on a quartz crystal microbalance with dissipation monitoring ( QCM - D ) sensor to measure in situ interfacial stability and mechanical properties of Candida antarctica Lipase B ( CAL B ) under varied conditions relating to ring - opening polymerization .", "entity": [{"entity": "quartz", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "The model was fabricated using a dual photochemical approach , where poly ( methyl methacrylate ) ( PMMA ) thin films were cross - linked by a photoactive benzophenone monolayer and blended cross - linking agent .", "entity": [{"entity": "poly ( methyl methacrylate )", "entity_type": "Chemical", "pos": [69, 97]}, {"entity": "PMMA", "entity_type": "Chemical", "pos": [100, 104]}, {"entity": "benzophenone", "entity_type": "Chemical", "pos": [155, 167]}], "task": "NER"}
{"text": "This process produces two - dimensional , homogeneous , rigid PMMA layers , which mimic commercial acrylic resins in a QCM - D experiment .", "entity": [{"entity": "PMMA", "entity_type": "Chemical", "pos": [62, 66]}, {"entity": "acrylic", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "Adsorption of CAL B to PMMA in QCM - D under varied buffer ionic strengths produces a viscoelastic enzyme surface that becomes more rigid as ionic strength increases .", "entity": [{"entity": "PMMA", "entity_type": "Chemical", "pos": [23, 27]}], "task": "NER"}
{"text": "The rigid CAL B / PMMA interface demonstrates up to 20 % desorption of enzyme with increasing trace water content .", "entity": [{"entity": "PMMA", "entity_type": "Chemical", "pos": [18, 22]}], "task": "NER"}
{"text": "Increased polycaprolactone ( PCL ) binding at the enzyme surface was also observed , indicating greater PCL affinity for a more hydrated enzyme surface .", "entity": [{"entity": "polycaprolactone", "entity_type": "Chemical", "pos": [10, 26]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [104, 107]}], "task": "NER"}
{"text": "The enzyme layer destabilized with increasing temperature , yielding near complete reversible catalyst desorption in the model .", "entity": [], "task": "NER"}
{"text": "Effects of the benzimidazole anthelmintic drug flubendazole on rat embryos in vitro .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [15, 28]}, {"entity": "flubendazole", "entity_type": "Chemical", "pos": [47, 59]}], "task": "NER"}
{"text": "Filarial diseases affect millions of people in poverty - stricken areas .", "entity": [], "task": "NER"}
{"text": "In 2011 , an investigation of the potential of flubendazole as a safe , highly efficacious , and field - usable macrofilaricidal drug was begun by Drug for Neglected Diseases initiative .", "entity": [{"entity": "flubendazole", "entity_type": "Chemical", "pos": [47, 59]}], "task": "NER"}
{"text": "As part of the preclinical development program , whole embryo culture was used to investigate the potential embryotoxicity of flubendazole and its metabolites , reduced and hydrolyzed flubendazole .", "entity": [{"entity": "flubendazole", "entity_type": "Chemical", "pos": [126, 138]}, {"entity": "flubendazole", "entity_type": "Chemical", "pos": [184, 196]}], "task": "NER"}
{"text": "Albendazole was included as a comparator .", "entity": [{"entity": "Albendazole", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Flubendazole and albendazole showed similar potency in affecting rat embryonic development in vitro , inducing retardation of growth and dysmorphogenic effects at concentrations >= 0 . 5 mu g / mL .", "entity": [{"entity": "Flubendazole", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "albendazole", "entity_type": "Chemical", "pos": [17, 28]}], "task": "NER"}
{"text": "The head , optic and otic systems , branchial arches and posterior body portion were affected .", "entity": [], "task": "NER"}
{"text": "Diffuse areas of cell death were seen in various embryonic districts .", "entity": [], "task": "NER"}
{"text": "The No Observed Effect Level ( NOEL ) was 0 . 25 mu g / mL for both drugs .", "entity": [], "task": "NER"}
{"text": "Reduced and hydrolyzed flubendazole were less embryotoxic than the parent compound , with NOELs 4 - fold and > 40 - fold higher than that of flubendazole , respectively .", "entity": [{"entity": "flubendazole", "entity_type": "Chemical", "pos": [23, 35]}, {"entity": "flubendazole", "entity_type": "Chemical", "pos": [141, 153]}], "task": "NER"}
{"text": "Effect of pigeon pea ( Cajanus cajan L . ) on high - fat diet - induced hypercholesterolemia in hamsters .", "entity": [], "task": "NER"}
{"text": "Obesity is associated with increased systemic and airway oxidative stress , which may result from a combination of adipokine imbalance and antioxidant defenses reduction .", "entity": [], "task": "NER"}
{"text": "Obesity - mediated oxidative stress plays an important role in the pathogenesis of dyslipidemia , vascular disease , and nonalcoholic hepatic steatosis .", "entity": [], "task": "NER"}
{"text": "The antidyslipidemic activity of pigeon pea were evaluated by high - fat diet ( HFD ) hamsters model , in which the level of high - density lipoprotein - cholesterol ( HDL - C ) , low - density lipoprotein - cholesterol ( LDL - C ) , total cholesterol ( TC ) , and total triglyceride ( TG ) were examined .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [154, 165]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [208, 219]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [240, 251]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [271, 283]}], "task": "NER"}
{"text": "We found that pigeon pea administration promoted cholesterol converting to bile acid in HFD - induced hamsters , thereby exerting hypolipidemic activity .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [75, 84]}], "task": "NER"}
{"text": "In the statistical results , pigeon pea significantly increased hepatic carnitine palmitoyltransferase - 1 ( CPT - 1 ) , LDL receptor , and cholesterol 7 alpha - hydroxylase ( also known as cytochrome P450 7A1 , CYP7A1 ) expression to attenuate dyslipidemia in HFD - fed hamsters ; and markedly elevated antioxidant enzymes in the liver of HFD - induced hamsters , further alleviating lipid peroxidation .", "entity": [{"entity": "carnitine", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [140, 151]}], "task": "NER"}
{"text": "These effects may attribute to pigeon pea contained large of unsaturated fatty acids ( UFA ; C18 : 2 ) and phytosterol ( beta - sitosterol , campesterol , and stigmasterol ) .", "entity": [{"entity": "unsaturated fatty acids", "entity_type": "Chemical", "pos": [61, 84]}, {"entity": "UFA", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "phytosterol", "entity_type": "Chemical", "pos": [107, 118]}, {"entity": "beta - sitosterol", "entity_type": "Chemical", "pos": [121, 138]}, {"entity": "campesterol", "entity_type": "Chemical", "pos": [141, 152]}, {"entity": "stigmasterol", "entity_type": "Chemical", "pos": [159, 171]}], "task": "NER"}
{"text": "Moreover , the effects of pigeon pea on dyslipidemia were greater than beta - sitosterol administration ( 4 % ) , suggesting that phytosterone in pigeon pea could prevent metabolic syndrome .", "entity": [{"entity": "beta - sitosterol", "entity_type": "Chemical", "pos": [71, 88]}, {"entity": "phytosterone", "entity_type": "Chemical", "pos": [130, 142]}], "task": "NER"}
{"text": "Novel treatment options for epilepsy : focus on perampanel .", "entity": [{"entity": "perampanel", "entity_type": "Chemical", "pos": [48, 58]}], "task": "NER"}
{"text": "Perampanel is a new chemical entity recently approved in the United States ( US ) and European Union ( EU ) as adjunctive treatment of partial - onset seizures with and without secondary generalization in patients with epilepsy aged 12 years and older .", "entity": [{"entity": "Perampanel", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Pharmacological studies suggest that perampanel acts with a new mechanism of action via non - competitive antagonism of the ionotropic alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazoleproprionic acid ( AMPA ) receptor of glutamate , the main mediator of excitatory neurotransmission in the central nervous system .", "entity": [{"entity": "perampanel", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazoleproprionic acid", "entity_type": "Chemical", "pos": [135, 206]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [209, 213]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [228, 237]}], "task": "NER"}
{"text": "Perampanel is completely absorbed after oral administration .", "entity": [{"entity": "Perampanel", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The drug is 95 % bound to plasma proteins and is extensively metabolized by oxidation followed by glucuronidation .", "entity": [], "task": "NER"}
{"text": "Perampanel has an elimination half - life of approximately 52 - 129h , allowing once daily dosing , with peak plasma levels observed 0 . 25 - 2h post - dose .", "entity": [{"entity": "Perampanel", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Randomized placebo - controlled trials of adjunctive treatment have demonstrated that once - daily perampanel doses of 4 - 12mg / day significantly reduced partial - onset seizure frequency in patients with pharmacoresistant epilepsy along with a favorable tolerability profile .", "entity": [{"entity": "perampanel", "entity_type": "Chemical", "pos": [99, 109]}], "task": "NER"}
{"text": "In perampanel pivotal trials , the most frequently reported treatment emergent adverse events ( > 10 % ) included dizziness , somnolence , fatigue and headache .", "entity": [{"entity": "perampanel", "entity_type": "Chemical", "pos": [3, 13]}], "task": "NER"}
{"text": "Perampanel therapeutic response was maintained in patients included in the long term open - label extension studies for up to 4 years .", "entity": [{"entity": "Perampanel", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Based on these data , perampanel offers a valuable option in the add - on treatment of partial - onset and secondarily generalized seizures .", "entity": [{"entity": "perampanel", "entity_type": "Chemical", "pos": [22, 32]}], "task": "NER"}
{"text": "SAR analysis of novel non - peptidic NPBWR1 ( GPR7 ) antagonists .", "entity": [], "task": "NER"}
{"text": "In this Letter we report on the advances in our NPBWR1 antagonist program aimed at optimizing the 5 - chloro - 2 - ( 3 , 5 - dimethylphenyl ) - 4 - ( 4 - methoxyphenoxy ) pyridazin - 3 ( 2H ) - one lead molecule previously obtained from a high - throughput screening ( HTS ) - derived hit .", "entity": [{"entity": "5 - chloro - 2 - ( 3 , 5 - dimethylphenyl ) - 4 - ( 4 - methoxyphenoxy ) pyridazin - 3 ( 2H ) - one", "entity_type": "Chemical", "pos": [98, 197]}], "task": "NER"}
{"text": "Synthesis and structure - activity relationships ( SAR ) studies around the 3 , 5 - dimethylphenyl and 4 - methoxyphenyl regions resulted in the identification of a novel series of non - peptidic submicromolar NPBWR1 antagonists based on a 5 - chloro - 4 - ( 4 - alkoxyphenoxy ) - 2 - ( benzyl ) pyridazin - 3 ( 2H ) - one chemotype .", "entity": [{"entity": "3 , 5 - dimethylphenyl", "entity_type": "Chemical", "pos": [76, 98]}, {"entity": "4 - methoxyphenyl", "entity_type": "Chemical", "pos": [103, 120]}, {"entity": "5 - chloro - 4 - ( 4 - alkoxyphenoxy ) - 2 - ( benzyl ) pyridazin - 3 ( 2H ) - one", "entity_type": "Chemical", "pos": [240, 322]}], "task": "NER"}
{"text": "Amongst them , 5 - chloro - 2 - ( 9H - fluoren - 9 - yl ) - 4 - ( 4 - methoxyphenoxy ) pyridazin - 3 ( 2H ) - one 9h ( CYM50769 ) inhibited NPW activation of NPBWR1 with a submicromolar IC ( 50 ) , and displayed high selectivity against a broad array of off - targets with pharmaceutical relevance .", "entity": [{"entity": "5 - chloro - 2 - ( 9H - fluoren - 9 - yl ) - 4 - ( 4 - methoxyphenoxy ) pyridazin - 3 ( 2H ) - one", "entity_type": "Chemical", "pos": [15, 113]}, {"entity": "CYM50769", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "Our medicinal chemistry study provides innovative non - peptidic selective NPBWR1 antagonists that may enable to clarify the biological role and therapeutic utility of the target receptor in the regulation of feeding behavior , pain , stress , and neuroendocrine function .", "entity": [], "task": "NER"}
{"text": "Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose - response model .", "entity": [{"entity": "iodide", "entity_type": "Chemical", "pos": [14, 20]}], "task": "NER"}
{"text": "A biologically based dose - response ( BBDR ) model for the hypothalamic - pituitary thyroid ( HPT ) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis .", "entity": [{"entity": "iodide", "entity_type": "Chemical", "pos": [197, 203]}], "task": "NER"}
{"text": "Model calibrations , carried out by adjusting key model parameters , were used as a technique to evaluate HPT axis adaptations to dietary iodide intake in euthyroid ( 4 . 1 - 39 micro g iodide / day ) and iodide - deficient ( 0 . 31 and 1 . 2 micro g iodide / day ) conditions .", "entity": [{"entity": "iodide", "entity_type": "Chemical", "pos": [138, 144]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [186, 192]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [205, 211]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [251, 257]}], "task": "NER"}
{"text": "Iodide - deficient conditions in both the dam and the pup were described with increased blood flow to the thyroid gland , TSH - mediated increase in thyroidal uptake of iodide and binding of iodide in the thyroid gland ( organification ) , and , in general , reduced thyroid hormone production and metabolism .", "entity": [{"entity": "Iodide", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [169, 175]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [191, 197]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [267, 282]}], "task": "NER"}
{"text": "Alterations in thyroxine ( T4 ) homeostasis were more apparent than for triiodothyronine ( T3 ) .", "entity": [{"entity": "thyroxine", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "triiodothyronine", "entity_type": "Chemical", "pos": [72, 88]}], "task": "NER"}
{"text": "Model - predicted average daily area - under - the - serum - concentration - curve ( nM - day ) values for T4 at steady state in the dam and pup decreased by 14 - 15 % for the 1 . 2 micro g iodide / day iodide - deficient diet and 42 - 52 % for the 0 . 31 micro g iodide / day iodide - deficient diet .", "entity": [{"entity": "iodide", "entity_type": "Chemical", "pos": [190, 196]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [203, 209]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [264, 270]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [277, 283]}], "task": "NER"}
{"text": "In rat pups that were iodide deficient during gestation and lactation , these decreases in serum T4 levels were associated with declines in thyroid hormone in the fetal brain and a suppression of synaptic responses in the hippocampal region of the brain of the adult offspring ( Gilbert et al . , 2013 ) .", "entity": [{"entity": "iodide", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [140, 155]}], "task": "NER"}
{"text": "Perspectives on the reaction force constant .", "entity": [], "task": "NER"}
{"text": "A synchronous , concerted chemical process is rigorously divided by the reaction force F ( R ) , the negative gradient of V ( R ) , into \" reactant \" and \" product \" regions which are dominated by structural changes and an intervening \" transition \" region which is electronically intensive .", "entity": [], "task": "NER"}
{"text": "The reaction force constant kappa ( R ) , the second derivative of V ( R ) , is negative throughout the transition region , not just at the nominal transition state , at which kappa ( R ) has a minimum .", "entity": [], "task": "NER"}
{"text": "This is consistent with experimental evidence that there is a transition region , not simply a specific point .", "entity": [], "task": "NER"}
{"text": "We show graphically that significant nonsynchronicity in the process is associated with the development of a maximum of kappa ( R ) in the transition region , which increases as the process becomes more nonsynchronous .", "entity": [], "task": "NER"}
{"text": "( We speculate that for a nonconcerted process this maximum is actually positive . ) Thus , kappa ( R ) can serve as an indicator of the level of nonsynchronicity .", "entity": [], "task": "NER"}
{"text": "Inhibition of matrix metalloproteinase - 9 expression by docosahexaenoic acid mediated by heme oxygenase 1 in 12 - O - tetradecanoylphorbol - 13 - acetate - induced MCF - 7 human breast cancer cells .", "entity": [{"entity": "docosahexaenoic acid", "entity_type": "Chemical", "pos": [57, 77]}, {"entity": "heme", "entity_type": "Chemical", "pos": [90, 94]}, {"entity": "12 - O - tetradecanoylphorbol - 13 - acetate", "entity_type": "Chemical", "pos": [110, 154]}], "task": "NER"}
{"text": "Matrix metalloproteinase - 9 ( MMP - 9 ) plays a crucial role in tumor metastasis .", "entity": [], "task": "NER"}
{"text": "Previous studies showed that polyunsaturated fatty acids exhibit an anti - cancer effect in various human carcinoma cells , but the effect of docosahexaenoic acid ( DHA ) and linoleic acid ( LA ) on metastasis of breast cancer cells is not fully clarified .", "entity": [{"entity": "polyunsaturated fatty acids", "entity_type": "Chemical", "pos": [29, 56]}, {"entity": "docosahexaenoic acid", "entity_type": "Chemical", "pos": [142, 162]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [165, 168]}, {"entity": "linoleic acid", "entity_type": "Chemical", "pos": [175, 188]}], "task": "NER"}
{"text": "We studied the anti - metastasis potential of DHA and LA in 12 - O - tetradecanoylphorbol - 13 - acetate ( TPA ) - induced MCF - 7 cells .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "12 - O - tetradecanoylphorbol - 13 - acetate", "entity_type": "Chemical", "pos": [60, 104]}, {"entity": "TPA", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "We found that TPA ( 100 ng / ml ) induced MMP - 9 enzyme activity both dose - and time - dependently , and 200 mu M DHA and LA significantly inhibited MMP - 9 mRNA and protein expression , enzyme activity , cell migration , and invasion .", "entity": [{"entity": "TPA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "Treatment with PD98059 ( 10 mu M ) , wortmannin ( 10 mu M ) , and GF109203X ( 0 . 5 mu M ) decreased TPA - induced MMP - 9 protein expression and enzyme activity .", "entity": [{"entity": "PD98059", "entity_type": "Chemical", "pos": [15, 22]}, {"entity": "wortmannin", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "GF109203X", "entity_type": "Chemical", "pos": [66, 75]}, {"entity": "TPA", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "TPA - induced activation of ERK1 , Akt , and PKC delta was attenuated by DHA , whereas LA attenuated only ERK1 activation .", "entity": [{"entity": "TPA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "GF109203X also suppressed ERK1 activation .", "entity": [{"entity": "GF109203X", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "EMSA showed that DHA , LA , PD98059 , and wortmannin decreased TPA - induced NF - kappa B and AP - 1 DNA - binding activity .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "PD98059", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "wortmannin", "entity_type": "Chemical", "pos": [42, 52]}, {"entity": "TPA", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "Furthermore , DHA rather than LA dose - dependently increased HO - 1 expression .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "HO - 1 siRNA alleviated the inhibition by DHA of TPA - induced MMP - 9 protein expression and enzyme activity in MCF - 7 cells , and HO - 1 knockdown reversed the DHA inhibition of cell migration .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "TPA", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [163, 166]}], "task": "NER"}
{"text": "These results suggest that DHA and LA have both similar and divergent signaling pathways in the suppression of TPA - induced MCF - 7 metastasis .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "TPA", "entity_type": "Chemical", "pos": [111, 114]}], "task": "NER"}
{"text": "Calculation of wave - functions with frozen orbitals in mixed quantum mechanics / molecular mechanics methods .", "entity": [], "task": "NER"}
{"text": "II .", "entity": [], "task": "NER"}
{"text": "Application of the local basis equation .", "entity": [], "task": "NER"}
{"text": "The application of the local basis equation ( Ferenczy and Adams , J . Chem . Phys . 2009 , 130 , 134108 ) in mixed quantum mechanics / molecular mechanics ( QM / MM ) and quantum mechanics / quantum mechanics ( QM / QM ) methods is investigated .", "entity": [], "task": "NER"}
{"text": "This equation is suitable to derive local basis nonorthogonal orbitals that minimize the energy of the system and it exhibits good convergence properties in a self - consistent field solution .", "entity": [], "task": "NER"}
{"text": "These features make the equation appropriate to be used in mixed QM / MM and QM / QM methods to optimize orbitals in the field of frozen localized orbitals connecting the subsystems .", "entity": [], "task": "NER"}
{"text": "Calculations performed for several properties in divers systems show that the method is robust with various choices of the frozen orbitals and frontier atom properties .", "entity": [], "task": "NER"}
{"text": "With appropriate basis set assignment , it gives results equivalent with those of a related approach [ G . G . Ferenczy previous paper in this issue ] using the Huzinaga equation .", "entity": [], "task": "NER"}
{"text": "Thus , the local basis equation can be used in mixed QM / MM methods with small size quantum subsystems to calculate properties in good agreement with reference Hartree - Fock - Roothaan results .", "entity": [], "task": "NER"}
{"text": "It is shown that bond charges are not necessary when the local basis equation is applied , although they are required for the self - consistent field solution of the Huzinaga equation based method .", "entity": [], "task": "NER"}
{"text": "Conversely , the deformation of the wave - function near to the boundary is observed without bond charges and this has a significant effect on deprotonation energies but a less pronounced effect when the total charge of the system is conserved .", "entity": [], "task": "NER"}
{"text": "The local basis equation can also be used to define a two layer quantum system with nonorthogonal localized orbitals surrounding the central delocalized quantum subsystem .", "entity": [], "task": "NER"}
{"text": "Materials for the active layer of organic photovoltaics : ternary solar cell approach .", "entity": [], "task": "NER"}
{"text": "Power conversion efficiencies in excess of 7 % have been achieved with bulk heterojunction ( BHJ ) - type organic solar cells using two components : p - and n - doped materials .", "entity": [], "task": "NER"}
{"text": "The energy level and absorption profile of the active layer can be tuned by introduction of an additional component .", "entity": [], "task": "NER"}
{"text": "Careful design of the additional component is required to achieve optimal panchromatic absorption , suitable energy - level offset , balanced electron and hole mobility , and good light - harvesting efficiency .", "entity": [], "task": "NER"}
{"text": "This article reviews the recent progress on ternary organic photovoltaic systems , including polymer / small molecule / functional fullerene , polymer / polymer / functional fullerene , small molecule / small molecule / functional fullerene , polymer / functional fullerene I / functional fullerene II , and polymer / quantum dot or metal / functional fullerene systems .", "entity": [{"entity": "fullerene", "entity_type": "Chemical", "pos": [131, 140]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [174, 183]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [231, 240]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [264, 273]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [289, 298]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [352, 361]}], "task": "NER"}
{"text": "Cell wounding activates phospholipase D in primary mouse keratinocytes .", "entity": [], "task": "NER"}
{"text": "Plasma membrane disruptions occur in mechanically active tissues such as the epidermis and can lead to cell death if the damage remains unrepaired .", "entity": [], "task": "NER"}
{"text": "Repair occurs through fusion of vesicle patches to the damaged membrane region .", "entity": [], "task": "NER"}
{"text": "The enzyme phospholipase D ( PLD ) is involved in membrane traffickiing ; therefore , the role of PLD in membrane repair was investigated .", "entity": [], "task": "NER"}
{"text": "Generation of membrane disruptions by lifting epidermal keratinocytes from the substratum induced PLD activation , whereas removal of cells from the substratum via trypsinization had no effect .", "entity": [], "task": "NER"}
{"text": "Pretreatment with 1 , 25 - dihydroxyvitamin D 3 , previously shown to increase PLD1 expression and activity , had no effect on , and a PLD2 - selective ( but not a PLD1 - selective ) inhibitor decreased , cell lifting - induced PLD activation , suggesting PLD2 as the isoform activated .", "entity": [{"entity": "1 , 25 - dihydroxyvitamin D 3", "entity_type": "Chemical", "pos": [18, 47]}], "task": "NER"}
{"text": "PLD2 interacts functionally with the glycerol channel aquaporin - 3 ( AQP3 ) to produce phosphatidylglycerol ( PG ) ; however , wounding resulted in decreased PG production , suggesting a potential PG deficiency in wounded cells .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "phosphatidylglycerol", "entity_type": "Chemical", "pos": [88, 108]}], "task": "NER"}
{"text": "Cell lifting - induced PLD activation was transient , consistent with a possible role in membrane repair , and PLD inhibitors inhibited membrane resealing upon laser injury .", "entity": [], "task": "NER"}
{"text": "In an in vivo full - thickness mouse skin wound model , PG accelerated wound healing .", "entity": [], "task": "NER"}
{"text": "These results suggest that PLD and the PLD2 / AQP3 signaling module may be involved in membrane repair and wound healing .", "entity": [], "task": "NER"}
{"text": "Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice .", "entity": [], "task": "NER"}
{"text": "The formation of the atherosclerotic lesion is a complex process influenced by an array of inflammatory and lipid metabolism pathways .", "entity": [], "task": "NER"}
{"text": "We previously demonstrated that NR4A nuclear receptors are highly induced in macrophages in response to inflammatory stimuli and modulate the expression of genes linked to inflammation in vitro .", "entity": [], "task": "NER"}
{"text": "Here we used mouse genetic models to assess the impact of NR4A expression on atherosclerosis development and macrophage polarization .", "entity": [], "task": "NER"}
{"text": "Transplantation of wild - type , Nur77 - / - , or Nor1 - / - null hematopoetic precursors into LDL receptor ( LDLR ) - / - recipient mice led to comparable development of atherosclerotic lesions after high - cholesterol diet .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [208, 219]}], "task": "NER"}
{"text": "We also observed comparable induction of genes linked to M1 and M2 responses in wild - type and Nur77 - null macrophages in response to lipopolysaccharides and interleukin ( IL ) - 4 , respectively .", "entity": [], "task": "NER"}
{"text": "In contrast , activation of the nuclear receptor liver X receptor ( LXR ) strongly suppressed M1 responses , and ablation of signal transductor and activator of transcription 6 ( STAT6 ) strongly suppressed M2 responses .", "entity": [], "task": "NER"}
{"text": "Recent studies have suggested that alterations in levels of Ly6C ( lo ) monocytes may be a contributor to inflammation and atherosclerosis .", "entity": [], "task": "NER"}
{"text": "In our study , loss of Nur77 , but not Nor1 , was associated with decreased abundance of Ly6C ( lo ) monocytes , but this change was not correlated with atherosclerotic lesion development .", "entity": [], "task": "NER"}
{"text": "Collectively , our results suggest that alterations in the Ly6C ( lo ) monocyte population and bone marrow NR4A expression do not play dominant roles in macrophage polarization or the development of atherosclerosis in mice .", "entity": [], "task": "NER"}
{"text": "Visualizing the perturbation of cellular cyclic di - GMP levels in bacterial cells .", "entity": [{"entity": "cyclic di - GMP", "entity_type": "Chemical", "pos": [41, 56]}], "task": "NER"}
{"text": "Cyclic di - GMP ( c - di - GMP ) has emerged as a prominent intracellular messenger that coordinates biofilm formation and pathogenicity in many bacterial species .", "entity": [{"entity": "Cyclic di - GMP", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [18, 30]}], "task": "NER"}
{"text": "Developing genetically encoded biosensors for c - di - GMP will help us understand how bacterial cells respond to environmental changes via the modulation of cellular c - di - GMP levels .", "entity": [{"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [46, 58]}, {"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [167, 179]}], "task": "NER"}
{"text": "Here we report the design of two genetically encoded c - di - GMP fluorescent biosensors with complementary dynamic ranges .", "entity": [{"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [53, 65]}], "task": "NER"}
{"text": "By using the biosensors , we found that several compounds known to promote biofilm dispersal trigger a decline in c - di - GMP levels in Escherichia coli cells .", "entity": [{"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [114, 126]}], "task": "NER"}
{"text": "In contrast , cellular c - di - GMP levels were elevated when the bacterial cells were treated with subinhibitory concentrations of biofilm - promoting antibiotics .", "entity": [{"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "The biosensors also revealed that E . coli cells engulfed by macrophages exhibit lower c - di - GMP levels , most likely as a response to the enormous pressures of survival during phagocytosis .", "entity": [{"entity": "c - di - GMP", "entity_type": "Chemical", "pos": [87, 99]}], "task": "NER"}
{"text": "On the azo / hydrazo equilibrium in Sudan I azo dye derivatives .", "entity": [{"entity": "azo", "entity_type": "Chemical", "pos": [7, 10]}, {"entity": "hydrazo", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "Sudan I", "entity_type": "Chemical", "pos": [36, 43]}, {"entity": "azo", "entity_type": "Chemical", "pos": [44, 47]}], "task": "NER"}
{"text": "In this study , Raman , infrared , UV / vis , NMR , and single crystal X - ray diffraction spectroscopies are used to elucidate the tautomeric equilibrium of azo dyes derived from 1 - phenyl - azo - 2 - naphthol ( Sudan I ) .", "entity": [{"entity": "azo", "entity_type": "Chemical", "pos": [158, 161]}, {"entity": "1 - phenyl - azo - 2 - naphthol", "entity_type": "Chemical", "pos": [180, 211]}, {"entity": "Sudan I", "entity_type": "Chemical", "pos": [214, 221]}], "task": "NER"}
{"text": "A new crystallographic structure is described for Sudan I , revealing the presence of intramolecular hydrogen bonds and supramolecular interactions , such as the unconventional C - H . . . O hydrogen bond type , pi - stacking , and charge - dipole interactions .", "entity": [{"entity": "Sudan I", "entity_type": "Chemical", "pos": [50, 57]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [101, 109]}, {"entity": "C - H", "entity_type": "Chemical", "pos": [177, 182]}, {"entity": "O", "entity_type": "Chemical", "pos": [189, 190]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [191, 199]}], "task": "NER"}
{"text": "All of these weak intermolecular interactions play a role in the stability of the crystalline structure .", "entity": [], "task": "NER"}
{"text": "Theoretical calculations are also reported for geometries , energy , and spectroscopic properties .", "entity": [], "task": "NER"}
{"text": "The predicted spectra are in accordance with the experiments carried out in the solid state and in solution of dichloromethane , carbon tetrachloride , and chloroform , suggesting the hydrazo form as the preferable tautomer in gas and condensate phases for Sudan I and its derivatives .", "entity": [{"entity": "dichloromethane", "entity_type": "Chemical", "pos": [111, 126]}, {"entity": "carbon tetrachloride", "entity_type": "Chemical", "pos": [129, 149]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [156, 166]}, {"entity": "hydrazo", "entity_type": "Chemical", "pos": [184, 191]}, {"entity": "Sudan I", "entity_type": "Chemical", "pos": [257, 264]}], "task": "NER"}
{"text": "Stereoselective Rh2 ( S - IBAZ ) 4 - catalyzed cyclopropanation of alkenes , alkynes , and allenes : asymmetric synthesis of diacceptor cyclopropylphosphonates and alkylidenecyclopropanes .", "entity": [{"entity": "Rh2 ( S - IBAZ ) 4", "entity_type": "Chemical", "pos": [16, 34]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "alkynes", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "allenes", "entity_type": "Chemical", "pos": [91, 98]}, {"entity": "cyclopropylphosphonates", "entity_type": "Chemical", "pos": [136, 159]}, {"entity": "alkylidenecyclopropanes", "entity_type": "Chemical", "pos": [164, 187]}], "task": "NER"}
{"text": "A mild and highly stereoselective rhodium ( II ) - catalyzed cyclopropanation of alkenes , alkynes , and allenes with diacceptor diazo compounds is reported .", "entity": [{"entity": "rhodium ( II )", "entity_type": "Chemical", "pos": [34, 48]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [81, 88]}, {"entity": "alkynes", "entity_type": "Chemical", "pos": [91, 98]}, {"entity": "allenes", "entity_type": "Chemical", "pos": [105, 112]}, {"entity": "diazo", "entity_type": "Chemical", "pos": [129, 134]}], "task": "NER"}
{"text": "Using the phosphonate moiety as an efficient trans - directing group , the first catalytic asymmetric route to diacceptor cycloprop ( en ) ylphosphonates was developed by employing an alpha - cyano diazophosphonate and Rh ( 2 ) ( S - IBAZ ) ( 4 ) as chiral catalyst .", "entity": [{"entity": "phosphonate", "entity_type": "Chemical", "pos": [10, 21]}, {"entity": "cycloprop ( en ) ylphosphonates", "entity_type": "Chemical", "pos": [122, 153]}, {"entity": "alpha - cyano diazophosphonate", "entity_type": "Chemical", "pos": [184, 214]}, {"entity": "Rh ( 2 ) ( S - IBAZ ) ( 4 )", "entity_type": "Chemical", "pos": [219, 246]}], "task": "NER"}
{"text": "The isosteric character of phosphonic and carboxylic acid derivatives allowed the alternative use of an alpha - cyano diazo ester in the process , leading to alpha - cyano cycloprop ( en ) ylcarboxylates in high yields and stereoselectivities .", "entity": [{"entity": "phosphonic and carboxylic acid", "entity_type": "Chemical", "pos": [27, 57]}, {"entity": "alpha - cyano diazo ester", "entity_type": "Chemical", "pos": [104, 129]}, {"entity": "alpha - cyano cycloprop ( en ) ylcarboxylates", "entity_type": "Chemical", "pos": [158, 203]}], "task": "NER"}
{"text": "Taking advantage of the particular reactivity of the cyanocarbene intermediates involved in this system , the scope of compatible substrates could be extended to substituted allenes , leading to the development of the first catalytic enantioselective method for the synthesis of diacceptor alkylidenecyclopropanes .", "entity": [{"entity": "cyanocarbene", "entity_type": "Chemical", "pos": [53, 65]}, {"entity": "allenes", "entity_type": "Chemical", "pos": [174, 181]}, {"entity": "alkylidenecyclopropanes", "entity_type": "Chemical", "pos": [290, 313]}], "task": "NER"}
{"text": "Discovery of thiazolidine - 2 , 4 - dione / biphenylcarbonitrile hybrid as dual PPAR alpha / gamma modulator with antidiabetic effect : in vitro , in silico and in vivo approaches .", "entity": [{"entity": "thiazolidine - 2 , 4 - dione", "entity_type": "Chemical", "pos": [13, 41]}, {"entity": "biphenylcarbonitrile", "entity_type": "Chemical", "pos": [44, 64]}], "task": "NER"}
{"text": "A small series of thiazolidine - 2 , 4 - dione and barbituric acid derivatives 1 - 4 was prepared using a short synthetic route , and all compounds were characterized by elemental analysis , mass spectrometry , and NMR ( ( 1 ) H , ( 13 ) C ) spectroscopy .", "entity": [{"entity": "thiazolidine - 2 , 4 - dione", "entity_type": "Chemical", "pos": [18, 46]}, {"entity": "barbituric acid", "entity_type": "Chemical", "pos": [51, 66]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [221, 228]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [231, 239]}], "task": "NER"}
{"text": "Their in vitro relative expression of peroxisome proliferator - activated receptor alpha and peroxisome proliferator - activated receptor gamma was evaluated .", "entity": [], "task": "NER"}
{"text": "Compound 1 showed an increase in the mRNA expression of both peroxisome proliferator - activated receptor isoforms , as well as the GLUT - 4 levels .", "entity": [], "task": "NER"}
{"text": "The antidiabetic activity of compound 1 was determined at 50 mg / kg single dose using a non - insulin - dependent diabetes mellitus rat model .", "entity": [], "task": "NER"}
{"text": "The results indicated a significant decrease in plasma glucose levels .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "Additionally , we performed a molecular docking of compound 1 into the ligand binding pocket of peroxisome proliferator - activated receptor alpha and peroxisome proliferator - activated receptor gamma .", "entity": [], "task": "NER"}
{"text": "In these binding models , compound 1 may bind into the active site of both isoforms showing important short contacts with the peroxisome proliferator - activated receptor gamma residues : Tyr 473 , His 449 , Ser 289 , His 323 ; and peroxisome proliferator - activated receptor alpha residues : Tyr 464 , His 440 , Ser 280 and Tyr 314 .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [188, 191]}, {"entity": "His", "entity_type": "Chemical", "pos": [198, 201]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [208, 211]}, {"entity": "His", "entity_type": "Chemical", "pos": [218, 221]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [294, 297]}, {"entity": "His", "entity_type": "Chemical", "pos": [304, 307]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [314, 317]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [326, 329]}], "task": "NER"}
{"text": "Anti - diabetic property of Tinospora cordifolia and its active compound is mediated through the expression of Glut - 4 in L6 myotubes .", "entity": [], "task": "NER"}
{"text": "Tinospora cordifolia is a well reported plant possessing numerous medicinal values including anti - diabetic property .", "entity": [], "task": "NER"}
{"text": "Aim of the present study is to study the mechanism of action of Tinospora cordifolia and its active compound in differentiated myocytes , L6 cells .", "entity": [], "task": "NER"}
{"text": "Key marker of diabetes in cells is the insulin dependent glucose transporter - 4 ( Glut - 4 ) which also responds to exogenous chemicals , and is over expressed up to 5 - and 4 - fold , by Tinospora cordifolia and palmatine , respectively .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "palmatine", "entity_type": "Chemical", "pos": [214, 223]}], "task": "NER"}
{"text": "Next to Glut - 4 , the predominant protein influencing glucose metabolism is PPAR alpha and gamma whose expressions were also positively modulated .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "Further , the inhibitors of insulin pathway prevented glucose uptake mediated by Tinospora cordifolia and palmatine which shows that the activity is majorly mediated through insulin pathway .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "palmatine", "entity_type": "Chemical", "pos": [106, 115]}], "task": "NER"}
{"text": "Dissolution of tablet - in - tablet formulations studied with ATR - FTIR spectroscopic imaging .", "entity": [], "task": "NER"}
{"text": "This work uses ATR - FTIR spectroscopic imaging to study the dissolution of delayed release and pH resistant compressed coating pharmaceutical tablets .", "entity": [], "task": "NER"}
{"text": "Tablets with an inner core and outer shell were constructed using a custom designed compaction cell .", "entity": [], "task": "NER"}
{"text": "The core of the delayed release tablets consisted of hydroxypropyl methylcellulose ( HPMC ) and caffeine .", "entity": [{"entity": "hydroxypropyl", "entity_type": "Chemical", "pos": [53, 66]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "The shell consisted of microcrystalline cellulose ( MCC ) and glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [62, 69]}], "task": "NER"}
{"text": "The core of the pH resistant formulations was an ibuprofen and PEG melt and the shell was constructed from HPMC and a basic buffer .", "entity": [{"entity": "ibuprofen", "entity_type": "Chemical", "pos": [49, 58]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "UV / vis spectroscopy was used to monitor the lag - time of drug release and visible optical video imaging was used as a complementary imaging technique with a larger field of view .", "entity": [], "task": "NER"}
{"text": "Two delayed release mechanisms were established .", "entity": [], "task": "NER"}
{"text": "For tablets with soluble shell sections , lag - time was dependent upon rapid shell dissolution .", "entity": [], "task": "NER"}
{"text": "For tablets with less soluble shells , the lag - time was controlled by the rate of dissolution medium ingress through the shell and the subsequent expansion of the wet HPMC core .", "entity": [], "task": "NER"}
{"text": "The pH resistant formulations prevented crystallization of the ibuprofen in the core during dissolution despite an acidic dissolution medium .", "entity": [{"entity": "ibuprofen", "entity_type": "Chemical", "pos": [63, 72]}], "task": "NER"}
{"text": "FTIR imaging produced important information about the physical and chemical processes occurring at the interface between tablet sections during dissolution .", "entity": [], "task": "NER"}
{"text": "Study of the recrystallization in coated pellets - Effect of coating on API crystallinity .", "entity": [], "task": "NER"}
{"text": "Coated diltiazem hydrochloride - containing pellets were prepared using the solution layering technique .", "entity": [{"entity": "diltiazem hydrochloride", "entity_type": "Chemical", "pos": [7, 30]}], "task": "NER"}
{"text": "Unusual thermal behavior was detected with differential scanning calorimetry ( DSC ) and its source was determined using thermogravimetry ( TG ) , X - ray powder diffraction ( XRPD ) and hot - stage microscopy .", "entity": [], "task": "NER"}
{"text": "The coated pellets contained diltiazem hydrochloride both in crystalline and amorphous form .", "entity": [{"entity": "diltiazem hydrochloride", "entity_type": "Chemical", "pos": [29, 52]}], "task": "NER"}
{"text": "Crystallization occurs on heat treatment causing an exothermic peak on the DSC curves that only appears in pellets containing both diltiazem hydrochloride and the coating .", "entity": [{"entity": "diltiazem hydrochloride", "entity_type": "Chemical", "pos": [131, 154]}], "task": "NER"}
{"text": "Results indicate that the amorphous fraction is situated in the coating layer .", "entity": [], "task": "NER"}
{"text": "The migration of drugs into the coating layer can cause changes in its degree of crystallinity .", "entity": [], "task": "NER"}
{"text": "Polymeric coating materials should therefore be investigated as possible crystallization inhibitors .", "entity": [], "task": "NER"}
{"text": "Substituted phenyl groups improve the pharmacokinetic profile and anti - inflammatory effect of urea - based soluble epoxide hydrolase inhibitors in murine models .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [12, 18]}, {"entity": "urea", "entity_type": "Chemical", "pos": [96, 100]}, {"entity": "epoxide", "entity_type": "Chemical", "pos": [117, 124]}], "task": "NER"}
{"text": "Soluble epoxide hydrolase inhibitors ( sEHIs ) are anti - inflammatory , analgesic , anti - hypertensive , cardio - and renal - protective in multiple animal models .", "entity": [{"entity": "epoxide", "entity_type": "Chemical", "pos": [8, 15]}], "task": "NER"}
{"text": "However , the earlier adamantyl - containing urea - based inhibitors are rapidly metabolized .", "entity": [{"entity": "adamantyl", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "urea", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "Therefore , new potent inhibitors with the adamantyl group replaced by a substituted phenyl group were synthesized to presumptively offer better pharmacokinetic ( PK ) properties .", "entity": [{"entity": "adamantyl", "entity_type": "Chemical", "pos": [43, 52]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [85, 91]}], "task": "NER"}
{"text": "Here we describe the improved PK profile of these inhibitors and the anti - inflammatory effect of the most promising one in a murine model .", "entity": [], "task": "NER"}
{"text": "The PK profiles of inhibitors were determined following p . o . administration and serial bleeding in mice .", "entity": [], "task": "NER"}
{"text": "The anti - inflammatory effect of 1 - trifluoromethoxyphenyl - 3 - ( 1 - propionylpiperidin - 4 - yl ) urea ( TPPU ) , the most promising inhibitor among the five sEHIs tested , was investigated in a lipopolysaccharide ( LPS ) - challenged murine model .", "entity": [{"entity": "1 - trifluoromethoxyphenyl - 3 - ( 1 - propionylpiperidin - 4 - yl ) urea", "entity_type": "Chemical", "pos": [34, 107]}, {"entity": "TPPU", "entity_type": "Chemical", "pos": [110, 114]}], "task": "NER"}
{"text": "The earlier broadly - used adamantyl - containing sEHI , trans - 4 - [ 4 - ( 3 - adamantan - 1 - yl - ureido ) - cyclohexyloxy ] - benzoic acid ( t - AUCB ) , was used for comparison .", "entity": [{"entity": "adamantyl", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "trans - 4 - [ 4 - ( 3 - adamantan - 1 - yl - ureido ) - cyclohexyloxy ] - benzoic acid", "entity_type": "Chemical", "pos": [57, 143]}, {"entity": "t - AUCB", "entity_type": "Chemical", "pos": [146, 154]}], "task": "NER"}
{"text": "Compared with the earlier adamantyl - containing urea - based inhibitors , substituted phenyl - containing urea - based inhibitors afford more favorable PK properties , such as higher Cmaxs , larger AUCs and longer t1 / 2s , which , as expected , show more stable metabolic stability .", "entity": [{"entity": "adamantyl", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "urea", "entity_type": "Chemical", "pos": [49, 53]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [87, 93]}, {"entity": "urea", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "Moreover , oral administration of TPPU dramatically reversed the shifts caused by LPS - challenge in plasma levels of inflammatory cytokines , epoxides and corresponding diols , which is more potent than t - AUCB .", "entity": [{"entity": "TPPU", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "epoxides", "entity_type": "Chemical", "pos": [143, 151]}, {"entity": "t - AUCB", "entity_type": "Chemical", "pos": [204, 212]}], "task": "NER"}
{"text": "The substituted phenyl - containing sEHIs are more metabolically stable than those with adamantyl group , resulting in more potent efficacy in vivo .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "adamantyl", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "This indicates a new strategy for development of sEHIs for further study toward clinical trials .", "entity": [], "task": "NER"}
{"text": "The oral cavity as a biological barrier system : Design of an advanced buccal in vitro permeability model .", "entity": [], "task": "NER"}
{"text": "An important area for future research lies in finding a drug delivery system across or into the oral mucosa .", "entity": [], "task": "NER"}
{"text": "However , to design such systems , simplified biological models are necessary so that the mechanisms and / or interactions of interest can readily be studied .", "entity": [], "task": "NER"}
{"text": "The oral epithelium is covered by a complex mucus layer , which enables exchange of nutrients and provides lubrication .", "entity": [], "task": "NER"}
{"text": "However , it has been demonstrated that mucus has an impact on the mobility of nanoparticles and drug molecules .", "entity": [], "task": "NER"}
{"text": "Thus , we aimed to develop an advanced buccal in vitro model for studying transport of nanoparticles , taking the mucus layer into account .", "entity": [], "task": "NER"}
{"text": "First , animal mucins ( porcine gastric , bovine submaxillary ) were compared with natural human mucin regarding chemical and morphological structure .", "entity": [], "task": "NER"}
{"text": "Second , an \" external \" mucus layer was prepared by a film method and deposited onto an oral cell line ( TR 146 ) , cultured on transwells (R) .", "entity": [], "task": "NER"}
{"text": "Adherence of the mucin fibers was evaluated and the viability of the model was assessed .", "entity": [], "task": "NER"}
{"text": "Nanoparticle transport studies were performed with this advanced in vitro model and an ex vivo diffusion system .", "entity": [], "task": "NER"}
{"text": "The results revealed that porcine mucin is most similar to human natural mucin in chemical structure and morphology .", "entity": [], "task": "NER"}
{"text": "Both the bovine and porcine mucin fibers adhered onto the oral cells : Due to the different morphology of bovine mucin , the viability of the oral cells decreased , whereas porcine mucin maintained the viability of the model for more than 48h .", "entity": [], "task": "NER"}
{"text": "Comparison of in vitro data with ex vivo data suggested reliability of the advanced buccal in vitro model .", "entity": [], "task": "NER"}
{"text": "Additionally , it was demonstrated that the mucus layer in the oral cavity also acts as a strong barrier for the mobility of nanoparticles .", "entity": [], "task": "NER"}
{"text": "Antioxidant activities of thiosemicarbazones from substituted benzaldehydes and N - ( tetra - O - acetyl - beta - D - galactopyranosyl ) thiosemicarbazide .", "entity": [{"entity": "thiosemicarbazones", "entity_type": "Chemical", "pos": [26, 44]}, {"entity": "benzaldehydes", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "N - ( tetra - O - acetyl - beta - D - galactopyranosyl ) thiosemicarbazide", "entity_type": "Chemical", "pos": [80, 154]}], "task": "NER"}
{"text": "Reaction of N - ( 2 , 3 , 4 , 6 - tetra - O - acetyl - beta - d - galactopyranosyl ) thiosemicarbazide and different substituted benzaldehydes gave some new substituted benzaldehyde N - ( 2 , 3 , 4 , 6 - tetra - O - acetyl - beta - d - galactopyranosyl ) thiosemicarbazones .", "entity": [{"entity": "N - ( 2 , 3 , 4 , 6 - tetra - O - acetyl - beta - d - galactopyranosyl ) thiosemicarbazide", "entity_type": "Chemical", "pos": [12, 102]}, {"entity": "benzaldehydes", "entity_type": "Chemical", "pos": [129, 142]}, {"entity": "benzaldehyde N - ( 2 , 3 , 4 , 6 - tetra - O - acetyl - beta - d - galactopyranosyl ) thiosemicarbazones", "entity_type": "Chemical", "pos": [169, 273]}], "task": "NER"}
{"text": "The reaction was performed using conventional and microwave - assisted heating methods .", "entity": [], "task": "NER"}
{"text": "The structures of thiosemicarbazones were confirmed by spectroscopic ( IR , ( 1 ) H NMR , ( 13 ) C NMR and ESI - MS ) method .", "entity": [{"entity": "thiosemicarbazones", "entity_type": "Chemical", "pos": [18, 36]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [76, 83]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "The antioxidant activity of these thiosemicarbazones was evaluated in vitro and in vivo , and it ' s shown that some of these compounds had significant antioxidant activity .", "entity": [{"entity": "thiosemicarbazones", "entity_type": "Chemical", "pos": [34, 52]}], "task": "NER"}
{"text": "Amongst the compounds screened for antioxidant activity , thiosemicarbazones 4a , 4b and 4c showed good antioxidant activity on DPPH .", "entity": [{"entity": "thiosemicarbazones", "entity_type": "Chemical", "pos": [58, 76]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [128, 132]}], "task": "NER"}
{"text": "The compounds 4g , 4i , 4l caused significant elevation of SOD activity and 4e , 4g , 4i , 4l had higher catalase activity , and only compounds 4c and 4f expressed the GSH - Px activity .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [168, 171]}], "task": "NER"}
{"text": "Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer ' s disease .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [27, 38]}], "task": "NER"}
{"text": "The disturbances of the cholesterol synthesis and metabolism described in Alzheimer ' s disease ( AD ) may be both a consequence of the neurodegenerative process and a contributor to the pathogenesis .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "These putative relationships and their underlying mechanisms are not well understood .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to evaluate the relationship between the cerebral and extracerebral cholesterol synthesis and metabolism , and the AD pathology as reflected by CSF markers in humans .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "We evaluated the relationships between the plasma and the cerebrospinal fluid ( CSF ) concentrations of cholesterol , the cholesterol precursors lanosterol , lathosterol and desmosterol , and the cholesterol elimination products 24S - hydroxycholesterol and 27 - hydroxycholesterol , and the CSF markers for AD pathology A beta 1 - 42 and p - tau181 in 86 subjects with normal cognition and in 107 AD patients .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [104, 115]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [122, 133]}, {"entity": "lanosterol", "entity_type": "Chemical", "pos": [145, 155]}, {"entity": "lathosterol", "entity_type": "Chemical", "pos": [158, 169]}, {"entity": "desmosterol", "entity_type": "Chemical", "pos": [174, 185]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [196, 207]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [229, 253]}, {"entity": "27 - hydroxycholesterol", "entity_type": "Chemical", "pos": [258, 281]}], "task": "NER"}
{"text": "CSF desmosterol , cholesterol and 24S - hydroxycholesterol in the AD group , and CSF 24S - hydroxycholesterol in the control group correlated with the p - tau181 levels .", "entity": [{"entity": "desmosterol", "entity_type": "Chemical", "pos": [4, 15]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [34, 58]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [85, 109]}], "task": "NER"}
{"text": "Neither CSF nor plasma concentrations of the included compounds correlated with the CSF A beta 1 - 42 levels .", "entity": [], "task": "NER"}
{"text": "In multivariate regression tests including age , gender , albumin ratio , number of the APOE epsilon 4 alleles , and diagnosis , p - tau181 levels independently predicted the CSF desmosterol , cholesterol and 24S - hydroxycholesterol concentrations .", "entity": [{"entity": "desmosterol", "entity_type": "Chemical", "pos": [179, 190]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [193, 204]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [209, 233]}], "task": "NER"}
{"text": "The associations remained significant for CSF cholesterol and 24S - hydroxycholesterol when analyses were separately performed in the AD group .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [46, 57]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [62, 86]}], "task": "NER"}
{"text": "The results suggest that alterations of CNS cholesterol de novo genesis and metabolism are related to neurodegeneration and in particular to the cerebral accumulation of phosphorylated tau .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [44, 55]}], "task": "NER"}
{"text": "Toxic effects of lead exposure in Wistar rats : involvement of oxidative stress and the beneficial role of edible jute ( Corchorus olitorius ) leaves .", "entity": [], "task": "NER"}
{"text": "Lead ( Pb ) is considered to be a multi - target toxicant .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [7, 9]}], "task": "NER"}
{"text": "The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves against Pb - acetate induced toxic manifestation in blood , liver , kidney , brain and heart of Wistar rats .", "entity": [{"entity": "Pb - acetate", "entity_type": "Chemical", "pos": [124, 136]}], "task": "NER"}
{"text": "The Pb - acetate ( 5mg / kg body weight ) treated rats exhibited a significant inhibition of co - enzymes Q , antioxidant enzymes and reduced glutathione levels in the tissues .", "entity": [{"entity": "Pb - acetate", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "co - enzymes Q", "entity_type": "Chemical", "pos": [93, 107]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [142, 153]}], "task": "NER"}
{"text": "In addition , the extent of lipid peroxidation , DNA fragmentation and haematological parameters were significantly altered in the Pb - acetate treated rats as compared to control .", "entity": [{"entity": "Pb - acetate", "entity_type": "Chemical", "pos": [131, 143]}], "task": "NER"}
{"text": "Simultaneous administration of test extract ( 25 , 50 and 100mg / kg body weight ) , could significantly restore the biochemical and haematological parameters near to the normal status through antioxidant activity and / or by preventing bioaccumulation of Pb within the tissues of experimental rats .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [256, 258]}], "task": "NER"}
{"text": "Presence of substantial quantity of phenolics and flavonoids in the extract may be responsible for the observed protective role against Pb - intoxication .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [36, 45]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [136, 138]}], "task": "NER"}
{"text": "Chemical composition and anticancer activity of essential oils of Mediterranean sage ( Salvia officinalis L . ) grown in different environmental conditions .", "entity": [], "task": "NER"}
{"text": "Salvia officinalis L . can be found worldwide and its leaves are commonly used as ingredient in food industry .", "entity": [], "task": "NER"}
{"text": "Sage essential oil is applied in the treatment of a range of diseases and has been shown to possess different biological activities .", "entity": [], "task": "NER"}
{"text": "The objectives of our research were to study the effects of environment on crop , chemical composition and anticancer activity on S . officinalis essential oil .", "entity": [], "task": "NER"}
{"text": "Sage was cultivated at eighteen experimental sites in south - central Italy ( Molise ) in different growing environments .", "entity": [], "task": "NER"}
{"text": "The essential oils ( S1 - S18 ) , extracted by hydrodistillation , were analyzed by GC and CG / MS .", "entity": [], "task": "NER"}
{"text": "Results show that the main components were alpha - thujone , camphor , borneol , gamma - muurolene and sclareol for all the samples , but the percentages of these compounds varied depending on environmental factors such as altitude , water availability and pedo - climatic conditions .", "entity": [{"entity": "alpha - thujone", "entity_type": "Chemical", "pos": [43, 58]}, {"entity": "camphor", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "borneol", "entity_type": "Chemical", "pos": [71, 78]}, {"entity": "gamma - muurolene", "entity_type": "Chemical", "pos": [81, 98]}, {"entity": "sclareol", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "The growth - inhibitory and proapoptotic effects of the eighteen sage essential oils were evaluated in three human melanoma cell lines , A375 , M14 , and A2058 .", "entity": [], "task": "NER"}
{"text": "Alkyl esters of gallic acid as anticancer agents : a review .", "entity": [{"entity": "Alkyl esters", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [16, 27]}], "task": "NER"}
{"text": "The current review presents the antitumoral properties of gallic acid and its ester derivatives .", "entity": [{"entity": "gallic acid", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "ester", "entity_type": "Chemical", "pos": [78, 83]}], "task": "NER"}
{"text": "Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid , and that this activity is related to their hydrophobic moiety .", "entity": [{"entity": "alkyl esters", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [103, 114]}], "task": "NER"}
{"text": "All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type .", "entity": [], "task": "NER"}
{"text": "The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer , either alone or in combination with other antitumor drugs to potentiate their effects .", "entity": [], "task": "NER"}
{"text": "Chlamydophila pneumoniae endonuclease IV prefers to remove mismatched 3 ' ribonucleotides : implication in proofreading mismatched 3 ' - terminal nucleotides in short - patch repair synthesis .", "entity": [{"entity": "3 ' ribonucleotides", "entity_type": "Chemical", "pos": [70, 89]}, {"entity": "nucleotides", "entity_type": "Chemical", "pos": [146, 157]}], "task": "NER"}
{"text": "DNA polymerase I ( DNApolI ) catalyzes DNA synthesis during Okazaki fragment maturation , base excision repair , and nucleotide excision repair .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [117, 127]}], "task": "NER"}
{"text": "Some bacterial DNApolIs are deficient in 3 ' - 5 ' exonuclease , which is required for removing an incorrectly incorporated 3 ' - terminal nucleotide during DNA elongation by DNA polymerase activity .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [139, 149]}], "task": "NER"}
{"text": "The key amino acid residues in the exonuclease center of Chlamydophila pneumoniae DNApolI ( CpDNApolI ) are naturally mutated , resulting in the loss of 3 ' - 5 ' exonuclease .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [8, 18]}], "task": "NER"}
{"text": "Hence , the manner by which CpDNApolI proofreads the incorrectly incorporated nucleotide during DNA synthesis warrants clarification .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [78, 88]}], "task": "NER"}
{"text": "C . pneumoniae encodes three 3 ' - 5 ' exonuclease activities : one endonuclease IV and two homologs of the epsilon subunit of replicative DNA polymerase III .", "entity": [], "task": "NER"}
{"text": "The three proteins were biochemically characterized using single - and double - stranded DNA substrate .", "entity": [], "task": "NER"}
{"text": "Among them , C . pneumoniae endonuclease IV ( CpendoIV ) possesses 3 ' - 5 ' exonuclease activity that prefers to remove mismatched 3 ' - terminal nucleotides in the nick , gap , and 3 ' recess of a double - stranded DNA ( dsDNA ) .", "entity": [{"entity": "nucleotides", "entity_type": "Chemical", "pos": [147, 158]}], "task": "NER"}
{"text": "Finally , we reconstituted the proofreading reaction of the mismatched 3 ' - terminal nucleotide using the dsDNA with a nick or 3 ' recess as substrate .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [86, 96]}], "task": "NER"}
{"text": "Upon proofreading of the mismatched 3 ' - terminal nucleotide by CpendoIV , CpDNApolI can correctly reincorporate the matched nucleotide and the nick is further sealed by DNA ligase .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [51, 61]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "Based on our biochemical results , we proposed that CpendoIV was responsible for proofreading the replication errors of CpDNApolI .", "entity": [], "task": "NER"}
{"text": "Nuclear receptor CAR specifically activates the two - pore K + channel Kcnk1 gene in male mouse livers , which attenuates phenobarbital - induced hepatic hyperplasia .", "entity": [{"entity": "K +", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "phenobarbital", "entity_type": "Chemical", "pos": [122, 135]}], "task": "NER"}
{"text": "KCNK1 , a member of the family of two - pore K ( + ) ion channels , is specifically induced in the livers of male mice after phenobarbital treatment .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [45, 52]}, {"entity": "phenobarbital", "entity_type": "Chemical", "pos": [125, 138]}], "task": "NER"}
{"text": "Here , we have determined the molecular mechanism of this male - specific activation of the Kcnk1 gene and characterized KCNK1 as a phenobarbital - inducible antihyperplasia factor .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [132, 145]}], "task": "NER"}
{"text": "Upon activation by phenobarbital , nuclear receptor CAR binds the 97 - bp response element ( - 2441 / - 2345 ) within the Kcnk1 promoter .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [19, 32]}], "task": "NER"}
{"text": "This binding is observed in the livers of male mice , but not in the livers of female mice and requires the pituitary gland , because hypophysectomy abrogates it .", "entity": [], "task": "NER"}
{"text": "Hyperplasia further progressed in the livers of Kcnk1 ( - / - ) male mice compared with those of Kcnk1 ( + / + ) males after phenobarbital treatment .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [125, 138]}], "task": "NER"}
{"text": "Thus , KCNK1 suppresses phenobarbital - induced hyperplasia .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [24, 37]}], "task": "NER"}
{"text": "These results indicate that phenobarbital treatment induces KCNK1 to elicit a male - specific and growth - suppressing signal .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [28, 41]}], "task": "NER"}
{"text": "Thus , KCNK1 and Kcnk1 ( - / - ) mice provide an experimental tool for further investigation into the molecular mechanism of CAR - mediated promotion of the development of hepatocellular carcinoma in mice .", "entity": [], "task": "NER"}
{"text": "Postweaning exposure to dietary zearalenone , a mycotoxin , promotes premature onset of puberty and disrupts early pregnancy events in female mice .", "entity": [{"entity": "zearalenone", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "Zearalenone ( ZEA ) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm .", "entity": [{"entity": "Zearalenone", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "ZEA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "It was hypothesized that ZEA , an endocrine disruptor , could affect puberty and early pregnancy .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [25, 28]}], "task": "NER"}
{"text": "To test this hypothesis , newly weaned ( 3 weeks old ) C57BL / 6J female mice were exposed to 0 , 0 . 002 , 4 , 10 , and 40 ppm ZEA and 0 . 05 ppm diethylstilbestrol ( positive control ) in phytoestrogen - free AIN - 93G diet .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "diethylstilbestrol", "entity_type": "Chemical", "pos": [147, 165]}], "task": "NER"}
{"text": "Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [26, 29]}], "task": "NER"}
{"text": "At 8 weeks old , all females were mated with untreated stud males on AIN - 93G diet during mating .", "entity": [], "task": "NER"}
{"text": "Treatment resumed upon identification of a vaginal plug on gestation day 0 . 5 ( D0 . 5 ) .", "entity": [], "task": "NER"}
{"text": "Embryo implantation was assessed on D4 . 5 .", "entity": [], "task": "NER"}
{"text": "Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites , distended uterine appearance , and retained expression of progesterone receptor in D4 . 5 uterine epithelium .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [159, 171]}], "task": "NER"}
{"text": "To determine the exposure timing and mechanisms of disrupted embryo implantation , four groups of females were fed with 0 or 40 ppm ZEA diets during premating ( weaning to mating ) and postmating ( D0 . 5 - D4 . 5 ) , respectively .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [132, 135]}], "task": "NER"}
{"text": "Premating exposure to 40 ppm ZEA diet reduced fertilization rate , whereas postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development , which subsequently affected embryo implantation .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "ZEA", "entity_type": "Chemical", "pos": [105, 108]}], "task": "NER"}
{"text": "These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "Autophagy inhibition for chemosensitization and radiosensitization in cancer : do the preclinical data support this therapeutic strategy ?", "entity": [], "task": "NER"}
{"text": "Recognition of the cytoprotective functions of autophagy that occur in tumor cells exposed to various forms of chemotherapy or radiation has generated intense interest in the possibility that pharmacological interference with autophagy could provide a clinical strategy for overcoming therapeutic resistance .", "entity": [], "task": "NER"}
{"text": "Multiple clinical trials are currently in progress to evaluate the antimalarial agent chloroquine ( generally in its clinical formulation as hydroxychloroquine ) and its impact on various forms of cancer therapy .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [86, 97]}, {"entity": "hydroxychloroquine", "entity_type": "Chemical", "pos": [141, 159]}], "task": "NER"}
{"text": "In this commentary / review , we focus on the relatively limited number of studies in the literature where chloroquine has been tested in combination with chemotherapy or radiation in experimental tumor - bearing animal models .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [107, 118]}], "task": "NER"}
{"text": "We also present recent data from our own laboratories , in cell culture experiments as well as in vivo studies , which demonstrate that neither chloroquine nor silencing of an autophagy regulatory gene was effective in conferring radiation sensitivity in an experimental model of breast cancer .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [144, 155]}], "task": "NER"}
{"text": "The capacity for sensitization by chloroquine appears to be quite wide - ranging , with dramatic effects for some drugs / tumor models and modest or minimal effects in others .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [34, 45]}], "task": "NER"}
{"text": "One possible caveat is that , with only a few exceptions , experiments have generally been performed in xenograft models , thereby eliminating the involvement of the immune system , which might ultimately be proven to play a central role in determining the effectiveness of autophagy inhibition in chemosensitization or radiosensitization .", "entity": [], "task": "NER"}
{"text": "Nevertheless , a careful review of the current literature suggests that caution is likely to be warranted in translating preclinical findings relating to autophagy inhibition as an adjunctive therapeutic strategy .", "entity": [], "task": "NER"}
{"text": "Synthesis of selenolate - protected Au18 ( SeC6H5 ) 14 nanoclusters .", "entity": [{"entity": "selenolate", "entity_type": "Chemical", "pos": [13, 23]}, {"entity": "Au18 ( SeC6H5 ) 14", "entity_type": "Chemical", "pos": [36, 54]}], "task": "NER"}
{"text": "This work reports the first synthesis of selenophenolate - protected Au ( 18 ) ( SePh ) ( 14 ) nanoclusters .", "entity": [{"entity": "selenophenolate", "entity_type": "Chemical", "pos": [41, 56]}, {"entity": "Au ( 18 ) ( SePh ) ( 14 )", "entity_type": "Chemical", "pos": [69, 94]}], "task": "NER"}
{"text": "This cluster exhibits distinct differences from its thiolate analogue in terms of optical absorption properties .", "entity": [], "task": "NER"}
{"text": "The Au ( 18 ) ( SePh ) ( 14 ) nanoclusters were obtained via a controlled reaction of Au ( 25 ) ( SCH ( 2 ) CH ( 2 ) Ph ) ( 18 ) with selenophenol .", "entity": [{"entity": "Au ( 18 ) ( SePh ) ( 14 )", "entity_type": "Chemical", "pos": [4, 29]}, {"entity": "Au ( 25 ) ( SCH ( 2 ) CH ( 2 ) Ph ) ( 18 )", "entity_type": "Chemical", "pos": [86, 128]}, {"entity": "selenophenol", "entity_type": "Chemical", "pos": [134, 146]}], "task": "NER"}
{"text": "Electrospray ionization time - of - flight mass spectrometry ( ESI - TOF - MS ) revealed the crude product to contain predominantly Au ( 18 ) ( SePh ) ( 14 ) nanoclusters , and side products include Au ( 15 ) ( SePh ) ( 13 ) , Au ( 19 ) ( SePh ) ( 15 ) and Au ( 20 ) ( SePh ) ( 16 ) .", "entity": [{"entity": "Au ( 18 ) ( SePh ) ( 14 )", "entity_type": "Chemical", "pos": [132, 157]}, {"entity": "Au ( 15 ) ( SePh ) ( 13 )", "entity_type": "Chemical", "pos": [199, 224]}, {"entity": "Au ( 19 ) ( SePh ) ( 15 )", "entity_type": "Chemical", "pos": [227, 252]}, {"entity": "Au ( 20 ) ( SePh ) ( 16 )", "entity_type": "Chemical", "pos": [257, 282]}], "task": "NER"}
{"text": "High - performance liquid chromatography ( HPLC ) was employed to isolate Au ( 18 ) ( SePh ) ( 14 ) nanoclusters .", "entity": [{"entity": "Au ( 18 ) ( SePh ) ( 14 )", "entity_type": "Chemical", "pos": [74, 99]}], "task": "NER"}
{"text": "The results of thermogravimetric analysis ( TGA ) , elemental analysis ( EA ) , and ( 1 ) H / ( 13 ) C NMR spectroscopy confirmed the cluster composition .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [84, 91]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "To the best of our knowledge , this is the first report of selenolate - protected Au ( 18 ) nanoclusters .", "entity": [{"entity": "selenolate", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "Au ( 18 )", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "Future theoretical and X - ray crystallographic work will reveal the geometric structure and the nature of selenolate - gold bonding in the nanocluster .", "entity": [{"entity": "selenolate", "entity_type": "Chemical", "pos": [107, 117]}], "task": "NER"}
{"text": "The physico - chemical \" anatomy \" of the tautomerization through the DPT of the biologically important pairs of hypoxanthine with DNA bases : QM and QTAIM perspectives .", "entity": [{"entity": "hypoxanthine", "entity_type": "Chemical", "pos": [113, 125]}], "task": "NER"}
{"text": "The biologically important tautomerization of the Hyp . Cyt , Hyp * . Thy and Hyp . Hyp base pairs to the Hyp * . Cyt * , Hyp . Thy * and Hyp * . Hyp * base pairs , respectively , by the double proton transfer ( DPT ) was comprehensively studied in vacuo and in the continuum with a low dielectric constant ( epsilon = 4 ) corresponding to hydrophobic interfaces of protein - nucleic acid interactions by combining theoretical investigations at the B3LYP / 6 - 311 + + G ( d , p ) level of QM theory with QTAIM topological analysis .", "entity": [{"entity": "Hyp", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [70, 73]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [106, 109]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [114, 117]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [122, 125]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [138, 141]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [146, 149]}], "task": "NER"}
{"text": "Based on the sweeps of the energetic , electron - topological , geometric and polar parameters , which describe the course of the tautomerization along the intrinsic reaction coordinate ( IRC ) , it was proved that the tautomerization through the DPT is concerted and asynchronous process for the Hyp . Cyt and Hyp * . Thy base pairs , while concerted and synchronous for the Hyp . Hyp homodimer .", "entity": [{"entity": "Hyp", "entity_type": "Chemical", "pos": [297, 300]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [303, 306]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [311, 314]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [319, 322]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [376, 379]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [382, 385]}], "task": "NER"}
{"text": "The continuum with epsilon = 4 does not affect qualitatively the course of the tautomerization reaction for all studied complexes .", "entity": [], "task": "NER"}
{"text": "The nine key points along the IRC of the Hyp . Cyt <--> Hyp * . Cyt * and Hyp * . Thy <--> Hyp . Thy * tautomerizations and the six key points of the Hyp . Hyp <--> Hyp * . Hyp * tautomerization have been identified and fully characterized .", "entity": [{"entity": "Hyp", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [74, 77]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [97, 100]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [150, 153]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [156, 159]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [165, 168]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [173, 176]}], "task": "NER"}
{"text": "These key points could be considered as electron - topological \" fingerprints \" of concerted asynchronous ( for Hyp . Cyt and Hyp * . Thy ) or synchronous ( for Hyp . Hyp ) tautomerization process via the DPT .", "entity": [{"entity": "Hyp", "entity_type": "Chemical", "pos": [112, 115]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [118, 121]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [126, 129]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [161, 164]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "It was found , that in the Hyp * . Cyt * , Hyp . Thy * , Hyp . Hyp and Hyp * . Hyp * base pairs all H - bonds are significantly cooperative and mutually reinforce each other , while the C2H ... O2 H - bond in the Hyp . Cyt base pair and the O6H ... O4 H - bond in the Hyp * . Thy base pair behave anti - cooperatively , i . e . , they become weakened , while two others become strengthened .", "entity": [{"entity": "Hyp", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [43, 46]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [57, 60]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [71, 74]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "H", "entity_type": "Chemical", "pos": [100, 101]}, {"entity": "C2H", "entity_type": "Chemical", "pos": [186, 189]}, {"entity": "O2 H", "entity_type": "Chemical", "pos": [194, 198]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [213, 216]}, {"entity": "Cyt", "entity_type": "Chemical", "pos": [219, 222]}, {"entity": "O6H", "entity_type": "Chemical", "pos": [241, 244]}, {"entity": "O4", "entity_type": "Chemical", "pos": [249, 251]}, {"entity": "H", "entity_type": "Chemical", "pos": [252, 253]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [268, 271]}, {"entity": "Thy", "entity_type": "Chemical", "pos": [276, 279]}], "task": "NER"}
{"text": "Zinc deficiency induced in Swiss 3T3 cells by a low - zinc medium impairs calcium entry and two mechanisms of entry are involved .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "Zinc deficiency in 3T3 cells induced by the use of diethylenetriaminepentaacetate ( DTPA ) has been shown to impair calcium entry associated with failure of proliferation when the cells are stimulated with polypeptide growth factors ( GF ) .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "diethylenetriaminepentaacetate", "entity_type": "Chemical", "pos": [51, 81]}, {"entity": "DTPA", "entity_type": "Chemical", "pos": [84, 88]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [116, 123]}], "task": "NER"}
{"text": "These functions of zinc have been evaluated here in the same clone of cells by simple depletion using a low - zinc medium ( 0 . 05 mu mol / L zinc ) without chelator .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [110, 114]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [142, 146]}], "task": "NER"}
{"text": "Confluent cells were maintained for 1 day in the low - zinc medium without GF , then loaded with Fluo - 4 , and stimulated with GF .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "Fluo - 4", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "Calcium entry was measured by the increase in sustained fluorescence .", "entity": [{"entity": "Calcium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "It was preceded by the release of stored calcium as observed in the previous study using DTPA .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "DTPA", "entity_type": "Chemical", "pos": [89, 93]}], "task": "NER"}
{"text": "Zinc deprivation decreased calcium entry when calcium was added at 0 or 0 . 05 mmol / L but not when 0 . 1 mmol / L or higher .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Cell proliferation reflected similar effects of zinc and calcium concentrations .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "In a newly acquired clone of 3T3 cells , GF did not induce internal calcium release but thapsigargin ( TG ) did .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "thapsigargin", "entity_type": "Chemical", "pos": [88, 100]}], "task": "NER"}
{"text": "When added in a low - calcium medium , both agonists stimulated calcium entry when external calcium was added , suggesting that two different mechanisms of entry were impaired by zinc deficiency .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [179, 183]}], "task": "NER"}
{"text": "Zinc deficiency produced by DTPA in the newer clones gave similar results , decreasing calcium entry induced by both agonists .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "DTPA", "entity_type": "Chemical", "pos": [28, 32]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [87, 94]}], "task": "NER"}
{"text": "The effects of GF and TG were not additive .", "entity": [], "task": "NER"}
{"text": "The results confirm the earlier observation that zinc deficiency impairs calcium entry into 3T3 cells when stimulated by GF and show that the cells can take up calcium by either store - operated or receptor - operated mechanisms .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [49, 53]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [160, 167]}], "task": "NER"}
{"text": "Theoretical investigation into optical and electronic properties of 1 , 8 - naphthalimide derivatives .", "entity": [{"entity": "1 , 8 - naphthalimide", "entity_type": "Chemical", "pos": [68, 89]}], "task": "NER"}
{"text": "A series of 1 , 8 - naphthalimide derivatives has been designed to explore their optical , electronic , and charge transport properties as charge transport and / or luminescent materials for organic light - emitting diodes ( OLEDs ) .", "entity": [{"entity": "1 , 8 - naphthalimide", "entity_type": "Chemical", "pos": [12, 33]}], "task": "NER"}
{"text": "The frontier molecular orbitals ( FMOs ) analysis have shown that the vertical electronic transitions of absorption and emission are characterized as intramolecular charge transfer ( ICT ) for electron - donating and aromatic groups substituted derivatives .", "entity": [], "task": "NER"}
{"text": "However , the ICT character of the electron - withdrawing substituted derivatives is not significant .", "entity": [], "task": "NER"}
{"text": "The calculated results show that their optical and electronic properties are affected by the substituent groups in 4 - position of 1 , 8 - naphthalimide .", "entity": [{"entity": "1 , 8 - naphthalimide", "entity_type": "Chemical", "pos": [131, 152]}], "task": "NER"}
{"text": "Our results suggest that 1 , 8 - naphthalimide derivatives with electron - donating - OCH3 and - N ( CH3 ) 2 ( 1 and 2 ) , electron - withdrawing - CN and - COCH3 ( 3 and 4 ) , 2 - ( thiophen - 2 - yl ) thiophene ( 5 ) , 2 , 3 - dihydrothieno [ 3 , 4 - b ] [ 1 , 4 ] dioxine ( 6 ) , 2 - phenyl - 1 , 3 , 4 - oxadiazole ( 7 ) , and benzo [ c ] [ 1 , 2 , 5 ] thiadiazole ( 8 ) fragments are expected to be promising candidates for luminescent materials for OLEDs , particularly for 5 and 7 .", "entity": [{"entity": "1 , 8 - naphthalimide", "entity_type": "Chemical", "pos": [25, 46]}, {"entity": "- OCH3", "entity_type": "Chemical", "pos": [84, 90]}, {"entity": "- N ( CH3 ) 2", "entity_type": "Chemical", "pos": [95, 108]}, {"entity": "- CN", "entity_type": "Chemical", "pos": [146, 150]}, {"entity": "- COCH3", "entity_type": "Chemical", "pos": [155, 162]}, {"entity": "2 - ( thiophen - 2 - yl ) thiophene", "entity_type": "Chemical", "pos": [177, 212]}, {"entity": "2 , 3 - dihydrothieno [ 3 , 4 - b ] [ 1 , 4 ] dioxine", "entity_type": "Chemical", "pos": [221, 274]}, {"entity": "2 - phenyl - 1 , 3 , 4 - oxadiazole", "entity_type": "Chemical", "pos": [283, 318]}, {"entity": "benzo [ c ] [ 1 , 2 , 5 ] thiadiazole", "entity_type": "Chemical", "pos": [331, 368]}], "task": "NER"}
{"text": "In addition , 3 and 7 can be used as promising hole transport materials for OLEDs .", "entity": [], "task": "NER"}
{"text": "This study should be helpful in further theoretical investigations on such kind of systems and also to the experimental study for charge transport and / or luminescent materials for OLEDs .", "entity": [], "task": "NER"}
{"text": "Polyethylene Glycol and Polyethylenimine Dual - Functionalized Nano - Graphene Oxide for Photothermally Enhanced Gene Delivery .", "entity": [{"entity": "Polyethylene Glycol", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "Polyethylenimine", "entity_type": "Chemical", "pos": [24, 40]}, {"entity": "Graphene Oxide", "entity_type": "Chemical", "pos": [70, 84]}], "task": "NER"}
{"text": "Graphene oxide ( GO ) has been extensively explored in nanomedicine for its excellent physiochemical , electrical , and optical properties .", "entity": [{"entity": "Graphene oxide", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Here , polyethylene glycol ( PEG ) and polyethylenimine ( PEI ) are covalently conjugated to GO via amide bonds , obtaining a physiologically stable dual - polymer - functionalized nano - GO conjugate ( NGO - PEG - PEI ) with ultra - small size .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [7, 26]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [39, 55]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [58, 61]}, {"entity": "amide", "entity_type": "Chemical", "pos": [100, 105]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [209, 212]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [215, 218]}], "task": "NER"}
{"text": "Compared with free PEI and the GO - PEI conjugate without PEGylation , NGO - PEG - PEI shows superior gene transfection efficiency without serum interference , as well as reduced cytotoxicity .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [58, 61]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Utilizing the NIR optical absorbance of NGO , the cellular uptake of NGO - PEG - PEI is shown to be enhanced under a low power NIR laser irradiation , owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "As the results , remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO - PEG - PEI as the light - responsive gene carrier .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [125, 128]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [131, 134]}], "task": "NER"}
{"text": "More importantly , it is shown that our NGO - PEG - PEI is able to deliver small interfering RNA ( siRNA ) into cells under the control of NIR light , resulting in obvious down - regulation of the target gene , Polo - like kinase 1 ( Plk1 ) , in the presence of laser irradiation .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light - controllable gene delivery .", "entity": [], "task": "NER"}
{"text": "This work also encourages further explorations of functionalized nano - GO as a photocontrollable nanovector for combined photothermal and gene therapies .", "entity": [], "task": "NER"}
{"text": "Effects of smoking on the oxidant / antioxidant balance and the blood lipids in pesticide sprayers .", "entity": [], "task": "NER"}
{"text": "The present study was conducted on 80 pesticide male sprayers ( 42 nonsmokers and 38 smokers ) .", "entity": [], "task": "NER"}
{"text": "Our aim was to estimate the smoking effects on blood lipids and oxidant / antioxidant status in pesticide sprayers .", "entity": [], "task": "NER"}
{"text": "Results revealed that cholesterol , low - density lipoprotein ( LDL ) and glutathion peroxidase ( GPx ) enzyme were significantly higher in the 38 smoker sprayers than in the 42 nonsmoker sprayers .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [22, 33]}, {"entity": "glutathion", "entity_type": "Chemical", "pos": [74, 84]}], "task": "NER"}
{"text": "Cholesterol and LDL were correlated with smoking index and high - density lipoprotein ( HDL ) , superoxide dismutase ( SOD ) enzyme and zinc ( Zn ) were inversely correlated with duration of pesticides ' exposure .", "entity": [{"entity": "Cholesterol", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [96, 106]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [143, 145]}], "task": "NER"}
{"text": "In nonsmokers , LDL and cholesterol were negatively correlated with SOD and correlated with malondialdehyde ( MDA ) , and cholesterol was negatively correlated with Zn .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [92, 107]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [122, 133]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [165, 167]}], "task": "NER"}
{"text": "HDL was negatively correlated with MDA in all the sprayers , but was correlated with GPx in smokers and with Zn in nonsmokers .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [109, 111]}], "task": "NER"}
{"text": "In smokers , LDL was negatively correlated with GPx , HDL was negatively correlated with MDA and triglycerides and very - low - density lipoprotein were negatively correlated with Zn .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [97, 110]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [180, 182]}], "task": "NER"}
{"text": "MDA was negatively correlated with SOD , GPx and Zn .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [49, 51]}], "task": "NER"}
{"text": "Smoking and pesticide exposure could be responsible for hyperlipidemia and oxidative stress .", "entity": [], "task": "NER"}
{"text": "Therefore , improvement in the antioxidant status is mandatory for pesticide sprayers especially the ones who smoke .", "entity": [], "task": "NER"}
{"text": "Agreement between chest radiography and high - resolution computed tomography in diagnosing dust - related interstitial lung fibrosis .", "entity": [], "task": "NER"}
{"text": "Although it has been suggested that high - resolution computed tomography ( HRCT ) scans can be obtained when plain radiographs are equivocal for the presence of interstitial lung fibrosis ( ILF ) caused by inhalation of dust , such as silica , asbestos fibres , etc . , the specificity of the findings remains in question .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [236, 242]}, {"entity": "asbestos", "entity_type": "Chemical", "pos": [245, 253]}], "task": "NER"}
{"text": "The present study was carried out to compare the relative efficacy of chest radiography by conventional method and HRCT in evaluating ILF which included 22 workers exposed to fibrogenic dust , who were subjected to clinical examination , pulmonary function testing , posteroanterior chest radiography and HRCT .", "entity": [], "task": "NER"}
{"text": "In the six subjects who had findings suggestive of ILF on HRCT , four had normal chest x - ray ( CXR ) while one each has been diagnosed as having tuberculosis and ILF on CXR .", "entity": [], "task": "NER"}
{"text": "The agreement analysis between HRCT and CXR suggests that there was a poor agreement between HRCT and CXR ( kappa = 0 . 34 ) .", "entity": [], "task": "NER"}
{"text": "Serum mineral status of long - term cigarette smokers .", "entity": [], "task": "NER"}
{"text": "This study was carried out to investigate comparatively some serum mineral levels of cigarette smokers .", "entity": [], "task": "NER"}
{"text": "A total of 25 nonsmokers ( control group ) and 50 long - term cigarette smokers ( smoking for at least 15 years ; smoker group ) were participated in the study .", "entity": [], "task": "NER"}
{"text": "Subjects were between 25 and 40 years old .", "entity": [], "task": "NER"}
{"text": "Control and smoker groups were matched for age , sex and body mass index status .", "entity": [], "task": "NER"}
{"text": "The blood samples were taken from smokers and nonsmokers after 12 h of fasting period .", "entity": [], "task": "NER"}
{"text": "The levels of zinc ( Zn ) , copper ( Cu ) , iron ( Fe ) , magnesium ( Mg ) , calcium ( Ca ) , potassium ( K ) , chlorine ( Cl ) , sodium ( Na ) and phosphorus ( P ) were measured by autoanalyzer using commercial kits .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "copper", "entity_type": "Chemical", "pos": [28, 34]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [37, 39]}, {"entity": "iron", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "magnesium", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [70, 72]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [87, 89]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [94, 103]}, {"entity": "K", "entity_type": "Chemical", "pos": [106, 107]}, {"entity": "chlorine", "entity_type": "Chemical", "pos": [112, 120]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [123, 125]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [130, 136]}, {"entity": "Na", "entity_type": "Chemical", "pos": [139, 141]}, {"entity": "phosphorus", "entity_type": "Chemical", "pos": [148, 158]}, {"entity": "P", "entity_type": "Chemical", "pos": [161, 162]}], "task": "NER"}
{"text": "Student ' s t test was used to compare the control and smoker groups , and p < 0 . 05 indicated a significant difference .", "entity": [], "task": "NER"}
{"text": "Pearson ' s correlation coefficient was used to demonstrate the relationship among parameters in smoker and control groups .", "entity": [], "task": "NER"}
{"text": "Although there was no statistical difference ( p > 0 . 05 ) between the groups regarding the levels of K , P , Mg , Na , Cl , Zn , Fe , Ca and Cu , some positive correlations were observed in controls but not in smokers .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [103, 104]}, {"entity": "P", "entity_type": "Chemical", "pos": [107, 108]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [111, 113]}, {"entity": "Na", "entity_type": "Chemical", "pos": [116, 118]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [121, 123]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [126, 128]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [131, 133]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [136, 138]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [143, 145]}], "task": "NER"}
{"text": "Therefore , it was concluded that smoking does not affect the serum mineral levels .", "entity": [], "task": "NER"}
{"text": "However , it may negatively affect some important positive correlations among minerals observed in healthy individuals .", "entity": [], "task": "NER"}
{"text": "Occupational hazards control of hazardous substances in clean room of semiconductor manufacturing plant using CFD analysis .", "entity": [], "task": "NER"}
{"text": "The manufacturing processes in chip industries are complex , and many kinds of raw materials and solvents of different nature are used , most of which are highly toxic and dangerous .", "entity": [], "task": "NER"}
{"text": "During the machine preventive maintenance period , these toxic and harmful substances will escape from the sealed reaction chamber to the clean workshop environment and endanger the health of the workers on - site , resulting in occupational diseases .", "entity": [], "task": "NER"}
{"text": "From the perspective of prevention , the spread and prediction of hydrochloric acid ( HCl ) that escaped from the metal - etching chamber during maintenance were studied in this article .", "entity": [{"entity": "hydrochloric acid", "entity_type": "Chemical", "pos": [66, 83]}, {"entity": "HCl", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "The computational fluid dynamics technology was used for a three - dimensional numerical simulation of the indoor air velocity field and the HCl concentration field , and the simulation results were then compared with the on - site monitoring data to verify the correctness and feasibility .", "entity": [{"entity": "HCl", "entity_type": "Chemical", "pos": [141, 144]}], "task": "NER"}
{"text": "The occupational hazards and control measures were analyzed based on the numerical simulation , and the optimal control measure was obtained .", "entity": [], "task": "NER"}
{"text": "In this article , using the method of ambient air to analyze the occupational exposure can provide a new idea to the field of occupational health research in the integrated circuit industry and had theoretical and practical significance .", "entity": [], "task": "NER"}
{"text": "Plasmon dynamics in colloidal Au 2 Cd alloy - CdSe core / shell nanocrystals .", "entity": [{"entity": "Au 2 Cd", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "Metal - semiconductor nanocrystal heterostructures are model systems for understanding the interplay between the localized surface plasmon resonances in the metal domain and the relaxation of the excited carriers in the semiconductor domain .", "entity": [], "task": "NER"}
{"text": "Here we report the synthesis of colloidal Au 2 Cd ( core ) / CdSe ( shell ) nanocrystal heterostructures , which were characterized extensively with several structural and optical techniques , including time - resolved fluorescence and broad - band transient absorption spectroscopy ( both below and above the CdSe band gap ) .", "entity": [{"entity": "Au 2 Cd", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [61, 65]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [310, 314]}], "task": "NER"}
{"text": "The dynamics of the transient plasmon peak was dominated by the relaxation of hot carriers in the metal core , its spectral shape was independent of the pump wavelength , and the bleaching lifetime was about half a picosecond , comparable with the value found in the AuCd seeds used for the synthesis .", "entity": [{"entity": "AuCd", "entity_type": "Chemical", "pos": [267, 271]}], "task": "NER"}
{"text": "Thermodynamic studies of ionic hydration and interactions for amino acid ionic liquids in aqueous solutions at 298 . 15 K .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [62, 72]}], "task": "NER"}
{"text": "Amino acid ionic liquids are a special class of ionic liquids due to their unique acid - base behavior , biological significance , and applications in different fields such as templates in synthetic chemistry , stabilizers for biological macromolecules , etc .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The physicochemical properties of these ionic liquids can easily be altered by making the different combinations of amino acids as anion along with possible cation modification which makes amino acid ionic liquids more suitable to understand the different kinds of molecular and ionic interactions with sufficient depth so that they can provide fruitful information for a molecular level understanding of more complicated biological processes .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [116, 127]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [189, 199]}], "task": "NER"}
{"text": "In this context , volumetric and osmotic coefficient measurements for aqueous solutions containing 1 - ethyl - 3 - methylimidazolium ( [ Emim ] ) based amino acid ionic liquids of glycine , alanine , valine , leucine , and isoleucine are reported at 298 . 15 K .", "entity": [{"entity": "1 - ethyl - 3 - methylimidazolium", "entity_type": "Chemical", "pos": [99, 132]}, {"entity": "Emim", "entity_type": "Chemical", "pos": [137, 141]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [152, 162]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [180, 187]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [190, 197]}, {"entity": "valine", "entity_type": "Chemical", "pos": [200, 206]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [209, 216]}, {"entity": "isoleucine", "entity_type": "Chemical", "pos": [223, 233]}], "task": "NER"}
{"text": "From experimental osmotic coefficient data , mean molal activity coefficients of ionic liquids were estimated and analyzed using the Debye - H u ckel and Pitzer models .", "entity": [], "task": "NER"}
{"text": "The hydration numbers of ionic liquids in aqueous solutions were obtained using activity data .", "entity": [], "task": "NER"}
{"text": "Pitzer ion interaction parameters are estimated and compared with other electrolytes reported in the literature .", "entity": [], "task": "NER"}
{"text": "The nonelectrolyte contribution to the aqueous solutions containing ionic liquids was studied by calculating the osmotic second virial coefficient through an application of the McMillan - Mayer theory of solution .", "entity": [], "task": "NER"}
{"text": "It has been found that the second osmotic virial coefficient which includes volume effects correlates linearly with the Pitzer ion interaction parameter estimated independently from osmotic data as well as the hydrophobicity of ionic liquids .", "entity": [], "task": "NER"}
{"text": "The enthalpy - entropy compensation effect , explained using the Starikov - Nord e n model of enthalpy - entropy compensation , and partial molar entropy analysis for aqueous [ Emim ] [ Gly ] solutions are made by using experimental Gibb ' s free energy data and literature enthalpy data .", "entity": [{"entity": "Emim", "entity_type": "Chemical", "pos": [177, 181]}, {"entity": "Gly", "entity_type": "Chemical", "pos": [186, 189]}], "task": "NER"}
{"text": "This study highlights that the hydrophobic interaction persists even in the limit of infinite dilution where the hydration effects are usually dominant , implying importance of hydrophobic hydration .", "entity": [], "task": "NER"}
{"text": "Analysis of the results further shows that the hydration of amino acid ionic liquids occurs through the cooperative H - bond formation with the kosmotropic effect in contrast to the usual inorganic salts or hydrophobic salts like tetraalkylammonium halides .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [60, 70]}, {"entity": "H", "entity_type": "Chemical", "pos": [116, 117]}, {"entity": "tetraalkylammonium halides", "entity_type": "Chemical", "pos": [230, 256]}], "task": "NER"}
{"text": "Chemical warfare agent and biological toxin - induced pulmonary toxicity : could stem cells provide potential therapies ?", "entity": [], "task": "NER"}
{"text": "Chemical warfare agents ( CWAs ) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks .", "entity": [], "task": "NER"}
{"text": "Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury ( ALI ) as well as acute respiratory distress syndrome ( ARDS ) .", "entity": [], "task": "NER"}
{"text": "The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high .", "entity": [], "task": "NER"}
{"text": "Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future .", "entity": [], "task": "NER"}
{"text": "The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing , thus understanding the mechanisms of toxicity and potential therapies is critical .", "entity": [], "task": "NER"}
{"text": "This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries .", "entity": [], "task": "NER"}
{"text": "Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC .", "entity": [{"entity": "avermectin", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "Avermectins ( AVEs ) , which are widely used for the treatment of agricultural parasitic diseases , belong to a family of 6 , 6 - spiroketal moiety - containing , macrolide natural products .", "entity": [{"entity": "Avermectins", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "AVEs", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "macrolide", "entity_type": "Chemical", "pos": [163, 172]}], "task": "NER"}
{"text": "AVE biosynthesis is known to employ a type I polyketide synthase ( PKS ) system to assemble the molecular skeleton for further functionalization .", "entity": [{"entity": "AVE", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "polyketide", "entity_type": "Chemical", "pos": [45, 55]}], "task": "NER"}
{"text": "It remains unknown how and when spiroketal formation proceeds , particularly regarding the role of AveC , a unique protein in the pathway that shares no sequence homology to any enzyme of known function .", "entity": [], "task": "NER"}
{"text": "Here , we report the unprecedented , dual function of AveC by correlating its activity with spiroketal formation and modification during the AVE biosynthetic process .", "entity": [{"entity": "AVE", "entity_type": "Chemical", "pos": [141, 144]}], "task": "NER"}
{"text": "The findings in this study were supported by characterizing extremely unstable intermediates , products and their spontaneous derivative products from the simplified chemical profile and by comparative analysis of in vitro biotransformations and in vivo complementations mediated by AveC and MeiC ( the counterpart in biosynthesizing the naturally occurring , AVE - like meilingmycins ) .", "entity": [{"entity": "AVE", "entity_type": "Chemical", "pos": [360, 363]}, {"entity": "meilingmycins", "entity_type": "Chemical", "pos": [371, 384]}], "task": "NER"}
{"text": "AveC catalyzes the stereospecific spiroketalization of a dihydroxy - ketone polyketide intermediate and the optional dehydration to determine the regiospecific saturation characteristics of spiroketal diversity .", "entity": [{"entity": "dihydroxy - ketone polyketide", "entity_type": "Chemical", "pos": [57, 86]}], "task": "NER"}
{"text": "These reactions take place between the closures of the hexene ring and 16 - membered macrolide and the formation of the hexahydrobenzofuran unit .", "entity": [{"entity": "hexene", "entity_type": "Chemical", "pos": [55, 61]}, {"entity": "macrolide", "entity_type": "Chemical", "pos": [85, 94]}, {"entity": "hexahydrobenzofuran", "entity_type": "Chemical", "pos": [120, 139]}], "task": "NER"}
{"text": "MeiC can replace the spirocyclase activity of AveC , but it lacks the independent dehydratase activity .", "entity": [], "task": "NER"}
{"text": "Elucidation of the generality and specificity of AveC - type proteins allows for the rationalization of previously published results that were not completely understood , suggesting that enzyme - mediated spiroketal formation was initially underestimated , but is , in fact , widespread in nature for the control of stereoselectivity .", "entity": [], "task": "NER"}
{"text": "Attenuating Staphylococcus aureus Virulence Gene Regulation : A Medicinal Chemistry Perspective .", "entity": [], "task": "NER"}
{"text": "Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two - component signal transduction systems .", "entity": [], "task": "NER"}
{"text": "There is now an emerging body of evidence to suggest that the blockade of S . aureus virulence gene expression significantly attenuates infection in experimental models .", "entity": [], "task": "NER"}
{"text": "In this Perspective , we will provide insights into medicinal chemistry strategies for the development of chemical reagents that have the capacity to inhibit staphylococcal virulence expression .", "entity": [], "task": "NER"}
{"text": "These reagents can be broadly grouped into four categories : ( 1 ) competitive inhibitors of the accessory gene regulator ( agr ) quorum sensing system , ( 2 ) inhibitors of AgrA - DNA interactions , ( 3 ) RNAIII transcription inhibitors , and ( 4 ) inhibitors of the SarA family of transcriptional regulators .", "entity": [], "task": "NER"}
{"text": "We discuss the potential of specific examples of antivirulence agents for the management and treatment of staphylococcal infections .", "entity": [], "task": "NER"}
{"text": "Development of new cyclic plasmin inhibitors with excellent potency and selectivity .", "entity": [], "task": "NER"}
{"text": "The trypsin - like serine protease plasmin is a target for the development of antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce excessive blood loss .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [19, 25]}], "task": "NER"}
{"text": "The optimization of our recently described substrate - analogue plasmin inhibitors , which were cyclized between their P3 and P2 side chains , provided a new series with improved efficacy and excellent selectivity .", "entity": [], "task": "NER"}
{"text": "The most potent inhibitor 8 binds to plasmin with an inhibition constant of 0 . 2 nM , whereas K ( i ) values > 1 mu M were determined for nearly all other tested trypsin - like serine proteases , with the exception of trypsin , which is also inhibited in the nanomolar range .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [178, 184]}], "task": "NER"}
{"text": "Docking studies revealed a potential binding mode in the widely open active site of plasmin that explains the strong potency and selectivity profile of these inhibitors .", "entity": [], "task": "NER"}
{"text": "The dialkylated piperazine - linker segment contributes to an excellent solubility of all analogues .", "entity": [{"entity": "piperazine", "entity_type": "Chemical", "pos": [16, 26]}], "task": "NER"}
{"text": "Based on their overall profile the presented inhibitors are well suited for further development as injectable antifibrinolytic drugs .", "entity": [], "task": "NER"}
{"text": "Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability .", "entity": [{"entity": "free fatty acid", "entity_type": "Chemical", "pos": [36, 51]}], "task": "NER"}
{"text": "The free fatty acid receptor 1 ( FFA1 , also known as GPR40 ) mediates enhancement of glucose - stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes .", "entity": [{"entity": "free fatty acid", "entity_type": "Chemical", "pos": [4, 19]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [86, 93]}], "task": "NER"}
{"text": "Several FFA1 agonists are known , but the majority of these suffer from high lipophilicity .", "entity": [], "task": "NER"}
{"text": "We have previously reported the FFA1 agonist 3 ( TUG - 424 ) .", "entity": [{"entity": "TUG - 424", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "We here describe the continued structure - activity exploration and optimization of this compound series , leading to the discovery of the more potent agonist 40 , a compound with low lipophilicity , excellent in vitro metabolic stability and permeability , complete oral bioavailability , and appreciable efficacy on glucose tolerance in mice .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [318, 325]}], "task": "NER"}
{"text": "A safety study on single intravenous dose of tetrachloro - diphenyl glycoluril [ iodogen ] dissolved in dimethyl sulphoxide ( DMSO ) .", "entity": [{"entity": "tetrachloro - diphenyl glycoluril", "entity_type": "Chemical", "pos": [45, 78]}, {"entity": "iodogen", "entity_type": "Chemical", "pos": [81, 88]}, {"entity": "dimethyl sulphoxide", "entity_type": "Chemical", "pos": [104, 123]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [126, 130]}], "task": "NER"}
{"text": "Iodogen ( tetrachloro - diphenyl glycoluril ) dissolved in DMSO ( dimethyl sulphoxide ) appears indispensable in radioiodination of hypericin for a new anticancer strategy .", "entity": [{"entity": "Iodogen", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "tetrachloro - diphenyl glycoluril", "entity_type": "Chemical", "pos": [10, 43]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [59, 63]}, {"entity": "dimethyl sulphoxide", "entity_type": "Chemical", "pos": [66, 85]}, {"entity": "hypericin", "entity_type": "Chemical", "pos": [132, 141]}], "task": "NER"}
{"text": "We studied the safety of intravenously administered iodogen / DMSO in mice ( n = 132 ) .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "Median lethal dose ( LD ( 50 ) ) of iodogen / DMSO was determined with doses of 40 . 0 , 50 . 0 , 55 . 0 , 60 . 0 , 65 . 0 and 70 . 0 mg / kg .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [36, 43]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "Next , toxicity of iodogen / DMSO at 30 . 0 mg / kg was evaluated using saline and DMSO as controls .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "Changes in behaviour , body weight and serum biochemistry were evaluated .", "entity": [], "task": "NER"}
{"text": "Histopathology of lungs , heart , liver and kidney was performed .", "entity": [], "task": "NER"}
{"text": "LD ( 50 ) values of iodogen / DMSO were 59 . 5 mg / kg ( 95 % confidence limits ( CI ) : 54 . 1 - 65 . 4 mg / kg ) and 61 . 0 mg / kg ( 95 % CI : 56 . 2 - 66 . 2 mg / kg ) for female and male mice , respectively .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "Similar to that of control groups , no animal deaths were encountered after iodogen / DMSO administration at 30 . 0 mg / kg .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [76, 83]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [86, 90]}], "task": "NER"}
{"text": "Body weights over 24 h were not altered in all groups , but significantly higher in iodogen / DMSO and DMSO groups ( p < 0 . 05 ) 14 d post - injection .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [84, 91]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [94, 98]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "Blood urea nitrogen and alkaline phosphatase increased ( p < 0 . 05 ) in iodogen / DMSO group without clinical symptoms .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "iodogen", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "No pathologies were found by gross and microscopic inspection .", "entity": [], "task": "NER"}
{"text": "A single dose of iodogen / DMSO up to 30 . 0 mg / kg , over 3000 times the dose in potential human applications , appears safe , with an LD ( 50 ) doubling that dose in mice .", "entity": [{"entity": "iodogen", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "DMSO", "entity_type": "Chemical", "pos": [27, 31]}], "task": "NER"}
{"text": "Fragment - based discovery of new highly substituted 1H - pyrrolo [ 2 , 3 - b ] - and 3H - imidazolo [ 4 , 5 - b ] - pyridines as focal adhesion kinase inhibitors .", "entity": [{"entity": "1H - pyrrolo [ 2 , 3 - b ] - and 3H - imidazolo [ 4 , 5 - b ] - pyridines", "entity_type": "Chemical", "pos": [53, 126]}], "task": "NER"}
{"text": "Focal adhesion kinase ( FAK ) is considered as an attractive target for oncology , and small - molecule inhibitors are reported to be in clinical testing .", "entity": [], "task": "NER"}
{"text": "In a surface plasmon resonance ( SPR ) - mediated fragment screening campaign , we discovered bicyclic scaffolds like 1H - pyrazolo [ 3 , 4 - d ] pyrimidines binding to the hinge region of FAK .", "entity": [{"entity": "1H - pyrazolo [ 3 , 4 - d ] pyrimidines", "entity_type": "Chemical", "pos": [118, 157]}], "task": "NER"}
{"text": "By an accelerated knowledge - based fragment growing approach , essential pharmacophores were added .", "entity": [], "task": "NER"}
{"text": "The establishment of highly substituted unprecedented 1H - pyrrolo [ 2 , 3 - b ] pyridine derivatizations provided compounds with submicromolar cellular FAK inhibition potential .", "entity": [{"entity": "1H - pyrrolo [ 2 , 3 - b ] pyridine", "entity_type": "Chemical", "pos": [54, 89]}], "task": "NER"}
{"text": "The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity .", "entity": [], "task": "NER"}
{"text": "Structural analysis revealed that the appropriately substituted pyrrolo [ 2 , 3 - b ] pyridine induced a rare helical DFG - loop conformation .", "entity": [{"entity": "pyrrolo [ 2 , 3 - b ] pyridine", "entity_type": "Chemical", "pos": [64, 94]}], "task": "NER"}
{"text": "The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7 - azaindole core .", "entity": [{"entity": "7 - azaindole", "entity_type": "Chemical", "pos": [135, 148]}], "task": "NER"}
{"text": "Melt granulation in fluidized bed : a comparative study of spray - on versus in situ procedure .", "entity": [], "task": "NER"}
{"text": "Abstract Objective : The aim of this study was to investigate the influence of process parameters , binder content and binder addition method on characteristics of the granules obtained by melt granulation ( MG ) in fluidized bed .", "entity": [], "task": "NER"}
{"text": "Methods : Spray - on experiments were performed according to 2 ( 3 ) full factorial design .", "entity": [], "task": "NER"}
{"text": "The effect of binder content , molten binder feed rate , and spray air pressure on granule size and size distribution , granule shape , fl owability and drug release rate was investigated .", "entity": [], "task": "NER"}
{"text": "In the in situ experiments , the influence of binder particle size and binder content was evaluated .", "entity": [], "task": "NER"}
{"text": "Solid - state characterization was performed by means of differential scanning calorimetry , X - ray powder diffraction and Fourier transform infrared spectroscopy .", "entity": [], "task": "NER"}
{"text": "Results : Size of the granules obtained by spray - on procedure was significantly influenced by binder content and spray air pressure , while the width of particle size distribution was mainly affected by binder feed rate .", "entity": [], "task": "NER"}
{"text": "Spray air pressure showed the most significant influence on granule shape .", "entity": [], "task": "NER"}
{"text": "It was shown that smooth and spherical particles with good flow properties may be obtained by both procedures , spray - on and in situ MG .", "entity": [], "task": "NER"}
{"text": "The results obtained indicated the influence of agglomeration mechanism on granule sphericity , with higher degree of granule sphericity observed when immersion and layering was the dominant mechanism .", "entity": [], "task": "NER"}
{"text": "Paracetamol release from granulates was very rapid , but after compression of the granules into tablets , drug release was considerably slower .", "entity": [{"entity": "Paracetamol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Solid - state analysis confirmed that the physical form of the granulate components remained unaffected after the MG process .", "entity": [], "task": "NER"}
{"text": "Conclusion : The results presented indicate that MG in fluidized bed could be a good alternative to conventional granulation techniques .", "entity": [], "task": "NER"}
{"text": "The mechanism of discrimination between oxidized and reduced coenzyme in the aldehyde dehydrogenase domain of Aldh1l1 .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [77, 85]}], "task": "NER"}
{"text": "Aldh1l1 , also known as 10 - formyltetrahydrofolate dehydrogenase ( FDH ) , contains the carboxy - terminal domain ( Ct - FDH ) , which is a structural and functional homolog of aldehyde dehydrogenases ( ALDHs ) .", "entity": [{"entity": "10 - formyltetrahydrofolate", "entity_type": "Chemical", "pos": [24, 51]}, {"entity": "carboxy", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [178, 186]}], "task": "NER"}
{"text": "This domain is capable of catalyzing the NADP ( + ) - dependent oxidation of short chain aldehydes to their corresponding acids , and similar to most ALDHs it has two conserved catalytic residues , Cys707 and Glu673 .", "entity": [{"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [89, 98]}, {"entity": "Cys707", "entity_type": "Chemical", "pos": [198, 204]}, {"entity": "Glu673", "entity_type": "Chemical", "pos": [209, 215]}], "task": "NER"}
{"text": "Previously , we demonstrated that in the Ct - FDH mechanism these residues define the conformation of the bound coenzyme and the affinity of its interaction with the protein .", "entity": [], "task": "NER"}
{"text": "Specifically , the replacement of Cys707 with an alanine resulted in the enzyme lacking the ability to differentiate between the oxidized and reduced coenzyme .", "entity": [{"entity": "Cys707", "entity_type": "Chemical", "pos": [34, 40]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [49, 56]}], "task": "NER"}
{"text": "We suggested that this was due to the loss of a covalent bond between the cysteine and the C4N atom of nicotinamide ring of NADP ( + ) formed during Ct - FDH catalysis .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [74, 82]}, {"entity": "nicotinamide", "entity_type": "Chemical", "pos": [103, 115]}, {"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "To obtain further insight into the functional significance of the covalent bond between Cys707 and the coenzyme , and the overall role of the two catalytic residues in the coenzyme binding and positioning , we have now solved crystal structures of Ct - FDH in the complex with thio - NADP ( + ) and the complexes of the C707S mutant with NADP ( + ) and NADPH .", "entity": [{"entity": "Cys707", "entity_type": "Chemical", "pos": [88, 94]}, {"entity": "thio - NADP ( + )", "entity_type": "Chemical", "pos": [277, 294]}, {"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [338, 348]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [353, 358]}], "task": "NER"}
{"text": "This study has allowed us to trap the coenzyme in the contracted conformation , which provided a snapshot of the conformational processing of the coenzyme during the transition from oxidized to reduced form .", "entity": [], "task": "NER"}
{"text": "Overall , the results of this study further support the previously proposed mechanism by which Cys707 helps to differentiate between the oxidized and reduced coenzyme during ALDH catalysis .", "entity": [{"entity": "Cys707", "entity_type": "Chemical", "pos": [95, 101]}], "task": "NER"}
{"text": "X - ray structure of the V301L aldo - keto reductase 1B10 complexed with NADP ( + ) and the potent aldose reductase inhibitor fidarestat : implications for inhibitor binding and selectivity .", "entity": [{"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [73, 83]}, {"entity": "aldose", "entity_type": "Chemical", "pos": [99, 105]}, {"entity": "fidarestat", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "Only one crystal structure is currently available for tumor marker AKR1B10 , complexed with NADP ( + ) and tolrestat , which is an aldose reductase inhibitor ( ARI ) of the carboxylic acid type .", "entity": [{"entity": "NADP ( + )", "entity_type": "Chemical", "pos": [92, 102]}, {"entity": "tolrestat", "entity_type": "Chemical", "pos": [107, 116]}, {"entity": "aldose", "entity_type": "Chemical", "pos": [131, 137]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [173, 188]}], "task": "NER"}
{"text": "Here , the X - ray structure of the complex of the V301L substituted AKR1B10 holoenzyme with fidarestat , an ARI of the cyclic imide type , was obtained at 1 . 60 A resolution by replacement soaking of crystals containing tolrestat .", "entity": [{"entity": "fidarestat", "entity_type": "Chemical", "pos": [93, 103]}, {"entity": "cyclic imide", "entity_type": "Chemical", "pos": [120, 132]}, {"entity": "tolrestat", "entity_type": "Chemical", "pos": [222, 231]}], "task": "NER"}
{"text": "Previously , fidarestat was found to be safe in phase III trials for diabetic neuropathy and , consistent with its low in vivo side effects , was highly selective for aldose reductase ( AR or AKR1B1 ) versus aldehyde reductase ( AKR1A1 ) .", "entity": [{"entity": "fidarestat", "entity_type": "Chemical", "pos": [13, 23]}, {"entity": "aldose", "entity_type": "Chemical", "pos": [167, 173]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [208, 216]}], "task": "NER"}
{"text": "Now , inhibition studies showed that fidarestat was indeed 1300 - fold more selective for AR as compared to AKR1B10 , while the change of Val to Leu ( found in AR ) caused a 20 - fold decrease in the IC50 value with fidarestat .", "entity": [{"entity": "fidarestat", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "Val", "entity_type": "Chemical", "pos": [138, 141]}, {"entity": "Leu", "entity_type": "Chemical", "pos": [145, 148]}, {"entity": "fidarestat", "entity_type": "Chemical", "pos": [216, 226]}], "task": "NER"}
{"text": "Structural analysis of the V301L AKR1B10 - fidarestat complex displayed enzyme - inhibitor interactions similar to those of the AR - fidarestat complex .", "entity": [{"entity": "fidarestat", "entity_type": "Chemical", "pos": [43, 53]}, {"entity": "fidarestat", "entity_type": "Chemical", "pos": [133, 143]}], "task": "NER"}
{"text": "However , a close inspection of both the new crystal structure and a computer model of the wild - type AKR1B10 complex with fidarestat revealed subtle changes that could affect fidarestat binding .", "entity": [{"entity": "fidarestat", "entity_type": "Chemical", "pos": [124, 134]}, {"entity": "fidarestat", "entity_type": "Chemical", "pos": [177, 187]}], "task": "NER"}
{"text": "In the crystal structure , a significant motion of loop A was observed between AR and V301L AKR1B10 , linked to a Phe - 122 / Phe - 123 side chain displacement .", "entity": [{"entity": "Phe", "entity_type": "Chemical", "pos": [114, 117]}, {"entity": "Phe", "entity_type": "Chemical", "pos": [126, 129]}], "task": "NER"}
{"text": "This was due to the presence of the more voluminous Gln - 303 side chain ( Ser - 302 in AR ) and of a water molecule buried in a subpocket located at the base of flexible loop A .", "entity": [{"entity": "Gln", "entity_type": "Chemical", "pos": [52, 55]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [75, 78]}], "task": "NER"}
{"text": "In the wild - type AKR1B10 model , a short contact was predicted between the Val - 301 side chain and fidarestat , but would not be present in AR or in V301L AKR1B10 .", "entity": [{"entity": "Val", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "fidarestat", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "Overall , these changes could contribute to the difference in inhibitory potency of fidarestat between AR and AKR1B10 .", "entity": [{"entity": "fidarestat", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "Potential monovalent cation - binding sites in aldehyde dehydrogenases .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [47, 55]}], "task": "NER"}
{"text": "Potassium ions are non - essential activators of several aldehyde dehydrogenases ( ALDHs ) , whereas a few others require the cation for activity .", "entity": [{"entity": "Potassium", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [57, 65]}], "task": "NER"}
{"text": "Two kinds of cation - binding sites , which we named intra - subunit and inter - subunit , have been observed in crystal structures of ALDHs , and based on reported crystallographic data , we here propose the existence of a third kind located in the central cavity of some tetrameric ALDHs .", "entity": [], "task": "NER"}
{"text": "Given the high structural similarity between these enzymes , cation - binding sites may be present in many other members of this superfamily .", "entity": [], "task": "NER"}
{"text": "To explore the prevalence of these sites , we compared 37 known crystal structures from 13 different ALDH families and evaluated the possible existence of a cation on the basis of the number , distance and geometry of its potential interactions , as well as of B - factor values of modeled cations obtained in new refinements of some reported crystal structures .", "entity": [], "task": "NER"}
{"text": "Also , by performing multiple alignments of 855 non - redundant amino acid sequences , we assessed the degree of conservation in their respective families of the amino acid residues putatively relevant for cation binding .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [64, 74]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [162, 172]}], "task": "NER"}
{"text": "Among the ALDH enzymes studied , and according to our analyses , potential intra - subunit cation - binding sites seem to be present in most members of ALDH2 , ALDH1L , ALDH4 , ALDH5 , ALDH7 , ALDH10 , and ALDH25 families , as well as in the bacterial and fungal members of the ALDH9 family and in a few ALDH1 , ALDH6 , ALDH11 and ALDH26 enzymes ; potential inter - subunit sites in members of ALDH1L , ALDH3 , ALDH4 from bacillales , ALDH5 , ALDH7 , ALDH9 , ALDH10 , ALDH11 and ALDH25 families ; and potential central - cavity sites only in some bacterial and animal ALDH9s and in most members of the ALDH1L family .", "entity": [], "task": "NER"}
{"text": "Because potassium is the most abundant intracellular cation , we propose that these are potassium - binding sites , but the specific structural and / or functional roles of the cation bound to these different sites remain to be investigated .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [8, 17]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "Specific surface area of titanium dioxide ( TiO2 ) particles influences cyto - and photo - toxicity .", "entity": [{"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [25, 41]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "The aim of this study is to examine how different specific surface areas of similar - sized titanium dioxide ( TiO ( 2 ) ) particles could influence both cytotoxicity and phototoxicity .", "entity": [{"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [92, 108]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [111, 120]}], "task": "NER"}
{"text": "TiO ( 2 ) particles of different specific surface areas were compared for their toxic effects on RAW264 . 7 cells in the absence and presence of UV light .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "From the results , TiO ( 2 ) particles with larger specific surface area were found to induce higher cyto - ( UV absent ) and photo - toxicity ( UV activated ) to cells after 24h incubation .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [19, 28]}], "task": "NER"}
{"text": "The observed cytotoxicity from TiO ( 2 ) particles with larger surface area could be explained from their interactions with biomolecules .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Upon photoactivation , a larger number of hydroxyl radicals were detected from TiO ( 2 ) particles with larger surface area , again suggesting a surface area dependent phototoxic effect .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [79, 88]}], "task": "NER"}
{"text": "On the other hand , pre - adsorbing TiO ( 2 ) particles with extracellular proteins were found to decrease toxicity effects .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [36, 45]}], "task": "NER"}
{"text": "Lack of transient receptor potential melastatin 8 activation by phthalate esters that enhance contact hypersensitivity in mice .", "entity": [{"entity": "phthalate esters", "entity_type": "Chemical", "pos": [64, 80]}], "task": "NER"}
{"text": "We studied the involvement of sensory neurons in skin sensitization to allergens using a mouse model in which the T - helper type 2 response is essential .", "entity": [], "task": "NER"}
{"text": "Skin sensitization to fluorescein isothiocyanate ( FITC ) has been shown to be enhanced by several phthalate esters , including dibutyl phthalate ( DBP ) .", "entity": [{"entity": "fluorescein isothiocyanate", "entity_type": "Chemical", "pos": [22, 48]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "phthalate esters", "entity_type": "Chemical", "pos": [99, 115]}, {"entity": "dibutyl phthalate", "entity_type": "Chemical", "pos": [128, 145]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "For different types of phthalate esters , we found a correlation between the ability of transient receptor potential ( TRP ) A1 activation and that of enhancing skin sensitization .", "entity": [{"entity": "phthalate esters", "entity_type": "Chemical", "pos": [23, 39]}], "task": "NER"}
{"text": "A TRPA1 - specific antagonist , HC - 030031 , was shown to suppress skin sensitization in the presence of DBP .", "entity": [{"entity": "HC - 030031", "entity_type": "Chemical", "pos": [32, 43]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "However , since phthalate esters also activate TRPV1 , phthalate esters could activate other types of TRP channels non - selectively .", "entity": [{"entity": "phthalate esters", "entity_type": "Chemical", "pos": [16, 32]}, {"entity": "phthalate esters", "entity_type": "Chemical", "pos": [55, 71]}], "task": "NER"}
{"text": "Furthermore , sensitization to FITC is also enhanced by menthol , which activates TRPA1 and TRPM8 .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "menthol", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "Here we established an in vitro system for measuring TRPM8 activation .", "entity": [], "task": "NER"}
{"text": "The selectivity for TRPM8 was established by the fact that two TRPM8 agonists ( menthol and icilin ) induced calcium mobilization , whereas agonists of TRPA1 and TRPV1 did not .", "entity": [{"entity": "menthol", "entity_type": "Chemical", "pos": [80, 87]}, {"entity": "icilin", "entity_type": "Chemical", "pos": [92, 98]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [109, 116]}], "task": "NER"}
{"text": "We demonstrated that phthalate esters do not activate TRPM8 .", "entity": [{"entity": "phthalate esters", "entity_type": "Chemical", "pos": [21, 37]}], "task": "NER"}
{"text": "TRPA1 - antagonist HC - 030031 did not inhibit TRPM8 activation induced by menthol or icilin .", "entity": [{"entity": "HC - 030031", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "menthol", "entity_type": "Chemical", "pos": [75, 82]}, {"entity": "icilin", "entity_type": "Chemical", "pos": [86, 92]}], "task": "NER"}
{"text": "These results show that phthalate esters activate TRPA1 and TRPV1 with selectivity .", "entity": [{"entity": "phthalate esters", "entity_type": "Chemical", "pos": [24, 40]}], "task": "NER"}
{"text": "TRPM8 activation is not likely to be involved in the sensitization to FITC .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "The genotoxicity of PEI - based nanoparticles is reduced by acetylation of polyethylenimine amines in human primary cells .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "polyethylenimine amines", "entity_type": "Chemical", "pos": [75, 98]}], "task": "NER"}
{"text": "The ultrasmall size and unique properties of polymeric nanoparticles ( NPs ) have led to raising concerns about their potential cyto - and genotoxicity on biological systems .", "entity": [], "task": "NER"}
{"text": "Polyethylenimine ( PEI ) is a highly positive charged polymer and is known to have varying degree of toxic effect to cells based on its chemical structure ( i . e . , amount of primary and secondary amine ) .", "entity": [{"entity": "Polyethylenimine", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "primary and secondary amine", "entity_type": "Chemical", "pos": [177, 204]}], "task": "NER"}
{"text": "Herein , drug delivery carriers such as PEI - PLGA nanoparticles ( PEI - NPs ) and acetylated PEI - PLGA nanoparticles ( AcPEI - NPs ) were utilized to examine the effect of acetylation on NPs biocompatibility and genotoxicity , using human primary cells as in vitro model .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [46, 50]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [67, 70]}, {"entity": "acetylated PEI", "entity_type": "Chemical", "pos": [83, 97]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [100, 104]}, {"entity": "AcPEI", "entity_type": "Chemical", "pos": [121, 126]}], "task": "NER"}
{"text": "Cell uptake of NPs was characterized along with their effects on cellular viability .", "entity": [], "task": "NER"}
{"text": "The results indicate that both NPs showed an equivalent behavior in terms of uptake and biocompatibility .", "entity": [], "task": "NER"}
{"text": "In depth analysis of NP uptake on cell biology evidenced that these nanoparticles induced dose dependant genotoxic effects .", "entity": [], "task": "NER"}
{"text": "This phenomenon was significantly reduced by PEI acetylation .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "Endocytosed PEI - NPs trigger an oxidative stress on cells by inducing the production of reactive oxygen species ( ROS ) , which cause DNA damage without apparently affecting cell viability .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [98, 104]}], "task": "NER"}
{"text": "Thus , the genotoxicity of nanoparticles , that could be used as non - viral drug carriers , should be evaluated based on the intracellular level of ROS generation and DNA damage even in absence of a significant cell death .", "entity": [], "task": "NER"}
{"text": "Graphene oxide for effective radionuclide removal .", "entity": [{"entity": "Graphene oxide", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Here we show the efficacy of graphene oxide ( GO ) for rapid removal of some of the most toxic and radioactive long - lived human - made radionuclides from contaminated water , even from acidic solutions ( pH < 2 ) .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [29, 43]}], "task": "NER"}
{"text": "The interaction of GO with actinides including Am ( III ) , Th ( IV ) , Pu ( IV ) , Np ( V ) , U ( VI ) and typical fission products Sr ( II ) , Eu ( III ) and Tc ( VII ) were studied , along with their sorption kinetics .", "entity": [{"entity": "actinides", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "Am ( III )", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "Th ( IV )", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "Pu ( IV )", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "Np ( V )", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "U ( VI )", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "Sr ( II )", "entity_type": "Chemical", "pos": [133, 142]}, {"entity": "Eu ( III )", "entity_type": "Chemical", "pos": [145, 155]}, {"entity": "Tc ( VII )", "entity_type": "Chemical", "pos": [160, 170]}], "task": "NER"}
{"text": "Cation / GO coagulation occurs with the formation of nanoparticle aggregates of GO sheets , facilitating their removal .", "entity": [], "task": "NER"}
{"text": "GO is far more effective in removal of transuranium elements from simulated nuclear waste solutions than other routinely used sorbents such as bentonite clays and activated carbon .", "entity": [{"entity": "transuranium", "entity_type": "Chemical", "pos": [39, 51]}, {"entity": "bentonite", "entity_type": "Chemical", "pos": [143, 152]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [173, 179]}], "task": "NER"}
{"text": "These results point toward a simple methodology to mollify the severity of nuclear waste contamination , thereby leading to effective measures for environmental remediation .", "entity": [], "task": "NER"}
{"text": "Ebullition rates and mercury concentrations in St .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [21, 28]}], "task": "NER"}
{"text": "Lawrence river sediments and a benthic invertebrate .", "entity": [], "task": "NER"}
{"text": "Ebullition , the release of gas from anaerobic decomposition in sediments , was recorded in a mercury - contaminated depositional zone ( Zone 1 ) of the St .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Lawrence River Area of Concern in Cornwall , Ontario , Canada .", "entity": [], "task": "NER"}
{"text": "The aim of the present study was to test if this disturbance affected the bioavailability of total mercury ( THg ) and methylmercury ( MeHg ) in surficial sediments to a benthic invertebrate ( Echinogammarus ischnus ) .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [99, 106]}, {"entity": "methylmercury", "entity_type": "Chemical", "pos": [119, 132]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "Ebullition rates ranged from < 1 to 2 , 800 ml / m ( 2 ) daily , with methane gas comprising 29 to 84 % of the total .", "entity": [{"entity": "methane", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "No direct effects of ebullition were found on either abiotic ( sediment or pore water THg or MeHg concentrations ) or biotic ( amphipod THg or MeHg concentrations ) variables measured .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [93, 97]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [143, 147]}], "task": "NER"}
{"text": "Instead , amphipod MeHg concentrations were best predicted by pore water THg and MeHg concentrations , organic matter of surficial sediments , and water depth and location .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "Trend surface analyses demonstrated that a shallow , southwestern part of Zone 1 was most contaminated with pore water mercury , which decreased in a gradient toward the northeast .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [119, 126]}], "task": "NER"}
{"text": "Further study is needed to determine if the amount of sediment resuspended by ebullition affects the spatial distribution of mercury .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "Ab initio molecular dynamics simulation on the formation process of He @ C 6 0 synthesized by explosion .", "entity": [{"entity": "He", "entity_type": "Chemical", "pos": [68, 70]}, {"entity": "C 6 0", "entity_type": "Chemical", "pos": [73, 78]}], "task": "NER"}
{"text": "The applications of endohedral non - metallic fullerenes are limited by their low production rate .", "entity": [{"entity": "fullerenes", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "Recently , an explosive method developed in our group shows promise to prepare He @ C 6 0 at fairly high yield , but the mechanism of He inserting into C 6 0 cage at explosive conditions was not clear .", "entity": [{"entity": "He", "entity_type": "Chemical", "pos": [79, 81]}, {"entity": "C 6 0", "entity_type": "Chemical", "pos": [84, 89]}, {"entity": "He", "entity_type": "Chemical", "pos": [134, 136]}, {"entity": "C 6 0", "entity_type": "Chemical", "pos": [152, 157]}], "task": "NER"}
{"text": "Here , ab initio molecular dynamics analysis has been used to simulate the collision between C 6 0 molecules at high - temperature and high - pressure induced by explosion .", "entity": [{"entity": "C 6 0", "entity_type": "Chemical", "pos": [93, 98]}], "task": "NER"}
{"text": "The results show that defects formed on the fullerene cage by collidsion can effectively decrease the reaction barrier for the insertion of He into C 6 0 , and the self - healing capability of the defects was also observed .", "entity": [{"entity": "fullerene", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "He", "entity_type": "Chemical", "pos": [140, 142]}, {"entity": "C 6 0", "entity_type": "Chemical", "pos": [148, 153]}], "task": "NER"}
{"text": "Biomimetic Methodology to Produce Polymeric Multilayered Particles for Biotechnological and Biomedical Applications .", "entity": [], "task": "NER"}
{"text": "The production of multi - compartmented particles for biomedical and biotechnological applications is challenging and the existing methods usually involve wet and aggressive conditions that compromise the encapsulation efficiency of bioactive agents and the viability of cells .", "entity": [], "task": "NER"}
{"text": "Biomimetic superhydrophobic surfaces allow construction of concentric multilayered polymeric systems , adding sequential layers where molecules or cells may be separately confined in compartments with high efficiency .", "entity": [], "task": "NER"}
{"text": "Cynomolgus monkey as a potential model to assess drug interactions involving hepatic organic anion transporting polypeptides : in vitro , in vivo , and in vitro - to - in vivo extrapolation .", "entity": [], "task": "NER"}
{"text": "Organic anion - transporting polypeptides ( OATP ) 1B1 , 1B3 , and 2B1 can serve as the loci of drug - drug interactions ( DDIs ) .", "entity": [], "task": "NER"}
{"text": "In the present work , the cynomolgus monkey was evaluated as a potential model for studying OATP - mediated DDIs .", "entity": [], "task": "NER"}
{"text": "Three cynomolgus monkey OATPs ( cOATPs ) , with a high degree of amino acid sequence identity ( 91 . 9 , 93 . 5 , and 96 . 6 % for OATP1B1 , 1B3 , and 2B1 , respectively ) to their human counterparts , were cloned , expressed , and characterized .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [65, 75]}], "task": "NER"}
{"text": "The cOATPs were stably transfected in human embryonic kidney cells and were functionally similar to the corresponding human OATPs ( hOATPs ) , as evident from the similar uptake rate of typical substrates ( estradiol - 17 beta - d - glucuronide , cholecystokinin octapeptide , and estrone - 3 - sulfate ) .", "entity": [{"entity": "estradiol - 17 beta - d - glucuronide", "entity_type": "Chemical", "pos": [207, 244]}, {"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [281, 302]}], "task": "NER"}
{"text": "Moreover , six known hOATP inhibitors exhibited similar IC ( 50 ) values against cOATPs .", "entity": [], "task": "NER"}
{"text": "To further evaluate the appropriateness of the cynomolgus monkey as a model , a known hOATP substrate [ rosuvastatin ( RSV ) ] - inhibitor [ rifampicin ( RIF ) ] pair was examined in vitro ; the monkey - derived parameters ( RSV K ( m ) and RIF IC ( 50 ) ) were similar ( within 3 . 5 - fold ) to those obtained with hOATPs and human primary hepatocytes .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [104, 116]}, {"entity": "RSV", "entity_type": "Chemical", "pos": [119, 122]}, {"entity": "rifampicin", "entity_type": "Chemical", "pos": [141, 151]}, {"entity": "RIF", "entity_type": "Chemical", "pos": [154, 157]}, {"entity": "RSV", "entity_type": "Chemical", "pos": [225, 228]}, {"entity": "RIF", "entity_type": "Chemical", "pos": [241, 244]}], "task": "NER"}
{"text": "In vivo , the area under the plasma concentration - time curve of RSV ( 3 mg / kg , oral ) given 1 hour after a single RIF dose ( 15 mg / kg , oral ) was increased 2 . 9 - fold in cynomolgus monkeys , consistent with the value ( 3 . 0 - fold ) reported in humans .", "entity": [{"entity": "RSV", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "RIF", "entity_type": "Chemical", "pos": [119, 122]}], "task": "NER"}
{"text": "A number of in vitro - in vivo extrapolation approaches , considering the fraction of the pathways affected and free versus total inhibitor concentrations , were also explored .", "entity": [], "task": "NER"}
{"text": "It is concluded that the cynomolgus monkey has the potential to serve as a useful model for the assessment of OATP - mediated DDIs in a nonclinical setting .", "entity": [], "task": "NER"}
{"text": "Pesticides in urban streams and early life stages of pacific coho salmon .", "entity": [], "task": "NER"}
{"text": "Pesticides are frequently detected in urban streams and are believed to be primarily the result of homeowner use .", "entity": [], "task": "NER"}
{"text": "Although concentrations in most cases are low ( < 1 micro g / L ) , there is concern that pesticide inputs threaten efforts to restore and enhance salmon habitat .", "entity": [], "task": "NER"}
{"text": "The authors exposed early life stages of coho salmon ( Oncorhynchus kisutch ) to a pesticide mixture ( \" cocktail \" ) representative of those pesticides most frequently reported in urban streams in western Washington State , USA .", "entity": [], "task": "NER"}
{"text": "Life stages were continuously exposed to pulses of the cocktail simulating those in urban streams in fall and winter when coho salmon eggs and sac fry are present .", "entity": [], "task": "NER"}
{"text": "Nominal concentrations of eight herbicides , two insecticides , a fungicide , and a breakdown product were the maximum detected .", "entity": [], "task": "NER"}
{"text": "Fertilization , hatching success , survival , deformities , and growth of fry were not significantly affected .", "entity": [], "task": "NER"}
{"text": "A reduction in fertilization success ( 19 - 25 % ) was not reproducible even when gametes were exposed to 100 times the maximum concentrations detected .", "entity": [], "task": "NER"}
{"text": "Based on the end points examined in the present study , the results suggest that direct exposure to the pesticides most frequently detected in urban streams in western Washington does not impair early life stages of coho salmon and is not a major factor governing the recovery of salmon populations .", "entity": [], "task": "NER"}
{"text": "The extent to which pesticide exposure would affect smoltification , outmigration , and ocean survival needs to be determined .", "entity": [], "task": "NER"}
{"text": "Resveratrol improves cardiomyopathy in dystrophin - deficient mice through SIRT1 protein - mediated modulation of p300 protein .", "entity": [{"entity": "Resveratrol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Cardiomyopathy is the main cause of death in Duchenne muscular dystrophy .", "entity": [], "task": "NER"}
{"text": "Here , we show that oral administration of resveratrol , which leads to activation of an NAD ( + ) - dependent protein deacetylase SIRT1 , suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin - deficient mdx mice .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "NAD ( + )", "entity_type": "Chemical", "pos": [89, 98]}], "task": "NER"}
{"text": "The pro - hypertrophic co - activator p300 protein but not p300 mRNA was up - regulated in the mdx heart , and resveratrol administration down - regulated the p300 protein level .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [111, 122]}], "task": "NER"}
{"text": "In cultured cardiomyocytes , cardiomyocyte hypertrophy induced by the alpha ( 1 ) - agonist phenylephrine was inhibited by the overexpression of SIRT1 as well as resveratrol , both of which down - regulated p300 protein levels but not p300 mRNA levels .", "entity": [{"entity": "phenylephrine", "entity_type": "Chemical", "pos": [92, 105]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "In addition , activation of atrial natriuretic peptide promoter by p300 was inhibited by SIRT1 .", "entity": [], "task": "NER"}
{"text": "We found that SIRT1 induced p300 down - regulation via the ubiquitin - proteasome pathway by deacetylation of lysine residues for ubiquitination .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "These findings indicate the pathological significance of p300 up - regulation in the dystrophic heart and indicate that SIRT1 activation has therapeutic potential for dystrophic cardiomyopathy .", "entity": [], "task": "NER"}
{"text": "The dynamics of dendrimers by NMR relaxation : interpretation pitfalls .", "entity": [], "task": "NER"}
{"text": "NMR is a powerful tool to study the dynamics of dendrimers .", "entity": [], "task": "NER"}
{"text": "By analogy to linear polymers , shorter T ( 1 ) relaxation times have been traditionally associated to less mobile nuclei and hence , dendrimers described with reduced local motions at either the core or the periphery .", "entity": [], "task": "NER"}
{"text": "Herein we report a NMR relaxation study [ ( 1 ) H and ( 13 ) C T ( 1 ) , T ( 2 ) ; ( 13 ) C { ( 1 ) H } NOE ; various fields and temperatures ] which reveals profound differences between the relaxation behavior of dendrimers and linear polymers .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [83, 91]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Dendrimers show slower dynamics at internal layers and on increasing generation and may display internal nuclei in the slow motional regime with larger T ( 1 ) values than the periphery .", "entity": [], "task": "NER"}
{"text": "In contrast to the relaxation properties of linear polymers , these T ( 1 ) increments should not be interpreted as resulting from faster dynamics .", "entity": [], "task": "NER"}
{"text": "Only the recording of T ( 1 ) data at various temperatures ( alternatively , T ( 2 ) or NOE at one temperature ) ensures the correct interpretation of dendrimer dynamics .", "entity": [], "task": "NER"}
{"text": "All - trans retinoic acid protects hepatocellular carcinoma cells against serum - starvation - induced cell death by upregulating collagen 8A2 .", "entity": [{"entity": "All - trans retinoic acid", "entity_type": "Chemical", "pos": [0, 25]}], "task": "NER"}
{"text": "As a therapeutic or chemopreventative agent for various cancers , all - trans retinoic acid ( atRA ) has been reported to inhibit growth , induce apoptosis or cause differentiation .", "entity": [{"entity": "all - trans retinoic acid", "entity_type": "Chemical", "pos": [66, 91]}, {"entity": "atRA", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "It was found that atRA could protect hepatocellular carcinoma ( HCC ) cells against cell death induced by serum starvation .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [18, 22]}], "task": "NER"}
{"text": "Furthermore , it was found that atRA could enhance cell adhesion , but had no effect on the cell cycle and apoptosis .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "Using an Illumina Human HT - 12 v4 expression microarray , 207 upregulated and 173 downregulated genes were identified in HepG2 cells treated with atRA .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "The most upregulated genes are cytochrome P450 family 26 subfamily A polypeptide 1 ( CYP26A1 ) , histidine triad nucleotide binding protein 3 ( HINT3 ) , miR - 1282 and cytochrome P450 family 26 subfamily B polypeptide 1 ( CYP26B1 ) , which showed more than fivefold greater expression .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [97, 106]}], "task": "NER"}
{"text": "Using Gene Ontology analysis , the greatest significance was found in extracellular - matrix - related molecular functions and the cellular component in upregulated genes .", "entity": [], "task": "NER"}
{"text": "The upregulation of collagen 8A2 ( COL8A2 ) was further confirmed using quantitative RT - PCR and western blotting .", "entity": [], "task": "NER"}
{"text": "Knockdown of COL8A2 blocked enhancement in the early stage of cell adhesion by atRA treatment .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "Re - expression of COL8A2 in COL8A2 - knocked - down HCC cells reversed the effect of small interfering RNA - COL8A2 .", "entity": [], "task": "NER"}
{"text": "In addition , COL8A2 could increase HCC cell migration and invasion .", "entity": [], "task": "NER"}
{"text": "Thus , COL8A2 was identified as the key protein involved in the enhancement of cell adhesion of atRA under serum - free conditions .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [96, 100]}], "task": "NER"}
{"text": "In conclusion , atRA protects HCC cells against serum - starvation - induced cell death by enhancing cell adhesion , and COL8A2 plays an important role in HCC cell migration and invasion .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [16, 20]}], "task": "NER"}
{"text": "Systemic leptin increases the electrical activity of supraoptic nucleus oxytocin neurones in virgin and late pregnant rats .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "In the rat hypothalamus , fasting attenuates the expression of oxytocin and this can be reversed by exogenous leptin administration .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "In the present study , we investigated the effects of systemically administered leptin on the electrical activity of magnocellular neurones in the supraoptic nucleus of urethane - anaesthetised rats .", "entity": [{"entity": "urethane", "entity_type": "Chemical", "pos": [169, 177]}], "task": "NER"}
{"text": "In virgin female rats , systemic leptin significantly excited identified oxytocin neurones with no detected effects on the patterning of activity , as reflected by hazard function analyses .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "The lowest dose that was consistently effective was 100 mu g / i . v . , and this dose had no significant effect on vasopressin neurones .", "entity": [{"entity": "vasopressin", "entity_type": "Chemical", "pos": [116, 127]}], "task": "NER"}
{"text": "In virgin rats fasted overnight , the spontaneous firing rate of oxytocin neurones was significantly lower than in unfasted rats , although leptin had a similar excitatory effect as in unfasted rats .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "In late pregnant rats ( days 19 - 21 of pregnancy ) , spontaneous firing rates of oxytocin neurones were higher than in virgins , and the initial response to leptin was similar to that in virgin rats , although the increase in activity was more persistent .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "In fasted pregnant rats , the mean spontaneous firing rate of oxytocin neurones was again lower than in unfasted rats , although leptin had no significant effect even at the higher dose of 1 mg / rat .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "Thus , fasting reduced the spontaneous firing rates of oxytocin neurones in nonpregnant rats , and this effect could be reversed by the excitatory effects of leptin .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "Pregnant rats showed some evidence of leptin resistance but only after an overnight fast .", "entity": [], "task": "NER"}
{"text": "Design and synthesis of potent inhibitor of apoptosis ( IAP ) proteins antagonists bearing an octahydropyrrolo [ 1 , 2 - a ] pyrazine scaffold as a novel proline mimetic .", "entity": [{"entity": "octahydropyrrolo [ 1 , 2 - a ] pyrazine", "entity_type": "Chemical", "pos": [94, 133]}, {"entity": "proline", "entity_type": "Chemical", "pos": [154, 161]}], "task": "NER"}
{"text": "To develop novel inhibitor of apoptosis ( IAP ) proteins antagonists , we designed a bicyclic octahydropyrrolo [ 1 , 2 - a ] pyrazine scaffold as a novel proline bioisostere .", "entity": [{"entity": "bicyclic octahydropyrrolo [ 1 , 2 - a ] pyrazine", "entity_type": "Chemical", "pos": [85, 133]}, {"entity": "proline", "entity_type": "Chemical", "pos": [154, 161]}], "task": "NER"}
{"text": "This design was based on the X - ray co - crystal structure of four N - terminal amino acid residues ( AVPI ) of the second mitochondria - derived activator of caspase ( Smac ) with the X - chromosome - linked IAP ( XIAP ) protein .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [68, 69]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [81, 91]}], "task": "NER"}
{"text": "Lead optimization of this scaffold to improve oral absorption yielded compound 45 , which showed potent cellular IAP1 ( cIAP1 IC ( 50 ) : 1 . 3 nM ) and XIAP ( IC ( 50 ) : 200 nM ) inhibitory activity , in addition to potent tumor growth inhibitory activity ( GI ( 50 ) : 1 . 8 nM ) in MDA - MB - 231 breast cancer cells .", "entity": [], "task": "NER"}
{"text": "X - ray crystallographic analysis of compound 45 bound to XIAP and to cIAP1 was achieved , revealing the various key interactions that contribute to the higher cIAPI affinity of compound 45 over XIAP .", "entity": [], "task": "NER"}
{"text": "Because of its potent IAP inhibitory activities , compound 45 ( T - 3256336 ) caused tumor regression in a MDA - MB - 231 tumor xenograft model ( T / C : - 53 % at 30 mg / kg ) .", "entity": [{"entity": "T - 3256336", "entity_type": "Chemical", "pos": [64, 75]}], "task": "NER"}
{"text": "Smart mesoporous SiO2 nanoparticles for the DNAzyme - induced multiplexed release of substrates .", "entity": [{"entity": "SiO2", "entity_type": "Chemical", "pos": [17, 21]}], "task": "NER"}
{"text": "The fluorescent dyes methylene blue , MB ( + ) , and thionine , Th ( + ) , can be trapped in the pores of mesoporous silica , MP - SiO ( 2 ) , by means of functional nanostructures consisting of the Mg ( 2 + ) - or Zn ( 2 + ) - dependent DNAzyme sequences .", "entity": [{"entity": "methylene blue", "entity_type": "Chemical", "pos": [21, 35]}, {"entity": "thionine", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "silica", "entity_type": "Chemical", "pos": [117, 123]}, {"entity": "SiO ( 2 )", "entity_type": "Chemical", "pos": [131, 140]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [199, 209]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [215, 225]}], "task": "NER"}
{"text": "In the presence of Mg ( 2 + ) or Zn ( 2 + ) ions the respective DNAzymes are activated , leading to the specific cleavage of the respective caps , and the selective release of MB ( + ) or Th ( + ) .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [19, 29]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "The enlargement of the conserved loop domains of the Mg ( 2 + ) - or Zn ( 2 + ) - dependent DNAzyme sequences with foreign nucleotides prohibits the formation of active DNAzymes and eliminates the release of the respective dyes .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "nucleotides", "entity_type": "Chemical", "pos": [123, 134]}], "task": "NER"}
{"text": "This is due to the flexibility of the loops that lacks affinity for the association of the ions .", "entity": [], "task": "NER"}
{"text": "The insertion of aptamer sequences ( e . g . , the adenosine - 5 ' - triphosphate ( ATP ) aptamer ) or ion - binding sequences ( e . g . , T - rich Hg ( 2 + ) ion - binding domains ) as foreign components to the loop regions allows the formation of active Mg ( 2 + ) - or Zn ( 2 + ) - dependent DNAzyme structures through the cooperative formation of aptamer - ATP complexes or T - Hg ( 2 + ) - T bridges .", "entity": [{"entity": "adenosine - 5 ' - triphosphate", "entity_type": "Chemical", "pos": [51, 81]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [148, 158]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [256, 266]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [272, 282]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [361, 364]}, {"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [382, 392]}], "task": "NER"}
{"text": "These aptamer - substrate complexes or T - Hg ( 2 + ) - T bridges allosterically stabilize and activate the DNAzymes , thus allowing the selective release of the fluorescent substrates MB ( + ) or Th ( + ) .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "The metal ion - driven DNAzyme release of substrates from the pores of MP - SiO ( 2 ) , and particularly the allosteric activation of the DNAzymes through cooperative aptamer - substrate complexes or metal - ion bridges , has important future nanomedical implications for targeted release of drugs .", "entity": [{"entity": "SiO ( 2 )", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "This is demonstrated with the triggered release of the anticancer drug , doxorubicin , by the Mg ( 2 + ) - DNAzyme - locked pores or by the aptamer - ATP complex - triggered activation of the Mg ( 2 + ) - dependent DNAzyme .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [150, 153]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [192, 202]}], "task": "NER"}
{"text": "Polymeric \" smart \" coatings to prevent foreign body response to implantable biosensors .", "entity": [], "task": "NER"}
{"text": "Application of implantable glucose biosensors for \" real - time \" monitoring is reliant on controlling the negative tissue reaction at the sensor tissue interphase .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "A novel polymer coating consisting of poly ( lactic - co - glycolic ) acid ( PLGA ) microsphere dispersed in poly ( vinyl alcohol ) ( PVA ) hydrogels was evaluated in combination with dummy sensors as a \" smart \" drug eluting biocompatible coating for implantable biosensors to prevent the foreign body response , and thus enhance sensor performance in vivo .", "entity": [{"entity": "poly ( lactic - co - glycolic ) acid", "entity_type": "Chemical", "pos": [38, 74]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [77, 81]}, {"entity": "poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [109, 131]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [134, 137]}], "task": "NER"}
{"text": "The polymeric microspheres slowly release tissue - modifying drugs at the implantation sites to control the inflammation and fibrous encapsulation , while the hydrogel allows rapid analyte diffusion to the sensing elements .", "entity": [], "task": "NER"}
{"text": "Dummy sensors with identical dimensions to that of the functional glucose sensors ( 0 . 5 x 0 . 5 x 5mm ) were coated with the PLGA / PVA composites using a mold fabrication process .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [127, 131]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [134, 137]}], "task": "NER"}
{"text": "Both normal and diabetic rats were used in the current study to investigate the effect of the diabetic state on tissue sensor interactions .", "entity": [], "task": "NER"}
{"text": "It was evident that the PLGA / PVA hydrogel composite was able to form a uniform coating around the dummy sensor and stayed intact throughout the course of the study ( one month ) .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [24, 28]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [31, 34]}], "task": "NER"}
{"text": "Tissue samples containing dummy sensors that were coated with dexamethasone free composites exhibited acute and chronic inflammation as well as fibrous encapsulation in both normal and diabetic rats .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [62, 75]}], "task": "NER"}
{"text": "However , the diabetic rats exhibited decreased intensity and delayed onset of the foreign body response following implantation of drug free dummy sensors in comparison to those of normal rats .", "entity": [], "task": "NER"}
{"text": "On the other hand , tissues containing dummy sensors that were coated with dexamethasone containing composites remained normal ( i . e . similar to untreated tissues ) , with no inflammatory reaction or fibrous encapsulation occurring over the one - month period in both the normal and diabetic rats .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [75, 88]}], "task": "NER"}
{"text": "The feasibility of utilizing PLGA microsphere / PVA hydrogel composites as coatings for implantable biosensors was demonstrated .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "This polymeric composite is an innovative approach to control the foreign body reaction at the tissue - device interface to prolong biosensor lifetime .", "entity": [], "task": "NER"}
{"text": "Facile sonochemical synthesis of novel pyrazolyne derivates at ambient conditions .", "entity": [{"entity": "pyrazolyne", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "Claisen - Schmidt condensation reaction of 4 - acetamidoacetophenone with aromatic aldehydes under ultrasonic irradiation affords acetylaminochalcones ( yields : 71 - 90 % ) which also under ultrasonic irradiation and in the presence of sodium acetate and acetic acid aqueous undergo facile and clean cyclocondensation with hydrazine to afford 3 - ( 4 - acetamidophenyl ) - 5 - ( aryl ) - 1 - H - pyrazolines .", "entity": [{"entity": "4 - acetamidoacetophenone", "entity_type": "Chemical", "pos": [43, 68]}, {"entity": "aromatic aldehydes", "entity_type": "Chemical", "pos": [74, 92]}, {"entity": "acetylaminochalcones", "entity_type": "Chemical", "pos": [130, 150]}, {"entity": "sodium acetate", "entity_type": "Chemical", "pos": [237, 251]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [256, 267]}, {"entity": "hydrazine", "entity_type": "Chemical", "pos": [324, 333]}, {"entity": "3 - ( 4 - acetamidophenyl ) - 5 - ( aryl ) - 1 - H - pyrazolines", "entity_type": "Chemical", "pos": [344, 408]}], "task": "NER"}
{"text": "The pyrazolines were obtained in good to excellent yields ( 81 - 89 % ) , and were characterized by conventional spectral data .", "entity": [{"entity": "pyrazolines", "entity_type": "Chemical", "pos": [4, 15]}], "task": "NER"}
{"text": "The work - up is simple and the results obtained indicate that , unlike classical heating , ultrasonic irradiation results in higher yields , shorter reaction times ( 1 . 5 - 2 . 3 h ) and milder conditions .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK - 441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice .", "entity": [{"entity": "TAK - 441", "entity_type": "Chemical", "pos": [67, 76]}], "task": "NER"}
{"text": "6 - Ethyl - N - [ 1 - ( hydroxyacetyl ) piperidin - 4 - yl ] - 1 - methyl - 4 - oxo - 5 - ( 2 - oxo - 2 - phenylethyl ) - 3 - ( 2 , 2 , 2 - trifluoroethoxy ) - 4 , 5 - dihydro - 1H - pyrrolo [ 3 , 2 - c ] pyridine - 2 - carboxamide ( TAK - 441 ) is a potent , selective hedgehog signaling pathway inhibitor that binds to Smo and is being developed for the treatment of cancer .", "entity": [{"entity": "6 - Ethyl - N - [ 1 - ( hydroxyacetyl ) piperidin - 4 - yl ] - 1 - methyl - 4 - oxo - 5 - ( 2 - oxo - 2 - phenylethyl ) - 3 - ( 2 , 2 , 2 - trifluoroethoxy ) - 4 , 5 - dihydro - 1H - pyrrolo [ 3 , 2 - c ] pyridine - 2 - carboxamide", "entity_type": "Chemical", "pos": [0, 231]}, {"entity": "TAK - 441", "entity_type": "Chemical", "pos": [234, 243]}], "task": "NER"}
{"text": "The objectives of these studies were to explore the possibility of establishing of a link between the pharmacokinetics of TAK - 441 and the responses of Gli1 mRNA in tumor - associated stromal or skin cells and the antitumor effect of hedgehog inhibition .", "entity": [{"entity": "TAK - 441", "entity_type": "Chemical", "pos": [122, 131]}], "task": "NER"}
{"text": "To this end , we built pharmacokinetic and pharmacodynamic models that describe the relationship of the concentrations of TAK - 441 plasma to the responses of Gli1 mRNA in the tumor ( target ) and skin ( surrogate ) and to tumor growth inhibition in mice bearing xenografts of human pancreatic tumors ( PAN - 04 ) .", "entity": [{"entity": "TAK - 441", "entity_type": "Chemical", "pos": [122, 131]}], "task": "NER"}
{"text": "The responses of Gli1 mRNA and tumor growth were described by an indirect response model and an exponential tumor growth model , respectively .", "entity": [], "task": "NER"}
{"text": "The IC50 values for Gli1 mRNA inhibition in the tumor and skin by TAK - 441 were estimated to be 0 . 0457 and 0 . 113 mu g / ml , respectively .", "entity": [{"entity": "TAK - 441", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "The IC90 value for tumor growth inhibition was estimated to be 0 . 68 mu g / ml .", "entity": [], "task": "NER"}
{"text": "These results suggest that a > 83 % inhibition of Gli1 mRNA expression in the skin or a > 94 % inhibition of Gli1 mRNA expression in the tumor would be required to sufficiently inhibit ( > 90 % ) hedgehog - related tumor growth in the xenografted model mice .", "entity": [], "task": "NER"}
{"text": "We conclude that Gli1 mRNA expression in the tumor and skin could be a useful biomarker for predicting the antitumor effect of hedgehog inhibitors .", "entity": [], "task": "NER"}
{"text": "Alternative splicing in the aldo - keto reductase superfamily : implications for protein nomenclature .", "entity": [], "task": "NER"}
{"text": "The aldo - keto reductase superfamily contains 173 proteins which are present in all phyla .", "entity": [], "task": "NER"}
{"text": "Examination of the human and mouse genomes has identified that in some instances a single AKR gene can give rise to alternatively spliced mRNA variants which in some cases can give rise to more than one protein isoform .", "entity": [], "task": "NER"}
{"text": "This is currently well documented in the AKR6A subfamily which contains the beta - subunits of the voltage - gated potassium ion channels .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "With the emergence of second generation sequencing it is likely that the occurrence of transcript variants and protein isoforms from a single AKR gene may become common place .", "entity": [], "task": "NER"}
{"text": "To deal with this issue we recommend that the Ensembl data - base nomenclature be used to annotate the transcript variants from a single AKR gene .", "entity": [], "task": "NER"}
{"text": "However , since multiple transcript variants could give rise to either the same or multiple protein isoforms from the same AKR gene we also propose to expand the nomenclature of the AKR protein superfamily , so that when a protein isoform is shown to be expressed and is functional it would be assigned the standard AKR name followed by a \" period or full - stop \" and a number for that unique isoform .", "entity": [], "task": "NER"}
{"text": "Numbers will be assigned chronologically and linked to the respective transcripts annotated in Ensembl e . g . AKR6A5 . 1 ( Kv beta 2 . 1 ) ( AKR6A5 - 001 , - 006 and - 201 ) , followed by AKR6A5 . 2 ( Kv beta 2 . 2 ) ( AKR6A5 - 002 , - 202 ) .", "entity": [], "task": "NER"}
{"text": "This nomenclature is expandable and it enables multiple protein isoforms to be assigned to their respective transcripts when they arise from the same AKR gene or for a single protein isoform to be assigned to multiple transcripts when the transcripts encode the same AKR protein .", "entity": [], "task": "NER"}
{"text": "Protective effects of alpha lipoic acid versus N - acetylcysteine on ifosfamide - induced nephrotoxicity .", "entity": [{"entity": "alpha lipoic acid", "entity_type": "Chemical", "pos": [22, 39]}, {"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [47, 65]}, {"entity": "ifosfamide", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "Ifosfamide ( IFO ) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors .", "entity": [{"entity": "Ifosfamide", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "IFO", "entity_type": "Chemical", "pos": [13, 16]}], "task": "NER"}
{"text": "However , its use is limited due to its serious side effect on kidneys .", "entity": [], "task": "NER"}
{"text": "The side - chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect .", "entity": [{"entity": "IFO", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "Therefore , this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO - induced nephrotoxicity , including free radical generation and the possible role of alpha lipoic acid ( ALA ) versus N - acetylcysteine ( NAC ) in protection against this toxicity .", "entity": [{"entity": "IFO", "entity_type": "Chemical", "pos": [113, 116]}, {"entity": "alpha lipoic acid", "entity_type": "Chemical", "pos": [203, 220]}, {"entity": "ALA", "entity_type": "Chemical", "pos": [223, 226]}, {"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [236, 254]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [257, 260]}], "task": "NER"}
{"text": "Male albino rats were injected intraperitoneally with saline , IFO ( 50 mg / kg daily for 5 days ) , IFO + ALA ( 100 mg / kg daily for 8 days ) and IFO + NAC ( 200 mg / kg daily for 8 days ) .", "entity": [{"entity": "IFO", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "IFO", "entity_type": "Chemical", "pos": [101, 104]}, {"entity": "ALA", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "IFO", "entity_type": "Chemical", "pos": [148, 151]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [154, 157]}], "task": "NER"}
{"text": "Kidney malondialdehyde , nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [7, 22]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [42, 53]}], "task": "NER"}
{"text": "Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO .", "entity": [{"entity": "ALA", "entity_type": "Chemical", "pos": [5, 8]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "IFO", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "NAC was more nephroprotective than ALA .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "ALA", "entity_type": "Chemical", "pos": [35, 38]}], "task": "NER"}
{"text": "This study suggests that oxidative stress is possibly involved in the IFO - induced nephrotoxicity in rats .", "entity": [{"entity": "IFO", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "The study also suggests the potential therapeutic role for ALA and NAC against IFO - induced nephrotoxicity .", "entity": [{"entity": "ALA", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [67, 70]}, {"entity": "IFO", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "Antioxidative , antiapoptotic , and proliferative effect of curcumin on liver regeneration after partial hepatectomy in rats .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "The aim of the present study was to assess the influence of curcumin on liver regeneration after partial hepatectomy ( PH ) in rats .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "A total of 24 male Sprague Dawley rats were divided into three groups : sham - operated ( SH ) , PH , and PH + curcumin ; each group contains eight animals .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "The rats in curcumin - treated groups were given curcumin ( in a dose of 100 mg / kg body weight ) once a day orally for 7 days , starting 3 days prior to hepatectomy operation .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "curcumin", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "At 7 days after resection , liver samples were collected .", "entity": [], "task": "NER"}
{"text": "The malondialdehyde ( MDA ) , superoxide dismutase ( SOD ) , and glutathione ( GSH ) levels were estimated in liver homogenates .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [4, 19]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [65, 76]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "Moreover , histopathological examination , mitotic index ( MI ) , proliferating cell nuclear antigen labeling , proliferation index ( PI ) , transferase - mediated 2 ' - deoxyuridine , 5 ' - triphosphate nick end - labeling assay , and apoptotic index ( AI ) were evaluated at 7 days after hepatectomy .", "entity": [{"entity": "2 ' - deoxyuridine", "entity_type": "Chemical", "pos": [164, 182]}, {"entity": "5 ' - triphosphate", "entity_type": "Chemical", "pos": [185, 203]}], "task": "NER"}
{"text": "As a result , curcumin significantly increased MI and PI and significantly decreased AI in PH rats .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [14, 22]}], "task": "NER"}
{"text": "Additionally , curcumin remarkably inhibited MDA elevation , restored impaired antioxidant SOD activity and GSH level and also attenuated hepatic vacuolar degeneration and sinusoidal congestion .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "These results suggested that curcumin treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy , probably due to its antioxidative , antiapoptotic , and proliferative properties .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Structure - based redesign of proteins for minimal T - cell epitope content .", "entity": [], "task": "NER"}
{"text": "The protein universe displays a wealth of therapeutically relevant activities , but T - cell driven immune responses to non - \" self \" biological agents present a major impediment to harnessing the full diversity of these molecular functions .", "entity": [], "task": "NER"}
{"text": "Mutagenic T - cell epitope deletion seeks to mitigate the immune response , but can typically address only a small number of epitopes .", "entity": [], "task": "NER"}
{"text": "Here , we pursue a \" bottom - up \" approach that redesigns an entire protein to remain native - like but contain few if any immunogenic epitopes .", "entity": [], "task": "NER"}
{"text": "We do so by extending the Rosetta flexible - backbone protein design software with an epitope scoring mechanism and appropriate constraints .", "entity": [], "task": "NER"}
{"text": "The method is benchmarked with a diverse panel of proteins and applied to three targets of therapeutic interest .", "entity": [], "task": "NER"}
{"text": "We show that the deimmunized designs indeed have minimal predicted epitope content and are native - like in terms of various quality measures , and moreover that they display levels of native sequence recovery comparable to those of non - deimmunized designs .", "entity": [], "task": "NER"}
{"text": "Long - range corrected functionals satisfy Koopmans ' theorem : calculation of correlation and relaxation energies .", "entity": [], "task": "NER"}
{"text": "In this article , we show that the long - range - corrected ( LC ) density functionals LC - BOP and LCgau - BOP reproduce frontier orbital energies and highest - occupied molecular orbital ( HOMO ) - lowest - unoccupied molecular orbital ( LUMO ) gaps better than other density functionals .", "entity": [], "task": "NER"}
{"text": "The negative of HOMO and LUMO energies are compared with the vertical ionization potentials ( IPs ) and electron affinities , respectively , using CCSD ( T ) / 6 - 311 + + G ( 3df , 3pd ) for 113 molecules , and we found LC functionals to satisfy Koopmans ' theorem .", "entity": [], "task": "NER"}
{"text": "We also report that the frontier orbital energies and the HOMO - LUMO gaps of LC - BOP and LCgau - BOP are better than those of recently proposed omega M05 - D ( Lin et al . , J . Chem . Phys . 2012 , 136 , 154109 ) .", "entity": [], "task": "NER"}
{"text": "We express the exact IP in terms of orbital relaxation , and correlation energies and hence calculate the relaxation and correlation energies for the same set of molecules .", "entity": [], "task": "NER"}
{"text": "It is found that the LC functionals , in general , includes more relaxation effect than Hartree - Fock and more correlation effect than the other density functionals without LC scheme .", "entity": [], "task": "NER"}
{"text": "Finally , we scan mu parameter in LC scheme from 0 . 1 to 0 . 6 bohr ( - 1 ) for the above test set molecules with LC - BOP functional and found our parameter value , 0 . 47 bohr ( - 1 ) , is usefully applicable to our tested systems .", "entity": [], "task": "NER"}
{"text": "Simultaneous determination and characterization of tannins and triterpene saponins from the fruits of various species of Terminalia and Phyllantus emblica using a UHPLC - UV - MS method : application to triphala .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [51, 58]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [63, 82]}], "task": "NER"}
{"text": "Terminalia species are a rich source of tannins .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [40, 47]}], "task": "NER"}
{"text": "Many preparations of these species are used in traditional medicine and have many different ethnobotanical applications .", "entity": [], "task": "NER"}
{"text": "A simple UHPLC method was developed for the simultaneous analysis of such hydrolysable tannins and triterpene saponins from the fruit rinds of different species of Terminalia ( T . chebula , T . arjuna , T . bellirica ) and Phyllantus emblica .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [99, 118]}], "task": "NER"}
{"text": "A separation by LC was achieved using a reversed - phase column and a water / acetonitrile mobile phase , both containing formic acid , using a gradient system and a temperature of 40 degrees C .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "formic acid", "entity_type": "Chemical", "pos": [122, 133]}], "task": "NER"}
{"text": "Eight hydrolysable tannins ( gallic acid , gallic acid methyl ester , corilagin , chebulagic acid , 1 , 2 , 3 , 6 - tetra - O - galloyl - beta - D - glucose , ellagic acid , chebulinic acid , and 1 , 2 , 3 , 4 , 6 - penta - O - galloyl - beta - D - glucose ) and six triterpene saponins ( arjunglucoside - I , arjunglucoside - III , chebuloside II , bellericoside , arjunetin , and arjunglucoside - II ) could be separated within 20 minutes .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [29, 40]}, {"entity": "gallic acid methyl ester", "entity_type": "Chemical", "pos": [43, 67]}, {"entity": "corilagin", "entity_type": "Chemical", "pos": [70, 79]}, {"entity": "chebulagic acid", "entity_type": "Chemical", "pos": [82, 97]}, {"entity": "1 , 2 , 3 , 6 - tetra - O - galloyl - beta - D - glucose", "entity_type": "Chemical", "pos": [100, 156]}, {"entity": "ellagic acid", "entity_type": "Chemical", "pos": [159, 171]}, {"entity": "chebulinic acid", "entity_type": "Chemical", "pos": [174, 189]}, {"entity": "1 , 2 , 3 , 4 , 6 - penta - O - galloyl - beta - D - glucose", "entity_type": "Chemical", "pos": [196, 256]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [267, 286]}, {"entity": "arjunglucoside - I", "entity_type": "Chemical", "pos": [289, 307]}, {"entity": "arjunglucoside - III", "entity_type": "Chemical", "pos": [310, 330]}, {"entity": "chebuloside II", "entity_type": "Chemical", "pos": [333, 347]}, {"entity": "bellericoside", "entity_type": "Chemical", "pos": [350, 363]}, {"entity": "arjunetin", "entity_type": "Chemical", "pos": [366, 375]}, {"entity": "arjunglucoside - II", "entity_type": "Chemical", "pos": [382, 401]}], "task": "NER"}
{"text": "The wavelength used for detection with the diode array detector was 254 and 275 nm for tannins and 205 nm for triterpene saponins .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [110, 129]}], "task": "NER"}
{"text": "The method was validated for linearity , repeatability , limits of detection , and limits of quantification .", "entity": [], "task": "NER"}
{"text": "The developed method is economical , fast , and especially suitable for quality control analysis of tannins and triterpene saponins in various plant samples and commercial products of Terminalia .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [100, 107]}, {"entity": "triterpene saponins", "entity_type": "Chemical", "pos": [112, 131]}], "task": "NER"}
{"text": "Fetal and neonatal outcomes in women reporting ingestion of licorice ( Glycyrrhiza uralensis ) during pregnancy .", "entity": [], "task": "NER"}
{"text": "Maternal intake of licorice from dietary sources has been associated with adverse maternal and fetal outcomes .", "entity": [], "task": "NER"}
{"text": "We prospectively studied the outcome of 185 singleton pregnancies who took over - the - counter or naturopathic formulations containing licorice during their pregnancy , and 370 age - matched singleton pregnant controls that were not exposed to any potential teratogen .", "entity": [], "task": "NER"}
{"text": "The indication in 56 . 8 % of the women taking licorice was for cough and cold control , with the maximum dose of 2104 mg / day and exposure occurring between the 4th day and 25th week of gestation .", "entity": [], "task": "NER"}
{"text": "The rate of stillbirths was marginally higher among women who took licorice than those who did not ( OR = 7 . 9 ; 95 % CI 0 . 9 - 71 . 5 ; p = 0 . 048 ) , and significantly higher when compared to the general population in the Republic of Korea ( OR = 13 . 3 ; 95 % CI 4 . 9 - 35 . 8 ; p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "Other fetal outcomes assessed in the study were similar between the two study groups , e . g . , the OR of major malformations was 3 . 9 ( 95 % CI 0 . 4 - 43 . 5 ; p = 0 . 27 ) .", "entity": [], "task": "NER"}
{"text": "In conclusion , the present study suggests that licorice is not a major teratogen .", "entity": [], "task": "NER"}
{"text": "However , whether licorice may increase the risk of stillbirths requires careful consideration in further studies with a larger sample size .", "entity": [], "task": "NER"}
{"text": "Antibodies against Yariv ' s reagent for immunolocalization of arabinogalactan - proteins in aerial parts of Echinacea purpurea .", "entity": [], "task": "NER"}
{"text": "Arabinogalactan - proteins are glycoproteins that occur in higher plants and are involved in important processes like cell differentiation and plant growth .", "entity": [], "task": "NER"}
{"text": "In the medicinal plant Echinacea purpurea L . , they belong to the putative immunomodulating compounds and are structurally well characterized .", "entity": [], "task": "NER"}
{"text": "For microscopic localization of arabinogalactan - proteins , synthetic ( beta - D - Glc ) 3 Yariv phenylglycoside that specifically binds to most plant arabinogalactan - proteins was used to label arabinogalactan - proteins in fresh cut sections of stems and petioles of Echinacea purpurea .", "entity": [{"entity": "( beta - D - Glc ) 3 Yariv phenylglycoside", "entity_type": "Chemical", "pos": [71, 113]}], "task": "NER"}
{"text": "Polyclonal antibodies against ( beta - D - Glc ) 3 Yariv phenylglycoside were used to detect the arabinogalactan - protein - ( beta - D - Glc ) 3 Yariv phenylglycoside complex .", "entity": [{"entity": "( beta - D - Glc ) 3 Yariv phenylglycoside", "entity_type": "Chemical", "pos": [30, 72]}, {"entity": "( beta - D - Glc ) 3 Yariv phenylglycoside", "entity_type": "Chemical", "pos": [125, 167]}], "task": "NER"}
{"text": "After addition of fluorescein isothiocyanate - conjugated secondary antibodies , the sections were analyzed by confocal laser scanning microscopy .", "entity": [{"entity": "fluorescein isothiocyanate", "entity_type": "Chemical", "pos": [18, 44]}], "task": "NER"}
{"text": "Arabinogalactan - proteins are localized mainly in the central cylinder in the collateral vascular bundles , especially in the area of the xylem .", "entity": [], "task": "NER"}
{"text": "In cell walls of fully differentiated vessels and tracheids , arabinogalactan - proteins have been detected mainly at the inner area of the wall close to the cell lumina .", "entity": [], "task": "NER"}
{"text": "Intense labeling occurs around pit canals connecting adjacent vessels .", "entity": [], "task": "NER"}
{"text": "Furthermore , arabinogalactan - proteins are present in the lumina of cells of the sclerenchyma caps and in companion cells of the phloem .", "entity": [], "task": "NER"}
{"text": "An in vitro model of human acute ethanol exposure that incorporates CXCR3 - and CXCR4 - dependent recruitment of immune cells .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [33, 40]}], "task": "NER"}
{"text": "Alcoholic liver disease ( ALD ) is one of the commonest causes of cirrhosis and liver failure in the developed world .", "entity": [], "task": "NER"}
{"text": "Hepatic inflammation is the critical stage in progression of both ALD and non - ALD , but it remains difficult to study the underlying mechanisms in a human system , and current animal models do not fully recapitulate human liver disease .", "entity": [], "task": "NER"}
{"text": "We developed a human tissue - based system to study lymphocyte recruitment in response to ethanol challenge .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "Precision - cut liver slices ( PCLS ) from human livers were incubated in culture , and hepatic function was determined by albumin production , 3 - ( 4 , 5 - dimethylthiazol ) - 2 , 5 - diphenyl tetrazolium bromide assay , glucose uptake responses , and morphometric assessment .", "entity": [{"entity": "3 - ( 4 , 5 - dimethylthiazol ) - 2 , 5 - diphenyl tetrazolium bromide", "entity_type": "Chemical", "pos": [144, 214]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [223, 230]}], "task": "NER"}
{"text": "Responses of tissue and lymphocytes to ethanol exposure were determined by PCR , flow cytometry , histology , and lymphocyte infiltration assays .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "Human PCLS demonstrated appropriate upregulation of CYP2E1 , ADH1 alpha , and ADH3 in response to ethanol treatment .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [98, 105]}], "task": "NER"}
{"text": "Ethanol also induced expression of endothelial VCAM - 1 and ICAM - 1 , production of sICAM - 1 and CXCL8 , and the chemokine receptors CXCR3 and CXCR4 on CD4 and CD8 lymphocytes .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "CXCR3 - and CXCR4 - dependent migration of lymphocytes into the tissue increased significantly in response to treatment with ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "We have demonstrated that ethanol increases chemokine receptor expression and lymphocyte recruitment into human liver tissue , suggesting that it may operate directly to promote hepatitis in ALD .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [26, 33]}], "task": "NER"}
{"text": "The physiological and pathophysiological responses of the PCLS to ethanol in vitro highlight the potential of this assay for dissecting the molecular mechanisms underlying human liver inflammation and as a screening tool for novel therapeutics .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [66, 73]}], "task": "NER"}
{"text": "Identification of propofol binding sites in a nicotinic acetylcholine receptor with a photoreactive propofol analog .", "entity": [{"entity": "propofol", "entity_type": "Chemical", "pos": [18, 26]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [56, 69]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "Propofol , a widely used intravenous general anesthetic , acts at anesthetic concentrations as a positive allosteric modulator of gamma - aminobutyric acid type A receptors and at higher concentration as an inhibitor of nicotinic acetylcholine receptors ( nAChRs ) .", "entity": [{"entity": "Propofol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [130, 155]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [230, 243]}], "task": "NER"}
{"text": "Here , we characterize propofol binding sites in a muscle - type nAChR by use of a photoreactive analog of propofol , 2 - isopropyl - 5 - [ 3 - ( trifluoromethyl ) - 3H - diazirin - 3 - yl ] phenol ( AziPm ) .", "entity": [{"entity": "propofol", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "2 - isopropyl - 5 - [ 3 - ( trifluoromethyl ) - 3H - diazirin - 3 - yl ] phenol", "entity_type": "Chemical", "pos": [118, 197]}, {"entity": "AziPm", "entity_type": "Chemical", "pos": [200, 205]}], "task": "NER"}
{"text": "Based upon radioligand binding assays , AziPm stabilized the Torpedo nAChR in the resting state , whereas propofol stabilized the desensitized state .", "entity": [{"entity": "AziPm", "entity_type": "Chemical", "pos": [40, 45]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "nAChR - rich membranes were photolabeled with [ ( 3 ) H ] AziPm , and labeled amino acids were identified by Edman degradation .", "entity": [{"entity": "[ ( 3 ) H ] AziPm", "entity_type": "Chemical", "pos": [46, 63]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [78, 89]}], "task": "NER"}
{"text": "[ ( 3 ) H ] AziPm binds at three sites within the nAChR transmembrane domain : ( i ) an intrasubunit site in the delta subunit helix bundle , photolabeling in the nAChR desensitized state ( + agonist ) delta M2 - 18 ' and two residues in delta M1 ( delta Phe - 232 and delta Cys - 236 ) ; ( ii ) in the ion channel , photolabeling in the nAChR resting , closed channel state ( - agonist ) amino acids in the M2 helices ( alpha M2 - 6 ' , beta M2 - 6 ' and - 13 ' , and delta M2 - 13 ' ) that line the channel lumen ( with photolabeling reduced by > 90 % in the desensitized state ) ; and ( iii ) at the gamma - alpha interface , photolabeling alpha M2 - 10 ' .", "entity": [{"entity": "[ ( 3 ) H ] AziPm", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "delta Phe", "entity_type": "Chemical", "pos": [249, 258]}, {"entity": "delta Cys", "entity_type": "Chemical", "pos": [269, 278]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [389, 400]}], "task": "NER"}
{"text": "Propofol enhanced [ ( 3 ) H ] AziPm photolabeling at alpha M2 - 10 ' .", "entity": [{"entity": "Propofol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "[ ( 3 ) H ] AziPm", "entity_type": "Chemical", "pos": [18, 35]}], "task": "NER"}
{"text": "Propofol inhibited [ ( 3 ) H ] AziPm photolabeling within the delta subunit helix bundle at lower concentrations ( IC50 = 40 mu m ) than it inhibited ion channel photolabeling ( IC50 = 125 mu m ) .", "entity": [{"entity": "Propofol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "[ ( 3 ) H ] AziPm", "entity_type": "Chemical", "pos": [19, 36]}], "task": "NER"}
{"text": "These results identify for the first time a single intrasubunit propofol binding site in the nAChR transmembrane domain and suggest that this is the functionally relevant inhibitory binding site .", "entity": [{"entity": "propofol", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "BSTA promotes mTORC2 - mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation .", "entity": [], "task": "NER"}
{"text": "Phosphorylation and activation of Akt1 is a crucial signaling event that promotes adipogenesis .", "entity": [], "task": "NER"}
{"text": "However , neither the complex multistep process that leads to activation of Akt1 through phosphorylation at Thr (3) 0 8 and Ser 4 7 (3) nor the mechanism by which Akt1 stimulates adipogenesis is fully understood .", "entity": [{"entity": "Thr", "entity_type": "Chemical", "pos": [108, 111]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "We found that the BSD domain - containing signal transducer and Akt interactor ( BSTA ) promoted phosphorylation of Akt1 at Ser 4 7 (3) in various human and murine cells , and we uncovered a function for the BSD domain in BSTA - Akt1 complex formation .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1 , and the BSTA - Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser 4 7 (3) in response to growth factor stimulation .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [235, 238]}], "task": "NER"}
{"text": "Furthermore , analyses of bsta gene - trap murine embryonic stem cells revealed an essential function for BSTA and phosphorylation of Akt1 at Ser 4 7 (3) in promoting adipocyte differentiation , which required suppression of the expression of the gene encoding the transcription factor FoxC2 .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "These findings indicate that BSTA is a molecular switch that promotes phosphorylation of Akt1 at Ser 4 7 (3) and reveal an mTORC2 - BSTA - Akt1 - FoxC2 - mediated signaling mechanism that is critical for adipocyte differentiation .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "Amino acid grafted chitosan for high performance gene delivery : comparison of amino acid hydrophobicity on vector and polyplex characteristics .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [79, 89]}], "task": "NER"}
{"text": "To develop a safe , effective , and biocompatible gene delivery vector , a series of hydrophobic amino acid grafted chitosan ( AGC ) derivatives were synthesized by carbodiimide mediated coupling reaction .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "carbodiimide", "entity_type": "Chemical", "pos": [165, 177]}], "task": "NER"}
{"text": "Chemical characterization of AGC polymers was performed by NMR and elemental analysis .", "entity": [], "task": "NER"}
{"text": "AGC polymers demonstrated excellent blood compatibility and cell viability , as evaluated by hemolysis and MTT assay , respectively .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "AGC polymers could effectively bind and condense plasmid DNA ( pDNA ) to form polyplexes in the size range of 161 - 263 nm and possessed net cationic charge .", "entity": [], "task": "NER"}
{"text": "The resultant polyplex showed 3 . 4 - 5 . 4 - fold greater cellular uptake and 13 - 30 - fold higher transfection efficiency in HEK 293 cells as compared to unmodified chitosan .", "entity": [], "task": "NER"}
{"text": "Moreover , both cellular uptake and transfection efficiency improved with the increasing amino acid hydrophobicity .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "Hydrophobic amino acid substitution contributed to the enhance pDNA release at cytosolic pH .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [12, 22]}], "task": "NER"}
{"text": "These data demonstrate AGC polymers as a promising novel nonviral gene delivery vector .", "entity": [], "task": "NER"}
{"text": "Improved self - healing of polyethylene / carbon black nanocomposites by their shape memory effect .", "entity": [{"entity": "polyethylene", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "carbon black", "entity_type": "Chemical", "pos": [42, 54]}], "task": "NER"}
{"text": "In this work , the improved self - healing of cross - linked polyethylene ( PE ) ( cPE ) / carbon black ( CB ) nanocomposites by their shape memory effect ( SME ) is investigated .", "entity": [{"entity": "polyethylene", "entity_type": "Chemical", "pos": [61, 73]}, {"entity": "carbon black", "entity_type": "Chemical", "pos": [91, 103]}], "task": "NER"}
{"text": "CB nanoparticles are found to be homogeneously dispersed in the PE matrix and significantly increase the strength of the materials .", "entity": [], "task": "NER"}
{"text": "Compared with the breaking of linear PE ( lPE ) at the melting temperature ( T ( m ) ) , the cPE and cPE / CB nanocomposites still have high strength above T ( m ) due to the formation of networks .", "entity": [], "task": "NER"}
{"text": "The cPE and cPE / CB nanocomposites show both high strain fixity ratio ( R ( f ) ) and high strain recovery ratio ( R ( r ) ) .", "entity": [], "task": "NER"}
{"text": "Crystallization - induced elongation is observed for all the prepared shape memory polymer ( SMP ) materials and the effect becomes less remarkable with increasing volume fraction of CB nanoparticles ( v ( CB ) ) .", "entity": [], "task": "NER"}
{"text": "The scratch self - healing tests show that the cross - linking of PE matrix , the addition of CB nanoparticles , and the previous stretching in the direction perpendicular to the scratch favor the closure of the scratch and its complete healing .", "entity": [], "task": "NER"}
{"text": "This SME - aided self - healing could have potential applications in diverse fields such as coating and structure materials .", "entity": [], "task": "NER"}
{"text": "Formulation study of a patch containing propranolol by design of experiments .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [40, 51]}], "task": "NER"}
{"text": "Abstract Objective : To evaluate the feasibility of a transdermal patch containing propranolol ( PR ) .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "Method : Skin penetration enhancers ( SPEs ) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2 ( 4 ) full factorial design .", "entity": [], "task": "NER"}
{"text": "The permeation profile of PR from the formulations was assessed in in vitro permeation studies performed by using Franz diffusion cells and human epidermis as membrane .", "entity": [], "task": "NER"}
{"text": "Finally , skin irritation was evaluated by the Draize test .", "entity": [], "task": "NER"}
{"text": "Results : N - methyl pyrrolidone ( NMP ) resulted as the best SPE : in addition , the critical factors influencing the PR diffusion through the human epidermis when loaded in the patch resulted in the matrix thickness ( X ( 1 ) , p = 0 . 0957 ) and PR content ( X ( 3 ) , p = 0 . 0004 ) which improved the flux ; conversely , NMP lacked its enhancement effect when loaded in the patch and the increase in its concentration ( X ( 4 ) , p = 0 . 006 ) affected the drug permeation through human epidermis .", "entity": [{"entity": "N - methyl pyrrolidone", "entity_type": "Chemical", "pos": [10, 32]}, {"entity": "NMP", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "NMP", "entity_type": "Chemical", "pos": [326, 329]}], "task": "NER"}
{"text": "The flux of optimal formulation was 12 . 7 mu g / cm ( 2 ) / h .", "entity": [], "task": "NER"}
{"text": "On the basis of the steady - state concentration and clearance of PR , the estimated patch surface was 100 - 120 cm ( 2 ) , since the activity of PR is related to its Senantiomer and no in vivo bioconversion occurs .", "entity": [], "task": "NER"}
{"text": "Conclusion : A patch containing ( S ) - PR was prepared and the ( S ) - PR flux ( 13 . 3 mu g / cm ( 2 ) / h ) permitted to confirm the suitability of a transdermal administration of PR .", "entity": [{"entity": "( S ) - PR", "entity_type": "Chemical", "pos": [32, 42]}, {"entity": "( S ) - PR", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "In particular , the use of a 50 mu m thick methacrylic matrix containing 8 % ( S ) - PR and 15 % NMP can allow to develop a patch non - irritating to the skin , in order to ensure a constant permeation flux of PR over 48 h .", "entity": [{"entity": "methacrylic", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "( S ) - PR", "entity_type": "Chemical", "pos": [77, 87]}, {"entity": "NMP", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "Nanoscale Dynamics and Protein Adhesivity of Alkylamine Self - Assembled Monolayers on Graphene .", "entity": [{"entity": "Alkylamine", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "Graphene", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Atomic - scale molecular dynamics computer simulations are used to probe the structure , dynamics , and energetics of alkylamine self - assembled monolayer ( SAM ) films on graphene and to model the formation of molecular bilayers and protein complexes on the films .", "entity": [{"entity": "alkylamine", "entity_type": "Chemical", "pos": [118, 128]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [173, 181]}], "task": "NER"}
{"text": "Routes toward the development and exploitation of functionalized graphene structures are detailed here , and we show that the SAM architecture can be tailored for use in emerging applications ( e . g . , electrically stimulated nerve fiber growth via the targeted binding of specific cell surface peptide sequences on the functionalized graphene scaffold ) .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [65, 73]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [337, 345]}], "task": "NER"}
{"text": "The simulations quantify the changes in film physisorption on graphene and the alkyl chain packing efficiency as the film surface is made more polar by changing the terminal groups from methyl ( - CH ( 3 ) ) to amine ( - NH ( 2 ) ) to hydroxyl ( - OH ) .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [79, 84]}, {"entity": "methyl", "entity_type": "Chemical", "pos": [186, 192]}, {"entity": "CH ( 3 )", "entity_type": "Chemical", "pos": [197, 205]}, {"entity": "amine", "entity_type": "Chemical", "pos": [211, 216]}, {"entity": "NH ( 2 )", "entity_type": "Chemical", "pos": [221, 229]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [235, 243]}, {"entity": "OH", "entity_type": "Chemical", "pos": [248, 250]}], "task": "NER"}
{"text": "The mode of molecule packing dictates the orientation and spacing between terminal groups on the surface of the SAM , which determines the way in which successive layers build up on the surface , whether via the formation of bilayers of the molecule or the immobilization of other ( macro ) molecules ( e . g . , proteins ) on the SAM .", "entity": [], "task": "NER"}
{"text": "The simulations show the formation of ordered , stable assemblies of monolayers and bilayers of decylamine - based molecules on graphene .", "entity": [{"entity": "decylamine", "entity_type": "Chemical", "pos": [96, 106]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "These films can serve as protein adsorption platforms , with a hydrophobin protein showing strong and selective adsorption by binding via its hydrophobic patch to methyl - terminated films and binding to amine - terminated films using its more hydrophilic surface regions .", "entity": [{"entity": "methyl", "entity_type": "Chemical", "pos": [163, 169]}, {"entity": "amine", "entity_type": "Chemical", "pos": [204, 209]}], "task": "NER"}
{"text": "Design rules obtained from modeling the atomic - scale structure of the films and interfaces may provide input into experiments for the rational design of assemblies in which the electronic , physicochemical , and mechanical properties of the substrate , film , and protein layer can be tuned to provide the desired functionality .", "entity": [], "task": "NER"}
{"text": "Inelastic X - ray scattering studies of the short - time collective vibrational motions in hydrated lysozyme powders and their possible relation to enzymatic function .", "entity": [], "task": "NER"}
{"text": "High - resolution inelastic X - ray scattering was used to investigate the collective vibrational excitations in hydrated lysozyme powders as a function of hydration level and temperature .", "entity": [], "task": "NER"}
{"text": "It is found that the samples with strong enzymatic function are \" soft \" , in the sense that they exhibit low frequency and large amplitude intraprotein collective vibrational motions on certain length scales .", "entity": [], "task": "NER"}
{"text": "This is not the case for samples with weak or no enzymatic activity .", "entity": [], "task": "NER"}
{"text": "Thus , we identify a possible correlation between the short - time intraprotein collective vibrational motions and the establishment of enzymatic function in hydrated lysozyme powders , and bring new insight to notions of protein \" conformational flexibility \" and \" softness \" in terms of these motions .", "entity": [], "task": "NER"}
{"text": "In vitro evaluation of ( 99m ) Tc - EDDA / tricine - HYNIC - Q - Litorin in gastrin - releasing peptide receptor positive tumor cell lines .", "entity": [{"entity": "( 99m ) Tc - EDDA / tricine - HYNIC - Q - Litorin", "entity_type": "Chemical", "pos": [23, 72]}], "task": "NER"}
{"text": "Abstract Bombesin and its derivatives exhibit a high affinity for gastrin - releasing peptide receptor ( GRPr ) , which is over - expressed in a variety of human cancers ( prostate , pancreatic , lung , etc . ) .", "entity": [{"entity": "Bombesin", "entity_type": "Chemical", "pos": [9, 17]}], "task": "NER"}
{"text": "The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide ( HYNIC ) - Q - Litorin .", "entity": [{"entity": "hydrazinonicotinamide", "entity_type": "Chemical", "pos": [71, 92]}, {"entity": "HYNIC", "entity_type": "Chemical", "pos": [95, 100]}, {"entity": "Litorin", "entity_type": "Chemical", "pos": [109, 116]}], "task": "NER"}
{"text": "( 99m ) Tc labeling was performed by using different co - ligands : tricine and ethylenediamine diacetic acid ( EDDA ) .", "entity": [{"entity": "( 99m ) Tc", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "tricine", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "ethylenediamine diacetic acid", "entity_type": "Chemical", "pos": [80, 109]}, {"entity": "EDDA", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "The in vitro cell uptake of ( 99m ) Tc - EDDA - HYNIC - Q - Litorin and ( 99m ) Tc - tricine - HYNIC - Q - Litorin were evaluated on pancreatic tumor and control cell lines .", "entity": [{"entity": "( 99m ) Tc - EDDA - HYNIC - Q - Litorin", "entity_type": "Chemical", "pos": [28, 67]}, {"entity": "( 99m ) Tc - tricine - HYNIC - Q - Litorin", "entity_type": "Chemical", "pos": [72, 114]}], "task": "NER"}
{"text": "Optimum specific activity and incubation time were determined for all the cell lines .", "entity": [], "task": "NER"}
{"text": "The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line .", "entity": [], "task": "NER"}
{"text": "The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging .", "entity": [], "task": "NER"}
{"text": "Single - walled carbon nanotube surface control of complement recognition and activation .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [16, 22]}], "task": "NER"}
{"text": "Carbon nanotubes ( CNTs ) are receiving considerable attention in site - specific drug and nucleic acid delivery , photodynamic therapy , and photoacoustic molecular imaging .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Despite these advances , nanotubes may activate the complement system ( an integral part of innate immunity ) , which can induce clinically significant anaphylaxis .", "entity": [], "task": "NER"}
{"text": "We demonstrate that single - walled CNTs coated with human serum albumin activate the complement system through C1q - mediated classical and the alternative pathways .", "entity": [], "task": "NER"}
{"text": "Surface coating with methoxypoly ( ethylene glycol ) - based amphiphiles , which confers solubility and prolongs circulation profiles of CNTs , activates the complement system differently , depending on the amphiphile structure .", "entity": [{"entity": "methoxypoly ( ethylene glycol )", "entity_type": "Chemical", "pos": [21, 52]}], "task": "NER"}
{"text": "CNTs with linear poly ( ethylene glycol ) amphiphiles trigger the lectin pathway of the complement through both L - ficolin and mannan - binding lectin recognition .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [17, 41]}], "task": "NER"}
{"text": "The lectin pathway activation , however , did not trigger the amplification loop of the alternative pathway .", "entity": [], "task": "NER"}
{"text": "An amphiphile with branched poly ( ethylene glycol ) architecture also activated the lectin pathway but only through L - ficolin recognition .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [28, 52]}], "task": "NER"}
{"text": "Importantly , this mode of activation neither generated anaphylatoxins nor induced triggering of the effector arm of the complement system .", "entity": [], "task": "NER"}
{"text": "These observations provide a major step toward nanomaterial surface modification with polymers that have the properties to significantly improve innate immunocompatibility by limiting the formation of complement C3 and C5 convertases .", "entity": [], "task": "NER"}
{"text": "Synthesis of novel phosphorylated guanidine derivatives from cyanamide and their anti - inflammatory activity .", "entity": [{"entity": "phosphorylated guanidine", "entity_type": "Chemical", "pos": [19, 43]}, {"entity": "cyanamide", "entity_type": "Chemical", "pos": [61, 70]}], "task": "NER"}
{"text": "A series of novel guanidine derivatives were synthesized in three steps and their anti - inflammatory activities in vitro and in vivo evaluated .", "entity": [{"entity": "guanidine", "entity_type": "Chemical", "pos": [18, 27]}], "task": "NER"}
{"text": "2 - Aminopyridin - 3 - ol ( 1 ) was reacted with thiophosphoryl chloride ( 2 ) to give a monochloride ( 3 ) .", "entity": [{"entity": "2 - Aminopyridin - 3 - ol", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "thiophosphoryl chloride", "entity_type": "Chemical", "pos": [49, 72]}, {"entity": "monochloride", "entity_type": "Chemical", "pos": [89, 101]}], "task": "NER"}
{"text": "It was further reacted with cyanamide to afford the corresponding cyanamine ( 4 ) , which was subsequently reacted with different heterocyclic amines to form the title compounds ( 5a - l ) .", "entity": [{"entity": "cyanamide", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "cyanamine", "entity_type": "Chemical", "pos": [66, 75]}, {"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [130, 149]}], "task": "NER"}
{"text": "The substituent in the guanidine function affected the potency of anti - inflammatory activity .", "entity": [{"entity": "guanidine", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "The compounds having benzothiazole , fluorophenyl , and piperazinyl moieties enhanced the anti - inflammatory activity .", "entity": [{"entity": "benzothiazole", "entity_type": "Chemical", "pos": [21, 34]}, {"entity": "fluorophenyl", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "piperazinyl", "entity_type": "Chemical", "pos": [56, 67]}], "task": "NER"}
{"text": "Discovering some novel 7 - chloroquinolines carrying a biologically active benzenesulfonamide moiety as a new class of anticancer agents .", "entity": [{"entity": "7 - chloroquinolines", "entity_type": "Chemical", "pos": [23, 43]}, {"entity": "benzenesulfonamide", "entity_type": "Chemical", "pos": [75, 93]}], "task": "NER"}
{"text": "Based on the reported anticancer activity of quinolines , a new series of 7 - chloroquinoline derivatives bearing the biologically active benzenesulfonamide moiety 2 - 17 and 19 - 25 were synthesized starting with 4 , 7 - dichloroquinolne 1 .", "entity": [{"entity": "quinolines", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "7 - chloroquinoline", "entity_type": "Chemical", "pos": [74, 93]}, {"entity": "benzenesulfonamide", "entity_type": "Chemical", "pos": [138, 156]}, {"entity": "4 , 7 - dichloroquinolne", "entity_type": "Chemical", "pos": [214, 238]}], "task": "NER"}
{"text": "Compound 17 was the most active compound with IC ( 50 ) value 64 . 41 , 75 . 05 and 30 . 71 micro M compared with Doxorubicin as reference drug with IC ( 50 ) values 82 . 53 , 88 . 32 and 73 . 72 micro M on breast cancer cells , skin cancer cells and neuroblastoma , respectively .", "entity": [{"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "All the synthesized compounds were evaluated for their in vitro anticancer activity on breast cancer cells , skin cancer cells and neuroblastoma cells .", "entity": [], "task": "NER"}
{"text": "Most of the synthesized compounds showed moderate activity .", "entity": [], "task": "NER"}
{"text": "In order to suggest the mechanism of action for their cytotoxic activity , molecular docking for all synthesized compounds was done on the active site of phosphoinositide kinase ( PI3K ) and good results were obtained .", "entity": [{"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [154, 170]}], "task": "NER"}
{"text": "Syntheses of 2 - deoxy - 2 , 3 - didehydro - N - acetylneuraminic acid analogues modified by alpha - acylaminoamido groups at the C - 4 position using isocyanide - based four - component coupling and biological evaluation as inhibitors of human parainfluenza virus type 1 .", "entity": [{"entity": "2 - deoxy - 2 , 3 - didehydro - N - acetylneuraminic acid", "entity_type": "Chemical", "pos": [13, 70]}, {"entity": "alpha - acylaminoamido", "entity_type": "Chemical", "pos": [93, 115]}, {"entity": "isocyanide", "entity_type": "Chemical", "pos": [151, 161]}], "task": "NER"}
{"text": "Novel sialidase inhibitors 11 having an alpha - acylaminoamido group at the C - 4 position of Neu5Ac2en 1 against human parainfluenza virus type 1 ( hPIV - 1 ) were synthesized using one - pot isocyanide - based four - component condensation , and their inhibitory activities against hPIV - 1 sialidase were studied .", "entity": [{"entity": "alpha - acylaminoamido", "entity_type": "Chemical", "pos": [40, 62]}, {"entity": "isocyanide", "entity_type": "Chemical", "pos": [193, 203]}], "task": "NER"}
{"text": "Compound 11b showed inhibitory activity ( IC ( 50 ) = 5 . 1 mM ) against hPIV - 1 sialidase .", "entity": [], "task": "NER"}
{"text": "The degree of inhibition of 11b was much weaker than that of 1 ( IC ( 50 ) = 0 . 3 mM ) .", "entity": [], "task": "NER"}
{"text": "Two new triterpenoid saponins from the root of Platycodon grandiflorum .", "entity": [{"entity": "triterpenoid saponins", "entity_type": "Chemical", "pos": [8, 29]}], "task": "NER"}
{"text": "Two new triterpenoid saponins , named platycodon A ( 3 - O - beta - D - glucopyranosyl - 16 - O - beta - D - glucopyranosyl - 2 beta , 3 beta , 16 beta , 21 beta - tetrahydroxyolean - 12 - en - 28 - oic acid ) and platycodon B ( 3 - O - beta - D - glucopyranosyl - 16 - O - beta - D - xylopyranosyl - 2 beta , 3 beta , 16 beta , 21 beta - tetrahydroxyolean - 12 - en - 28 - oic acid ) were isolated from the roots of Platycodon grandiflorum .", "entity": [{"entity": "triterpenoid saponins", "entity_type": "Chemical", "pos": [8, 29]}, {"entity": "platycodon A", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "3 - O - beta - D - glucopyranosyl - 16 - O - beta - D - glucopyranosyl - 2 beta , 3 beta , 16 beta , 21 beta - tetrahydroxyolean - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [53, 207]}, {"entity": "platycodon B", "entity_type": "Chemical", "pos": [214, 226]}, {"entity": "3 - O - beta - D - glucopyranosyl - 16 - O - beta - D - xylopyranosyl - 2 beta , 3 beta , 16 beta , 21 beta - tetrahydroxyolean - 12 - en - 28 - oic acid", "entity_type": "Chemical", "pos": [229, 382]}], "task": "NER"}
{"text": "The structures of these compounds were elucidated by means of various spectroscopic analyses .", "entity": [], "task": "NER"}
{"text": "Compounds 1 and 2 were tested in HepG - 2 , A549 and DU145 human cancer cell lines and showed remarkable cytotoxic activities against HepG - 2 and A549 cancer cell lines with IC ( 50 ) values ranging from 4 . 9 to 9 . 4 micro M , but they displayed weak cytotoxic activities against DU145 cancer cell line with IC ( 50 ) values greater than 10 micro M .", "entity": [], "task": "NER"}
{"text": "Comparative toxicity of eight metals on freshwater fish .", "entity": [], "task": "NER"}
{"text": "Two freshwater fish , Rasbora sumatrana ( Cyprinidae ) and Poecilia reticulata ( guppy ; Poeciliidae ) , were exposed to a range of eight heavy metals ( copper ( Cu ) , cadmium ( Cd ) , zinc ( Zn ) , lead ( Pb ) , nickel ( Ni ) , iron ( Fe ) , aluminium ( Al ) , and manganese ( Mn ) ) at varied concentrations for 96 h in the laboratory .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [153, 159]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [162, 164]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [169, 176]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [179, 181]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [186, 190]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [193, 195]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [207, 209]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [214, 220]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [223, 225]}, {"entity": "iron", "entity_type": "Chemical", "pos": [230, 234]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [237, 239]}, {"entity": "aluminium", "entity_type": "Chemical", "pos": [244, 253]}, {"entity": "Al", "entity_type": "Chemical", "pos": [256, 258]}, {"entity": "manganese", "entity_type": "Chemical", "pos": [267, 276]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [279, 281]}], "task": "NER"}
{"text": "Mortality was assessed and median lethal concentrations ( LC ( 50 ) ) were calculated .", "entity": [], "task": "NER"}
{"text": "It was observed that the LC ( 50 ) values increased with a decrease in mean exposure times , for all metals and for both fish types .", "entity": [], "task": "NER"}
{"text": "The 96 - h LC ( 50 ) values for Cu , Cd , Zn , Pb , Ni , Fe , Al , and Mn were 0 . 006 , 0 . 10 , 0 . 46 , 0 . 63 , 0 . 83 , 1 . 71 , 1 . 53 , and 5 . 71 mg / L for R . sumatrana and 0 . 038 , 0 . 17 , 1 . 06 , 1 . 99 , 15 . 62 , 1 . 46 , 6 . 76 , and 23 . 91 mg / L for P . reticulata , respectively .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [32, 34]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [37, 39]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [47, 49]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [57, 59]}, {"entity": "Al", "entity_type": "Chemical", "pos": [62, 64]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [71, 73]}], "task": "NER"}
{"text": "The metal toxicity trend for R . sumatrana and P . reticulata from most to least toxic was Cu > Cd > Zn > Pb > Ni > Al > Fe > Mn and Cu > Cd > Zn > Fe > Pb > Al > Ni > Mn , respectively .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [91, 93]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [96, 98]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [101, 103]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [106, 108]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [111, 113]}, {"entity": "Al", "entity_type": "Chemical", "pos": [116, 118]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [121, 123]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [126, 128]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [133, 135]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [138, 140]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [143, 145]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [148, 150]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [153, 155]}, {"entity": "Al", "entity_type": "Chemical", "pos": [158, 160]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [163, 165]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [168, 170]}], "task": "NER"}
{"text": "Results indicated that Cu was the most toxic metal on both fish , and R . sumatrana was more sensitive than P . reticulata to all the eight metals .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [23, 25]}], "task": "NER"}
{"text": "Vertical flow immunoassay ( VFA ) biosensor for a rapid one - step immunoassay .", "entity": [], "task": "NER"}
{"text": "A highly rapid , one - step immunoassay of high sensitivity C - reactive protein ( hsCRP ) using a biosensor with a vertical flow immunoassay ( VFA ) was developed .", "entity": [], "task": "NER"}
{"text": "The VFA biosensor was primarily composed of a sample pad , conjugate pad , FTH film and nitrocellulose ( NC ) membrane , which were all vertically stacked upon one another .", "entity": [], "task": "NER"}
{"text": "Anti - hsCRP and secondary antibodies were consecutively immobilized on the NC membrane at the position below the holes .", "entity": [], "task": "NER"}
{"text": "Gold nanoparticles ( AuNPs ) conjugated with another anti - hsCRP antibody were encapsulated in the conjugation pad .", "entity": [], "task": "NER"}
{"text": "Various assay conditions , including the size of the hole and the sample volume , were optimized .", "entity": [], "task": "NER"}
{"text": "Under optimized conditions , hsCRP concentrations from 0 . 01 to 10 mu g mL ( - 1 ) were detected within 2 min .", "entity": [], "task": "NER"}
{"text": "In comparison with a lateral flow assay ( LFA ) system , the VFA sensor showed a gradual increase of signal in a concentration - dependent manner without a hook effect in the tested range .", "entity": [], "task": "NER"}
{"text": "Synthesis and characterization of an MRI Gd - based probe designed to target the translocator protein .", "entity": [{"entity": "Gd", "entity_type": "Chemical", "pos": [41, 43]}], "task": "NER"}
{"text": "DPA - 713 is the lead compound of a recently reported pyrazolo [ 1 , 5 - a ] pyrimidineacetamide series , targeting the translocator protein ( TSPO 18 kDa ) , and as such , this structure , as well as closely related derivatives , have been already successfully used as positron emission tomography radioligands .", "entity": [{"entity": "DPA - 713", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "pyrazolo [ 1 , 5 - a ] pyrimidineacetamide", "entity_type": "Chemical", "pos": [54, 96]}], "task": "NER"}
{"text": "On the basis of the pharmacological core of this ligands series , a new magnetic resonance imaging probe , coded DPA - C ( 6 ) - ( Gd ) DOTAMA was designed and successfully synthesized in six steps and 13 % overall yield from DPA - 713 .", "entity": [{"entity": "DPA - C ( 6 ) - ( Gd ) DOTAMA", "entity_type": "Chemical", "pos": [113, 142]}, {"entity": "DPA - 713", "entity_type": "Chemical", "pos": [226, 235]}], "task": "NER"}
{"text": "The Gd - DOTA monoamide cage ( DOTA = 1 , 4 , 7 , 10 - tetraazacyclododecane - 1 , 4 , 7 , 10 - tetraacetic acid ) represents the magnetic resonance imaging reporter , which is spaced from the phenylpyrazolo [ 1 , 5 - a ] pyrimidineacetamide moiety ( DPA - 713 motif ) by a six carbon - atom chain .", "entity": [{"entity": "Gd - DOTA monoamide", "entity_type": "Chemical", "pos": [4, 23]}, {"entity": "DOTA", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "1 , 4 , 7 , 10 - tetraazacyclododecane - 1 , 4 , 7 , 10 - tetraacetic acid", "entity_type": "Chemical", "pos": [38, 112]}, {"entity": "phenylpyrazolo [ 1 , 5 - a ] pyrimidineacetamide", "entity_type": "Chemical", "pos": [193, 241]}, {"entity": "DPA - 713", "entity_type": "Chemical", "pos": [251, 260]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [278, 284]}], "task": "NER"}
{"text": "DPA - C ( 6 ) - ( Gd ) DOTAMA relaxometric characterization showed the typical behavior of a small - sized molecule ( relaxivity value : 6 . 02 mM ( - 1 ) s ( - 1 ) at 20 MHz ) .", "entity": [{"entity": "DPA - C ( 6 ) - ( Gd ) DOTAMA", "entity_type": "Chemical", "pos": [0, 29]}], "task": "NER"}
{"text": "The good hydrophilicity of the metal chelate makes DPA - C ( 6 ) - ( Gd ) DOTAMA soluble in water , affecting thus its biodistribution with respect to the parent lipophilic DPA - 713 molecule .", "entity": [{"entity": "DPA - C ( 6 ) - ( Gd ) DOTAMA", "entity_type": "Chemical", "pos": [51, 80]}, {"entity": "DPA - 713", "entity_type": "Chemical", "pos": [173, 182]}], "task": "NER"}
{"text": "For this reason , it was deemed of interest to load the probe to a large carrier in order to increase its residence lifetime in blood .", "entity": [], "task": "NER"}
{"text": "Whereas DPA - C ( 6 ) - ( Gd ) DOTAMA binds to serum albumin with a low affinity constant , it can be entrapped into liposomes ( both in the membrane and in the inner aqueous cavity ) .", "entity": [{"entity": "DPA - C ( 6 ) - ( Gd ) DOTAMA", "entity_type": "Chemical", "pos": [8, 37]}], "task": "NER"}
{"text": "The stability of the supramolecular adduct formed by the Gd - complex and liposomes was assessed by a competition test with albumin .", "entity": [{"entity": "Gd", "entity_type": "Chemical", "pos": [57, 59]}], "task": "NER"}
{"text": "2 - Carbaborane - 3 - phenyl - 1H - indoles - - synthesis via McMurry reaction and cyclooxygenase ( COX ) inhibition activity .", "entity": [{"entity": "2 - Carbaborane - 3 - phenyl - 1H - indoles", "entity_type": "Chemical", "pos": [0, 43]}], "task": "NER"}
{"text": "Cyclooxygenase - 2 ( COX - 2 ) inhibitors have been the focus of medicinal chemistry efforts for years , and many compounds that exhibit high selectivity and affinity have been developed .", "entity": [], "task": "NER"}
{"text": "As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development , this paper presents the synthesis of carbaboranyl derivatives of COX - 2 - selective 2 , 3 - disubstituted indoles .", "entity": [{"entity": "carbaboranes", "entity_type": "Chemical", "pos": [3, 15]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [56, 62]}, {"entity": "carbaboranyl", "entity_type": "Chemical", "pos": [131, 143]}, {"entity": "2 , 3 - disubstituted indoles", "entity_type": "Chemical", "pos": [179, 208]}], "task": "NER"}
{"text": "Despite the lability of carbaboranes under reducing conditions , 2 - carbaborane - 3 - phenyl - 1H - indoles could be synthesized by McMurry cyclization of the corresponding amides .", "entity": [{"entity": "carbaboranes", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "2 - carbaborane - 3 - phenyl - 1H - indoles", "entity_type": "Chemical", "pos": [65, 108]}, {"entity": "amides", "entity_type": "Chemical", "pos": [174, 180]}], "task": "NER"}
{"text": "Whereas the meta - carbaboranyl - substituted derivatives lacked COX inhibitory activity , an ortho - carbaboranyl analogue was active , but showed a selectivity shift toward COX - 1 .", "entity": [{"entity": "meta - carbaboranyl", "entity_type": "Chemical", "pos": [12, 31]}, {"entity": "ortho - carbaboranyl", "entity_type": "Chemical", "pos": [94, 114]}], "task": "NER"}
{"text": "Unwinding of primer - templates by archaeal family - B DNA polymerases in response to template - strand uracil .", "entity": [{"entity": "uracil", "entity_type": "Chemical", "pos": [104, 110]}], "task": "NER"}
{"text": "Archaeal family - B DNA polymerases bind tightly to deaminated bases and stall replication on encountering uracil in template strands , four bases ahead of the primer - template junction .", "entity": [{"entity": "uracil", "entity_type": "Chemical", "pos": [107, 113]}], "task": "NER"}
{"text": "Should the polymerase progress further towards the uracil , for example , to position uracil only two bases in front of the junction , 3 ' - 5 ' proof - reading exonuclease activity becomes stimulated , trimming the primer and re - setting uracil to the + 4 position .", "entity": [{"entity": "uracil", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "uracil", "entity_type": "Chemical", "pos": [86, 92]}, {"entity": "uracil", "entity_type": "Chemical", "pos": [240, 246]}], "task": "NER"}
{"text": "Uracil sensing prevents copying of the deaminated base and permanent mutation in 50 % of the progeny .", "entity": [{"entity": "Uracil", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "This publication uses both steady - state and time - resolved 2 - aminopurine fluorescence to show pronounced unwinding of primer - templates with Pyrococcus furiosus ( Pfu ) polymerase - DNA complexes containing uracil at + 2 ; much less strand separation is seen with uracil at + 4 .", "entity": [{"entity": "2 - aminopurine", "entity_type": "Chemical", "pos": [62, 77]}, {"entity": "uracil", "entity_type": "Chemical", "pos": [213, 219]}, {"entity": "uracil", "entity_type": "Chemical", "pos": [270, 276]}], "task": "NER"}
{"text": "DNA unwinding has long been recognized as necessary for proof - reading exonuclease activity .", "entity": [], "task": "NER"}
{"text": "The roles of M247 and Y261 , amino acids suggested by structural studies to play a role in primer - template unwinding , have been probed .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [29, 40]}], "task": "NER"}
{"text": "M247 appears to be unimportant , but 2 - aminopurine fluorescence measurements show that Y261 plays a role in primer - template strand separation .", "entity": [{"entity": "2 - aminopurine", "entity_type": "Chemical", "pos": [37, 52]}], "task": "NER"}
{"text": "Y261 is also required for full exonuclease activity and contributes to the fidelity of the polymerase .", "entity": [], "task": "NER"}
{"text": "An evolutionarily conserved signaling mechanism mediates far - red light responses in land plants .", "entity": [], "task": "NER"}
{"text": "Phytochromes are plant photoreceptors important for development and adaptation to the environment .", "entity": [], "task": "NER"}
{"text": "Phytochrome A ( PHYA ) is essential for the far - red ( FR ) high - irradiance responses ( HIRs ) , which are of particular ecological relevance as they enable plants to establish under shade conditions .", "entity": [], "task": "NER"}
{"text": "PHYA and HIRs have been considered unique to seed plants because the divergence of seed plants and cryptogams ( e . g . , ferns and mosses ) preceded the evolution of PHYA .", "entity": [], "task": "NER"}
{"text": "Seed plant phytochromes translocate into the nucleus and regulate gene expression .", "entity": [], "task": "NER"}
{"text": "By contrast , there has been little evidence of a nuclear localization and function of cryptogam phytochromes .", "entity": [], "task": "NER"}
{"text": "Here , we identified responses to FR light in cryptogams , which are highly reminiscent of PHYA signaling in seed plants .", "entity": [], "task": "NER"}
{"text": "In the moss Physcomitrella patens and the fern Adiantum capillus - veneris , phytochromes accumulate in the nucleus in response to light .", "entity": [], "task": "NER"}
{"text": "Although P . patens phytochromes evolved independently of PHYA , we have found that one clade of P . patens phytochromes exhibits the molecular properties of PHYA .", "entity": [], "task": "NER"}
{"text": "We suggest that HIR - like responses had evolved in the last common ancestor of modern seed plants and cryptogams and that HIR signaling is more ancient than PHYA .", "entity": [], "task": "NER"}
{"text": "Thus , other phytochromes in seed plants may have lost the capacity to mediate HIRs during evolution , rather than that PHYA acquired it .", "entity": [], "task": "NER"}
{"text": "Current progresses of novel natural products and their derivatives / analogs as anti - Alzheimer candidates : an update .", "entity": [], "task": "NER"}
{"text": "Alzheimer ' s disease ( AD ) is one of the most threatening diseases affecting the aged with high incidence .", "entity": [], "task": "NER"}
{"text": "Though AD has been defined for more than 100 years , it is still incurable .", "entity": [], "task": "NER"}
{"text": "The drugs clinically used for the treatment of this disease , such as acetylcholinesterase inhibitors ( AChEIs ) and N - methyl - D - aspartate ( NMDA ) receptor antagonist , can only provide a limited therapeutic effect .", "entity": [{"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [117, 143]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [146, 150]}], "task": "NER"}
{"text": "The need of effective drugs has stimulated the search for new compounds with potential clinical utility .", "entity": [], "task": "NER"}
{"text": "Natural products are rich and unexplored sources for discovering novel leading compounds .", "entity": [], "task": "NER"}
{"text": "Currently , a great number of natural products have been found possessing anti - AD property counteracting different etiological factors of AD .", "entity": [], "task": "NER"}
{"text": "This review will give an update demonstration on the novel anti - AD natural products and their derivatives / analogues , which have been divided into five subgroups according to their different action mechanisms : AChEIs , antioxidants , neuroprotective agents , monoamine oxidase ( MAO ) inhibitors , and tau hyperphosphorylation inhibitors .", "entity": [{"entity": "monoamine", "entity_type": "Chemical", "pos": [264, 273]}], "task": "NER"}
{"text": "We put special emphasis on the findings in the past 5 years .", "entity": [], "task": "NER"}
{"text": "Besides , the drug design strategy as well as the structure - activity relationship of the relevant compounds is also discussed when it is possible .", "entity": [], "task": "NER"}
{"text": "Comparison of antiproliferative effects of metformine and progesterone on estrogen - induced endometrial hyperplasia in rats .", "entity": [{"entity": "metformine", "entity_type": "Chemical", "pos": [43, 53]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [58, 70]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "Metformin has been shown to inhibit the growth of endometriotic implants , and reverse endometrial hyperplasia when combined with oral contraceptive in a case report .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The aim of this study is to compare the antiproliferative effects of medroxyprogesterone acetate ( MPA ) , and metformin in oopherectomized rat endometrium .", "entity": [{"entity": "medroxyprogesterone acetate", "entity_type": "Chemical", "pos": [69, 96]}, {"entity": "MPA", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "metformin", "entity_type": "Chemical", "pos": [111, 120]}], "task": "NER"}
{"text": "Forty oopherectomized Wistar - Albino rats were used , and assigned to receive saline , 17 beta Estradiol hemihydrate ( 4 mg / kg ) , 17 beta Estradiol hemihydrate ( 4 mg / kg ) and metformin ( 50 mg / kg ) , 17 beta Estradiol hemihydrate ( 4 mg / kg ) and MPA ( 1 mg / day ) for 14 days .", "entity": [{"entity": "17 beta Estradiol hemihydrate", "entity_type": "Chemical", "pos": [88, 117]}, {"entity": "17 beta Estradiol hemihydrate", "entity_type": "Chemical", "pos": [134, 163]}, {"entity": "metformin", "entity_type": "Chemical", "pos": [182, 191]}, {"entity": "17 beta Estradiol hemihydrate", "entity_type": "Chemical", "pos": [209, 238]}, {"entity": "MPA", "entity_type": "Chemical", "pos": [257, 260]}], "task": "NER"}
{"text": "Histological markers of uterotrophy , including endometrial height , luminal ephitelial cell height and density of endometrial glands on hysterectomy speciments were quantified for each specimen .", "entity": [], "task": "NER"}
{"text": "Rats treated with estradiol had significantly increased in endometrial height , endomerial luminal epithelial height and endometrial gland densitiy than the other groups .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [18, 27]}], "task": "NER"}
{"text": "Metformin and MPA acetate significantly reduced all parameters indicating endometrial hyperplasia , and uterotrophy with respect to the control group .", "entity": [{"entity": "Metformin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "MPA acetate", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Antiproliferative effects of metformin , and MPA was found to be comparable for all three parameters .", "entity": [{"entity": "metformin", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "MPA", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "In conclusion , metformin attenuates estrogen - induced endometrial hyperplasia in ooferectomized rats to the same degree as progesterone .", "entity": [{"entity": "metformin", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [125, 137]}], "task": "NER"}
{"text": "Photophysical and electrochemical investigations of the fluorescent probe , 4 , 4 ' - bis ( 2 - benzoxazolyl ) stilbene .", "entity": [{"entity": "4 , 4 ' - bis ( 2 - benzoxazolyl ) stilbene", "entity_type": "Chemical", "pos": [76, 119]}], "task": "NER"}
{"text": "In solution , 4 , 4 ' - bis ( 2 - benzoxazolyl ) stilbene ( BBS ) was found to exhibit consistently high absolute fluorescence quantum yields ( Phi ( fl ) >= 0 . 88 ) and a monoexponential lifetime , both independent of BBS concentration .", "entity": [{"entity": "4 , 4 ' - bis ( 2 - benzoxazolyl ) stilbene", "entity_type": "Chemical", "pos": [14, 57]}, {"entity": "BBS", "entity_type": "Chemical", "pos": [60, 63]}, {"entity": "BBS", "entity_type": "Chemical", "pos": [220, 223]}], "task": "NER"}
{"text": "The BBS steady - state and time - resolved photophysics were investigated by different techniques to understand the various deactivation pathways .", "entity": [{"entity": "BBS", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "Nonradiative deactivation of BBS singlet excited state by intersystem crossing was found to be negligible .", "entity": [{"entity": "BBS", "entity_type": "Chemical", "pos": [29, 32]}], "task": "NER"}
{"text": "Other than fluorescence , the excited state of BBS was found to be deactivated by trans - cis photoisomerization .", "entity": [{"entity": "BBS", "entity_type": "Chemical", "pos": [47, 50]}], "task": "NER"}
{"text": "At low concentrations ( =~ 5 mu g / mL ) , UV spectroscopy and laser flash photolysis showed concordant results that the photoinduced cis isomer gradually replaced the original absorption spectrum of the pure trans isomer .", "entity": [], "task": "NER"}
{"text": "However , at high concentrations ( =~ 0 . 2 mg / mL ) , ( 1 ) H NMR and DOSY measurements confirmed that irradiating BBS at 350 nm induced a conversion from the trans - BBS into its cis isomer by photoisomerization .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "BBS", "entity_type": "Chemical", "pos": [117, 120]}, {"entity": "trans - BBS", "entity_type": "Chemical", "pos": [161, 172]}], "task": "NER"}
{"text": "It was further found that the stilbene moiety of both isomers was photocleaved .", "entity": [{"entity": "stilbene", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "The resulting photoproduct was an aldehyde that was oxidized under ambient conditions to its corresponding carboxylic acid , i . e . , 4 - ( 1 , 3 - benzoxazol - 2 - yl ) benzoic acid .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [34, 42]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [107, 122]}, {"entity": "4 - ( 1 , 3 - benzoxazol - 2 - yl ) benzoic acid", "entity_type": "Chemical", "pos": [135, 183]}], "task": "NER"}
{"text": "The structure of the photoproduct was unequivocally confirmed by X - ray diffraction .", "entity": [], "task": "NER"}
{"text": "Spectroscopic investigation of BBS showed a limited photoisomerization after irradiation at 350 nm of a trans solution .", "entity": [{"entity": "BBS", "entity_type": "Chemical", "pos": [31, 34]}], "task": "NER"}
{"text": "The BBS electrochemistry showed irreversible oxidation , resulting in an unstable and highly reactive radical cation .", "entity": [{"entity": "BBS", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "Similarly , the cathodic process was also found to be irreversible , giving rise to a radical anion and showing its n - doping character .", "entity": [], "task": "NER"}
{"text": "Validating a faster method for reconstitution of Crotalidae Polyvalent Immune Fab ( ovine ) .", "entity": [], "task": "NER"}
{"text": "BACKGROUND : Reconstitution of CroFab ( (R) ) ( Crotalidae Polyvalent Immune Fab [ ovine ] ) lyophilized drug product was previously performed using 10 mL sterile water for injection followed by up to 36 min of gentle swirling of the vial .", "entity": [], "task": "NER"}
{"text": "CroFab has been clinically demonstrated to be most effective when administered within 6 h of snake envenomation , and improved clinical outcomes are correlated with quicker timing of administration .", "entity": [], "task": "NER"}
{"text": "An alternate reconstitution method was devised , using 18 mL 0 . 9 % saline with manual inversion , with the goal of shortening reconstitution time while maintaining a high quality , efficacious product .", "entity": [], "task": "NER"}
{"text": "METHODS : An analytical study was designed to compare the physicochemical properties of 3 separate batches of CroFab when reconstituted using the standard procedure ( 10 mL WFI with gentle swirling ) and a modified rapid procedure using 18 mL 0 . 9 % saline and manual inversion .", "entity": [], "task": "NER"}
{"text": "The physical and chemical characteristics of the same 3 batches were assessed using various analytic methodologies associated with routine quality control release testing .", "entity": [], "task": "NER"}
{"text": "In addition further analytical methodologies were applied in order to elucidate possible structural changes that may be induced by the changed reconstitution procedure .", "entity": [], "task": "NER"}
{"text": "RESULTS : Batches A , B , and C required mean reconstitution times of 25 min 51 s using the label method and 3 min 07 s ( a 88 . 0 % mean decrease ) using the modified method .", "entity": [], "task": "NER"}
{"text": "Physicochemical characteristics ( color and clarity , pH , purity , protein content , potency ) were found to be highly comparable .", "entity": [], "task": "NER"}
{"text": "Characterization assays ( dynamic light scattering , analytical ultracentrifugation , LC - MS , SDS - PAGE and circular dichroism spectroscopy were also all found to be comparable between methods .", "entity": [], "task": "NER"}
{"text": "DISCUSSION : When comparing CroFab batches that were reconstituted using the labeled and modified methods , the physicochemical and biological ( potency ) characteristics of CroFab were not significantly changed when challenged by the various standard analytical methodologies applied in routine quality control analysis .", "entity": [], "task": "NER"}
{"text": "Additionally , no changes in the CroFab molecule regarding degradation , aggregation , purity , structure , or mass were observed .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : The analyses performed validated the use of the more rapid reconstitution method using 18 mL 0 . 9 % saline in order to allow a significantly reduced time to administration of CroFab to patients in need .", "entity": [], "task": "NER"}
{"text": "Neuroecology : a fly ' s bug detector .", "entity": [], "task": "NER"}
{"text": "Drosophila avoid food contaminated by pathogenic bacteria and fungi using an olfactory pathway that is exquisitely tuned to a single microbial odour .", "entity": [], "task": "NER"}
{"text": "Synthesis and dual biological effects of hydroxycinnamoyl phenylalanyl / prolyl hydroxamic acid derivatives as tyrosinase inhibitor and antioxidant .", "entity": [{"entity": "hydroxycinnamoyl phenylalanyl", "entity_type": "Chemical", "pos": [41, 70]}, {"entity": "prolyl hydroxamic acid", "entity_type": "Chemical", "pos": [73, 95]}], "task": "NER"}
{"text": "We previously reported that caffeoyl - amino acidyl - hydroxamic acid ( CA - Xaa - NHOH ) acted as both a good antioxidant and tyrosinase inhibitor , in particular when caffeic acid was conjugated with proline or amino acids having aromatic ring like phenylalanine .", "entity": [{"entity": "caffeoyl - amino acidyl - hydroxamic acid", "entity_type": "Chemical", "pos": [28, 69]}, {"entity": "CA - Xaa - NHOH", "entity_type": "Chemical", "pos": [72, 87]}, {"entity": "caffeic acid", "entity_type": "Chemical", "pos": [169, 181]}, {"entity": "proline", "entity_type": "Chemical", "pos": [202, 209]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [213, 224]}, {"entity": "phenylalanine", "entity_type": "Chemical", "pos": [251, 264]}], "task": "NER"}
{"text": "Here , various hydroxycinnamic acid ( HCA ) derivatives were further conjugated with phenylalanyl hydroxamic acid and prolyl hydroxamic acid ( HCA - Phe - NHOH and HCA - Pro - NHOH ) to study the structure and activity relationship as both antioxidants and tyrosinase inhibitors .", "entity": [{"entity": "hydroxycinnamic acid", "entity_type": "Chemical", "pos": [15, 35]}, {"entity": "HCA", "entity_type": "Chemical", "pos": [38, 41]}, {"entity": "phenylalanyl hydroxamic acid", "entity_type": "Chemical", "pos": [85, 113]}, {"entity": "prolyl hydroxamic acid", "entity_type": "Chemical", "pos": [118, 140]}, {"entity": "HCA - Phe - NHOH", "entity_type": "Chemical", "pos": [143, 159]}, {"entity": "HCA - Pro - NHOH", "entity_type": "Chemical", "pos": [164, 180]}], "task": "NER"}
{"text": "When their biological activities were evaluated , all HCA - Phe - NHOH and HCA - Pro - NHOH exhibited enhanced antioxidant activity compared to HCA alone .", "entity": [{"entity": "HCA - Phe - NHOH", "entity_type": "Chemical", "pos": [54, 70]}, {"entity": "HCA - Pro - NHOH", "entity_type": "Chemical", "pos": [75, 91]}, {"entity": "HCA", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "Moreover , derivatives of caffeic acid , ferulic acid , and sinapic acid inhibited lipid peroxidation more efficiently than vitamin E analogue ( Trolox ) .", "entity": [{"entity": "caffeic acid", "entity_type": "Chemical", "pos": [26, 38]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "sinapic acid", "entity_type": "Chemical", "pos": [60, 72]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [124, 133]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [145, 151]}], "task": "NER"}
{"text": "In addition , derivatives of caffeic acid and sinapic acid efficiently inhibited tyrosinase activity and reduced melanin content in melanocytes Mel - Ab cell .", "entity": [{"entity": "caffeic acid", "entity_type": "Chemical", "pos": [29, 41]}, {"entity": "sinapic acid", "entity_type": "Chemical", "pos": [46, 58]}], "task": "NER"}
{"text": "Discovery of a small - molecule antiviral targeting the HIV - 1 matrix protein .", "entity": [], "task": "NER"}
{"text": "Due to the emergence of drug - resistant strains and the cumulative toxicities associated with current therapies , demand remains for new inhibitors of HIV - 1 replication .", "entity": [], "task": "NER"}
{"text": "The HIV - 1 matrix ( MA ) protein is an essential viral component with established roles in the assembly of the virus .", "entity": [], "task": "NER"}
{"text": "Using virtual and surface plasmon resonance ( SPR ) - based screening , we describe the identification of the first small molecule to bind to the HIV - 1 MA protein and to possess broad range anti - HIV properties .", "entity": [], "task": "NER"}
{"text": "Two distinct mechanisms of Topoisomerase 1 - dependent mutagenesis in yeast .", "entity": [], "task": "NER"}
{"text": "Topoisomerase 1 ( Top1 ) resolves transcription - associated supercoils by generating transient single - strand breaks in DNA .", "entity": [], "task": "NER"}
{"text": "Top1 activity in yeast is a major source of transcription - associated mutagenesis , generating a distinctive mutation signature characterized by deletions in short , tandem repeats .", "entity": [], "task": "NER"}
{"text": "A similar signature is associated with the persistence of ribonucleoside monophosphates ( rNMPs ) in DNA , and it also depends on Top1 activity .", "entity": [{"entity": "ribonucleoside monophosphates", "entity_type": "Chemical", "pos": [58, 87]}, {"entity": "rNMPs", "entity_type": "Chemical", "pos": [90, 95]}], "task": "NER"}
{"text": "There is only partial overlap , however , between Top1 - dependent deletion hotspots identified in highly transcribed DNA and those associated with rNMPs , suggesting the existence of both rNMP - dependent and rNMP - independent events .", "entity": [{"entity": "rNMPs", "entity_type": "Chemical", "pos": [148, 153]}, {"entity": "rNMP", "entity_type": "Chemical", "pos": [189, 193]}, {"entity": "rNMP", "entity_type": "Chemical", "pos": [210, 214]}], "task": "NER"}
{"text": "Here , we present genetic studies confirming that there are two distinct types of hotspots .", "entity": [], "task": "NER"}
{"text": "Data suggest a novel model in which rNMP - dependent hotspots are generated by sequential Top1 reactions and are consistent with rNMP - independent hotspots reflecting processing of a trapped Top1 cleavage complex .", "entity": [{"entity": "rNMP", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "rNMP", "entity_type": "Chemical", "pos": [129, 133]}], "task": "NER"}
{"text": "The role of individual gastric emptying of pellets in the prediction of diclofenac in vivo dissolution .", "entity": [{"entity": "diclofenac", "entity_type": "Chemical", "pos": [72, 82]}], "task": "NER"}
{"text": "The objective of the present study was to check for the possibility to successfully predict individual in vivo dissolution / absorption profiles resulting from fasted administration of a diclofenac extended release pellet formulation .", "entity": [{"entity": "diclofenac", "entity_type": "Chemical", "pos": [187, 197]}], "task": "NER"}
{"text": "For this purpose dissolution profiles were generated with different dissolution setups using a set of media reflecting pH - conditions in the different segments of the gastrointestinal tract .", "entity": [], "task": "NER"}
{"text": "Since gastric emptying of pellets seemed to be a critical factor for in vivo drug release , a set of different gastric residence times was screened in in vitro studies .", "entity": [], "task": "NER"}
{"text": "Subsequently , in vitro release profiles were first directly compared with the individual in vivo absorption profiles and in a second step a mathematical model , which had been developed in a previous study , was applied to calculate predicted individual in vivo release profiles based on in vitro release profiles and individual gastric emptying .", "entity": [], "task": "NER"}
{"text": "The comparison of predicted individual in vivo release profiles and individual in vivo absorption profiles showed a high degree of similarity , thus confirming the suitability of a set of different gastric residence times used in in vitro drug release testing .", "entity": [], "task": "NER"}
{"text": "Additionally , obtained results indicated that a substantial part of variability of diclofenac absorption profiles can be explained by the variability of pellet gastric emptying kinetics .", "entity": [{"entity": "diclofenac", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "The colon carcinogen 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine ( PhIP ) is actively secreted in the distal colon of the rat : an integrated view on the role of PhIP transport and metabolism in PhIP - induced colon carcinogenesis .", "entity": [{"entity": "2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine", "entity_type": "Chemical", "pos": [21, 86]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [89, 93]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [184, 188]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [217, 221]}], "task": "NER"}
{"text": "Epidemiological studies show that a positive correlation exists between the consumption of strongly heated meat and fish and the development of colorectal tumours .", "entity": [], "task": "NER"}
{"text": "In this context , it has been postulated that the uptake of toxic substances formed during meat and fish processing such as heterocyclic aromatic amines ( HCAs ) may be causally related to colon carcinogenesis .", "entity": [{"entity": "heterocyclic aromatic amines", "entity_type": "Chemical", "pos": [124, 152]}, {"entity": "HCAs", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "In a previous study , we have shown that 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine ( PhIP ) , the most abundantly formed HCA in the above - mentioned food items , is mainly absorbed in the small intestine ( i . e . proximal jejunum ) of the rat .", "entity": [{"entity": "2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine", "entity_type": "Chemical", "pos": [41, 106]}, {"entity": "PhIP", "entity_type": "Chemical", "pos": [109, 113]}, {"entity": "HCA", "entity_type": "Chemical", "pos": [145, 148]}], "task": "NER"}
{"text": "In the present study , we analysed whether PhIP can actively be secreted by enterocytes in the rat proximal jejunum and distal colon .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [43, 47]}], "task": "NER"}
{"text": "Unidirectional PhIP flux rates from the mucosal - to - the serosal compartment ( J ms ) and in the opposite direction ( J sm ) were examined in Ussing chambers with ( 14 ) C - PhIP as radiotracer and in the absence of electrochemical gradients .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "( 14 ) C - PhIP", "entity_type": "Chemical", "pos": [165, 180]}], "task": "NER"}
{"text": "Under these experimental conditions , significant negative net flux rates ( J net = J ms - J sm ) can only be explained by an active secretion of PhIP into the luminal compartment , and such an effect was observed in the rat distal colon , but not in the proximal jejunum .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [146, 150]}], "task": "NER"}
{"text": "Moreover , the data obtained suggest that the breast cancer resistance protein , the multidrug resistance protein 4 and P - glycoprotein are not involved in the active secretion of PhIP in the rat distal colon .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [181, 185]}], "task": "NER"}
{"text": "The potential role of PhIP transport in colon carcinogenesis is discussed .", "entity": [{"entity": "PhIP", "entity_type": "Chemical", "pos": [22, 26]}], "task": "NER"}
{"text": "Warfarin dose prediction in children using pharmacometric bridging - comparison with published pharmacogenetic dosing algorithms .", "entity": [{"entity": "Warfarin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "PURPOSE : Numerous studies have investigated causes of warfarin dose variability in adults , whereas studies in children are limited both in numbers and size .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "Mechanism - based population modelling provides an opportunity to condense and propagate prior knowledge from one population to another .", "entity": [], "task": "NER"}
{"text": "The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children , and to compare accuracy in dose prediction relative to published warfarin algorithms for children .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [113, 121]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [207, 215]}], "task": "NER"}
{"text": "METHOD : An adult population pharmacokinetic / pharmacodynamic ( PK / PD ) model for warfarin , with CYP2C9 and VKORC1 genotype , age and target international normalized ratio ( INR ) as dose predictors , was bridged to children using allometric scaling methods .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [85, 93]}], "task": "NER"}
{"text": "Its predictive properties were evaluated in an external data set of children 0 - 18 years old , including comparison of dose prediction accuracy with three pharmacogenetics - based algorithms for children .", "entity": [], "task": "NER"}
{"text": "RESULTS : Overall , the bridged model predicted INR response well in 64 warfarin - treated Swedish children ( median age 4 . 3 years ) , but with a tendency to overpredict INR in children <= 2 years old .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "The bridged model predicted 20 of 49 children ( 41 % ) within +/- 20 % of actual maintenance dose ( median age 7 . 2 years ) .", "entity": [], "task": "NER"}
{"text": "In comparison , the published dosing algorithms predicted 33 - 41 % of the children within +/- 20 % of actual dose .", "entity": [], "task": "NER"}
{"text": "Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within +/- 20 % of actual dose to 70 % .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : A mechanism - based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "p300 - mediated acetylation of TRF2 is required for maintaining functional telomeres .", "entity": [], "task": "NER"}
{"text": "The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure .", "entity": [], "task": "NER"}
{"text": "Post - translational modifications of TRF2 such as phosphorylation , ubiquitination , SUMOylation , methylation and poly ( ADP - ribosyl ) ation have been shown to play important roles in telomere function .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "Here we show that TRF2 specifically interacts with the histone acetyltransferase p300 , and that p300 acetylates the lysine residue at position 293 of TRF2 .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [117, 123]}], "task": "NER"}
{"text": "We also report that p300 - mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin - dependent proteolysis and is required for efficient telomere binding of TRF2 .", "entity": [], "task": "NER"}
{"text": "Furthermore , overexpression of the acetylation - deficient mutant , K293R , induces DNA - damage response foci at telomeres , thereby leading to induction of impaired cell growth , cellular senescence and altered cell cycle distribution .", "entity": [], "task": "NER"}
{"text": "A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends , suggesting an aberrant telomere structure .", "entity": [], "task": "NER"}
{"text": "These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere - associated DNA - damage response , thus providing a new route for modulating telomere protection function .", "entity": [], "task": "NER"}
{"text": "Development and characterization of new peptidomimetic inhibitors of the West Nile virus NS2B - NS3 protease .", "entity": [], "task": "NER"}
{"text": "A series of new substrate analogue inhibitors of the WNV NS2B - NS3 protease containing decarboxylated arginine mimetics at the P1 position was developed .", "entity": [{"entity": "decarboxylated arginine", "entity_type": "Chemical", "pos": [88, 111]}], "task": "NER"}
{"text": "Among the various analogues , trans - ( 4 - guanidino ) cyclohexylmethylamide ( GCMA ) was identified as the most suitable P1 residue .", "entity": [{"entity": "trans - ( 4 - guanidino ) cyclohexylmethylamide", "entity_type": "Chemical", "pos": [30, 77]}, {"entity": "GCMA", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "In combination with dichloro - substituted phenylacetyl groups at the P4 position , three inhibitors with inhibition constants of < 0 . 2 mu M were obtained .", "entity": [{"entity": "dichloro - substituted phenylacetyl", "entity_type": "Chemical", "pos": [20, 55]}], "task": "NER"}
{"text": "These GCMA inhibitors have a better selectivity profile than the previously described agmatine analogues , and possess negligible affinity for the trypsin - like serine proteases thrombin , factor Xa , and matriptase .", "entity": [{"entity": "GCMA", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "agmatine", "entity_type": "Chemical", "pos": [86, 94]}, {"entity": "serine", "entity_type": "Chemical", "pos": [162, 168]}], "task": "NER"}
{"text": "A crystal structure in complex with the WNV protease was determined for one of the most potent inhibitors , 3 , 4 - dichlorophenylacetyl - Lys - Lys - GCMA ( K ( i ) = 0 . 13 mu M ) .", "entity": [{"entity": "3 , 4 - dichlorophenylacetyl - Lys - Lys - GCMA", "entity_type": "Chemical", "pos": [108, 155]}], "task": "NER"}
{"text": "The inhibitor adopts a horseshoe - like conformation , most likely due to a hydrophobic contact between the P4 phenyl ring and the P1 cyclohexyl group , which is further stabilized by an intramolecular hydrogen bond between the P1 guanidino group and the P4 carbonyl oxygen atom .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [111, 117]}, {"entity": "cyclohexyl", "entity_type": "Chemical", "pos": [134, 144]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [202, 210]}, {"entity": "guanidino", "entity_type": "Chemical", "pos": [231, 240]}, {"entity": "carbonyl oxygen", "entity_type": "Chemical", "pos": [258, 273]}], "task": "NER"}
{"text": "These inhibitors are stable , readily accessible , and have a noncovalent binding mode .", "entity": [], "task": "NER"}
{"text": "Therefore , they may serve as suitable lead structures for further development .", "entity": [], "task": "NER"}
{"text": "Synthesis of a potent antimalarial agent through natural products conjugation .", "entity": [], "task": "NER"}
{"text": "Au naturel !", "entity": [], "task": "NER"}
{"text": "( + ) - Usnic acid ( green ) is a weak antimalarial agent , however , in conjugation with known antimalarial scaffolds and drugs , such as dihydroartemisinin ( blue ) , potent activity against the blood - stage parasite can be seen both in vitro and in vivo .", "entity": [{"entity": "( + ) - Usnic acid", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "dihydroartemisinin", "entity_type": "Chemical", "pos": [139, 157]}], "task": "NER"}
{"text": "The compound shown exhibits an IC ( 50 ) value of 1 . 4 nM against Plasmodium falciparum in vitro and proved nearly as efficacious as artesunate in a mouse model of infection .", "entity": [{"entity": "artesunate", "entity_type": "Chemical", "pos": [134, 144]}], "task": "NER"}
{"text": "Combined inhibition of mTORC1 and mTORC2 signaling pathways is a promising therapeutic option in inhibiting pheochromocytoma tumor growth : in vitro and in vivo studies in female athymic nude mice .", "entity": [], "task": "NER"}
{"text": "Several lines of evidence , including the recent discovery of novel susceptibility genes , point out an important role for the mammalian target of rapamycin ( mTOR ) signaling pathway in the development of pheochromocytoma .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [147, 156]}], "task": "NER"}
{"text": "Analyzing a set of pheochromocytomas from patients with different genetic backgrounds , we observed and confirmed a significant overexpression of key mTOR complex ( mTORC ) signaling mediators .", "entity": [], "task": "NER"}
{"text": "Using selective ATP - competitive inhibitors targeting both mTORC1 and mTORC2 , we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt / mTOR signaling pathway .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [16, 19]}], "task": "NER"}
{"text": "Moreover , AZD8055 , a selective ATP - competitive dual mTORC1 / 2 small molecular inhibitor , significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice .", "entity": [{"entity": "AZD8055", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma .", "entity": [], "task": "NER"}
{"text": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin - induced hypertension : The beneficial effects of melatonin .", "entity": [{"entity": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [0, 47]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "Objective : The purpose of the present study was to evaluate the effects of melatonin on biochemical and cardiovascular changes resulting from exposure to 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) , a polychlorinated dibenzo - para - dioxin . Methods : A total of 24 Sprague - Dawley rats were divided equally into the following four groups : ( 1 ) control group was administered with 0 . 5 mL corn oil by gavage and 0 . 5 cc vehicle of melatonin ( proportionally nine parts physiological serum + one part ethyl alcohol ) intraperitoneally for 4 weeks , ( 2 ) the melatonin group was given 5 mg / kg / day melatonin intraperitoneally for 4 weeks , ( 3 ) the TCDD group was given 500 ng / kg / day TCDD by gavage for 4 weeks and ( 4 ) the TCDD + melatonin group was given TCDD ( 500 ng / kg / day ) by gavage and melatonin ( 5 mg / kg / day ) intraperitoneally simultaneously for 4 weeks .", "entity": [{"entity": "melatonin", "entity_type": "Chemical", "pos": [76, 85]}, {"entity": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [155, 202]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [205, 209]}, {"entity": "polychlorinated dibenzo - para - dioxin", "entity_type": "Chemical", "pos": [216, 255]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [452, 461]}, {"entity": "ethyl alcohol", "entity_type": "Chemical", "pos": [521, 534]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [579, 588]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [621, 630]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [673, 677]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [712, 716]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [753, 757]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [760, 769]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [786, 790]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [827, 836]}], "task": "NER"}
{"text": "Systolic blood pressure was evaluated by the tail - cuff method .", "entity": [], "task": "NER"}
{"text": "Vascular responses to phenylephrine and acetylcholine were evaluated in the isolated thoracic aortas . Results : TCDD not only augmented the systolic blood pressure but also increased the contractile responses to phenylephrine in aorta .", "entity": [{"entity": "phenylephrine", "entity_type": "Chemical", "pos": [22, 35]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [40, 53]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [113, 117]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [213, 226]}], "task": "NER"}
{"text": "Melatonin reversed the blood pressure augmented by TCDD and decreased the contractile responses to phenylephrine in aorta .", "entity": [{"entity": "Melatonin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "phenylephrine", "entity_type": "Chemical", "pos": [99, 112]}], "task": "NER"}
{"text": "TCDD induced an increase in the malondialdehyde levels in kidney tissue and melatonin did not change it .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [32, 47]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Therefore , TCDD caused a decrease in glutathione levels in kidney tissues and melatonin reversed it . Conclusion : Present data demonstrated that TCDD may lead to an increase in blood pressure via increased renal oxidative stress and vascular reactivity .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [38, 49]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "However , melatonin might ameliorate the blood pressure disturbed by TCDD in part by decreasing the oxidant activity induced by TCDD .", "entity": [{"entity": "melatonin", "entity_type": "Chemical", "pos": [10, 19]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [69, 73]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [128, 132]}], "task": "NER"}
{"text": "Progress in the synthesis of canthine alkaloids and ring - truncated congeners .", "entity": [{"entity": "canthine alkaloids", "entity_type": "Chemical", "pos": [29, 47]}], "task": "NER"}
{"text": "The canthines represent a fairly large subclass of beta - carboline alkaloids , with the first members described 75 years ago .", "entity": [{"entity": "canthines", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "beta - carboline alkaloids", "entity_type": "Chemical", "pos": [51, 77]}], "task": "NER"}
{"text": "Over the last 60 years , many members of the parent compound , canthin - 6 - one ( 1 ) , have been isolated from various plant sources , principally the Rutaceae and Simaroubaceae families , and recently from fungi .", "entity": [{"entity": "canthin - 6 - one", "entity_type": "Chemical", "pos": [63, 80]}], "task": "NER"}
{"text": "Structures isolated from these sources have been the subject of total synthesis , which continues to the present day .", "entity": [], "task": "NER"}
{"text": "This review gives a broad overview of synthetic approaches to canthines over a 30 - year period from 1982 to 2012 and summarizes recent reports on the synthesis of less well known ring - truncated congeners .", "entity": [{"entity": "canthines", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "These include C - ring - truncated ( \" ABD \" , 2 ) and A - ring - truncated ( \" BCD \" , 3 ) ring systems , which are providing new scaffolds for potentially useful therapeutic applications .", "entity": [], "task": "NER"}
{"text": "Diels - Alder mediated controlled release from a poly ( ethylene glycol ) based hydrogel .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [49, 73]}], "task": "NER"}
{"text": "A synthetic amino acid bearing a furan functionality was developed and incorporated into peptide sequences using solid phase synthesis .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "furan", "entity_type": "Chemical", "pos": [33, 38]}], "task": "NER"}
{"text": "Peptides expressing the furan moiety were attached to poly ( ethylene glycol ) ( PEG ) hydrogels through a thermally reversible covalent bond formed by a Diels - Alder reaction .", "entity": [{"entity": "furan", "entity_type": "Chemical", "pos": [24, 29]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [54, 78]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Reactions of thiol and maleimide PEG macromers in an off - stoichiometric Michael addition were performed , such that the maleimide moiety was in excess , to create hydrogel networks with pendant Diels - Alder compatible tethering sites , that is , the maleimide .", "entity": [{"entity": "thiol", "entity_type": "Chemical", "pos": [13, 18]}, {"entity": "maleimide PEG", "entity_type": "Chemical", "pos": [23, 36]}, {"entity": "maleimide", "entity_type": "Chemical", "pos": [122, 131]}, {"entity": "maleimide", "entity_type": "Chemical", "pos": [253, 262]}], "task": "NER"}
{"text": "By making use of the Diels - Alder reaction , it was possible to control the release rate of reversibly bound moieties from the hydrogel by changing the temperature ; higher temperatures favor a faster retro - Diels - Alder reaction and , therefore , a faster release from the polymer network .", "entity": [], "task": "NER"}
{"text": "This concept was demonstrated by incorporating a fluorescently labeled furan - RGDS sequence into a hydrogel possessing excess maleimide functionalities and monitoring the subsequent liberation of RGDS at various temperatures , illustrating a Diels - Alder mediated release mechanism .", "entity": [{"entity": "furan", "entity_type": "Chemical", "pos": [71, 76]}, {"entity": "maleimide", "entity_type": "Chemical", "pos": [127, 136]}], "task": "NER"}
{"text": "The release profile was quantified at temperatures ranging from physiological ( 37 degrees C ) to 80 degrees C .", "entity": [], "task": "NER"}
{"text": "By changing the temperature , varying extents of release were attained over the time course of several days , ranging from 40 % release for lower temperatures to complete release for the highest temperature considered .", "entity": [], "task": "NER"}
{"text": "Further confirmation of a reaction - diffusion controlled release mechanism was obtained through comparison of experimental release data to a reaction - diffusion model of the release .", "entity": [], "task": "NER"}
{"text": "In addition to thermal modulation , tuning of the release rate was accomplished by altering the number of possible Diels - Alder tethering sites present in the hydrogel .", "entity": [], "task": "NER"}
{"text": "Increasing the amount of free maleimide and , therefore , the number of potential Diels - Alder reaction sites , effectively slowed the release of peptide from the polymer .", "entity": [{"entity": "maleimide", "entity_type": "Chemical", "pos": [30, 39]}], "task": "NER"}
{"text": "For instance , doubling the amount of maleimide sites present in the hydrogel system decreased the amount of peptide released from approximately 60 % to about 40 % in the same span of time .", "entity": [{"entity": "maleimide", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "Bottom - up approach to creating three - dimensional nanoring arrays composed of Au nanoparticles .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [81, 83]}], "task": "NER"}
{"text": "A bottom - up approach to creating 3D assemblies of Au nanorings by drying aqueous dispersions of PS colloidal particles and Au NPs is shown .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "Au", "entity_type": "Chemical", "pos": [125, 127]}], "task": "NER"}
{"text": "The evaporation of water from the dispersion allowed for the formation of hexagonally assembled colloidal crystals and nanorings composed of Au nanoparticles among the PS colloidal particles .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [141, 143]}], "task": "NER"}
{"text": "The size of the nanorings could be controlled on a scale of tens to hundreds of nanometers .", "entity": [], "task": "NER"}
{"text": "After sintering , the Au NPs formed Au nanorings .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "Au", "entity_type": "Chemical", "pos": [36, 38]}], "task": "NER"}
{"text": "This simple approach supplies a potentially useful path to novel plasmonic materials and unique metamaterials for the visible light region .", "entity": [], "task": "NER"}
{"text": "Covalent Layer - by - Layer Assembly of Redox - Active Polymer Multilayers .", "entity": [], "task": "NER"}
{"text": "Poly ( ferrocenyl ( 3 - bromopropyl ) methylsilane ) and poly ( ethylene imine ) are employed in a layer - by - layer deposition process to form covalently connected , redox - active multilayer thin films by means of an amine alkylation reaction .", "entity": [{"entity": "Poly ( ferrocenyl ( 3 - bromopropyl ) methylsilane )", "entity_type": "Chemical", "pos": [0, 52]}, {"entity": "poly ( ethylene imine )", "entity_type": "Chemical", "pos": [57, 80]}, {"entity": "amine", "entity_type": "Chemical", "pos": [220, 225]}], "task": "NER"}
{"text": "The stepwise buildup of these multilayers on silicon , ITO , and quartz substrates was monitored by UV - vis absorption spectroscopy , Fourier transform infrared spectroscopy ( FTIR ) , static contact angle measurements , surface plasmon resonance ( SPR ) , atomic force microscopy , ellipsometry , and cyclic voltammetry , which provide evidence for a linear increase in multilayer thickness with the number of deposited bilayers .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [45, 52]}, {"entity": "ITO", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "quartz", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "Upon oxidation and reduction , these covalently interconnected layers do not disassemble , in contrast to poly ( ferrocenylsilane ) ( PFS ) layers featuring similar backbone structures that are held together by electrostatic forces .", "entity": [{"entity": "poly ( ferrocenylsilane )", "entity_type": "Chemical", "pos": [106, 131]}, {"entity": "PFS", "entity_type": "Chemical", "pos": [134, 137]}], "task": "NER"}
{"text": "The PFS / PEI multilayers are effective for the electrochemical sensing of ascorbic acid and hydrogen peroxide and show improved sensing performance at higher bilayer numbers .", "entity": [{"entity": "PFS", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [10, 13]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [75, 88]}, {"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [93, 110]}], "task": "NER"}
{"text": "These covalently linked layers are readily derivatized further and can therefore be regarded as a versatile platform for creating robust , tailorable , redox - active interfaces with applications in sensing and biofuel cells .", "entity": [], "task": "NER"}
{"text": "Tipping the energy balance toward longevity .", "entity": [], "task": "NER"}
{"text": "AMPK is a cellular energy sensor conserved across eukaryotes that in C . elegans prolongs life span and mimics dietary restriction .", "entity": [], "task": "NER"}
{"text": "Stenesen and colleagues ( 2012 ) activate AMPK both directly and indirectly by altering AMP biosynthesis to slow aging in Drosophila , highlighting AMPK as a conserved life span modulator that links energy sensing to longevity .", "entity": [{"entity": "AMP", "entity_type": "Chemical", "pos": [42, 45]}], "task": "NER"}
{"text": "Quantitative photoacoustic imaging of nanoparticles in cells and tissues .", "entity": [], "task": "NER"}
{"text": "Quantitative visualization of nanoparticles in cells and tissues , while preserving the spatial information , is very challenging .", "entity": [], "task": "NER"}
{"text": "A photoacoustic imaging technique to depict the presence and quantity of nanoparticles is presented .", "entity": [], "task": "NER"}
{"text": "This technique is based on the dependence of the photoacoustic signal on both the nanoparticle quantity and the laser fluence .", "entity": [], "task": "NER"}
{"text": "Quantitative photoacoustic imaging is a robust technique that does not require knowledge of the local fluence , but a relative change in the fluence .", "entity": [], "task": "NER"}
{"text": "This eliminates the need for sophisticated methods or models to determine the energy distribution of light in turbid media .", "entity": [], "task": "NER"}
{"text": "Quantitative photoacoustic imaging was first applied to nanoparticle - loaded cells , and quantitation was validated by inductively coupled plasma mass spectrometry .", "entity": [], "task": "NER"}
{"text": "Quantitative photoacoustic imaging was then extended to xenograft tumor tissue sections , and excellent agreement with traditional histopathological analysis was demonstrated .", "entity": [], "task": "NER"}
{"text": "Our results suggest that quantitative photoacoustic imaging may be used in many applications including the determination of the efficiency and effectiveness of molecular targeting strategies for cell studies and animal models , the quantitative assessment of photoacoustic contrast agent biodistribution , and the validation of in vivo photoacoustic imaging .", "entity": [], "task": "NER"}
{"text": "A comparative protease stability study of synthetic macrocyclic peptides that mimic two endocrine hormones .", "entity": [], "task": "NER"}
{"text": "Peptide therapeutics have traditionally faced many challenges including low bioavailability , poor proteolytic stability and difficult cellular uptake .", "entity": [], "task": "NER"}
{"text": "Conformationally constraining the backbone of a peptide into a macrocyclic ring often ameliorates these problems and allows for the development of a variety of new drugs .", "entity": [], "task": "NER"}
{"text": "Such peptide - based pharmaceuticals can enhance the multi - faceted functionality of peptide side chains , permitting the peptides to bind cellular targets and receptors necessary to impart their role , while protecting them from degrading cellular influences .", "entity": [], "task": "NER"}
{"text": "In the work described here , we developed three cyclic peptides , VP mimic1 , VP mimic2 and OT mimic1 , which mimic endocrine hormones vasopressin and oxytocin .", "entity": [{"entity": "vasopressin", "entity_type": "Chemical", "pos": [135, 146]}, {"entity": "oxytocin", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "Making notable changes to the overall structure and composition of the parent hormones , we synthesized the mimics and tested their durability against treatment with three proteases chosen for their specificity : pepsin , alpha - chymotrypsin , and pronase .", "entity": [], "task": "NER"}
{"text": "Vasopressin and oxytocin contain a disulfide linkage leaving them particularly vulnerable to deactivation from the reducing environment inside the cell .", "entity": [{"entity": "Vasopressin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "oxytocin", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "Thus , we increased the complexity of our assays by adding reducing agent glutathione to each mixture .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [74, 85]}], "task": "NER"}
{"text": "Subsequently , we discovered each of our mimics withstood protease treatment with less degradation and / or a slower rate of degradation as compared to both parent hormones and a linear control peptide .", "entity": [], "task": "NER"}
{"text": "Highly selective 2 , 4 - diaminopyrimidine - 5 - carboxamide inhibitors of Sky kinase .", "entity": [{"entity": "2 , 4 - diaminopyrimidine - 5 - carboxamide", "entity_type": "Chemical", "pos": [17, 60]}], "task": "NER"}
{"text": "We report the SAR around a series of 2 , 4 - diaminopyrimidine - 5 - carboxamide inhibitors of Sky kinase .", "entity": [{"entity": "2 , 4 - diaminopyrimidine - 5 - carboxamide", "entity_type": "Chemical", "pos": [37, 80]}], "task": "NER"}
{"text": "2 - Aminophenethyl analogs demonstrate excellent potency but moderate kinase selectivity , while 2 - aminobenzyl analogs that fill the Ala571 subpocket exhibit good inhibition activity and excellent kinase selectivity .", "entity": [{"entity": "2 - Aminophenethyl", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "2 - aminobenzyl", "entity_type": "Chemical", "pos": [97, 112]}], "task": "NER"}
{"text": "Synthesis and antibacterial evaluation of a novel tricyclic oxaborole - fused fluoroquinolone .", "entity": [{"entity": "tricyclic oxaborole", "entity_type": "Chemical", "pos": [50, 69]}, {"entity": "fluoroquinolone", "entity_type": "Chemical", "pos": [78, 93]}], "task": "NER"}
{"text": "We have designed and synthesized a novel class of compounds based on fluoroquinolone antibacterial prototype .", "entity": [{"entity": "fluoroquinolone", "entity_type": "Chemical", "pos": [69, 84]}], "task": "NER"}
{"text": "The design concept involved the replacement of the 3 - carboxylic acid in ciprofloxacin with an oxaborole - fused ring as an acid - mimicking group .", "entity": [{"entity": "3 - carboxylic acid", "entity_type": "Chemical", "pos": [51, 70]}, {"entity": "ciprofloxacin", "entity_type": "Chemical", "pos": [74, 87]}, {"entity": "oxaborole", "entity_type": "Chemical", "pos": [96, 105]}], "task": "NER"}
{"text": "The synthetic method employed in this work provides a good example of incorporating boron atom in complex molecules with multiple functional groups .", "entity": [{"entity": "boron", "entity_type": "Chemical", "pos": [84, 89]}], "task": "NER"}
{"text": "The antibacterial activity of the newly synthesized compounds has been evaluated .", "entity": [], "task": "NER"}
{"text": "Vinclozolin - - no transgenerational inheritance of anti - androgenic effects after maternal exposure during organogenesis via the intraperitoneal route .", "entity": [{"entity": "Vinclozolin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The goal of this study was to examine the potential transgenerational inheritance of anti - androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats ( Crl : WI [ Han ] ) .", "entity": [{"entity": "Vinclozolin", "entity_type": "Chemical", "pos": [122, 133]}], "task": "NER"}
{"text": "Dams were dosed with Vinclozolin at 0 , 4 or 100mg / kg bw / d on gestation days 6 - 15 .", "entity": [{"entity": "Vinclozolin", "entity_type": "Chemical", "pos": [21, 32]}], "task": "NER"}
{"text": "Male offspring of F1 - F3 generations were bred with untreated females to yield F2 - F4 offspring .", "entity": [], "task": "NER"}
{"text": "No evident anti - androgenic effects were observed at 4mg / kg bw / d , but a case of hypospadias as well as delayed sexual maturation in F1 male offspring was observed as a sign of anti - androgenicity at 100mg / kg bw / d .", "entity": [], "task": "NER"}
{"text": "However , F1 - F3 males developed normally to sexual maturity and were able to mate and to generate healthy progeny .", "entity": [], "task": "NER"}
{"text": "Sperm count , morphology and motility were not affected in F1 - F4 generation male offspring .", "entity": [], "task": "NER"}
{"text": "In conclusion , transgenerational inheritance of Vinclozolin ' s anti - androgenic effects was not evident in outbred Wistar rats .", "entity": [{"entity": "Vinclozolin", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Enhancing nicotine vaccine immunogenicity with liposomes .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "A major liability of existing nicotine vaccine candidates is the wide variation in anti - nicotine immune responses among clinical trial participants .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "In order to address this liability , significant emphasis has been directed at evaluating adjuvants and delivery systems that confer more robust potentiation of the anti - nicotine immune response .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [172, 180]}], "task": "NER"}
{"text": "Toward that end , we have initiated work that seeks to exploit the adjuvant effect of liposomes , with or without Toll - like receptor agonist ( s ) .", "entity": [], "task": "NER"}
{"text": "The results of the murine immunization study described herein support the hypothesis that a liposomal nicotine vaccine formulation may provide a means for addressing the immunogenicity challenge .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "Triglyceride accumulation inhibitory effects of phenylpropanoid glycosides from Boschniakia rossica Fedtsch et Flerov .", "entity": [{"entity": "Triglyceride", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "phenylpropanoid glycosides", "entity_type": "Chemical", "pos": [48, 74]}], "task": "NER"}
{"text": "Bioassay - guided fractionation led to isolation of five new phenylpropanol glycosides , rossicasides G ( 1 ) , H ( 2 ) , I ( 3 ) , J ( 4 ) , and K ( 5 ) , together with seven known compounds ( 6 - 12 ) from Boschniakia rossica .", "entity": [{"entity": "phenylpropanol glycosides", "entity_type": "Chemical", "pos": [61, 86]}, {"entity": "rossicasides", "entity_type": "Chemical", "pos": [89, 101]}], "task": "NER"}
{"text": "Their structures were elucidated by chemical and spectroscopic methods ( UV , IR , HRESI - TOF - MS , 1D and 2D NMR ) .", "entity": [], "task": "NER"}
{"text": "Activity screening results showed that some isolates had TG accumulation inhibitory effects in HepG2 cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , the structure - activity relationship was partly clarified .", "entity": [], "task": "NER"}
{"text": "Computational identification and quantification of trabecular microarchitecture classes by 3 - D texture analysis - based clustering .", "entity": [], "task": "NER"}
{"text": "High resolution peripheral quantitative computed tomography ( HR - pQCT ) permits the non - invasive assessment of cortical and trabecular bone density , geometry , and microarchitecture .", "entity": [], "task": "NER"}
{"text": "Although researchers have developed various post - processing algorithms to quantify HR - pQCT image properties , few of these techniques capture image features beyond global structure - based metrics .", "entity": [], "task": "NER"}
{"text": "While 3D - texture analysis is a key approach in computer vision , it has been utilized only infrequently in HR - pQCT research .", "entity": [], "task": "NER"}
{"text": "Motivated by high isotropic spatial resolution and the information density provided by HR - pQCT scans , we have developed and evaluated a post - processing algorithm that quantifies microarchitecture characteristics via texture features in HR - pQCT scans .", "entity": [], "task": "NER"}
{"text": "During a training phase in which clustering was applied to texture features extracted from each voxel of trabecular bone , three distinct clusters , or trabecular microarchitecture classes ( TMACs ) were identified .", "entity": [], "task": "NER"}
{"text": "These TMACs represent trabecular bone regions with common texture characteristics .", "entity": [], "task": "NER"}
{"text": "The TMACs were then used to automatically segment the voxels of new data into three regions corresponding to the trained cluster features .", "entity": [], "task": "NER"}
{"text": "Regional trabecular bone texture was described by the histogram of relative trabecular bone volume covered by each cluster .", "entity": [], "task": "NER"}
{"text": "We evaluated the intra - scanner and inter - scanner reproducibility by assessing the precision errors ( PE ) , intra class correlation coefficients ( ICC ) and Dice coefficients ( DC ) of the method on 14 ultradistal radius samples scanned on two HR - pQCT systems .", "entity": [], "task": "NER"}
{"text": "DC showed good reproducibility in intra - scanner set - up with a mean of 0 . 870 +/- 0 . 027 ( no unit ) .", "entity": [], "task": "NER"}
{"text": "Even in the inter - scanner set - up the ICC showed high reproducibility , ranging from 0 . 814 to 0 . 964 .", "entity": [], "task": "NER"}
{"text": "In a preliminary clinical test application , the TMAC histograms appear to be a good indicator , when differentiating between postmenopausal women with ( n = 18 ) and without ( n = 18 ) prevalent fragility fractures .", "entity": [], "task": "NER"}
{"text": "In conclusion , we could demonstrate that 3D - texture analysis and feature clustering seems to be a promising new HR - pQCT post - processing tool with good reproducibility , even between two different scanners .", "entity": [], "task": "NER"}
{"text": "Anti - apoptotic activity of hydroxytyrosol and hydroxytyrosyl laurate .", "entity": [{"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [29, 43]}, {"entity": "hydroxytyrosyl laurate", "entity_type": "Chemical", "pos": [48, 70]}], "task": "NER"}
{"text": "Hydroxytyrosol ( HyT ) is a polyphenol primarily released in olive mill wastewater and in olive oil .", "entity": [{"entity": "Hydroxytyrosol", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "HyT", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "polyphenol", "entity_type": "Chemical", "pos": [28, 38]}], "task": "NER"}
{"text": "In animal and cell model studies , HyT and its metabolites have strong antioxidant and antimicrobial activities , as well as beneficial effects on the cardiovascular system and in several human diseases .", "entity": [{"entity": "HyT", "entity_type": "Chemical", "pos": [35, 38]}], "task": "NER"}
{"text": "Differently , many researchers reported that HyT down - regulates tumor cell viability and cell cycle progression , and induces reactive oxygen species ( ROS ) production and apoptosis .", "entity": [{"entity": "HyT", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [137, 143]}], "task": "NER"}
{"text": "In this study we have investigated the effects of HyT and the corresponding ester hydroxytyrosyl laurate in U937 cells , a human monocytoid cell line , and in C2C12 myoblasts , a murine proliferating muscle cell model , after apoptotic death induction .", "entity": [{"entity": "HyT", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "hydroxytyrosyl laurate", "entity_type": "Chemical", "pos": [82, 104]}], "task": "NER"}
{"text": "Inverted , light and transmission electron microscopy have been utilized to characterize cell death patterns .", "entity": [], "task": "NER"}
{"text": "H2O2 , at the concentrations known to induce apoptosis , was utilized as cell death trigger .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The results obtained show that laur - HyT has a protective antioxidant effect against H2O2 treatment , greater than HyT , so having a role in the prevention of apoptotic death in normal and tumor cells .", "entity": [{"entity": "laur - HyT", "entity_type": "Chemical", "pos": [31, 41]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [86, 90]}, {"entity": "HyT", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "These data suggest these compounds as good candidate for novel therapeutic strategies .", "entity": [], "task": "NER"}
{"text": "Zinc protection against aluminium induced altered lipid profile and membrane integrity .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "aluminium", "entity_type": "Chemical", "pos": [24, 33]}], "task": "NER"}
{"text": "The aim of the present study was to investigate the effects of Zinc ( Zn ) supplementation on lipid profile and fluidity of cerebrum and cerebellum membranes of rats treated with aluminium ( Al ) .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [70, 72]}, {"entity": "aluminium", "entity_type": "Chemical", "pos": [179, 188]}, {"entity": "Al", "entity_type": "Chemical", "pos": [191, 193]}], "task": "NER"}
{"text": "Sprague dawley male rats were divided into four different treatment groups viz : Control , aluminium treated , zinc treated and aluminium + zinc treated .", "entity": [{"entity": "aluminium", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [111, 115]}, {"entity": "aluminium", "entity_type": "Chemical", "pos": [128, 137]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "Aluminium ( AlCl3 ) was administered orally at a dose of 100mg / kgb . wt . / day ( dissolved in drinking water ) .", "entity": [{"entity": "Aluminium", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "AlCl3", "entity_type": "Chemical", "pos": [12, 17]}], "task": "NER"}
{"text": "Zinc as zinc sulphate was supplemented to rats at a dose of 227mg / l in drinking water .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "zinc sulphate", "entity_type": "Chemical", "pos": [8, 21]}], "task": "NER"}
{"text": "A significant decrease in the levels of total lipids , glycolipids , phospholipids , cholesterol and gangliosides contents were observed in both the cerebrum and cerebellum following Al exposure , which were found to be significantly increased following Zn supplementation .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [85, 96]}, {"entity": "gangliosides", "entity_type": "Chemical", "pos": [101, 113]}, {"entity": "Al", "entity_type": "Chemical", "pos": [183, 185]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [254, 256]}], "task": "NER"}
{"text": "On the contrary , Al treatment caused a significant increase in the formation of conjugated dienes , which were observed to be reduced on Zn co - treatment .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "dienes", "entity_type": "Chemical", "pos": [92, 98]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [138, 140]}], "task": "NER"}
{"text": "Further , Al treatment significantly elevated the fluorescence polarization , anisotropy and order parameter , which however were normalized upon Zn co - administration .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [10, 12]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [146, 148]}], "task": "NER"}
{"text": "Hence , the present study depicts the potential of Zn in moderating the changes caused by Al on membrane composition and fluidity in rat brain .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "Al", "entity_type": "Chemical", "pos": [90, 92]}], "task": "NER"}
{"text": "FXR - dependent and - independent interaction of glucocorticoids with the regulatory pathways involved in the control of bile acid handling by the liver .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [121, 130]}], "task": "NER"}
{"text": "Treatment with glucocorticoids ( GCs ) may cause adverse effects , including cholestasis .", "entity": [], "task": "NER"}
{"text": "The ability of dexamethasone , prednisolone and budesonide to affect the liver handling of bile acids ( BAs ) has been investigated .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [15, 28]}, {"entity": "prednisolone", "entity_type": "Chemical", "pos": [31, 43]}, {"entity": "budesonide", "entity_type": "Chemical", "pos": [48, 58]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [91, 101]}], "task": "NER"}
{"text": "In rats treated with GCs for 4 days , altered serum and bile BA levels , changed conjugation pattern , and delayed and decreased ability to conjugate / secrete exogenously administered deoxycholate , were found using HPLC - MS / MS .", "entity": [{"entity": "deoxycholate", "entity_type": "Chemical", "pos": [185, 197]}], "task": "NER"}
{"text": "RT - QPCR analyses revealed that GC treatment also induced a down - regulation of liver nuclear receptors ( Fxr , Gr and Shp ) , transporters ( Ntcp , Mrp4 and Bcrp ) and enzymes ( Cyp7a1 and Baat ) , whereas Bsep , Mrp2 and Cyp27a1 were up - regulated .", "entity": [], "task": "NER"}
{"text": "Human HepG2 and Alexander cell lines were used as in vitro models of liver cells with and without constitutive FXR expression , respectively .", "entity": [], "task": "NER"}
{"text": "In HepG2 cells , GCs induced a decreased expression of FXR and SHP , and inhibited the regulatory effect of GW4064 on FXR - target genes .", "entity": [{"entity": "GW4064", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "In Alexander cells , only when they were transfected with FXR + RXR , GW4064 caused up - regulation of SHP and OST beta , and a down - regulation of CYP27A1 .", "entity": [{"entity": "GW4064", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "GCs had the opposite effect on these genes , both in the absence and in the presence of FXR expression .", "entity": [], "task": "NER"}
{"text": "Co - transfection of Alexander cells with IR - 1 - Luc and FXR + RXR revealed that GCs did not inhibit but moderately enhanced FXR activity .", "entity": [], "task": "NER"}
{"text": "Moreover , GCs have a synergistic effect on GW4064 - induced FXR activation , whereas chenodeoxycholate and GW4064 have an additive effect .", "entity": [{"entity": "GW4064", "entity_type": "Chemical", "pos": [44, 50]}, {"entity": "chenodeoxycholate", "entity_type": "Chemical", "pos": [86, 103]}, {"entity": "GW4064", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "In conclusion , GCs are able to directly or indirectly activate FXR but they also antagonize , through FXR - independent mechanisms , the expression of FXR and FXR target genes involved in the hepatic handling of BAs .", "entity": [], "task": "NER"}
{"text": "Toxic effects of dietary exposure to T - 2 toxin on intestinal and hepatic biotransformation enzymes and drug transporter systems in broiler chickens .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [37, 48]}], "task": "NER"}
{"text": "The effects of the mycotoxin T - 2 on hepatic and intestinal drug - metabolizing enzymes ( cytochrome P450 ) and drug transporter systems ( MDR1 and MRP2 ) in poultry were investigated during this study .", "entity": [{"entity": "mycotoxin T - 2", "entity_type": "Chemical", "pos": [19, 34]}], "task": "NER"}
{"text": "Broiler chickens received either uncontaminated feed , feed contaminated with 68 mu g / kg or 752 mu g / kg T - 2 toxin .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [108, 119]}], "task": "NER"}
{"text": "After 3weeks , the animals were euthanized and MDR1 , MRP2 , CYP1A4 , CYP1A5 and CYP3A37 mRNA expression were analyzed using qRT - PCR .", "entity": [], "task": "NER"}
{"text": "Along the entire length of the small intestine no significant differences were observed .", "entity": [], "task": "NER"}
{"text": "In the liver , genes coding for CYP1A4 , CYP1A5 and CYP3A37 were significantly down - regulated in the group exposed to 752 mu g / kg T - 2 .", "entity": [], "task": "NER"}
{"text": "For CYP1A4 , even a contamination level of 68 mu g / kg T - 2 caused a significant decrease in mRNA expression .", "entity": [], "task": "NER"}
{"text": "Expression of MDR1 was not significantly decreased in the liver .", "entity": [], "task": "NER"}
{"text": "In contrast , hepatic MRP2 expression was significantly down - regulated after exposure to 752 mu g / kg T - 2 .", "entity": [], "task": "NER"}
{"text": "Hepatic and intestinal microsomes were prepared to test the enzymatic activity of CYP3A .", "entity": [], "task": "NER"}
{"text": "In the ileum and liver CYP3A activity was significantly increased in the group receiving 752 mu g / kg T - 2 compared to the control group .", "entity": [], "task": "NER"}
{"text": "The results of this study show that drug metabolizing enzymes and drug transporter mechanisms can be influenced due to prolonged exposure to relevant doses of T - 2 .", "entity": [], "task": "NER"}
{"text": "Enhanced chemopreventive activity of hydroxytyrosol on HL60 and HL60R cells by chemical conversion into thio derivatives .", "entity": [{"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [37, 51]}, {"entity": "thio", "entity_type": "Chemical", "pos": [104, 108]}], "task": "NER"}
{"text": "Thio derivatives of hydroxytyrosol containing thiol , thioacetate and disulfide functionalities were synthesized from natural hydroxytyrosol ( 3 , 4 - DHPEA ) via 3 , 4 - dihydroxyphenethyl halides .", "entity": [{"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [20, 34]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "thioacetate", "entity_type": "Chemical", "pos": [54, 65]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [70, 79]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [126, 140]}, {"entity": "3 , 4 - DHPEA", "entity_type": "Chemical", "pos": [143, 156]}, {"entity": "3 , 4 - dihydroxyphenethyl halides", "entity_type": "Chemical", "pos": [163, 197]}], "task": "NER"}
{"text": "These compounds , containing the combination of catechol moiety and divalent sulfur functions , were tested for the pro - apoptotic and anti - proliferative activities on both parental HL60 and multi - drug resistant HL60R cells .", "entity": [{"entity": "catechol", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "It was found that all synthesized compounds were more effective than 3 , 4 - DHPEA in inducing apoptosis on HL60R cells , and that the hydroxytyrosol disulfide was the most active pro - apoptotic and anti - proliferative compound on both HL60 and HL60R cells .", "entity": [{"entity": "3 , 4 - DHPEA", "entity_type": "Chemical", "pos": [69, 82]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [135, 149]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [150, 159]}], "task": "NER"}
{"text": "Different from 3 , 4 - DHPEA , all thio derivatives of hydroxytyrosol induced apoptosis by a mechanism not involving the release of H ( 2 ) O ( 2 ) in the culture medium .", "entity": [{"entity": "3 , 4 - DHPEA", "entity_type": "Chemical", "pos": [15, 28]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [55, 69]}, {"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [132, 147]}], "task": "NER"}
{"text": "The data on HL60R cells suggest that these compounds could be able to reverse the resistance toward the most common drugs in cancer therapy .", "entity": [], "task": "NER"}
{"text": "In - line monitoring of the drug content of powder mixtures and tablets by near - infrared spectroscopy during the continuous direct compression tableting process .", "entity": [], "task": "NER"}
{"text": "Continuous manufacturing methods offer economic and quality advantages when compared with batch manufacturing methods .", "entity": [], "task": "NER"}
{"text": "In continuous manufacturing , one requires real time assurance of quality of product via the implementation of PAT tools .", "entity": [], "task": "NER"}
{"text": "This study focuses on an in - line near - infrared ( NIR ) spectroscopic method for determining the drug content of powder mixtures and tablets during a continuous tableting process .", "entity": [], "task": "NER"}
{"text": "Tablets consisting of acetaminophen ( 20 - 30 % ) , lactose ( 69 . 07 - 78 . 93 % ) and magnesium stearate ( 0 . 93 - 1 . 07 % ) were prepared in a continuous direct compression line that consisted of two loss - in - weight feeders , one for acetaminophen and one for premixed lactose and magnesium stearate , and a continuous mixer followed by a rotary tablet press .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [22, 35]}, {"entity": "lactose", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "magnesium stearate", "entity_type": "Chemical", "pos": [88, 106]}, {"entity": "acetaminophen", "entity_type": "Chemical", "pos": [242, 255]}, {"entity": "lactose", "entity_type": "Chemical", "pos": [277, 284]}, {"entity": "magnesium stearate", "entity_type": "Chemical", "pos": [289, 307]}], "task": "NER"}
{"text": "NIR spectroscopy was applied to the continuous mixer and tablet press to perform a 100 % product check at full tableting speed .", "entity": [], "task": "NER"}
{"text": "The UV - spectrophotometric method was used as an off - line reference method to determine the acetaminophen content in the samples .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "The powder mixture and tablet samples were taken during the process for the calibration of continuous mixer and tablet press , respectively .", "entity": [], "task": "NER"}
{"text": "For the continuous mixer , model creation with the PLS method yielded R - Square and RMSEC ( root mean square error of calibration ) values of 0 . 975 % and 0 . 56 % , respectively .", "entity": [], "task": "NER"}
{"text": "For the tablet press , the corresponding R - Square and RMSEC values were 0 . 943 % and 0 . 75 % , respectively .", "entity": [], "task": "NER"}
{"text": "A test run demonstrated good predictability in the estimation of the API content in the powder mixtures and tablets during the continuous tableting process .", "entity": [], "task": "NER"}
{"text": "For the continuous mixer and tablet press , the RMSEP ( root mean square error of prediction ) values were 0 . 96 % and 1 . 37 % , respectively .", "entity": [], "task": "NER"}
{"text": "This study demonstrates that an NIR instrument capable of fast spectra acquisition can be a valuable tool for the in - line monitoring of the continuous mixing and tableting processes .", "entity": [], "task": "NER"}
{"text": "OAT1 and OAT3 : targets of drug - drug interaction between entecavir and JBP485 .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [59, 68]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "Entecavir and JBP485 ( a dipeptide ) exhibit the antihepatitis activities and it is possible for the two drugs to be coadministered in the treatment of hepatitis .", "entity": [{"entity": "Entecavir", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "dipeptide", "entity_type": "Chemical", "pos": [25, 34]}], "task": "NER"}
{"text": "We aimed to elucidate whether entecavir was a substrate of OAT1 , OAT3 , OCT , and PEPT1 and to investigate the targets of drug - drug interactions between entecavir and JBP485 .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [30, 39]}, {"entity": "entecavir", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [170, 176]}], "task": "NER"}
{"text": "Plasma and urine concentrations of entecavir following intravenous and oral administration in vivo , uptake of entecavir in kidney slices and transfected cells in vitro , were determined by LC - MS / MS .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "entecavir", "entity_type": "Chemical", "pos": [111, 120]}], "task": "NER"}
{"text": "Following intravenous co - administration of entecavir and JBP485 in rats , entecavir AUC increased 1 . 93 - fold , t1 / 2 beta was prolonged 2 . 08 - fold , CLP decreased 49 % , CLR decreased 73 % , and accumulated urinary excretion decreased 54 % .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [59, 65]}, {"entity": "entecavir", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "However , following oral co - administration , the entecavir Tmax and Cmax were not affected ; the degree of change in other pharmacokinetic parameters ( AUC , t1 / 2 beta , CLP , and accumulated urinary excretion ) was similar to that of intravenous administration .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "The uptake of entecavir was nearly identical in hPEPT1 - as in vector - HELA cells .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "In rat kidney slices , uptake of entecavir was markedly inhibited by p - aminohippurate , benzylpenicillin , JBP485 , and tetraethyl ammonium .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "p - aminohippurate", "entity_type": "Chemical", "pos": [69, 87]}, {"entity": "benzylpenicillin", "entity_type": "Chemical", "pos": [90, 106]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [109, 115]}, {"entity": "tetraethyl ammonium", "entity_type": "Chemical", "pos": [122, 141]}], "task": "NER"}
{"text": "In hOAT1 - and hOAT3 - HEK293 cells , uptake of entecavir was significantly higher compared to vector - HEK293 cells and was markedly inhibited by p - aminohippurate , benzylpenicillin , and JBP485 .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "p - aminohippurate", "entity_type": "Chemical", "pos": [147, 165]}, {"entity": "benzylpenicillin", "entity_type": "Chemical", "pos": [168, 184]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [191, 197]}], "task": "NER"}
{"text": "Km and Vmax values of entecavir were 250 mu M and 0 . 83 nmol / mg protein / 30s ( OAT1 ) and 23 mu M and 1 . 1 nmol / mg protein / 30 s ( OAT3 ) , respectively .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [22, 31]}], "task": "NER"}
{"text": "Entecavir is the substrate of OAT1 , OAT3 , and OCT .", "entity": [{"entity": "Entecavir", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Moreover , OAT1 and OAT3 are the targets of DDI between entecavir and JBP485 .", "entity": [{"entity": "entecavir", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "JBP485", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "Bioactive barrigenol type triterpenoids from the leaves of Xanthoceras sorbifolia Bunge .", "entity": [{"entity": "barrigenol", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "triterpenoids", "entity_type": "Chemical", "pos": [26, 39]}], "task": "NER"}
{"text": "In order to find out new natural barrigenol type triterpenenoids as antitumor agent and reveal the difference on material basis of different parts of Xanthoceras sorbifolia Bunge , the bioassay - directed separation of the saponin fraction from leaves of X . sorbifolia Bunge was carried out to afford 5 new barrigenol type triterpenoids ( 1 - 5 ) , together with 2 known ones .", "entity": [{"entity": "barrigenol", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "triterpenenoids", "entity_type": "Chemical", "pos": [49, 64]}, {"entity": "saponin", "entity_type": "Chemical", "pos": [223, 230]}, {"entity": "barrigenol", "entity_type": "Chemical", "pos": [308, 318]}, {"entity": "triterpenoids", "entity_type": "Chemical", "pos": [324, 337]}], "task": "NER"}
{"text": "The antitumor activities were evaluated and compounds 2 and 7 showed significant cytotoxic activity .", "entity": [], "task": "NER"}
{"text": "Furthermore , the SAR was discussed briefly .", "entity": [], "task": "NER"}
{"text": "On the basis of our research work and related literature , the difference of chemical constituents from different parts of X . sorbifolia was analyzed and concluded .", "entity": [], "task": "NER"}
{"text": "The result can be a useful reference for phytochemistry taxology and safe and rational drug use of X . sorbifolia .", "entity": [], "task": "NER"}
{"text": "Synthesis of quinoline derivatives : discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer ' s disease .", "entity": [{"entity": "quinoline", "entity_type": "Chemical", "pos": [13, 22]}], "task": "NER"}
{"text": "Phosphodiesterase type 5 ( PDE5 ) mediates the degradation of cGMP in a variety of tissues including brain .", "entity": [{"entity": "cGMP", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "Recent studies have demonstrated the importance of the nitric oxide / cGMP / cAMP - responsive element - binding protein ( CREB ) pathway to the process of learning and memory .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [55, 67]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [70, 74]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "Thus , PDE5 inhibitors ( PDE5Is ) are thought to be promising new therapeutic agents for the treatment of Alzheimer ' s disease ( AD ) , a neurodegenerative disorder characterized by memory loss .", "entity": [], "task": "NER"}
{"text": "To explore this possibility , a series of quinoline derivatives were synthesized and evaluated .", "entity": [{"entity": "quinoline", "entity_type": "Chemical", "pos": [42, 51]}], "task": "NER"}
{"text": "We found that compound 7a selectively inhibits PDE5 with an IC ( 50 ) of 0 . 27 nM and readily crosses the blood brain barrier .", "entity": [], "task": "NER"}
{"text": "In an in vivo mouse model of AD , compound 7a rescues synaptic and memory defects .", "entity": [], "task": "NER"}
{"text": "Quinoline - based , CNS - permeant PDE5Is have potential for AD therapeutic development .", "entity": [{"entity": "Quinoline", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Benzo [ alpha ] pyrene repressed DNA mismatch repair in human breast cancer cells .", "entity": [{"entity": "Benzo [ alpha ] pyrene", "entity_type": "Chemical", "pos": [0, 22]}], "task": "NER"}
{"text": "DNA mismatch repair ( MMR ) has been recently implicated to play a significant role in breast cancer progression , however , few studies have examined how various carcinogens affect MMR system in breast cancer cells .", "entity": [], "task": "NER"}
{"text": "The present study employs an in vivo MMR assay developed in our laboratory to assess how prevalent environmental carcinogens such as polycyclic aromatic hydrocarbons ( PAHs ) affect MMR activity in human breast carcinoma cells .", "entity": [{"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [133, 165]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [168, 172]}], "task": "NER"}
{"text": "Specifically , we quantitatively measured MMR activity in ZR75 - 1 cells after they were exposed to benzo [ alpha ] pyrene ( BaP ) , a prototypical PAH , at various concentrations .", "entity": [{"entity": "benzo [ alpha ] pyrene", "entity_type": "Chemical", "pos": [100, 122]}, {"entity": "BaP", "entity_type": "Chemical", "pos": [125, 128]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "Our findings revealed that BaP exposure at high concentrations of 1 and 5 mu M induced significant inhibition of MMR activity in ZR75 - 1 cells .", "entity": [{"entity": "BaP", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "Further , we also identified that MMR repression induced by 5 mu M BaP was mediated through one of the MMR key proteins MSH6 as significant reduction in protein level was detected by western blot .", "entity": [{"entity": "BaP", "entity_type": "Chemical", "pos": [67, 70]}], "task": "NER"}
{"text": "More importantly , ectopic expression of hMSH6 restored MMR activity in the BaP treated cells to the same level as in the control cells .", "entity": [{"entity": "BaP", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "Impaired MMR plays an important role in carcinogenesis .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that BaP induced repression of MMR activity may also contribute to the progression of mutagenesis event .", "entity": [{"entity": "BaP", "entity_type": "Chemical", "pos": [26, 29]}], "task": "NER"}
{"text": "Meanwhile , the present study also for the first demonstrated that our in vivo DNA MMR assay can be applied in the field of environmental toxicology .", "entity": [], "task": "NER"}
{"text": "Detoxification of aldehydes by histidine - containing dipeptides : from chemistry to clinical implications .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis , myocardial and cerebral ischemia , diabetes , neurodegenerative diseases and trauma .", "entity": [{"entity": "Aldehydes", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "carbohydrates", "entity_type": "Chemical", "pos": [47, 60]}], "task": "NER"}
{"text": "In most tissues , aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines , such as glutathione and histidine dipeptides .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [110, 119]}, {"entity": "thiols", "entity_type": "Chemical", "pos": [188, 194]}, {"entity": "amines", "entity_type": "Chemical", "pos": [199, 205]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [216, 227]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [232, 241]}], "task": "NER"}
{"text": "Histidine dipeptides are present in micromolar to millimolar range in the tissues of vertebrates , where they are involved in a variety of physiological functions such as pH buffering , metal chelation , oxidant and aldehyde scavenging .", "entity": [{"entity": "Histidine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [216, 224]}], "task": "NER"}
{"text": "Histidine dipeptides such as carnosine form Michael adducts with lipid - derived unsaturated aldehydes , and react with carbohydrate - derived oxo - and hydroxy - aldehydes forming products of unknown structure .", "entity": [{"entity": "Histidine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "carnosine", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "unsaturated aldehydes", "entity_type": "Chemical", "pos": [81, 102]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [120, 132]}, {"entity": "oxo - and hydroxy - aldehydes", "entity_type": "Chemical", "pos": [143, 172]}], "task": "NER"}
{"text": "Although these peptides react with electrophilic molecules at lower rate than glutathione , they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione - depleted cells or extracellular space where glutathione is scarce .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [78, 89]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [180, 188]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [202, 213]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [260, 271]}], "task": "NER"}
{"text": "Consistent with in vitro findings , treatment with carnosine has been shown to diminish ischemic injury , improve glucose control , ameliorate the development of complications in animal models of diabetes and obesity , promote wound healing and decrease atherosclerosis .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "The protective effects of carnosine have been linked to its anti - oxidant properties , its ability to promote glycolysis , detoxify reactive aldehydes and enhance histamine levels .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [142, 151]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [164, 173]}], "task": "NER"}
{"text": "Thus , treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [159, 167]}], "task": "NER"}
{"text": "The effect of manganese on dopamine toxicity and dopamine transporter ( DAT ) in control and DAT transfected HEK cells .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Chronic exposure to Mn results in the development of a neurological disorder known as manganism characterized by neurological deficits resembling that seen in Parkinsonism .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [20, 22]}], "task": "NER"}
{"text": "Although dopaminergic neurons within the nigrostriatal pathway appear intact , Mn - induced irregularities in DA transmission have been observed including decreased amphetamine - induced DA release and loss of the dopamine transporter ( DAT ) .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [79, 81]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [165, 176]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [214, 222]}], "task": "NER"}
{"text": "Results of studies to evaluate the effect of Mn and DA on cell viability in control and DAT - transfected HEK cells reveal that Mn is equally toxic to both cell lines whereas DA was only toxic to cells containing DAT .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [45, 47]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [128, 130]}], "task": "NER"}
{"text": "DA toxicity was saturable suggesting that transport may be rate limiting .", "entity": [], "task": "NER"}
{"text": "When Mn and DA were added simultaneously to the media , cell toxicity was similar to that produced by Mn alone suggesting that Mn may suppress DA uptake in the DAT containing cells .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [5, 7]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [102, 104]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [127, 129]}], "task": "NER"}
{"text": "Preincubation of DA prior to the addition of Mn resulted in cell death which was essentially additive with that produced independently by the two agents .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [45, 47]}], "task": "NER"}
{"text": "Mn was also shown to decrease DA uptake and amphetamine - induced DA efflux in DAT containing cells .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [44, 55]}], "task": "NER"}
{"text": "Time - lapsed confocal microscopy indicates that Mn can promote trafficking of cell surface DAT into intracellular compartments which may account for the decrease in DA uptake and DA efflux in these cells .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [49, 51]}], "task": "NER"}
{"text": "Mn - induced internalization of DAT may provide an explanation for disruption in DA transmission previously reported in the striatum .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Flavonoids profiles , antioxidant , acetylcholinesterase inhibition activities of extract from Dryoathyrium boryanum ( Willd . ) Ching .", "entity": [{"entity": "Flavonoids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The profiles and bioactivities of flavonoids extracted from Dryoathyrium boryanum ( Willd . ) Ching were investigated .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "The total flavonoids content in extract from D . boryanum is about 145 . 8mg / g .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [10, 20]}], "task": "NER"}
{"text": "By means of HPLC - DAD - ESI - MS , the main flavonoids in D . boryanum were tentatively identified as 3 - hydroxyphloretin 6 ' - O - hexoside , quercetin - 7 - hexoside , apigenin7 - O - glucoside , luteolin 7 - O - glucoside , apigenin 7 - O - galactoside , acacetin 7 - O - ( alpha - D - apio - furanosyl ) ( 1 --> 6 ) - beta - d - glucoside , 3 - hydroxy phloretin 6 - O - hexoside , luteolin - 6 - C - glucoside .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "3 - hydroxyphloretin 6 ' - O - hexoside", "entity_type": "Chemical", "pos": [103, 142]}, {"entity": "quercetin - 7 - hexoside", "entity_type": "Chemical", "pos": [145, 169]}, {"entity": "apigenin7 - O - glucoside", "entity_type": "Chemical", "pos": [172, 197]}, {"entity": "luteolin 7 - O - glucoside", "entity_type": "Chemical", "pos": [200, 226]}, {"entity": "apigenin 7 - O - galactoside", "entity_type": "Chemical", "pos": [229, 257]}, {"entity": "acacetin 7 - O - ( alpha - D - apio - furanosyl ) ( 1 --> 6 ) - beta - d - glucoside", "entity_type": "Chemical", "pos": [260, 344]}, {"entity": "3 - hydroxy phloretin 6 - O - hexoside", "entity_type": "Chemical", "pos": [347, 385]}, {"entity": "luteolin - 6 - C - glucoside", "entity_type": "Chemical", "pos": [388, 416]}], "task": "NER"}
{"text": "0 . 21mg / ml flavonoids extract from D . boryanum showed very strong superoxide anion radical scavenging potential , which is higher than that of rutin ( 0 . 25mg / ml ) .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [70, 80]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [147, 152]}], "task": "NER"}
{"text": "The extract ( 0 . 21mg / ml of flavonoids ) from D . boryanum exhibited similar DPPH scavenging potential with that of rutin ( 0 . 25mg / ml ) .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [31, 41]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [80, 84]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [119, 124]}], "task": "NER"}
{"text": "However , rutin ( 0 . 25mg / ml ) showed a significantly higher reducing power and ABTS scavenging potential than that of 0 . 21mg / ml flavonoids extract from D . boryanum .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [10, 15]}, {"entity": "ABTS", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [136, 146]}], "task": "NER"}
{"text": "It had no effect on acetylcholinesterase .", "entity": [], "task": "NER"}
{"text": "D . boryanum can be considered as a medicinal plant and the flavonoids from D . boryanum are excellent antioxidants .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [60, 70]}], "task": "NER"}
{"text": "Profiling of neuraminidase inhibitory polyphenols from the seeds of Paeonia lactiflora .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [38, 49]}], "task": "NER"}
{"text": "Bacterial neuraminidase ( NA ) is a lynch pin enzyme in the formation of biofilms .", "entity": [], "task": "NER"}
{"text": "Thus NA continues to be one of the key enzymes targeted by bacterial infection .", "entity": [], "task": "NER"}
{"text": "The purpose of this manuscript is to communicate four new naturally derived inhibitors of neuraminidase ( IC50s 3 . 7 - 24 . 4 mu M ) .", "entity": [], "task": "NER"}
{"text": "All these active species ( 1 - 4 ) contained a resveratrol chemotype , however resveratrol itself was inactive ( IC50 > 100 mu M ) .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [79, 90]}], "task": "NER"}
{"text": "1 - 4 were isolated from the 60 % aqueous ethanol extract of seeds of Paeonia lactiflora , which exhibited potent neuraminidase inhibition .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [42, 49]}], "task": "NER"}
{"text": "Purification of the extracts yielded four chiral polyphenols , suffruticosol A ( 1 ) , suffruticosol B ( 2 ) , trans - epsilon - viniferin ( 3 ) , and trans - gnetin H ( 4 ) .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "suffruticosol A", "entity_type": "Chemical", "pos": [63, 78]}, {"entity": "suffruticosol B", "entity_type": "Chemical", "pos": [87, 102]}, {"entity": "trans - epsilon - viniferin", "entity_type": "Chemical", "pos": [111, 138]}, {"entity": "trans - gnetin H", "entity_type": "Chemical", "pos": [151, 167]}], "task": "NER"}
{"text": "Mechanistic analysis of 1 - 4 ' s inhibition showed that they were all reversible , noncompetitive inhibitors .", "entity": [], "task": "NER"}
{"text": "Trans - epsilon - viniferin ( 3 ) underwent trans - cis isomerization , which led to a reduction in inhibition potency .", "entity": [{"entity": "Trans - epsilon - viniferin", "entity_type": "Chemical", "pos": [0, 27]}], "task": "NER"}
{"text": "This correlates with the fact that the cis - isomer is a weaker inhibitor of neuraminidase than the trans - isomer .", "entity": [], "task": "NER"}
{"text": "Importantly , significantly different optical rotations ( [ alpha ] D ) compared to previous reports were found for suffruticosols A ( + 95 vs - 34 ) and B ( + 136 vs + 13 ) .", "entity": [{"entity": "suffruticosols A ( + 95 vs - 34 ) and B", "entity_type": "Chemical", "pos": [116, 155]}], "task": "NER"}
{"text": "These two species are the most important standard metabolites in the whole paeoniaceae family and therefore correction of this error is important .", "entity": [], "task": "NER"}
{"text": "Identification of novel antimycobacterial chemical agents through the in silico multi - conformational structure - based drug screening of a large - scale chemical library .", "entity": [], "task": "NER"}
{"text": "The increasing prevalence of drug - resistant tuberculosis , which is resistant to effective multiple antibiotic , presents a major global health threat .", "entity": [], "task": "NER"}
{"text": "The thymidine monophosphate kinase ( TMPK ) of Mycobacterium tuberculosis ( M . tuberculosis ) , which is an essential enzyme for the maintenance of the thymidine triphosphate pools , is considered an attractive target for the development of effective antibiotics against tuberculosis .", "entity": [{"entity": "thymidine monophosphate", "entity_type": "Chemical", "pos": [4, 27]}, {"entity": "thymidine triphosphate", "entity_type": "Chemical", "pos": [153, 175]}], "task": "NER"}
{"text": "In this study , we attempted to identify novel chemical compounds that specifically target the M . tuberculosis TMPK ( mtTMPK ) .", "entity": [], "task": "NER"}
{"text": "We performed in silico structure - based drug screening using the crystal structure data of mtTMPK and a large - scale virtual compound library , which is composed of 6 , 192 , 930 chemicals .", "entity": [], "task": "NER"}
{"text": "Through a three - step screening method using the DOCK and GOLD , we identified ten chemical compounds that were predicted to have high binding affinity to the active site cleft of the mtTMPK .", "entity": [], "task": "NER"}
{"text": "We then evaluated the antibiotic effects of these chemical compounds on model mycobacteria strains .", "entity": [], "task": "NER"}
{"text": "As a result , we found that a chemical compound , K10 , completely inhibited the growth of Mycobacterium vanbaalenii ( M . vanbaalenii ) and Mycobacterium smegmatis ( M . smegmatis ) .", "entity": [], "task": "NER"}
{"text": "Moreover , K10 does not exhibit any toxic effects on the growth of enterobacteria and mammalian cells .", "entity": [], "task": "NER"}
{"text": "The structural and experimental information regarding this novel chemical compound , K10 , is likely to be useful for the hit - to - lead optimization of new antibiotics for the treatment of tuberculosis .", "entity": [], "task": "NER"}
{"text": "Monocyclic beta - lactams as antibacterial agents : facing antioxidant activity of N - methylthio - azetidinones .", "entity": [{"entity": "Monocyclic beta - lactams", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "N - methylthio - azetidinones", "entity_type": "Chemical", "pos": [83, 112]}], "task": "NER"}
{"text": "A series of N - methylthio - beta - lactams with antibacterial activity were thoroughly evaluated as antioxidants .", "entity": [{"entity": "N - methylthio - beta - lactams", "entity_type": "Chemical", "pos": [12, 43]}], "task": "NER"}
{"text": "We found that only the presence of a polyphenolic moiety anchored to the beta - lactam ring ensured an adequate antioxidant potency .", "entity": [{"entity": "polyphenolic", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "beta - lactam", "entity_type": "Chemical", "pos": [73, 86]}], "task": "NER"}
{"text": "New compounds , efficiently combining in one structure antioxidant and antibacterial activity , may provide a promising basis for the development of new leads useful in adverse clinical conditions such as in cystic fibrosis patients , in whom colonization by MRSA and epithelial damage by chronic pulmonary oxidative stress take place .", "entity": [], "task": "NER"}
{"text": "Antimicrobial activity of various 4 - and 5 - substituted 1 - phenylnaphthalenes .", "entity": [{"entity": "4 - and 5 - substituted 1 - phenylnaphthalenes", "entity_type": "Chemical", "pos": [34, 80]}], "task": "NER"}
{"text": "Bacterial cell division occurs in conjunction with the formation of a cytokinetic Z - ring structure comprised of FtsZ subunits .", "entity": [], "task": "NER"}
{"text": "Agents that can disrupt Z - ring formation have the potential , through this unique mechanism , to be effective against several of the newly emerging multi - drug resistant strains of infectious bacteria .", "entity": [], "task": "NER"}
{"text": "1 - and 12 - Aryl substituted benzo [ c ] phenanthridines have been identified as antibacterial agents that could exert their activity by disruption of Z - ring formation .", "entity": [{"entity": "1 - and 12 - Aryl substituted benzo [ c ] phenanthridines", "entity_type": "Chemical", "pos": [0, 57]}], "task": "NER"}
{"text": "Substituted 4 - and 5 - amino - 1 - phenylnaphthalenes represent substructures within the pharmacophore of these benzo [ c ] phenanthridines .", "entity": [{"entity": "4 - and 5 - amino - 1 - phenylnaphthalenes", "entity_type": "Chemical", "pos": [12, 54]}, {"entity": "benzo [ c ] phenanthridines", "entity_type": "Chemical", "pos": [113, 140]}], "task": "NER"}
{"text": "Several 4 - and 5 - substituted 1 - phenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis .", "entity": [{"entity": "4 - and 5 - substituted 1 - phenylnaphthalenes", "entity_type": "Chemical", "pos": [8, 54]}], "task": "NER"}
{"text": "The impact of select compounds on the polymerization dynamics of S . aureus FtsZ was also assessed .", "entity": [], "task": "NER"}
{"text": "Fragment - based design , synthesis , and biological evaluation of N - substituted - 5 - ( 4 - isopropylthiophenol ) - 2 - hydroxynicotinamide derivatives as novel Mcl - 1 inhibitors .", "entity": [{"entity": "N - substituted - 5 - ( 4 - isopropylthiophenol ) - 2 - hydroxynicotinamide", "entity_type": "Chemical", "pos": [67, 142]}], "task": "NER"}
{"text": "We have previously reported a nanomolar inhibitor of antiapoptotic Mcl - 1 protein , 3 - thiomorpholin - 8 - oxo - 8H - acenaphtho [ 1 , 2 - b ] pyrrole - 9 - carbonitrile ( S1 ) .", "entity": [{"entity": "3 - thiomorpholin - 8 - oxo - 8H - acenaphtho [ 1 , 2 - b ] pyrrole - 9 - carbonitrile", "entity_type": "Chemical", "pos": [85, 171]}], "task": "NER"}
{"text": "S1 plays its function by binding to the BH3 groove of Mcl - 1 .", "entity": [], "task": "NER"}
{"text": "Basing on this spacial structural characteristic , we developed a novel class of Mcl - 1 inhibitor using fragment - based drug discovery approach .", "entity": [], "task": "NER"}
{"text": "By dissecting S1 , we identified the compound 4 with a 2 - hydroxypyridine core as the starting fragment .", "entity": [{"entity": "2 - hydroxypyridine", "entity_type": "Chemical", "pos": [55, 74]}], "task": "NER"}
{"text": "In the following molecular growth , we used the ligand efficiency evaluation and fit quality score to assess the fragments .", "entity": [], "task": "NER"}
{"text": "A novel potent compound , N - benzyl - 5 - ( 4 - isopropylthiophenol ) - 2 - hydroxyl nicotinamide ( 12c ) , which binds Mcl - 1 with an IC ( 50 ) value of 54 nM was obtained .", "entity": [{"entity": "N - benzyl - 5 - ( 4 - isopropylthiophenol ) - 2 - hydroxyl nicotinamide", "entity_type": "Chemical", "pos": [26, 98]}], "task": "NER"}
{"text": "Compound 12c demonstrated a better aqueous solubility than S1 .", "entity": [], "task": "NER"}
{"text": "Cellular and molecular mechanisms of accelerated fracture healing by COX2 gene therapy : studies in a mouse model of multiple fractures .", "entity": [], "task": "NER"}
{"text": "This study sought to determine the cellular and molecular mechanisms of cyclooxygenase - 2 ( COX2 ) gene therapy to accelerate fracture repair in a mouse multiple tibial fractures model .", "entity": [], "task": "NER"}
{"text": "The lenti - COX2 ( or lenti - gfp control vector ) was injected into fractures on day 1 post - fracture .", "entity": [], "task": "NER"}
{"text": "At days 3 - 7 , the COX2 treatment increased Sdf1 - , Cxcr4 - , Nes - , and Podxl - expressing mesenchymal stem cells ( MSCs ) within fracture calluses , suggesting an enhanced MSC recruitment or expansion .", "entity": [], "task": "NER"}
{"text": "The COX2 - treated mice formed smaller cartilaginous calluses that had less cartilage tissues than control mice .", "entity": [], "task": "NER"}
{"text": "The expression of Sox9 mRNA was 7 - fold less in COX2 - treated than in control calluses at day 14 , implying that COX2 reduces chondrocytic differentiation of MSCs .", "entity": [], "task": "NER"}
{"text": "The therapy also enhanced angiogenesis as reflected by increased immunostaining of CD31 , vWF , and alpha - SMA over controls in the cartilaginous callus at day 14 - 21 .", "entity": [], "task": "NER"}
{"text": "At which time , the COX2 gene therapy promoted bony remodeling of the cartilaginous callus to bridge the fracture gap that was accompanied by 2 - fold increase in osteoclasts along the surface of the woven bone and an onset of osteogenesis .", "entity": [], "task": "NER"}
{"text": "Blocking angiogenesis with daily injection of endostatin from day 4 to day 10 into fracture sites blocked the COX2 - mediated reduction of callus size that was associated with an increase in hypertrophic chondrocytes and concomitant reduction in osteoclasts .", "entity": [], "task": "NER"}
{"text": "In conclusion , COX2 accelerates fracture healing in part through three biological actions : 1 ) increased recruitment / expansion of MSCs ; 2 ) decreased cartilaginous callus formation ; and 3 ) increased angiogenesis - dependent cartilage remodeling .", "entity": [], "task": "NER"}
{"text": "These effects were associated with an earlier onset of bony bridging of the fracture gap .", "entity": [], "task": "NER"}
{"text": "Singular phase nano - optics in plasmonic metamaterials for label - free single - molecule detection .", "entity": [], "task": "NER"}
{"text": "The non - trivial behaviour of phase is crucial for many important physical phenomena , such as , for example , the Aharonov - Bohm effect and the Berry phase .", "entity": [], "task": "NER"}
{"text": "By manipulating the phase of light one can create ' twisted ' photons , vortex knots and dislocations which has led to the emergence of the field of singular optics relying on abrupt phase changes .", "entity": [], "task": "NER"}
{"text": "Here we demonstrate the feasibility of singular visible - light nano - optics which exploits the benefits of both plasmonic field enhancement and the peculiarities of the phase of light .", "entity": [], "task": "NER"}
{"text": "We show that properly designed plasmonic metamaterials exhibit topologically protected zero reflection yielding to sharp phase changes nearby , which can be employed to radically improve the sensitivity of detectors based on plasmon resonances .", "entity": [], "task": "NER"}
{"text": "By using reversible hydrogenation of graphene and binding of streptavidin - biotin , we demonstrate an areal mass sensitivity at a level of fg mm ( - 2 ) and detection of individual biomolecules , respectively .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "biotin", "entity_type": "Chemical", "pos": [76, 82]}], "task": "NER"}
{"text": "Our proof - of - concept results offer a route towards simple and scalable single - molecule label - free biosensing technologies .", "entity": [], "task": "NER"}
{"text": "A physiologically based pharmacokinetic model for the oxime TMB - 4 : simulation of rodent and human data .", "entity": [{"entity": "oxime", "entity_type": "Chemical", "pos": [54, 59]}, {"entity": "TMB - 4", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "Multiple oximes have been synthesized and evaluated for use as countermeasures against chemical warfare nerve agents .", "entity": [{"entity": "oximes", "entity_type": "Chemical", "pos": [9, 15]}], "task": "NER"}
{"text": "The current U . S . military and civilian oxime countermeasure , 2 - [ ( hydroxyimino ) methyl ] - 1 - methylpyridin - 1 - ium chloride ( 2 - PAM ) , is under consideration for replacement with a more effective acetylcholinesterase reactivator , 1 , 1 ' - methylenebis { 4 - hydroxyiminomethyl } pyridinium dimethanesulfonate ( MMB - 4 ) .", "entity": [{"entity": "oxime", "entity_type": "Chemical", "pos": [42, 47]}, {"entity": "2 - [ ( hydroxyimino ) methyl ] - 1 - methylpyridin - 1 - ium chloride", "entity_type": "Chemical", "pos": [65, 135]}, {"entity": "2 - PAM", "entity_type": "Chemical", "pos": [138, 145]}, {"entity": "1 , 1 ' - methylenebis { 4 - hydroxyiminomethyl } pyridinium dimethanesulfonate", "entity_type": "Chemical", "pos": [246, 325]}, {"entity": "MMB - 4", "entity_type": "Chemical", "pos": [328, 335]}], "task": "NER"}
{"text": "Kinetic data in the scientific literature for MMB - 4 are limited ; therefore , a physiologically based pharmacokinetic ( PBPK ) model was developed for a structurally related oxime , 1 , 1 ' - trimethylenebis { 4 - hydroximinomethyl } pyridinium dibromide .", "entity": [{"entity": "MMB - 4", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "oxime", "entity_type": "Chemical", "pos": [176, 181]}, {"entity": "1 , 1 ' - trimethylenebis { 4 - hydroximinomethyl } pyridinium dibromide", "entity_type": "Chemical", "pos": [184, 256]}], "task": "NER"}
{"text": "Based on a previous model structure for the organophosphate diisopropylfluorophosphate , the model includes key sites of acetylcholinesterase inhibition ( brain and diaphragm ) , as well as fat , kidney , liver , rapidly perfused tissues and slowly perfused tissues .", "entity": [{"entity": "organophosphate", "entity_type": "Chemical", "pos": [44, 59]}, {"entity": "diisopropylfluorophosphate", "entity_type": "Chemical", "pos": [60, 86]}], "task": "NER"}
{"text": "All tissue compartments are diffusion limited .", "entity": [], "task": "NER"}
{"text": "Model parameters were collected from the literature , predicted using quantitative structure - property relationships or , when necessary , fit to available pharmacokinetic data from the literature .", "entity": [], "task": "NER"}
{"text": "The model was parameterized using rat plasma , tissue and urine time course data from intramuscular administration , as well as human blood and urine data from intravenous and intramuscular administration ; sensitivity analyses were performed .", "entity": [], "task": "NER"}
{"text": "The PBPK model successfully simulates rat and human data sets and has been evaluated by predicting intravenous mouse and intramuscular human data not used in the development of the model .", "entity": [], "task": "NER"}
{"text": "Monte Carlo analyses were performed to quantify human population kinetic variability in the human evaluation data set .", "entity": [], "task": "NER"}
{"text": "The model identifies potential pharmacokinetic differences between rodents and humans , indicated by differences in model parameters between species .", "entity": [], "task": "NER"}
{"text": "The PBPK model can be used to optimize the dosing regimen to improve oxime therapeutic efficacy in a human population .", "entity": [{"entity": "oxime", "entity_type": "Chemical", "pos": [69, 74]}], "task": "NER"}
{"text": "Improving the dispersity of detonation nanodiamond : differential scanning calorimetry as a new method of controlling the aggregation state of nanodiamond powders .", "entity": [], "task": "NER"}
{"text": "Detonation nanodiamond ( ND ) is a suitable source material to produce unique samples consisting of almost uniform diamond nanocrystals ( d = 3 - 5 nm ) .", "entity": [{"entity": "diamond", "entity_type": "Chemical", "pos": [15, 22]}], "task": "NER"}
{"text": "Such samples exist in the form of long stable aqueous dispersions with narrow size distribution of diamond particles .", "entity": [{"entity": "diamond", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "The material is finding ever increasing application in biomedicine .", "entity": [], "task": "NER"}
{"text": "The major problem in producing monodispersed diamond colloids lies in the necessity of deagglomeration of detonation soot and / or removing of clusters formed by already isolated core particles in dry powders .", "entity": [{"entity": "diamond", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "To do this one must have an effective method to monitor the aggregation state or dispersity of powders and gels prior to the preparation of aqueous dispersions .", "entity": [], "task": "NER"}
{"text": "In the absence of dispersity control at various stages of preparation the reproducibility of properties of existing ND materials is poor .", "entity": [], "task": "NER"}
{"text": "In this paper we introduce differential scanning calorimetry ( DSC ) as a new tool capable to distinguish the state of aggregation in dry and wetted ND materials and to follow changes in this state under different types of treatment .", "entity": [], "task": "NER"}
{"text": "Samples with identical X - ray diffraction patterns ( XRD ) and high resolution transmission electron microscopy ( HRTEM ) images gave visibly different DSC traces .", "entity": [], "task": "NER"}
{"text": "Strong correlation was found between dynamic light scattering ( DLS ) data for colloids and DSC parameters for gels and powders of the same material .", "entity": [], "task": "NER"}
{"text": "Based on DSC data we improved dispersity of existing ND materials and isolated samples with the best possible DSC parameters .", "entity": [], "task": "NER"}
{"text": "These were true monodispersed easily dispersible fractions of ND particles with diameters of ca .", "entity": [], "task": "NER"}
{"text": "3 nm .", "entity": [], "task": "NER"}
{"text": "The sequence of the enterococcal cytolysin imparts unusual lanthionine stereochemistry .", "entity": [{"entity": "lanthionine", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "The enterococcal cytolysin is a two - component lantibiotic of unknown structure with hemolytic activity that is important for virulence .", "entity": [], "task": "NER"}
{"text": "We prepared cytolysin by coexpression of each precursor peptide with the synthetase CylM in Escherichia coli and characterized its structure .", "entity": [], "task": "NER"}
{"text": "Unexpectedly , cytolysin is to our knowledge the first example of a lantibiotic containing lanthionine and methyllanthionine structures with different stereochemistries in the same peptide .", "entity": [{"entity": "lanthionine", "entity_type": "Chemical", "pos": [91, 102]}, {"entity": "methyllanthionine", "entity_type": "Chemical", "pos": [107, 124]}], "task": "NER"}
{"text": "The stereochemistry is determined by the sequence of the substrate peptide .", "entity": [], "task": "NER"}
{"text": "Fibronectin in the palatine tonsil as a susceptibility marker in Egyptian rheumatic families : Histological and immunohistochemical studies .", "entity": [], "task": "NER"}
{"text": "Rheumatic fever ( RF ) and rheumatic heart disease ( RHD ) are the multisystem autoimmune sequel of group A streptococci ( GAS ) infection of the upper respiratory passages , mainly tonsillopharyngitis .", "entity": [], "task": "NER"}
{"text": "The major receptor on the surface of human palatine tonsil for GAS is fibronectin ( FN ; adhesin receptor ) .", "entity": [], "task": "NER"}
{"text": "Early detection of RF susceptibility is considered as an important aim of this study .", "entity": [], "task": "NER"}
{"text": "Therefore , the present study aimed to use FN immunoreactivity ( FN - ir ) as a marker for early detection of rheumatic susceptible children with palatine tonsil crypts surface epithelium .", "entity": [], "task": "NER"}
{"text": "A total of 30 palatine tonsillar specimens were obtained from children aged from 3 to 15 years .", "entity": [], "task": "NER"}
{"text": "Histological studies showed moderate vascular changes and more than four apparent epithelial disruptions in the crypt epithelium .", "entity": [], "task": "NER"}
{"text": "FN - ir showed a significant increase in FN in the basal layers of surface epithelium , subepithelial connective tissue and interfollicular areas .", "entity": [], "task": "NER"}
{"text": "Tonsils of children in rheumatic families showed significant increase in FN in subepithelial connective tissue areas with more than one apparent crypt epithelial disruption compared to normal children .", "entity": [], "task": "NER"}
{"text": "We can conclude that FN plays a central role in the RF and differentially distributed in the functional compartments of the palatine tonsil in children with RHD , so FN - ir can be used as a marker for rheumatic susceptibility .", "entity": [], "task": "NER"}
{"text": "Relationship between oxidative stress and chronic daily headache in children .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to investigate the relationship between oxidative stress and chronic daily headache ( CDH ) in children .", "entity": [], "task": "NER"}
{"text": "Although there are reports that oxidative injury may play a role in the pathophysiology of some neurologic disorders , such as migraine and epilepsy , by disrupting or destroying cell membranes through the formation of free radical and reactive oxygen species , the pathophysiology of headache is not clearly established .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [245, 251]}], "task": "NER"}
{"text": "A total of 38 children ( 16 boys and 22 girls ) with CDH , aged between 7 and 15 years , were enrolled in the study .", "entity": [], "task": "NER"}
{"text": "The control group consisted of 39 healthy children ( 17 boys and 22 girls ) , aged between 7 and 14 years .", "entity": [], "task": "NER"}
{"text": "The mean age was 10 . 9 +/- 2 . 2 years for both the groups .", "entity": [], "task": "NER"}
{"text": "Activities of erythrocyte superoxide dismutase ( SOD ) , catalase ( CAT ) , and glutathione peroxidase ( GPx ) as well as malondialdehyde ( MDA ) levels in all the children of both the groups were measured .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [26, 36]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [80, 91]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [122, 137]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [140, 143]}], "task": "NER"}
{"text": "Mean activities of erythrocyte SOD , CAT , and GPx as well as MDA levels were significantly higher in the study group than in the control group ( p < 0 . 001 ) .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [62, 65]}], "task": "NER"}
{"text": "The findings of this study suggest that oxidative stress may play a causal or consequential role in children with CDH .", "entity": [], "task": "NER"}
{"text": "Study of intracellular delivery of doxorubicin from poly ( lactide - co - glycolide ) nanoparticles by means of fluorescence lifetime imaging and confocal Raman microscopy .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "poly ( lactide - co - glycolide )", "entity_type": "Chemical", "pos": [52, 85]}], "task": "NER"}
{"text": "The intracellular delivery of Doxorubicin ( Dox ) from poly ( lactide - co - glycolide ) ( PLGA ) nanoparticles stabilised with bovine serum albumin , in HepG2 cells , is studied via flow cytometry , fluorescence lifetime imaging microscopy ( FLIM ) , confocal Raman microscopy ( CRM ) and cell viability studies .", "entity": [{"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [30, 41]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [44, 47]}, {"entity": "poly ( lactide - co - glycolide )", "entity_type": "Chemical", "pos": [55, 88]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "Flow cytometry shows that the initial uptake of PLGA and Dox follow the same kinetics .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [57, 60]}], "task": "NER"}
{"text": "However , following 8 h of incubation , the fluorescence intensity and cellular uptake of Dox decreases , while in the case of PLGA both parameters remain constant .", "entity": [{"entity": "Dox", "entity_type": "Chemical", "pos": [90, 93]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [127, 131]}], "task": "NER"}
{"text": "FLIM shows the presence of a single - lifetime species , with a lifetime of 1 . 15 ns when measured inside the cells .", "entity": [], "task": "NER"}
{"text": "Cell viability decreases by approximately 20 % when incubated for 24 h with PLGA loaded with Dox , with a particle concentration of 100 micro g . mL ( - 1 ) .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [76, 80]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [93, 96]}], "task": "NER"}
{"text": "At the single - cell level , CRM shows changes in the bands from DNA and proteins in the cell nucleus when incubated with PLGA loaded with Dox .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [122, 126]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "Modern subunit vaccines : development , components , and research opportunities .", "entity": [], "task": "NER"}
{"text": "Traditional vaccines , based on the administration of killed or attenuated microorganisms , have proven to be among the most effective methods for disease prevention .", "entity": [], "task": "NER"}
{"text": "Safety issues related to administering these complex mixtures , however , prevent their universal application .", "entity": [], "task": "NER"}
{"text": "Through identification of the microbial components responsible for protective immunity , vaccine formulations can be simplified , enabling molecular - level vaccine characterization , improved safety profiles , prospects to develop new high - priority vaccines ( e . g . for HIV , tuberculosis , and malaria ) , and the opportunity for extensive vaccine component optimization .", "entity": [], "task": "NER"}
{"text": "This subunit approach , however , comes at the expense of decreased immunity , requiring the addition of immunostimulatory agents ( adjuvants ) .", "entity": [], "task": "NER"}
{"text": "As few adjuvants are currently used in licensed vaccines , adjuvant development represents an exciting area for medicinal chemists to play a role in the future of vaccine development .", "entity": [], "task": "NER"}
{"text": "In addition , immune responses can be further customized though optimization of delivery systems , tuning the size of particulate vaccines , targeting specific cells of the immune system ( e . g . dendritic cells ) , and adding components to aid vaccine efficacy in whole immunized populations ( e . g . promiscuous T - helper epitopes ) .", "entity": [], "task": "NER"}
{"text": "Herein we review the current state of the art and future direction in subunit vaccine development , with a focus on the described components and their potential to steer the immune response toward a desired response .", "entity": [], "task": "NER"}
{"text": "Directed motion of colloidal particles in a galvanic microreactor .", "entity": [], "task": "NER"}
{"text": "The mechanisms leading to the deposition of colloidal particles in a copper - gold galvanic microreactor are investigated .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [69, 75]}], "task": "NER"}
{"text": "Using in situ current density measurements and particle velocimetry , we establish correlations between the spatial arrangement and the geometry of the electrodes , current density distribution , and particle aggregation behavior .", "entity": [], "task": "NER"}
{"text": "Ionic transport phenomena are responsible for the occurrence of strongly localized high current density at the edges and corners of the copper electrodes at large electrode separation , leading to a preferential aggregation of colloidal particles at the electrode edges .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [136, 142]}], "task": "NER"}
{"text": "Preferential aggregation appears to be the result of a combination of electrophoretic effects and changes in bulk electrolyte flow patterns .", "entity": [], "task": "NER"}
{"text": "We demonstrate that electrolyte flow is most likely driven by electrochemical potential gradients of reaction products formed during the inhomogeneous copper dissolution .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [151, 157]}], "task": "NER"}
{"text": "New prospects for vinblastine analogues as anticancer agents .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [18, 29]}], "task": "NER"}
{"text": "Boger et al . synthesized a series of C20 ' urea derivatives of vinblastine that matched or exceeded the potency of vinblastine in cell growth inhibition assays .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "vinblastine", "entity_type": "Chemical", "pos": [64, 75]}, {"entity": "vinblastine", "entity_type": "Chemical", "pos": [116, 127]}], "task": "NER"}
{"text": "The studies demonstrated the importance of the H - bond donor on the C20 ' position and revealed the presence of a space surrounding the C20 ' substituent that tolerates a wide variety of substituents , remarkably enhancing potency of vinblastine analogues .", "entity": [{"entity": "H", "entity_type": "Chemical", "pos": [47, 48]}, {"entity": "vinblastine", "entity_type": "Chemical", "pos": [235, 246]}], "task": "NER"}
{"text": "Rheological study of mutarotation of fructose in anhydrous state .", "entity": [{"entity": "fructose", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "Rheological measurement was employed to study the mutarotation of D - fructose in anhydrous state .", "entity": [{"entity": "D - fructose", "entity_type": "Chemical", "pos": [66, 78]}], "task": "NER"}
{"text": "By monitoring the evolution of shear viscosity with time , rate constants for mutarotation were estimated , and two different stages of this reaction were identified .", "entity": [], "task": "NER"}
{"text": "One of the mutarotation stages is rapid and has a low activation energy , whereas the other is much slower and has a much higher activation energy .", "entity": [], "task": "NER"}
{"text": "Possible conversions corresponding to these two phases are discussed .", "entity": [], "task": "NER"}
{"text": "This work demonstrates that , in addition to the routine techniques such polarimetry and gas - liquid chromatography , rheological measurement can be used as an alternative method to continuously monitor the mutarotation of sugars .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [224, 230]}], "task": "NER"}
{"text": "One - pot synthesis of tin - embedded carbon / silica nanocomposites for anode materials in lithium - ion batteries .", "entity": [{"entity": "tin", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [38, 44]}, {"entity": "silica", "entity_type": "Chemical", "pos": [47, 53]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "We report a facile \" one - pot \" method for the synthesis of Sn - embedded carbon - silica ( CS ) mesostructured ( nanostructured ) composites through the selective interaction of resol ( carbon precursor ) , tetraethylorthosilicate ( TEOS ) , and tributylphenyltin ( Sn precursor ) with an amphiphilic diblock copolymer , poly ( ethylene oxide - b - styrene ) , PEO - b - PS .", "entity": [{"entity": "Sn", "entity_type": "Chemical", "pos": [61, 63]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "silica", "entity_type": "Chemical", "pos": [84, 90]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [188, 194]}, {"entity": "tetraethylorthosilicate", "entity_type": "Chemical", "pos": [209, 232]}, {"entity": "TEOS", "entity_type": "Chemical", "pos": [235, 239]}, {"entity": "tributylphenyltin", "entity_type": "Chemical", "pos": [248, 265]}, {"entity": "Sn", "entity_type": "Chemical", "pos": [268, 270]}, {"entity": "poly ( ethylene oxide - b - styrene )", "entity_type": "Chemical", "pos": [323, 360]}, {"entity": "PEO - b - PS", "entity_type": "Chemical", "pos": [363, 375]}], "task": "NER"}
{"text": "A unique morphology transition from Sn nanowires to spherical Sn nanoparticles embedded in CS framework has been obtained .", "entity": [{"entity": "Sn", "entity_type": "Chemical", "pos": [36, 38]}, {"entity": "Sn", "entity_type": "Chemical", "pos": [62, 64]}], "task": "NER"}
{"text": "Metallic Sn species are homogeneously embedded in a rigid CS framework and are effectively confined within the nanostructures .", "entity": [{"entity": "Sn", "entity_type": "Chemical", "pos": [9, 11]}], "task": "NER"}
{"text": "The resulting composites are used as anode materials for lithium - ion batteries and exhibit high specific capacities ( 600 mA h g - (1) at a current density of 45 mA g - (1) , and 440 mA h g - (1) at a current density of 300 mA g - (1) ) and an excellent cyclability of over 100 cycles with high Coulombic efficiency .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "Most of all , the novel method developed in this work for synthesizing functional hybrid materials can be extended to the preparation of various functional nanocomposites owing to its versatility and facileness .", "entity": [], "task": "NER"}
{"text": "Enhancement of angiogenesis by a 27 kDa lectin from perivitelline fluid of horseshoe crab embryos through upregulation of VEGF and its receptor .", "entity": [], "task": "NER"}
{"text": "Angiogenesis , the expansion of a capillary network , is implicated in several pathological conditions .", "entity": [], "task": "NER"}
{"text": "Drug - based inhibition of angiogenesis is being explored as therapy .", "entity": [], "task": "NER"}
{"text": "Conversely , therapeutic angiogenesis contributes to control conditions such as ischemia .", "entity": [], "task": "NER"}
{"text": "Here we report pro - angiogenic activity of perivitelline fluid ( PVF ) from Indian horseshoe crab embryos and one of its purified fractions , a 27 kDa lectin , using the chick embryonic chorioallantoic membrane assay .", "entity": [], "task": "NER"}
{"text": "Enhancement in number and diameter of blood vessels after treatment with PVF and lectin suggested their pro - angiogenic effect .", "entity": [], "task": "NER"}
{"text": "Quantitative RT - PCR showed that this effect is mediated through modulation of expression of VEGF and VEGFR - 2 / kinase domain receptor genes .", "entity": [], "task": "NER"}
{"text": "Novel insights into the pervasive role of M ( 3 ) muscarinic receptor in cardiac diseases .", "entity": [], "task": "NER"}
{"text": "Cardiac diseases remain the leading cause of morbidity and mortality worldwide .", "entity": [], "task": "NER"}
{"text": "Heart functions are regulated by autonomic nervous systems through their transmitters and modulators , binding to cell surface receptors .", "entity": [], "task": "NER"}
{"text": "Among them , the cardiac M ( 3 ) muscarinic acetylcholine receptor ( M ( 3 ) - mAChR ) has been studied for more than 2 decades since its first discovery in mammalian heart in 1990s .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [44, 57]}], "task": "NER"}
{"text": "The location and pathophysiological role of M ( 3 ) - mAChR in the cardiovascular system have been extensively studied and many pathways involved have been uncovered .", "entity": [], "task": "NER"}
{"text": "Gain - and loss - of - function studies have revealed the ubiquitous roles of M ( 3 ) - mAChR in physiological and pathological conditions .", "entity": [], "task": "NER"}
{"text": "Recently , many new findings have been uncovered about the relationship between M ( 3 ) - mAChR and cardiac diseases , including cardiac ischemia , pathological cardiac hypertrophy , cardiac arrhythmias , cardiac conduction and heart failure .", "entity": [], "task": "NER"}
{"text": "Furthermore , the novel potential cardioprotective role of M ( 3 ) - mAChR against heart injury by regulation of microRNAs ( miRNAs ) has been revealed in the most updated research .", "entity": [], "task": "NER"}
{"text": "In this review , the current new findings on the role of M ( 3 ) - mAChR in heart diseases are updated , the downstream signaling pathways are summarized , perspectives and challenges of M ( 3 ) - mAChR as therapeutic targets are discussed .", "entity": [], "task": "NER"}
{"text": "Growth of Pt nanowires by atomic layer deposition on highly ordered pyrolytic graphite .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [10, 12]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [78, 86]}], "task": "NER"}
{"text": "The formation of Pt nanowires ( NWs ) by atomic layer deposition on highly ordered pyrolytic graphite ( HOPG ) is investigated .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [17, 19]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "Pt is deposited only at the step edges of HOPG and not on the basal planes , leading to the formation of laterally aligned Pt NWs .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [123, 125]}], "task": "NER"}
{"text": "A growth model involving a morphological transition from 0 - D to 1 - D structures via coalescence is presented .", "entity": [], "task": "NER"}
{"text": "The width of the NWs grows at a rate greater than twice the vertical growth rate .", "entity": [], "task": "NER"}
{"text": "This asymmetry is ascribed to the wetting properties of Pt on HOPG as influenced by the formation of graphene oxide .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "graphene oxide", "entity_type": "Chemical", "pos": [101, 115]}], "task": "NER"}
{"text": "A difference in Pt growth kinetics based on crystallographic orientation may also contribute .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [16, 18]}], "task": "NER"}
{"text": "The impact of oxidative stress on islet transplantation and monitoring the graft survival by non - invasive imaging .", "entity": [], "task": "NER"}
{"text": "Islet transplantation is an attractive strategy to treat severe diabetic conditions in patients suffering from autoimmune derived diabetes , and it has currently been considered a forefront research arena in diabetes .", "entity": [], "task": "NER"}
{"text": "Major aim of islet transplantation is to achieve successful insulin independent disease free survival .", "entity": [], "task": "NER"}
{"text": "The key challenges in transplanted islets are the generation of reactive oxygen species ( ROS ) and associated oxidative stress , pro - inflammatory cytokine - ( TNF alpha ) mediated apoptotic induction , attack by immune cells , and achieving revascularization with minimal hypoxic microenvironment .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "Free radicals and their derivatives are constantly produced in living systems , but at relatively low level , and in a balanced state .", "entity": [], "task": "NER"}
{"text": "Oxidative stress , which occurs as a result of an imbalance between the intracellular free radicals production and the cellular antioxidant defense mechanisms in the transplanted islets , can lead to cell death .", "entity": [], "task": "NER"}
{"text": "The balance between oxidants and antioxidants in a cell can be easily disturbed by increase in ROS production or reduction in the level of cellular antioxidant defensive substances , which can cause many metabolic complications , including pancreatic beta - cell damage .", "entity": [], "task": "NER"}
{"text": "Antioxidants function as blockers of radical processes by eliminating harmful ROS produced during normal cellular metabolism .", "entity": [], "task": "NER"}
{"text": "A complex antioxidant defense mechanism has been developed by nature in cells to protect the cellular homeostasis .", "entity": [], "task": "NER"}
{"text": "This system mainly includes antioxidant enzymes , vitamins and minerals .", "entity": [], "task": "NER"}
{"text": "As transplanted islet survival is crucial for achieving successful therapy , most of these antioxidants can be used as a supplement to scavenge the local ROS thereby improving the survival of transplanted islets .", "entity": [], "task": "NER"}
{"text": "Currently , very few techniques have been routinely used to qualitatively and quantitatively assess the survival and function of islet grafts , especially to confirm the success of treatment , which includes metabolic parameters such as blood glucose , insulin and C - peptide levels .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [243, 250]}], "task": "NER"}
{"text": "These biochemical measurements provide markers at only the late stages of islet rejection .", "entity": [], "task": "NER"}
{"text": "Use of molecular imaging techniques has the potential for real - time non - invasive monitoring of the functional status and viability of transplanted islet grafts in living animals .", "entity": [], "task": "NER"}
{"text": "This review mainly focuses on the current status of islet transplantations , potential preventive strategies used to reduce oxidative stress - mediated toxicity in islet grafts , and use of molecular imaging as a tool to quantitatively evaluate the functional status of the transplanted islets in living animals .", "entity": [], "task": "NER"}
{"text": "Computational peptidology : a new and promising approach to therapeutic Peptide design .", "entity": [], "task": "NER"}
{"text": "The recent focus on protein - protein interaction networks has increasingly been shifted towards the disruption of protein complexes , which either are mediated by the binding of a globular domain in one protein to a short peptide stretch in another , or involve flat , large , and hydrophobic interfaces that classical small - molecule agents are not always ideally suited .", "entity": [], "task": "NER"}
{"text": "Rational design of therapeutic peptides with high affinity targeting such interactions has emerged as a new and promising tool in discovery of potential drug candidates against associated diseases .", "entity": [], "task": "NER"}
{"text": "The design is commonly based on bioinformatics methods or molecular modeling techniques , indirectly exploiting structure - activity relationship at the level of peptide sequence or directly deriving lead entities from protein complex architecture .", "entity": [], "task": "NER"}
{"text": "Here , a newly rising subfield called computational peptidology that focuses on the use of computational and theoretical approaches to treat peptiderelated problems is comprehensively reviewed on the design and discovery of peptide agents targeting protein - protein interactions .", "entity": [], "task": "NER"}
{"text": "We address a systematic discussion on several representative cases in which the computational peptidology is successfully employed to develop peptide therapeutics .", "entity": [], "task": "NER"}
{"text": "Besides , some problems and pitfalls accompanied with the current use of computational methods in peptide modeling and design are also present .", "entity": [], "task": "NER"}
{"text": "Thermal sintering : a novel technique used in the design , optimization and biopharmaceutical evaluation of propranolol HCl gastric floating tablets .", "entity": [{"entity": "propranolol HCl", "entity_type": "Chemical", "pos": [108, 123]}], "task": "NER"}
{"text": "Abstract The objective of the present investigation was to study the applicability of thermal sintering technique for the development of gastric floating tablets of propranolol HCl .", "entity": [{"entity": "propranolol HCl", "entity_type": "Chemical", "pos": [165, 180]}], "task": "NER"}
{"text": "Formulations were prepared using four independent variables , namely ( i ) polymer quantity , ( ii ) sodium bicarbonate concentration , ( iii ) sintering temperature and ( iv ) sintering time .", "entity": [{"entity": "sodium bicarbonate", "entity_type": "Chemical", "pos": [101, 119]}], "task": "NER"}
{"text": "Floating lag time and t ( 95 ) were taken as dependent variables .", "entity": [], "task": "NER"}
{"text": "Tablets were prepared by the direct compression method and were evaluated for physicochemical properties , in vitro buoyancy and dissolution studies .", "entity": [], "task": "NER"}
{"text": "From the drug release studies , it was observed that drug retarding property mainly depends upon the sintering temperature and time of exposure .", "entity": [], "task": "NER"}
{"text": "The statistically optimized formulation ( PTSso ) was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry studies , and no significant chemical interaction between drug and polymer was observed .", "entity": [], "task": "NER"}
{"text": "Optimized formulation was stable at accelerated conditions for a period of six months .", "entity": [], "task": "NER"}
{"text": "PTSso was evaluated for in vivo buoyancy studies in humans for both fed and fasted states and found that gastric residence time of the floating tablets were enhanced by fed stage but not in fasted state .", "entity": [], "task": "NER"}
{"text": "Optimized formulation PTSso and commercial formulation Ciplar LA 80 were subjected to bioavailability studies in healthy human volunteers by estimating pharmacokinetic parameters such as C ( max ) , T ( max ) , area under curve ( AUC ) ( , ) elimination rate constant ( K ( el ) ) , biological half - life ( t ( 1 / 2 ) ) and mean residence time ( MRT ) .", "entity": [{"entity": "Ciplar LA 80", "entity_type": "Chemical", "pos": [55, 67]}], "task": "NER"}
{"text": "There was a significant increase in the bioavailability of the propranolol HCl from PTSso formulation , which was evident from increased AUC levels and larger MRT values than Ciplar LA 80 .", "entity": [{"entity": "propranolol HCl", "entity_type": "Chemical", "pos": [63, 78]}, {"entity": "Ciplar LA 80", "entity_type": "Chemical", "pos": [175, 187]}], "task": "NER"}
{"text": "Study of the scale formation mechanism on gold modified with an alkanethiol monolayer .", "entity": [{"entity": "alkanethiol", "entity_type": "Chemical", "pos": [64, 75]}], "task": "NER"}
{"text": "Scaling is a problem in many industrial processes .", "entity": [], "task": "NER"}
{"text": "To control and minimize it , it is important to understand the dynamics of the scale formation .", "entity": [], "task": "NER"}
{"text": "In this paper , the scale formation was examined on two kinds of gold surfaces .", "entity": [], "task": "NER"}
{"text": "One was a pure metallic gold surface , and the other was a gold surface modified with an alkanethiol self - assembled monolayer .", "entity": [{"entity": "alkanethiol", "entity_type": "Chemical", "pos": [89, 100]}], "task": "NER"}
{"text": "A series of surface characterization experiments were performed to ensure a good understanding of the gold - thiol bond stability in a caustic solution .", "entity": [{"entity": "gold - thiol", "entity_type": "Chemical", "pos": [102, 114]}], "task": "NER"}
{"text": "A multivalent approach towards linked dual - pharmacology prostaglandin F receptor agonist / carbonic anhydrase - II inhibitors for the treatment of glaucoma .", "entity": [{"entity": "prostaglandin F", "entity_type": "Chemical", "pos": [58, 73]}], "task": "NER"}
{"text": "Lowering of intra - ocular pressure is the primary pharmacologic approach for the treatment of glaucoma and a number of distinct mechanisms of action have been clinically validated .", "entity": [], "task": "NER"}
{"text": "Targeting of multiple mechanisms in combination therapies has proven effective both clinically and commercially although potential improvements with regards to efficacy , tolerability and dosing frequency remain .", "entity": [], "task": "NER"}
{"text": "Application of Theravance ' s multivalent approach to drug discovery towards linked dual - pharmacology prostaglandin F receptor ( FP ) agonist / carbonic anhydrase ( CA ) - II inhibitor compounds is described .", "entity": [{"entity": "prostaglandin F", "entity_type": "Chemical", "pos": [104, 119]}], "task": "NER"}
{"text": "Compound 29 exhibits weak potency ( pEC ( 50 ) = 5 . 7 , IA > 1 . 0 ) as an FP agonist with high binding affinity ( pK ( i ) = 8 . 1 ) to the CA - II enzyme , and has comparable corneal permeability to the CA - II inhibitor dorzolamide .", "entity": [{"entity": "dorzolamide", "entity_type": "Chemical", "pos": [224, 235]}], "task": "NER"}
{"text": "The cancer biology of whole - chromosome instability .", "entity": [], "task": "NER"}
{"text": "One form of chromosome instability ( CIN ) , the recurrent missegregation of whole chromosomes during cell division ( W - CIN ) , leads to aneuploidy .", "entity": [], "task": "NER"}
{"text": "Although W - CIN is a hallmark of most cancers , mutations in genes involved in chromosome segregation are exceedingly rare .", "entity": [], "task": "NER"}
{"text": "We discuss an oncogene - induced mitotic stress model that provides a mechanistic framework to explain this paradox .", "entity": [], "task": "NER"}
{"text": "We also review the tumor - promoting and tumor - suppressing consequences of W - CIN .", "entity": [], "task": "NER"}
{"text": "Importantly , we do this in the context of cancer as a complex systemic disease , rather than as a simple linearly progressing disorder that arises from a single abnormal cell population .", "entity": [], "task": "NER"}
{"text": "Accordingly , we highlight the often neglected effects of W - CIN on key non - cell - autonomous entities , such as the immune system and the tumor microenvironment .", "entity": [], "task": "NER"}
{"text": "Distinct tissue - specific susceptibilities to W - CIN - induced tumorigenesis and the clinical implications of W - CIN are also discussed . Oncogene advance online publication , 14 January 2013 ; doi : 10 . 1038 / onc . 2012 . 616 .", "entity": [], "task": "NER"}
{"text": "Neuroprotective efficacy and pharmacokinetic behavior of novel anti - inflammatory para - phenyl substituted diindolylmethanes in a mouse model of Parkinson ' s disease .", "entity": [{"entity": "para - phenyl substituted diindolylmethanes", "entity_type": "Chemical", "pos": [83, 126]}], "task": "NER"}
{"text": "There are currently no registered drugs that slow the progression of neurodegenerative diseases , in part because translation from animal models to the clinic has been hampered by poor distribution to the brain .", "entity": [], "task": "NER"}
{"text": "The present studies examined a selected series of para - phenyl - substituted diindolylmethane ( C - DIM ) compounds that display anti - inflammatory and neuroprotective efficacy in vitro .", "entity": [{"entity": "para - phenyl - substituted diindolylmethane", "entity_type": "Chemical", "pos": [50, 94]}], "task": "NER"}
{"text": "We postulated that the pharmacokinetic behavior of C - DIM compounds after oral administration would correlate with neuroprotective efficacy in vivo in a mouse model of Parkinson ' s disease .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetics and metabolism of 1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( p - methoxyphenyl ) methane ( C - DIM5 ) , 1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( phenyl ) methane , 1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( p - hydroxyphenyl ) methane ( C - DIM8 ) , and 1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( p - chlorophenyl ) methane ( C - DIM12 ) were determined in plasma and brain of C57Bl / 6 mice after oral and intravenous administration at 10 and 1 mg / Kg , respectively .", "entity": [{"entity": "1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( p - methoxyphenyl ) methane", "entity_type": "Chemical", "pos": [35, 100]}, {"entity": "1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( phenyl ) methane", "entity_type": "Chemical", "pos": [116, 170]}, {"entity": "1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( p - hydroxyphenyl ) methane", "entity_type": "Chemical", "pos": [173, 238]}, {"entity": "1 , 1 - bis ( 3 ' - indolyl ) - 1 - ( p - chlorophenyl ) methane", "entity_type": "Chemical", "pos": [258, 322]}], "task": "NER"}
{"text": "Putative metabolites were measured in plasma , liver , and urine .", "entity": [], "task": "NER"}
{"text": "C - DIM compounds given orally displayed the highest area under the curve , Cmax , and Tmax levels , and C - DIM12 exhibited the most favorable pharmacokinetics of the compounds tested .", "entity": [], "task": "NER"}
{"text": "Oral bioavailability of each compound ranged from 6 % ( C - DIM8 ) to 42 % ( C - DIM12 ) .", "entity": [], "task": "NER"}
{"text": "After pharmacokinetic studies , the neuroprotective efficacy of C - DIM5 , C - DIM8 , and C - DIM12 ( 50 mg / Kg per oral ) was examined in mice exposed to 1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine ( MPTP ) and probenecid for 14 days , a model of progressive neurodegeneration with a strong neuroinflammatory component .", "entity": [{"entity": "1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine", "entity_type": "Chemical", "pos": [156, 216]}, {"entity": "MPTP", "entity_type": "Chemical", "pos": [219, 223]}, {"entity": "probenecid", "entity_type": "Chemical", "pos": [230, 240]}], "task": "NER"}
{"text": "C - DIM5 and C - DIM12 given orally once daily after one week of exposure to MPTP and probenecid prevented further loss of dopaminergic neurons in the substantia nigra pars compacta and striatal dopamine terminals , indicating that these compounds could be effective therapeutic agents to prevent neurodegeneration .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [77, 81]}, {"entity": "probenecid", "entity_type": "Chemical", "pos": [86, 96]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [123, 131]}], "task": "NER"}
{"text": "Peroxynitrite mediates testosterone - induced vasodilation of microvascular resistance vessels .", "entity": [{"entity": "Peroxynitrite", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "Our knowledge of how androgens influence the cardiovascular system is far from complete , and this lack of understanding is especially true of how androgens affect resistance vessels .", "entity": [{"entity": "androgens", "entity_type": "Chemical", "pos": [21, 30]}, {"entity": "androgens", "entity_type": "Chemical", "pos": [147, 156]}], "task": "NER"}
{"text": "Our aim was to identify the signaling mechanisms stimulated by testosterone ( TES ) in microvascular arteries and to understand how these mechanisms mediate TES - induced vasodilation .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [63, 75]}, {"entity": "TES", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "TES", "entity_type": "Chemical", "pos": [157, 160]}], "task": "NER"}
{"text": "Mesenteric microvessels were isolated from male Sprague - Dawley rats .", "entity": [], "task": "NER"}
{"text": "Tension studies demonstrated a rapid , concentration - dependent , vasodilatory response to TES that did not involve protein synthesis or aromatization to 17 beta - estradiol .", "entity": [{"entity": "TES", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [155, 174]}], "task": "NER"}
{"text": "Dichlorofluorescein fluorescence and nitrotyrosine immunoblot experiments indicated that TES stimulated peroxynitrite formation in microvessels , and functional studies demonstrated that TES - induced vasodilation was inhibited by scavenging peroxynitrite .", "entity": [{"entity": "Dichlorofluorescein", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "nitrotyrosine", "entity_type": "Chemical", "pos": [37, 50]}, {"entity": "TES", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [104, 117]}, {"entity": "TES", "entity_type": "Chemical", "pos": [187, 190]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [242, 255]}], "task": "NER"}
{"text": "As predicted , TES enhanced the production of both peroxynitrite precursors ( i . e . , superoxide and nitic oxide ) , and xanthine oxidase was identified as the likely source of TES - stimulated superoxide production .", "entity": [{"entity": "TES", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [51, 64]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [88, 98]}, {"entity": "nitic oxide", "entity_type": "Chemical", "pos": [103, 114]}, {"entity": "xanthine", "entity_type": "Chemical", "pos": [123, 131]}, {"entity": "TES", "entity_type": "Chemical", "pos": [179, 182]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [196, 206]}], "task": "NER"}
{"text": "Functional and biochemical studies indicated that TES signaling involved activity of the phosphoinositide 3 ( PI3 ) kinase - protein kinase B ( Akt ) cascade initiated by activation of the androgen receptor and culminated in enhanced production of cGMP and microvascular vasodilation .", "entity": [{"entity": "TES", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [89, 105]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [189, 197]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [248, 252]}], "task": "NER"}
{"text": "These findings , derived from a variety of analytical and functional approaches , provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature : TES - stimulated vasodilation mediated primarily by peroxynitrite formed from xanthine oxidase - generated superoxide and NO .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [146, 154]}, {"entity": "TES", "entity_type": "Chemical", "pos": [188, 191]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [240, 253]}, {"entity": "xanthine", "entity_type": "Chemical", "pos": [266, 274]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [295, 305]}, {"entity": "NO", "entity_type": "Chemical", "pos": [310, 312]}], "task": "NER"}
{"text": "This response was associated with activation of the PI3 kinase - Akt signaling cascade initiated by activation of the androgen receptor .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [118, 126]}], "task": "NER"}
{"text": "We propose this mechanism could account for TES - stimulated cGMP production in microvessels and , ultimately , vasodilation .", "entity": [{"entity": "TES", "entity_type": "Chemical", "pos": [44, 47]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [61, 65]}], "task": "NER"}
{"text": "Ordered mesoporous boron - doped carbons as metal - free electrocatalysts for the oxygen reduction reaction in alkaline solution .", "entity": [{"entity": "boron - doped carbons", "entity_type": "Chemical", "pos": [19, 40]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [82, 88]}], "task": "NER"}
{"text": "Ordered mesoporous boron - doped carbons ( BOMCs ) were prepared by co - impregnation and carbonization of sucrose and 4 - hydroxyphenylboronic acid into SBA - 15 silica template .", "entity": [{"entity": "boron - doped carbons", "entity_type": "Chemical", "pos": [19, 40]}, {"entity": "sucrose", "entity_type": "Chemical", "pos": [107, 114]}, {"entity": "4 - hydroxyphenylboronic acid", "entity_type": "Chemical", "pos": [119, 148]}, {"entity": "SBA - 15", "entity_type": "Chemical", "pos": [154, 162]}, {"entity": "silica", "entity_type": "Chemical", "pos": [163, 169]}], "task": "NER"}
{"text": "Nitrogen sorption , small angle X - ray diffraction ( XRD ) , and transmission electron microscopy ( TEM ) reveals that BOMCs possess highly ordered mesoporous structure , uniform pore size distribution , and high surface area .", "entity": [{"entity": "Nitrogen", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "X - ray photoelectron spectroscopy ( XPS ) analysis demonstrates that B atoms can be successfully doped into the framework of OMCs .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [70, 71]}], "task": "NER"}
{"text": "Due to the desirable characteristics of BOMCs , BOMCs are highly active , cheap , and selective metal - free electrocatalysts for the oxygen reduction reaction ( ORR ) in alkaline solution .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [134, 140]}], "task": "NER"}
{"text": "Although B content is a key factor in determining ORR activity , the ORR activity of BOMCs is also dependent on the surface area .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [9, 10]}], "task": "NER"}
{"text": "The high surface area of BOMCs facilitates the exposure of the active sites for ORR .", "entity": [], "task": "NER"}
{"text": "BOMCs may be further exploited as potentially efficient and inexpensive metal - free ORR catalysts with good long - term stability in alkaline solution .", "entity": [], "task": "NER"}
{"text": "Elevated vaspin and leptin levels are associated with obesity in prepubertal Korean children .", "entity": [], "task": "NER"}
{"text": "Adipokines are associated with obesity .", "entity": [], "task": "NER"}
{"text": "However , the relationships between adipokines , specifically vaspin , obesity , and obesity - related variables remain controversial , and only a few studies have been conducted which examines them in children .", "entity": [], "task": "NER"}
{"text": "We investigated the relationships between obesity in prepubertal Korean children and three types of adipokines : vaspin , leptin , and visfatin .", "entity": [], "task": "NER"}
{"text": "In this cross - sectional study , 168 nine - year - old boys and 176 nine - year - old girls participated in a school - based health examination program .", "entity": [], "task": "NER"}
{"text": "Children were classified as overweight using the Korean Pediatric Society 2007 guidelines .", "entity": [], "task": "NER"}
{"text": "Overweight boys and girls had higher leptin and vaspin levels than both boys and girls of normal weight , whereas only overweight boys had higher visfatin levels than normal weight boys .", "entity": [], "task": "NER"}
{"text": "Leptin , visfatin and vaspin concentrations were correlated with obesity - related variables .", "entity": [], "task": "NER"}
{"text": "A multiple logistic regression analysis showed that systolic blood pressure ( SBP ) , total cholesterol ( TC ) , alanine aminotransferase ( ALT ) , homeostasis model assessment of insulin resistance ( HOMA - IR ) , leptin , and vaspin were associated with an increased risk of being overweight , whereas high - density lipoprotein ( HDL ) cholesterol was associated with a decreased risk of being overweight .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [92, 103]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [113, 120]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [339, 350]}], "task": "NER"}
{"text": "Peginesatide clearance , distribution , metabolism , and excretion in monkeys following intravenous administration .", "entity": [{"entity": "Peginesatide", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Peginesatide , a polyethylene glycol ( PEG ) ylated peptide - based erythropoiesis - stimulating agent , stimulates the erythropoietin receptor dimer that governs erythropoiesis .", "entity": [{"entity": "Peginesatide", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [17, 36]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "Studies were designed to determine the erythropoietic response , pharmacokinetics ( PK ) , tissue distribution , metabolism , and excretion of peginesatide in nonhuman primates following a single i . v . dose .", "entity": [{"entity": "peginesatide", "entity_type": "Chemical", "pos": [143, 155]}], "task": "NER"}
{"text": "The PK profile of peginesatide ( 0 . 1 - 5 mg / kg ) is characterized by low , dose - dependent plasma clearance ; small volume of distribution ; and long half - life .", "entity": [{"entity": "peginesatide", "entity_type": "Chemical", "pos": [18, 30]}], "task": "NER"}
{"text": "The peginesatide PK profile following a single i . v . dose is consistent with the sustained erythropoiesis .", "entity": [{"entity": "peginesatide", "entity_type": "Chemical", "pos": [4, 16]}], "task": "NER"}
{"text": "Biodistribution quantitative whole - body autoradiography demonstrated high peginesatide levels in bone marrow ( i . e . , primary hematopoietic site ) as well as other known hematopoietic sites persisting through at least 3 weeks at 2 . 1 mg / kg .", "entity": [{"entity": "peginesatide", "entity_type": "Chemical", "pos": [76, 88]}], "task": "NER"}
{"text": "Microautoradiography analysis at 48 hours postdose revealed uniform and high distribution of radioactivity in the bone marrow and splenic red pulp with less extensive distribution in the renal cortex ( glomeruli , associated ducts , interstitial cells ) .", "entity": [], "task": "NER"}
{"text": "Radioactivity in the kidney was most prominent in the outer medullary and papillary interstitium .", "entity": [], "task": "NER"}
{"text": "At 2 weeks after dosing , cumulative radioactivity recovery in the urine and feces was 60 and 7 % of the administered dose , respectively , with most of the radioactivity associated with the parent molecule .", "entity": [], "task": "NER"}
{"text": "In conclusion , the PK characteristics are consistent with a PEGylated peptide of a 45 - kDa molecular mass , specifically low volume of distribution and long half - life .", "entity": [], "task": "NER"}
{"text": "Drug was localized principally to hematopoietic sites , and nonspecific tissue retention was not observed .", "entity": [], "task": "NER"}
{"text": "The nonhuman primate data indicate that peginesatide is metabolically stable and primarily excreted in the urine .", "entity": [{"entity": "peginesatide", "entity_type": "Chemical", "pos": [40, 52]}], "task": "NER"}
{"text": "Effects of nicotine , its metabolites and tobacco extracts on human platelet function in vitro .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "Cigarette smoking is a leading cause of cardiovascular disease .", "entity": [], "task": "NER"}
{"text": "The cardiovascular effects of smoking are probably multifactorial , including effects on platelets .", "entity": [], "task": "NER"}
{"text": "Previous reports investigating the effects of nicotine and tobacco on platelet function are inconsistent .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [46, 54]}], "task": "NER"}
{"text": "The present study investigated in vitro effects of nicotine , its major metabolites , tobacco extracts and extract of tobacco - free snuff on human platelets .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [51, 59]}], "task": "NER"}
{"text": "None of the metabolites cotinine , cotinine - N - oxide , nicotine - 1 ' - N - oxide or trans - 3 ' - hydroxycotinine ( 0 . 1 - 10 mu M ) affected platelet aggregation or P - selectin expression .", "entity": [{"entity": "cotinine", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "cotinine - N - oxide", "entity_type": "Chemical", "pos": [35, 55]}, {"entity": "nicotine - 1 ' - N - oxide", "entity_type": "Chemical", "pos": [58, 84]}, {"entity": "trans - 3 ' - hydroxycotinine", "entity_type": "Chemical", "pos": [88, 117]}], "task": "NER"}
{"text": "Nicotine ( 10 mu M ) weakly increased platelet aggregation , whereas trans - 3 ' - hydroxycotinine ( 0 . 1 mu M ) and nicotine - 1 ' - N - oxide ( 1 - 10 mu M ) weakly inhibited adhesion to fibrinogen .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "trans - 3 ' - hydroxycotinine", "entity_type": "Chemical", "pos": [69, 98]}, {"entity": "nicotine - 1 ' - N - oxide", "entity_type": "Chemical", "pos": [118, 144]}], "task": "NER"}
{"text": "To elucidate the influence of other tobacco compounds , we investigated the impact of moist tobacco and smoke extracts on platelet function .", "entity": [], "task": "NER"}
{"text": "Filtered extracts of oral snuff , cigarette smoke and tobacco free snuff inhibited platelet adhesion concentration - dependently .", "entity": [], "task": "NER"}
{"text": "The inhibitory effects of tobacco extracts on platelet adhesion were independent of nicotine content and the nitric - oxide - pathway and not mediated through a platelet - nicotine - receptor .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "nitric - oxide", "entity_type": "Chemical", "pos": [109, 123]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [172, 180]}], "task": "NER"}
{"text": "Taken together , tobacco extracts inhibit platelet activation during short - term in vitro challenge .", "entity": [], "task": "NER"}
{"text": "As only limited effects of nicotine and nicotine metabolites were seen , the tobacco - induced platelet inhibition are likely induced by other compounds present in tobacco and tobacco free snuff .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "Re - print of \" Intestinal luminal nitrogen metabolism : role of the gut microbiota and consequences for the host \" .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "Alimentary and endogenous proteins are mixed in the small intestinal lumen with the microbiota .", "entity": [], "task": "NER"}
{"text": "Although experimental evidences suggest that the intestinal microbiota is able to incorporate and degrade some of the available amino acids , it appears that the microbiota is also able to synthesize amino acids raising the view that amino acid exchange between the microbiota and host can proceed in both directions .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [128, 139]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [200, 211]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [234, 244]}], "task": "NER"}
{"text": "Although the net result of such exchanges remains to be determined , it is likely that a significant part of the amino acids recovered from the alimentary proteins are used by the microbiota .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [113, 124]}], "task": "NER"}
{"text": "In the large intestine , where the density of bacteria is much higher than in the small intestine and the transit time much longer , the residual undigested luminal proteins and peptides can be degraded in amino acids by the microbiota .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [206, 217]}], "task": "NER"}
{"text": "These amino acids cannot be absorbed to a significant extent by the colonic epithelium , but are precursors for the synthesis of numerous metabolic end products in reactions made by the microbiota .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [6, 17]}], "task": "NER"}
{"text": "Among these products , some like short - chain fatty acids and organic acids are energy substrates for the colonic mucosa and several peripheral tissues while others like sulfide and ammonia can affect the energy metabolism of colonic epithelial cells .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "sulfide", "entity_type": "Chemical", "pos": [171, 178]}, {"entity": "ammonia", "entity_type": "Chemical", "pos": [183, 190]}], "task": "NER"}
{"text": "More work is needed to clarify the overall effects of the intestinal microbiota on nitrogenous compound metabolism and consequences on gut and more generally host health .", "entity": [], "task": "NER"}
{"text": "Impaired in vitro erythropoiesis following deletion of the Scl ( Tal1 ) + 40 enhancer is largely compensated for in vivo despite a significant reduction in expression .", "entity": [], "task": "NER"}
{"text": "The Scl ( Tal1 ) gene encodes a helix - loop - helix transcription factor essential for hematopoietic stem cell and erythroid development .", "entity": [], "task": "NER"}
{"text": "The Scl + 40 enhancer is situated downstream of Map17 , the 3 ' flanking gene of Scl , and is active in transgenic mice during primitive and definitive erythropoiesis .", "entity": [], "task": "NER"}
{"text": "To analyze the in vivo function of the Scl + 40 enhancer within the Scl / Map17 transcriptional domain , we deleted this element in the germ line .", "entity": [], "task": "NER"}
{"text": "Scl ( Delta 40 / Delta 40 ) mice were viable with reduced numbers of erythroid CFU in both bone marrow and spleen yet displayed a normal response to stress hematopoiesis .", "entity": [], "task": "NER"}
{"text": "Analysis of Scl ( Delta 40 / Delta 40 ) embryonic stem ( ES ) cells revealed impaired erythroid differentiation , which was accompanied by a failure to upregulate Scl when erythropoiesis was initiated .", "entity": [], "task": "NER"}
{"text": "Map17 expression was also reduced in hematopoietic tissues and differentiating ES cells , and the Scl + 40 element was able to enhance activity of the Map17 promoter .", "entity": [], "task": "NER"}
{"text": "However , only Scl but not Map17 could rescue the Scl ( Delta 40 / Delta 40 ) ES phenotype .", "entity": [], "task": "NER"}
{"text": "Together , these data demonstrate that the Scl + 40 enhancer is an erythroid cell - specific enhancer that regulates the expression of both Scl and Map17 .", "entity": [], "task": "NER"}
{"text": "Moreover , deletion of the + 40 enhancer causes a novel erythroid phenotype , which can be rescued by ectopic expression of Scl but not Map17 .", "entity": [], "task": "NER"}
{"text": "Long - term physicochemical and immunological stability of a liquid formulated intact ovine immunoglobulin - based antivenom .", "entity": [], "task": "NER"}
{"text": "An antivenom should be stable under the conditions that it will be both transferred and stored .", "entity": [], "task": "NER"}
{"text": "Thus instability may lead to a loss of efficacy and an increased incidence and severity of adverse effects .", "entity": [], "task": "NER"}
{"text": "Stability is a particular problem in countries where the temperatures and humidity are high .", "entity": [], "task": "NER"}
{"text": "Here we investigate the stability of a liquid - formulated , intact ovine immunoglobulin - based antivenom , EchiTAbG (TM) , which is used extensively in Nigeria to treat envenoming by the West African saw - scaled viper , Echis ocellatus .", "entity": [], "task": "NER"}
{"text": "Ampoules of antivenom were assessed as to their specific antibody content by small scale affinity chromatography and their purity by size exclusion gel filtration and turbidity .", "entity": [], "task": "NER"}
{"text": "Three different batches of the antivenom revealed no significant changes , using these assessment techniques , during 42 months storage at 4 degrees C or at ambient temperature , followed by one month at 37 degrees C .", "entity": [], "task": "NER"}
{"text": "These real - time studies indicate that the antivenom remains stable for a minimum of 3 . 5 years and that it can be exposed to tropical temperatures without any loss in immunoglobulin binding activity .", "entity": [], "task": "NER"}
{"text": "This further highlights the clinical utility of liquid formulated ovine IgG antivenoms by demonstrating their retention of potency in the event of a short term failing in the cold chain .", "entity": [], "task": "NER"}
{"text": "Spontaneous and experimental intoxication of cattle by Simarouba versicolor A .", "entity": [], "task": "NER"}
{"text": "St . - Hill ( Simaroubaceae ) .", "entity": [], "task": "NER"}
{"text": "This study describes an outbreak of Simarouba versicolor intoxication in cattle from Mato Grosso do Sul , Brazil , and reproduces it experimentally .", "entity": [], "task": "NER"}
{"text": "Clinical signs of the affected animals were weakness , tremors , hind limbs incoordination , reluctance to move , sternal and lateral recumbency and death .", "entity": [], "task": "NER"}
{"text": "The main necropsy findings , observed in the abomasum and in segments of the small and large intestines , were diffuse redness and mucosal and serosal swelling .", "entity": [], "task": "NER"}
{"text": "Histological examination revealed necrosis of lymphoid tissues and necrotizing enterocolitis .", "entity": [], "task": "NER"}
{"text": "One experiment was carried out using 3 male calves to test the toxicity of a single dose of S . versicolor leaves at 15 g / kg , 5 g / kg and 2 . 5 g / kg .", "entity": [], "task": "NER"}
{"text": "Clinical signs , necropsy findings and histological examination of calves receiving 15 g / kg and 5 g / kg leaves were similar to those of cattle from the intoxication outbreak .", "entity": [], "task": "NER"}
{"text": "The calf fed 2 . 5 g / kg leaves developed clinical symptoms of poisoning and recovered naturally .", "entity": [], "task": "NER"}
{"text": "In a second experiment , two male calves received daily administration of S . versicolor leaves at 1 . 5 g / kg and 2 . 5 g / kg for 10 days .", "entity": [], "task": "NER"}
{"text": "They developed clinical signs of intoxication within 24 h and recovered eight to nine days after the leaves were administered .", "entity": [], "task": "NER"}
{"text": "These findings suggest that S . versicolor was responsible for the outbreak studied , although this plant does not have cumulative intoxication effects on cattle .", "entity": [], "task": "NER"}
{"text": "Effective fragment potential method in Q - CHEM : A guide for users and developers .", "entity": [], "task": "NER"}
{"text": "A detailed description of the implementation of the effective fragment potential ( EFP ) method in the Q - CHEM electronic structure package is presented .", "entity": [], "task": "NER"}
{"text": "The Q - CHEM implementation interfaces EFP with standard quantum mechanical ( QM ) methods such as Hartree - Fock , density functional theory , perturbation theory , and coupled - cluster methods , as well as with methods for electronically excited and open - shell species , for example , configuration interaction , time - dependent density functional theory , and equation - of - motion coupled - cluster models .", "entity": [], "task": "NER"}
{"text": "In addition to the QM / EFP functionality , a \" fragment - only \" feature is also available ( when the system is described by effective fragments only ) .", "entity": [], "task": "NER"}
{"text": "To aid further developments of the EFP methodology , a detailed description of the C + + classes and EFP module ' s workflow is presented .", "entity": [], "task": "NER"}
{"text": "The EFP input structure and EFP job options are described .", "entity": [], "task": "NER"}
{"text": "To assist setting up and performing EFP calculations , a collection of Perl service scripts is provided .", "entity": [], "task": "NER"}
{"text": "The precomputed EFP parameters for standard fragments such as common solvents are stored in Q - CHEM ' s auxiliary library ; they can be easily invoked , similar to specifying standard basis sets .", "entity": [], "task": "NER"}
{"text": "The instructions for generating user - defined EFP parameters are given .", "entity": [], "task": "NER"}
{"text": "Fragments positions can be specified by their center of mass coordinates and Euler angles .", "entity": [], "task": "NER"}
{"text": "The interface with the IQMOL and WEBMO software is also described .", "entity": [], "task": "NER"}
{"text": "(c) 2013 Wiley Periodicals , Inc .", "entity": [], "task": "NER"}
{"text": "Strategic applications of gene expression : from drug discovery / development to bedside .", "entity": [], "task": "NER"}
{"text": "Gene expression is useful for identifying the molecular signature of a disease and for correlating a pharmacodynamic marker with the dose - dependent cellular responses to exposure of a drug .", "entity": [], "task": "NER"}
{"text": "Gene expression offers utility to guide drug discovery by illustrating engagement of the desired cellular pathways / networks , as well as avoidance of acting on the toxicological pathways .", "entity": [], "task": "NER"}
{"text": "Successful employment of gene - expression signatures in the later stages of drug development depends on their linkage to clinically meaningful phenotypic characteristics and requires a biologically meaningful mechanism combined with a stringent statistical rigor .", "entity": [], "task": "NER"}
{"text": "Much of the success in clinical drug development is hinged on predefining the signature genes for their fitness for purposes of application .", "entity": [], "task": "NER"}
{"text": "Specific examples are highlighted to illustrate the breadth and depth of the potential utility of gene - expression signatures in drug discovery and clinical development to targeted therapeutics at the bedside .", "entity": [], "task": "NER"}
{"text": "ICA - 105574 interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels .", "entity": [{"entity": "ICA - 105574", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "Rapid and voltage - dependent inactivation greatly attenuates outward currents in ether - a - go - go - related gene ( ERG ) K ( + ) channels .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [82, 87]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "In contrast , inactivation of related ether - a - go - go ( EAG ) K ( + ) channels is very slow and minimally reduces outward currents .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [38, 43]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [66, 73]}], "task": "NER"}
{"text": "ICA - 105574 ( ICA , or 3 - nitro - N - [ 4 - phenoxyphenyl ] - benzamide ) has opposite effects on inactivation of these two channel types .", "entity": [{"entity": "ICA - 105574", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "ICA", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "3 - nitro - N - [ 4 - phenoxyphenyl ] - benzamide", "entity_type": "Chemical", "pos": [24, 73]}], "task": "NER"}
{"text": "Although ICA greatly attenuates ERG inactivation by shifting its voltage dependence to more positive potentials , it enhances the rate and extent of EAG inactivation without altering its voltage dependence .", "entity": [{"entity": "ICA", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "Here , we investigate whether the inverse functional response to ICA in EAG and ERG channels is related to differences in ICA binding site or to intrinsic mechanisms of inactivation .", "entity": [{"entity": "ICA", "entity_type": "Chemical", "pos": [65, 68]}, {"entity": "ICA", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "Molecular modeling coupled with site - directed mutagenesis suggests that ICA binds in a channel - specific orientation to a hydrophobic pocket bounded by the S5 / pore helix / S6 of one subunit and S6 of an adjacent subunit .", "entity": [{"entity": "ICA", "entity_type": "Chemical", "pos": [74, 77]}], "task": "NER"}
{"text": "ICA is a mixed agonist of mutant EAG and EAG / ERG chimera channels that inactivate by a combination of slow and fast mechanisms .", "entity": [{"entity": "ICA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "With the exception of three residues , the specific amino acids that form the putative binding pocket for ICA in ERG are conserved in EAG .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "ICA", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "Mutations introduced into EAG to replicate the ICA binding site in ERG did not alter the functional response to ICA .", "entity": [{"entity": "ICA", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "ICA", "entity_type": "Chemical", "pos": [112, 115]}], "task": "NER"}
{"text": "Together these findings suggest that ICA binds to the same site in EAG and ERG channels to elicit opposite functional effects .", "entity": [{"entity": "ICA", "entity_type": "Chemical", "pos": [37, 40]}], "task": "NER"}
{"text": "The resultant agonist or antagonist activity is determined solely by channel - specific differences in the mechanisms of inactivation gating .", "entity": [], "task": "NER"}
{"text": "The pharmacology of L - DOPA - induced dyskinesia in Parkinson ' s disease .", "entity": [{"entity": "L - DOPA", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "L - 3 , 4 - Dihydroxyphenylalanine ( L - DOPA ) remains the most effective symptomatic treatment of Parkinson ' s disease ( PD ) .", "entity": [{"entity": "L - 3 , 4 - Dihydroxyphenylalanine", "entity_type": "Chemical", "pos": [0, 34]}, {"entity": "L - DOPA", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "However , long - term administration of L - DOPA is marred by the emergence of abnormal involuntary movements , i . e . , L - DOPA - induced dyskinesia ( LID ) .", "entity": [{"entity": "L - DOPA", "entity_type": "Chemical", "pos": [40, 48]}, {"entity": "L - DOPA", "entity_type": "Chemical", "pos": [122, 130]}], "task": "NER"}
{"text": "Years of intensive research have yielded significant progress in the quest to elucidate the mechanisms leading to the development and expression of dyskinesia and maintenance of the dyskinetic state , but the search for a complete understanding is still ongoing .", "entity": [], "task": "NER"}
{"text": "Herein , we summarize the current knowledge of the pharmacology of LID in PD .", "entity": [], "task": "NER"}
{"text": "Specifically , we review evidence gathered from postmortem and pharmacological studies , both preclinical and clinical , and discuss the involvement of dopaminergic and nondopaminergic systems , including glutamatergic , opioid , serotonergic , gamma - aminobutyric acid ( GABA ) - ergic , adenosine , cannabinoid , adrenergic , histaminergic , and cholinergic systems .", "entity": [{"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [245, 270]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [273, 277]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [290, 299]}], "task": "NER"}
{"text": "Moreover , we discuss changes occurring in transcription factors , intracellular signaling , and gene expression in the dyskinetic phenotype .", "entity": [], "task": "NER"}
{"text": "Inasmuch as a multitude of neurotransmitters and receptors play a role in the etiology of dyskinesia , we propose that to optimally alleviate this motor complication , it may be necessary to develop combined treatment approaches that will target simultaneously more than one neurotransmitter system .", "entity": [], "task": "NER"}
{"text": "This could be achieved via three ways as follows : 1 ) by developing compounds that will interact simultaneously to a multitude of receptors with the required agonist / antagonist effect at each target , 2 ) by targeting intracellular signaling cascades where the signals mediated by multiple receptors converge , and / or 3 ) to regulate gene expression in a manner that has effects on signaling by multiple pathways .", "entity": [], "task": "NER"}
{"text": "It is the outside that counts : chemical and physical control of dynamic surfaces .", "entity": [], "task": "NER"}
{"text": "Materials capable of dynamically controlling surface chemistry and topography are highly desirable .", "entity": [], "task": "NER"}
{"text": "We have designed a system that is uniquely able to remotely control the presented functionality and geometry at a given time by using a functionalizable shape memory material .", "entity": [], "task": "NER"}
{"text": "This was accomplished by incorporating controlled amounts of an azide - containing monomer into a shape memory polymeric material .", "entity": [{"entity": "azide", "entity_type": "Chemical", "pos": [64, 69]}], "task": "NER"}
{"text": "These materials are capable of physically changing surface geometry over a broad range of length scales from > 1 mm to 100 nm .", "entity": [], "task": "NER"}
{"text": "Using copper - assisted click chemistry , they can be functionalized with a variety of molecules to yield different surfaces .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [6, 12]}], "task": "NER"}
{"text": "Combining these features gave materials that can change both the presented geometry and functionality at tunable transition temperatures .", "entity": [], "task": "NER"}
{"text": "Development of a novel bioerodible dexamethasone implant for uveitis and postoperative cataract inflammation .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [35, 48]}], "task": "NER"}
{"text": "Delivery of anti - inflammatory steroids concurrently to both anterior and posterior segments of the eye is a challenge .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "The anterior ocular structures limit topical delivery .", "entity": [], "task": "NER"}
{"text": "Injection can be disproportionately and repeatedly invasive and selective for only one ocular hemisphere .", "entity": [], "task": "NER"}
{"text": "We developed a novel implant that can compensate for the limited conveyance of topical medicine and reduce the repetitive invasiveness of injection from the capsular bag allowing dexamethasone ( DXM ) delivery to both the anterior and posterior chambers .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [179, 192]}, {"entity": "DXM", "entity_type": "Chemical", "pos": [195, 198]}], "task": "NER"}
{"text": "To establish proof of concept , microparticles were prepared with PLGA [ poly ( d , l - lactide - co - glycolide ) , 50 : 50 , MW . 7000 - 17000 ] , hydroxypropyl methyl cellulose ( HPMC ) , and DXM by oil - in - water emulsion / solvent evaporation technique .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [66, 70]}, {"entity": "poly ( d , l - lactide - co - glycolide )", "entity_type": "Chemical", "pos": [73, 114]}, {"entity": "hydroxypropyl methyl", "entity_type": "Chemical", "pos": [149, 169]}, {"entity": "DXM", "entity_type": "Chemical", "pos": [195, 198]}], "task": "NER"}
{"text": "Zeatsizer Nano and SEM ( scanning electron microscopy ) results showed microspheres in the range of 8 +/- 1 micro m .", "entity": [], "task": "NER"}
{"text": "The target load of DXM in the microparticles was ~ 20 . 0 % with a % recovery of 99 . 9 % ( w / w ) .", "entity": [{"entity": "DXM", "entity_type": "Chemical", "pos": [19, 22]}], "task": "NER"}
{"text": "Dose related pharmacokinetics with near zero order kinetics was observed for up to 6 weeks in rabbits with intracapsular bag implants .", "entity": [], "task": "NER"}
{"text": "DXM flow was bidirectional from the endocapsular space and significant concentrations were found in the anterior and posterior chambers after up to 6 weeks .", "entity": [{"entity": "DXM", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Whereas , with topical drops the exposure was minimal in all the ocular tissues with greater systemic exposure .", "entity": [], "task": "NER"}
{"text": "Intraocular pressure was normal in all of the study groups ; slit lamp biomicroscopy examinations revealed that no cells or fibrin formation in the anterior and posterior chamber with implants but flare , cells and fibrin was present in the topical drops group .", "entity": [], "task": "NER"}
{"text": "Histological examination revealed normal tissues and no signs of inflammation in all the groups .", "entity": [], "task": "NER"}
{"text": "The implant did not migrate to the center of the eye or obstruct the visual axis .", "entity": [], "task": "NER"}
{"text": "We believe these findings demonstrate the feasibility of drug delivery from the capsular bag to the anterior and posterior segments effectively compared to topical alternatives .", "entity": [], "task": "NER"}
{"text": "Meta - analysis of telomere length in 19 713 subjects reveals high heritability , stronger maternal inheritance and a paternal age effect .", "entity": [], "task": "NER"}
{"text": "Telomere length ( TL ) has been associated with aging and mortality , but individual differences are also influenced by genetic factors , with previous studies reporting heritability estimates ranging from 34 to 82 % .", "entity": [], "task": "NER"}
{"text": "Here we investigate the heritability , mode of inheritance and the influence of parental age at birth on TL in six large , independent cohort studies with a total of 19 713 participants .", "entity": [], "task": "NER"}
{"text": "The meta - analysis estimate of TL heritability was 0 . 70 ( 95 % CI 0 . 64 - 0 . 76 ) and is based on a pattern of results that is highly similar for twins and other family members .", "entity": [], "task": "NER"}
{"text": "We observed a stronger mother - offspring ( r = 0 . 42 ; P - value = 3 . 60 x 10 ( - 61 ) ) than father - offspring correlation ( r = 0 . 33 ; P - value = 7 . 01 x 10 ( - 5 ) ) , and a significant positive association with paternal age at offspring birth ( beta = 0 . 005 ; P - value = 7 . 01 x 10 ( - 5 ) ) .", "entity": [], "task": "NER"}
{"text": "Interestingly , a significant and quite substantial correlation in TL between spouses ( r = 0 . 25 ; P - value = 2 . 82 x 10 ( - 30 ) ) was seen , which appeared stronger in older spouse pairs ( mean age >= 55 years ; r = 0 . 31 ; P - value = 4 . 27 x 10 ( - 23 ) ) than in younger pairs ( mean age < 55 years ; r = 0 . 20 ; P - value = 3 . 24 x 10 ( - 10 ) ) .", "entity": [], "task": "NER"}
{"text": "In summary , we find a high and very consistent heritability estimate for TL , evidence for a maternal inheritance component and a positive association with paternal age . European Journal of Human Genetics advance online publication , 16 January 2013 ; doi : 10 . 1038 / ejhg . 2012 . 303 .", "entity": [], "task": "NER"}
{"text": "Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats .", "entity": [{"entity": "Caffeine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [47, 59]}], "task": "NER"}
{"text": "In order to assess whether caffeine and theophylline have the same potency and efficacy to reverse the impairment of motor function caused by acute or chronic interruption of striatal dopamine transmission , a comparison of their dose - response relationship was made in the acute model of haloperidol - induced catalepsy , and the chronic model of unilateral lesion of the dopamine nigrostriatal pathway with 6 - hydroxydopamine .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [40, 52]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [184, 192]}, {"entity": "haloperidol", "entity_type": "Chemical", "pos": [290, 301]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [374, 382]}, {"entity": "6 - hydroxydopamine", "entity_type": "Chemical", "pos": [410, 429]}], "task": "NER"}
{"text": "At equimolar doses , both drugs reduced catalepsy intensity and increased its onset latency in a dose - dependent fashion , showing comparable potencies and attaining the maximal effect at similar doses .", "entity": [], "task": "NER"}
{"text": "Catalepsy intensity : caffeine ED50 = 24 . 1 mu mol / kg [ 95 % CI , 18 . 4 - 31 . 5 ] ; theophylline ED50 = 22 . 0 mu mol / kg [ 95 % CI , 17 . 0 - 28 . 4 ] .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [89, 101]}], "task": "NER"}
{"text": "Catalepsy latency : caffeine ED50 = 27 . 0 mu mol / kg [ 95 % CI , 21 . 1 - 34 . 6 ] ; theophylline ED50 = 28 . 8 mu mol / kg [ 95 % CI , 22 . 5 - 36 . 7 ] .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [87, 99]}], "task": "NER"}
{"text": "In one group of hemiparkinsonian rats ( n = 5 ) , caffeine caused a dose - dependent recovery of the contralateral forepaw stepping : ED50 = 2 . 4 mu mol / kg / day [ 95 % CI , 1 . 9 - 3 . 1 ] ) , reaching its maximum at the dose of 5 . 15 mu mol / kg / day .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "When the treatment of these same rats was switched to 5 . 15 mu mol / kg / day of theophylline , the stepping recovery was only 51 +/- 12 % of that induced by caffeine .", "entity": [{"entity": "theophylline", "entity_type": "Chemical", "pos": [82, 94]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [159, 167]}], "task": "NER"}
{"text": "Assessing the dose - response relationship of theophylline in another group of hemiparkinsonian rats ( n = 7 ) revealed that it caused stepping recovery in an all - or - none fashion .", "entity": [{"entity": "theophylline", "entity_type": "Chemical", "pos": [46, 58]}], "task": "NER"}
{"text": "Thus , the three lower doses had no effect , but at the dose of 5 . 15 mu mol / kg / day theophylline suddenly increased the stepping to 56 +/- 5 % of the maximal effect observed when the treatment of these same rats was switched to an equimolar dose of caffeine .", "entity": [{"entity": "theophylline", "entity_type": "Chemical", "pos": [89, 101]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [254, 262]}], "task": "NER"}
{"text": "Increasing the dose of theophylline up to 15 . 45 mu mol / kg / day caused no further stepping improvement since it was only 41 +/- 6 % of the maximal effect produced by caffeine at the dose of 5 . 15 mu mol / kg / day .", "entity": [{"entity": "theophylline", "entity_type": "Chemical", "pos": [23, 35]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [170, 178]}], "task": "NER"}
{"text": "Given that theophylline showed less potency and efficacy than caffeine to reverse the motor impairment caused by chronic , but not acute , interruption of striatal dopaminergic transmission in rats , it is suggested that caffeine would provide more benefits than theophylline to improve the motor function in patients with Parkinson ' s disease .", "entity": [{"entity": "theophylline", "entity_type": "Chemical", "pos": [11, 23]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [221, 229]}, {"entity": "theophylline", "entity_type": "Chemical", "pos": [263, 275]}], "task": "NER"}
{"text": "Arsenic present in the soil - vine - wine chain in vineyards situated in an old mining area in Trentino , Italy .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "The present study follows arsenic ( As ) transfer through the chain of soil - vine - leaves - grapes - wine to assess the possible risk of arsenic intake related to consuming grapes and wines produced in 10 vineyards located in a mining area rich in this element .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [26, 33]}, {"entity": "As", "entity_type": "Chemical", "pos": [36, 38]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "The results are compared with date from 18 uncontaminated areas .", "entity": [], "task": "NER"}
{"text": "In the soil , the content of As extracted with acqua regia and that extracted with ammonium acetate , were analyzed .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "ammonium acetate", "entity_type": "Chemical", "pos": [83, 99]}], "task": "NER"}
{"text": "Leaves and berries were analyzed after washing with acidified aqueous solution and acid mineralization in a closed vessel , whereas wines were simply diluted before analysis .", "entity": [], "task": "NER"}
{"text": "All analyses were performed using an inductively coupled plasma mass - spectrometer .", "entity": [], "task": "NER"}
{"text": "The aqua regia extractable As concentration in soil ranged from 3 . 7 to 283 mg / kg , whereas available As varied from 18 to 639 micro g / kg , and As total concentration ranged from 16 . 3 to 579 micro g / kg dry weight in leaves and from < 0 . 1 to 36 . 8 micro g / kg dry weight in grapes .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [27, 29]}, {"entity": "As", "entity_type": "Chemical", "pos": [105, 107]}, {"entity": "As", "entity_type": "Chemical", "pos": [149, 151]}], "task": "NER"}
{"text": "Arsenic levels in wines were always below 1 . 62 micro g / L , with higher concentration in red wines than in white wines .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Significant and positive correlations between the As concentrations in soils , leaves , and berries are highlighted , with the samples collected near the mining area having significantly higher values .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [50, 52]}], "task": "NER"}
{"text": "Nevertheless , As levels in wines were always well below the limit ( 200 micro g / L ) suggested by the International Organization of Vine and Wine .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [15, 17]}], "task": "NER"}
{"text": "Reduced Blood Leukocyte and Neutrophil Numbers in the Pathogenesis of Type 1 Diabetes .", "entity": [], "task": "NER"}
{"text": "Very little is known about the role of the innate immune system in the course of human type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "Here we investigated neutrophil numbers along with other leukocyte populations in patients at diagnosis of type 1 diabetes and during prediabetes .", "entity": [], "task": "NER"}
{"text": "Complete and differential blood counts were analyzed from 107 adult patients with newly diagnosed type 1 diabetes , 21 children with persistent islet autoantibodies and a family history of type 1 diabetes , and 1 238 age and gender matched control subjects , all individuals without any signs of acute infection . Adult patients with newly diagnosed type 1 diabetes had significantly lower total WBC ( p < 1 x 10 - 6 ) , neutrophil ( p < 1 x 10 - 6 ) , basophil ( p < 1 x 10 - 6 ) , monocyte ( p = 4 x 10 - 6 ) and lymphocyte ( p < 1 x 10 - 6 ) counts compared to control subjects .", "entity": [], "task": "NER"}
{"text": "Erythrocyte , eosinophil and platelet counts did not differ between groups .", "entity": [], "task": "NER"}
{"text": "Similarly , children with persistent islet autoantibodies had decreased WBC ( p = 0 . 001 ) , neutrophils ( p = 0 . 003 ) , and lymphocytes ( p = 0 . 006 ) in comparison to control children .", "entity": [], "task": "NER"}
{"text": "Our findings demonstrate a perturbation of leukocyte homeostasis at and prior to onset of type 1 diabetes suggesting a general involvement of the innate immune system in the pathogenesis of type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "A genome - wide siRNA screen reveals positive and negative regulators of the NOD2 and NF - kappa B signaling pathways .", "entity": [], "task": "NER"}
{"text": "The cytoplasmic receptor NOD2 ( nucleotide - binding oligomerization domain 2 ) senses peptidoglycan fragments and triggers host defense pathways , including activation of nuclear factor kappa B ( NF - kappa B ) signaling , which lead to inflammatory immune responses .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [32, 42]}], "task": "NER"}
{"text": "Dysregulation of NOD2 signaling is associated with inflammatory diseases , such as Crohn ' s disease and Blau syndrome .", "entity": [], "task": "NER"}
{"text": "We used a genome - wide small interfering RNA screen to identify regulators of the NOD2 signaling pathway .", "entity": [], "task": "NER"}
{"text": "Several genes associated with Crohn ' s disease risk were identified in the screen .", "entity": [], "task": "NER"}
{"text": "A comparison of candidates from this screen with other \" omics \" data sets revealed interconnected networks of genes implicated in NF - kappa B signaling , thus supporting a role for NOD2 and NF - kappa B pathways in the pathogenesis of Crohn ' s disease .", "entity": [], "task": "NER"}
{"text": "Many of these regulators were validated in secondary assays , such as measurement of interleukin - 8 secretion , which is partially dependent on NF - kappa B .", "entity": [], "task": "NER"}
{"text": "Knockdown of putative regulators in human embryonic kidney 293 cells followed by stimulation with tumor necrosis factor - alpha revealed that most of the genes identified were general regulators of NF - kappa B signaling .", "entity": [], "task": "NER"}
{"text": "Overall , the genes identified here provide a resource to facilitate the elucidation of the molecular mechanisms that regulate NOD2 - and NF - kappa B - mediated inflammation .", "entity": [], "task": "NER"}
{"text": "Cloning and functional characterization of the pig ( Sus scrofa ) organic anion transporting polypeptide 1a2 .", "entity": [], "task": "NER"}
{"text": "Organic anion transporting polypeptides ( OATPs ) are a family of transporter proteins that have been extensively recognized as key determinants of absorption , distribution , metabolism and excretion of various drugs .", "entity": [], "task": "NER"}
{"text": "Human OATP1A2 has been demonstrated to transport wide spectrum of endogenous and exogenous compounds .", "entity": [], "task": "NER"}
{"text": "Study on OATP1A2 orthologues of other species , however , is still limited .", "entity": [], "task": "NER"}
{"text": "Here , we described the cloning and functional characterization of a member of the OATP / Oatp family member obtained from pig ( Sus scrofa ) liver .", "entity": [], "task": "NER"}
{"text": "Sequence analysis suggested that it has a high homology with human OATP1A2 and bovine Oatp1a2 .", "entity": [], "task": "NER"}
{"text": "Prototypic substrates estrone - 3 - sulfate ( E - 3 - S ) and taurocholic acid were transported by the protein .", "entity": [{"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [22, 43]}, {"entity": "E - 3 - S", "entity_type": "Chemical", "pos": [46, 55]}, {"entity": "taurocholic acid", "entity_type": "Chemical", "pos": [62, 78]}], "task": "NER"}
{"text": "The transport of these two substrates is pH - dependent , with lower pH showing higher uptake function .", "entity": [], "task": "NER"}
{"text": "Kinetic study showed the transport of these two substrates have a K ( m ) of 42 . 5 +/- 12 . 1 and 33 . 1 +/- 8 . 7 micro M , respectively .", "entity": [], "task": "NER"}
{"text": "Pig Slco1a2 has the highest expression level in the liver , and to a less extend in the brain and small intestine .", "entity": [], "task": "NER"}
{"text": "In conclusion , an OATP member was cloned from pig liver .", "entity": [], "task": "NER"}
{"text": "Sequence analysis and phylogenic study revealed it as an orthologue of human OATP1A2 .", "entity": [], "task": "NER"}
{"text": "Its kinetic characteristic for prototypic substrates and organ distribution are similar with that of OATP1A2 .", "entity": [], "task": "NER"}
{"text": "Folic acid modified cationic gamma - cyclodextrin - oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery .", "entity": [{"entity": "Folic acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "gamma - cyclodextrin", "entity_type": "Chemical", "pos": [29, 49]}, {"entity": "oligoethylenimine", "entity_type": "Chemical", "pos": [52, 69]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "For an efficient folate - targeted delivery , while the interaction between the folate on the carriers and the folate receptor ( FR ) on the cells is necessary , the recovering and recycling of FR to maintain a high density level of FR on the cellular membrane is also important .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [17, 23]}, {"entity": "folate", "entity_type": "Chemical", "pos": [80, 86]}, {"entity": "folate", "entity_type": "Chemical", "pos": [111, 117]}], "task": "NER"}
{"text": "Herein , we demonstrate a design and synthesis of a new star - shaped cationic polymer containing a gamma - cyclodextrin ( gamma - CD ) core and multiple oligoethylenimine ( OEI ) arms with folic acid ( FA ) linked by a bioreducible disulfide bond for efficient targeted gene delivery .", "entity": [{"entity": "gamma - cyclodextrin", "entity_type": "Chemical", "pos": [100, 120]}, {"entity": "gamma - CD", "entity_type": "Chemical", "pos": [123, 133]}, {"entity": "oligoethylenimine", "entity_type": "Chemical", "pos": [154, 171]}, {"entity": "OEI", "entity_type": "Chemical", "pos": [174, 177]}, {"entity": "folic acid", "entity_type": "Chemical", "pos": [190, 200]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [233, 242]}], "task": "NER"}
{"text": "The newly synthesized cationic polymer , named gamma - CD - OEI - SS - FA , could be cleaved efficiently , and FA was readily released under reductive condition similar to intracellular environment .", "entity": [{"entity": "gamma - CD - OEI - SS - FA", "entity_type": "Chemical", "pos": [47, 73]}], "task": "NER"}
{"text": "The gamma - CD - OEI - SS - FA polymer was well - characterized and studied in terms of its gene delivery properties in FR - positive KB cells and FR - negative A549 cells under various conditions , in comparison with cationic polymers such as high molecular weight branched polyethylenimine ( PEI ) , gamma - CD - OEI star - shaped cationic polymer , gamma - CD - OEI - FA polymer where FA was directed linked to the star polymer without disulfide linker .", "entity": [{"entity": "gamma - CD - OEI - SS - FA", "entity_type": "Chemical", "pos": [4, 30]}, {"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [275, 291]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [294, 297]}, {"entity": "gamma - CD - OEI", "entity_type": "Chemical", "pos": [302, 318]}, {"entity": "gamma - CD - OEI - FA", "entity_type": "Chemical", "pos": [352, 373]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [439, 448]}], "task": "NER"}
{"text": "Our data have demonstrated that the new gamma - CD - OEI - SS - FA gene carrier had low cytotoxicity and possessed capacity to target and deliver DNA to specific tumor cells that overexpress FRs , as well as functions to recover and recycle FRs onto cellular membranes to facilitate continuous FR - mediated endocytosis to achieve very high levels of gene expression .", "entity": [{"entity": "gamma - CD - OEI - SS - FA", "entity_type": "Chemical", "pos": [40, 66]}], "task": "NER"}
{"text": "This study has expanded the strategy of FA - targeted delivery by combining the smart FR - recycling function to achieve the significant enhancement of gene expression .", "entity": [], "task": "NER"}
{"text": "The new FA - targeted and bioreducible carrier may be a promising efficient gene delivery system for potential cancer gene therapy .", "entity": [], "task": "NER"}
{"text": "Diterpenoid alkaloids from Aconitum kirinense .", "entity": [{"entity": "Diterpenoid alkaloids", "entity_type": "Chemical", "pos": [0, 21]}], "task": "NER"}
{"text": "A new C ( 18 ) - diterpenoid alkaloid , kirinenine A ( 1 ) , was isolated from the root of Aconitum kirinense , along with eight known diterpenoid alkaloids .", "entity": [{"entity": "C ( 18 ) - diterpenoid alkaloid", "entity_type": "Chemical", "pos": [6, 37]}, {"entity": "kirinenine A", "entity_type": "Chemical", "pos": [40, 52]}, {"entity": "diterpenoid alkaloids", "entity_type": "Chemical", "pos": [135, 156]}], "task": "NER"}
{"text": "The structures of all compounds were characterized on the basis of extensive NMR and MS analyses and by comparison with literature values , and the new one was further confirmed by X - ray crystallographic diffraction .", "entity": [], "task": "NER"}
{"text": "All the compounds were isolated from the title plant for the first time .", "entity": [], "task": "NER"}
{"text": "A new compound from liquid fermentation broth of Armillaria mellea and the determination of its absolute configuration .", "entity": [], "task": "NER"}
{"text": "A new 2 , 5 - diketopiperazine , ( R ) - 2 - ( 2 - ( furan - 2 - yl ) - oxoethyl ) - octahydropyrrolo [ 1 , 2 - a ] pyrazine - 1 , 4 - dione , and seven known compounds were isolated from the ethyl acetate extract of liquid fermentation broth of Armillaria mellea .", "entity": [{"entity": "2 , 5 - diketopiperazine", "entity_type": "Chemical", "pos": [6, 30]}, {"entity": "( R ) - 2 - ( 2 - ( furan - 2 - yl ) - oxoethyl ) - octahydropyrrolo [ 1 , 2 - a ] pyrazine - 1 , 4 - dione", "entity_type": "Chemical", "pos": [33, 140]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [192, 205]}], "task": "NER"}
{"text": "The structures of the isolated compounds were established from NMR and HR - MS data .", "entity": [], "task": "NER"}
{"text": "The absolute configuration of the new compound was established by comparing the experimental electronic circular dichroism ( ECD ) spectrum with the calculated ECD data .", "entity": [], "task": "NER"}
{"text": "Dissecting single - molecule signal transduction in carbon nanotube circuits with protein engineering .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [52, 58]}], "task": "NER"}
{"text": "Single - molecule experimental methods have provided new insights into biomolecular function , dynamic disorder , and transient states that are all invisible to conventional measurements .", "entity": [], "task": "NER"}
{"text": "A novel , nonfluorescent single - molecule technique involves attaching single molecules to single - walled carbon nanotube field - effective transistors ( SWNT FETs ) .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "These ultrasensitive electronic devices provide long - duration , label - free monitoring of biomolecules and their dynamic motions .", "entity": [], "task": "NER"}
{"text": "However , generalization of the SWNT FET technique first requires design rules that can predict the success and applicability of these devices .", "entity": [], "task": "NER"}
{"text": "Here , we report on the transduction mechanism linking enzymatic processivity to electrical signal generation by a SWNT FET .", "entity": [], "task": "NER"}
{"text": "The interaction between SWNT FETs and the enzyme lysozyme was systematically dissected using eight different lysozyme variants synthesized by protein engineering .", "entity": [], "task": "NER"}
{"text": "The data prove that effective signal generation can be accomplished using a single charged amino acid , when appropriately located , providing a foundation to widely apply SWNT FET sensitivity to other biomolecular systems .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [91, 101]}], "task": "NER"}
{"text": "A new di - O - prenylated flavone from an actinomycete Streptomyces sp .", "entity": [{"entity": "di - O - prenylated flavone", "entity_type": "Chemical", "pos": [6, 33]}], "task": "NER"}
{"text": "MA - 12 .", "entity": [], "task": "NER"}
{"text": "A new di - O - prenylated flavone , named 7 , 3 ' - di - ( gamma , gamma - dimethylallyloxy ) - 5 - hydroxy - 4 ' - methoxyflavone ( 1 ) , was isolated from the culture broth of the endophytic actinomycete Streptomyces sp .", "entity": [{"entity": "di - O - prenylated flavone", "entity_type": "Chemical", "pos": [6, 33]}, {"entity": "7 , 3 ' - di - ( gamma , gamma - dimethylallyloxy ) - 5 - hydroxy - 4 ' - methoxyflavone", "entity_type": "Chemical", "pos": [42, 130]}], "task": "NER"}
{"text": "MA - 12 isolated from the root of the semi - mangrove plant Myoporum bontioides A .", "entity": [], "task": "NER"}
{"text": "Gray .", "entity": [], "task": "NER"}
{"text": "The structure of 1 was determined by comprehensive spectroscopic methods , including 1D and 2D NMR experiments ( COSY , HMQC , and HMBC ) .", "entity": [], "task": "NER"}
{"text": "Primary bioassays showed that 1 at concentration of 0 . 25 mM had moderate inhibitory activity against three plant pathogenic fungi including Colletotrichum musae , Gibberella zeae ( Schweinitz ) Petch , and Penicillium citrinum Thom .", "entity": [], "task": "NER"}
{"text": "New tetraterpene glycosides from the fruits of Lycium chinense .", "entity": [{"entity": "tetraterpene glycosides", "entity_type": "Chemical", "pos": [4, 27]}], "task": "NER"}
{"text": "Two new compounds lyciumtetraterpenic hexaarabinoside ( 1 ) and tetraterpenyl hexaarabinoside ( 2 ) , along with two known compounds , were isolated from the methanol extract of the fruits of Lycium chinense Miller ( Solanaceae ) , and their structures have been elucidated as 6 - ( 1 , 1 , 5 - trimethyl - 5 alpha - hydroxycyclohexanyl ) - 6 ' - ( 1 ' , 1 ' , 5 ' - trimethyl - 2 ' beta - hydroxycyclohexanyl ) - 9 , 13 , 9 ' , 13 ' - tetramethyloctadec - 7 , 9 , 11 , 13 , 15 , 7 ' , 9 ' , 11 ' , 13 ' - nonene - 5 alpha - D - arabinopyranosyl ( 2a --> 1b ) - beta - D - arabinopyranosyl - ( 2b --> 1c ) - beta - D - arabinopyranosyl - 2 ' - beta - D - arabinopyranosyl - ( 2d --> 1e ) - alpha - D - arabinopyranosyl - ( 2e --> 1f ) - alpha - D - arabinopyranoside ( 1 ) and 1 ( 6 ) , 11 ( 12 ) , 13 ( 14 ) , 1 ' ( 6 ' ) , 11 ' ( 12 ' ) , 13 ' ( 14 ' ) - dodecahydro - beta - caroten - 4 beta , 4 ' beta - diol - 4 beta - L - arabinopyranosyl - ( 2a --> 1b ) - beta - L - arabinopyranosyl - ( 2b --> 1c ) - beta - D - arabinopyranosido - 4 ' beta - L - arabinopyranosyl - ( 2d --> 1e ) - beta - L - arabinopyranosyl - ( 2e --> 1f ) - beta - D - arabinopyranoside ( 2 ) on the basis of spectral data analysis and chemical reactions .", "entity": [{"entity": "lyciumtetraterpenic hexaarabinoside", "entity_type": "Chemical", "pos": [18, 53]}, {"entity": "tetraterpenyl hexaarabinoside", "entity_type": "Chemical", "pos": [64, 93]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [158, 166]}, {"entity": "6 - ( 1 , 1 , 5 - trimethyl - 5 alpha - hydroxycyclohexanyl ) - 6 ' - ( 1 ' , 1 ' , 5 ' - trimethyl - 2 ' beta - hydroxycyclohexanyl ) - 9 , 13 , 9 ' , 13 ' - tetramethyloctadec - 7 , 9 , 11 , 13 , 15 , 7 ' , 9 ' , 11 ' , 13 ' - nonene - 5 alpha - D - arabinopyranosyl ( 2a --> 1b ) - beta - D - arabinopyranosyl - ( 2b --> 1c ) - beta - D - arabinopyranosyl - 2 ' - beta - D - arabinopyranosyl - ( 2d --> 1e ) - alpha - D - arabinopyranosyl - ( 2e --> 1f ) - alpha - D - arabinopyranoside", "entity_type": "Chemical", "pos": [277, 766]}, {"entity": "1 ( 6 ) , 11 ( 12 ) , 13 ( 14 ) , 1 ' ( 6 ' ) , 11 ' ( 12 ' ) , 13 ' ( 14 ' ) - dodecahydro - beta - caroten - 4 beta , 4 ' beta - diol - 4 beta - L - arabinopyranosyl - ( 2a --> 1b ) - beta - L - arabinopyranosyl - ( 2b --> 1c ) - beta - D - arabinopyranosido - 4 ' beta - L - arabinopyranosyl - ( 2d --> 1e ) - beta - L - arabinopyranosyl - ( 2e --> 1f ) - beta - D - arabinopyranoside", "entity_type": "Chemical", "pos": [777, 1164]}], "task": "NER"}
{"text": "Evolution of novel tricyclic CRTh2 receptor antagonists from a ( E ) - 2 - cyano - 3 - ( 1H - indol - 3 - yl ) acrylamide scaffold .", "entity": [{"entity": "( E ) - 2 - cyano - 3 - ( 1H - indol - 3 - yl ) acrylamide", "entity_type": "Chemical", "pos": [63, 121]}], "task": "NER"}
{"text": "( E ) - 2 - ( 3 - ( 3 - ( ( 3 - Bromophenyl ) amino ) - 2 - cyano - 3 - oxoprop - 1 - en - 1 - yl ) - 1H - indol - 1 - yl ) acetic acid ( 1 ) was discovered in a HTS campaign for CRTh2 receptor antagonists .", "entity": [{"entity": "( E ) - 2 - ( 3 - ( 3 - ( ( 3 - Bromophenyl ) amino ) - 2 - cyano - 3 - oxoprop - 1 - en - 1 - yl ) - 1H - indol - 1 - yl ) acetic acid", "entity_type": "Chemical", "pos": [0, 135]}], "task": "NER"}
{"text": "An SAR around this hit could be established and representatives with interesting activity profiles were obtained .", "entity": [], "task": "NER"}
{"text": "Ring closing tactics to convert this hit series into a novel 2 , 3 , 4 , 5 - tetrahydro - 1H - pyrido [ 4 , 3 - b ] indole based CRTh2 receptor antagonist series is presented .", "entity": [{"entity": "2 , 3 , 4 , 5 - tetrahydro - 1H - pyrido [ 4 , 3 - b ] indole", "entity_type": "Chemical", "pos": [61, 122]}], "task": "NER"}
{"text": "Genetic association study of WNT10B polymorphisms with BMD and adiposity parameters in Danish and Belgian males .", "entity": [], "task": "NER"}
{"text": "Because of the importance of the Wnt pathway in the development and maintenance of both adipose and bone tissue , we wanted to evaluate the involvement of WNT10B , a Wnt pathway activator , in adipogenesis and osteoblastogenesis in humans .", "entity": [], "task": "NER"}
{"text": "Genetic association between WNT10B polymorphisms and adiposity parameters as well as bone mineral density ( BMD ) measurements was analysed in two independent populations .", "entity": [], "task": "NER"}
{"text": "The first is a population of 1 , 228 Danish men ( 702 aged 20 - 29 years ; 532 aged 60 - 74 years ) from the Odense Androgen Study ( OAS ) , which was designed as a cross - sectional , population - based study .", "entity": [{"entity": "Androgen", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "The second population , called SIBLOS , includes 922 Belgian men ( 34 +/- 5 years old ) and contains siblings selected from over 500 families .", "entity": [], "task": "NER"}
{"text": "Four tagSNPs ( rs833840 , rs833841 , rs10875902 and rs4018511 ) that capture variation of ten SNPs ( MAF > 5 % ) in a 15 . 2 kb region spanning the WNT10B gene and its flanking regions were genotyped .", "entity": [], "task": "NER"}
{"text": "Although no association with body mass index was found , we found all tagSNPs to be associated with BMD parameters ( BMD whole body , total hip and femoral neck ) and height in the OAS population .", "entity": [], "task": "NER"}
{"text": "The association of rs10875902 was most prominent ( nominal p = 0 . 012 ) and confirmed a previously shown negative effect on BMD .", "entity": [], "task": "NER"}
{"text": "No significant associations were observed in the SIBLOS population .", "entity": [], "task": "NER"}
{"text": "In the present study , no association between WNT10B polymorphisms and adiposity parameters was found .", "entity": [], "task": "NER"}
{"text": "However , our results clearly illustrate a role for WNT10B variants in determining human BMD .", "entity": [], "task": "NER"}
{"text": "The effect of WNT10B polymorphisms on height should be evaluated in additional populations .", "entity": [], "task": "NER"}
{"text": "The 5 - HT1D / 1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [35, 46]}], "task": "NER"}
{"text": "This study measured the effects of the preferential 5 - HT1D / 1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test ( SPST ) , which recruits the neural network involved in panic disorder and social anxiety disorder .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "In a double - blind , randomised experiment , 36 males received placebo ( 12 ) , 50 mg ( 12 ) or 100 mg ( 12 ) of sumatriptan 2 h before the SPST .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "Subjective , physiological and hormonal measures were taken before , during and after the test .", "entity": [], "task": "NER"}
{"text": "The dose of 100 mg of sumatriptan increased speech - induced fear more than either a 50mg dose of the drug or placebo .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "The largest dose of sumatriptan also enhanced vigilance more than placebo , without any change in blood pressure , heart rate or electrical skin conductance .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [20, 31]}], "task": "NER"}
{"text": "Sumatriptan decreased plasma levels of prolactin .", "entity": [{"entity": "Sumatriptan", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "A significant but moderate increase in plasma cortisol after SPST occurred , independent of treatment .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [46, 54]}], "task": "NER"}
{"text": "Because sumatriptan decreases 5 - HT release into the extracellular space , the potentiation of SPST - induced fear caused by the drug supports the hypothesis that 5 - HT attenuates this emotional state .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [8, 19]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [164, 170]}], "task": "NER"}
{"text": "As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin , in contrast to sumatriptan , the 5 - HT regulation of stress - hormone release is likely to be different from that of emotion .", "entity": [{"entity": "sumatriptan", "entity_type": "Chemical", "pos": [135, 146]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [153, 159]}], "task": "NER"}
{"text": "Increases in triglyceride levels are associated with clinical response to clozapine treatment .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [13, 25]}, {"entity": "clozapine", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "Increases in serum triglyceride ( TG ) levels are associated with clinical response to clozapine treatment .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [19, 31]}, {"entity": "clozapine", "entity_type": "Chemical", "pos": [87, 96]}], "task": "NER"}
{"text": "Clozapine is the most efficacious therapy for treatment of refractory schizophrenia , although its use is well recognised to be associated with substantial metabolic dysfunction .", "entity": [{"entity": "Clozapine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Interestingly , there is some evidence that the therapeutic benefit of clozapine is associated with treatment - emergent weight gain and dyslipidaemia , specifically hypertriglyceridaemia .", "entity": [{"entity": "clozapine", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "In this prospective observational study , we examine associations between therapeutic response to clozapine in 49 patients with treatment - resistant schizophrenia and lipid dysregulation .", "entity": [{"entity": "clozapine", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "An increase in TG levels was strongly predictive of clinical improvement ( B = 9 . 33 , t = 3 . 56 , df = 4 , p < 0 . 001 ) and of improvement in positive PANSS scores ( B = 2 . 85 , t = 3 . 61 , df = 4 , p = 0 . 001 ) as well as negative PANSS scores ( B = 1 . 93 , t = 2 . 36 , df = 4 , p = 0 . 02 ) , when controlling for potential confounds of weight gain , change in waist circumference , baseline antipsychotic polypharmacy and serum clozapine levels .", "entity": [{"entity": "clozapine", "entity_type": "Chemical", "pos": [440, 449]}], "task": "NER"}
{"text": "This finding suggests that clozapine ' s therapeutic efficacy is linked to serum lipid changes .", "entity": [{"entity": "clozapine", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "Hypertriglyceridaemia as a predictor of clinical response in patients treated with clozapine merits further investigation in order to better elucidate its effect on the pharmacological activity of clozapine .", "entity": [{"entity": "clozapine", "entity_type": "Chemical", "pos": [83, 92]}, {"entity": "clozapine", "entity_type": "Chemical", "pos": [197, 206]}], "task": "NER"}
{"text": "Design and synthesis of some new quinazolin - 4 - ( 3H ) - ones as anticonvulsant and antidepressant agents .", "entity": [{"entity": "quinazolin - 4 - ( 3H ) - ones", "entity_type": "Chemical", "pos": [33, 63]}], "task": "NER"}
{"text": "A series of 3 - [ ( 4 - substituted - benzylidene ) - amino ] - 2 - phenyl - 3H - quinazolin - 4 - ones ( 5a - k ) were synthesized by reacting 3 - amino - 2 - phenyl - 1H - quinazolin - 4 - one with p - hydroxybenzaldehyde , and then further with various alkyl / benzyl halides or substituted phenacyl bromides .", "entity": [{"entity": "3 - [ ( 4 - substituted - benzylidene ) - amino ] - 2 - phenyl - 3H - quinazolin - 4 - ones", "entity_type": "Chemical", "pos": [12, 103]}, {"entity": "3 - amino - 2 - phenyl - 1H - quinazolin - 4 - one", "entity_type": "Chemical", "pos": [144, 194]}, {"entity": "p - hydroxybenzaldehyde", "entity_type": "Chemical", "pos": [200, 223]}, {"entity": "alkyl / benzyl halides", "entity_type": "Chemical", "pos": [256, 278]}, {"entity": "phenacyl bromides", "entity_type": "Chemical", "pos": [294, 311]}], "task": "NER"}
{"text": "The structures of the compounds were confirmed on the basis of IR , NMR , MS and elemental analysis .", "entity": [], "task": "NER"}
{"text": "Anticonvulsant activities were evaluated using the MES and scPTZ tests .", "entity": [], "task": "NER"}
{"text": "Some of the selected compounds were evaluated for antidepressant activity by forced swim pool test .", "entity": [], "task": "NER"}
{"text": "Compound 3 - [ ( 4 - butoxy - benzylidene ) - amino ] - 2 - phenyl - 3H - quinazolin - 4 - one was emerged as the most promising anticonvulsant agent without any motor impairment effect .", "entity": [{"entity": "3 - [ ( 4 - butoxy - benzylidene ) - amino ] - 2 - phenyl - 3H - quinazolin - 4 - one", "entity_type": "Chemical", "pos": [9, 94]}], "task": "NER"}
{"text": "The whole brain GABA estimation of brain homogenate indicated that the anticonvulsant activity of above mentioned quinazolinone derivatives might be due to an increased GABA concentration .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [16, 20]}, {"entity": "quinazolinone", "entity_type": "Chemical", "pos": [114, 127]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [169, 173]}], "task": "NER"}
{"text": "An autonomous chromatin / DNA - PK mechanism for localized DNA damage signaling in mammalian cells .", "entity": [], "task": "NER"}
{"text": "Rapid phosphorylation of histone variant H2AX proximal to DNA breaks is an initiating event and a hallmark of eukaryotic DNA damage responses .", "entity": [], "task": "NER"}
{"text": "Three mammalian kinases are known to phosphorylate H2AX in response to DNA damage .", "entity": [], "task": "NER"}
{"text": "However , the mechanism ( s ) for damage - localized phosphorylation remains incompletely understood .", "entity": [], "task": "NER"}
{"text": "The DNA - dependent protein kinase ( DNA - PK ) is the most abundant H2AX - modifying kinases and uniquely activated by binding DNA termini .", "entity": [], "task": "NER"}
{"text": "Here , we have developed a novel approach to examine enzyme activity and substrate properties by executing biochemical assays on intact cellular structures .", "entity": [], "task": "NER"}
{"text": "We apply this approach to examine the mechanisms of localized protein modification in chromatin within fixed cells .", "entity": [], "task": "NER"}
{"text": "DNA - PK retains substrate specificity and independently generates break - localized gamma H2AX foci in chromatin .", "entity": [], "task": "NER"}
{"text": "In situ DNA - PK activity recapitulates localization and intensity of in vivo H2AX phosphorylation and requires no active cellular processes .", "entity": [], "task": "NER"}
{"text": "Nuclease treatments or addition of exogenous DNA resulted in genome - wide H2AX phosphorylation , showing that DNA termini dictated the locality of H2AX phosphorylation in situ .", "entity": [], "task": "NER"}
{"text": "DNA - PK also reconstituted focal phosphorylation of structural maintenance of chromatin protein 1 , but not activating transcription factor 2 .", "entity": [], "task": "NER"}
{"text": "Allosteric regulation of DNA - PK by DNA termini protruding from chromatin constitutes an autonomous mechanism for break - localized protein phosphorylation that generates sub - nuclear foci .", "entity": [], "task": "NER"}
{"text": "We discuss generalized implications of this mechanism in localizing mammalian DNA damage responses .", "entity": [], "task": "NER"}
{"text": "Use of a Routh - Russel deformation map to achieve film formation of a latex with a high glass transition temperature .", "entity": [], "task": "NER"}
{"text": "In the film formation of latex , particle deformation can occur by processes of wet sintering , dry sintering , or capillary action .", "entity": [], "task": "NER"}
{"text": "When latex films dry nonuniformly and when particles deform and coalesce while the film is still wet , a detrimental skin layer will develop at the film surface .", "entity": [], "task": "NER"}
{"text": "In their process model , Routh and Russel proposed that the operative particle deformation mechanism can be determined by the values of control parameters on a deformation map .", "entity": [], "task": "NER"}
{"text": "Here , the film formation processes of three methyl methacrylate / butyl acrylate copolymer latexes with high glass transition temperatures ( T ( g ) ) , ranging from 45 to 64 degrees C , have been studied when heated by infrared radiation .", "entity": [{"entity": "methyl methacrylate", "entity_type": "Chemical", "pos": [45, 64]}, {"entity": "butyl acrylate", "entity_type": "Chemical", "pos": [67, 81]}], "task": "NER"}
{"text": "Adjusting the infrared ( IR ) power density enables the film temperature , polymer viscosity , and evaporation rate during latex film formation to be controlled precisely .", "entity": [], "task": "NER"}
{"text": "Different polymer particle deformation mechanisms have been demonstrated for the same latex under a variety of film formation process conditions .", "entity": [], "task": "NER"}
{"text": "When the temperature is too high , a skin layer develops .", "entity": [], "task": "NER"}
{"text": "On the other hand , when the temperature is too low , particles deform by dry sintering , and the process requires extended time periods .", "entity": [], "task": "NER"}
{"text": "The deduced mechanisms can be interpreted and explained by the Routh - Russel deformation maps .", "entity": [], "task": "NER"}
{"text": "Film formation of hard ( high T ( g ) ) coatings is achieved without using coalescing aids that emit volatile organic compounds ( VOCs ) , which is a significant technical achievement .", "entity": [], "task": "NER"}
{"text": "Dynamic Domains in Polymersomes : Mixtures of Polyanionic and Neutral Diblocks Respond More Rapidly to Changes in Calcium than to pH .", "entity": [{"entity": "Calcium", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "Chemical triggering of membrane domain dynamics is of broad relevance to cell signaling through lipid bilayers and might also be exploited in application of phase - separated vesicles .", "entity": [], "task": "NER"}
{"text": "Here we describe the morphodynamics and remixing kinetics of spotted polymersomes made with mixtures of polyanionic and neutral amphiphiles plus calcium .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [145, 152]}], "task": "NER"}
{"text": "Addition of the calcium chelator EDTA to vesicle dispersions produced a decrease in domain size within minutes , whereas increasing the pH with NaOH led to the viscous fingering of domains and decreased domain size over hours .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "EDTA", "entity_type": "Chemical", "pos": [33, 37]}, {"entity": "NaOH", "entity_type": "Chemical", "pos": [144, 148]}], "task": "NER"}
{"text": "Although the latter suggests that the charge of the polyanion contributes to domain formation , the remixing of more negative chains at high pH is surprising .", "entity": [], "task": "NER"}
{"text": "Domain roughening at high pH is also accelerated by EDTA , which highlights the dominance of cross - bridging .", "entity": [{"entity": "EDTA", "entity_type": "Chemical", "pos": [52, 56]}], "task": "NER"}
{"text": "Importantly , even though vesicles were perturbed only externally , the inner and outer leaflets remain coupled throughout , consistent with molecular dynamics simulations and suggestive of an order - disorder transition that underlies the remixing kinetics .", "entity": [], "task": "NER"}
{"text": "Quasiclassical Trajectory Study of CH ( 3 ) NO ( 2 ) Decomposition via Roaming Mediated Isomerization Using a Global Potential Energy Surface .", "entity": [{"entity": "CH ( 3 ) NO ( 2 )", "entity_type": "Chemical", "pos": [35, 52]}], "task": "NER"}
{"text": "We report a global potential energy surface ( PES ) for CH ( 3 ) NO ( 2 ) based on fitting roughly 114 000 density functional theory ( UB3LYP / 6 - 311 + g ( d , p ) ) electronic energies .", "entity": [{"entity": "CH ( 3 ) NO ( 2 )", "entity_type": "Chemical", "pos": [56, 73]}], "task": "NER"}
{"text": "The PES is a precise , permutationally invariant fit to these energies .", "entity": [], "task": "NER"}
{"text": "Properties of the PES are described , as are some preliminary quasiclassical trajectory calculations .", "entity": [], "task": "NER"}
{"text": "An isomerization - roaming pathway to the CH ( 3 ) ONO isomer and then to the CH ( 3 ) O + NO products is found .", "entity": [{"entity": "CH ( 3 ) ONO", "entity_type": "Chemical", "pos": [42, 54]}, {"entity": "CH ( 3 ) O", "entity_type": "Chemical", "pos": [78, 88]}, {"entity": "NO", "entity_type": "Chemical", "pos": [91, 93]}], "task": "NER"}
{"text": "Although the pathway occurs at larger distances than a related loose saddle - point on the PES , the pathway supports the supposition of such a pathway based on locating a loose first - order saddle point and associated IRC , reported previously by Zhu and Lin [ Zhu , R . S . and Lin , M . C . Chem . Phys . Lett . 2009 , 478 , 11 ] .", "entity": [], "task": "NER"}
{"text": "Selective inhibition of extracellular thioredoxin by asymmetric disulfides .", "entity": [{"entity": "disulfides", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "Whereas the role of mammalian thioredoxin ( Trx ) as an intracellular protein cofactor is widely appreciated , its function in the extracellular environment is not well - understood .", "entity": [], "task": "NER"}
{"text": "Only few extracellular targets of Trx - mediated thiol - disulfide exchange are known .", "entity": [{"entity": "thiol - disulfide", "entity_type": "Chemical", "pos": [49, 66]}], "task": "NER"}
{"text": "For example , Trx activates extracellular transglutaminase 2 ( TG2 ) via reduction of an intramolecular disulfide bond .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "Because hyperactive TG2 is thought to play a role in various diseases , understanding the biological role of extracellular Trx may provide critical insight into the pathogenesis of these disorders .", "entity": [], "task": "NER"}
{"text": "Starting from a clinical - stage asymmetric disulfide lead , we have identified analogs with > 100 - fold specificity for Trx .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "Structure - activity relationship and computational docking model analyses have provided insights into the features important for enhancing potency and specificity .", "entity": [], "task": "NER"}
{"text": "The most active compound identified had an IC ( 50 ) below 0 . 1 mu M in cell culture and may be appropriate for in vivo use to interrogate the role of extracellular Trx in health and disease .", "entity": [], "task": "NER"}
{"text": "Invasive lobular carcinoma stable for 4 . 5 years in a postmenopausal woman user of hormone therapy for 25 years .", "entity": [], "task": "NER"}
{"text": "We present a case of a 72 - year - old woman referred to the breast disorder service due to abnormalities on mammography and breast ultrasound .", "entity": [], "task": "NER"}
{"text": "The patient reported using different hormone therapy ( HT ) formulations during 25 years and had stopped taking HT for 4 years .", "entity": [], "task": "NER"}
{"text": "Physical examination showed no alterations in the breasts or axilla .", "entity": [], "task": "NER"}
{"text": "Mammography from 2012 detected asymmetry at the 3 o ' clock position in the anterior right breast .", "entity": [], "task": "NER"}
{"text": "Ultrasound revealed an irregular , hypoechoic mass with indistinct margins , and posterior acoustic shadowing .", "entity": [], "task": "NER"}
{"text": "A retrospective analysis of mammographies from 2007 , 2009 and 2010 showed that a very subtle asymmetry had existed since 2007 .", "entity": [], "task": "NER"}
{"text": "Follow - up imaging demonstrated no change in asymmetry during 4 . 5 years .", "entity": [], "task": "NER"}
{"text": "The patient underwent breast - conserving therapy and sentinel lymph node biopsy .", "entity": [], "task": "NER"}
{"text": "Histopathologic examination demonstrated classic invasive lobular carcinoma .", "entity": [], "task": "NER"}
{"text": "There were no sentinel node metastases .", "entity": [], "task": "NER"}
{"text": "The patient received radiotherapy and endrocrine therapy .", "entity": [], "task": "NER"}
{"text": "This case demonstrates that breast cancer may remain stable and not grow for many years .", "entity": [], "task": "NER"}
{"text": "This aspect should be kept in mind by all professionals dealing with women ' s healthcare , in particular HT users who may develop breast cancer with a less aggressive behavior .", "entity": [], "task": "NER"}
{"text": "Any suspicious finding on mammography , despite being unchanged for a number of years , must be investigated .", "entity": [], "task": "NER"}
{"text": "Dibenzocyclooctadiene lignans and norlignans from fruits of Schisandra wilsoniana .", "entity": [{"entity": "Dibenzocyclooctadiene lignans", "entity_type": "Chemical", "pos": [0, 29]}, {"entity": "norlignans", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "Seven new dibenzocyclooctadiene lignans , marlignans M - S ( 1 - 7 ) , four new norlignans , marphenols C - F ( 8 - 11 ) , and 21 known compounds ( 12 - 32 ) were isolated from the fruits of Schisandra wilsoniana .", "entity": [{"entity": "dibenzocyclooctadiene lignans", "entity_type": "Chemical", "pos": [10, 39]}, {"entity": "marlignans M - S", "entity_type": "Chemical", "pos": [42, 58]}, {"entity": "norlignans", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "marphenols C - F", "entity_type": "Chemical", "pos": [93, 109]}], "task": "NER"}
{"text": "The structures of 1 - 11 were elucidated by spectroscopic methods including 1D - and 2D - NMR techniques and CD experiments .", "entity": [], "task": "NER"}
{"text": "Compounds 1 - 11 were evaluated for their anti - HIV activities and showed EC ( 50 ) values in the range 2 . 97 - 6 . 18 mu g / mL and therapeutic index values of 5 . 33 - 29 . 13 .", "entity": [], "task": "NER"}
{"text": "Acutely administered antipsychotic drugs are highly selective for dopamine D2 over D3 receptors .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "We showed previously , using [ ( 3 ) H ] - ( + ) - 4 - propyl - 9 - hydroxynaphthoxazine ( [ ( 3 ) H ] - ( + ) - PHNO ) autoradiography , that several antipsychotic drugs do not occupy dopamine D3 receptors at clinically - relevant doses in rat .", "entity": [{"entity": "[ ( 3 ) H ] - ( + ) - 4 - propyl - 9 - hydroxynaphthoxazine", "entity_type": "Chemical", "pos": [29, 88]}, {"entity": "[ ( 3 ) H ] - ( + ) - PHNO", "entity_type": "Chemical", "pos": [91, 117]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [185, 193]}], "task": "NER"}
{"text": "This is an unexpected finding considering the near - equivalent in vitro affinity of these drugs for D2 and D3 receptors .", "entity": [], "task": "NER"}
{"text": "The purpose of the current study was to address two possible methodological limitations of our previous report , namely that ( 1 ) [ ( 3 ) H ] - ( + ) - PHNO may have been administered at non - tracer dose , potentially causing underestimate of D3 receptor occupancy , and ( 2 ) antipsychotic drugs were administered chronically , potentially causing increased D3 receptor expression not accounted for in the vehicle - treated control group .", "entity": [{"entity": "[ ( 3 ) H ] - ( + ) - PHNO", "entity_type": "Chemical", "pos": [131, 157]}], "task": "NER"}
{"text": "We found that decreasing [ ( 3 ) H ] - ( + ) - PHNO dose from 5 . 6nmol / kg ( our previous dose ) to 0 . 6nmol / kg caused a > 60 % increase in [ ( 3 ) H ] - ( + ) - PHNO binding to D3 receptors in cerebellar lobes 9 and 10 , indicating that our previous study was indeed conducted under non - tracer dose conditions .", "entity": [{"entity": "[ ( 3 ) H ] - ( + ) - PHNO", "entity_type": "Chemical", "pos": [25, 51]}, {"entity": "[ ( 3 ) H ] - ( + ) - PHNO", "entity_type": "Chemical", "pos": [145, 171]}], "task": "NER"}
{"text": "However , neither reducing [ ( 3 ) H ] - ( + ) - PHNO dose further to 0 . 3nmol / kg ( a tracer dose ) , nor administering antipsychotics acutely affected antipsychotic receptor occupancy .", "entity": [{"entity": "[ ( 3 ) H ] - ( + ) - PHNO", "entity_type": "Chemical", "pos": [27, 53]}], "task": "NER"}
{"text": "At clinically - relevant levels of D2 occupancy ( 57 - 82 % inhibition of striatal binding ) , neither olanzapine nor haloperidol occupied D3 receptors , while clozapine occupied D3 receptors at levels similar to our previous report ( 33 % ) .", "entity": [{"entity": "olanzapine", "entity_type": "Chemical", "pos": [103, 113]}, {"entity": "haloperidol", "entity_type": "Chemical", "pos": [118, 129]}, {"entity": "clozapine", "entity_type": "Chemical", "pos": [160, 169]}], "task": "NER"}
{"text": "Risperidone moderately occupied D3 receptors ( 40 % ) , but at a dose occupying > 90 % of D2 receptors and therefore of questionable clinical relevance .", "entity": [{"entity": "Risperidone", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "These findings demonstrate that the lack of antipsychotic occupancy of D3 receptors is not attributable to limitations of our previous study .", "entity": [], "task": "NER"}
{"text": "These results suggest that D3 receptor blockade is not necessary for the therapeutic effects of the antipsychotic drugs examined .", "entity": [], "task": "NER"}
{"text": "Lifestyle and osteoporosis in middle - aged and elderly women : Chiba bone survey .", "entity": [], "task": "NER"}
{"text": "Osteoporosis causes an enormous health and economic impact in Japan .", "entity": [], "task": "NER"}
{"text": "We investigated the relation between lifestyle and bone fracture in middle - aged and elderly women .", "entity": [], "task": "NER"}
{"text": "This was a population - based , multicenter , cross - sectional survey for postmenopausal osteoporosis in Chiba City , Japan ( Chiba bone survey ) .", "entity": [], "task": "NER"}
{"text": "This survey included 64 , 809 Japanese women aged > 40 years .", "entity": [], "task": "NER"}
{"text": "All participants underwent anthropometric measurements including bone mineral density ( BMD ) and completed a structured , nurse - assisted , self - administered questionnaire also including patient lifestyle .", "entity": [], "task": "NER"}
{"text": "Bone fracture during the recent 5 years was observed in 5 . 3 % , and the fracture group had significantly higher age , BMI , and number of births , family histories of kyphosis and hip fracture , diabetes mellitus ( DM ) , dyslipidemia , kidney disease , exercise , fall , and osteoporosis , and had significantly lower BMD and proportion of menstruating participants .", "entity": [], "task": "NER"}
{"text": "Logistic regression analysis revealed that bone fracture was closely associated with not only low bone mass but also age , fall , family histories of kyphosis and hip fracture , DM , kidney disease , menopause , and lifestyle factors of dieting , exercise , and alcohol .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [262, 269]}], "task": "NER"}
{"text": "Women ' s health care focusing on lifestyle - related fracture risks such as dieting , exercise , and alcohol appears necessary to prevent bone fracture in postmenopausal osteoporosis .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "Transport by OATP1B1 and OATP1B3 enhances the cytotoxicity of epigallocatechin 3 - O - gallate and several quercetin derivatives .", "entity": [{"entity": "epigallocatechin 3 - O - gallate", "entity_type": "Chemical", "pos": [62, 94]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [107, 116]}], "task": "NER"}
{"text": "Organic anion transporting polypeptides ( OATPs ) 1B1 and 1B3 are transporters that are expressed selectively in human hepatocytes under normal conditions .", "entity": [], "task": "NER"}
{"text": "OATP1B3 is also expressed in certain cancers .", "entity": [], "task": "NER"}
{"text": "Flavonoids such as green tea catechins and quercetin glycosides have been shown to modulate the function of some OATPs .", "entity": [{"entity": "Flavonoids", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "catechins", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "quercetin glycosides", "entity_type": "Chemical", "pos": [43, 63]}], "task": "NER"}
{"text": "In the present study , the extent to which six substituted quercetin derivatives ( 1 - 6 ) affected the function of OATP1B1 and OATP1B3 was investigated .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [59, 68]}], "task": "NER"}
{"text": "Uptake of the radiolabeled model substrates estradiol 17 beta - glucuronide , estrone 3 - sulfate , and dehydroepiandrosterone sulfate ( DHEAS ) was determined in the absence and presence of compounds 1 - 6 using Chinese hamster ovary ( CHO ) cells stably expressing either OATP1B1 or OATP1B3 .", "entity": [{"entity": "estradiol 17 beta - glucuronide", "entity_type": "Chemical", "pos": [44, 75]}, {"entity": "estrone 3 - sulfate", "entity_type": "Chemical", "pos": [78, 97]}, {"entity": "dehydroepiandrosterone sulfate", "entity_type": "Chemical", "pos": [104, 134]}, {"entity": "DHEAS", "entity_type": "Chemical", "pos": [137, 142]}], "task": "NER"}
{"text": "Several of compounds 1 - 6 inhibited OATP - mediated uptake of all three model substrates , suggesting that they could also be potential substrates .", "entity": [], "task": "NER"}
{"text": "Compound 6 stimulated OATP1B3 - mediated estradiol 17 beta - glucuronide uptake by increasing the apparent affinity of OATP1B3 for its substrate .", "entity": [{"entity": "estradiol 17 beta - glucuronide", "entity_type": "Chemical", "pos": [41, 72]}], "task": "NER"}
{"text": "Cytotoxicity assays demonstrated that epigallocatechin 3 - O - gallate ( EGCG ) and most of compounds 1 - 6 killed preferentially OATP - expressing CHO cells .", "entity": [{"entity": "epigallocatechin 3 - O - gallate", "entity_type": "Chemical", "pos": [38, 70]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "EGCG , 1 , and 3 were the most potent cytotoxic compounds , with EGCG and 3 selectively killing OATP1B3 - expressing cells .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "Given that OATP1B3 is expressed in several cancers , EGCG and some of the quercetin derivatives studied might be promising lead compounds for the development of novel anticancer drugs .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [53, 57]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "Labdane - type diterpenoids from the fruits of Vitex trifolia .", "entity": [{"entity": "Labdane", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "diterpenoids", "entity_type": "Chemical", "pos": [15, 27]}], "task": "NER"}
{"text": "Seven new labdane - type diterpenoids , vitextrifolins A - G ( 1 - 7 ) , along with eight previously reported analogues , were isolated from the fruits of Vitex trifolia .", "entity": [{"entity": "labdane", "entity_type": "Chemical", "pos": [10, 17]}, {"entity": "diterpenoids", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "vitextrifolins A - G", "entity_type": "Chemical", "pos": [40, 60]}], "task": "NER"}
{"text": "The structures of 1 - 7 were elucidated by spectroscopic data interpretation .", "entity": [], "task": "NER"}
{"text": "The isolates were evaluated for their cytotoxicity against four human cancer cell lines ( A549 , HCT116 , HL - 60 , and ZR - 75 - 30 ) , but all were inactive ( IC ( 50 ) < 5 mu g / mL ) .", "entity": [], "task": "NER"}
{"text": "Injectable hyaluronic acid - tyramine hydrogels incorporating interferon - alpha 2a for liver cancer therapy .", "entity": [{"entity": "tyramine", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "We report an injectable hydrogel system that incorporates interferon - alpha 2a ( IFN - alpha 2a ) for liver cancer therapy .", "entity": [], "task": "NER"}
{"text": "IFN - alpha 2a was incorporated in hydrogels composed of hyaluronic acid - tyramine ( HA - Tyr ) conjugates through the oxidative coupling of Tyr moieties with hydrogen peroxide ( H2O2 ) and horseradish peroxidase ( HRP ) .", "entity": [{"entity": "tyramine", "entity_type": "Chemical", "pos": [75, 83]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [142, 145]}, {"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [160, 177]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [180, 184]}], "task": "NER"}
{"text": "IFN - alpha 2a - incorporated HA - Tyr hydrogels of varying stiffness were formed by changing the H2O2 concentration .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [98, 102]}], "task": "NER"}
{"text": "The incorporation of IFN - alpha 2a did not affect the rheological properties of the hydrogels .", "entity": [], "task": "NER"}
{"text": "The activity of IFN - alpha 2a was furthermore well - maintained in the hydrogels with lower stiffness .", "entity": [], "task": "NER"}
{"text": "Through the caspase - 3 / 7 pathway in vitro , IFN - alpha 2a released from HA - Tyr hydrogels inhibited the proliferation of liver cancer cells and induced apoptosis .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "In the study of the pharmacokinetics , a higher concentration of IFN - alpha 2a was shown in the plasma of mice treated with IFN - alpha 2a - incorporated hydrogels after 4h post injection , with a much higher amount of IFN - alpha 2a delivered at the tumor tissue comparing to that of injecting an IFN - alpha 2a solution .", "entity": [], "task": "NER"}
{"text": "The tumor regression study revealed that IFN - alpha 2a - incorporated HA - Tyr hydrogels effectively inhibited tumor growth , while the injection of an IFN - alpha 2a solution did not demonstrate antitumor efficacy .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "Histological studies confirmed that tumor tissues in mice treated with IFN - alpha 2a - incorporated HA - Tyr hydrogels showed lower cell density , with more apoptotic and less proliferating cells compared with tissues treated with an IFN - alpha 2a solution .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "In addition , the IFN - alpha 2a - incorporated hydrogel treatment greatly inhibited the angiogenesis of tumor tissues .", "entity": [], "task": "NER"}
{"text": "Nonalcoholic fatty liver disease : current issues and novel treatment approaches .", "entity": [], "task": "NER"}
{"text": "Nonalcoholic fatty liver disease ( NAFLD ) is considered the most common liver disorder in the Western world .", "entity": [], "task": "NER"}
{"text": "It is commonly associated with insulin resistance , obesity , dyslipidaemia , type 2 diabetes mellitus ( T2DM ) and cardiovascular disease .", "entity": [], "task": "NER"}
{"text": "Nonalcoholic steatohepatitis ( NASH ) is characterized by steatosis with necroinflammation and eventual fibrosis , which can lead to end - stage liver disease and hepatocellular carcinoma .", "entity": [], "task": "NER"}
{"text": "Its pathogenesis is complex , and involves a state of ' lipotoxicity ' in which insulin resistance , with increased free fatty acid release from adipose tissue to the liver , play a key role in the onset of a ' lipotoxic liver disease ' and its progression to NASH .", "entity": [{"entity": "free fatty acid", "entity_type": "Chemical", "pos": [116, 131]}], "task": "NER"}
{"text": "The diagnosis of NASH is challenging , as most affected patients are symptom free and the role of routine screening is not clearly established .", "entity": [], "task": "NER"}
{"text": "A complete medical history is important to rule out other causes of fatty liver disease ( alcohol abuse , medications , other ) .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "Plasma aminotransferase levels and liver ultrasound are helpful in the diagnosis of NAFLD / NASH , but a liver biopsy is often required for a definitive diagnosis .", "entity": [], "task": "NER"}
{"text": "However , there is an active search for plasma biomarkers and imaging techniques that may non - invasively aid in the diagnosis .", "entity": [], "task": "NER"}
{"text": "The treatment of NASH requires a multifaceted approach .", "entity": [], "task": "NER"}
{"text": "The goal is to reverse obesity - associated lipotoxicity and insulin resistance via lifestyle intervention .", "entity": [], "task": "NER"}
{"text": "Although there is no pharmacological agent approved for the treatment of NAFLD , vitamin E ( in patients without T2DM ) and the thiazolidinedione pioglitazone ( in patients with and without T2DM ) have shown the most consistent results in randomized controlled trials .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "pioglitazone", "entity_type": "Chemical", "pos": [146, 158]}], "task": "NER"}
{"text": "This review concentrates on our current understanding of the disease , with a focus on the existing therapeutic approaches and potential future pharmacological developments for NAFLD and NASH .", "entity": [], "task": "NER"}
{"text": "Ranolazine : a review of its use as add - on therapy in patients with chronic stable angina pectoris .", "entity": [{"entity": "Ranolazine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Extended - release ranolazine ( ranolazine ER ) [ Ranexa ( (R) ) ] is an antianginal agent that achieves its effects via a novel mechanism of action ( inhibition of the late phase of the inward sodium current ) , without affecting heart rate or blood pressure ( BP ) .", "entity": [{"entity": "Extended - release ranolazine", "entity_type": "Chemical", "pos": [0, 29]}, {"entity": "ranolazine ER", "entity_type": "Chemical", "pos": [32, 45]}, {"entity": "Ranexa", "entity_type": "Chemical", "pos": [50, 56]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [194, 200]}], "task": "NER"}
{"text": "This article reviews the efficacy , safety and tolerability of ranolazine ER as add - on therapy in patients with chronic stable angina pectoris , as well as summarizing its pharmacological properties and its use in non - ST - elevation acute coronary syndromes .", "entity": [{"entity": "ranolazine ER", "entity_type": "Chemical", "pos": [63, 76]}], "task": "NER"}
{"text": "In the CARISA and ERICA trials , add - on therapy with ranolazine ER improved exercise tolerance and / or reduced angina frequency and nitroglycerin use in patients with chronic stable angina ; benefits were seen across a variety of patient subgroups .", "entity": [{"entity": "ranolazine ER", "entity_type": "Chemical", "pos": [55, 68]}, {"entity": "nitroglycerin", "entity_type": "Chemical", "pos": [135, 148]}], "task": "NER"}
{"text": "Although results of the MERLIN - TIMI 36 trial do not support the use of ranolazine ER in the acute management of non - ST - elevation acute coronary syndromes , they do support its use as an antianginal therapy .", "entity": [{"entity": "ranolazine ER", "entity_type": "Chemical", "pos": [73, 86]}], "task": "NER"}
{"text": "Ranolazine ER was generally well tolerated , with the most commonly reported adverse events including dizziness , nausea , asthenia and constipation .", "entity": [{"entity": "Ranolazine ER", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Despite being associated with modest increases in the corrected QT interval , ranolazine ER demonstrated antiarrhythmic effects in the MERLIN - TIMI 36 trial .", "entity": [{"entity": "ranolazine ER", "entity_type": "Chemical", "pos": [78, 91]}], "task": "NER"}
{"text": "In conclusion , ranolazine ER provides an important option for use as add - on therapy to reduce symptoms in patients with chronic stable angina .", "entity": [{"entity": "ranolazine ER", "entity_type": "Chemical", "pos": [16, 29]}], "task": "NER"}
{"text": "Recognition of viral RNA stem - loops by the tandem double - stranded RNA binding domains of PKR .", "entity": [], "task": "NER"}
{"text": "In humans , the double - stranded RNA ( dsRNA ) - activated protein kinase ( PKR ) is expressed in late stages of the innate immune response to viral infection by the interferon pathway .", "entity": [], "task": "NER"}
{"text": "PKR consists of tandem dsRNA binding motifs ( dsRBMs ) connected via a flexible linker to a Ser / Thr kinase domain .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "Thr", "entity_type": "Chemical", "pos": [98, 101]}], "task": "NER"}
{"text": "Upon interaction with viral dsRNA , PKR is converted into a catalytically active enzyme capable of phosphorylating a number of target proteins that often results in host cell translational repression .", "entity": [], "task": "NER"}
{"text": "A number of high - resolution structural studies involving individual dsRBMs from proteins other than PKR have highlighted the key features required for interaction with perfectly duplexed RNA substrates .", "entity": [], "task": "NER"}
{"text": "However , viral dsRNA molecules are highly structured and often contain deviations from perfect A - form RNA helices .", "entity": [], "task": "NER"}
{"text": "By use of small - angle X - ray scattering ( SAXS ) , we present solution conformations of the tandem dsRBMs of PKR in complex with two imperfectly base - paired viral dsRNA stem - loops ; HIV - 1 TAR and adenovirus VA ( I ) - AS .", "entity": [], "task": "NER"}
{"text": "Both individual components and complexes were purified by size exclusion chromatography and characterized by dynamic light scattering at multiple concentrations to ensure monodispersity .", "entity": [], "task": "NER"}
{"text": "SAXS ab initio solution conformations of the individual components and RNA - protein complexes were determined and highlight the potential of PKR to interact with both stem and loop regions of the RNA .", "entity": [], "task": "NER"}
{"text": "Excellent agreement between experimental and model - based hydrodynamic parameter determination heightens our confidence in the obtained models .", "entity": [], "task": "NER"}
{"text": "Taken together , these data support and provide a framework for the existing biochemical data regarding the tolerance of imperfectly base - paired viral dsRNA by PKR .", "entity": [], "task": "NER"}
{"text": "Nuclear receptors in bile acid metabolism .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Bile acids are signaling molecules that activate nuclear receptors , such as farnesoid X receptor , pregnane X receptor , constitutive androstane receptor , and vitamin D receptor , and play a critical role in the regulation of lipid , glucose , energy , and drug metabolism .", "entity": [{"entity": "Bile acids", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "pregnane", "entity_type": "Chemical", "pos": [100, 108]}, {"entity": "androstane", "entity_type": "Chemical", "pos": [135, 145]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [161, 170]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [236, 243]}], "task": "NER"}
{"text": "These xenobiotic / endobiotic - sensing nuclear receptors regulate phase I oxidation , phase II conjugation , and phase III transport in bile acid and drug metabolism in the digestive system .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [137, 146]}], "task": "NER"}
{"text": "Integration of bile acid metabolism with drug metabolism controls absorption , transport , and metabolism of nutrients and drugs to maintain metabolic homeostasis and also protects against liver injury , inflammation , and related metabolic diseases , such as nonalcoholic fatty liver disease , diabetes , and obesity .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "Bile - acid - based drugs targeting nuclear receptors are in clinical trials for treating cholestatic liver diseases and fatty liver disease .", "entity": [{"entity": "Bile - acid", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Bioanalytical assay strategies for the development of antibody - drug conjugate biotherapeutics .", "entity": [], "task": "NER"}
{"text": "Antibody - drug conjugates ( ADCs ) are monoclonal antibodies with covalently bound cytotoxic drugs .", "entity": [], "task": "NER"}
{"text": "They are designed to target tumor antigens selectively and offer the hope of cancer treatment without the debilitating side - effects of conventional therapies .", "entity": [], "task": "NER"}
{"text": "The concept of ADCs is not new ; however , development of these therapeutics is challenging and only recently are promising clinical data emerging .", "entity": [], "task": "NER"}
{"text": "These challenges include ADC bioanalysis , such as quantifying in serum / plasma for PK studies and strategies for assessing immunogenicity .", "entity": [], "task": "NER"}
{"text": "ADCs have complex molecular structures incorporating large - and small - molecule characteristics and require diverse analytical methods , including ligand - binding assays and MS - based methods .", "entity": [], "task": "NER"}
{"text": "ADCs are typically mixtures with a range of drug - to - antibody ratios .", "entity": [], "task": "NER"}
{"text": "Biotransformations in vivo can lead to additional changes in drug - to - antibody ratios resulting in dynamically changing mixtures .", "entity": [], "task": "NER"}
{"text": "Thus , a standard calibration curve consisting of the reference standard may not be appropriate for quantification of analytes in vivo and represents a unique challenge .", "entity": [], "task": "NER"}
{"text": "This paper will share our perspective on why ADC bioanalysis is so complex and describe the strategies and rationale that we have used for ADCs , with highlights of original data from a variety of nonclinical and clinical case studies .", "entity": [], "task": "NER"}
{"text": "Our strategy has involved novel protein structural characterization tools to help understand ADC biotransformations in vivo and use of the analyte knowledge gained to guide the development of quantitative bioanalytical assays .", "entity": [], "task": "NER"}
{"text": "Electrokinetic charging and evidence for charge evaporation in liquid microjets of aqueous salt solution .", "entity": [], "task": "NER"}
{"text": "Electrokinetic charging of aqueous microjets was characterized by measuring streaming currents as a function of sodium iodide salt concentration .", "entity": [{"entity": "sodium iodide", "entity_type": "Chemical", "pos": [112, 125]}], "task": "NER"}
{"text": "Measured streaming currents at high salt concentrations ( up to 0 . 5 M ) varied nonmonotonically with the jet velocity and can be explained by a multipolar charge distribution at the nozzle - water interface .", "entity": [], "task": "NER"}
{"text": "In the case of potassium fluoride no multipolar charge distribution is observed .", "entity": [{"entity": "potassium fluoride", "entity_type": "Chemical", "pos": [15, 33]}], "task": "NER"}
{"text": "Electrokinetic potentials were estimated from the streaming currents , under the assumption that all excess charges are confined within the liquid jet .", "entity": [], "task": "NER"}
{"text": "Measured photoelectron spectra indicate much smaller streaming potentials .", "entity": [], "task": "NER"}
{"text": "To resolve the apparent discrepancy , we propose that a significant fraction of excess charges evaporates in the form of ion - water clusters .", "entity": [], "task": "NER"}
{"text": "Multilayered hierarchical capsules providing cell adhesion sites .", "entity": [], "task": "NER"}
{"text": "Liquified capsules featuring ( i ) an external shell by layer - by - layer assembly of poly ( l - lysine ) , alginate , and chitosan , and encapsulating ( ii ) surface functionalized poly ( l - lactic acid ) ( PLLA ) microparticles were developed .", "entity": [{"entity": "poly ( l - lysine )", "entity_type": "Chemical", "pos": [87, 106]}, {"entity": "poly ( l - lactic acid )", "entity_type": "Chemical", "pos": [183, 207]}, {"entity": "PLLA", "entity_type": "Chemical", "pos": [210, 214]}], "task": "NER"}
{"text": "We hypothesize that , while the liquified environment enhances the diffusion of essential molecules for cell survival , microparticles dispersed in the liquified core of capsules provide the physical support required for cellular functions of anchorage - dependent cells .", "entity": [], "task": "NER"}
{"text": "The influence of the incorporation of PLL on the regime growth , thickness , and stability was analyzed .", "entity": [{"entity": "PLL", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Results show a more resistant and thicker film with an exponential build - up growth regime .", "entity": [], "task": "NER"}
{"text": "Moreover , capsules ability to support cell survival was assessed .", "entity": [], "task": "NER"}
{"text": "Capsules containing microparticles revealed an enhanced biological outcome in cell metabolic activity and proliferation , suggesting their potential to boost the development of innovative biomaterial designs for bioencapsulation systems and tissue engineering products .", "entity": [], "task": "NER"}
{"text": "Interaction between group IIb divalent transition - metal cations and 3 - mercaptopropionic acid : a computational and topological perspective .", "entity": [{"entity": "group IIb divalent transition - metal", "entity_type": "Chemical", "pos": [20, 57]}, {"entity": "3 - mercaptopropionic acid", "entity_type": "Chemical", "pos": [70, 96]}], "task": "NER"}
{"text": "Density functional theory was applied to study the interaction of group IIb transition - metal cations ( Zn ( 2 + ) , Cd ( 2 + ) , and Hg ( 2 + ) ) with one and two fully or partially deprotonated 3 - mercaptopropionic acid ligands .", "entity": [{"entity": "group IIb transition - metal", "entity_type": "Chemical", "pos": [66, 94]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "Cd ( 2 + )", "entity_type": "Chemical", "pos": [118, 128]}, {"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [135, 145]}, {"entity": "3 - mercaptopropionic acid", "entity_type": "Chemical", "pos": [197, 223]}], "task": "NER"}
{"text": "In this investigation , we determined the geometries of all possible complexes resulting from the coordination of the metal ions with the ligands at different binding sites selected on each ligand .", "entity": [], "task": "NER"}
{"text": "The relative energies of the complexes , metal - ion affinities , free energies , and entropies were also determined .", "entity": [], "task": "NER"}
{"text": "The natures of the bonds were critically analyzed by natural bond orbital ( NBO ) analysis and clarified further using the atoms - in - molecules ( AIM ) approach .", "entity": [], "task": "NER"}
{"text": "The substantial influence of the solvent ( water ) polarization on the energetics , geometries , and bonding of the molecular complexes was also investigated by the conductor - like screening solvation model ( COSMO ) .", "entity": [], "task": "NER"}
{"text": "In an attempt to simulate the complexes in an aqueous environment , water molecules were added explicitly to complete the coordination sphere of the metal cations , and the corresponding metal - ion affinities were calculated to study the effect of microhydration .", "entity": [], "task": "NER"}
{"text": "Planar to 3D transition in the B6H ( y ) anions .", "entity": [{"entity": "B6H ( y )", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Potential energy surfaces of anionic B ( 6 ) H ( y ) clusters were sampled using the coalescence kick method .", "entity": [{"entity": "B ( 6 ) H ( y )", "entity_type": "Chemical", "pos": [37, 52]}], "task": "NER"}
{"text": "We found that the planar to three - dimensional transition occurs in this system when y = 4 .", "entity": [], "task": "NER"}
{"text": "This is an important discovery because this transition suggests a major structural change as a function of dehydrogenation for the stoichiometric B ( n ) H ( n ) ( - ) polyhedral boranes .", "entity": [{"entity": "B ( n ) H ( n ) ( - )", "entity_type": "Chemical", "pos": [146, 167]}, {"entity": "polyhedral boranes", "entity_type": "Chemical", "pos": [168, 186]}], "task": "NER"}
{"text": "We also found that the B ( 6 ) H ( 3 ) ( - ) global minimum structure has an optical isomer .", "entity": [{"entity": "B ( 6 ) H ( 3 ) ( - )", "entity_type": "Chemical", "pos": [23, 44]}], "task": "NER"}
{"text": "The chemical bonding patterns revealed by the adaptive natural density partitioning ( AdNDP ) analysis explain the geometric structure of all clusters presented here .", "entity": [], "task": "NER"}
{"text": "From our chemical bonding analysis , we concluded that the 2D - 3D transition occurs at B ( 6 ) H ( 4 ) ( - ) because the addition of one extra hydrogen atom further destroys the network of the peripheral 2c - 2e B - B sigma - bonding , making planar structures less stable , and because the distorted octahedral structure provides some occupation of all s - and p - AOs of boron , avoiding the presence of any empty atomic orbitals .", "entity": [{"entity": "B ( 6 ) H ( 4 ) ( - )", "entity_type": "Chemical", "pos": [88, 109]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [144, 152]}, {"entity": "B - B", "entity_type": "Chemical", "pos": [213, 218]}, {"entity": "boron", "entity_type": "Chemical", "pos": [374, 379]}], "task": "NER"}
{"text": "Theoretical vertical electron detachment energies ( VDEs ) were calculated for comparison with future experimental work .", "entity": [], "task": "NER"}
{"text": "The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress .", "entity": [], "task": "NER"}
{"text": "The homeodomain transcription factor Pitx3 is critical for the survival of midbrain dopaminergic ( mDA ) neurons .", "entity": [], "task": "NER"}
{"text": "Pitx3 - deficient mice exhibit severe but selective developmental loss of mDA neurons , with accompanying locomotor deficits resembling those seen in Parkinson ' s disease ( PD ) models .", "entity": [], "task": "NER"}
{"text": "Here , we identify specific mDA cell subpopulations that are consistently spared in adult Pitx3 - hypomorphic ( aphakia ) mice , demonstrating that Pitx3 is not indiscriminately required by all mDA neurons for their survival .", "entity": [], "task": "NER"}
{"text": "In aphakia mice , virtually all surviving mDA neurons in the substantia nigra ( SN ) and the majority of neurons in the adjacent ventral tegmental area ( VTA ) also express calbindin - D28k , a calcium - binding protein previously associated with resistance to injury in PD and in animal models .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [194, 201]}], "task": "NER"}
{"text": "Cell - mapping studies in wild - type mice revealed that Pitx3 is primarily expressed in the ventral SN , a region particularly susceptible to MPTP and other dopaminergic neurotoxins .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [143, 147]}], "task": "NER"}
{"text": "Furthermore , Pitx3 - expressing SN cells are preferentially lost following MPTP treatment .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "Finally , SN mDA neurons in Pitx3 hemizygous mice show increased sensitivity when exposed to MPTP .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [93, 97]}], "task": "NER"}
{"text": "Thus , SN mDA neurons are represented by at least two distinct subpopulations including MPTP - resistant Pitx3 - autonomous , calbindin - positive neurons , and calbindin - negative Pitx - 3 - dependent cells that display elevated vulnerability to toxic injury , and probably correspond to the subpopulation that degenerates in PD .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [88, 92]}], "task": "NER"}
{"text": "Impairment of Pitx3 - dependent pathways therefore increases vulnerability of mDA neurons to toxic injury .", "entity": [], "task": "NER"}
{"text": "Together , these data suggest a novel link between Pitx3 function and the selective pattern of mDA cell loss observed in PD .", "entity": [], "task": "NER"}
{"text": "Fundamental studies of electrochemically controlled surface oxidation and hydrophobicity of natural enargite .", "entity": [{"entity": "enargite", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "The surface oxidation and hydrophobicity of natural enargite ( Cu ( 3 ) AsS ( 4 ) ) and the formation of oxidation species at the mineral surface have been examined by a novel experimental approach that combines electrochemical techniques and atomic force microscopy ( AFM ) .", "entity": [{"entity": "enargite", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "Cu ( 3 ) AsS ( 4 )", "entity_type": "Chemical", "pos": [63, 81]}], "task": "NER"}
{"text": "This approach allows for in - situ , synchronized electrochemical control and examination of the oxidative surface morphology of enargite .", "entity": [{"entity": "enargite", "entity_type": "Chemical", "pos": [129, 137]}], "task": "NER"}
{"text": "Combined with ex - situ cryo X - ray photoelectron spectroscopy surface analysis , the surface speciation of enargite surface oxidation has been obtained , comparing the newly fractured natural enargite surface with those that have been electrochemically oxidized at pHs 4 and 10 .", "entity": [{"entity": "enargite", "entity_type": "Chemical", "pos": [109, 117]}, {"entity": "enargite", "entity_type": "Chemical", "pos": [194, 202]}], "task": "NER"}
{"text": "At pH 4 , surface layer formations consisting of metal - deficient sulfide and elemental sulfur were identified , associated with a limited increase in root - mean - square ( rms ) roughness ( 1 . 228 to 3 . 143 nm ) and apparent heterogeneous distribution of surface products as demonstrated by AFM imaging .", "entity": [{"entity": "sulfide", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "A mechanism of initial rapid dissolution of Cu followed by diffusion - limited surface layer deposition was identified .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [44, 46]}], "task": "NER"}
{"text": "At pH 10 , a similar mechanism was identified although the differences between the initial and diffusion - limited phases were less definitive .", "entity": [], "task": "NER"}
{"text": "Surface species were identified as copper sulfate and copper hydroxide .", "entity": [{"entity": "copper sulfate", "entity_type": "Chemical", "pos": [35, 49]}, {"entity": "copper hydroxide", "entity_type": "Chemical", "pos": [54, 70]}], "task": "NER"}
{"text": "A significant increase in surface roughness was found as rms roughness increased from 0 . 795 to 9 . 723 nm .", "entity": [], "task": "NER"}
{"text": "Dynamic ( receding ) contact angle measurements were obtained by a droplet evaporation method .", "entity": [], "task": "NER"}
{"text": "No significant difference in the contact angle on a surface oxidized at pH 10 and the freshly polished surface was found .", "entity": [], "task": "NER"}
{"text": "A significant difference was found between the polished surface and that oxidized at pH 4 , with an increase in contact angle of about 13 degrees ( 46 degrees to 59 degrees ) after oxidation .", "entity": [], "task": "NER"}
{"text": "Competing effects of hydrophilic ( copper oxides and hydroxides ) and hydrophobic ( elemental sulfur ) species on the mineral surface under oxidizing conditions at pH 4 and the change in surface roughness at pH 10 may contribute to the observed effects of electrochemically controlled oxidation on enargite hydrophobicity .", "entity": [{"entity": "copper oxides and hydroxides", "entity_type": "Chemical", "pos": [35, 63]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [94, 100]}, {"entity": "enargite", "entity_type": "Chemical", "pos": [298, 306]}], "task": "NER"}
{"text": "Crystal and magnetic structures and physical properties of a new pyroxene NaMnGe2O6 synthesized under high pressure .", "entity": [{"entity": "pyroxene", "entity_type": "Chemical", "pos": [65, 73]}, {"entity": "NaMnGe2O6", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "A new pyroxene compound , NaMnGe ( 2 ) O ( 6 ) , has been synthesized at 3 GPa and 800 degrees C and fully characterized by X - ray single - crystal diffraction , neutron powder diffraction , and measurements of magnetization and specific heat .", "entity": [{"entity": "pyroxene", "entity_type": "Chemical", "pos": [6, 14]}, {"entity": "NaMnGe ( 2 ) O ( 6 )", "entity_type": "Chemical", "pos": [26, 46]}], "task": "NER"}
{"text": "NaMnGe ( 2 ) O ( 6 ) crystallizes into a monoclinic C2 / c structure with unit - cell parameters a = 9 . 859 ( 2 ) A , b = 8 . 7507 ( 18 ) A , c = 5 . 5724 ( 11 ) A , and beta = 105 . 64 ( 3 ) degrees at 153 K .", "entity": [{"entity": "NaMnGe ( 2 ) O ( 6 )", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "A cooperative Jahn - Teller distortion is formed by an ordering of the longest Mn - O bonds between two neighboring octahedra along the chain direction .", "entity": [{"entity": "Mn - O", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "This feature distinguishes NaMnGe ( 2 ) O ( 6 ) from other pyroxene compounds without Jahn - Teller active cations and suggests that the Jahn - Teller distortion competes with the intrinsic local distortion in the pyroxene structure .", "entity": [{"entity": "NaMnGe ( 2 ) O ( 6 )", "entity_type": "Chemical", "pos": [27, 47]}, {"entity": "pyroxene", "entity_type": "Chemical", "pos": [59, 67]}, {"entity": "pyroxene", "entity_type": "Chemical", "pos": [214, 222]}], "task": "NER"}
{"text": "No orbital order - disorder transition has been found up to 750 K .", "entity": [], "task": "NER"}
{"text": "Like other alkali - metal pyroxenes with S > ( 1 ) / ( 2 ) , NaMnGe ( 2 ) O ( 6 ) ( S = 2 ) was found to undergo a long - range antiferromagnetic ( AF ) ordering at T ( N ) = 7 K due to intrachain and interchain exchange interactions .", "entity": [{"entity": "pyroxenes", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "NaMnGe ( 2 ) O ( 6 )", "entity_type": "Chemical", "pos": [61, 81]}], "task": "NER"}
{"text": "Due to the peculiar structural features and the corresponding magnetic coupling , the weak AF spin ordering gives way to a ferromagnetic - like state at a sufficiently high magnetic field .", "entity": [], "task": "NER"}
{"text": "Specific - heat measurements demonstrated that a large portion of the magnetic entropy , > 60 % , has been removed above T ( N ) as a result of strong spin correlations within the quasi - one - dimensional Mn ( 3 + ) - spin chains .", "entity": [{"entity": "Mn ( 3 + )", "entity_type": "Chemical", "pos": [206, 216]}], "task": "NER"}
{"text": "The Reitveld refinement of neutron powder diffraction data gives a commensurate magnetic structure defined by k = [ 0 0 0 . 5 ] with Mn moments aligned mainly along the c - axis with a small component along both a - and b - axes .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [133, 135]}], "task": "NER"}
{"text": "Sequence - specific transcription factor NF - Y displays histone - like DNA binding and H2B - like ubiquitination .", "entity": [], "task": "NER"}
{"text": "The sequence - specific transcription factor NF - Y binds the CCAAT box , one of the sequence elements most frequently found in eukaryotic promoters .", "entity": [], "task": "NER"}
{"text": "NF - Y is composed of the NF - YA and NF - YB / NF - YC subunits , the latter two hosting histone - fold domains ( HFDs ) .", "entity": [], "task": "NER"}
{"text": "The crystal structure of NF - Y bound to a 25 bp CCAAT oligonucleotide shows that the HFD dimer binds to the DNA sugar - phosphate backbone , mimicking the nucleosome H2A / H2B - DNA assembly .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [113, 118]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [121, 130]}], "task": "NER"}
{"text": "NF - YA both binds to NF - YB / NF - YC and inserts an alpha helix deeply into the DNA minor groove , providing sequence - specific contacts to the CCAAT box .", "entity": [], "task": "NER"}
{"text": "Structural considerations and mutational data indicate that NF - YB ubiquitination at Lys138 precedes and is equivalent to H2B Lys120 monoubiquitination , important in transcriptional activation .", "entity": [{"entity": "Lys138", "entity_type": "Chemical", "pos": [86, 92]}, {"entity": "Lys120", "entity_type": "Chemical", "pos": [127, 133]}], "task": "NER"}
{"text": "Thus , NF - Y is a sequence - specific transcription factor with nucleosome - like properties of nonspecific DNA binding and helps establish permissive chromatin modifications at CCAAT promoters .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that other HFD - containing proteins may function in similar ways .", "entity": [], "task": "NER"}
{"text": "Physical exercise and its effects on coronary artery disease .", "entity": [], "task": "NER"}
{"text": "The beneficial effects of physical exercise on stable coronary artery disease ( CAD ) have been shown by an increasing number of studies .", "entity": [], "task": "NER"}
{"text": "Exercise training leads to an improved bioavailability of the endothelial nitric oxide and partially attenuates endothelial dysfunction .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [74, 86]}], "task": "NER"}
{"text": "Further effects are an economization of ventricular function and a reduction of cardiovascular risk factors .", "entity": [], "task": "NER"}
{"text": "In clinical studies exercise training was associated with a decreased total and cardiovascular mortality and a reduced angina pectoris threshold .", "entity": [], "task": "NER"}
{"text": "Thus exercise training has developed to an evidence - based therapeutic option of stable CAD with a Class Ia recommendation in the guidelines .", "entity": [], "task": "NER"}
{"text": "Composition and anti - oxidant , anti - cancer and anti - inflammatory activities of Artemisia herba - alba , Ruta chalpensis L . and Peganum harmala L .", "entity": [], "task": "NER"}
{"text": "In this study , biological activities of methanolic extracts from Artemisia herba - alba , Ruta chalpensis L . and Peganum harmala L . plants , collected in Centre of Tunisia , were investigated .", "entity": [], "task": "NER"}
{"text": "Results showed an important phenolic composition of Artemisia herba - alba ( 123 . 95 +/- 4 . 3g GAE / kg of dry mass ) .", "entity": [], "task": "NER"}
{"text": "The extract of this plant showed , using different antioxidant assays ( DPPH , ABTS and AAPH / linoleic acid methods ) and an IFN - gamma / LPS induced RAW 264 . 7 murine macrophages ' assay , the highest antioxidant ( IC50 ( DPPH assay ) 20 . 64 +/- 0 . 84mg / L ) and anti - inflammatory ( 72 % inhibition at 150mg / L ) activities , respectively .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [72, 76]}, {"entity": "ABTS", "entity_type": "Chemical", "pos": [79, 83]}, {"entity": "AAPH", "entity_type": "Chemical", "pos": [88, 92]}, {"entity": "linoleic acid", "entity_type": "Chemical", "pos": [95, 108]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [226, 230]}], "task": "NER"}
{"text": "Excepting Peganum harmala L . extract , the two other extracts showed a high anticancer activity against several cell lines ( human bladder carcinoma RT112 , human laryngeal carcinoma Hep2 and human myelogenous leukemia K562 ) , for A . herba - laba IC50 = 81 . 59 +/- 4 . 4 , 59 . 05 +/- 3 . 66 and 90 . 96mg / L respectively , but not on normal peripheral blood mononuclear cells .", "entity": [], "task": "NER"}
{"text": "All these biological activities are well correlated with the phenolic contents of these extracts .", "entity": [], "task": "NER"}
{"text": "These findings demonstrate the remarkable potential of these plants as valuable source of antioxidants with exhibit original and interesting anti - inflammatory and anticancer capacities .", "entity": [], "task": "NER"}
{"text": "Areca nut procyanidins ameliorate streptozocin - induced hyperglycemia by regulating gluconeogenesis .", "entity": [{"entity": "procyanidins", "entity_type": "Chemical", "pos": [10, 22]}, {"entity": "streptozocin", "entity_type": "Chemical", "pos": [34, 46]}], "task": "NER"}
{"text": "Hepatic gluconeogenesis is a major contributor to blood glucose in diabetes mellitus .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "Our previous study indicated that areca nut extract enriched with catechin - based procyanidins from oligomers to polymers gave rise to anti - inflammatory effects in vitro and in vivo .", "entity": [{"entity": "catechin", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "procyanidins", "entity_type": "Chemical", "pos": [83, 95]}], "task": "NER"}
{"text": "Here we have surveyed the molecular features of areca nut procyanidins ( ANPs ) using quadrupole time - of - flight liquid chromatography / mass spectrometry ( Q - TOF LC / MS ) and the resulting mass spectrum accurately described ANP from monomer to hexadecamer .", "entity": [{"entity": "procyanidins", "entity_type": "Chemical", "pos": [58, 70]}], "task": "NER"}
{"text": "Furthermore , the potential of ANP in terms of blood glucose homeostasis was explored using cyclic adenosine monophosphate ( cAMP ) / dexamethasone stimulated primary mouse hepatocytes and multiple low dose streptozocin ( MLD - STZ ) treated mice .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [53, 60]}, {"entity": "cyclic adenosine monophosphate", "entity_type": "Chemical", "pos": [92, 122]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [125, 129]}, {"entity": "dexamethasone", "entity_type": "Chemical", "pos": [134, 147]}, {"entity": "streptozocin", "entity_type": "Chemical", "pos": [207, 219]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [228, 231]}], "task": "NER"}
{"text": "With the primary hepatocytes , ANP dose - dependently inhibited gluconeogenesis and reduced the mRNA expression of two gluconeogenic key enzymes , phosphoenol - pyruvate carboxykinase ( PEPCK ) and glucose - 6 - phosphatase ( G6Pase ) .", "entity": [{"entity": "phosphoenol - pyruvate", "entity_type": "Chemical", "pos": [147, 169]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [198, 205]}], "task": "NER"}
{"text": "Intragastrically feeding of 10mg / kg ANP for 4weeks reduced the levels of fasting blood glucose , PEPCK and G6Pase in MLD - STZ mice .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [125, 128]}], "task": "NER"}
{"text": "In additional , the level of 5 ' - AMP - activated protein kinase ( AMPK ) expression showed a trend towards being restored in the ANP treated MLD - STZ - mice .", "entity": [{"entity": "5 ' - AMP", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [149, 152]}], "task": "NER"}
{"text": "This study indicated that ANP has the potential to improve hyperglycemia by regulating gluconeogenic related kinases in MLD - STZ - mice .", "entity": [{"entity": "STZ", "entity_type": "Chemical", "pos": [126, 129]}], "task": "NER"}
{"text": "Suppression of Src / ERK and GSK - 3 / beta - catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Pinosylvin , a naturally occurring trans - stilbenoid mainly found in Pinus species , has exhibited a potential cancer chemopreventive activity .", "entity": [{"entity": "Pinosylvin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "trans - stilbenoid", "entity_type": "Chemical", "pos": [35, 53]}], "task": "NER"}
{"text": "However , the growth inhibitory activity against cancer cells and the underlying molecular mechanisms remain to be elucidated .", "entity": [], "task": "NER"}
{"text": "Therefore , the anti - proliferative activity of pinosylvin was investigated in human colorectal HCT 116 cancer cells .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [49, 59]}], "task": "NER"}
{"text": "Pinosylvin inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1 , cyclin E , cyclin A , cyclin dependent kinase 2 ( CDK2 ) , CDK4 , c - Myc , and retinoblastoma protein ( pRb ) , and the upregulation of p21 ( WAF1 / CIP1 ) and p53 .", "entity": [{"entity": "Pinosylvin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Pinosylvin was also found to attenuate the activation of proteins involved in focal adhesion kinase ( FAK ) / c - Src / extracellular signal - regulated kinase ( ERK ) signaling , and phosphoinositide 3 - kinase ( PI3K ) / Akt / glycogen synthase kinase 3 beta ( GSK - 3 beta ) signaling pathway .", "entity": [{"entity": "Pinosylvin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [184, 200]}], "task": "NER"}
{"text": "Subsequently , pinosylvin suppressed the nuclear translocation of beta - catenin , one of downstream molecules of PI3K / Akt / GSK - 3 beta signaling , and these events led to the sequential downregulation of beta - catenin - mediated transcription of target genes including BMP4 , ID2 , survivin , cyclin D1 , MMP7 , and c - Myc .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [15, 25]}], "task": "NER"}
{"text": "These findings demonstrate that the anti - proliferative activity of pinosylvin might be associated with the cell cycle arrest and downregulation of cell proliferation regulating signaling pathways in human colorectal cancer cells .", "entity": [{"entity": "pinosylvin", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "Comparative pharmacokinetic profiles of picrosides I and II from kutkin , Picrorhiza kurroa extract and its formulation in rats .", "entity": [{"entity": "picrosides I and II", "entity_type": "Chemical", "pos": [40, 59]}], "task": "NER"}
{"text": "Picrosides I and II are the active chemical constituents , present in the roots and rhizomes of Picrorhiza kurroa Royle ( family : Scrophulariaceae ) .", "entity": [{"entity": "Picrosides I and II", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "The plant is ethnomedically claimed for the treatment of liver and upper respiratory tract infection , fever , dyspepsia and scorpion sting .", "entity": [], "task": "NER"}
{"text": "This study attempts to determine the in vivo pharmacokinetic profile of picrosides I and II in rats after oral administration of three different preparations namely , kutkin ( a mixture of picrosides I and II ) , P . kurroa extract and Picrolax (R) capsule ( marketed formulation ) .", "entity": [{"entity": "picrosides I and II", "entity_type": "Chemical", "pos": [72, 91]}, {"entity": "kutkin", "entity_type": "Chemical", "pos": [167, 173]}, {"entity": "picrosides I and II", "entity_type": "Chemical", "pos": [189, 208]}], "task": "NER"}
{"text": "A simple , precise , specific and sensitive method was developed for simultaneous quantification of picrosides I and II in rat plasma and was applied for the pharmacokinetic study .", "entity": [{"entity": "picrosides I and II", "entity_type": "Chemical", "pos": [100, 119]}], "task": "NER"}
{"text": "Pharmacokinetic parameters were calculated from the observed plasma concentration of picrosides I and II .", "entity": [{"entity": "picrosides I and II", "entity_type": "Chemical", "pos": [85, 104]}], "task": "NER"}
{"text": "The results showed a significant difference ( p <= 0 . 05 ) in oral bioavailability of picrosides I and II from different preparations .", "entity": [{"entity": "picrosides I and II", "entity_type": "Chemical", "pos": [87, 106]}], "task": "NER"}
{"text": "Both the compounds were found to be more bioavailable from P . kurroa extract followed by Picrolax (R) capsule and kutkin .", "entity": [{"entity": "kutkin", "entity_type": "Chemical", "pos": [115, 121]}], "task": "NER"}
{"text": "Moreover , we also developed a novel method for isolation of kutkin from roots of P . kurroa with a high yield of 2 . 4 % w / w .", "entity": [{"entity": "kutkin", "entity_type": "Chemical", "pos": [61, 67]}], "task": "NER"}
{"text": "The information gained from this study provides a meaningful basis for clinical application and mechanistic study of such phytochemicals .", "entity": [], "task": "NER"}
{"text": "Correlation between the antibacterial activity and the composition of extracts derived from various Spanish Cistus species .", "entity": [], "task": "NER"}
{"text": "Cistaceae is a large family of shrubs commonly distributed in the Mediterranean ecosystem .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to explore the potential antimicrobial properties against Escherichia coli and / or Staphylococcus aureus of different extracts obtained from four Cistaceae species that are especially abundant in Spanish semi - arid regions .", "entity": [], "task": "NER"}
{"text": "MIC50 values of the extracts of C . salviifolius exhibited potent bacteriostatic effects against S . aureus compared with the other Cistus species tested .", "entity": [], "task": "NER"}
{"text": "Spray - drying had less impact on the antimicrobial activities and polyphenolic contents than did evaporation followed by freeze - drying .", "entity": [{"entity": "polyphenolic", "entity_type": "Chemical", "pos": [67, 79]}], "task": "NER"}
{"text": "When C . salviifolius extract was concentrated and the polar fraction was removed , its bacteriostatic and bactericidal activities against both strains were significantly enhanced .", "entity": [], "task": "NER"}
{"text": "Seasonal influences on the composition have also been found .", "entity": [], "task": "NER"}
{"text": "Up to 48 compounds were found in the aqueous extract of C . salviifolius using RRLC - ESI - TOF - MS .", "entity": [], "task": "NER"}
{"text": "The analysis of the composition of the extracts revealed that the inhibitory activity against E . coli may be related to the presence of galloylated flavanols and specific flavonols , whereas the inhibitory capacity against S . aureus may be related primarily to polar compounds and to other flavonols .", "entity": [{"entity": "galloylated flavanols", "entity_type": "Chemical", "pos": [137, 158]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [172, 181]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [292, 301]}], "task": "NER"}
{"text": "Potential synergistic effects among polyphenols may deserve further studies .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [36, 47]}], "task": "NER"}
{"text": "These extracts may serve as an alternative source of antimicrobial ingredients focused on medical devices or cosmetics .", "entity": [], "task": "NER"}
{"text": "I kappa B kinase epsilon ( IKK epsilon ) : a therapeutic target in inflammation and cancer .", "entity": [], "task": "NER"}
{"text": "The innate immune system forms our first line of defense against invading pathogens and relies for a major part on the activation of two transcription factors , NF - kappa B and IRF3 .", "entity": [], "task": "NER"}
{"text": "Signaling pathways that activate these transcription factors are intertwined at the level of the canonical I kappa B kinases ( IKK alpha , IKK beta ) and non - canonical IKK - related kinases ( IKK epsilon , TBK1 ) .", "entity": [], "task": "NER"}
{"text": "Recently , significant progress has been made in understanding the function and mechanism of action of IKK epsilon in immune signaling .", "entity": [], "task": "NER"}
{"text": "In addition , IKK epsilon impacts on cell proliferation and transformation , and is thereby also classified as an oncogene .", "entity": [], "task": "NER"}
{"text": "Studies with IKK epsilon knockout mice have illustrated a key role for IKK epsilon in inflammatory and metabolic diseases .", "entity": [], "task": "NER"}
{"text": "In this review we will highlight the mechanisms by which IKK epsilon impacts on signaling pathways involved in disease development and discuss its potential as a novel therapeutic target .", "entity": [], "task": "NER"}
{"text": "Genotoxic and inflammatory effects of organic extracts from traffic - related particulate matter in human lung epithelial A549 cells : the role of quinones .", "entity": [{"entity": "quinones", "entity_type": "Chemical", "pos": [147, 155]}], "task": "NER"}
{"text": "Traffic - related particulate matter ( PM ) is associated with adverse health effects .", "entity": [], "task": "NER"}
{"text": "Quinones present in the traffic - related PM are hypothesized to contribute to these harmful effects through reactive oxygen species ( ROS ) generation .", "entity": [{"entity": "Quinones", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [118, 124]}], "task": "NER"}
{"text": "However , the impacts of the traffic - related PM and quinones on inflammatory processes and genotoxic damages are less well known .", "entity": [{"entity": "quinones", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "In present study we aimed to examine the genotoxic and inflammatory impacts of organic extracts from traffic - related PM ( oTRP ) in human lung epithelial A549 cells , and reveal the contributions from quinones .", "entity": [{"entity": "quinones", "entity_type": "Chemical", "pos": [203, 211]}], "task": "NER"}
{"text": "Significant cytotoxicity and DNA damage were caused by oTRP .", "entity": [], "task": "NER"}
{"text": "The pro - inflammatory genes , interleukin - 6 ( Il - 6 ) , interleukin - 8 ( Il - 8 ) and tumor necrosis factor ( Tnf ) , and two aromatic hydrocarbon receptor - regulated genes , Cyp1a1 and 1b1 , were significantly up - regulated by oTRP .", "entity": [{"entity": "aromatic hydrocarbon", "entity_type": "Chemical", "pos": [131, 151]}], "task": "NER"}
{"text": "A concomitant increase in ROS was observed , suggesting that oTRP may mediate genotoxic and inflammatory effects through oxidative stress pathway .", "entity": [], "task": "NER"}
{"text": "Second , the effects from two typical airborne quinones , 9 , 10 - anthraquinone ( AQ ) and 1 , 4 - naphthroquinone ( NQ ) were compared .", "entity": [{"entity": "quinones", "entity_type": "Chemical", "pos": [47, 55]}, {"entity": "9 , 10 - anthraquinone", "entity_type": "Chemical", "pos": [58, 80]}, {"entity": "1 , 4 - naphthroquinone", "entity_type": "Chemical", "pos": [92, 115]}], "task": "NER"}
{"text": "NQ , but not AQ , induced significant DNA damage in A549 cells .", "entity": [], "task": "NER"}
{"text": "NQ up - regulated Il - 8 , Tnf , and Mcp - 1 genes , while AQ induced the expression of Rantes gene .", "entity": [], "task": "NER"}
{"text": "These results suggest that the NQ and AQ may participate in the pro - inflammatory responses through releasing different types of cytokines / chemokines .", "entity": [], "task": "NER"}
{"text": "Activation of Rac1 GTPase by nanoparticulate structures in human macrophages .", "entity": [], "task": "NER"}
{"text": "Inflammatory activation of alveolar macrophages by ambient particles can be facilitated via Toll - like receptors ( TLR ) .", "entity": [], "task": "NER"}
{"text": "The action of TLR agonists and antagonists has been reported to depend on the formation of nanoparticulate structures .", "entity": [], "task": "NER"}
{"text": "Aim of the present study was to identify the signaling pathways induced by nanoparticulate structures in human macrophages , which might be critical for inflammatory cell activation .", "entity": [], "task": "NER"}
{"text": "METHODS : Studies were performed in primary human alveolar macrophages or in differentiated THP - 1 macrophages .", "entity": [], "task": "NER"}
{"text": "Silica nanoparticles were prepared by St o ber synthesis and characterized by dynamic light scattering and scanning electron microscopy .", "entity": [{"entity": "Silica", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Mycobacterial DNA was isolated from Mycobacterium bovis BCG , and nanoparticle formation was assessed by atomic force microscopy and dynamic light scattering .", "entity": [], "task": "NER"}
{"text": "Actin polymerization was measured by phalloidin - TRITC staining , and cell activation was determined by reverse transcription quantitative PCR analysis , L929 cytotoxicity assay ( cytokine induction ) , and pull - down assays ( Rho GTPases ) .", "entity": [{"entity": "phalloidin", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "TRITC", "entity_type": "Chemical", "pos": [50, 55]}], "task": "NER"}
{"text": "RESULTS : In contrast to immune stimulatory sequence ISS 1018 , BCG DNA spontaneously formed nanoparticulate structures and induced actin polymerization as did synthetic silica nanoparticles .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [170, 176]}], "task": "NER"}
{"text": "Co - incubation with silica nanoparticles amplified the responsiveness of macrophages toward the TLR9 ligand ISS 1018 .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [21, 27]}], "task": "NER"}
{"text": "The activation of Rac1 was induced by silica nanoparticles as well as BCG DNA and is suggested as the critical signaling event inducing both cytoskeleton changes as well as inflammatory cell activation .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [38, 44]}], "task": "NER"}
{"text": "CONCLUSION : Nanoparticles can induce signaling pathways , which amplify an inflammatory response in macrophages .", "entity": [], "task": "NER"}
{"text": "Administration of the optimized beta - Lapachone - poloxamer - cyclodextrin ternary system induces apoptosis , DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model .", "entity": [{"entity": "beta - Lapachone", "entity_type": "Chemical", "pos": [32, 48]}, {"entity": "poloxamer", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "beta - Lapachone ( beta - Lap ) is a 1 , 2 - orthonaphthoquinone that selectively induces cell death in human cancer cells through NAD ( P ) H : quinone oxidoreductase - 1 ( NQO1 ) .", "entity": [{"entity": "beta - Lapachone", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "beta - Lap", "entity_type": "Chemical", "pos": [19, 29]}, {"entity": "1 , 2 - orthonaphthoquinone", "entity_type": "Chemical", "pos": [37, 64]}, {"entity": "NAD ( P ) H", "entity_type": "Chemical", "pos": [131, 142]}, {"entity": "quinone", "entity_type": "Chemical", "pos": [145, 152]}], "task": "NER"}
{"text": "NQO1 is overexpressed in a variety of tumors , as compared to normal adjacent tissue .", "entity": [], "task": "NER"}
{"text": "However , the low solubility and non - specific distribution of beta - Lap limit its suitability for clinical assays .", "entity": [{"entity": "beta - Lap", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "We formulated beta - Lap in an optimal random methylated - beta - cyclodextrin / poloxamer 407 mixture ( i . e . , beta - Lap ternary system ) and , using human breast adenocarcinoma MCF - 7 cells and immunodeficient mice , performed in vitro and in vivo evaluation of its anti - tumor effects on proliferation , cell cycle , apoptosis , DNA damage , and tumor growth .", "entity": [{"entity": "beta - Lap", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "methylated - beta - cyclodextrin", "entity_type": "Chemical", "pos": [46, 78]}, {"entity": "poloxamer 407", "entity_type": "Chemical", "pos": [81, 94]}, {"entity": "beta - Lap", "entity_type": "Chemical", "pos": [115, 125]}], "task": "NER"}
{"text": "This ternary system is fluid at room temperature , gels over 29 degrees C , and provides a significant amount of drug , thus facilitating intratumoral delivery , in situ gelation , and the formation of a depot for time - release .", "entity": [], "task": "NER"}
{"text": "Administration of beta - Lap ternary system to MCF - 7 cells induces an increase in apoptosis and DNA damage , while producing no changes in cell cycle .", "entity": [{"entity": "beta - Lap", "entity_type": "Chemical", "pos": [18, 28]}], "task": "NER"}
{"text": "Moreover , in a mouse xenograft tumor model , intratumoral injection of the system significantly reduces tumor volume , while increasing apoptosis and DNA damage without visible toxicity to liver or kidney .", "entity": [], "task": "NER"}
{"text": "These anti - tumoral effects and lack of visible toxicity make this system a promising new therapeutic agent for breast cancer treatment .", "entity": [], "task": "NER"}
{"text": "Hydrophobicity of rare - earth oxide ceramics .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [31, 36]}], "task": "NER"}
{"text": "Hydrophobic materials that are robust to harsh environments are needed in a broad range of applications .", "entity": [], "task": "NER"}
{"text": "Although durable materials such as metals and ceramics , which are generally hydrophilic , can be rendered hydrophobic by polymeric modifiers , these deteriorate in harsh environments .", "entity": [], "task": "NER"}
{"text": "Here we show that a class of ceramics comprising the entire lanthanide oxide series , ranging from ceria to lutecia , is intrinsically hydrophobic .", "entity": [{"entity": "lanthanide oxide", "entity_type": "Chemical", "pos": [60, 76]}], "task": "NER"}
{"text": "We attribute their hydrophobicity to their unique electronic structure , which inhibits hydrogen bonding with interfacial water molecules .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "We also show with surface - energy measurements that polar interactions are minimized at these surfaces and with Fourier transform infrared / grazing - angle attenuated total reflection that interfacial water molecules are oriented in the hydrophobic hydration structure .", "entity": [], "task": "NER"}
{"text": "Moreover , we demonstrate that these ceramic materials promote dropwise condensation , repel impinging water droplets , and sustain hydrophobicity even after exposure to harsh environments .", "entity": [], "task": "NER"}
{"text": "Rare - earth oxide ceramics should find widespread applicability as robust hydrophobic surfaces .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [13, 18]}], "task": "NER"}
{"text": "Microcalcifications in breast cancer : Lessons from physiological mineralization .", "entity": [], "task": "NER"}
{"text": "Mammographic mammary microcalcifications are routinely used for the early detection of breast cancer , however the mechanisms by which they form remain unclear .", "entity": [], "task": "NER"}
{"text": "Two species of mammary microcalcifications have been identified ; calcium oxalate and hydroxyapatite .", "entity": [{"entity": "calcium oxalate", "entity_type": "Chemical", "pos": [66, 81]}, {"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [86, 100]}], "task": "NER"}
{"text": "Calcium oxalate is mostly associated with benign lesions of the breast , whereas hydroxyapatite is associated with both benign and malignant tumors .", "entity": [{"entity": "Calcium oxalate", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [81, 95]}], "task": "NER"}
{"text": "The way in which hydroxyapatite forms within mammary tissue remains largely unexplored , however lessons can be learned from the process of physiological mineralization .", "entity": [{"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [17, 31]}], "task": "NER"}
{"text": "Normal physiological mineralization by osteoblasts results in hydroxyapatite deposition in bone .", "entity": [{"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [62, 76]}], "task": "NER"}
{"text": "This review brings together existing knowledge from the field of physiological mineralization and juxtaposes it with our current understanding of the genesis of mammary microcalcifications .", "entity": [], "task": "NER"}
{"text": "As an increasing number of breast cancers are being detected in their non - palpable stage through mammographic microcalcifications , it is important that future studies investigate the underlying mechanisms of their formation in order to fully understand the significance of this unique early marker of breast cancer .", "entity": [], "task": "NER"}
{"text": "Self - assembly of double helical nanostructures inside carbon nanotubes .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [56, 62]}], "task": "NER"}
{"text": "We use molecular dynamics ( MD ) simulations to show that a DNA - like double helix of two poly ( acetylene ) ( PA ) chains can form inside single - walled carbon nanotubes ( SWNTs ) .", "entity": [{"entity": "poly ( acetylene )", "entity_type": "Chemical", "pos": [91, 109]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [156, 162]}], "task": "NER"}
{"text": "The computational results indicate that SWNTs can activate and guide the self - assembly of polymer chains , allowing them to adopt a helical configuration in a SWNT through the combined action of the van der Waals potential well and the pi - pi stacking interaction between the polymer and the inner surface of SWNTs .", "entity": [], "task": "NER"}
{"text": "Meanwhile both the SWNT size and polymer chain stiffness determine the outcome of the nanostructure .", "entity": [], "task": "NER"}
{"text": "Furthermore , we also found that water clusters encourage the self - assembly of PA helical structures in the tube .", "entity": [], "task": "NER"}
{"text": "This molecular model may lead to a better understanding of the formation of a double helix biological molecule inside SWNTs .", "entity": [], "task": "NER"}
{"text": "Alternatively , it could form the basis of a novel nanoscale material by utilizing the ' empty ' spaces of SWNTs .", "entity": [], "task": "NER"}
{"text": "Human skin neural crest progenitor cells are susceptible to BRAF ( V600E ) - induced transformation .", "entity": [], "task": "NER"}
{"text": "Adult stem cells are multipotent and persist in small numbers in adult tissues throughout the lifespan of an organism .", "entity": [], "task": "NER"}
{"text": "Unlike differentiated cells , adult stem cells are intrinsically resistant to senescence .", "entity": [], "task": "NER"}
{"text": "It is unclear how adult stem cells in solid organs respond to oncogenic stimulation and whether these cells have a role in tumor initiation .", "entity": [], "task": "NER"}
{"text": "We report here that expression of BRAF ( V600E ) in human neural crest progenitor cells ( hNCPCs ) did not induce growth arrest as seen in human melanocytes , but instead , increased their cell proliferation capacity .", "entity": [], "task": "NER"}
{"text": "These cells ( hNCPCs ( V600E ) ) acquired anchorage - independent growth ability and were weakly tumorigenic in vivo .", "entity": [], "task": "NER"}
{"text": "Unlike in human melanocytes , BRAF ( V600E ) expression in hNCPCs did not induce p16 ( INK4a ) expression .", "entity": [], "task": "NER"}
{"text": "BRAF ( V600E ) induced elevated expression of CDK2 , CDK4 , MITF and EST1 / 2 protein in hNCPCs , and also induced melanocytic differentiation of these cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , overexpression of MITF in hNCPCs ( V600E ) dramatically increased their tumorigenicity and resulted in fully transformed tumor cells .", "entity": [], "task": "NER"}
{"text": "These findings indicate that hNCPCs are susceptible to BRAF ( V600E ) - induced transformation , and MITF potentiates the oncogenic effect of BRAF ( V600E ) in these progenitor cells .", "entity": [], "task": "NER"}
{"text": "These results suggest that the hNCPCs are potential targets for BRAF ( V600E ) - induced melanocytic tumor formation . Oncogene advance online publication , 21 January 2013 ; doi : 10 . 1038 / onc . 2012 . 642 .", "entity": [], "task": "NER"}
{"text": "Almorexant effects on CYP3A4 activity studied by its simultaneous and time - separated administration with simvastatin and atorvastatin .", "entity": [{"entity": "Almorexant", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "simvastatin", "entity_type": "Chemical", "pos": [107, 118]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [123, 135]}], "task": "NER"}
{"text": "PURPOSE : To characterise further the previously observed cytochrome P450 3A4 ( CYP3A4 ) interaction of the dual orexin receptor antagonist almorexant .", "entity": [{"entity": "almorexant", "entity_type": "Chemical", "pos": [140, 150]}], "task": "NER"}
{"text": "METHODS : Pharmacokinetic interactions were investigated ( n = 14 healthy male subjects in two treatment groups ) between almorexant at steady - state when administered either concomitantly or 2 h after administration of single doses of simvastatin ( 40 mg ) or atorvastatin ( 40 mg ) .", "entity": [{"entity": "almorexant", "entity_type": "Chemical", "pos": [122, 132]}, {"entity": "simvastatin", "entity_type": "Chemical", "pos": [237, 248]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [262, 274]}], "task": "NER"}
{"text": "RESULTS : Almorexant dose - dependently increased simvastatin exposure ( AUC ( 0 - infinity ) ) when administered concomitantly [ geometric mean ratios ( 90 % CI ) : 2 . 5 ( 2 . 1 , 2 . 9 ) ( 100 mg ) , 3 . 9 ( 3 . 3 , 4 . 6 ) ( 200 mg ) ] , but not C ( max ) [ 3 . 7 ( 3 . 0 , 4 . 5 ) for both doses ] .", "entity": [{"entity": "Almorexant", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "simvastatin", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "Time - separated administration resulted in relevant reductions of the interaction [ AUC ( 0 - infinity ) : 1 . 4 ( 1 . 2 , 1 . 7 ) ( 100 mg ) , 1 . 7 ( 1 . 5 , 2 . 0 ) ( 200 mg ) ; C ( max ) : 1 . 5 ( 1 . 3 , 1 . 9 ) ( 100 mg ) , 1 . 9 ( 1 . 6 , 2 . 4 ) ( 200 mg ) ] .", "entity": [], "task": "NER"}
{"text": "Similar results were obtained for hydroxyacid simvastatin .", "entity": [{"entity": "hydroxyacid simvastatin", "entity_type": "Chemical", "pos": [34, 57]}], "task": "NER"}
{"text": "Independent of almorexant dose and relative time of administration , AUC ( 0 - infinity ) and C ( max ) of atorvastatin increased ( ratios ranged from 1 . 1 to 1 . 5 ) .", "entity": [{"entity": "almorexant", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [107, 119]}], "task": "NER"}
{"text": "AUC ( 0 - infinity ) and C ( max ) of o - hydroxy atorvastatin decreased dose - independently [ AUC ( 0 - infinity ) : 0 . 8 ( 0 . 8 , 0 . 9 ) ( 100 mg ) , 0 . 6 ( 0 . 5 , 0 . 6 ) ( 200 mg ) ; C ( max ) : 0 . 3 ( 0 . 3 , 0 . 4 ) ( 100 mg ) , 0 . 2 ( 0 . 2 , 0 . 3 ) ( 200 mg ) ] when atorvastatin was concomitantly administered .", "entity": [{"entity": "o - hydroxy atorvastatin", "entity_type": "Chemical", "pos": [38, 62]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [284, 296]}], "task": "NER"}
{"text": "C ( max ) of o - hydroxy atorvastatin slightly decreased ( 0 . 8 for both doses ) following time - separated administration ; AUC ( 0 - infinity ) was unchanged .", "entity": [{"entity": "o - hydroxy atorvastatin", "entity_type": "Chemical", "pos": [13, 37]}], "task": "NER"}
{"text": "CONCLUSIONS : Whereas almorexant increased simvastatin exposure dose - and relative time of administration - dependently , atorvastatin exposure increased to a smaller extent and irrespective of dose and time .", "entity": [{"entity": "almorexant", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "simvastatin", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [123, 135]}], "task": "NER"}
{"text": "This suggests that the observed interaction of almorexant with simvastatin is mainly caused by intestinal CYP3A4 inhibition , whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition .", "entity": [{"entity": "almorexant", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "simvastatin", "entity_type": "Chemical", "pos": [63, 74]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [155, 167]}], "task": "NER"}
{"text": "Designing high - performance electrochemical energy - storage nanoarchitectures to balance rate and capacity .", "entity": [], "task": "NER"}
{"text": "The impressive specific capacitance and high - rate performance reported for many nanometric charge - storing films on planar substrates cannot impact a technology space beyond microdevices unless such performance translates into a macroscale form factor .", "entity": [], "task": "NER"}
{"text": "In this report , we explore how the nanoscale - to - macroscale properties of the electrode architecture ( pore size / distribution , void volume , thickness ) define energy and power performance when scaled to technologically relevant dimensions .", "entity": [], "task": "NER"}
{"text": "Our test bed is a device - ready electrode architecture in which scalable , manufacturable carbon nanofoam papers with tunable pore sizes ( 5 - 200 nm ) and thickness ( 100 - 300 mu m ) are painted with ~ 10 nm coatings of manganese oxide ( MnOx ) .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [91, 97]}, {"entity": "manganese oxide", "entity_type": "Chemical", "pos": [223, 238]}, {"entity": "MnOx", "entity_type": "Chemical", "pos": [241, 245]}], "task": "NER"}
{"text": "The quantity of capacitance and the rate at which it is delivered for four different MnOx - C variants was assessed by fabricating symmetric electrochemical capacitors using a concentrated aqueous electrolyte .", "entity": [{"entity": "MnOx", "entity_type": "Chemical", "pos": [85, 89]}, {"entity": "C", "entity_type": "Chemical", "pos": [92, 93]}], "task": "NER"}
{"text": "Carbon nanofoam papers containing primarily 10 - 20 nm mesopores support high MnOx loadings ( 60 wt % ) and device - level capacitance ( 30 F g ( - 1 ) ) , but the small mesoporous network hinders electrolyte transport and the low void volume restricts the quantity of charge - compensating ions within the electrode , making the full capacitance only accessible at slow rates ( 5 mV s ( - 1 ) ) .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "MnOx", "entity_type": "Chemical", "pos": [78, 82]}], "task": "NER"}
{"text": "Carbon nanofoam papers with macropores ( 100 - 200 nm ) facilitate high rate operation ( 50 mV s ( - 1 ) ) , but deliver significantly lower device capacitance ( 13 F g ( - 1 ) ) as a result of lower MnOx loadings ( 41 wt % ) .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "MnOx", "entity_type": "Chemical", "pos": [200, 204]}], "task": "NER"}
{"text": "Devices comprising MnOx - carbon nanofoams with interconnecting networks of meso - and macropores balance capacitance and rate performance , delivering 33 F g ( - 1 ) at 5 mV s ( - 1 ) and 23 F g ( - 1 ) at 50 mV s ( - 1 ) .", "entity": [{"entity": "MnOx", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [26, 32]}], "task": "NER"}
{"text": "The use of carbon nanofoam papers with size - tunable pore structures and thickness provides the opportunity to engineer the electrode architecture to deliver scalable quantities of capacitance ( F cm ( - 2 ) ) in tens of seconds with a single device .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [11, 17]}], "task": "NER"}
{"text": "Microfluidic chemostat for measuring single cell dynamics in bacteria .", "entity": [], "task": "NER"}
{"text": "We designed a microfluidic chemostat consisting of 600 sub - micron trapping / growth channels connected to two feeding channels .", "entity": [], "task": "NER"}
{"text": "The microchemostat traps E . coli cells and forces them to grow in lines for over 50 generations .", "entity": [], "task": "NER"}
{"text": "Excess cells , including the mother cells captured at the start of the process , are removed from both ends of the growth channels by the media flow .", "entity": [], "task": "NER"}
{"text": "With the aid of time - lapse microscopy , we have monitored dynamic properties such as growth rate and GFP expression at the single - cell level for many generations while maintaining a population of bacteria of similar age .", "entity": [], "task": "NER"}
{"text": "We also use the microchemostat to show how the population responds to dynamic changes in the environment .", "entity": [], "task": "NER"}
{"text": "Since more than 100 individual bacterial cells are aligned and immobilized in a single field of view , the microchemostat is an ideal platform for high - throughput intracellular measurements .", "entity": [], "task": "NER"}
{"text": "We demonstrate this capability by tracking with sub - diffraction resolution the movements of fluorescently tagged loci in more than one thousand cells on a single device .", "entity": [], "task": "NER"}
{"text": "The device yields results comparable to conventional agar microscopy experiments with substantial increases in throughput and ease of analysis .", "entity": [], "task": "NER"}
{"text": "High - grade prostate cancer and biochemical recurrence after radical prostatectomy among men using 5 alpha - reductase inhibitors and alpha - blockers .", "entity": [], "task": "NER"}
{"text": "BACKGROUND : Two clinical trials have shown that users of 5 alpha - reductase inhibitors finasteride and dutasteride ( 5 - ARIs ) have reduced overall prostate cancer risk , while the proportion of high - grade tumors is increased .", "entity": [{"entity": "finasteride", "entity_type": "Chemical", "pos": [89, 100]}, {"entity": "dutasteride", "entity_type": "Chemical", "pos": [105, 116]}], "task": "NER"}
{"text": "We studied tumor characteristics , risk of biochemical recurrence and mortality after radical prostatectomy in 5 - ARI and alpha - blocker users .", "entity": [], "task": "NER"}
{"text": "METHODS : The study cohort consisted of 1 , 315 men who underwent radical prostatectomy at the Tampere University Hospital during 1995 - 2009 .", "entity": [], "task": "NER"}
{"text": "Biochemical relapse was defined as serum PSA >= 0 . 2 ng / ml after the operation .", "entity": [], "task": "NER"}
{"text": "Information on mortality and medication purchases was obtained from national registries .", "entity": [], "task": "NER"}
{"text": "Cox proportional regression was used to analyze hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CI ) of biochemical relapse and death .", "entity": [], "task": "NER"}
{"text": "RESULTS : The proportion of high - grade ( Gleason 7 - 10 ) tumors was significantly elevated among men who had used 5 - ARIs for 4 years or longer compared to the non - users ( 83 . 3 % vs . 53 . 3 % , respectively ) .", "entity": [], "task": "NER"}
{"text": "Survival curves for biochemical relapse - free survival differed between long - term and short - term 5 - ARI users , but the hazard ratio remained statistically non - significant .", "entity": [], "task": "NER"}
{"text": "Risk of biochemical recurrence was elevated among alpha - blocker users ( HR 1 . 68 , 95 % CI 1 . 37 - 2 . 06 ) , but in sensitivity analyses this was evident only in men using alpha - blockers after prostatectomy .", "entity": [], "task": "NER"}
{"text": "Mortality was not associated with medication usage .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Long - term users of finasteride or dutasteride had more often high - grade prostate cancer .", "entity": [{"entity": "finasteride", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "dutasteride", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "Our results suggest also worse progression - free survival .", "entity": [], "task": "NER"}
{"text": "The association between risk of biochemical recurrence and post - operative alpha - blocker usage suggests that voiding or storage symptoms after prostatectomy may predict biochemical relapse .", "entity": [], "task": "NER"}
{"text": "Prostate (c) 2013 Wiley Periodicals , Inc .", "entity": [], "task": "NER"}
{"text": "Fluocinolone acetonide intravitreal implant ( Iluvien (R) ) : in diabetic macular oedema .", "entity": [{"entity": "Fluocinolone acetonide", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "Iluvien", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Fluocinolone acetonide intravitreal implant ( Iluvien (R) ) is an injectable , non - erodible , corticosteroid implant that is approved in several European countries for the treatment of chronic diabetic macular oedema ( DMO ) .", "entity": [{"entity": "Fluocinolone acetonide", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "Iluvien", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "corticosteroid", "entity_type": "Chemical", "pos": [96, 110]}], "task": "NER"}
{"text": "In analyses of two multinational trials in patients with DMO previously treated with macular laser photocoagulation , fluocinolone acetonide intravitreal implant 0 . 2 mu g / day was significantly more efficacious than sham injection in improving visual acuity .", "entity": [{"entity": "fluocinolone acetonide", "entity_type": "Chemical", "pos": [118, 140]}], "task": "NER"}
{"text": "At 24 months post injection , 29 % of fluocinolone acetonide intravitreal implant 0 . 2 mu g / day recipients had an improvement in the best - corrected visual acuity ( BCVA ) letter score of >= 15 compared with 16 % in the sham injection group ( p = 0 . 002 ) [ primary endpoint ] .", "entity": [{"entity": "fluocinolone acetonide", "entity_type": "Chemical", "pos": [38, 60]}], "task": "NER"}
{"text": "Treatment benefit was most evident in the subgroup of patients whose duration of DMO was >= 3 years .", "entity": [], "task": "NER"}
{"text": "In this subgroup at 36 months , 34 % of fluocinolone acetonide intravitreal implant 0 . 2 mu g / day recipients had an increase in the BCVA score of >= 15 , compared with 13 % of sham injection recipients ( p < 0 . 001 ) .", "entity": [{"entity": "fluocinolone acetonide", "entity_type": "Chemical", "pos": [40, 62]}], "task": "NER"}
{"text": "Fluocinolone acetonide intravitreal implant recipients also had generally greater benefits than sham injection recipients on secondary endpoints .", "entity": [{"entity": "Fluocinolone acetonide", "entity_type": "Chemical", "pos": [0, 22]}], "task": "NER"}
{"text": "In patients who were phakic in the study eye at baseline , cataracts occurred in 82 % of fluocinolone acetonide intravitreal implant 0 . 2 mu g / day recipients and 51 % of sham injection recipients .", "entity": [{"entity": "fluocinolone acetonide", "entity_type": "Chemical", "pos": [89, 111]}], "task": "NER"}
{"text": "Overall , 37 % and 12 % of patients in the fluocinolone acetonide intravitreal implant and sham injection groups developed raised intraocular pressure ( IOP ) , which was generally controlled with IOP - lowering drugs .", "entity": [{"entity": "fluocinolone acetonide", "entity_type": "Chemical", "pos": [43, 65]}], "task": "NER"}
{"text": "Group I mGluRs evoke K - ATP current by intracellular Ca2 + mobilization in rat subthalamus neurons .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [21, 22]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "Ca2 +", "entity_type": "Chemical", "pos": [54, 59]}], "task": "NER"}
{"text": "We reported previously that Ca ( 2 + ) influx through N - methly - d - aspartate - gated channels evokes ATP - sensitive K ( + ) ( K - ATP ) currents in rat subthalamic nucleus ( STN ) neurons .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "N - methly - d - aspartate", "entity_type": "Chemical", "pos": [54, 80]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [105, 108]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [121, 128]}, {"entity": "K", "entity_type": "Chemical", "pos": [131, 132]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [135, 138]}], "task": "NER"}
{"text": "By using whole - cell patch clamp recordings in brain slices , we investigated the ability of ( RS ) - 3 , 5 - dihydroxyphenylglycine ( DHPG ) , a group I metabotropic glutamate receptor ( mGluR ) agonist , to evoke K - ATP currents .", "entity": [{"entity": "( RS ) - 3 , 5 - dihydroxyphenylglycine", "entity_type": "Chemical", "pos": [94, 133]}, {"entity": "DHPG", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [168, 177]}, {"entity": "K", "entity_type": "Chemical", "pos": [216, 217]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [220, 223]}], "task": "NER"}
{"text": "DHPG ( 20 micro M ) evoked outward current at - 70 mV and was associated with a positive slope conductance of 2 . 7 nS .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The sulfonylurea agent tolbutamide ( 100 micro M ) converted the positive slope to negative slope conductance , indicating mediation by K - ATP channels ( ATP - sensitive K + channels ) .", "entity": [{"entity": "sulfonylurea", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "K", "entity_type": "Chemical", "pos": [136, 137]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [140, 143]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [155, 158]}, {"entity": "K +", "entity_type": "Chemical", "pos": [171, 174]}], "task": "NER"}
{"text": "Currents evoked by DHPG were significantly reduced by a combination of mGluR1 and mGluR5 negative allosteric modulators .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [19, 23]}], "task": "NER"}
{"text": "DHPG - evoked outward current was blocked by cyclopiazonic acid and thapsigargin and mimicked by caffeine , suggesting mediation by release of intracellular Ca ( 2 + ) .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "cyclopiazonic acid", "entity_type": "Chemical", "pos": [45, 63]}, {"entity": "thapsigargin", "entity_type": "Chemical", "pos": [68, 80]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [97, 105]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [157, 167]}], "task": "NER"}
{"text": "DHPG outward current was also blocked by ryanodine and 2 - aminoethoxydiphenylborane , suggesting mediation by ryanodine - and inositol 1 , 4 , 5 - triphosphate - sensitive Ca ( 2 + ) release .", "entity": [{"entity": "DHPG", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "ryanodine", "entity_type": "Chemical", "pos": [41, 50]}, {"entity": "2 - aminoethoxydiphenylborane", "entity_type": "Chemical", "pos": [55, 84]}, {"entity": "ryanodine", "entity_type": "Chemical", "pos": [111, 120]}, {"entity": "inositol 1 , 4 , 5 - triphosphate", "entity_type": "Chemical", "pos": [127, 160]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [173, 183]}], "task": "NER"}
{"text": "The nitric oxide synthase inhibitor N ( G ) - nitro - l - arginine methyl ester and inhibitors of protein kinase G activity also suppressed DHPG - induced outward current .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "N ( G ) - nitro - l - arginine methyl ester", "entity_type": "Chemical", "pos": [36, 79]}, {"entity": "DHPG", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "Voltage recordings showed that tolbutamide prolonged depolarizing plateau potentials and increased the spontaneous firing rate of STN neurons recorded in the presence of DHPG .", "entity": [{"entity": "tolbutamide", "entity_type": "Chemical", "pos": [31, 42]}, {"entity": "DHPG", "entity_type": "Chemical", "pos": [170, 174]}], "task": "NER"}
{"text": "These results show that group I mGluR stimulation generates K - ATP current by a nitric oxide - and protein kinase G - dependent process that is mediated by release of Ca ( 2 + ) from intracellular stores .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [60, 61]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [168, 178]}], "task": "NER"}
{"text": "Because burst firing is linked to symptoms of Parkinson ' s disease , we suggest that K - ATP channels might provide a physiologically important inhibitory influence on STN neuronal activity .", "entity": [{"entity": "K", "entity_type": "Chemical", "pos": [86, 87]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [90, 93]}], "task": "NER"}
{"text": "Internalization Pathways of Anisotropic Disc - Shaped Zeolite L Nanocrystals with Different Surface Properties in HeLa Cancer Cells .", "entity": [{"entity": "Zeolite L", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "Information about the mechanisms underlying the interactions of nanoparticles with living cells is crucial for their medical application and also provides indications of the putative toxicity of such materials .", "entity": [], "task": "NER"}
{"text": "Here the uptake and intracellular delivery of disc - shaped zeolite L nanocrystals as porous aminosilicates with well - defined crystal structure , uncoated as well as with COOH - , NH ( 2 ) - , polyethyleneglycol ( PEG ) - and polyallylamine hydrochloride ( PAH ) surface coatings are reported .", "entity": [{"entity": "zeolite L", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "aminosilicates", "entity_type": "Chemical", "pos": [93, 107]}, {"entity": "COOH -", "entity_type": "Chemical", "pos": [173, 179]}, {"entity": "NH ( 2 ) -", "entity_type": "Chemical", "pos": [182, 192]}, {"entity": "polyethyleneglycol", "entity_type": "Chemical", "pos": [195, 213]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [216, 219]}, {"entity": "polyallylamine hydrochloride", "entity_type": "Chemical", "pos": [228, 256]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [259, 262]}], "task": "NER"}
{"text": "HeLa cells are used as a model system to demonstrate the relation between these particles and cancer cells .", "entity": [], "task": "NER"}
{"text": "Interactions are studied in terms of their fates under diverse in vitro cell culture conditions .", "entity": [], "task": "NER"}
{"text": "Differently charged coatings demonstrated dissimilar behavior in terms of agglomeration in media , serum protein adsorption , nanoparticle cytotoxicity and cell internalization .", "entity": [], "task": "NER"}
{"text": "It is also found that functionalized disc - shaped zeolite L particles enter the cancer cells via different , partly not yet characterized , pathways .", "entity": [], "task": "NER"}
{"text": "These in vitro results provide additional insight about low - aspect ratio anisotropic nanoparticle interactions with cancer cells and demonstrate the possibility to manipulate the interactions of nanoparticles and cells by surface coating for the use of nanoparticles in medical applications .", "entity": [], "task": "NER"}
{"text": "Nanostructural anisotropy underlies anisotropic electrical bistability .", "entity": [], "task": "NER"}
{"text": "Regular arrays of nanorods having asymmetric cross - sections are fabricated by a combination of electrodeposition and glancing - angle deposition ( GLAD ) .", "entity": [], "task": "NER"}
{"text": "When these nanorods are embedded in a polymer matrix , they give rise to composite materials in which the structural anisotropy at the nanoscale translates into functional anisotropy in the form of direction - dependent electrical bistability .", "entity": [], "task": "NER"}
{"text": "The degree of this directional bistability depends on and can be controlled by the spacing between the nearby nanorods .", "entity": [], "task": "NER"}
{"text": "Comparative toxicological study of the novel protein phosphatase inhibitor 19 - Epi - okadaic acid in primary cultures of rat cerebellar cells .", "entity": [{"entity": "19 - Epi - okadaic acid", "entity_type": "Chemical", "pos": [75, 98]}], "task": "NER"}
{"text": "Okadaic acid ( OKA ) and analogues are frequent contaminants of coastal waters and seafood .", "entity": [{"entity": "Okadaic acid", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [15, 18]}], "task": "NER"}
{"text": "Structure analysis of the isolated OKA analogue 19 - epi - OKA showed important conformation differences expected to result in lower protein phosphatase ( PP ) inhibitory potencies than OKA .", "entity": [{"entity": "OKA", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [48, 62]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [186, 189]}], "task": "NER"}
{"text": "However , 19 - epi - OKA and OKA inhibitory activities versus PP2A were unexpectedly found to be virtually equipotent .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [10, 24]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [29, 32]}], "task": "NER"}
{"text": "To investigate the toxicological relevance of these findings , we tested the effects of 19 - epi - OKA on cultured cerebellar cells and compared them with those of OKA and its isomer dinophysistoxin - 2 .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [88, 102]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [164, 167]}, {"entity": "dinophysistoxin - 2", "entity_type": "Chemical", "pos": [183, 202]}], "task": "NER"}
{"text": "19 - epi - OKA caused degeneration of neurites and neuronal death with much lower potency than its congeners .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "The concentration of 19 - epi - OKA that reduced after 24h the maximum neuronal survival ( EC5024 ) by 50 % was ~ 300nM compared with ~ 2nM and ~ 8nM for OKA and dinophysistoxin - 2 , respectively .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [21, 35]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [154, 157]}, {"entity": "dinophysistoxin - 2", "entity_type": "Chemical", "pos": [162, 181]}], "task": "NER"}
{"text": "Exposure to 19 - epi - OKA resulted also in less toxicity for cultured glial cells ( EC5024 , 19 - epi - OKA ~ 600nM ; EC5024 , OKA ~ 20nM ) .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [12, 26]}, {"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [94, 108]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "19 - epi - OKA induced apoptotic condensation and fragmentation of chromatin , activation of caspases , and activation of ERK1 / 2 MAP kinases , features previously reported for OKA and dinophysistoxin - 2 .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [178, 181]}, {"entity": "dinophysistoxin - 2", "entity_type": "Chemical", "pos": [186, 205]}], "task": "NER"}
{"text": "Also , differential sensitivity to 19 - epi - OKA was observed between neuronal and glial cells , a specific characteristic shared by OKA and dinophysistoxin - 2 but not by other toxins .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [35, 49]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "dinophysistoxin - 2", "entity_type": "Chemical", "pos": [142, 161]}], "task": "NER"}
{"text": "Our results are consistent with 19 - epi - OKA being included among the group of toxins of OKA and derivatives and support the suitability of cellular bioassays for the detection of these compounds .", "entity": [{"entity": "19 - epi - OKA", "entity_type": "Chemical", "pos": [32, 46]}, {"entity": "OKA", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "Hypoxia stress test reveals exaggerated cardiovascular effects in hypertensive rats after exposure to the air pollutant acrolein .", "entity": [{"entity": "acrolein", "entity_type": "Chemical", "pos": [120, 128]}], "task": "NER"}
{"text": "Exposure to air pollution increases the risk of cardiovascular morbidity and mortality , especially in susceptible populations .", "entity": [], "task": "NER"}
{"text": "Despite increased risk , adverse responses are often delayed and require additional stress tests to reveal latent effects of exposure .", "entity": [], "task": "NER"}
{"text": "The goal of this study was to use an episode of \" transient hypoxia \" as an extrinsic stressor to uncover latent susceptibility to environmental pollutants in a rodent model of hypertension .", "entity": [], "task": "NER"}
{"text": "We hypothesized that exposure to acrolein , an unsaturated aldehyde and mucosal irritant found in cigarette smoke , diesel exhaust , and power plant emissions , would increase cardiopulmonary sensitivity to hypoxia , particularly in hypertensive rats .", "entity": [{"entity": "acrolein", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "Spontaneously hypertensive and Wistar Kyoto ( normotensive ) rats , implanted with radiotelemeters , were exposed once for 3h to 3 ppm acrolein gas or filtered air in whole - body plethysmograph chambers and challenged with a 10 % oxygen atmosphere ( 10min ) 24h later .", "entity": [{"entity": "acrolein", "entity_type": "Chemical", "pos": [135, 143]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [231, 237]}], "task": "NER"}
{"text": "Acrolein exposure increased heart rate , blood pressure , breathing frequency , and minute volume in hypertensive rats and also increased the heart rate variability parameter LF , suggesting a potential role for increased sympathetic tone .", "entity": [{"entity": "Acrolein", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Normotensive rats only had increased blood pressure during acrolein exposure .", "entity": [{"entity": "acrolein", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "The hypoxia stress test after acrolein exposure revealed increased diastolic blood pressure only in hypertensive rats and increased minute volume and expiratory time only in normotensive rats .", "entity": [{"entity": "acrolein", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "These results suggest that hypertension confers exaggerated sensitivity to air pollution and that the hypoxia stress test is a novel tool to reveal the potential latent effects of air pollution exposure .", "entity": [], "task": "NER"}
{"text": "Gobichelin A and B : Mixed - Ligand Siderophores Discovered Using Proteomics .", "entity": [{"entity": "Gobichelin A and B", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "\" Omic \" strategies have been increasingly applied to natural product discovery processes , with ( meta - ) genome sequencing and mining implemented in many laboratories to date .", "entity": [], "task": "NER"}
{"text": "Using the proteomics - based discovery platform called PrISM ( Proteomic Investigation of Secondary Metabolism ) , we discovered two new siderophores gobichelin A and B from Streptomyces sp .", "entity": [{"entity": "gobichelin A and B", "entity_type": "Chemical", "pos": [150, 168]}], "task": "NER"}
{"text": "NRRL F - 4415 , a strain without a sequenced genome .", "entity": [], "task": "NER"}
{"text": "Using the proteomics information as a guide , the 37 kb gene cluster responsible for production of gobichelins was sequenced and its 20 open reading frames interpreted into a biosynthetic scheme .", "entity": [{"entity": "gobichelins", "entity_type": "Chemical", "pos": [99, 110]}], "task": "NER"}
{"text": "This led to the targeted detection and structure elucidation of the new compounds produced by nonribosomal peptide ( NRP ) synthesis .", "entity": [], "task": "NER"}
{"text": "Mechanistic insight into inhibition of two - component system signaling .", "entity": [], "task": "NER"}
{"text": "Two - component signal transduction systems ( TCSs ) are commonly used by bacteria to couple environmental stimuli to adaptive responses .", "entity": [], "task": "NER"}
{"text": "Targeting the highly conserved kinase domain in these systems represents a promising strategy for the design of a broad - spectrum antibiotic ; however , development of such compounds has been marred by an incomplete understanding of the conserved binding features within the active site that could be exploited in molecule design .", "entity": [], "task": "NER"}
{"text": "Consequently , a large percentage of the available TCS inhibitors demonstrate poor target specificity and act via multiple mechanisms , with aggregation of the kinase being the most notable .", "entity": [], "task": "NER"}
{"text": "In order to elucidate the mode of action of some of these compounds , molecular modeling was employed to dock a suite of molecules into the ATP - binding domain of several histidine kinases .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [140, 143]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [172, 181]}], "task": "NER"}
{"text": "This effort revealed a key structural feature of the domain that is likely interacting with several known inhibitors and is also highly conserved .", "entity": [], "task": "NER"}
{"text": "Furthermore , generation of several simplified scaffolds derived from a reported inhibitor and characterization of these compounds using activity assays , protein aggregation studies and saturation transfer differential ( STD ) NMR suggests that targeting of this protein feature may provide a basis for the design of ATP - competitive compounds .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [318, 321]}], "task": "NER"}
{"text": "5 - Hydroxytryptamine type 7 receptor neuroprotection against NMDA - induced excitotoxicity is PDGF beta receptor dependent .", "entity": [{"entity": "5 - Hydroxytryptamine", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "The serotonin ( 5 - HT ) type 7 receptor is expressed throughout the CNS including the hippocampus .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [16, 22]}], "task": "NER"}
{"text": "Long - term ( 2 - 24 h ) activation of 5 - HT7 receptors regulates growth factor receptor expression , including the expression of platelet - derived growth factor ( PDGF ) beta receptors .", "entity": [], "task": "NER"}
{"text": "Direct activation of PDGF beta receptors in primary hippocampal and cortical neurons inhibits NMDA receptor activity and attenuates NMDA receptor - induced neurotoxicity .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [94, 98]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [132, 136]}], "task": "NER"}
{"text": "Our objective was to investigate whether the 5 - HT7 receptor - induced increase in PDGF beta receptor expression would be similarly neuroprotective .", "entity": [], "task": "NER"}
{"text": "We demonstrate that 5 - HT7 receptor agonist treatment in primary hippocampal neurons also increases the expression of phospholipase C ( PLC ) gamma , a downstream effector of PDGF beta receptors associated with the inhibition of NMDA receptor activity .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [230, 234]}], "task": "NER"}
{"text": "To determine if the up - regulation of PDGF beta receptors is neuroprotective , primary hippocampal neurons were incubated with the 5 - HT7 receptor agonist , LP 12 , for 24 h .", "entity": [{"entity": "LP 12", "entity_type": "Chemical", "pos": [159, 164]}], "task": "NER"}
{"text": "Indeed , LP 12 treatment prevented NMDA - induced neurotoxicity and this effect was dependent on PDGF beta receptor kinase activity .", "entity": [{"entity": "LP 12", "entity_type": "Chemical", "pos": [9, 14]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [35, 39]}], "task": "NER"}
{"text": "Treatment of primary neurons with LP 12 also differentially altered NMDA receptor subunit expression , reducing the expression of NR1 and NR2B , but not NR2A .", "entity": [{"entity": "LP 12", "entity_type": "Chemical", "pos": [34, 39]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "These findings demonstrate the potential for providing growth factor receptor - dependent neuroprotective effects using small - molecule ligands of G protein - coupled receptors .", "entity": [], "task": "NER"}
{"text": "Mixed valency in hydrogen bonded ' dimers of dimers ' .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "Dimolybdenum quadruply bonded compounds containing a pendant lactam functional group form self - complementary hydrogen bonded ' dimers of dimers ' in the solid - state and CH ( 2 ) Cl ( 2 ) solutions .", "entity": [{"entity": "Dimolybdenum", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "lactam", "entity_type": "Chemical", "pos": [61, 67]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [111, 119]}, {"entity": "CH ( 2 ) Cl ( 2 )", "entity_type": "Chemical", "pos": [173, 190]}], "task": "NER"}
{"text": "Electrochemical studies in CH ( 2 ) Cl ( 2 ) show two consecutive one - electron redox processes corresponding to oxidation of the Mo ( 2 ) ( 4 + ) cores .", "entity": [{"entity": "CH ( 2 ) Cl ( 2 )", "entity_type": "Chemical", "pos": [27, 44]}, {"entity": "Mo ( 2 ) ( 4 + )", "entity_type": "Chemical", "pos": [131, 147]}], "task": "NER"}
{"text": "Spectroelectrochemical studies on the ' dimers of dimers ' show no evidence of intervalence charge transfer bands in the mixed valence radical cations formed by one - electron oxidation , indicating that they are examples of proton - coupled mixed valency .", "entity": [], "task": "NER"}
{"text": "Lower physical activity is a risk factor for a clustering of metabolic risk factors in non - obese and obese Japanese subjects : The Takahata study .", "entity": [], "task": "NER"}
{"text": "In several countries including Japan , people without obesity but with a clustering of metabolic risk factors ( MetRFs ) were not considered to have the metabolic syndrome ( MetS ) .", "entity": [], "task": "NER"}
{"text": "Here , we examined whether lifestyle characteristics differed between non - obese and obese subjects with or without a clustering of MetRFs .", "entity": [], "task": "NER"}
{"text": "From a population - based cross - sectional study of Japanese subjects aged >= 40 years , 1 , 601 subjects ( age : 61 . 9 +/- 10 . 3 years ; 710 / 891 men / women ) were recruited .", "entity": [], "task": "NER"}
{"text": "Physical activity status and daily nutritional intake were estimated using questionnaires .", "entity": [], "task": "NER"}
{"text": "A clustering of MetRFs was defined based on the presence of at least two non - essential risk factors for the diagnosis of the MetS in Japan .", "entity": [], "task": "NER"}
{"text": "Energy intake was not higher in subjects with a clustering of MetRFs compared with those without .", "entity": [], "task": "NER"}
{"text": "Among men , energy expenditure at work was significantly lower in non - obese ( 9 . 0 +/- 8 . 2 vs . 11 . 3 +/- 9 . 3 METs ( metabolic equivalents ) , P = . 025 ) and obese ( 9 . 0 +/- 7 . 9 vs . 11 . 6 +/- 9 . 4 METs , P = . 017 ) subjects with a clustering of MetRFs than in those without .", "entity": [], "task": "NER"}
{"text": "Multiple logistic regression analysis showed that energy expenditure at work was significantly associated with a clustering of MetRFs after adjusting for possible confounding factors including total energy intake .", "entity": [], "task": "NER"}
{"text": "The ORs ( per 1 MET ( metabolic equivalent ) ) were 0 . 970 ( 95 % CI , 0 . 944 - 0 . 997 ; P = . 032 ) in non - obese men and 0 . 962 ( 0 . 926 - 0 . 999 ; P = . 043 ) in obese men .", "entity": [], "task": "NER"}
{"text": "Similar associations were not observed in women .", "entity": [], "task": "NER"}
{"text": "In Japanese males , lower physical activity , but not excessive energy intake , is a risk factor for a clustering of MetRFs independent of their obesity status .", "entity": [], "task": "NER"}
{"text": "Drug shortages in the United States : a critical evaluation of root causes and the need for action .", "entity": [], "task": "NER"}
{"text": "Every day it is easy to find news articles detailing the impact of drug shortages on patients .", "entity": [], "task": "NER"}
{"text": "Where this was once only a concern of patients with rare , orphan diseases , it is now the concern of patients receiving even the most common chemotherapeutic regimens , the most efficacious antimicrobial therapy , or even the most rapid - acting analgesics , largely as a result of manufacturing quality problems .", "entity": [], "task": "NER"}
{"text": "Unfortunately for many of these patients , there are no efficacious alternatives .", "entity": [], "task": "NER"}
{"text": "Call to action : finding solutions for the drug shortage crisis in the United States .", "entity": [], "task": "NER"}
{"text": "In their article in this issue of CPT , Woodcock and Wosinska are the first to clearly outline the quality and manufacturing problems causing drug shortages of generic injectables .", "entity": [], "task": "NER"}
{"text": "These authors have focused on the main issue , namely , that manufacturing problems and the lack of incentives for quality products are the primary reasons for most recent shortages of generic injectable drugs .", "entity": [], "task": "NER"}
{"text": "Anagliptin , a DPP - 4 inhibitor , suppresses proliferation of vascular smooth muscles and monocyte inflammatory reaction and attenuates atherosclerosis in male apo E - deficient mice .", "entity": [{"entity": "Anagliptin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Dipeptyl peptidase - 4 ( DPP - 4 ) inhibitors modulate the progression of atherosclerosis .", "entity": [{"entity": "Dipeptyl", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "To gain insights into their mechanism of action , 9 - wk - old male apolipoprotein E ( apoE ) - deficient mice were fed a DPP - 4 inhibitor , anagliptin - containing diet .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [142, 152]}], "task": "NER"}
{"text": "The effects of anagliptin were investigated in , a monocyte cell line , human THP - 1 cells , and rat smooth muscle cells ( SMCs ) .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [15, 25]}], "task": "NER"}
{"text": "Treatment with anagliptin for 16 wk significantly reduced accumulation of monocytes and macrophages in the vascular wall , SMC content in plaque areas , and oil red O - stained area around the aortic valve without affecting glucose tolerance or body weight .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "oil red O", "entity_type": "Chemical", "pos": [157, 166]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [224, 231]}], "task": "NER"}
{"text": "Serum DPP - 4 concentrations were significantly higher in apoE - deficient mice than control mice , and the levels increased with aging , suggesting the involvement of DPP - 4 in the progression of atherosclerosis .", "entity": [], "task": "NER"}
{"text": "Indeed , soluble DPP - 4 augmented cultured SMC proliferation , and anagliptin suppressed the proliferation by inhibiting ERK phosphorylation .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [68, 78]}], "task": "NER"}
{"text": "In THP - 1 cells , anagliptin reduced lipopolysaccharide - induced TNF - alpha production with inhibiting ERK phosphorylation and nuclear translocation of nuclear factor - kappa B .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "Quantitative analysis also showed that anagliptin reduced the area of atherosclerotic lesion in apoE - deficient mice .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "These results indicated that the anti - atherosclerotic effect of anagliptin is mediated , at least in part , through its direct inhibition of SMC proliferation and inflammatory reaction of monocytes .", "entity": [{"entity": "anagliptin", "entity_type": "Chemical", "pos": [66, 76]}], "task": "NER"}
{"text": "Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non - human primates .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [21, 32]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Prevalent use of bisphenol - A ( BPA ) in the manufacture of resins , plastics and paper products has led to frequent exposure of most people to this endocrine disruptor .", "entity": [{"entity": "bisphenol - A", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "Some rodent studies have suggested that BPA can exert detrimental effects on brain development .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "However as rodent models cannot be relied on to predict consequences of human exposure to BPA during development , it is important to investigate the effects of BPA on non - human primate brain development .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [90, 93]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [161, 164]}], "task": "NER"}
{"text": "Previous research suggests that BPA preferentially targets dopamine neurons in ventral mesencephalon and glutamatergic neurons in hippocampus , so the present work examined the susceptibility of these systems to low dose BPA exposure at the fetal and juvenile stages of development in non - human primates .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [32, 35]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [59, 67]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [221, 224]}], "task": "NER"}
{"text": "Exposure of pregnant rhesus monkeys to relatively low levels of BPA during the final 2 months of gestation , induced abnormalities in fetal ventral mesencephalon and hippocampus .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Specifically , light microscopy revealed a decrease in tyrosine hydroxylase - expressing ( dopamine ) neurons in the midbrain of BPA - exposed fetuses and electron microscopy identified a reduction in spine synapses in the CA1 region of hippocampus .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "In contrast , administration of BPA to juvenile vervet monkeys ( 14 - 18 months of age ) was without effect on these indices , or on dopamine and serotonin concentrations in striatum and prefrontal cortex , or on performance of a cognitive task that tests working memory capacity .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [32, 35]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [133, 141]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [146, 155]}], "task": "NER"}
{"text": "These data indicate that BPA exerts an age - dependent detrimental impact on primate brain development , at blood levels within the range measured in humans having only environmental contact with BPA .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [196, 199]}], "task": "NER"}
{"text": "Assessment of emerging biomarkers of liver injury in human subjects .", "entity": [], "task": "NER"}
{"text": "Hepatotoxicity remains a major challenge in drug development .", "entity": [], "task": "NER"}
{"text": "Although alanine aminotransferase ( ALT ) remains the gold standard biomarker of liver injury , alternative biomarker strategies to better predict the potential for severe drug - induced liver injury ( DILI ) are essential .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [9, 16]}], "task": "NER"}
{"text": "In this study , we evaluated the utility of glutamate dehydrogenase ( GLDH ) , purine nucleoside phosphorylase ( PNP ) , malate dehydrogenase ( MDH ) , and paraxonase 1 ( PON1 ) as indicators of liver injury in cohorts of human subjects , including healthy subjects across age and gender , subjects with a variety of liver impairments , and several cases of acetaminophen poisoning .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "purine nucleoside", "entity_type": "Chemical", "pos": [79, 96]}, {"entity": "malate", "entity_type": "Chemical", "pos": [121, 127]}, {"entity": "acetaminophen", "entity_type": "Chemical", "pos": [358, 371]}], "task": "NER"}
{"text": "In the healthy subjects , levels of GLDH and MDH were not affected by age or gender .", "entity": [], "task": "NER"}
{"text": "Reference ranges for GLDH and MDH in healthy subjects were 1 - 10 and 79 - 176U / L , respectively .", "entity": [], "task": "NER"}
{"text": "In contrast , the levels of PON1 and PNP were not consistent across cohorts of healthy subjects .", "entity": [], "task": "NER"}
{"text": "Furthermore , GLDH and MDH had a strong correlation with elevated ALT levels and possessed a high predictive power for liver injury , as determined by ROC analysis .", "entity": [], "task": "NER"}
{"text": "In contrast , PON1 and PNP did not detect liver injury in our study .", "entity": [], "task": "NER"}
{"text": "Finally , evaluation of patients with acetaminophen - induced liver injury provided evidence that both GLDH and MDH might have utility as biomarkers of DILI in humans .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [38, 51]}], "task": "NER"}
{"text": "This study is the first to evaluate GLDH , MDH , PON1 , and PNP in a large number of human subjects and , and it provides an impetus for prospective clinical studies to fully evaluate the diagnostic value of GLDH and MDH for detection of liver injury .", "entity": [], "task": "NER"}
{"text": "Graphene nanoribbons as an advanced precursor for making carbon fiber .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [57, 63]}], "task": "NER"}
{"text": "Graphene oxide nanoribbons ( GONRs ) and chemically reduced graphene nanoribbons ( crGNRs ) were dispersed at high concentrations in chlorosulfonic acid to form anisotropic liquid crystal phases .", "entity": [{"entity": "Graphene oxide", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "reduced graphene", "entity_type": "Chemical", "pos": [52, 68]}, {"entity": "chlorosulfonic acid", "entity_type": "Chemical", "pos": [133, 152]}], "task": "NER"}
{"text": "The liquid crystal solutions were spun directly into hundreds of meters of continuous macroscopic fibers .", "entity": [], "task": "NER"}
{"text": "The relationship of fiber morphology to coagulation bath conditions was studied .", "entity": [], "task": "NER"}
{"text": "The effects of colloid concentration , annealing temperature , spinning air gap , and pretension during annealing on the fibers ' performance were also investigated .", "entity": [], "task": "NER"}
{"text": "Heat treatment of the as - spun GONR fibers at 1500 degrees C produced thermally reduced graphene nanoribbon ( trGNR ) fibers with a tensile strength of 378 MPa , Young ' s modulus of 36 . 2 GPa , and electrical conductivity of 285 S / cm , which is considerably higher than that in other reported graphene - derived fibers .", "entity": [{"entity": "reduced graphene", "entity_type": "Chemical", "pos": [81, 97]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [298, 306]}], "task": "NER"}
{"text": "This better trGNR fiber performance was due to the air gap spinning and annealing with pretension that produced higher molecular alignment within the fibers , as determined by X - ray diffraction and scanning electron microscopy .", "entity": [], "task": "NER"}
{"text": "The specific modulus of trGNR fibers is higher than that of the commercial general purpose carbon fibers and commonly used metals such as Al , Cu , and steel .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [91, 97]}, {"entity": "Al", "entity_type": "Chemical", "pos": [138, 140]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [143, 145]}, {"entity": "steel", "entity_type": "Chemical", "pos": [152, 157]}], "task": "NER"}
{"text": "The properties of trGNR fibers can be further improved by optimizing the spinning conditions with higher draw ratio , annealing conditions with higher pretensions , and using longer flake GONRs .", "entity": [], "task": "NER"}
{"text": "This technique is a new high - carbon - yield approach to make the next generation carbon fibers based on solution - based liquid crystal phase spinning .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [83, 89]}], "task": "NER"}
{"text": "Time - dependent changes in hepatic and intestinal induction of cytochrome P450 3A after administration of dexamethasone to rats .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [107, 120]}], "task": "NER"}
{"text": "Abstract 1 . We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A ( CYP3A ) in rats using dexamethasone 21 - phosphate ( DEX - P ) and midazolam ( MDZ ) as an inducer and a substrate to CYP3A , respectively .", "entity": [{"entity": "dexamethasone 21 - phosphate", "entity_type": "Chemical", "pos": [207, 235]}, {"entity": "DEX - P", "entity_type": "Chemical", "pos": [238, 245]}, {"entity": "midazolam", "entity_type": "Chemical", "pos": [252, 261]}, {"entity": "MDZ", "entity_type": "Chemical", "pos": [264, 267]}], "task": "NER"}
{"text": "2 . The number of times DEX - P was administered was not a significant factor in the induction of either hepatic or intestinal CYP3A ; however , administration of DEX - P multiple times markedly decreased the bioavailability of DEX - P by self - induction of CYP3A .", "entity": [{"entity": "DEX - P", "entity_type": "Chemical", "pos": [24, 31]}, {"entity": "DEX - P", "entity_type": "Chemical", "pos": [163, 170]}, {"entity": "DEX - P", "entity_type": "Chemical", "pos": [228, 235]}], "task": "NER"}
{"text": "3 . CYP3A induction in the liver increased depending on the dose of DEX - P , whereas that in intestine showed a mild increase , but the induction level was almost constant regardless of the dose of DEX - P .", "entity": [{"entity": "DEX - P", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "DEX - P", "entity_type": "Chemical", "pos": [199, 206]}], "task": "NER"}
{"text": "4 . Administration of a single dose of DEX - P showed a temporal increase in CYP3A activity in both tissues and the induction ratios reached maximum values at 12 h after DEX - P administration .", "entity": [{"entity": "DEX - P", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "DEX - P", "entity_type": "Chemical", "pos": [170, 177]}], "task": "NER"}
{"text": "On the other hand , a mild increase of CYP3A activity , which lasted for at least 48 h , was observed in both tissues after administration of multiple doses .", "entity": [], "task": "NER"}
{"text": "5 . Some physiological compounds such as cytokines might be involved in decreasing the CYP3A activity to maintain homeostasis of the body .", "entity": [], "task": "NER"}
{"text": "Photoinduced formation mechanism of the thymine - thymine ( 6 - 4 ) adduct .", "entity": [{"entity": "thymine - thymine ( 6 - 4 )", "entity_type": "Chemical", "pos": [40, 67]}], "task": "NER"}
{"text": "The photoinduced mechanism leading to the formation of the thymine - thymine ( 6 - 4 ) photolesion has been studied by using the CASPT2 / / CASSCF approach over a dinucleotide model in vacuo .", "entity": [{"entity": "thymine - thymine ( 6 - 4 )", "entity_type": "Chemical", "pos": [59, 86]}, {"entity": "dinucleotide", "entity_type": "Chemical", "pos": [163, 175]}], "task": "NER"}
{"text": "Following light absorption , localization of the excitation on a single thymine leads to fast singlet - triplet crossing that populates the triplet ( 3 ) ( n pi * ) state of thymine .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [72, 79]}, {"entity": "thymine", "entity_type": "Chemical", "pos": [174, 181]}], "task": "NER"}
{"text": "This state , displaying an elongated C ( 4 ) = O bond , triggers ( 6 - 4 ) dimer formation by reaction with the C ( 5 ) = C ( 6 ) double bond of the adjacent thymine , followed by a second intersystem crossing , which acts as a gate between the excited state of the reactant and the ground state of the photoproduct .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [158, 165]}], "task": "NER"}
{"text": "The requirement of localized excitation on just one thymine , whose main decay channel ( by radiationless repopulation of its ground state ) is nonphotochemical , can rationalize the experimentally observed low quantum yield of formation for the thymine - thymine ( 6 - 4 ) adduct .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "thymine - thymine ( 6 - 4 )", "entity_type": "Chemical", "pos": [246, 273]}], "task": "NER"}
{"text": "Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five - drug cocktail approach .", "entity": [], "task": "NER"}
{"text": "Abstract Background and objective : To evaluate the effects of ischemia and reperfusion ( IR ) and ischemic preconditioning ( IPC ) on the metabolic activities of cytochrome P450 ( CYP ) isozymes in rats by a five - drug cocktail approach .", "entity": [], "task": "NER"}
{"text": "Methods : Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2 , CYP2C9 , CYP2E1 , CYP2D6 and CYP3A4 , which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs : caffeine , chlorzoxazone , tolbutamide , metoprolol and midazolam , respectively .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [242, 250]}, {"entity": "chlorzoxazone", "entity_type": "Chemical", "pos": [253, 266]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [269, 280]}, {"entity": "metoprolol", "entity_type": "Chemical", "pos": [283, 293]}, {"entity": "midazolam", "entity_type": "Chemical", "pos": [298, 307]}], "task": "NER"}
{"text": "Rats were randomly divided into IR , IPC and sham groups , and then injected the mixture of five probe drugs .", "entity": [], "task": "NER"}
{"text": "Blood samples were collected at a series of time - points and the concentrations of probe drugs in plasma were determined by a HPLC method with UV detection .", "entity": [], "task": "NER"}
{"text": "The pharmacokinetic parameters were calculated by the software of DAS 2 . 0 .", "entity": [], "task": "NER"}
{"text": "Results : The parameters including t ( 1 / 2 beta ) , CLs , AUC , MRT and K ( 10 ) exhibited a similar tendency for both IR and IPC groups .", "entity": [], "task": "NER"}
{"text": "Compared with sham group , CLs and K ( 10 ) of five probe drugs were significantly lower ( p < 0 . 05 ) , AUC and t ( 1 / 2 beta ) of five or some probe drugs were significantly increased in IR and IPC groups ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Compared with IPC group , CLs of five probe drugs were decreased and AUC were significantly increased in the IR group ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Conclusion : IR can variably decrease the activities of CYP isozymes in rats and this decrease can be attenuated by IPC .", "entity": [], "task": "NER"}
{"text": "In vitro toxicity of camalexin derivatives in human cancer and non - cancer cells .", "entity": [{"entity": "camalexin", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "The aim of the study was to investigate the cytotoxic activity of camalexin and its five synthetic derivatives in cancer and non - cancer cells .", "entity": [{"entity": "camalexin", "entity_type": "Chemical", "pos": [66, 75]}], "task": "NER"}
{"text": "In cancer cells the benzocamalexin ( BC ) displayed the most potent activity with an IC value of 23 . 3 - 30 . 1 mu mol / L .", "entity": [{"entity": "benzocamalexin", "entity_type": "Chemical", "pos": [20, 34]}], "task": "NER"}
{"text": "On the other hand , minimal toxicity ( IC > 100 . 0 mu mol / L ) in non - cancer cells was observed .", "entity": [], "task": "NER"}
{"text": "Based on these results , BC was selected for further studies .", "entity": [], "task": "NER"}
{"text": "Flow cytometric analysis revealed a BC - induced arrest of the cell cycle in the G2 phase associated with downregulation of alpha - tubulin , alpha 1 - tubulin , beta 5 - tubulin expression .", "entity": [], "task": "NER"}
{"text": "These findings suggest that the inhibitory effect of BC is mediated via inhibition of microtubule formation .", "entity": [], "task": "NER"}
{"text": "Moreover , BC downregulated the expression of microtubule - related protein indicating the effect of this compound on microtubule assembly .", "entity": [], "task": "NER"}
{"text": "After treatment with BC increase of the sub - G DNA content fraction was noted which is considered to be a marker of apoptotic cell death .", "entity": [], "task": "NER"}
{"text": "Apoptosis was also confirmed by DNA fragmentation assay .", "entity": [], "task": "NER"}
{"text": "Moreover , quantitative real - time PCR showed that BC downregulated the expression of antiapoptotic genes Bcl - 2 and Bcl - xL and upregulated the expression of proapoptotic Bax .", "entity": [], "task": "NER"}
{"text": "Taken together , our study suggests that the blockade of cell cycle progression and initiation of apoptosis may play an important role in the antiproliferative activity of BC in human cancer cells .", "entity": [], "task": "NER"}
{"text": "Antivenom therapy of carpet viper ( Echis ocellatus ) envenoming : Effectiveness and strategies for delivery in West Africa .", "entity": [], "task": "NER"}
{"text": "In West Africa , response to specific , geographically appropriate , antivenom is often dramatic following carpet viper ( Echis ocellatus ) envenoming with rapid restoration of blood coagulability and resolution of spontaneous haemorrhage .", "entity": [], "task": "NER"}
{"text": "Envenoming from Australasian snakes causing similar coagulopathies may respond less dramatically and the effectiveness of antivenom is being questioned .", "entity": [], "task": "NER"}
{"text": "Here we have reviewed and re - analysed all published preclinical and clinical studies on envenoming and antivenom therapy conducted in West Africa to determine the effectiveness of antivenom .", "entity": [], "task": "NER"}
{"text": "22 studies provided relevant information : 12 observational studies , 4 RCTs and 6 preclinical studies .", "entity": [], "task": "NER"}
{"text": "Four comparative studies confirmed statistically significant protection against mortality ranging from 57 to 87 % using specific antivenoms compared to non - specific or no antivenoms .", "entity": [], "task": "NER"}
{"text": "Meta - analysis estimated combined Odds Ratio ( 95 % CI ) of 0 . 25 ( 0 . 14 - 0 . 45 ) of dying among those treated with specific antivenom or 75 % ( 95 % CI : 55 - 86 % ) protection against death .", "entity": [], "task": "NER"}
{"text": "Mortality more than doubled during times when stocks of reliable antivenoms ran out , with Relative Risk ( 95 % CI ) ] of 2 . 33 ( 1 . 26 - 4 . 06 ) .", "entity": [], "task": "NER"}
{"text": "Serum kinetics of venom antigen / antivenom levels also confirmed that decline of venom antigen levels coincided with resolution of coagulopathy while decline of antivenom levels was associated with venom antigen reappearance and recurrence of coagulopathy .", "entity": [], "task": "NER"}
{"text": "Preclinical and antivenomics analysis confirmed efficacy of regionally appropriate antivenoms against E . ocellatus and related species ' venoms in Sub - Saharan Africa but not against Asian Echis carinatus venom .", "entity": [], "task": "NER"}
{"text": "Antivenoms raised against E . carinatus were ineffective in human studies .", "entity": [], "task": "NER"}
{"text": "In West Africa , specific antivenom is effective in managing carpet viper envenoming .", "entity": [], "task": "NER"}
{"text": "A centralized hub - and - spoke strategy is suggested for broadening antivenom access to endemic rural areas together with instituting quality assurance , standardization and manpower training .", "entity": [], "task": "NER"}
{"text": "Benefits , risks , cost - effectiveness and feasibility of the approach should be formally assessed .", "entity": [], "task": "NER"}
{"text": "Medical aspects of bio - terrorism .", "entity": [], "task": "NER"}
{"text": "INTRODUCTION : Bioterrorism is a terrorist action involving the intentional release or dissemination of a biological warfare agent ( BWA ) , which includes some bacteria , viruses , rickettsiae , fungi or biological toxins .", "entity": [], "task": "NER"}
{"text": "BWA is a naturally occurring or human - modified form that may kill or incapacitate humans , animals or plants as an act of war or terrorism .", "entity": [], "task": "NER"}
{"text": "BWA is a weapon of choice for mass destruction and terrorism , because of the incubation period , less effective amount than chemical warfare agents , easily distribution , odorless , colorless , difficult to detect , no need of specialized equipment for production and naturally distribution which can easily be obtained .", "entity": [], "task": "NER"}
{"text": "BWA may be disseminating as an aerosol , spray , explosive device , and by food or water .", "entity": [], "task": "NER"}
{"text": "CLASSIFICATION : Based on the risk for human health , BWAs have been prioritized into three categories of A , B and C .", "entity": [], "task": "NER"}
{"text": "Category A includes microorganisms or toxins that easily spread , leading to intoxication with high death rates such as Anthrax , Botulism , Plague , Smallpox , Tularemia and Viral hemorrhagic fevers .", "entity": [], "task": "NER"}
{"text": "Category B has lower toxicity with wider range , including Staphylococcal Entrotoxin type B ( SEB ) , Epsilon toxin of Clostridium perfringens , Ricin , Saxotoxins , Abrin and Trichothecene mycotoxins .", "entity": [{"entity": "Saxotoxins", "entity_type": "Chemical", "pos": [153, 163]}, {"entity": "Trichothecene", "entity_type": "Chemical", "pos": [176, 189]}], "task": "NER"}
{"text": "The C category includes emerging pathogens that could also be engineered for mass spread such as Hanta viruses , multidrug - resistant tuberculosis , Nipah virus , the tick - borne encephalitis viruses , hemorrhagic fever viruses and yellow fever .", "entity": [], "task": "NER"}
{"text": "CLINICAL MANIFESTATIONS OF BIOTOXINS IN HUMAN : Clinical features and severity of intoxication depend on the agent and exposed dose , route of entry , individual variation and environmental factors .", "entity": [], "task": "NER"}
{"text": "Onset of symptoms varies from 2 - 24 h in Ricin to 24 - 96 h in Botulism .", "entity": [], "task": "NER"}
{"text": "Clinical manifestations also vary from irritation of the eyes , skin and mucus membranes in T ( 2 ) toxin to an acute flaccid paralysis of bilateral cranial nerve impairment of descending manner in botulism .", "entity": [{"entity": "T ( 2 ) toxin", "entity_type": "Chemical", "pos": [92, 105]}], "task": "NER"}
{"text": "Most of the pyrogenic toxins such as SEB produce the same signs and symptoms as toxic shock syndrome including a rapid drop in blood pressure , elevated temperature , and multiple organ failure .", "entity": [], "task": "NER"}
{"text": "MANAGEMENT : There is no specific antidote or effective treatment for most of the biotoxins .", "entity": [], "task": "NER"}
{"text": "The clinical management is thus more supportive and symptomatic .", "entity": [], "task": "NER"}
{"text": "Fortunately vaccines are now available for most of BWA .", "entity": [], "task": "NER"}
{"text": "Therefore , immunization of personnel at risk of exposure is recommended .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : Biotoxins are very wide and bioterrorism is a heath and security threat that may induce national and international problems .", "entity": [], "task": "NER"}
{"text": "Therefore , the security authorities , health professional and even public should be aware of bioterrorism .", "entity": [], "task": "NER"}
{"text": "Sonochemical effects on free phenolic acids under ultrasound treatment in a model system .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [29, 43]}], "task": "NER"}
{"text": "Sonochemical effects on seven free phenolic acids under ultrasound treatment in a model system have been investigated .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [35, 49]}], "task": "NER"}
{"text": "The degradation products have also been tentatively identified by FTIR and HPLC - UV - ESIMS .", "entity": [], "task": "NER"}
{"text": "Five phenolic acids ( protocatechuic acid , p - hydroxybenzoic acid , vanillic acid , p - coumaric acid , and ferulic acid ) proved to be stable , while two others ( caffeic acid and sinapic acid ) were degraded under ultrasound treatment .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [5, 19]}, {"entity": "protocatechuic acid", "entity_type": "Chemical", "pos": [22, 41]}, {"entity": "p - hydroxybenzoic acid", "entity_type": "Chemical", "pos": [44, 67]}, {"entity": "vanillic acid", "entity_type": "Chemical", "pos": [70, 83]}, {"entity": "p - coumaric acid", "entity_type": "Chemical", "pos": [86, 103]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [110, 122]}, {"entity": "caffeic acid", "entity_type": "Chemical", "pos": [166, 178]}, {"entity": "sinapic acid", "entity_type": "Chemical", "pos": [183, 195]}], "task": "NER"}
{"text": "The nature of the solvent and the temperature has been identified as important factors in determining the degradation reaction .", "entity": [], "task": "NER"}
{"text": "Liquid height , ultrasonic intensity , and duty cycle of the ultrasound exposure affected only the degradation rate and did not change the nature of the degradation .", "entity": [], "task": "NER"}
{"text": "The degradation rates of caffeic acid and sinapic acid decreased with increasing temperature .", "entity": [{"entity": "caffeic acid", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "sinapic acid", "entity_type": "Chemical", "pos": [42, 54]}], "task": "NER"}
{"text": "The degradation kinetics of these two acids under ultrasound conformed to zeroth - order reactions at - 5 to 25 degrees C .", "entity": [], "task": "NER"}
{"text": "Both decomposition and polymerization reactions occurred when caffeic acid and sinapic acid were subjected to ultrasound .", "entity": [{"entity": "caffeic acid", "entity_type": "Chemical", "pos": [62, 74]}, {"entity": "sinapic acid", "entity_type": "Chemical", "pos": [79, 91]}], "task": "NER"}
{"text": "Degradation products , such as the corresponding decarboxylation products and their dimers , have been tentatively identified .", "entity": [], "task": "NER"}
{"text": "Characterization of a key aminoglycoside phosphotransferase in gentamicin biosynthesis .", "entity": [{"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [26, 40]}, {"entity": "gentamicin", "entity_type": "Chemical", "pos": [63, 73]}], "task": "NER"}
{"text": "Gentamicin is an aminoglycoside antibiotic obtained from cultures of Micromonospora as the important anti - infective agents .", "entity": [{"entity": "Gentamicin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [17, 31]}], "task": "NER"}
{"text": "Gentamicin which lacks 3 ' - hydroxyl group can avoid the attack from the modification enzymes of antibiotic - resistant bacteria in clinic .", "entity": [{"entity": "Gentamicin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "3 ' - hydroxyl", "entity_type": "Chemical", "pos": [23, 37]}], "task": "NER"}
{"text": "Consequently , C - 3 ' dehydroxylation is the key step in gentamicins biosynthesis .", "entity": [{"entity": "gentamicins", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "We suppose that there are some enzymes responsible for converting intermediate JI - 20A to 3 ' , 4 ' - bisdehydroxylated final product gentamicin C ( 1a ) , while phosphorylation of 3 ' - OH is possibly the first step for C - 3 ' dehydroxylation .", "entity": [{"entity": "JI - 20A", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "gentamicin C", "entity_type": "Chemical", "pos": [135, 147]}, {"entity": "3 ' - OH", "entity_type": "Chemical", "pos": [182, 190]}], "task": "NER"}
{"text": "The gentamicin biosynthetic gene gntI , encoding an aminoglycoside phosphotransferase , was cloned from Micromonospora echinospora ATCC15835 and overexpressed in Escherichia coli .", "entity": [{"entity": "gentamicin", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [52, 66]}], "task": "NER"}
{"text": "The resulting phosphotransferase was purified , and the kinetic parameters for Kanamycin A , Kanamycin B , Neomycin B and Amikacin were determined .", "entity": [{"entity": "Kanamycin A", "entity_type": "Chemical", "pos": [79, 90]}, {"entity": "Kanamycin B", "entity_type": "Chemical", "pos": [93, 104]}, {"entity": "Neomycin B", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "Amikacin", "entity_type": "Chemical", "pos": [122, 130]}], "task": "NER"}
{"text": "Elucidation of NMR data of phosphorylated kanamycin B has unambiguously demonstrated a regiospecific phosphorylation of 3 ' - hydroxyl of the 6 - aminohexose ring .", "entity": [{"entity": "phosphorylated kanamycin B", "entity_type": "Chemical", "pos": [27, 53]}, {"entity": "3 ' - hydroxyl", "entity_type": "Chemical", "pos": [120, 134]}, {"entity": "6 - aminohexose", "entity_type": "Chemical", "pos": [142, 157]}], "task": "NER"}
{"text": "The results described here partly confirm that the 3 ' - dehydroxylation step is preceded by a 3 ' phosphorylation step .", "entity": [], "task": "NER"}
{"text": "It is predicted that GntI belongs to a new aminoglycoside phosphotransferase group involved with aminoglycoside antibiotics biosynthesis pathway .", "entity": [{"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [43, 57]}, {"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [97, 111]}], "task": "NER"}
{"text": "Relationship of cellular topoisomerase II alpha inhibition to cytotoxicity and published genotoxicity of fluoroquinolone antibiotics in V79 cells .", "entity": [{"entity": "fluoroquinolone", "entity_type": "Chemical", "pos": [105, 120]}], "task": "NER"}
{"text": "Fluoroquinolone ( FQ ) antibiotics are bacteriocidal through inhibition of the bacterial gyrase and at sufficient concentrations in vitro , they can inhibit the homologous eukaryotic topoisomerase ( TOPO ) II enzyme .", "entity": [{"entity": "Fluoroquinolone", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "FQ exert a variety of genotoxic effects in mammalian systems through mechanisms not yet established , but which are postulated to involve inhibition of TOPO II enzymes .", "entity": [], "task": "NER"}
{"text": "To assess the relationship of inhibition of cell nuclear TOPO II to cytotoxicity and reported genotoxicity , two FQ , clinafloxacin ( CLFX ) and lomefloxacin ( LOFX ) , having available genotoxicity data showing substantial differences with CLFX being more potent than LOFX , were selected for study .", "entity": [{"entity": "clinafloxacin", "entity_type": "Chemical", "pos": [118, 131]}, {"entity": "CLFX", "entity_type": "Chemical", "pos": [134, 138]}, {"entity": "lomefloxacin", "entity_type": "Chemical", "pos": [145, 157]}, {"entity": "LOFX", "entity_type": "Chemical", "pos": [160, 164]}, {"entity": "CLFX", "entity_type": "Chemical", "pos": [241, 245]}, {"entity": "LOFX", "entity_type": "Chemical", "pos": [269, 273]}], "task": "NER"}
{"text": "The relative inhibitory activities of these FQ on nuclear TOPO II alpha in cultured Chinese hamster lung fibroblasts ( V79 cells ) over dose ranges and at equimolar concentrations were assessed by measuring nuclear stabilized cleavage complexes of TOPO II alpha - DNA .", "entity": [], "task": "NER"}
{"text": "Cytotoxicity was measured by relative cell counts .", "entity": [], "task": "NER"}
{"text": "Both FQ inhibited V79 cell nuclear TOPO II alpha .", "entity": [], "task": "NER"}
{"text": "The lowest - observed - adverse - effect levels for TOPO II alpha inhibition were 55 mu M for CLFX , and 516 mu M for LOFX .", "entity": [{"entity": "CLFX", "entity_type": "Chemical", "pos": [94, 98]}, {"entity": "LOFX", "entity_type": "Chemical", "pos": [118, 122]}], "task": "NER"}
{"text": "The no - observed - adverse - effect - levels were 41 mu M for CLFX , and 258 mu M for LOFX .", "entity": [{"entity": "CLFX", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "LOFX", "entity_type": "Chemical", "pos": [87, 91]}], "task": "NER"}
{"text": "At equimolar concentrations ( 175 mu M ) , CLFX was more potent than LOFX .", "entity": [{"entity": "CLFX", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "LOFX", "entity_type": "Chemical", "pos": [69, 73]}], "task": "NER"}
{"text": "Likewise , CLFX was more cytotoxic than LOFX .", "entity": [{"entity": "CLFX", "entity_type": "Chemical", "pos": [11, 15]}, {"entity": "LOFX", "entity_type": "Chemical", "pos": [40, 44]}], "task": "NER"}
{"text": "Thus , the two FQ , inhibited TOPO II alpha in intact V79 cells , differed in their potencies and exhibited no - observed - adverse - effect levels .", "entity": [], "task": "NER"}
{"text": "These findings are in concordance with published genotoxicity data and observed cytotoxicity .", "entity": [], "task": "NER"}
{"text": "IGF - I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells .", "entity": [], "task": "NER"}
{"text": "FSH and IGF - I synergistically stimulate gonadal steroid production ; conversely , silencing the FSH or the IGF - I genes leads to infertility and hypogonadism .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "To determine the molecular link between these hormones , we examined the signaling cross talk downstream of their receptors .", "entity": [], "task": "NER"}
{"text": "In human and rodent granulosa cells ( GCs ) , IGF - I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [101, 105]}], "task": "NER"}
{"text": "In contrast , inhibition of IGF - I receptor ( IGF - IR ) activity or expression using pharmacological , genetic , or biochemical approaches prevented the FSH - and cAMP - induced expression of steroidogenic genes and estradiol production .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [165, 169]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [218, 227]}], "task": "NER"}
{"text": "In vivo experiments demonstrated that IGF - IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins .", "entity": [], "task": "NER"}
{"text": "FSH or IGF - I alone stimulated protein kinase B ( PKB ) , which is also known as AKT and in combination synergistically increased AKT phosphorylation .", "entity": [], "task": "NER"}
{"text": "Remarkably , blocking IGF - IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH .", "entity": [], "task": "NER"}
{"text": "In GCs lacking IGF - IR activity , FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT .", "entity": [], "task": "NER"}
{"text": "Our findings demonstrate , for the first time , that in human , mouse , and rat GCs , the well - known stimulatory effect of FSH on Cyp19 and AKT depends on IGF - I and on the expression and activation of the IGF - IR .", "entity": [], "task": "NER"}
{"text": "Palladium nanoparticles supported on nitrogen - doped HOPG : a surface science and electrochemical study .", "entity": [{"entity": "Palladium", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "We have investigated by photoemission spectroscopy and scanning tunnelling microscopy what are the chemical and structural changes induced by nitrogen ion implantation ( 500 eV ) on highly oriented pyrolytic graphite and how the defects induced by this process modify the growth and thermal stability of palladium nanoparticles , deposited in situ by physical vapour deposition .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [142, 150]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [208, 216]}, {"entity": "palladium", "entity_type": "Chemical", "pos": [304, 313]}], "task": "NER"}
{"text": "Since nitrogen derived defects are mostly buried below the surface , they are not accessible for a chemical interaction with metal nanoparticles ; however , the amorphization induced by the ion beam in the outermost layers of the substrate beneficially affects the metal morphology , limiting the size of the nanoparticles and improving their thermal stability .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [6, 14]}], "task": "NER"}
{"text": "The supported nanoparticles have been tested towards the oxygen reduction reaction indicating that the electrochemical activity does not depend significantly on the ion implantation , but mostly on the amount of palladium .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [57, 63]}, {"entity": "palladium", "entity_type": "Chemical", "pos": [212, 221]}], "task": "NER"}
{"text": "Metabolic profiles of brain metastases .", "entity": [], "task": "NER"}
{"text": "Metastasis to the brain is a feared complication of systemic cancer , associated with significant morbidity and poor prognosis .", "entity": [], "task": "NER"}
{"text": "A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases .", "entity": [], "task": "NER"}
{"text": "The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning ( HR - MAS ) magnetic resonance spectroscopy ( MRS ) to correlate the metabolic profiles to clinical and pathological information .", "entity": [], "task": "NER"}
{"text": "Biopsy samples of human brain metastases ( n = 49 ) were investigated .", "entity": [], "task": "NER"}
{"text": "A significant correlation between lipid signals and necrosis in brain metastases was observed ( p < 0 . 01 ) , irrespective of their primary origin .", "entity": [], "task": "NER"}
{"text": "The principal component analysis ( PCA ) showed that brain metastases from malignant melanomas cluster together , while lung carcinomas were metabolically heterogeneous and overlap with other subtypes .", "entity": [], "task": "NER"}
{"text": "Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases .", "entity": [{"entity": "glycerophosphocholine", "entity_type": "Chemical", "pos": [44, 65]}], "task": "NER"}
{"text": "A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas ( p = 0 . 01 ) , indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets .", "entity": [{"entity": "Nile Red", "entity_type": "Chemical", "pos": [86, 94]}], "task": "NER"}
{"text": "MRS - based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors .", "entity": [], "task": "NER"}
{"text": "Low oxygen tension maintains multipotency , whereas normoxia increases differentiation of mouse bone marrow stromal cells .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [4, 10]}], "task": "NER"}
{"text": "Optimization of mesenchymal stem cells ( MSC ) culture conditions is of great importance for their more successful application in regenerative medicine .", "entity": [], "task": "NER"}
{"text": "O ( 2 ) regulates various aspects of cellular biology and , in vivo , MSC are exposed to different O ( 2 ) concentrations spanning from very low tension in the bone marrow niche , to higher amounts in wounds .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "In our present work , we isolated mouse bone marrow stromal cells ( BMSC ) and showed that they contained a population meeting requirements for MSC definition .", "entity": [], "task": "NER"}
{"text": "In order to establish the effect of low O ( 2 ) on cellular properties , we examined BSMC cultured under hypoxic ( 3 % O ( 2 ) ) conditions .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [40, 47]}, {"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [119, 126]}], "task": "NER"}
{"text": "Our results demonstrate that 3 % O ( 2 ) augmented proliferation of BMSC , as well as the formation of colonies in the colony - forming unit assay ( CFU - A ) , the percentage of quiescent cells , and the expression of stemness markers Rex - 1 and Oct - 4 , thereby suggesting an increase in the stemness of culture when exposed to hypoxia .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [33, 40]}], "task": "NER"}
{"text": "In contrast , intrinsic differentiation processes were inhibited by 3 % O ( 2 ) .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [72, 79]}], "task": "NER"}
{"text": "Overall yield of differentiation was dependent on the adjustment of O ( 2 ) tension to the specific stage of BMSC culture .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [68, 75]}], "task": "NER"}
{"text": "Thus , we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3 % O ( 2 ) , followed by differentiation stage at 21 % O ( 2 ) .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "We also demonstrated that 3 % O ( 2 ) affected BMSC differentiation in p53 and reactive oxygen species ( ROS ) independent pathways .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [88, 94]}], "task": "NER"}
{"text": "Our findings can significantly contribute to the obtaining of high - quality MSC for effective cell therapy .", "entity": [], "task": "NER"}
{"text": "The first dehydration and the competing reaction pathways of glucose homogeneously and heterogeneously catalyzed by acids .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [61, 68]}], "task": "NER"}
{"text": "The dehydration mechanisms for glucose in beta - pyranose ( BP ) and in open - chain ( OC ) forms , catalyzed by acids homogeneously and heterogeneously , were investigated using density functional and two - layer ONIOM calculations .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "beta - pyranose", "entity_type": "Chemical", "pos": [42, 57]}], "task": "NER"}
{"text": "The first dehydration reaction and competing reaction pathways are the main focus of the present study .", "entity": [], "task": "NER"}
{"text": "The energetics of five dehydration and two isomerization pathways were examined for the protonated form of BP in acidic aqueous solutions and the most favorable pathway of these was found to be the dehydration at the anomeric site .", "entity": [], "task": "NER"}
{"text": "No dehydration pathway of OC glucose is favored over its isomerization to BP or to fructose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [29, 36]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "The relative ease of dehydration over isomerization depends on the selection of the reaction media for the protonated form of BP .", "entity": [], "task": "NER"}
{"text": "These two reaction pathways catalyzed by a surface Br o nsted acid site were then examined and the isomerization pathway was found to be more favorable than dehydration at the anomeric site on a surface acid site .", "entity": [], "task": "NER"}
{"text": "These mechanistic insights provide an important guide for the catalyst design / selection of the reaction media for glucose dehydration .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [116, 123]}], "task": "NER"}
{"text": "Early - Adulthood Cardiovascular Disease Risk Factor Profiles Among Individuals With and Without Diabetes in the Framingham Heart Study .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEMany studies of diabetes have examined risk factors at the time of diabetes diagnosis instead of considering the lifetime burden of adverse risk factor levels .", "entity": [], "task": "NER"}
{"text": "We examined the 30 - year cardiovascular disease ( CVD ) risk factor burden that participants have up to the time of diabetes diagnosis . RESEARCH DESIGN AND METHODSAmong participants free of CVD , incident diabetes cases ( fasting plasma glucose >= 126 mg / dL or treatment ) occurring at examinations 2 through 8 ( 1979 - 2008 ) of the Framingham Heart Study Offspring cohort were age - and sex - matched 1 : 2 to controls .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [239, 246]}], "task": "NER"}
{"text": "CVD risk factors ( hypertension , high LDL cholesterol , low HDL cholesterol , high triglycerides , obesity ) were measured at the time of diabetes diagnosis and at time points 10 , 20 , and 30 years prior .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [65, 76]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [84, 97]}], "task": "NER"}
{"text": "Conditional logistic regression was used to compare risk factor levels at each time point between diabetes cases and controls . RESULTSWe identified 525 participants with new - onset diabetes who were matched to 1 , 049 controls ( mean age , 60 years ; 40 % women ) .", "entity": [], "task": "NER"}
{"text": "Compared with those without diabetes , individuals who eventually developed diabetes had higher levels of hypertension ( odds ratio [ OR ] , 2 . 2 ; P = 0 . 003 ) , high LDL ( OR , 1 . 5 ; P = 0 . 04 ) , low HDL ( OR , 2 . 1 ; P = 0 . 0001 ) , high triglycerides ( OR , 1 . 7 ; P = 0 . 04 ) , and obesity ( OR , 3 . 3 ; P < 0 . 0001 ) at time points 30 years before diabetes diagnosis .", "entity": [{"entity": "triglycerides", "entity_type": "Chemical", "pos": [249, 262]}], "task": "NER"}
{"text": "After further adjustment for BMI , the ORs for hypertension ( OR , 1 . 9 ; P = 0 . 02 ) and low HDL ( OR , 1 . 7 ; P = 0 . 01 ) remained statistically significant . CONCLUSIONSCVD risk factors are increased up to 30 years before diagnosis of diabetes .", "entity": [], "task": "NER"}
{"text": "These findings highlight the importance of a life course approach to CVD risk factor identification among individuals at risk for diabetes .", "entity": [], "task": "NER"}
{"text": "Television Viewing and Low Leisure - Time Physical Activity in Adolescence Independently Predict the Metabolic Syndrome in Mid - Adulthood .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEWe investigated whether television ( TV ) viewing and low leisure - time physical activity in adolescence predict the metabolic syndrome in mid - adulthood . RESEARCH DESIGN AND METHODSTV viewing habits and participation in leisure - time physical activity at age 16 years were assessed by self - administered questionnaires in a population - based cohort in Northern Sweden .", "entity": [], "task": "NER"}
{"text": "The presence of the metabolic syndrome at age 43 years was ascertained in 888 participants ( 82 % of the baseline sample ) using the International Diabetes Federation criteria .", "entity": [], "task": "NER"}
{"text": "Odds ratios ( ORs ) and CIs were calculated using logistic regression . RESULTSThe overall prevalence of the metabolic syndrome at age 43 years was 26 . 9 % .", "entity": [], "task": "NER"}
{"text": "Adjusted OR for the metabolic syndrome at age 43 years was 2 . 14 ( 95 % CI 1 . 24 - 3 . 71 ) for those who reported \" watching several shows a day \" versus \" one show / week \" or less and 2 . 31 ( 1 . 13 - 4 . 69 ) for leisure - time physical activity \" several times / month \" or less compared with \" daily \" leisure - time physical activity at age 16 years .", "entity": [], "task": "NER"}
{"text": "TV viewing at age 16 years was associated with central obesity , low HDL cholesterol , and hypertension at age 43 years , whereas low leisure - time physical activity at age 16 years was associated with central obesity and triglycerides at age 43 years . CONCLUSIONSBoth TV viewing and low leisure - time physical activity in adolescence independently predicted the metabolic syndrome and several of the metabolic syndrome components in mid - adulthood .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [223, 236]}], "task": "NER"}
{"text": "These findings suggest that reduced TV viewing in adolescence , in addition to regular physical activity , may contribute to cardiometabolic health later in life .", "entity": [], "task": "NER"}
{"text": "25 - Hydroxyvitamin D in Obese Youth Across the Spectrum of Glucose Tolerance From Normal to Prediabetes to Type 2 Diabetes .", "entity": [{"entity": "25 - Hydroxyvitamin D", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "Glucose", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "OBJECTIVETo 1 ) determine if plasma 25 - hydroxyvitamin D ( 25 [ OH ] D ) concentrations differ among obese youth with normal glucose tolerance ( NGT ) versus prediabetes versus type 2 diabetes , and 2 ) assess the relationships between 25 ( OH ) D and in vivo insulin sensitivity and beta - cell function in this cohort . RESEARCH DESIGN AND METHODSPlasma 25 ( OH ) D concentrations were examined in banked specimens in 9 - to 20 - year - old obese youth ( n = 175 ; male 42 . 3 % , black 46 . 3 % ) ( NGT , n = 105 ; impaired glucose tolerance [ IGT ] , n = 43 ; type 2 diabetes , n = 27 ) who had in vivo insulin sensitivity and secretion measured by hyperinsulinemic - euglycemic and hyperglycemic clamp techniques and had an assessment of total body composition and abdominal adiposity . RESULTSThe mean age and BMI of the subjects were 14 . 3 +/- 2 . 1 years and 35 . 7 +/- 5 . 6 kg / m ( 2 ) , respectively .", "entity": [{"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [36, 57]}, {"entity": "25 [ OH ] D", "entity_type": "Chemical", "pos": [60, 71]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [126, 133]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [237, 248]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [357, 368]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [528, 535]}], "task": "NER"}
{"text": "BMI , plasma 25 ( OH ) D , and the proportion of vitamin D - deficient and - insufficient children did not differ across the three groups .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [13, 24]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "Furthermore , there was no association between 25 ( OH ) D and in vivo insulin sensitivity or beta - cell function relative to insulin sensitivity ( disposition index ) in all groups combined or in each group separately . CONCLUSIONSOur data in obese youth show 1 ) no differences in plasma 25 ( OH ) D concentrations across the glucose tolerance groups , and 2 ) no relationship between 25 ( OH ) D and in vivo insulin sensitivity and beta - cell function relative to insulin sensitivity in any of the groups .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [291, 302]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [329, 336]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [388, 399]}], "task": "NER"}
{"text": "It remains uncertain if enhancement of the vitamin D status could improve pathophysiological mechanisms of prediabetes and type 2 diabetes in obese youth .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [43, 52]}], "task": "NER"}
{"text": "Serum 25 - hydroxyvitamin D , parathyroid hormone , and their association with metabolic syndrome in Chinese .", "entity": [{"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [6, 27]}], "task": "NER"}
{"text": "Increasing evidence suggests that 25 - hydroxyvitamin D [ 25 ( OH ) D ] and parathyroid hormone ( PTH ) levels are associated with metabolic syndrome ( MetS ) .", "entity": [{"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [34, 55]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "In 2010 , we explored the association of serum 25 ( OH ) D and PTH levels with MetS in 1 , 390 Chinese participants , aged 20 - 83 years .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [47, 58]}], "task": "NER"}
{"text": "Anthropometric phenotypes , blood pressure , and the incidence of MetS were evaluated .", "entity": [], "task": "NER"}
{"text": "In addition , serum lipids , 25 ( OH ) D , and PTH were measured .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [29, 40]}], "task": "NER"}
{"text": "The median concentration of 25 ( OH ) D and PTH were 55 . 3 nmol / l and 2 . 8 pmol / l , respectively .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "The prevalence of vitamin D deficiency ( < 50 nmol / l ) was 39 . 9 % , with 34 . 5 % in men and 47 . 8 % in women .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [18, 27]}], "task": "NER"}
{"text": "After accounting for confounding factors and serum PTH , a 10 nmol / l higher serum 25 ( OH ) D level was associated with a 10 % lower risk of MetS ( OR = 0 . 90 , 95 % CI 0 . 84 - 0 . 96 , P = 0 . 0007 ) .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [84, 95]}], "task": "NER"}
{"text": "Furthermore , participants with vitamin D sufficiency had a 35 % lower risk of MetS than those with vitamin D deficiency ( OR = 0 . 65 , 95 % CI 0 . 51 - 0 . 84 , P = 0 . 0009 ) .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [100, 109]}], "task": "NER"}
{"text": "PTH was not associated with the risk of MetS after adjustment for confounding factors .", "entity": [], "task": "NER"}
{"text": "These results were confirmed in both men and women .", "entity": [], "task": "NER"}
{"text": "Thus in this cohort of Chinese individuals , vitamin D deficiency is common and optimal vitamin D level is inversely associated with MetS , independent of several confounders and PTH level .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "The clinical significance of these findings warrants further study .", "entity": [], "task": "NER"}
{"text": "Novel type II fatty acid biosynthesis ( FAS II ) inhibitors as multistage antimalarial agents .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world .", "entity": [], "task": "NER"}
{"text": "The development of new , affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics .", "entity": [], "task": "NER"}
{"text": "In addition , most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood .", "entity": [], "task": "NER"}
{"text": "At this point , a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito .", "entity": [], "task": "NER"}
{"text": "These insects act as a vector , subsequently spreading the disease to other humans .", "entity": [], "task": "NER"}
{"text": "In order to cure not only malaria but prevent transmission as well , a drug must target both the blood - and pre - erythrocytic liver stages of the parasite .", "entity": [], "task": "NER"}
{"text": "P . falciparum ( Pf ) enoyl acyl carrier protein ( ACP ) reductase ( ENR ) is a key enzyme of plasmodial type II fatty acid biosynthesis ( FAS II ) .", "entity": [{"entity": "enoyl acyl", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "It has been shown to be essential for liver - stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis .", "entity": [], "task": "NER"}
{"text": "Using virtual screening based on two crystal structures of PfENR , we identified a structurally novel class of FAS inhibitors .", "entity": [], "task": "NER"}
{"text": "Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite .", "entity": [], "task": "NER"}
{"text": "These two most promising derivatives were found to inhibit blood - stage parasite growth with IC ( 50 ) values of 1 . 7 and 3 . 0 mu M and lead to a more prominent developmental attenuation of liver - stage parasites than the gold - standard drug , primaquine .", "entity": [{"entity": "primaquine", "entity_type": "Chemical", "pos": [249, 259]}], "task": "NER"}
{"text": "A Robust Route to Enzymatically Functional , Hierarchically Self - Assembled Peptide Frameworks .", "entity": [], "task": "NER"}
{"text": "The addition of enzyme biofunctionality to self - assembling peptide nanofibers is challenging since such additions can inhibit functionality or self - assembly .", "entity": [], "task": "NER"}
{"text": "We introduce a method for peptide nanofiber enzyme functionalization , demonstrated by the attachment of a polymerization synthase to peptide nanofibers .", "entity": [], "task": "NER"}
{"text": "The enzyme generates a biocompatible , biodegradable biopolyester coat on the fibers with applicablity in medical engineering .", "entity": [], "task": "NER"}
{"text": "This approach provides a template for generation of functional bionanomaterials .", "entity": [], "task": "NER"}
{"text": "Solid - state NMR study reveals collagen I structural modifications of amino acid side chains upon fibrillogenesis .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [71, 81]}], "task": "NER"}
{"text": "In vivo , collagen I , the major structural protein in human body , is found assembled into fibrils .", "entity": [], "task": "NER"}
{"text": "In the present work , we study a high concentrated collagen sample in its soluble , fibrillar , and denatured states using one and two dimensional { ( 1 ) H } - ( 13 ) C solid - state NMR spectroscopy .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [149, 156]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [161, 169]}], "task": "NER"}
{"text": "We interpret ( 13 ) C chemical shift variations in terms of dihedral angle conformation changes .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [13, 21]}], "task": "NER"}
{"text": "Our data show that fibrillogenesis increases the side chain and backbone structural complexity .", "entity": [], "task": "NER"}
{"text": "Nevertheless , only three to five rotameric equilibria are found for each amino acid residue , indicating a relatively low structural heterogeneity of collagen upon fibrillogenesis .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [74, 84]}], "task": "NER"}
{"text": "Using side chain statistical data , we calculate equilibrium constants for a great number of amino acid residues .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [93, 103]}], "task": "NER"}
{"text": "Moreover , based on a ( 13 ) C quantitative spectrum , we estimate the percentage of residues implicated in each equilibrium .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [22, 30]}], "task": "NER"}
{"text": "Our data indicate that fibril formation greatly affects hydroxyproline and proline prolyl pucker ring conformation .", "entity": [{"entity": "hydroxyproline", "entity_type": "Chemical", "pos": [56, 70]}, {"entity": "proline prolyl", "entity_type": "Chemical", "pos": [75, 89]}], "task": "NER"}
{"text": "Finally , we discuss the implication of these structural data and propose a model in which the attractive force of fibrillogenesis comes from a structural reorganization of 10 to 15 % of the amino acids .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [191, 202]}], "task": "NER"}
{"text": "These results allow us to further understand the self - assembling process and fibrillar structure of collagen .", "entity": [], "task": "NER"}
{"text": "Detecting Allosteric Sites of HIV - 1 Reverse Transcriptase by X - ray Crystallographic Fragment Screening .", "entity": [], "task": "NER"}
{"text": "HIV - 1 reverse transcriptase ( RT ) undergoes a series of conformational changes during viral replication and is a central target for antiretroviral therapy .", "entity": [], "task": "NER"}
{"text": "The intrinsic flexibility of RT can provide novel allosteric sites for inhibition .", "entity": [], "task": "NER"}
{"text": "Crystals of RT that diffract X - rays to better than 2 A resolution facilitated the probing of RT for new druggable sites using fragment screening by X - ray crystallography .", "entity": [], "task": "NER"}
{"text": "A total of 775 fragments were grouped into 143 cocktails , which were soaked into crystals of RT in complex with the non - nucleoside drug rilpivirine ( TMC278 ) .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [123, 133]}, {"entity": "rilpivirine", "entity_type": "Chemical", "pos": [139, 150]}, {"entity": "TMC278", "entity_type": "Chemical", "pos": [153, 159]}], "task": "NER"}
{"text": "Seven new sites were discovered , including the Incoming Nucleotide Binding , Knuckles , NNRTI Adjacent , and 399 sites , located in the polymerase region of RT , and the 428 , RNase H Primer Grip Adjacent , and 507 sites , located in the RNase H region .", "entity": [{"entity": "Nucleotide", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "Three of these sites ( Knuckles , NNRTI Adjacent , and Incoming Nucleotide Binding ) are inhibitory and provide opportunities for discovery of new anti - AIDS drugs .", "entity": [{"entity": "Nucleotide", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "Cluster phases of decorated micellar solutions with macrocyclic ligands .", "entity": [], "task": "NER"}
{"text": "An aqueous self - assembled micellar system ( sodium dodecyl sulfate , SDS , decorated with various adhesive sites , cryptand Kryptofix 222 and crown ether 18 - Crown - 6 molecules ) has been investigated by dynamic light scattering ( DLS ) and small angle x - ray scattering ( SAXS ) to have insights into the micellar structure , the micellar interactions , and the aggregation properties of the system .", "entity": [{"entity": "sodium dodecyl sulfate", "entity_type": "Chemical", "pos": [46, 68]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [71, 74]}, {"entity": "cryptand", "entity_type": "Chemical", "pos": [117, 125]}, {"entity": "Kryptofix 222", "entity_type": "Chemical", "pos": [126, 139]}, {"entity": "crown ether", "entity_type": "Chemical", "pos": [144, 155]}, {"entity": "18 - Crown - 6", "entity_type": "Chemical", "pos": [156, 170]}], "task": "NER"}
{"text": "DLS demonstrates the existence of populations of aggregates in the submicrometer / micrometer range , while the Guinier analysis of the SAXS curves helps in detailing objects smaller than 30 nm .", "entity": [], "task": "NER"}
{"text": "The aggregates of micelles are here named cluster phases of micelles ( CPMs ) .", "entity": [], "task": "NER"}
{"text": "Considering that SDS micelles in water do not aggregate at low concentration , it is shown that macrocyclic ligands induce the SDS micelle aggregation as a function of the concentration ( i . e . , investigated ligand / SDS molar ratios are 5 . 0 , 1 . 5 , 1 . 0 , and 0 . 5 ) and hydrophobicity of the adhesive sites .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [127, 130]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [220, 223]}], "task": "NER"}
{"text": "The sizes and the percentages of the micelles and the CPMs have been monitored to test the stability and reversibility of the system .", "entity": [], "task": "NER"}
{"text": "DLS results clearly show that the aggregation processes of the decorated micelles are reproducible at time intervals of the order of 1 month , while the stability may not be entirely maintained after a year .", "entity": [], "task": "NER"}
{"text": "As an issue of particular relevance , the higher the ligand / surfactant molar ratio , the larger are the CPMs induced .", "entity": [], "task": "NER"}
{"text": "The K222 ligand results in being more effective in promoting the micellar aggregation than 18C6 as a consequence of the different hydrophobicity .", "entity": [{"entity": "K222", "entity_type": "Chemical", "pos": [4, 8]}, {"entity": "18C6", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "Personality and the acute subjective effects of d - amphetamine in humans .", "entity": [{"entity": "d - amphetamine", "entity_type": "Chemical", "pos": [48, 63]}], "task": "NER"}
{"text": "There is evidence that subjective responses to psychoactive drugs are related to personality traits .", "entity": [], "task": "NER"}
{"text": "Here , we extend previous findings by examining personality measures in relation to acute responses to d - amphetamine ( AMPH ) in a large sample of healthy volunteers .", "entity": [{"entity": "d - amphetamine", "entity_type": "Chemical", "pos": [103, 118]}, {"entity": "AMPH", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "Healthy adults ( n = 286 ) completed the Multidimensional Personality Questionnaire Brief Form ( MPQ - BF ) and participated in four sessions during which they received oral AMPH ( 0 , 5 , 10 , 20 mg ) , under double - blind conditions .", "entity": [{"entity": "AMPH", "entity_type": "Chemical", "pos": [174, 178]}], "task": "NER"}
{"text": "Subjective responses to the drug were measured using the Profile of Mood States , Addiction Research Center Inventory , and Drug Effects Questionnaire .", "entity": [], "task": "NER"}
{"text": "Drug responses were reduced via principal components analysis to three higher - order factors ( ' Euphoria ' , ' Arousal ' , ' Dysphoria ' ) .", "entity": [], "task": "NER"}
{"text": "Participants were rank ordered on selected MPQ - BF scales ; the top and bottom third on each trait were compared on the drug response factors .", "entity": [], "task": "NER"}
{"text": "High trait physical fearlessness was significantly associated with greater amphetamine - related Arousal , and high trait reward sensitivity was significantly associated with greater Euphoria .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "In addition , high trait impulsivity was significantly associated with greater Arousal and Euphoria .", "entity": [], "task": "NER"}
{"text": "These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality , and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems .", "entity": [{"entity": "AMPH", "entity_type": "Chemical", "pos": [96, 100]}], "task": "NER"}
{"text": "In - plane coassembly route to atomically thick inorganic - organic hybrid nanosheets .", "entity": [], "task": "NER"}
{"text": "Control over the anisotropic assembly of small building blocks into organized structures is considered an effective way to design organic nanosheets and atomically thick inorganic nanosheets with nonlayered structure .", "entity": [], "task": "NER"}
{"text": "However , there is still no available route so far to control the assembly of inorganic and organic building blocks into a flattened hybrid nanosheet with atomic thickness .", "entity": [], "task": "NER"}
{"text": "Herein , we highlight for the first time a universal in - plane coassembly process for the design and synthesis of transition - metal chalcogenide - alkylamine inorganic - organic hybrid nanosheets with atomic thickness .", "entity": [{"entity": "transition - metal chalcogenide - alkylamine", "entity_type": "Chemical", "pos": [115, 159]}], "task": "NER"}
{"text": "The structure , formation mechanism , and stability of the hybrid nanosheets were investigated in detail by taking the Co 9 S 8 - oleylamine ( Co 9 S 8 - OA ) hybrid nanosheets as an example .", "entity": [{"entity": "Co 9 S 8", "entity_type": "Chemical", "pos": [119, 127]}, {"entity": "oleylamine", "entity_type": "Chemical", "pos": [130, 140]}, {"entity": "Co 9 S 8", "entity_type": "Chemical", "pos": [143, 151]}], "task": "NER"}
{"text": "Both experimental data and theoretical simulations demonstrate that the hybrid nanosheets were formed by in - plane connection of small two - dimensional ( 2D ) Co 9 S 8 nanoplates via oleylamine molecules adsorbed at the side surface and corner sites of the nanoplates .", "entity": [{"entity": "Co 9 S 8", "entity_type": "Chemical", "pos": [161, 169]}, {"entity": "oleylamine", "entity_type": "Chemical", "pos": [185, 195]}], "task": "NER"}
{"text": "X - ray absorption fine structure spectroscopy study reveals the structure distortion of the small 2D Co 9 S 8 nanoplates that endows structural stability of the atomically thick Co 9 S 8 - OA hybrid nanosheets .", "entity": [{"entity": "Co 9 S 8", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "Co 9 S 8", "entity_type": "Chemical", "pos": [179, 187]}], "task": "NER"}
{"text": "The brand new atomically thick nanosheets with inorganic - organic hybrid network nanostructure will not only enrich the family of atomically thick 2D nanosheets but also inspire more interest in their potential applications .", "entity": [], "task": "NER"}
{"text": "Targeted drug delivery to treat pain and cerebral hypoxia .", "entity": [], "task": "NER"}
{"text": "Limited drug penetration is an obstacle that is often encountered in treatment of central nervous system ( CNS ) diseases including pain and cerebral hypoxia .", "entity": [], "task": "NER"}
{"text": "Over the past several years , biochemical characteristics of the brain ( i . e . , tight junction protein complexes at brain barrier sites , expression of influx and efflux transporters ) have been shown to be directly involved in determining CNS permeation of therapeutic agents ; however , the vast majority of these studies have focused on understanding those mechanisms that prevent drugs from entering the CNS .", "entity": [], "task": "NER"}
{"text": "Recently , this paradigm has shifted toward identifying and characterizing brain targets that facilitate CNS drug delivery .", "entity": [], "task": "NER"}
{"text": "Such targets include the organic anion - transporting polypeptides ( OATPs in humans ; Oatps in rodents ) , a family of sodium - independent transporters that are endogenously expressed in the brain and are involved in drug uptake .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [120, 126]}], "task": "NER"}
{"text": "OATP / Oatp substrates include drugs that are efficacious in treatment of pain and / or cerebral hypoxia ( i . e . , opioid analgesic peptides , 3 - hydroxy - 3 - methylglutaryl coenzyme A reductase inhibitors ) .", "entity": [{"entity": "3 - hydroxy - 3 - methylglutaryl coenzyme A", "entity_type": "Chemical", "pos": [145, 188]}], "task": "NER"}
{"text": "This clearly suggests that OATP / Oatp isoforms are viable transporter targets that can be exploited for optimization of drug delivery to the brain and , therefore , improved treatment of CNS diseases .", "entity": [], "task": "NER"}
{"text": "This review summarizes recent knowledge in this area and emphasizes the potential that therapeutic targeting of OATP / Oatp isoforms may have in facilitating CNS drug delivery and distribution .", "entity": [], "task": "NER"}
{"text": "Additionally , information presented in this review will point to novel strategies that can be used for treatment of pain and cerebral hypoxia .", "entity": [], "task": "NER"}
{"text": "A Molecular - Modeling Toolbox Aimed at Bridging the Gap between Medicinal Chemistry and Computational Sciences .", "entity": [], "task": "NER"}
{"text": "In the current era of high - throughput drug discovery and development , molecular modeling has become an indispensable tool for identifying , optimizing and prioritizing small - molecule drug candidates .", "entity": [], "task": "NER"}
{"text": "The required background in computational chemistry and the knowledge of how to handle the complex underlying protocols , however , might keep medicinal chemists from routinely using in silico technologies .", "entity": [], "task": "NER"}
{"text": "Our objective is to encourage those researchers to exploit existing modeling technologies more frequently through easy - to - use graphical user interfaces .", "entity": [], "task": "NER"}
{"text": "In this account , we present two innovative tools ( which we are prepared to share with academic institutions ) facilitating computational tasks commonly utilized in drug discovery and development : ( 1 ) the VirtualDesignLab estimates the binding affinity of small molecules by simulating and quantifying their binding to the three - dimensional structure of a target protein ; and ( 2 ) the MD Client launches molecular dynamics simulations aimed at exploring the time - dependent stability of ligand - protein complexes and provides residue - based interaction energies .", "entity": [], "task": "NER"}
{"text": "This allows medicinal chemists to identify sites of potential improvement in their candidate molecule .", "entity": [], "task": "NER"}
{"text": "As a case study , we present the application of our tools towards the design of novel antagonists for the FimH adhesin .", "entity": [], "task": "NER"}
{"text": "Bioactivity and applications of sulphated polysaccharides from marine microalgae .", "entity": [], "task": "NER"}
{"text": "Marine microalgae have been used for a long time as food for humans , such as Arthrospira ( formerly , Spirulina ) , and for animals in aquaculture .", "entity": [], "task": "NER"}
{"text": "The biomass of these microalgae and the compounds they produce have been shown to possess several biological applications with numerous health benefits .", "entity": [], "task": "NER"}
{"text": "The present review puts up - to - date the research on the biological activities and applications of polysaccharides , active biocompounds synthesized by marine unicellular algae , which are , most of the times , released into the surrounding medium ( exo - or extracellular polysaccharides , EPS ) .", "entity": [], "task": "NER"}
{"text": "It goes through the most studied activities of sulphated polysaccharides ( sPS ) or their derivatives , but also highlights lesser known applications as hypolipidaemic or hypoglycaemic , or as biolubricant agents and drag - reducers .", "entity": [], "task": "NER"}
{"text": "Therefore , the great potentials of sPS from marine microalgae to be used as nutraceuticals , therapeutic agents , cosmetics , or in other areas , such as engineering , are approached in this review .", "entity": [], "task": "NER"}
{"text": "Catalytic transformation of alcohols to carboxylic acid salts and H2 using water as the oxygen atom source .", "entity": [{"entity": "alcohols", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [40, 55]}, {"entity": "H2", "entity_type": "Chemical", "pos": [66, 68]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [88, 94]}], "task": "NER"}
{"text": "The oxidation of alcohols to carboxylic acids is an important industrial reaction used in the synthesis of bulk and fine chemicals .", "entity": [{"entity": "alcohols", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "carboxylic acids", "entity_type": "Chemical", "pos": [29, 45]}], "task": "NER"}
{"text": "Most current processes are performed by making use of either stoichiometric amounts of toxic oxidizing agents or the use of pressurized dioxygen .", "entity": [{"entity": "dioxygen", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Here , we describe an alternative dehydrogenative pathway effected by water and base with the concomitant generation of hydrogen gas .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "A homogeneous ruthenium complex catalyses the transformation of primary alcohols to carboxylic acid salts at low catalyst loadings ( 0 . 2 mol % ) in basic aqueous solution .", "entity": [{"entity": "ruthenium", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "alcohols", "entity_type": "Chemical", "pos": [72, 80]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [84, 99]}], "task": "NER"}
{"text": "A consequence of this finding could be a safer and cleaner process for the synthesis of carboxylic acids and their derivatives at both laboratory and industrial scales .", "entity": [{"entity": "carboxylic acids", "entity_type": "Chemical", "pos": [88, 104]}], "task": "NER"}
{"text": "Increased impulsive choice for saccharin during PCP withdrawal in female monkeys : influence of menstrual cycle phase .", "entity": [{"entity": "saccharin", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "BACKGROUND : In previous studies with male and female rhesus monkeys , withdrawal of access to oral phencyclidine ( PCP ) self - administration reduced responding for food under a high fixed - ratio ( FR ) schedule more in males than females , and with a delay discounting ( DD ) task with saccharin ( SACC ) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females .", "entity": [{"entity": "phencyclidine", "entity_type": "Chemical", "pos": [100, 113]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [116, 119]}, {"entity": "saccharin", "entity_type": "Chemical", "pos": [290, 299]}, {"entity": "SACC", "entity_type": "Chemical", "pos": [302, 306]}, {"entity": "SACC", "entity_type": "Chemical", "pos": [348, 352]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [370, 373]}], "task": "NER"}
{"text": "OBJECTIVES : The goal of the present study was to examine the effect of PCP ( 0 . 25 or 0 . 5 mg / ml ) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "SACC", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "MATERIALS AND METHODS : In component 1 , PCP and water were available from two drinking spouts for 1 . 5 h sessions under concurrent FR 16 schedules .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "In component 2 , a SACC solution was available for 45 min under a DD schedule .", "entity": [{"entity": "SACC", "entity_type": "Chemical", "pos": [19, 23]}], "task": "NER"}
{"text": "Monkeys had a choice of one immediate SACC delivery ( 0 . 6 ml ) or six delayed SACC deliveries , and the delay was increased by 1 s after a response on the delayed lever and decreased by 1 s after a response on the immediate lever .", "entity": [{"entity": "SACC", "entity_type": "Chemical", "pos": [38, 42]}, {"entity": "SACC", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "There was then a 10 - day water substitution phase , or PCP withdrawal , that occurred during the mid - follicular phase ( days 7 - 11 ) or the late luteal phase ( days 24 - 28 ) of the menstrual cycle .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "Access to PCP and concurrent water was then restored , and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [10, 13]}, {"entity": "PCP", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "RESULTS : PCP deliveries were higher during the luteal ( vs follicular ) phase .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "Impulsive choice was greater during the luteal ( vs follicular ) phase during withdrawal of the higher PCP concentration .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [103, 106]}], "task": "NER"}
{"text": "CONCLUSIONS : PCP withdrawal was associated with elevated impulsive choice for SACC , especially in the luteal ( vs follicular ) phase of the menstrual cycle in female monkeys .", "entity": [{"entity": "PCP", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "SACC", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "A donor - acceptor type organic dye connected with a quinoidal thiophene for dye - sensitized solar cells .", "entity": [{"entity": "quinoidal thiophene", "entity_type": "Chemical", "pos": [53, 72]}], "task": "NER"}
{"text": "A donor - acceptor type organic dye connected with a quinoidal thiophene as a pi - conjugated chain , cyano - [ 5 ' - ( 4 ' ' - ( N , N - dimethylamino ) benzylidene ) - 5H - thiophen - 2 ' - ylidene ] acetic acid , was synthesized and applied to dye - sensitized solar cells ( DSSCs ) .", "entity": [{"entity": "quinoidal thiophene", "entity_type": "Chemical", "pos": [53, 72]}, {"entity": "cyano - [ 5 ' - ( 4 ' ' - ( N , N - dimethylamino ) benzylidene ) - 5H - thiophen - 2 ' - ylidene ] acetic acid", "entity_type": "Chemical", "pos": [102, 213]}], "task": "NER"}
{"text": "The absorption band of this quinoidal thiophene dye appeared at longer wavelengths than those of dyes with similar pi - conjugation length , indicating the effective pi - conjugation through the quinoidal structure .", "entity": [{"entity": "quinoidal thiophene", "entity_type": "Chemical", "pos": [28, 47]}], "task": "NER"}
{"text": "Although the excited state of the quinoidal thiophene dye is deactivated within several picoseconds even in solution , the DSSCs using the quinoidal thiophene dye showed incident photon to current conversion efficiency ( IPCE ) values of more than 90 % , demonstrating the fast and efficient electron injection from the excited dye to TiO ( 2 ) .", "entity": [{"entity": "quinoidal thiophene", "entity_type": "Chemical", "pos": [34, 53]}, {"entity": "quinoidal thiophene", "entity_type": "Chemical", "pos": [139, 158]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [335, 344]}], "task": "NER"}
{"text": "By optimizing the fabrication conditions , the DSSC using this dye afforded a photoelectric conversion efficiency of 5 . 2 % , without enlarging the molecular size .", "entity": [], "task": "NER"}
{"text": "Oxidative stress and alteration of biochemical markers in liver and kidney by malathion in rat pups .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [78, 87]}], "task": "NER"}
{"text": "The present study was undertaken to determine the effects of malathion exposure through maternal milk on oxidative stress , functional an metabolic parameters in kidney and liver of rat pups .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [61, 70]}], "task": "NER"}
{"text": "We found that lactational exposure to malation ( 200 mg / kg , body weight ( bw ) ) induced an oxidative stress status assessed by an increase in malondialdhyde ( MDA ) content , reflecting lipoperoxidation , a decrease in thiol groups ' content as well as depletion of enzyme activities as a superoxide dismutase ( SOD ) and catalase ( CAT ) on postnatal days ( Pnds ) 21 and 51 .", "entity": [{"entity": "malation", "entity_type": "Chemical", "pos": [38, 46]}, {"entity": "malondialdhyde", "entity_type": "Chemical", "pos": [146, 160]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [163, 166]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [223, 228]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [293, 303]}], "task": "NER"}
{"text": "Moreover , the current study showed that malathion induced liver and kidney dysfunctions demonstrated by considerable increase in phosphatase alkaline ( PAL ) , aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) activities as well as total and direct bilirubin , creatinine urea and acid uric contents .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [41, 50]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [161, 170]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [200, 207]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [272, 281]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [284, 294]}, {"entity": "urea", "entity_type": "Chemical", "pos": [295, 299]}, {"entity": "acid uric", "entity_type": "Chemical", "pos": [304, 313]}], "task": "NER"}
{"text": "We also observed an increase in triglyceride ( TG ) , total cholesterol ( TC ) , low - density lipoprotein cholesterol ( LDL - C ) and a decrease in high - density lipoprotein cholesterol ( HDL - C ) in the plasma of treated rat pups .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [32, 44]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [60, 71]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [107, 118]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [176, 187]}], "task": "NER"}
{"text": "These findings evidenced that malathion exposure during lactation through maternal milk of rats pups induced kidney and liver oxidative stress as well as functional and metabolic disorders that play a role in the development of others pathologies as cardiovascular diseases and cancers .", "entity": [{"entity": "malathion", "entity_type": "Chemical", "pos": [30, 39]}], "task": "NER"}
{"text": "Interleukin - 10 involvement in exposure to low dose of benzene .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "OBJECTIVE : To establish if serum levels of interleukin - 10 ( IL - 10 ) in subjects exposed to benzene are connected with age , working years , and employment age .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [96, 103]}], "task": "NER"}
{"text": "METHODS : We evaluated serum levels of IL - 10 in 51 employees working in oil refinery ( group A ) and in 16 office workers who resided in the same area ( group B ) .", "entity": [], "task": "NER"}
{"text": "RESULTS : There was no statistically significant difference between serum concentrations of IL - 10 in groups A and B .", "entity": [], "task": "NER"}
{"text": "There was a statistically significant dependent relationship in group A between age , working years , and serum concentration of IL - 10 .", "entity": [], "task": "NER"}
{"text": "There was a statistically significant and positive dependent relationship in group A between serum concentration of IL - 10 and employment age .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : The role played by IL - 10 in benzene immune suppression may be relevant and attention should be directed toward assessment of age , working years , and employment age in benzene - exposed populations .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [44, 51]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [185, 192]}], "task": "NER"}
{"text": "Regulation of sodium and calcium in Daphnia magna exposed to silver nanoparticles .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "silver", "entity_type": "Chemical", "pos": [61, 67]}], "task": "NER"}
{"text": "The toxicity of manufactured silver nanoparticles ( AgNPs ) has been widely studied , but the influence of AgNPs on the major ions ( such as sodium [ Na ] and calcium [ Ca ] ) regulations are unknown .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [29, 35]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [141, 147]}, {"entity": "Na", "entity_type": "Chemical", "pos": [150, 152]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [159, 166]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [169, 171]}], "task": "NER"}
{"text": "In the present study , a freshwater cladoceran Daphnia magna was exposed to commercial AgNPs coated with polyvinylpyrrolidone .", "entity": [{"entity": "polyvinylpyrrolidone", "entity_type": "Chemical", "pos": [105, 125]}], "task": "NER"}
{"text": "After 48 h , the Na body content was significantly reduced by AgNO3 exposure , but the Ca body content was significantly increased under AgNO3 and AgNP exposures , respectively .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [17, 19]}, {"entity": "AgNO3", "entity_type": "Chemical", "pos": [62, 67]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [87, 89]}, {"entity": "AgNO3", "entity_type": "Chemical", "pos": [137, 142]}], "task": "NER"}
{"text": "No effect was observed on the body concentrations of Na and Ca at 50 to 500 micro g / L AgNPs with 1 - micro M cysteine addition .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [53, 55]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [60, 62]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "Exposure of AgNO3 and AgNPs inhibited the Na influx and elevated the Na efflux .", "entity": [{"entity": "AgNO3", "entity_type": "Chemical", "pos": [12, 17]}, {"entity": "Na", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "Na", "entity_type": "Chemical", "pos": [69, 71]}], "task": "NER"}
{"text": "In contrast , their exposure increased the Ca influx , but did not affect the Ca efflux .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [43, 45]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [78, 80]}], "task": "NER"}
{"text": "The results of the present study demonstrated the significant influences of AgNO3 and AgNPs ( without cysteine ) on Na and Ca regulations .", "entity": [{"entity": "AgNO3", "entity_type": "Chemical", "pos": [76, 81]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "Na", "entity_type": "Chemical", "pos": [116, 118]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [123, 125]}], "task": "NER"}
{"text": "Such effect of AgNPs on Na and Ca regulation disappeared after cysteine addition , indicating that the soluble Ag released from AgNPs played a major role in the ionoregulatory dysfunction .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [24, 26]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [31, 33]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [63, 71]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [111, 113]}], "task": "NER"}
{"text": "Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus - Merzbacher disease .", "entity": [], "task": "NER"}
{"text": "Missense mutations in the proteolipid protein 1 ( PLP1 ) gene cause a wide spectrum of hypomyelinating disorders , from mild spastic paraplegia type 2 to severe Pelizaeus - Merzbacher disease ( PMD ) .", "entity": [], "task": "NER"}
{"text": "Mutant PLP1 accumulates in the endoplasmic reticulum ( ER ) and induces ER stress .", "entity": [], "task": "NER"}
{"text": "However , the link between the clinical severity of PMD and the cellular response induced by mutant PLP1 remains largely unknown .", "entity": [], "task": "NER"}
{"text": "Accumulation of misfolded proteins in the ER generally leads to up - regulation of ER chaperones to alleviate ER stress .", "entity": [], "task": "NER"}
{"text": "Here , we found that expression of the PLP1 - A243V mutant , which causes severe disease , depletes some ER chaperones with a KDEL ( Lys - Asp - Glu - Leu ) motif , in HeLa cells , MO3 . 13 oligodendrocytic cells , and primary oligodendrocytes .", "entity": [{"entity": "Lys - Asp - Glu - Leu", "entity_type": "Chemical", "pos": [133, 154]}], "task": "NER"}
{"text": "The same PLP1 mutant also induces fragmentation of the Golgi apparatus ( GA ) .", "entity": [], "task": "NER"}
{"text": "These organelle changes are less prominent in cells with milder disease - associated PLP1 mutants .", "entity": [], "task": "NER"}
{"text": "Similar changes are also observed in cells expressing another disease - causing gene that triggers ER stress , as well as in cells treated with brefeldin A , which induces ER stress and GA fragmentation by inhibiting GA to ER trafficking .", "entity": [{"entity": "brefeldin A", "entity_type": "Chemical", "pos": [144, 155]}], "task": "NER"}
{"text": "We also found that mutant PLP1 disturbs localization of the KDEL receptor , which transports the chaperones with the KDEL motif from the GA to the ER .", "entity": [], "task": "NER"}
{"text": "These data show that PLP1 mutants inhibit GA to ER trafficking , which reduces the supply of ER chaperones and induces GA fragmentation .", "entity": [], "task": "NER"}
{"text": "We propose that depletion of ER chaperones and GA fragmentation induced by mutant misfolded proteins contribute to the pathogenesis of inherited ER stress - related diseases and affect the disease severity .", "entity": [], "task": "NER"}
{"text": "Topoisomerase II beta deficiency enhances camptothecin - induced apoptosis .", "entity": [{"entity": "camptothecin", "entity_type": "Chemical", "pos": [42, 54]}], "task": "NER"}
{"text": "Camptothecin ( CPT ) , a topoisomerase ( Top ) I - targeting drug that stabilizes Top1 - DNA covalent adducts , can induce S - phase - specific cytotoxicity due to the arrest of progressing replication forks .", "entity": [{"entity": "Camptothecin", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [15, 18]}], "task": "NER"}
{"text": "However , CPT - induced non - S - phase cytotoxicity is less well characterized .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "In this study , we have identified topoisomerase II beta ( Top2 beta ) as a specific determinant for CPT sensitivity , but not for many other cytotoxic agents , in non - S - phase cells .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "First , quiescent mouse embryonic fibroblasts ( MEFs ) lacking Top2 beta were shown to be hypersensitive to CPT with prominent induction of apoptosis .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Second , ICRF - 187 , a Top2 catalytic inhibitor known to deplete Top2 beta , specifically sensitized MEFs to CPT .", "entity": [{"entity": "ICRF - 187", "entity_type": "Chemical", "pos": [9, 19]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "To explore the molecular basis for CPT hypersensitivity in Top2 beta - deficient cells , we found that upon CPT exposure , the RNA polymerase II large subunit ( RNAP LS ) became progressively depleted , followed by recovery to nearly the original level in wild - type MEFs , whereas RNAP LS remained depleted without recovery in Top2 beta - deficient cells .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Concomitant with the reduction of the RNAP LS level , the p53 protein level was greatly induced .", "entity": [], "task": "NER"}
{"text": "Interestingly , RNAP LS depletion has been well documented to lead to p53 - dependent apoptosis .", "entity": [], "task": "NER"}
{"text": "Altogether , our findings support a model in which Top2 beta deficiency promotes CPT - induced apoptosis in quiescent non - S - phase cells , possibly due to RNAP LS depletion and p53 accumulation .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Two novel mutations in CYP11B1 and modeling the consequent alterations of the translated protein in classic congenital adrenal hyperplasia patients .", "entity": [], "task": "NER"}
{"text": "Mutations in the 11 beta - hydroxylase ( CYP11B1 ) gene are the second leading cause of congenital adrenal hyperplasia ( CAH ) , an autosomal recessive disorder characterized by adrenal insufficiency , virilization of female external genitalia , and hypertension with or without hypokalemic alkalosis .", "entity": [], "task": "NER"}
{"text": "Molecular analysis of CYP11B1 gene in CAH patients with 11 beta - hydroxylase deficiency was performed in this study .", "entity": [], "task": "NER"}
{"text": "Cycle sequencing of 9 exons in CYP11B1 was performed in 5 unrelated families with 11 beta - hydroxylase deficient children .", "entity": [], "task": "NER"}
{"text": "Three - dimensional models for the normal and mutant proteins and their affinity to their known substrates were examined .", "entity": [], "task": "NER"}
{"text": "Analysis of the CYP11B1 gene revealed two novel mutations , a small insertion in exon 7 ( InsAG393 ) and a small deletion in exon 2 ( DelG766 ) , and three previously known missense mutations ( T318M , Q356X , and R427H ) .", "entity": [], "task": "NER"}
{"text": "According to docking results , the affinity of the protein to its substrates is highly reduced by these novel mutations .", "entity": [], "task": "NER"}
{"text": "DelG766 has more negative impact on the protein in comparison to InsAG393 .", "entity": [], "task": "NER"}
{"text": "The novel mutations , InsAG393 and DelG766 , change the folding of the protein and disrupt the enzyme ' s active site as it was measured in the protein modeling and substrate binding analysis .", "entity": [], "task": "NER"}
{"text": "Molecular modeling and sequence conservation were predictive of clinical severity of the disease and correlated with the clinical diagnosis of the patients .", "entity": [], "task": "NER"}
{"text": "Isolation and synthesis of melodamide A , a new anti - inflammatory phenolic amide from the leaves of Melodorum fruticosum .", "entity": [{"entity": "melodamide A", "entity_type": "Chemical", "pos": [27, 39]}, {"entity": "phenolic amide", "entity_type": "Chemical", "pos": [68, 82]}], "task": "NER"}
{"text": "Together with twelve known compounds ( 2 - 13 ) , melodamide A ( 1 ) , a new phenolic amide possessing p - quinol moiety , was purified and characterized from the methanolic extracts of the leaves of Melodorum fruticosum .", "entity": [{"entity": "melodamide A", "entity_type": "Chemical", "pos": [50, 62]}, {"entity": "phenolic amide", "entity_type": "Chemical", "pos": [77, 91]}, {"entity": "p - quinol", "entity_type": "Chemical", "pos": [103, 113]}], "task": "NER"}
{"text": "The structure of melodamide A ( 1 ) was established with a combination of 2D NMR experiments , HR - ESI - MS and X - ray analyses .", "entity": [{"entity": "melodamide A", "entity_type": "Chemical", "pos": [17, 29]}], "task": "NER"}
{"text": "The other known compounds were identified by comparison of their spectroscopic and physical data with those reported in the literature .", "entity": [], "task": "NER"}
{"text": "Moreover , some isolated compounds were examined for their inhibitory activity towards superoxide anion generation and elastase release in human neutrophils .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [87, 97]}], "task": "NER"}
{"text": "Among the tested compounds , 1 , 3 , and 5 exhibited strong inhibition of superoxide anion generation with IC50 values ranging from 5 . 25 to 8 . 65 micro M .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [74, 84]}], "task": "NER"}
{"text": "Furthermore , synthesis and biological evaluation of melodamide A ( 1 ) and its analogs ( 14a - p ) were described .", "entity": [{"entity": "melodamide A", "entity_type": "Chemical", "pos": [53, 65]}], "task": "NER"}
{"text": "Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds .", "entity": [], "task": "NER"}
{"text": "In cancer tumors , growth , invasion , and formation of metastasis at a secondary site play a pivotal role , participating in diverse processes in the development of the pathology , such as degradation of extracellular matrix .", "entity": [], "task": "NER"}
{"text": "Bauhinia seeds contain relatively large quantities of peptidase inhibitors , and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species , B . bauhinoides cruzipain inhibitor , which is a cysteine and serine peptidase inhibitor , and B . bauhinioides kallikrein inhibitor , which is a serine peptidase inhibitor .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [231, 239]}, {"entity": "serine", "entity_type": "Chemical", "pos": [244, 250]}, {"entity": "serine", "entity_type": "Chemical", "pos": [328, 334]}], "task": "NER"}
{"text": "While recombinant B . bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L , recombinant B . bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "The effects of recombinant B . bauhinoides cruzipain inhibitor and recombinant B . bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5 - fluorouracil .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [265, 281]}], "task": "NER"}
{"text": "At 12 . 5 micro M concentration , recombinant B . bauhinoides cruzipain inhibitor and recombinant B . bauhinioides kallikrein inhibitor were more efficient than 5 - fluorouracil in inhibiting MKN - 28 and Hs746T ( gastric ) , HCT116 and HT29 ( colorectal ) , SkBr - 3 and MCF - 7 ( breast ) , and THP - 1 and K562 ( leukemia ) cell lines .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [161, 177]}], "task": "NER"}
{"text": "Additionally , recombinant B . bauhinoides cruzipain inhibitor inhibited 40 % of the migration of Hs746T , the most invasive gastric cell line , while recombinant B . bauhinioides kallikrein inhibitor did not affect cell migration .", "entity": [], "task": "NER"}
{"text": "Recombinant B . bauhinioides kallikrein inhibitor and recombinant B . bauhinoides cruzipain inhibitor , even at high doses , did not affect hMSC proliferation while 5 - fluorouracil greatly reduced the proliferation rates of hMSCs .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [165, 181]}], "task": "NER"}
{"text": "Therefore , both recombinant B . bauhinoides cruzipain inhibitor and recombinant B . bauhinioides kallikrein inhibitor might be considered for further studies to block peptidase activities in order to target specific peptidase - mediated growth and invasion characteristics of individual tumors , mainly in patients resistant to 5 - fluorouracil chemotherapy .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [329, 345]}], "task": "NER"}
{"text": "Mass spectrometry method to identify aging pathways of Sp - and Rp - tabun adducts on human butyrylcholinesterase based on the acid labile P - N bond .", "entity": [{"entity": "Sp - and Rp - tabun", "entity_type": "Chemical", "pos": [55, 74]}, {"entity": "P - N", "entity_type": "Chemical", "pos": [139, 144]}], "task": "NER"}
{"text": "The phosphoramidate nerve agent tabun inhibits butyrylcholinesterase ( BChE ) and acetylcholinesterase by making a covalent bond on the active site serine .", "entity": [{"entity": "phosphoramidate", "entity_type": "Chemical", "pos": [4, 19]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [32, 37]}, {"entity": "serine", "entity_type": "Chemical", "pos": [148, 154]}], "task": "NER"}
{"text": "The adduct loses an alkyl group in a process called aging .", "entity": [{"entity": "alkyl", "entity_type": "Chemical", "pos": [20, 25]}], "task": "NER"}
{"text": "The mechanism of aging of the tabun adduct is controversial .", "entity": [{"entity": "tabun", "entity_type": "Chemical", "pos": [30, 35]}], "task": "NER"}
{"text": "Some studies claim that aging proceeds through deamination , whereas crystal structure studies show aging by O - dealkylation .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [109, 110]}], "task": "NER"}
{"text": "Our goal was to develop a method that clearly distinguishes between deamination and O - dealkylation .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "We began by studying the tetraisopropyl pyrophosphoramide adduct of BChE because this adduct has two P - N bonds .", "entity": [{"entity": "tetraisopropyl pyrophosphoramide", "entity_type": "Chemical", "pos": [25, 57]}, {"entity": "P - N", "entity_type": "Chemical", "pos": [101, 106]}], "task": "NER"}
{"text": "Mass spectra showed that the P - N bonds were stable during trypsin digestion at pH 8 but were cleaved during pepsin digestion at pH 2 .", "entity": [{"entity": "P - N", "entity_type": "Chemical", "pos": [29, 34]}], "task": "NER"}
{"text": "The P - N bond in tabun was also acid labile , whereas the P - O bond was stable .", "entity": [{"entity": "P - N", "entity_type": "Chemical", "pos": [4, 9]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [18, 23]}, {"entity": "P - O", "entity_type": "Chemical", "pos": [59, 64]}], "task": "NER"}
{"text": "A scheme to distinguish aging by deamination from aging by O - dealkylation was based on the acid labile P - N bond .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [59, 60]}, {"entity": "P - N", "entity_type": "Chemical", "pos": [105, 110]}], "task": "NER"}
{"text": "BChE was inhibited with Sp - and Rp - tabun thiocholine nerve agent model compounds to make adducts identical to those of tabun with known stereochemistry .", "entity": [{"entity": "Sp - and Rp - tabun thiocholine", "entity_type": "Chemical", "pos": [24, 55]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [122, 127]}], "task": "NER"}
{"text": "After aging and digestion with pepsin at pH 2 , peptide FGES198AGAAS from Sp - tabun thiocholine had a mass of 902 . 2 m / z in negative mode , indicating that it had aged by deamination , whereas peptide FGES198AGAAS from Rp - tabun thiocholine had a mass of 874 . 2 m / z in negative mode , indicating that it had aged by O - dealkylation .", "entity": [{"entity": "Sp - tabun thiocholine", "entity_type": "Chemical", "pos": [74, 96]}, {"entity": "Rp - tabun thiocholine", "entity_type": "Chemical", "pos": [223, 245]}, {"entity": "O", "entity_type": "Chemical", "pos": [324, 325]}], "task": "NER"}
{"text": "BChE inhibited by authentic , racemic tabun yielded both 902 . 2 and 874 . 2 m / z peptides , indicating that both stereoisomers reacted with BChE and aged either by deamination or dealkylation .", "entity": [{"entity": "racemic tabun", "entity_type": "Chemical", "pos": [30, 43]}], "task": "NER"}
{"text": "Synthesis of antioxidants for prevention of age - related macular degeneration .", "entity": [], "task": "NER"}
{"text": "Photooxidation of A2E may be involved in diseases of the macula , and antioxidants could serve as therapeutic agents for these diseases .", "entity": [], "task": "NER"}
{"text": "Inhibitors of A2E photooxidation were prepared by Mannich reaction of the antioxidant quercetin .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [86, 95]}], "task": "NER"}
{"text": "These compounds contain water - solubilizing amine groups , and several were more potent inhibitors of A2E photooxidation than quercetin .", "entity": [{"entity": "amine", "entity_type": "Chemical", "pos": [45, 50]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [127, 136]}], "task": "NER"}
{"text": "The mannose 6 - phosphate - binding sites of M6P / IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells .", "entity": [{"entity": "mannose 6 - phosphate", "entity_type": "Chemical", "pos": [4, 25]}, {"entity": "M6P", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "The M6P ( mannose 6 - phosphate ) / IGF2R ( insulin - like growth factor II receptor ) interacts with a variety of factors that impinge on tumour invasion and metastasis .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "mannose 6 - phosphate", "entity_type": "Chemical", "pos": [10, 31]}], "task": "NER"}
{"text": "It has been shown that expression of wild - type M6P / IGF2R reduces the tumorigenic and invasive properties of receptor - deficient SCC - VII squamous cell carcinoma cells .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [49, 52]}], "task": "NER"}
{"text": "We have now used mutant forms of M6P / IGF2R to assess the relevance of the different ligand - binding sites of the receptor for its biological activities in this cellular system .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "The results of the present study demonstrate that M6P / IGF2R does not require a functional binding site for insulin - like growth factor II for inhibition of anchorage - independent growth and matrix invasion by SCC - VII cells .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "In contrast , the simultaneous mutation of both M6P - binding sites is sufficient to impair all cellular functions of the receptor tested .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "These findings highlight that the interaction between M6P / IGF2R and M6P - modified ligands is not only important for intracellular accumulation of lysosomal enzymes and formation of dense lysosomes , but is also crucial for the ability of the receptor to suppress SCC - VII growth and invasion .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "M6P", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "The present study also shows that some of the biological activities of M6P / IGF2R in SCC - VII cells strongly depend on a functional M6P - binding site within domain 3 , thus providing further evidence for the non - redundant cellular functions of the individual carbohydrate - binding domains of the receptor .", "entity": [{"entity": "M6P", "entity_type": "Chemical", "pos": [71, 74]}, {"entity": "M6P", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [264, 276]}], "task": "NER"}
{"text": "Recombinant Luteinizing Hormone supplementation in poor responders undergoing IVF : a systematic review and meta - analysis .", "entity": [], "task": "NER"}
{"text": "The results of several studies about the effectiveness of recombinant luteinizing hormone ( rLH ) supplementation in poor responder in vitro fertilization ( IVF ) patients were conflicting .", "entity": [], "task": "NER"}
{"text": "To evaluate the current available data regarding the efficacy of rLH supplementation in poor responders , a meta - analysis was performed .", "entity": [], "task": "NER"}
{"text": "A systemic search was performed without language limitation but restricted to randomized controlled trial ( RCT ) .", "entity": [], "task": "NER"}
{"text": "We mainly explored MEDLINE , EMBASE , CNKI and Cochrane Library for the relevant studies .", "entity": [], "task": "NER"}
{"text": "Three studies were considered eligible for inclusion .", "entity": [], "task": "NER"}
{"text": "The meta - analysis indicated that rLH supplementation did not increase the ongoing pregnancy rate in poor responders ( OR 1 . 30 , 95 % CI : 0 . 80 , 2 . 11 ) .", "entity": [], "task": "NER"}
{"text": "Furthermore , there was no significant difference in the number of oocytes retrieved , total dose of rFSH used , total duration of stimulation , number of retrieved metaphase II oocytes and cycle cancellation rate between the study and control groups .", "entity": [], "task": "NER"}
{"text": "In conclusions , the available evidence does not support the addition of rLH in poor responders treated with rFSH and GnRHa for IVF .", "entity": [], "task": "NER"}
{"text": "It was inconclusive .", "entity": [], "task": "NER"}
{"text": "Future research should be based on strict criteria to define poor responders , and large , well - designed RCTs are necessary to definitively answer the important question of whether there was need to use rLH in poor responders undergoing IVF .", "entity": [], "task": "NER"}
{"text": "Catalytic DNAs that harness violet light to repair thymine dimers in a DNA substrate .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "UV1C is an in vitro selected catalytic DNA that shows efficient photolyase activity , using light of < 310 nm wavelength to photo - reactivate CPD thymine dimers within a substrate DNA .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [147, 154]}], "task": "NER"}
{"text": "We show here that a minimal mutational strategy of substituting a guanine analogue , 6MI , for single guanine residues within UV1C extends the DNAzyme ' s activity into the violet region of the spectrum .", "entity": [{"entity": "guanine", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "guanine", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "These 6MI point mutant DNAzymes fall into three distinct functional classes , which photo - reactivate the thymine dimer along different pathways .", "entity": [{"entity": "thymine", "entity_type": "Chemical", "pos": [107, 114]}], "task": "NER"}
{"text": "Cumulatively , they reveal the modus operandi of the original UV1C DNAzyme to be a surprisingly versatile one .", "entity": [], "task": "NER"}
{"text": "The interchangeable properties of no less than six of the G --> 6MI point mutants highlight UV1C ' s built - in functional flexibility , which may serve as a starting point for the creation of efficient , visible light - harnessing , photolyase DNAzymes for either the prophylaxis or therapy of UV damage to human skin .", "entity": [], "task": "NER"}
{"text": "Supramolecular hydrogels from in situ host - guest inclusion between chemically modified cellulose nanocrystals and cyclodextrin .", "entity": [], "task": "NER"}
{"text": "When grafted beta - cyclodextrin is used as targeting sites , Pluronic polymers have been introduced on the surface of cellulose nanocrystals by means of inclusion interaction between beta - cyclodextrin and hydrophobic segment of the polymer .", "entity": [{"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [13, 32]}, {"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [184, 203]}], "task": "NER"}
{"text": "Because of the steric stabilization effect , surface poly ( ethylene glycol ) chains facilitate the dispersion and compatibility of nanocrystals , which also enhance the loading levels of nanocrystals in the hydrogel system .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [53, 77]}], "task": "NER"}
{"text": "Meanwhile , uncovered poly ( ethylene glycol ) segments render the participating inclusion of alpha - cyclodextrin for the architecture of in situ hydrogels .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [22, 46]}, {"entity": "alpha - cyclodextrin", "entity_type": "Chemical", "pos": [94, 114]}], "task": "NER"}
{"text": "Surface grafting and inclusion reactions were proved by solid ( 13 ) C NMR and FTIR .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "Grafting efficiency of beta - cyclodextrin and inclusion efficiency of Pluronic on the surface of nanocrystals were confirmed by UV spectroscopy and elemental analysis .", "entity": [{"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [23, 42]}], "task": "NER"}
{"text": "A significant enhancement of the structural and thermal stability of in situ hydrogels with high loading levels of modified nanocrystals ( > 5 . 77 wt % ) was observed by rheological analysis .", "entity": [], "task": "NER"}
{"text": "Further study reveals the performance and behavior of hydrogels under a different pH environment .", "entity": [], "task": "NER"}
{"text": "Finally , in situ hydrogels were used as drug carrier for in vitro release of doxorubicin and exhibit the behavior of prolonged drug release with special release kinetics .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [78, 89]}], "task": "NER"}
{"text": "Structure of polyelectrolyte brushes subject to normal electric fields .", "entity": [], "task": "NER"}
{"text": "Molecular dynamic simulations of salt - free polyelectrolyte brushes subject to external fields applied normal to the grafting substrate reveal the three - dimensional monomer and counterion distributions .", "entity": [], "task": "NER"}
{"text": "It is found that below a critical electric field , local electroneutrality holds for densely grafted brushes and the brush height remains independent of field intensity .", "entity": [], "task": "NER"}
{"text": "Above this critical field ( which scales as 1 / 3 with grafting density ) brush height increases smoothly , and the fraction of condensed counterions decreases .", "entity": [], "task": "NER"}
{"text": "The brush bifurcates into two subpopulations of stretched and collapsed chains when the grafting density is not low .", "entity": [], "task": "NER"}
{"text": "At intermediate grafting densities , the majority of chains are stretched and the minority are nonstretched .", "entity": [], "task": "NER"}
{"text": "At high grafting densities bifurcation and brush height growth occur consecutively .", "entity": [], "task": "NER"}
{"text": "The majority of the chains are nonstretched at high grafting densities .", "entity": [], "task": "NER"}
{"text": "Although not observed prior to overstretching of the chain model , it is predicted that the two subpopulations will re - merge to a single highly stretched phase when field intensity reaches a third critical value .", "entity": [], "task": "NER"}
{"text": "The ability to control subpopulations of chains suggests that utilizing electric fields normal to polyelectrolyte brushes holds potential as controllable gates in microfluidic devices .", "entity": [], "task": "NER"}
{"text": "Nanocomposites derived from montmorillonite and metallosupramolecular polyelectrolytes : modular compounds for electrorheological fluids .", "entity": [{"entity": "montmorillonite", "entity_type": "Chemical", "pos": [28, 43]}], "task": "NER"}
{"text": "Nanocomposites made from Na - montmorillonite and metallo - supramolecular polyelectrolytes ( MEPE ) based on nickel and ditopic bis - terpyridine ligands are prepared by an aqueous synthesis .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "montmorillonite", "entity_type": "Chemical", "pos": [30, 45]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [110, 116]}, {"entity": "bis - terpyridine", "entity_type": "Chemical", "pos": [129, 146]}], "task": "NER"}
{"text": "Intercalation is confirmed by IR - spectroscopy , thermogravimetric analysis , and X - ray powder diffraction .", "entity": [], "task": "NER"}
{"text": "The rheological response in the presence of an electric field of the dispersed nanocomposites in silicone oil is measured with a rheometer .", "entity": [], "task": "NER"}
{"text": "The nanocomposites show a distinct electrorheological effect depending on the concentration and the kind of intercalated species .", "entity": [], "task": "NER"}
{"text": "The effect occurs with a low content of active material while only very small currents are observed .", "entity": [], "task": "NER"}
{"text": "Adsorption and dilational rheology of mixed beta - casein / DoTAB layers formed by sequential and simultaneous adsorption at the water / hexane interface .", "entity": [{"entity": "DoTAB", "entity_type": "Chemical", "pos": [60, 65]}, {"entity": "hexane", "entity_type": "Chemical", "pos": [137, 143]}], "task": "NER"}
{"text": "The interfacial behavior of beta - casein ( beta CS ) has been investigated in presence of the cationic surfactant dodecyl trimethyl ammonium bromide ( DoTAB ) at the water / hexane interface and compared to that obtained for the water / air interface .", "entity": [{"entity": "dodecyl trimethyl ammonium bromide", "entity_type": "Chemical", "pos": [115, 149]}, {"entity": "DoTAB", "entity_type": "Chemical", "pos": [152, 157]}, {"entity": "hexane", "entity_type": "Chemical", "pos": [175, 181]}], "task": "NER"}
{"text": "The used experimental technique is a drop profile analysis tensiometer specially equipped with a coaxial double capillary , which allows investigation of sequential adsorption of individual components besides the traditional simultaneous adsorption of two species .", "entity": [], "task": "NER"}
{"text": "This method also provides the dilational rheological measurements based on low frequency harmonic drop oscillations .", "entity": [], "task": "NER"}
{"text": "The tensiometric results show that the equilibrium states of the mixed beta CS / DoTAB layers built up on the two different routes do not differ significantly , that is , the general compositions of the mixed layers are similar .", "entity": [{"entity": "DoTAB", "entity_type": "Chemical", "pos": [81, 86]}], "task": "NER"}
{"text": "However , the results of dilational rheology for the two adsorption strategies are remarkably different indicating different dynamic characteristics of the adsorbed layers .", "entity": [], "task": "NER"}
{"text": "These findings suggest that the respective mixed layers are more proteinlike if they are formed via sequential adsorption and more surfactant - like after simultaneous adsorption .", "entity": [], "task": "NER"}
{"text": "In contrast to the W / A interface , at the W / H interface proteins remain at the interface once adsorbed and cannot be displaced just by competitive adsorption of surfactants .", "entity": [], "task": "NER"}
{"text": "5 - Iodo - 2 - aminoindan ( 5 - IAI ) : chemistry , pharmacology , and toxicology of a research chemical producing MDMA - like effects .", "entity": [{"entity": "5 - Iodo - 2 - aminoindan", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "5 - IAI", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [115, 119]}], "task": "NER"}
{"text": "In 2010 , an internet snapshot of EMCDDA anticipated the presence of 5 - iodo - 2 - aminoindan ( 5 - IAI ) within the recreational drug market .", "entity": [{"entity": "5 - iodo - 2 - aminoindan", "entity_type": "Chemical", "pos": [69, 94]}, {"entity": "5 - IAI", "entity_type": "Chemical", "pos": [97, 104]}], "task": "NER"}
{"text": "In 2011 , this compound , a psychoactive derivative of 2 - aminoindane , was identified in recreational products sold in the United Kingdom .", "entity": [{"entity": "2 - aminoindane", "entity_type": "Chemical", "pos": [55, 70]}], "task": "NER"}
{"text": "5 - IAI is a rigid analogue of p - iodoamphetamine producing MDMA - like effects .", "entity": [{"entity": "5 - IAI", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "p - iodoamphetamine", "entity_type": "Chemical", "pos": [31, 50]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [61, 65]}], "task": "NER"}
{"text": "The aim of this paper is to summarize the clinical , pharmacological , and toxicological information about this new potential drug of abuse .", "entity": [], "task": "NER"}
{"text": "Morphine withdrawal produces ERK - dependent and ERK - independent epigenetic marks in neurons of the nucleus accumbens and lateral septum .", "entity": [{"entity": "Morphine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Epigenetic changes such as covalent modifications of histone proteins represent complex molecular signatures that provide a cellular memory of previously experienced stimuli without irreversible changes of the genetic code .", "entity": [], "task": "NER"}
{"text": "In this study we show that new gene expression induced in vivo by morphine withdrawal occurs with concomitant epigenetic modifications in brain regions critically involved in drug - dependent behaviors .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "We found that naloxone - precipitated withdrawal , but not chronic morphine administration , caused a strong induction of phospho - histone H3 immunoreactivity in the nucleus accumbens ( NAc ) shell / core and in the lateral septum ( LS ) , a change that was accompanied by augmented H3 acetylation ( lys14 ) in neurons of the NAc shell .", "entity": [{"entity": "naloxone", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [67, 75]}, {"entity": "phospho", "entity_type": "Chemical", "pos": [122, 129]}, {"entity": "lys14", "entity_type": "Chemical", "pos": [301, 306]}], "task": "NER"}
{"text": "Morphine withdrawal induced the phosphorylation of the epigenetic factor methyl - CpG - binding protein 2 ( MeCP2 ) in Ser421 both in the LS and the NAc shell .", "entity": [{"entity": "Morphine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "methyl", "entity_type": "Chemical", "pos": [73, 79]}, {"entity": "CpG", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "Ser421", "entity_type": "Chemical", "pos": [119, 125]}], "task": "NER"}
{"text": "These epigenetic changes were accompanied by the activation of members of the ERK pathway as well as increased expression of the immediate early genes ( IEG ) c - fos and activity - regulated cytoskeleton - associated protein ( Arc / Arg3 . 1 ) .", "entity": [], "task": "NER"}
{"text": "Using a pharmacological approach , we found that H3 phosphorylation and IEG expression were partially dependent on ERK activation , while MeCP2 phosphorylation was fully ERK - independent .", "entity": [], "task": "NER"}
{"text": "These findings provide new important information on the role of the ERK pathway in the regulation of epigenetic marks and gene expression that may concur to regulate in vivo the cellular changes underlying the onset of the opioid withdrawal syndrome .", "entity": [], "task": "NER"}
{"text": "Motivational properties of D2 and D3 dopamine receptors agonists and cocaine , but not with D1 dopamine receptors agonist and l - dopa , in bilateral 6 - OHDA - lesioned rat .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [69, 76]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "l - dopa", "entity_type": "Chemical", "pos": [126, 134]}, {"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [150, 158]}], "task": "NER"}
{"text": "Dopamine dysregulation syndrome in Parkinson ' s disease ( PD ) has been attributed to dopamine replacement therapy ( DRT ) .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "We hypothesize that DRT can induce a potential rewarding effect in an animal model of PD .", "entity": [], "task": "NER"}
{"text": "Using the conditioned place preference ( CPP ) paradigm , we investigated the motivational effects of l - dopa , dopamine receptor agonists ( DRAs ) , and cocaine in rat with a bilateral 6 - OHDA lesion of the nigrostriatal dopaminergic pathway .", "entity": [{"entity": "l - dopa", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [113, 121]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [155, 162]}, {"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [187, 195]}], "task": "NER"}
{"text": "In 6 - OHDA animals , D1 receptors agonist ( SKF81297 ) revealed significantly a conditioned place aversion ( CPA ) at 3 mg / kg and 9 mg / kg doses .", "entity": [{"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [3, 11]}, {"entity": "SKF81297", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "D2 receptors agonist ( bromocriptine ) induced both CPP and CPA at 1 mg / kg and 10 mg / kg doses respectively .", "entity": [{"entity": "bromocriptine", "entity_type": "Chemical", "pos": [23, 36]}], "task": "NER"}
{"text": "D3 receptors agonist ( PD128907 ) induced a CPP only at 1 mg / kg , comparable to that of cocaine .", "entity": [{"entity": "PD128907", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "Sham animals revealed biphasic CPP curves , with significant dose effect , for the intermediate dose of the 3 DRAs .", "entity": [], "task": "NER"}
{"text": "However , l - dopa induced no significant effect while cocaine induced CPP in both lesioned and sham animals .", "entity": [{"entity": "l - dopa", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "In conclusion , this study confirms the predominant roles of D2R class , and most specifically D3R subtypes , in rewarding properties of DRT .", "entity": [], "task": "NER"}
{"text": "New insight into the discharge mechanism of silicon - air batteries using electrochemical impedance spectroscopy .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "The mechanism of discharge termination in silicon - air batteries , employing a silicon wafer anode , a room - temperature fluorohydrogenate ionic liquid electrolyte and an air cathode membrane , is investigated using a wide range of tools .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [80, 87]}], "task": "NER"}
{"text": "EIS studies indicate that the interfacial impedance between the electrolyte and the silicon wafer increases upon continuous discharge .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "In addition , it is shown that the impedance of the air cathode - electrolyte interface is several orders of magnitude lower than that of the anode .", "entity": [], "task": "NER"}
{"text": "Equivalent circuit fitting parameters indicate the difference in the anode - electrolyte interface characteristics for different types of silicon wafers .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "Evolution of porous silicon surfaces at the anode and their properties , by means of estimated circuit parameters , is also presented .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [20, 27]}], "task": "NER"}
{"text": "Moreover , it is found that the silicon anode potential has the highest negative impact on the battery discharge voltage , while the air cathode potential is actually stable and invariable along the whole discharge period .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [32, 39]}], "task": "NER"}
{"text": "The discharge capacity of the battery can be increased significantly by mechanically replacing the silicon anode .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "The effect of apricots on the experimental cataract model formed by sodium selenite .", "entity": [{"entity": "sodium selenite", "entity_type": "Chemical", "pos": [68, 83]}], "task": "NER"}
{"text": "This study was designed in order to investigate whether sun dried apricots have a preventive effect on the experimental cataract model formed by sodium selenite in rats .", "entity": [{"entity": "sodium selenite", "entity_type": "Chemical", "pos": [145, 160]}], "task": "NER"}
{"text": "Fifty - nine Spraque - Dawley rat pups were divided into three groups .", "entity": [], "task": "NER"}
{"text": "Group 1 ( control group ) consisted of twenty rat pups , born from the rats nourished ad libitum .", "entity": [], "task": "NER"}
{"text": "Group 2 consisted of 18 newborn rats , born from the rats nourished ad libitum with 10 % sun dried natural apricots .", "entity": [], "task": "NER"}
{"text": "Group 3 consisted of 21 newborn rats , born from the rats nourished ad libitum .", "entity": [], "task": "NER"}
{"text": "Subcutaneous ( 30nmol / gr ) sodium selenite injection was applied to all the newborn rats except the control group ( Group 1 ) on postpartum day 10 .", "entity": [{"entity": "sodium selenite", "entity_type": "Chemical", "pos": [29, 44]}], "task": "NER"}
{"text": "Cataract development was graded by slit - lamp examination and photography .", "entity": [], "task": "NER"}
{"text": "Encapsulated lenses were analyzed for reduced glutathione ( GSH ) and malondialdehyde ( MDA ) , a marker of lipid per oxidation .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [46, 57]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [60, 63]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [70, 85]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "Lenses were also analyzed for total nitrite ( TN ) .", "entity": [{"entity": "nitrite", "entity_type": "Chemical", "pos": [36, 43]}], "task": "NER"}
{"text": "The presence of oxidative stress in selenite cataract development and its prevention by sun dried apricots .", "entity": [{"entity": "selenite", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Anti - inflammatory activity of patchouli alcohol in RAW264 . 7 and HT - 29 cells .", "entity": [{"entity": "patchouli alcohol", "entity_type": "Chemical", "pos": [32, 49]}], "task": "NER"}
{"text": "Patchouli alcohol ( PA ) is a chemical compound extracted from patchouli which belongs to the genus Pogostemon , herb of mint family .", "entity": [{"entity": "Patchouli alcohol", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Recently , it has been reported that PA inhibits the production of inflammatory mediators .", "entity": [], "task": "NER"}
{"text": "However , the biological mechanisms of PA for anti - inflammatory activities have not been studied .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated whether PA decreases the production of inflammatory mediators through downregulation of the NF - kappa B and ERK pathway .", "entity": [], "task": "NER"}
{"text": "Our data indicated that PA inhibits the over - expression of iNOS and IL - 6 in protein and mRNA levels in LPS - stimulated RAW264 . 7 and TNF - alpha stimulated HT - 29 cells .", "entity": [], "task": "NER"}
{"text": "PA inhibited I kappa B - alpha degradation and p65 nuclear translocation , and subsequently suppressed transcriptional activity of NF - kappa B in LPS - stimulated RAW264 . 7 and TNF - alpha - stimulated HT - 29 cells .", "entity": [], "task": "NER"}
{"text": "In addition , PA inhibited LPS - or TNF - alpha - stimulated ERK1 / 2 activation by decreasing phosphorylation of ERK1 / 2 .", "entity": [], "task": "NER"}
{"text": "These findings suggest that PA shows anti - inflammatory activities through suppressing ERK - mediated NF - kappa B pathway in mouse macrophage and human colorectal cancer cells .", "entity": [], "task": "NER"}
{"text": "ALDH16A1 is a novel non - catalytic enzyme that may be involved in the etiology of gout via protein - protein interactions with HPRT1 .", "entity": [], "task": "NER"}
{"text": "Gout , a common form of inflammatory arthritis , is strongly associated with elevated uric acid concentrations in the blood ( hyperuricemia ) .", "entity": [{"entity": "uric acid", "entity_type": "Chemical", "pos": [86, 95]}], "task": "NER"}
{"text": "A recent study in Icelanders identified a rare missense single nucleotide polymorphism ( SNP ) in the ALDH16A1 gene , ALDH16A1 * 2 , to be associated with gout and serum uric acid levels .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "uric acid", "entity_type": "Chemical", "pos": [170, 179]}], "task": "NER"}
{"text": "ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures .", "entity": [], "task": "NER"}
{"text": "ALDH16 genes are present in fish , amphibians , protista , bacteria but absent from archaea , fungi and plants .", "entity": [], "task": "NER"}
{"text": "In most mammalian species , two ALDH16A1 spliced variants ( ALDH16A1 , long form and ALDH16A1 _ v2 , short form ) have been identified and both are expressed in HepG - 2 , HK - 2 and HK - 293 human cell lines .", "entity": [], "task": "NER"}
{"text": "The ALDH16 proteins contain two ALDH domains ( as opposed to one in the other members of the superfamily ) , four transmembrane and one coiled - coil domains .", "entity": [], "task": "NER"}
{"text": "The active site of ALDH16 proteins from bacterial , frog and lower animals contain the catalytically important cysteine residue ( Cys - 302 ) ; this residue is absent from the mammalian and fish orthologs .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [111, 119]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [130, 133]}], "task": "NER"}
{"text": "Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine - guanine phosphoribosyltransferase ( HPRT1 ) protein , a key enzyme involved in uric acid metabolism and gout .", "entity": [{"entity": "hypoxanthine", "entity_type": "Chemical", "pos": [145, 157]}, {"entity": "guanine", "entity_type": "Chemical", "pos": [160, 167]}, {"entity": "uric acid", "entity_type": "Chemical", "pos": [239, 248]}], "task": "NER"}
{"text": "Interestingly , such protein - protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A1 * 2 .", "entity": [], "task": "NER"}
{"text": "These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1 * 2 carriers .", "entity": [], "task": "NER"}
{"text": "Kava for the Treatment of Generalized Anxiety Disorder RCT : Analysis of Adverse Reactions , Liver Function , Addiction , and Sexual Effects .", "entity": [], "task": "NER"}
{"text": "Presently , little is known about a number issues concerning kava ( Piper methysticum ) , including ( i ) whether kava has any withdrawal or addictive effects ; ( ii ) if genetic polymorphisms of the cytochrome ( CYP ) P450 2D6 liver enzyme moderates any potential adverse effects ; and ( iii ) if medicinal application of kava has any negative or beneficial effect on sexual function and experience .", "entity": [], "task": "NER"}
{"text": "The study design was a 6 - week , double - blind , randomized controlled trial ( n = 75 ) involving chronic administration of kava ( one tablet of kava twice per day ; 120 mg of kavalactones per day , titrated in non - response to two tablets of kava twice per day ; 240 mg of kavalactones ) or placebo for participants with generalized anxiety disorder .", "entity": [{"entity": "kavalactones", "entity_type": "Chemical", "pos": [178, 190]}, {"entity": "kavalactones", "entity_type": "Chemical", "pos": [277, 289]}], "task": "NER"}
{"text": "Results showed no significant differences across groups for liver function tests , nor were there any significant adverse reactions that could be attributed to kava .", "entity": [], "task": "NER"}
{"text": "No differences in withdrawal or addiction were found between groups .", "entity": [], "task": "NER"}
{"text": "Interesting , kava significantly increased female ' s sexual drive compared to placebo ( p = 0 . 040 ) on a sub - domain of the Arizona Sexual Experience Scale ( ASEX ) , with no negative effects seen in males .", "entity": [], "task": "NER"}
{"text": "Further , it was found that there was a highly significant correlation between ASEX reduction ( improved sexual function and performance ) and anxiety reduction in the whole sample .", "entity": [], "task": "NER"}
{"text": "Copyright (c) 2013 John Wiley & Sons , Ltd .", "entity": [], "task": "NER"}
{"text": "Evaluation of suppressive and pro - resolving effects of EPA and DHA in human primary monocytes and T - helper cells .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [57, 60]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "Despite their beneficial anti - inflammatory properties , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) may increase the infection risk at high doses , likely by generating an immune - depressed state .", "entity": [{"entity": "eicosapentaenoic acid", "entity_type": "Chemical", "pos": [58, 79]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "docosahexaenoic acid", "entity_type": "Chemical", "pos": [92, 112]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "To assess the contribution of different immune cell populations to the immunomodulatory fatty acid effect , we comparatively investigated several aspects of inflammation in human T - helper ( Th ) cells and monocytes .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [88, 98]}], "task": "NER"}
{"text": "Both fatty acids , but DHA to a lesser extent compared with EPA , selectively and dose - dependently reduced the percentage of cytokine - expressing Th cells in a peroxisome proliferator - activated receptor ( PPAR ) gamma - dependent fashion , whereas the expression of the cell surface marker CD69 was unaltered on activated T cells .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [5, 16]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "In monocytes , both EPA and DHA increased interleukin ( IL ) - 10 without affecting tumor necrosis factor ( TNF ) - alpha and IL - 6 .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "Cellular incorporation of EPA and DHA occurred mainly at the expense of arachidonic acid .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [72, 88]}], "task": "NER"}
{"text": "Concomitantly , thromboxane B ( TXB ) 2 and leukotriene B ( LTB ) 4 in supernatants decreased , while levels of TXB3 and LTB5 increased .", "entity": [{"entity": "thromboxane B", "entity_type": "Chemical", "pos": [16, 29]}, {"entity": "( TXB ) 2", "entity_type": "Chemical", "pos": [30, 39]}, {"entity": "leukotriene B", "entity_type": "Chemical", "pos": [44, 57]}, {"entity": "( LTB ) 4", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "TXB3", "entity_type": "Chemical", "pos": [112, 116]}, {"entity": "LTB5", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "This increase was independent of activation and in accordance with cyclooxygenase expression patterns in monocytes .", "entity": [], "task": "NER"}
{"text": "Moreover , EPA and DHA gave rise to a variety of mono - and trihydroxy derivatives of highly anti - inflammatory potential , such as resolvins and their precursors .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [11, 14]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "mono - and trihydroxy", "entity_type": "Chemical", "pos": [49, 70]}, {"entity": "resolvins", "entity_type": "Chemical", "pos": [133, 142]}], "task": "NER"}
{"text": "Our results suggest that EPA and DHA do not generally affect immune cell functions in an inhibitory manner but rather promote pro - resolving responses .", "entity": [{"entity": "EPA", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "Activation of islet autoreactive naive T cells in infants is influenced by homeostatic mechanisms and antigen presenting capacity .", "entity": [], "task": "NER"}
{"text": "Islet autoimmunity precedes type 1 diabetes onset .", "entity": [], "task": "NER"}
{"text": "We previously found that islet autoimmunity rarely starts before age six months but reaches its highest incidence already at around 1 year of age .", "entity": [], "task": "NER"}
{"text": "We now examine whether homeostatic expansion and immune competence changes seen in a maturating immune system may account for this marked variation in islet autoimmunity risk in the first year of life .", "entity": [], "task": "NER"}
{"text": "We found na i ve proinsulin - and GAD65 - responsive T cells in cord blood of healthy newborns , with highest responses observed in children with type 1 diabetes susceptible HLA - DRB1 / DQB1 genotypes .", "entity": [], "task": "NER"}
{"text": "Homeostatic expansion characteristics with increased IL - 7 concentrations and enhanced T cell responsiveness to IL - 7 were observed throughout the first year of life .", "entity": [], "task": "NER"}
{"text": "However , the ability of antigen - presenting cells to activate na i ve T cells was compromised at birth , and cord blood monocytes had low surface expression of CD40 and HLA class II .", "entity": [], "task": "NER"}
{"text": "In contrast , antigen presentation and expression of these molecules had reached competent adult levels by the high incidence age of 8 months .", "entity": [], "task": "NER"}
{"text": "We propose that temporal changes in islet autoimmunity seroconversion in infants are a consequence of the changing balance between homeostatic drive and antigen presentation competence .", "entity": [], "task": "NER"}
{"text": "These findings are relevant for early prevention of type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "Reduction of reactive oxygen species ameliorates metabolism - secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "We previously demonstrated that impaired glucose - induced insulin secretion ( IS ) and ATP elevation in islets of Goto - Kakizaki ( GK ) rats , a non - obese model of diabetes , were significantly restored by 30 ~ 60 min suppression of endogenous reactive oxygen species ( ROS ) overproduction .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [88, 91]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [257, 263]}], "task": "NER"}
{"text": "In this study , we investigated the effect of longer ( 12 h ) suppression of ROS on metabolism - secretion coupling in beta - cells by exposure to tempol , a superoxide dismutase mimic , plus ebselen , a glutathione peroxidase mimic ( TE - treatment ) .", "entity": [{"entity": "tempol", "entity_type": "Chemical", "pos": [147, 153]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [158, 168]}, {"entity": "ebselen", "entity_type": "Chemical", "pos": [192, 199]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [204, 215]}], "task": "NER"}
{"text": "In GK islets , both H ( 2 ) O ( 2 ) and superoxide were sufficiently reduced and glucose - induced IS and ATP elevation were improved by TE - treatment .", "entity": [{"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [20, 35]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [40, 50]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [81, 88]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "Glucose oxidation , an indicator of Krebs cycle velocity , also was improved by TE - treatment at high glucose , whereas glucokinase activity , which determines glycolytic velocity , was not affected .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "Lactate production was markedly increased in GK islets and TE - treatment reduced lactate production and protein expression of lactate dehydrogenase and hypoxia - inducible factor 1 alpha ( HIF1 alpha ) .", "entity": [{"entity": "Lactate", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [82, 89]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "These results indicate that the Warburg - like effect , which is characteristic of aerobic metabolism in cancer cells by which lactate is overproduced with reduced linking to mitochondria metabolism , plays an important role in impaired metabolism - secretion coupling in diabetic beta - cells and suggest that ROS reduction can improve mitochondrial metabolism by suppressinglactate overproduction through inhibition of HIF1 alpha stabilization .", "entity": [{"entity": "lactate", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "suppressinglactate", "entity_type": "Chemical", "pos": [365, 383]}], "task": "NER"}
{"text": "The type 2 diabetes associated gene Ide is required for insulin secretion and suppression of alpha - synuclein levels in beta - cells .", "entity": [], "task": "NER"}
{"text": "Genome wide association studies have identified several type 2 diabetes ( T2D ) risk loci linked to impaired beta - cell function .", "entity": [], "task": "NER"}
{"text": "The identity and function of the causal genes in these susceptibility loci remain , however , elusive .", "entity": [], "task": "NER"}
{"text": "The HHEX / IDE T2D locus is associated with decreased insulin secretion in response to oral glucose stimulation in humans .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "Here we have assessed beta - cell function in Ide knock - out ( KO ) mice .", "entity": [], "task": "NER"}
{"text": "We find that glucose stimulated insulin secretion ( GSIS ) is decreased in Ide KO mice due to impaired replenishment of the releasable pool of granules and that the Ide gene is haploinsufficient .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [13, 20]}], "task": "NER"}
{"text": "We also show that autophagic flux and microtubule content is reduced in beta - cells of Ide KO mice .", "entity": [], "task": "NER"}
{"text": "One important cellular role for IDE involves the neutralization of amyloidogenic proteins and we find that alpha - synuclein and IDE levels are inversely correlated in beta - cells of Ide KO mice and T2D patients .", "entity": [], "task": "NER"}
{"text": "Moreover , we provide evidence that both gain - and loss - of - function of alpha - synuclein in beta - cells in vivo not only impair GSIS but also autophagy .", "entity": [], "task": "NER"}
{"text": "Together , these data identify the Ide gene as a regulator of GSIS , suggest a molecular mechanism for beta - cell degeneration as a consequence of Ide deficiency , and additionally corroborates and extends a previously established important role for alpha - synuclein in beta - cell function .", "entity": [], "task": "NER"}
{"text": "Enhanced NF kappa B Activity Impairs Vascular Function through PARP - 1 , SP - 1 and COX2 - Dependent Mechanisms in Type 2 Diabetes .", "entity": [], "task": "NER"}
{"text": "Type 2 diabetes ( T2D ) is associated with vascular dysfunction .", "entity": [], "task": "NER"}
{"text": "We hypothesized that increased nuclear factor kappa B ( NF kappa B ) signaling contributes to vascular dysfunction in T2D .", "entity": [], "task": "NER"}
{"text": "We have treated type 2 diabetic ( db ( - ) / db ( - ) ) and control ( db ( - ) / db ( + ) ) mice with two NF kappa B inhibitors ( DHMEQ , 6mg / kg , twice a week and IKK - NBD peptide , 500 mu g / kg / day ) for four weeks .", "entity": [{"entity": "DHMEQ", "entity_type": "Chemical", "pos": [130, 135]}], "task": "NER"}
{"text": "Pressure - induced myogenic tone ( MT ) was significantly potentiated , while endothelium dependent relaxation ( EDR ) was impaired in small coronary arterioles ( CA ) and mesenteric resistance artery ( MRA ) from diabetic mice compared to control .", "entity": [], "task": "NER"}
{"text": "Interestingly , diabetic mice treated with NF kappa B inhibitors significantly reduced MT potentiation and improved EDR .", "entity": [], "task": "NER"}
{"text": "Importantly , vascular function was also rescued in db ( - ) / db ( - p50NF kappa B - / - ) and db ( - ) / db ( - PARP - 1 - / - ) double knockout mice compared to db ( - ) / db ( - ) mice .", "entity": [], "task": "NER"}
{"text": "Additionally , the acute in vitro down regulation of NF kappa B - p65 using p65NF kappa B shRNA lentivirus in arteries from db ( - ) / db ( - ) mice also improved vascular function .", "entity": [], "task": "NER"}
{"text": "The NF kappa B inhibition did not affect blood glucose level and body weight .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [47, 54]}], "task": "NER"}
{"text": "The RNA levels for Sp - 1 and eNOS phosphorylation were decreased , while p65NF kappa B phosphorylation , cleaved PARP - 1 and COX - 2 expression were increased in arteries from diabetic mice , which were restored after NF kappa B inhibition and in db ( - ) / db ( - p50NF kappa B - / - ) and db ( - ) / db ( - PARP - 1 - / - ) mice . In the present study , we provided evidence that enhanced NF kappa B activity impairs vascular function by PARP - 1 , Sp - 1 and COX - 2 - dependent mechanisms in male type 2 diabetic mice .", "entity": [], "task": "NER"}
{"text": "Therefore , NF kappa B could be a potential target to overcome diabetes - induced vascular dysfunction .", "entity": [], "task": "NER"}
{"text": "Intracellular drug release from curcumin - loaded PLGA nanoparticles induces G2 / M block in breast cancer cells .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [32, 40]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases , thanks to their in vivo stability and tumor localization exploiting the well - documented \" enhanced permeation and retention \" ( EPR ) effect .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "In this paper , we have developed uniform curcumin - bearing PLGA nanoparticles by a single - emulsion process , which exhibited a curcumin release following a Fickian - law diffusion over 10 days in vitro .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [61, 65]}, {"entity": "curcumin", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "PLGA nanoparticles were about 120 nm in size , as determined by dynamic light scattering , with a surface negative charge of - 30 mV .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt % .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "PLGA encapsulation provided efficient protection of curcumin from environment , as determined by fluorescence emission experiments .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "curcumin", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Next , we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2 / M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm , which provided direct evidence on the mechanism of action of our nanocomplex .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [188, 196]}], "task": "NER"}
{"text": "This study was carried out using Annexin V - based cell death analysis , MTT assessment of proliferation , flow cytometry , and confocal laser scanning microscopy .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "PLGA nanoparticles proved to be completely safe , suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "curcumin", "entity_type": "Chemical", "pos": [158, 166]}], "task": "NER"}
{"text": "Molecular reorganization in organic field - effect transistors and its effect on two - dimensional charge transport pathways .", "entity": [], "task": "NER"}
{"text": "Charge transport in organic thin film transistors takes place in the first few molecular layers in contact with the gate dielectric .", "entity": [], "task": "NER"}
{"text": "Here we demonstrate that the charge transport pathways in these devices are extremely sensitive to the orientational defects of the first monolayers , which arise from specific growth conditions .", "entity": [], "task": "NER"}
{"text": "Although these defects partially heal during the growth , they cause depletion of charge carriers in the first monolayer , and drive the current to flow in the monolayers above the first one .", "entity": [], "task": "NER"}
{"text": "Moreover , the residual defects induce lower crystalline order and charge mobility .", "entity": [], "task": "NER"}
{"text": "These results , which are not intuitively explained by electrostatics arguments , have been obtained by combining in situ real time structural and electrical characterization together with ex situ AFM measurements , on thin films of a relevant n - type organic semiconductor , N , N ' - bis ( n - octyl ) - dicyanoperylene - 3 , 4 : 9 , 10 - bis dicarboximide grown by sublimation in a quasi - layer - by - layer mode at different substrate temperatures .", "entity": [{"entity": "N , N ' - bis ( n - octyl ) - dicyanoperylene - 3 , 4 : 9 , 10 - bis dicarboximide", "entity_type": "Chemical", "pos": [277, 359]}], "task": "NER"}
{"text": "Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma : From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA .", "entity": [], "task": "NER"}
{"text": "Epstein - Barr virus ( EBV ) infects more than 90 % of the world population .", "entity": [], "task": "NER"}
{"text": "Following primary infection , Epstein - Barr virus persists in an asymptomatic latent state .", "entity": [], "task": "NER"}
{"text": "Occasionally , it may switch to lytic infection .", "entity": [], "task": "NER"}
{"text": "Latent EBV infection has been associated with several diseases , such as Burkitt lymphoma ( BL ) .", "entity": [], "task": "NER"}
{"text": "To date , there are no available drugs to target latent EBV , and the existing broad - spectrum antiviral drugs are mainly active against lytic viral infection .", "entity": [], "task": "NER"}
{"text": "Thus , using computational molecular docking , a virtual screen of a library of small molecules , including xanthones and flavonoids ( described with potential for antiviral activity against EBV ) , was carried out targeting EBV proteins .", "entity": [{"entity": "xanthones", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [122, 132]}], "task": "NER"}
{"text": "The more interesting molecules were selected for further computational analysis , and sub - sequently , the compounds were tested in the Raji ( BL ) cell line , to evaluate their activity against latent EBV .", "entity": [], "task": "NER"}
{"text": "This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL .", "entity": [], "task": "NER"}
{"text": "Therefore , the in silico screening presents a good approach for the development of new anti - EBV agents .", "entity": [], "task": "NER"}
{"text": "Genome wide association studies for diabetes : perspective on results and challenges .", "entity": [], "task": "NER"}
{"text": "Recent results of genome wide association study ( GWAS ) for diabetes genes , while reaching impressive technical milestones and implicating new findings for research , have been uniformly disappointing in terms of immediate clinical utility .", "entity": [], "task": "NER"}
{"text": "The relative risk associated with any of the newly reported genetic loci , or even considering all of them together , is far less than simply that which can be obtained by taking a history and a physical exam .", "entity": [], "task": "NER"}
{"text": "For type 2 diabetes ( T2D ) , GWAS have implicated novel pathways , supported previously known associations , and highlighted the importance of the beta cell and insulin secretion .", "entity": [], "task": "NER"}
{"text": "Monogenic forms of diabetes , on the other hand , continue to yield interesting insights into genes controlling human beta cell function but most cases of monogenic diabetes are simply not diagnosed .", "entity": [], "task": "NER"}
{"text": "Here , we briefly review recent results related to type 1 , type 2 and maturity onset diabetes of youth ( MODY ) diabetes and suggest that future studies emphasizing quantitative traits are likely to yield even more insights .", "entity": [], "task": "NER"}
{"text": "Chiral bicyclic tetramates as non - planar templates for chemical library synthesis .", "entity": [], "task": "NER"}
{"text": "Chemoselective Dieckmann cyclization reactions may be used on oxazolidine and thiazolidine templates derived from various aldehydes to access bicyclic tetramates , which have potential as templates for chemical library construction .", "entity": [{"entity": "oxazolidine", "entity_type": "Chemical", "pos": [62, 73]}, {"entity": "thiazolidine", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [122, 131]}], "task": "NER"}
{"text": "Bioassay against Staphylococcus aureus and Escherichia coli showed that these systems have little or no intrinsic antibacterial bioactivity .", "entity": [], "task": "NER"}
{"text": "Pyrrolopyrazines as Selective Spleen Tyrosine Kinase Inhibitors .", "entity": [{"entity": "Pyrrolopyrazines", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "Tyrosine", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies .", "entity": [{"entity": "pyrrolopyrazines", "entity_type": "Chemical", "pos": [37, 53]}], "task": "NER"}
{"text": "Ultimately , our mouse model revealed unexpected toxicity that precluded us from further advancing this series .", "entity": [], "task": "NER"}
{"text": "Termini of bottom - up fabricated graphene nanoribbons .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "Atomically precise graphene nanoribbons ( GNRs ) can be obtained via thermally induced polymerization of suitable precursor molecules on a metal surface .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [19, 27]}], "task": "NER"}
{"text": "This communication discusses the atomic structure found at the termini of armchair GNRs obtained via this bottom - up approach .", "entity": [], "task": "NER"}
{"text": "The short zigzag edge at the termini of the GNRs under study gives rise to a localized midgap state with a characteristic signature in scanning tunneling microscopy ( STM ) .", "entity": [], "task": "NER"}
{"text": "By combining STM experiments with large - scale density functional theory calculations , we demonstrate that the termini are passivated by hydrogen .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "Our results suggest that the length of nanoribbons grown by this protocol may be limited by hydrogen passivation during the polymerization step .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "Copper ( I ) - catalyzed borylative exo - cyclization of alkenyl halides containing unactivated double bond .", "entity": [{"entity": "Copper ( I )", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "alkenyl halides", "entity_type": "Chemical", "pos": [57, 72]}], "task": "NER"}
{"text": "A borylative exo - cyclization of alkenyl halides has been reported .", "entity": [{"entity": "alkenyl halides", "entity_type": "Chemical", "pos": [34, 49]}], "task": "NER"}
{"text": "The reaction includes the regioselective addition of a borylcopper ( I ) intermediate to unactivated terminal alkenes , followed by the intramolecular substitution of the resulting alkylcopper ( I ) moiety for the halide leaving groups .", "entity": [{"entity": "borylcopper ( I )", "entity_type": "Chemical", "pos": [55, 72]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [110, 117]}, {"entity": "alkylcopper ( I )", "entity_type": "Chemical", "pos": [181, 198]}, {"entity": "halide", "entity_type": "Chemical", "pos": [214, 220]}], "task": "NER"}
{"text": "Experimental and theoretical investigations of the reaction mechanism have also been described .", "entity": [], "task": "NER"}
{"text": "This reaction provides a new method for the synthesis of alkylboronates containing strained cycloalkyl structures from simple starting materials .", "entity": [{"entity": "alkylboronates", "entity_type": "Chemical", "pos": [57, 71]}], "task": "NER"}
{"text": "Chemogenomics Approaches to Rationalizing the Mode - of - Action of Traditional Chinese and Ayurvedic Medicines .", "entity": [], "task": "NER"}
{"text": "Traditional Chinese medicine ( TCM ) and Ayurveda have been used in humans for thousands of years .", "entity": [], "task": "NER"}
{"text": "While the link to a particular indication has been established in man , the mode - of - action ( MOA ) of the formulations often remains unknown .", "entity": [], "task": "NER"}
{"text": "In this study , we aim to understand the MOA of formulations used in traditional medicine using an in silico target prediction algorithm , which aims to predict protein targets ( and hence MOAs ) , given the chemical structure of a compound .", "entity": [], "task": "NER"}
{"text": "Following this approach we were able to establish several links between suggested MOAs and experimental evidence .", "entity": [], "task": "NER"}
{"text": "In particular , compounds from the ' tonifying and replenishing medicinal ' class from TCM exhibit a hypoglycemic effect which can be related to activity of the ingredients against the Sodium - Glucose Transporters ( SGLT ) 1 and 2 as well as Protein Tyrosine Phosphatase ( PTP ) .", "entity": [{"entity": "Sodium", "entity_type": "Chemical", "pos": [185, 191]}, {"entity": "Glucose", "entity_type": "Chemical", "pos": [194, 201]}, {"entity": "Tyrosine", "entity_type": "Chemical", "pos": [251, 259]}], "task": "NER"}
{"text": "Similar results were obtained for Ayurvedic anticancer drugs .", "entity": [], "task": "NER"}
{"text": "Here , both primary anticancer targets ( those directly involved in cancer pathogenesis ) such as steroid - 5 - alpha - reductase 1 and 2 were predicted as well as targets which act synergistically with the primary target , such as the efflux pump P - glycoprotein ( P - gp ) .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [98, 105]}], "task": "NER"}
{"text": "In addition , we were able to elucidate some targets which may point us to novel MOAs as well as explain side effects .", "entity": [], "task": "NER"}
{"text": "Most notably , GPBAR1 , which was predicted as a target for both ' tonifying and replenishing medicinal ' and anticancer classes , suggests an influence of the compounds on metabolism .", "entity": [], "task": "NER"}
{"text": "Understanding the MOA of these compounds is beneficial as it provides a resource for NMEs with possibly higher efficacy in the clinic than those identified by single - target biochemical assays .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetics , tissue distribution and excretion study of resveratrol and its prodrug 3 , 5 , 4 ' - tri - O - acetylresveratrol in rats .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [62, 73]}, {"entity": "3 , 5 , 4 ' - tri - O - acetylresveratrol", "entity_type": "Chemical", "pos": [90, 131]}], "task": "NER"}
{"text": "3 , 5 , 4 ' - Tri - O - acetylresveratrol ( TARES ) synthesized by acetylating three hydroxyl groups of resveratrol ( RES ) is a prodrug of RES .", "entity": [{"entity": "3 , 5 , 4 ' - Tri - O - acetylresveratrol", "entity_type": "Chemical", "pos": [0, 41]}, {"entity": "TARES", "entity_type": "Chemical", "pos": [44, 49]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [104, 115]}, {"entity": "RES", "entity_type": "Chemical", "pos": [118, 121]}, {"entity": "RES", "entity_type": "Chemical", "pos": [140, 143]}], "task": "NER"}
{"text": "The aim of this study was to investigate and compare the pharmacokinetics , tissue distribution and excretion of TARES and RES in rats following a single intragastric gavage ( i . g . ) administration .", "entity": [{"entity": "TARES", "entity_type": "Chemical", "pos": [113, 118]}, {"entity": "RES", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "After RES is transformed into TARES , its pharmacokinetic properties are improved , such as the t1 / 2 has been prolonged and the AUC has been enhanced .", "entity": [{"entity": "RES", "entity_type": "Chemical", "pos": [6, 9]}, {"entity": "TARES", "entity_type": "Chemical", "pos": [30, 35]}], "task": "NER"}
{"text": "And TARES follows linear plasma pharmacokinetics across the investigated dosage range in rats ( 77 . 5 - 310mg / kg ) .", "entity": [{"entity": "TARES", "entity_type": "Chemical", "pos": [4, 9]}], "task": "NER"}
{"text": "The major distribution tissues of TARES or RES in rats were liver , spleen , heart and lung .", "entity": [{"entity": "TARES", "entity_type": "Chemical", "pos": [34, 39]}, {"entity": "RES", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "TARES can increase the content of RES in lung significantly .", "entity": [{"entity": "TARES", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "RES", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "There was no long - term accumulation of RES in rat tissues .", "entity": [{"entity": "RES", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "Whether we administrated to rats of equimolar TARES or RES , total recoveries of RES in urine and feces within 36h were low ( 0 . 99 % or 0 . 07 % in urine and 1 . 69 % or 0 . 15 % in feces ) .", "entity": [{"entity": "TARES", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "RES", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "RES", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Biofilm inhibitors that target amyloid proteins .", "entity": [], "task": "NER"}
{"text": "Bacteria establish stable communities , known as biofilms , that are resistant to antimicrobials .", "entity": [], "task": "NER"}
{"text": "Biofilm robustness is due to the presence of an extracellular matrix , which for several species - among them Bacillus subtilis - includes amyloid - like protein fibers .", "entity": [], "task": "NER"}
{"text": "In this work , we show that B . subtilis biofilms can be a simple and reliable tool for screening of molecules with antiamyloid activity .", "entity": [], "task": "NER"}
{"text": "We identified two molecules , AA - 861 and parthenolide , which efficiently inhibited biofilms by preventing the formation of amyloid - like fibers .", "entity": [{"entity": "AA - 861", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "parthenolide", "entity_type": "Chemical", "pos": [43, 55]}], "task": "NER"}
{"text": "Parthenolide also disrupted pre - established biofilms .", "entity": [{"entity": "Parthenolide", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "These molecules also impeded the formation of biofilms of other bacterial species that secrete amyloid proteins , such as Bacillus cereus and Escherichia coli .", "entity": [], "task": "NER"}
{"text": "Furthermore , the identified molecules decreased the conversion of the yeast protein New1 to the prion state in a heterologous host , indicating the broad range of activity of the molecules .", "entity": [], "task": "NER"}
{"text": "Development of amino - pyrimidine inhibitors of c - Jun N - terminal kinase ( JNK ) : kinase profiling guided optimization of a 1 , 2 , 3 - benzotriazole lead .", "entity": [{"entity": "amino - pyrimidine", "entity_type": "Chemical", "pos": [15, 33]}, {"entity": "N", "entity_type": "Chemical", "pos": [56, 57]}, {"entity": "1 , 2 , 3 - benzotriazole", "entity_type": "Chemical", "pos": [128, 153]}], "task": "NER"}
{"text": "A series of amino - pyrimidines was developed based upon an initial kinase cross - screening hit from a CDK2 program .", "entity": [{"entity": "amino - pyrimidines", "entity_type": "Chemical", "pos": [12, 31]}], "task": "NER"}
{"text": "Kinase profiling and structure - based drug design guided the optimization from the initial 1 , 2 , 3 - benzotriazole hit to a potent and selective JNK inhibitor , compound 24f ( JNK1 and 2 IC ( 50 ) = 16 and 66 nM , respectively ) , with bioavailability in rats and suitable for further in vivo pharmacological evaluation .", "entity": [{"entity": "1 , 2 , 3 - benzotriazole", "entity_type": "Chemical", "pos": [92, 117]}], "task": "NER"}
{"text": "Comparative properties of A beta 1 - 42 , A beta 11 - 42 , and [ Pyr (1) (1) ] A beta 11 - 42 generated from O - acyl isopeptides .", "entity": [{"entity": "O - acyl", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "The use of water - soluble O - acyl isopeptides enabled us to investigate the biochemical properties of A beta 11 - 42 species , by preparing highly concentrated stock solutions after a pretreatment .", "entity": [{"entity": "O - acyl", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "A beta 11 - 42 and [ Pyr ( 11 ) ] A beta 11 - 42 showed comparable aggregation capability and cytotoxicity , suggesting that the pyroglutamate modification at Glu ( 11 ) does not have a crucial role in these events .", "entity": [{"entity": "Pyr", "entity_type": "Chemical", "pos": [21, 24]}, {"entity": "pyroglutamate", "entity_type": "Chemical", "pos": [129, 142]}, {"entity": "Glu", "entity_type": "Chemical", "pos": [159, 162]}], "task": "NER"}
{"text": "However , given that A beta 11 - 42 is converted to [ Pyr ( 11 ) ] A beta 11 - 42 by a glutamyl cyclase in vivo , the potential aggregative and cytotoxic nature of [ Pyr ( 11 ) ] A beta 11 - 42 that was observed in the present study provides valuable insights into the pathological functions of pyroglutamate - modified A beta species in Alzheimer ' s disease .", "entity": [{"entity": "Pyr", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "glutamyl", "entity_type": "Chemical", "pos": [87, 95]}, {"entity": "Pyr", "entity_type": "Chemical", "pos": [166, 169]}, {"entity": "pyroglutamate", "entity_type": "Chemical", "pos": [295, 308]}], "task": "NER"}
{"text": "Menopause , atherosclerosis , and coronary artery disease .", "entity": [], "task": "NER"}
{"text": "Women have coronary heart disease ( CHD ) later than men .", "entity": [], "task": "NER"}
{"text": "This review describes studies of CHD risk factors or outcomes based on studies of premenopausal women followed through the menopause transition , and prospective cohort studies of younger or older women with CHD risk markers or disease outcomes in the context of their menopause history .", "entity": [], "task": "NER"}
{"text": "Major early reports from both types of studies are included in order to put more recent work in context .", "entity": [], "task": "NER"}
{"text": "Most attention has been paid to the Healthy Women Study ( HWS ) , Study of Women ' s Health across the Nation ( SWAN ) , the Nurses ' Health Study ( NHS ) , and the Rancho Bernardo Study ( RBS ) because they continue to produce recent publications designed to distinguish the effect of age from the effect of menopause .", "entity": [], "task": "NER"}
{"text": "Understanding these differences has important implications for women ' s cardiovascular health , but remains incomplete .", "entity": [], "task": "NER"}
{"text": "Transition studies have relatively short ( < 10 years ) follow - up and exclude women with surgical menopause .", "entity": [], "task": "NER"}
{"text": "Cohort studies suggest that women with oophorectomy are at greater risk for CHD than intact women , pointing to a greater risk from testosterone deficiency than from estradiol levels .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [132, 144]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [166, 175]}], "task": "NER"}
{"text": "Perfluorocarbon - loaded lipid nanocapsules as oxygen sensors for tumor tissue pO ( 2 ) assessment .", "entity": [{"entity": "Perfluorocarbon", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "The assessment of tumor oxygenation is a crucial factor in cancer therapy and may be carried out using fluorine MRI once fluorine probes have been distributed within the tumor .", "entity": [{"entity": "fluorine", "entity_type": "Chemical", "pos": [103, 111]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [121, 129]}], "task": "NER"}
{"text": "However , the deposit of those highly fluorinated compounds often jeopardizes anatomical image quality and requires emulsification of the probes .", "entity": [], "task": "NER"}
{"text": "Due to the high density and the high lipophilicity of perfluorocarbons , nanoemulsion of these molecules usually requires high - energy processes .", "entity": [{"entity": "perfluorocarbons", "entity_type": "Chemical", "pos": [54, 70]}], "task": "NER"}
{"text": "In the present work , we discuss the synthesis and the physico - chemical characterization of perfluorocarbon nanocapsules using a low - energy phase - inversion process .", "entity": [{"entity": "perfluorocarbon", "entity_type": "Chemical", "pos": [94, 109]}], "task": "NER"}
{"text": "The nanocapsules were tested on a mouse tumor brain model to assess oxygenation .", "entity": [], "task": "NER"}
{"text": "Ultrasonic gene and drug delivery using eLiposomes .", "entity": [], "task": "NER"}
{"text": "eLiposomes are liposomes encapsulating emulsions and therapeutics for targeted delivery .", "entity": [], "task": "NER"}
{"text": "By applying ultrasound to eLiposomes , emulsion droplets can transform from liquid to gas and rupture the lipid bilayer of the eLiposome to release a drug or plasmid .", "entity": [], "task": "NER"}
{"text": "In this study , perfluoropentane ( PFC5 ) emulsions were encapsulated inside folated eLiposomes carrying a model drug ( calcein ) or a model GFP plasmid to examine the effects of a folate ligand , PFC5 emulsion and various ultrasonic acoustic parameters in drug delivery and gene transfection into HeLa cells .", "entity": [{"entity": "perfluoropentane", "entity_type": "Chemical", "pos": [16, 32]}, {"entity": "PFC5", "entity_type": "Chemical", "pos": [35, 39]}, {"entity": "calcein", "entity_type": "Chemical", "pos": [120, 127]}, {"entity": "folate", "entity_type": "Chemical", "pos": [181, 187]}, {"entity": "PFC5", "entity_type": "Chemical", "pos": [197, 201]}], "task": "NER"}
{"text": "Confocal microscopy was used to quantify drug delivery and the level of plasmid transfection into HeLa cells .", "entity": [], "task": "NER"}
{"text": "The results showed that drug delivery or transfection was minimal without incorporation of internal PFC5 emulsions and folate ligand on the eLiposome surface .", "entity": [{"entity": "PFC5", "entity_type": "Chemical", "pos": [100, 104]}, {"entity": "folate", "entity_type": "Chemical", "pos": [119, 125]}], "task": "NER"}
{"text": "It was also shown that application of ultrasound greatly enhanced the drug delivery and plasmid transfection .", "entity": [], "task": "NER"}
{"text": "Delivery of these therapeutics appears to be to the cytosol , indicating that the expansion of the emulsion droplets disrupted both the eLiposomes and the endosomes .", "entity": [], "task": "NER"}
{"text": "Models of drug - induced liver injury for evaluation of phytotherapeutics and other natural products .", "entity": [], "task": "NER"}
{"text": "Extracts from medicinal plants , many of which have been used for centuries , are increasingly tested in models of hepatotoxicity .", "entity": [], "task": "NER"}
{"text": "One of the most popular models to evaluate the hepatoprotective potential of natural products is acetaminophen ( APAP ) - induced liver injury , although other hepatotoxicity models such as carbon tetrachloride , thioacetamide , ethanol and endotoxin are occasionally used .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [97, 110]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [113, 117]}, {"entity": "carbon tetrachloride", "entity_type": "Chemical", "pos": [190, 210]}, {"entity": "thioacetamide", "entity_type": "Chemical", "pos": [213, 226]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [229, 236]}], "task": "NER"}
{"text": "APAP overdose is a clinically relevant model of drug - induced liver injury .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Critical mechanisms and signaling pathways , which trigger necrotic cell death and sterile inflammation , are discussed .", "entity": [], "task": "NER"}
{"text": "Although there is increasing understanding of the pathophysiology of APAP - induced liver injury , the mechanism is complex and prone to misinterpretation , especially when unknown chemicals such as plant extracts are tested .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [69, 73]}], "task": "NER"}
{"text": "This review discusses the fundamental aspects that need to be considered when using this model , such as selection of the animal species or in vitro system , timing and dose - responses of signaling events , metabolic activation and protein adduct formation , the role of lipid peroxidation and apoptotic versus necrotic cell death , and the impact of the ensuing sterile inflammatory response .", "entity": [], "task": "NER"}
{"text": "The goal is to enable researchers to select the appropriate model and experimental conditions for testing of natural products that will yield clinically relevant results and allow valid interpretations of the pharmacological mechanisms .", "entity": [], "task": "NER"}
{"text": "Feasibility of spray drying bacteriophages into respirable powders to combat pulmonary bacterial infections .", "entity": [], "task": "NER"}
{"text": "The use of bacterial viruses for antibacterial treatment ( bacteriophage therapy ) is currently being reevaluated .", "entity": [], "task": "NER"}
{"text": "In this study , we analyze the potential of processing bacteriophages in a dry powder formulation , using a laboratory spray dryer .", "entity": [], "task": "NER"}
{"text": "The phages were dried in the presence of lactose , trehalose or dextran 35 , serving as an excipient to give the resulting powder the necessary bulk mass and offer protection to the delicate phage structure .", "entity": [{"entity": "lactose", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "trehalose", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "Out of the three excipients tested , trehalose was found to be the most efficient in protecting the phages from temperature and shear stress throughout the spray drying process .", "entity": [{"entity": "trehalose", "entity_type": "Chemical", "pos": [37, 46]}], "task": "NER"}
{"text": "A low inlet air temperature and atomizing force appeared to be the best parameter conditions for phage survival .", "entity": [], "task": "NER"}
{"text": "Pseudomonas podovirus LUZ19 was remarkably stable , suffering less than 1 logarithmic unit reduction in phage titer .", "entity": [], "task": "NER"}
{"text": "The phage titer of Staphyloccus phage Romulus - containing powders , a member of the Myoviridae family , showed more than 2 . 5 logarithmic units reduction .", "entity": [], "task": "NER"}
{"text": "On the other hand , Romulus - containing powders showed more favorable characteristics for pulmonary delivery , with a high percentage of dry powder particles in the pulmonary deposition fraction ( 1 - 5 mu m particle diameter ) .", "entity": [], "task": "NER"}
{"text": "Even though the parameters for spray drying all phages were not optimized , it was demonstrated that spray drying phages with this industrial relevant and scalable set up was possible .", "entity": [], "task": "NER"}
{"text": "The resulting powders had desirable size ranges for pulmonary delivery of phages with dry powder inhalers ( DPIs ) .", "entity": [], "task": "NER"}
{"text": "Sonhafouonic acid , a new cytotoxic and antifungal hopene - triterpenoid from Zehneria scabra camerunensis .", "entity": [{"entity": "Sonhafouonic acid", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "hopene", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "triterpenoid", "entity_type": "Chemical", "pos": [60, 72]}], "task": "NER"}
{"text": "A new hopene - type triterpenoid , namely sonhafouonic acid 1a was isolated from Zehneria scabra camerunensis , together with eight known compounds .", "entity": [{"entity": "hopene", "entity_type": "Chemical", "pos": [6, 12]}, {"entity": "triterpenoid", "entity_type": "Chemical", "pos": [20, 32]}, {"entity": "sonhafouonic acid", "entity_type": "Chemical", "pos": [42, 59]}], "task": "NER"}
{"text": "The structure of 1a was established by extensive NMR and high resolution MS techniques and confirmed by single - crystal X - ray crystallographic analysis .", "entity": [], "task": "NER"}
{"text": "Compound 1a exhibited inhibitory activity against mycelial growth of two peronosporomycete phytopathogens Pythium ultimum and Aphanomyces cochliodes and cytotoxicity towards brine shrimp larvae ( Artemia salina ) at 10 mu g / mL .", "entity": [], "task": "NER"}
{"text": "Pestaloficiols Q - S from the plant endophytic fungus Pestalotiopsis fici .", "entity": [{"entity": "Pestaloficiols Q - S", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "Two new isoprenylated chromone derivatives , pestaloficiols Q ( 1 ) and R ( 2 ) , and one new benzofuran derivative , pestaloficiol S ( 3 ) , along with three known metabolites , anofinic acid ( 4 ) , siccayne ( 5 ) , and pyrenophorol ( 6 ) were isolated from solid cultures of the plant endophytic fungus Pestalotiopsis fici .", "entity": [{"entity": "isoprenylated chromone", "entity_type": "Chemical", "pos": [8, 30]}, {"entity": "pestaloficiols Q ( 1 ) and R", "entity_type": "Chemical", "pos": [45, 73]}, {"entity": "benzofuran", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "pestaloficiol S", "entity_type": "Chemical", "pos": [118, 133]}, {"entity": "anofinic acid", "entity_type": "Chemical", "pos": [179, 192]}, {"entity": "siccayne", "entity_type": "Chemical", "pos": [201, 209]}, {"entity": "pyrenophorol", "entity_type": "Chemical", "pos": [222, 234]}], "task": "NER"}
{"text": "Their structures were elucidated primarily by NMR spectroscopy , and the absolute of the C - 6 secondary alcohol in 1 was deduced on the basis of circular dichroism ( CD ) data .", "entity": [{"entity": "secondary alcohol", "entity_type": "Chemical", "pos": [95, 112]}], "task": "NER"}
{"text": "Compound 5 showed cytotoxic activity against the human cancer cell lines , HeLa and HT29 , with IC50 values of 48 . 2 and 33 . 9 mu M , respectively .", "entity": [], "task": "NER"}
{"text": "Syntheses and anti - allergic activity of 2 - ( ( bis ( trimethylsilyl ) methylthio / methylsulfonyl ) methyl ) - 5 - aryl - 1 , 3 , 4 - oxadiazoles .", "entity": [{"entity": "2 - ( ( bis ( trimethylsilyl ) methylthio / methylsulfonyl ) methyl ) - 5 - aryl - 1 , 3 , 4 - oxadiazoles", "entity_type": "Chemical", "pos": [42, 148]}], "task": "NER"}
{"text": "A new class of sila - substituted 1 , 3 , 4 - oxadiazoles was synthesized by a convenient synthetic method .", "entity": [{"entity": "sila - substituted 1 , 3 , 4 - oxadiazoles", "entity_type": "Chemical", "pos": [15, 57]}], "task": "NER"}
{"text": "Both silathio / silasulfonyl acetic acids were efficiently condensed with benzohydrazides in the presence of phosphorus oxychloride to give sila - substituted 1 , 3 , 4 - oxadiazoles in high yields .", "entity": [{"entity": "silathio / silasulfonyl acetic acids", "entity_type": "Chemical", "pos": [5, 41]}, {"entity": "benzohydrazides", "entity_type": "Chemical", "pos": [74, 89]}, {"entity": "phosphorus oxychloride", "entity_type": "Chemical", "pos": [109, 131]}, {"entity": "sila - substituted 1 , 3 , 4 - oxadiazoles", "entity_type": "Chemical", "pos": [140, 182]}], "task": "NER"}
{"text": "The compounds displayed variable extent of anti - allergic activity on IgE / Ag - stimulated RBL - 2H3 cells at 50 and 100 mu M concentrations .", "entity": [], "task": "NER"}
{"text": "Compounds having sulfonyl moiety with bis ( trimethylsilyl ) - 1 , 3 , 4 - oxadiazoles ( 5a - c ) , exhibited better anti - allergic activities than those of compounds having sulphur moiety with bis ( trimethylsilyl ) - 1 , 3 , 4 - oxadiazoles ( 4a - c ) .", "entity": [{"entity": "sulfonyl", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "bis ( trimethylsilyl ) - 1 , 3 , 4 - oxadiazoles", "entity_type": "Chemical", "pos": [38, 86]}, {"entity": "sulphur", "entity_type": "Chemical", "pos": [175, 182]}, {"entity": "bis ( trimethylsilyl ) - 1 , 3 , 4 - oxadiazoles", "entity_type": "Chemical", "pos": [195, 243]}], "task": "NER"}
{"text": "Anti - hepatitis B virus and anti - cancer activities of novel isoflavone analogs .", "entity": [{"entity": "isoflavone", "entity_type": "Chemical", "pos": [63, 73]}], "task": "NER"}
{"text": "We have synthesized a series of novel isoflavone analogs and evaluated their anti - HBV and anti - cancer activities in vitro .", "entity": [{"entity": "isoflavone", "entity_type": "Chemical", "pos": [38, 48]}], "task": "NER"}
{"text": "The bioassays showed that the majority of the resultant compounds exerted inhibitory effects on HBsAg and HBeAg levels , HBV DNA replication , as well as the growth of four human cancer cell lines to various extents , which supported the rationale of the design .", "entity": [], "task": "NER"}
{"text": "In particular , compound 8f showed the highest activity against HBV infection and HBV - related liver cancer .", "entity": [], "task": "NER"}
{"text": "Compound 7l ( IC50 = 0 . 47 mu M ) also exerted remarkable inhibitory effect on the growth lung cancer cell line A - 549 .", "entity": [], "task": "NER"}
{"text": "Design , synthesis and SAR of piperidyl - oxadiazoles as 11 beta - hydroxysteroid dehydrogenase 1 inhibitors .", "entity": [{"entity": "piperidyl - oxadiazoles", "entity_type": "Chemical", "pos": [30, 53]}, {"entity": "11 beta - hydroxysteroid", "entity_type": "Chemical", "pos": [57, 81]}], "task": "NER"}
{"text": "The potential roles of 11 beta - HSD1 inhibitors in metabolic syndrome , T2D and obesity were well established and currently several classes of 11 beta - HSD1 inhibitors have been developed as promising agents against metabolic diseases .", "entity": [], "task": "NER"}
{"text": "To find potent compounds with good pharmacokinetics , we used the bioisosterism approach , and designed the compound 2 and 3 bearing an 1 , 2 , 4 - oxadiazole ring to replace the amide group in compound 1 .", "entity": [{"entity": "1 , 2 , 4 - oxadiazole", "entity_type": "Chemical", "pos": [136, 158]}, {"entity": "amide", "entity_type": "Chemical", "pos": [179, 184]}], "task": "NER"}
{"text": "Guided by docking study , we then transformed compound 3 into a potent lead compound 4a by changing sulfonamide group to amide .", "entity": [{"entity": "sulfonamide", "entity_type": "Chemical", "pos": [100, 111]}, {"entity": "amide", "entity_type": "Chemical", "pos": [121, 126]}], "task": "NER"}
{"text": "To elaborate this series of piperidyl - oxadiazole derivatives as human 11 beta - HSD1 inhibitors , we explored the structure - activity relationship of several parts of the lead compound .", "entity": [{"entity": "piperidyl - oxadiazole", "entity_type": "Chemical", "pos": [28, 50]}], "task": "NER"}
{"text": "Based on their potency toward human 11 beta - HSD1 two compounds 4h and 4q were advanced to pharmacokinetic study .", "entity": [], "task": "NER"}
{"text": "It was found that 4h and 4q are potent and selective human 11 beta - HSD1 inhibitors with better pharmacokinetic properties than those of the original piperidine - 3 - carboxamide compound 1 , and suitable for further in vivo preclinical study in primate model .", "entity": [{"entity": "piperidine - 3 - carboxamide", "entity_type": "Chemical", "pos": [151, 179]}], "task": "NER"}
{"text": "( E ) - 4 - Aryl - 4 - oxo - 2 - butenoic acid amides , chalcone - aroylacrylic acid chimeras : Design , antiproliferative activity and inhibition of tubulin polymerization .", "entity": [{"entity": "( E ) - 4 - Aryl - 4 - oxo - 2 - butenoic acid amides", "entity_type": "Chemical", "pos": [0, 53]}, {"entity": "chalcone - aroylacrylic acid", "entity_type": "Chemical", "pos": [56, 84]}], "task": "NER"}
{"text": "Antiproliferative activity of twenty - nine ( E ) - 4 - aryl - 4 - oxo - 2 - butenoic acid amides against three human tumor cell lines ( HeLa , FemX , and K562 ) is reported .", "entity": [{"entity": "( E ) - 4 - aryl - 4 - oxo - 2 - butenoic acid amides", "entity_type": "Chemical", "pos": [44, 97]}], "task": "NER"}
{"text": "Compounds showed antiproliferative activity in one - digit micromolar to submicromolar concentrations .", "entity": [], "task": "NER"}
{"text": "The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules .", "entity": [{"entity": "alkyl", "entity_type": "Chemical", "pos": [66, 71]}], "task": "NER"}
{"text": "Fourteen compounds showed tubulin assembly inhibition at concentrations < 20 mu M .", "entity": [], "task": "NER"}
{"text": "The most potent inhibitor of tubulin assembly was unsubstituted compound 1 , with IC50 = 2 . 9 mu M .", "entity": [], "task": "NER"}
{"text": "Compound 23 had an oral LD50in vivo of 45 mg / kg in mice .", "entity": [], "task": "NER"}
{"text": "Cell cycle analysis on K562 cells showed that compounds 1 , 2 and 23 caused accumulation of cells in the G2 / M phase , but inhibition of microtubule polymerization is not the principal mode of action of the compounds .", "entity": [], "task": "NER"}
{"text": "Nevertheless , they may be useful leads for the design of a new class of antitubulin agents .", "entity": [], "task": "NER"}
{"text": "Design , synthesis and biological evaluation of novel hybrid compounds of imidazole scaffold - based 2 - benzylbenzofuran as potent anticancer agents .", "entity": [{"entity": "imidazole", "entity_type": "Chemical", "pos": [74, 83]}, {"entity": "2 - benzylbenzofuran", "entity_type": "Chemical", "pos": [101, 121]}], "task": "NER"}
{"text": "A series of novel hybrid compounds between 2 - benzylbenzofuran and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines .", "entity": [{"entity": "2 - benzylbenzofuran", "entity_type": "Chemical", "pos": [43, 63]}, {"entity": "imidazole", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "The results suggest that the existence of benzimidazole ring and substitution of the imidazolyl - 3 - position with a naphthylacyl or 4 - methoxyphenacyl group were vital for modulating cytotoxic activity .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "imidazolyl", "entity_type": "Chemical", "pos": [85, 95]}, {"entity": "naphthylacyl", "entity_type": "Chemical", "pos": [118, 130]}, {"entity": "4 - methoxyphenacyl", "entity_type": "Chemical", "pos": [134, 153]}], "task": "NER"}
{"text": "In particular , hybrid compounds 46 and 47 were found to be the most potent derivatives against 5 strains human tumor cell lines and more active than cisplatin ( DDP ) , and exhibited cytotoxic activities selectively against breast carcinoma ( MCF - 7 ) and myeloid liver carcinoma ( SMMC - 7721 ) , respectively .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [150, 159]}, {"entity": "DDP", "entity_type": "Chemical", "pos": [162, 165]}], "task": "NER"}
{"text": "Inhibition of enterovirus 71 infections and viral IRES activity by Fructus gardeniae and geniposide .", "entity": [{"entity": "geniposide", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "Fructus gardeniae has long been used by traditional Chinese medical practitioners for its anti - inflammatory , anti - oxidant , anti - tumor and anti - hyperlipidemic characteristics .", "entity": [], "task": "NER"}
{"text": "Here we describe our finding that F . gardeniae greatly reduces anti - enterovirus 71 ( EV71 ) activity , resulting in significant decreases in EV71 virus yields , EV71 infections , and internal ribosome entry site activity .", "entity": [], "task": "NER"}
{"text": "We also found that geniposide , a primary F . gardeniae component , inhibited both EV71 replication and viral IRES activity .", "entity": [{"entity": "geniposide", "entity_type": "Chemical", "pos": [19, 29]}], "task": "NER"}
{"text": "Our data suggest the presence of a mechanism that blocks viral protein translation .", "entity": [], "task": "NER"}
{"text": "According to our findings , F . gardeniae and geniposide deserve a closer look as potential chemopreventive agents against EV71 infections .", "entity": [{"entity": "geniposide", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "Multifunctional terpolymeric MRI contrast agent with superior signal enhancement in blood and tumor .", "entity": [], "task": "NER"}
{"text": "A new multifunctional terpolymeric system for simultaneous imaging and drug delivery has been recently developed in our laboratory .", "entity": [], "task": "NER"}
{"text": "Herein we report the investigation of terpolymeric contrast agent for magnetic resonance imaging and doxorubicin ( Dox ) delivery .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [101, 112]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "The polymer was synthesized by graft polymerization of methacrylic acid ( MAA ) and polysorbate 80 ( PS 80 ) onto starch with multiple , chemically bound diethylenetriaminepenta acetic acid ( DTPA ) groups for gadolinium chelating .", "entity": [{"entity": "methacrylic acid", "entity_type": "Chemical", "pos": [55, 71]}, {"entity": "MAA", "entity_type": "Chemical", "pos": [74, 77]}, {"entity": "polysorbate 80", "entity_type": "Chemical", "pos": [84, 98]}, {"entity": "PS 80", "entity_type": "Chemical", "pos": [101, 106]}, {"entity": "diethylenetriaminepenta acetic acid", "entity_type": "Chemical", "pos": [154, 189]}, {"entity": "DTPA", "entity_type": "Chemical", "pos": [192, 196]}, {"entity": "gadolinium", "entity_type": "Chemical", "pos": [210, 220]}], "task": "NER"}
{"text": "The terpolymer self - assembled to form nanoparticles upon addition of doxorubicin which binds with the PMAA chain .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [71, 82]}, {"entity": "PMAA", "entity_type": "Chemical", "pos": [104, 108]}], "task": "NER"}
{"text": "The physicochemical , biological and pharmacokinetic properties of the polymeric system were characterized and their contrast enhancement capability was evaluated in vitro and in vivo .", "entity": [], "task": "NER"}
{"text": "The polymer was able to load gadolinium with high thermodynamic stability and exhibited low cytotoxicity .", "entity": [{"entity": "gadolinium", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "The Gd - loaded polymer ( PolyGd ) , and Gd - Dox co - loaded nanoparticles ( PolyGd - Dox ) significantly enhanced MR signals , with ionic T1 relaxivities 3 - 5 times higher than those from Omniscan (R) , a small molecule contrast agent .", "entity": [{"entity": "Gd", "entity_type": "Chemical", "pos": [4, 6]}, {"entity": "PolyGd", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "Gd", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "Dox", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "PolyGd - Dox", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "Omniscan", "entity_type": "Chemical", "pos": [191, 199]}], "task": "NER"}
{"text": "In vivo studies showed superior and prolonged contrast enhancement compared to Omniscan (R) at one fourth the equivalent dose , without adverse effects .", "entity": [{"entity": "Omniscan", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "The PolyGd and PolyGd - Dox accumulated in the tumor and painted the tumor boundaries clearly for at least 48h .", "entity": [{"entity": "Dox", "entity_type": "Chemical", "pos": [24, 27]}], "task": "NER"}
{"text": "The PolyGd also enhanced angiogram contrast with contrast to noise ratio values of up to 55 - fold and a blood half - life time of 200min .", "entity": [], "task": "NER"}
{"text": "Seven days after intravenous administration , only relatively small amounts of gadolinium could be detected in the major organs of the mice ( supplementary materials ) .", "entity": [{"entity": "gadolinium", "entity_type": "Chemical", "pos": [79, 89]}], "task": "NER"}
{"text": "These results suggest that the new terpolymeric system is useful as a theranostic platform for contrast enhanced MR imaging of vasculature and tumor as well as Dox delivery .", "entity": [{"entity": "Dox", "entity_type": "Chemical", "pos": [160, 163]}], "task": "NER"}
{"text": "Silica - lipid hybrid ( SLH ) formulations enhance the oral bioavailability and efficacy of celecoxib : An in vivo evaluation .", "entity": [{"entity": "Silica", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [92, 101]}], "task": "NER"}
{"text": "This study is the first to demonstrate in canines the ability of silica - lipid hybrid ( SLH ) microparticles to enhance the bioavailability and efficacy of a poorly water - soluble drug after oral administration .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "Spray - dried SLH microparticles comprising Capmul MCM ( mono - diglycerides of C8 / C12 fatty acids ) and silica nanoparticles ( Aerosil (R) 380 ) were shown to significantly enhance the fasted state oral bioavailability of celecoxib ( CEL ) ( 6 . 5 fold , relative to an aqueous suspension and more than 2 - fold higher relative to the fed state ) after oral administration to beagle dogs .", "entity": [{"entity": "Capmul MCM", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "mono - diglycerides", "entity_type": "Chemical", "pos": [57, 76]}, {"entity": "fatty acids", "entity_type": "Chemical", "pos": [89, 100]}, {"entity": "silica", "entity_type": "Chemical", "pos": [107, 113]}, {"entity": "Aerosil", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [225, 234]}, {"entity": "CEL", "entity_type": "Chemical", "pos": [237, 240]}], "task": "NER"}
{"text": "Comparable bioavailability was observed between the SLH microparticle formulation and a conventional Capmul lipid solution , however , plasma concentrations were observed to be higher ( Cmax , 1 . 1 +/- 0 . 06 vs . 0 . 8 +/- 0 . 03 mu g / mL ) ( p <= 0 . 05 ) with the SLH microparticle system .", "entity": [{"entity": "Capmul", "entity_type": "Chemical", "pos": [101, 107]}], "task": "NER"}
{"text": "The enhanced bioavailability of CEL observed with the SLH microparticles was reflected in a subsequent efficacy study conducted in an adjuvant - induced arthritis model in the rat .", "entity": [{"entity": "CEL", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Reduced clinical and histological severity was observed at a dose of 3mg / kg / day , with the progression of arthritic symptoms and tissue damage reduced to a similar degree to that of a higher dose administered at 5mg / kg / day and prepared in an aqueous suspension . , The enhanced bioavailability and improved efficacy observed with the SLH microparticles were attributed to the maintenance of CEL in a solubilised form during digestion of the lipid vehicle .", "entity": [{"entity": "CEL", "entity_type": "Chemical", "pos": [399, 402]}], "task": "NER"}
{"text": "We hypothesise that the presence of silica in the formulation may have contributed to the prevention of drug precipitation in the intestinal lumen by providing an alternative binding site for CEL to adsorb to prior to re - solubilisation and absorption .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "CEL", "entity_type": "Chemical", "pos": [192, 195]}], "task": "NER"}
{"text": "The study highlights the potential utility of novel SLH microparticle formulations as stable dry powders that possess the properties of a lipid - based formulation for the enhanced delivery and efficacy of poorly water - soluble drugs .", "entity": [], "task": "NER"}
{"text": "Gender - specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "Chronic psychosocial isolation stress ( CPSI ) modulates glucocorticoid receptor ( GR ) functioning in Wistar male rat hippocampus ( HIPPO ) through alteration of nuclear GR phosphorylation and its upstream kinases signaling , which parallels animal depressive - like behavior .", "entity": [], "task": "NER"}
{"text": "The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine ( FLU ) on GR signaling in HIPPO and depressive - like behavior in CPSI animals .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [123, 133]}, {"entity": "FLU", "entity_type": "Chemical", "pos": [136, 139]}], "task": "NER"}
{"text": "FLU was administrated to female and male na i ve or CPSI rats for 21 days and GR protein , its phosphorylation status and upstream kinases , as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone ( CORT ) and depressive - like behavior .", "entity": [{"entity": "FLU", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "corticosterone", "entity_type": "Chemical", "pos": [219, 233]}, {"entity": "CORT", "entity_type": "Chemical", "pos": [236, 240]}], "task": "NER"}
{"text": "The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232 - Cdk5 pathway and JNK signaling in a gender - specific way .", "entity": [], "task": "NER"}
{"text": "In contrast , in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF .", "entity": [{"entity": "CORT", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Concomitant FLU normalized the depressive - like behavior and altered the nuclear pGR232 - Cdk5 signaling in a gender - specific manner .", "entity": [{"entity": "FLU", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "In both females and males , FLU reversed the nuclear levels of GR and pGR246 without affecting CORT and GR mRNA levels .", "entity": [{"entity": "FLU", "entity_type": "Chemical", "pos": [28, 31]}, {"entity": "CORT", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "In contrast , FLU exhibited gender - specific effect on BDNF mRNA in CPSI animals , by increasing it in females , but not in males .", "entity": [{"entity": "FLU", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "In spite of normalization the total nuclear GR level upon FLU treatment in both gender , down - regulation of GR mRNA is possibly maintained through prevalence of pGR232 isoform only in males .", "entity": [{"entity": "FLU", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "The gender - specific alterations of pGR232 - Cdk5 signaling and BDNF gene expression in HIPPO and normalization of depressive - like behavior upon FLU treatment distinguishes this signaling pathway as potential future antidepressant target for gender - specific therapy of stress related mood disorders .", "entity": [{"entity": "FLU", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "Improved pharmaceutical stability of a boronphenylalanine mannitol formulation for boron neutron capture therapy .", "entity": [{"entity": "boronphenylalanine mannitol", "entity_type": "Chemical", "pos": [39, 66]}, {"entity": "boron", "entity_type": "Chemical", "pos": [83, 88]}], "task": "NER"}
{"text": "Boron neutron capture therapy ( BNCT ) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug .", "entity": [{"entity": "Boron", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "boron", "entity_type": "Chemical", "pos": [150, 155]}], "task": "NER"}
{"text": "These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf - life and clinical acceptability of the current fructose based L - boronphenylalanine ( BPA ) formulation .", "entity": [{"entity": "fructose", "entity_type": "Chemical", "pos": [166, 174]}, {"entity": "L - boronphenylalanine", "entity_type": "Chemical", "pos": [181, 203]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [206, 209]}], "task": "NER"}
{"text": "Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated .", "entity": [{"entity": "mannitol BPA", "entity_type": "Chemical", "pos": [108, 120]}], "task": "NER"}
{"text": "A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures .", "entity": [{"entity": "mannitol BPA", "entity_type": "Chemical", "pos": [2, 14]}], "task": "NER"}
{"text": "After suitable periods the formulation was analysed by HPLC for BPA and degradation products .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products .", "entity": [{"entity": "mannitol BPA", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Autoclaving the solution induced and accelerated degradation .", "entity": [], "task": "NER"}
{"text": "A solution or lyophilised mannitol BPA formulation has a shelf - life of between 1 and 4 years respectively , a marked improvement over the current fructose formulation .", "entity": [{"entity": "mannitol BPA", "entity_type": "Chemical", "pos": [26, 38]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [148, 156]}], "task": "NER"}
{"text": "Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving .", "entity": [], "task": "NER"}
{"text": "The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT .", "entity": [{"entity": "mannitol", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [117, 120]}], "task": "NER"}
{"text": "Methods for analysis of citrinin in human blood and urine .", "entity": [{"entity": "citrinin", "entity_type": "Chemical", "pos": [24, 32]}], "task": "NER"}
{"text": "Citrinin ( CIT ) , produced by several Penicillium , Aspergillus , and Monascus species , has been detected as contaminant in feeds , grains , and other food commodities .", "entity": [{"entity": "Citrinin", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "CIT", "entity_type": "Chemical", "pos": [11, 14]}], "task": "NER"}
{"text": "CIT can co - occur with ochratoxin A ( OTA ) , a mycotoxin also known for its nephrotoxicity , and this raises concern regarding possible combined effects .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "ochratoxin A", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "But , in contrast to OTA , data on CIT contamination in foods for human consumption are scarce , and CIT biomonitoring has not been conducted so far due a lack of suitable methods for human specimen .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [21, 24]}, {"entity": "CIT", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "CIT", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Thus , it was the aim of the present study to develop sensitive methods for the analysis of CIT in human blood and urine to investigate human exposure .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [92, 95]}], "task": "NER"}
{"text": "To this end , we assessed different methods of sample preparation and instrumental analysis for these matrices .", "entity": [], "task": "NER"}
{"text": "Clean - up of blood plasma by protein precipitation followed by LC - MS / MS - based analysis allowed robust detection of CIT ( LOD 0 . 07 ng / mL , LOQ 0 . 15 ng / mL ) .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "For urine , sample clean - up by an immunoaffinity column ( CitriTest ( (R) ) ) proved to be clearly superior to SPE with RP ( 18 ) material for subsequent analysis by LC - MS / MS .", "entity": [], "task": "NER"}
{"text": "For CIT and its metabolite dihydrocitrinone ( HO - CIT ) , the LOD and LOQ determined by external calibration curves in matrix were 0 . 02 and 0 . 05 ng / mL for CIT , and those for HO - CIT were 0 . 05 and 0 . 1 ng / mL urine .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "dihydrocitrinone", "entity_type": "Chemical", "pos": [27, 43]}, {"entity": "HO - CIT", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "CIT", "entity_type": "Chemical", "pos": [162, 165]}, {"entity": "HO - CIT", "entity_type": "Chemical", "pos": [182, 190]}], "task": "NER"}
{"text": "The newly developed method was applied in a small pilot study : CIT was present in all plasma samples from 8 German adults , at concentrations ranging from 0 . 11 to 0 . 26 ng / mL .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "The molar ( nM ) concentrations of CIT are similar to those measured for OTA in these samples as a result of dietary mycotoxin intake .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [35, 38]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "CIT was detected in 8 / 10 urines ( from 4 adults and 6 infants ) in a range of 0 . 16 - 0 . 79 ng / mL , and HO - CIT was present in 5 / 10 samples at similar concentrations .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "HO - CIT", "entity_type": "Chemical", "pos": [110, 118]}], "task": "NER"}
{"text": "Thus , CIT is excreted in urine as parent compound and also as metabolite .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [7, 10]}], "task": "NER"}
{"text": "These first results in humans point to the need for further studies on CIT exposure .", "entity": [{"entity": "CIT", "entity_type": "Chemical", "pos": [71, 74]}], "task": "NER"}
{"text": "Bioactive microconstituents and antioxidant properties of wild edible mushrooms from the island of Lesvos , Greece .", "entity": [], "task": "NER"}
{"text": "Crude composition , fatty acids , sterols , total phenolic content ( TPC ) , individual polyphenols and terpenic acids were determined in five wild edible mushrooms species ( Lactarius deliciosus , Lactarius sanguifluus , Lactarius semisanguifluus , Russula delica , Suillus bellinii ) from Lesvos Island , Greece .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [20, 31]}, {"entity": "sterols", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "terpenic acids", "entity_type": "Chemical", "pos": [104, 118]}], "task": "NER"}
{"text": "In addition , the DPPH scavenging capacity , the ferric ion reducing power ( FRAP ) and the ferrous ion chelating activity of mushroom methanolic extracts were assessed .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "ferric", "entity_type": "Chemical", "pos": [49, 55]}, {"entity": "ferrous", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "Among sterols , ergosterol predominated at concentrations 9 . 2 - 18 . 0mg / 100g fw .", "entity": [{"entity": "sterols", "entity_type": "Chemical", "pos": [6, 13]}, {"entity": "ergosterol", "entity_type": "Chemical", "pos": [16, 26]}], "task": "NER"}
{"text": "Total phenolic content of mushroom extracts ranged from 6 . 0 to 20 . 8mg GAE / 100g fw .", "entity": [], "task": "NER"}
{"text": "Up to 19 simple polyphenols were determined in mushrooms extracts , the more abundant being p - OH - benzoic acid , p - OH - phenylacetic acid , o - coumaric acid , ferulic acid and chrysin .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "p - OH - benzoic acid", "entity_type": "Chemical", "pos": [92, 113]}, {"entity": "p - OH - phenylacetic acid", "entity_type": "Chemical", "pos": [116, 142]}, {"entity": "o - coumaric acid", "entity_type": "Chemical", "pos": [145, 162]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [165, 177]}, {"entity": "chrysin", "entity_type": "Chemical", "pos": [182, 189]}], "task": "NER"}
{"text": "In addition , the triterpenic acids oleanolic and ursolic were detected for the first time in mushrooms .", "entity": [{"entity": "triterpenic acids", "entity_type": "Chemical", "pos": [18, 35]}, {"entity": "oleanolic", "entity_type": "Chemical", "pos": [36, 45]}, {"entity": "ursolic", "entity_type": "Chemical", "pos": [50, 57]}], "task": "NER"}
{"text": "All species exerted antioxidant activity and ferrous ion chelating capacity .", "entity": [{"entity": "ferrous", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "Principal component analysis revealed good correlations between TPC , DPPH and FRAP but not with metal chelating activity .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "It seems that mushrooms polyphenols exert antiradical and reducing activities , but they are not strong metal chelators , the observed chelating ability being probably due to other classes of compounds .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "To our knowledge , this is the first report on the bioactive microconstituents and antioxidant activity of wild Greek edible mushrooms .", "entity": [], "task": "NER"}
{"text": "Subchronic memantine induced concurrent functional disconnectivity and altered ultra - structural tissue integrity in the rodent brain : revealed by multimodal MRI .", "entity": [{"entity": "memantine", "entity_type": "Chemical", "pos": [11, 20]}], "task": "NER"}
{"text": "BACKGROUND : An effective NMDA antagonist imaging model may find key utility in advancing schizophrenia drug discovery research .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "We investigated effects of subchronic treatment with the NMDA antagonist memantine by using behavioural observation and multimodal MRI .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [57, 61]}, {"entity": "memantine", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "METHODS : Pharmacological MRI ( phMRI ) was used to map the neuroanatomical binding sites of memantine after acute and subchronic treatment .", "entity": [{"entity": "memantine", "entity_type": "Chemical", "pos": [93, 102]}], "task": "NER"}
{"text": "Resting state fMRI ( rs - fMRI ) and diffusion MRI were used to study the changes in functional connectivity ( FC ) and ultra - structural tissue integrity before and after subchronic memantine treatment .", "entity": [{"entity": "memantine", "entity_type": "Chemical", "pos": [184, 193]}], "task": "NER"}
{"text": "Further corroborating behavioural evidences were documented .", "entity": [], "task": "NER"}
{"text": "RESULTS : Dose - dependent phMRI activation was observed in the prelimbic cortex following acute doses of memantine .", "entity": [{"entity": "memantine", "entity_type": "Chemical", "pos": [106, 115]}], "task": "NER"}
{"text": "Subchronic treatment revealed significant effects in the hippocampus , cingulate , prelimbic and retrosplenial cortices .", "entity": [], "task": "NER"}
{"text": "Decreases in FC amongst the hippocampal and frontal cortical structures ( prelimbic , cingulate ) were apparent through rs - fMRI investigation , indicating a loss of connectivity .", "entity": [], "task": "NER"}
{"text": "Diffusion kurtosis MRI showed decreases in fractional anisotropy and mean diffusivity changes , suggesting ultra - structural changes in the hippocampus and cingulate cortex .", "entity": [], "task": "NER"}
{"text": "Limited behavioural assessment suggested that memantine induced behavioural effects comparable to other NMDA antagonists as measured by locomotor hyperactivity and that the effects could be reversed by antipsychotic drugs .", "entity": [{"entity": "memantine", "entity_type": "Chemical", "pos": [46, 55]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [104, 108]}], "task": "NER"}
{"text": "CONCLUSION : Our findings substantiate the hypothesis that repeated NMDA receptor blockade with nonspecific , noncompetitive NMDA antagonists may lead to functional and ultra - structural alterations , particularly in the hippocampus and cingulate cortex .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [68, 72]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [125, 129]}], "task": "NER"}
{"text": "These changes may underlie the behavioural effects .", "entity": [], "task": "NER"}
{"text": "Furthermore , the present findings underscore the utility and the translational potential of multimodal MR imaging and acute / subchronic memantine model in the search for novel disease - modifying treatments for schizophrenia .", "entity": [{"entity": "memantine", "entity_type": "Chemical", "pos": [138, 147]}], "task": "NER"}
{"text": "A prospective study of selenium concentration and risk of preeclampsia in pregnant Iranian women : a nested case - control study .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "Preeclampsia remains a leading cause of maternal and perinatal mortality and morbidity worldwide ; however , its specific etiology still remains obscure .", "entity": [], "task": "NER"}
{"text": "Some studies implicate poor maternal selenium status predisposing the mother to preeclampsia .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "This study was designed to determine changes in plasma selenium levels in women having preeclampsia as compared with those with normal pregnancy .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "In a nested case - control study , 650 normal primigravida in their first 24 - 28 weeks participated in the study .", "entity": [], "task": "NER"}
{"text": "After 3 months of follow - up of all subjects , blood selenium levels were measured in 38 women presenting consecutively with preeclampsia and in 38 women having a normal pregnancy by atomic absorption spectrophotometry .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "Birth outcomes were recorded , such as gestational age at delivery , height , weight , birth head circumflex and 1 - min Apgar score .", "entity": [], "task": "NER"}
{"text": "Preeclampsia affects about 5 . 84 % of pregnancies , and in our study , there were no significant differences in age , anthropometric indices , and family history of preeclampsia between the preeclamptic and control groups .", "entity": [], "task": "NER"}
{"text": "The selenium concentrations in plasma in women with preeclampsia were significantly lower as compared with those in women with normal pregnancy ( 70 . 63 +/- 21 . 41 versus 82 . 03 +/- 15 . 54 mu g / L , p < 0 . 05 ) .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "Being in the bottom tertile of selenium concentration ( less than 62 . 2 mu g / L ) was associated with greater risk of preeclampsia in pregnant women .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [31, 39]}], "task": "NER"}
{"text": "The reduced selenium in the maternal circulations observed in the preeclamptic mothers support the hypothesis that insufficient selenium concentration may be a contributing factor to the pathophysiological mechanisms associated with preeclampsia , and optimizing the dietary selenium intake through supplementation could produce demonstrable clinical benefits .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [275, 283]}], "task": "NER"}
{"text": "Environmental concentrations and bioaccumulations of cadmium and zinc in coastal watersheds along the Chinese Northern Bohai and Yellow Seas .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [53, 60]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "Cadmium ( Cd ) and zinc ( Zn ) in surface water , sediment , carp , and crab samples collected from upstream and downstream regions of coastal watersheds along the Chinese Northern Bohai and Yellow Seas were analyzed to provide a comprehensive understanding and assessment of their environmental concentrations and bioaccumulations .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [10, 12]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [26, 28]}], "task": "NER"}
{"text": "The results showed that downstream waters contaminated with Zn would have adverse effects on aquatic organisms .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [60, 62]}], "task": "NER"}
{"text": "Although nearly all sediments were contaminated with Cd due to human activities , little potential existed for Cd toxicity in sediment - dwelling fauna .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [53, 55]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [111, 113]}], "task": "NER"}
{"text": "Concentrations of Cd and Zn in most water , sediment , carp , and crab were less than published values .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [25, 27]}], "task": "NER"}
{"text": "The downstream carp and crabs had higher mean bioaccumulation factors and biota - sediment accumulation factors for Cd but lower mean biota - sediment accumulation factors for Zn than the upstream carp and crabs .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [116, 118]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [176, 178]}], "task": "NER"}
{"text": "Based on the relationships among Cd and Zn concentrations in water , sediment , and biota , the authors conclude that Cd and Zn in crabs primarily derived from sediment exposure .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [33, 35]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [118, 120]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [125, 127]}], "task": "NER"}
{"text": "Although Cd and Zn in water and sediment originated from some of the same sources , the sources of Cd or Zn in water were likely different from those in sediment .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [9, 11]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [16, 18]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [99, 101]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [105, 107]}], "task": "NER"}
{"text": "The reversal of inhibitors in congenital hemophilia .", "entity": [], "task": "NER"}
{"text": "Hemophilias A and B are heritable bleeding disorders characterized by deficient baseline levels of factor VIII ( fVIII ) and factor IX ( fIX ) , respectively .", "entity": [], "task": "NER"}
{"text": "Standard treatment for acute bleeding events and for prophylaxis in patients with severe disease consists of recombinant fVIII and fIX infusions .", "entity": [], "task": "NER"}
{"text": "The development of alloantibodies , or inhibitors , is a serious complication of congenital hemophilia that may impair the effectiveness of fVIII and fIX , leading to increased morbidity and cost of therapy .", "entity": [], "task": "NER"}
{"text": "When inhibitors are present , bypassing agents such as recombinant activated factor VII and factor eight inhibitor bypass agent are available for treatment of bleeding events .", "entity": [], "task": "NER"}
{"text": "Although usually effective , they are costly treatments .", "entity": [], "task": "NER"}
{"text": "Immune - modulatory therapy may reverse inhibitors , allowing fVIII and fIX to be used again .", "entity": [], "task": "NER"}
{"text": "Immune tolerance induction is the chief treatment option to decrease inhibitor levels , but about 20 - 30 % of patients fail this treatment .", "entity": [], "task": "NER"}
{"text": "Alternatively , multiple immune - modulating agents have been tried with limited success .", "entity": [], "task": "NER"}
{"text": "Rituximab , an anti - CD20 monoclonal antibody , is one therapy that has been successful in reducing inhibitor titers in multiple case reports .", "entity": [], "task": "NER"}
{"text": "Although current evidence is limited and questions regarding its use and place in therapy still exist , this agent shows promise for the future .", "entity": [], "task": "NER"}
{"text": "3 - Methylglutaconic aciduria - lessons from 50 genes and 977 patients .", "entity": [{"entity": "3 - Methylglutaconic", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "Elevated urinary excretion of 3 - methylglutaconic acid is considered rare in patients suspected of a metabolic disorder .", "entity": [{"entity": "3 - methylglutaconic acid", "entity_type": "Chemical", "pos": [30, 55]}], "task": "NER"}
{"text": "In 3 - methylglutaconyl - CoA hydratase deficiency ( mutations in AUH ) , it derives from leucine degradation .", "entity": [{"entity": "3 - methylglutaconyl - CoA", "entity_type": "Chemical", "pos": [3, 29]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "In all other disorders with 3 - methylglutaconic aciduria the origin is unknown , yet mitochondrial dysfunction is thought to be the common denominator .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [28, 48]}], "task": "NER"}
{"text": "We investigate the biochemical , clinical and genetic data of 388 patients referred to our centre under suspicion of a metabolic disorder showing 3 - methylglutaconic aciduria in routine metabolic screening .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [146, 166]}], "task": "NER"}
{"text": "Furthermore , we investigate 591 patients with 50 different , genetically proven , mitochondrial disorders for the presence of 3 - methylglutaconic aciduria .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [127, 147]}], "task": "NER"}
{"text": "Three percent of all urine samples of the patients referred showed 3 - methylglutaconic aciduria , often in correlation with disorders not reported earlier in association with 3 - methylglutaconic aciduria ( e . g . organic acidurias , urea cycle disorders , haematological and neuromuscular disorders ) .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [67, 87]}, {"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [176, 196]}, {"entity": "urea", "entity_type": "Chemical", "pos": [236, 240]}], "task": "NER"}
{"text": "In the patient cohort with genetically proven mitochondrial disorders 11 % presented 3 - methylglutaconic aciduria .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [85, 105]}], "task": "NER"}
{"text": "It was more frequently seen in ATPase related disorders , with mitochondrial DNA depletion or deletion , but not in patients with single respiratory chain complex deficiencies .", "entity": [], "task": "NER"}
{"text": "Besides , it was a consistent feature of patients with mutations in TAZ , SERAC1 , OPA3 , DNAJC19 and TMEM70 accounting for mitochondrial membrane related pathology .", "entity": [], "task": "NER"}
{"text": "3 - methylglutaconic aciduria is found quite frequently in patients suspected of a metabolic disorder , and mitochondrial dysfunction is indeed a common denominator .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "It is only a discriminative feature of patients with mutations in AUH , TAZ , SERAC1 , OPA3 , DNAJC19 TMEM70 .", "entity": [], "task": "NER"}
{"text": "These conditions should therefore be referred to as inborn errors of metabolism with 3 - methylglutaconic aciduria as discriminative feature .", "entity": [{"entity": "3 - methylglutaconic", "entity_type": "Chemical", "pos": [85, 105]}], "task": "NER"}
{"text": "Gas Dielectric Transistor of CuPc Single Crystalline Nanowire for SO2 Detection Down to Sub - ppm Levels at Room Temperature .", "entity": [{"entity": "CuPc", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "SO2", "entity_type": "Chemical", "pos": [66, 69]}], "task": "NER"}
{"text": "A room - temperature highly - sensitive SO2 sensor with fast response and complete recovery is constructed based on gas dielectric field - effect transistor ( FET ) of CuPc single crystalline nanowire .", "entity": [{"entity": "SO2", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "CuPc", "entity_type": "Chemical", "pos": [168, 172]}], "task": "NER"}
{"text": "The exposed conductive channel by gas dielectric is responsible for the high sensitivity to SO2 and the adsorption of the SO2 molecules dramatically enhances the field - effect mobility .", "entity": [{"entity": "SO2", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "SO2", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "These results not only open up new opportunities to develop new SO2 sensors , but also provide an efficient way to improve the performance of organic FETs .", "entity": [{"entity": "SO2", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Efficient stacking on protein amide fragments .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [30, 35]}], "task": "NER"}
{"text": "The less polar pi - surface of protein amide groups is exposed in many receptor binding sites , either as part of the backbone or in Gln / Asn side chains .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "Gln", "entity_type": "Chemical", "pos": [133, 136]}, {"entity": "Asn", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "Using quantum chemical calculations and Protein Data Bank ( PDB ) searches on model systems , we investigate the energetics and geometric preferences for the stacking on amide groups of a large number of heteroarenes that are relevant to medicinal chemistry .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [170, 175]}, {"entity": "heteroarenes", "entity_type": "Chemical", "pos": [204, 216]}], "task": "NER"}
{"text": "From this study , we discern that the stacking energy of an aromatic ligand substituent can be improved by : 1 ) orienting the fragment dipole vector such that it is aligned in an antiparallel fashion with the dipole of the interacting protein amide group , 2 ) increasing its dipole moment , and 3 ) decreasing its pi - electron density .", "entity": [{"entity": "amide", "entity_type": "Chemical", "pos": [244, 249]}], "task": "NER"}
{"text": "These guidelines should be helpful to more rationally exploit this interaction type in future structure - based drug design .", "entity": [], "task": "NER"}
{"text": "Relation between respiratory function tests and life habits of the university students .", "entity": [], "task": "NER"}
{"text": "Among the university students especially in adolescence period , smoking habits and unhealthy lifestyles are major problems in social life .", "entity": [], "task": "NER"}
{"text": "In this study , it is intended to reveal smoking habits and lifestyles of the students from Suleyman Demirel University and to determine the effects of smoking and lifestyles on pulmonary functions .", "entity": [], "task": "NER"}
{"text": "Materials and methods : Participants were 94 university students who were getting formal education in the Suleyman Demirel University central campus .", "entity": [], "task": "NER"}
{"text": "Data were analysed by analysis of variance and chi - square tests .", "entity": [], "task": "NER"}
{"text": "For all analysis , p value of < 0 . 05 was considered significant .", "entity": [], "task": "NER"}
{"text": "Results : Students ' mean age was 19 . 9 +/- 0 . 9 years , and of all the students 74 ( 78 . 7 % ) were undergraduate students ; remaining 20 ( 21 . 3 % ) were graduate students .", "entity": [], "task": "NER"}
{"text": "Of all the students , 27 ( 28 . 7 % ) , which comprised the largest group of the students , were living in state dormitory .", "entity": [], "task": "NER"}
{"text": "Body mass index ( BMI ) was examined for the study group ; according to BMI , body weight was generally within normal limits but 17 . 39 % of girls ' were found to be underweight .", "entity": [], "task": "NER"}
{"text": "Conclusions : Respiratory parameters can be affected by many factors .", "entity": [], "task": "NER"}
{"text": "Smoking habit of university students can be prevented , and it is an important point that they have a healthy lifestyle both for their own health and for future generations .", "entity": [], "task": "NER"}
{"text": "Lapatinib - mediated cyclooxygenase - 2 expression via epidermal growth factor receptor / HuR interaction enhances the aggressiveness of triple - negative breast cancer cells .", "entity": [{"entity": "Lapatinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Lapatinib , a dual epidermal growth factor receptor ( EGFR ) / human epidermal growth factor receptor 2 ( HER2 ) kinase inhibitor , showed clinical benefits in advanced HER2 - positive breast cancer patients .", "entity": [{"entity": "Lapatinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Because some triple - negative breast cancers ( TNBCs ) frequently overexpress EGFR , the antitumor activity of lapatinib in such diseases was also tested .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [112, 121]}], "task": "NER"}
{"text": "However , the results showed a worse event - free survival rate .", "entity": [], "task": "NER"}
{"text": "It remains unknown whether and how lapatinib elicits the aggressiveness of such cancer cells .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "In this study , our results demonstrated that lapatinib facilitated axillary and lung metastases of triple - negative MDA - MB - 231 breast cancer cells without affecting their viability , leading to worse survival in orthotopic xenograft mice .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [46, 55]}], "task": "NER"}
{"text": "The lapatinib - increased motility was attributed by the elevation of EGFR through the downregulation of microRNA - 7 and by the subsequent overexpression of cyclooxygenase - 2 ( COX - 2 ) .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [4, 13]}], "task": "NER"}
{"text": "Strikingly , independent of its kinase activity , the elevated EGFR at least partly stabilized COX - 2 expression by enhancing the binding of HuR to COX - 2 mRNA .", "entity": [], "task": "NER"}
{"text": "Our results suggest that lapatinib may increase the migration and invasion of MDA - MB - 231 cells by upregulating EGFR and COX - 2 through the downregulation of microRNA - 7 , providing a potential explanation for the worse clinical outcome of TNBC patients who receive lapatinib - based treatment .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [25, 34]}, {"entity": "lapatinib", "entity_type": "Chemical", "pos": [271, 280]}], "task": "NER"}
{"text": "These findings also shed new light on the molecular mechanism of COX - 2 mRNA stabilization by EGFR in a kinase - independent manner .", "entity": [], "task": "NER"}
{"text": "Dispersion and Filtration of Carbon Nanotubes ( CNTs ) and Measurement of Nanoparticle Agglomerates in Diesel Exhaust .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [29, 35]}], "task": "NER"}
{"text": "Carbon nanotubes ( CNTs ) tend to form bundles due to their geometry and van der Walls forces , which usually complicates studies of the CNT properties .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Dispersion plays a significant role in CNT studies and we summarize dispersion techniques to generate airborne CNTs from suspensions or powders .", "entity": [], "task": "NER"}
{"text": "We describe in detail our technique of CNT aerosolization with controlled degree of agglomeration using an electrospray system .", "entity": [], "task": "NER"}
{"text": "The results of animal inhalation studies using the electrosprayed CNTs are presented .", "entity": [], "task": "NER"}
{"text": "We have performed filtration experiments for CNTs through a screen filter .", "entity": [], "task": "NER"}
{"text": "A numerical model has been established to simulate the CNT filtration experiments .", "entity": [], "task": "NER"}
{"text": "Both the modeling and experimental results show that the CNT penetration is less than the penetration for a sphere with the same mobility diameter , which is mainly due to the larger interception length of the CNTs .", "entity": [], "task": "NER"}
{"text": "There is a need for instruments capable of fast and online measurement of gas - borne nanoparticle agglomerates .", "entity": [], "task": "NER"}
{"text": "We developed an instrument Universal NanoParticle Analyzer ( UNPA ) and the measurement results for diesel exhaust particulates are presented .", "entity": [], "task": "NER"}
{"text": "The results presented here are pertinent to non - spherical aerosol particles , and illustrate the effects of particle morphology on aerosol behaviors .", "entity": [], "task": "NER"}
{"text": "Design and synthesis of cyclopropylamide analogues of combretastatin - A4 as novel microtubule - stabilizing agents .", "entity": [{"entity": "cyclopropylamide", "entity_type": "Chemical", "pos": [24, 40]}, {"entity": "combretastatin - A4", "entity_type": "Chemical", "pos": [54, 73]}], "task": "NER"}
{"text": "A series of novel cyclopropylamide analogues of combretastatin - A4 ( CA - 4 ) were designed and synthesized .", "entity": [{"entity": "cyclopropylamide", "entity_type": "Chemical", "pos": [18, 34]}, {"entity": "combretastatin - A4", "entity_type": "Chemical", "pos": [48, 67]}, {"entity": "CA - 4", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "Most of them had significant in vitro antiproliferative activities , particularly for compounds 7i4 , 7c4 , 8a4 , and 8c4 .", "entity": [], "task": "NER"}
{"text": "Moreover , compound 8c4 was also equally potent against paclitaxel resistant cancer cells .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [56, 66]}], "task": "NER"}
{"text": "Interestingly , the novel cyclopropylamide analogues had different binding mechanisms from CA - 4 .", "entity": [{"entity": "cyclopropylamide", "entity_type": "Chemical", "pos": [26, 42]}, {"entity": "CA - 4", "entity_type": "Chemical", "pos": [91, 97]}], "task": "NER"}
{"text": "Instead of inhibiting tubulin polymerization , these CA - 4 derivatives were able to stimulate tubulin polymerization .", "entity": [{"entity": "CA - 4", "entity_type": "Chemical", "pos": [53, 59]}], "task": "NER"}
{"text": "Flow cytometry revealed that compound 8c4 arrested A549 cancer cells in the G2 / M phase and resulted in cellular apoptosis .", "entity": [], "task": "NER"}
{"text": "Further immunofluorescence assays revealed that compound 8c4 induced mitotic arrest in A549 cells through disrupting microtubule dynamics .", "entity": [], "task": "NER"}
{"text": "In addition , compound 8c4 also effectively inhibited the tumor growth in the A549 xenograft model without causing significant loss of body weight .", "entity": [], "task": "NER"}
{"text": "Compound 8c4 represents a novel class of microtubule - stabilizing agent and can be used as a promising lead for the development of new antitumor agents .", "entity": [], "task": "NER"}
{"text": "A new iridoid glycoside and potential MRB inhibitory activity of isolated compounds from the rhizomes of Cyperus rotundus L .", "entity": [{"entity": "iridoid glycoside", "entity_type": "Chemical", "pos": [6, 23]}], "task": "NER"}
{"text": "A new iridoid glycoside , rotunduside ( 1 ) , along with four known iridoid glycosides , 10 - O - p - hydroxybenzoyltheviridoside ( 2 ) , 10 - O - vanilloyltheviridoside ( 3 ) , 6 '' - O - ( trans - p - coumaroyl ) - procumbide ( 4 ) and loganic acid ( 5 ) , was isolated from the rhizomes of Cyperus rotundus L .", "entity": [{"entity": "iridoid glycoside", "entity_type": "Chemical", "pos": [6, 23]}, {"entity": "rotunduside", "entity_type": "Chemical", "pos": [26, 37]}, {"entity": "iridoid glycosides", "entity_type": "Chemical", "pos": [68, 86]}, {"entity": "10 - O - p - hydroxybenzoyltheviridoside", "entity_type": "Chemical", "pos": [89, 129]}, {"entity": "10 - O - vanilloyltheviridoside", "entity_type": "Chemical", "pos": [138, 169]}, {"entity": "6 '' - O - ( trans - p - coumaroyl ) - procumbide", "entity_type": "Chemical", "pos": [178, 227]}, {"entity": "loganic acid", "entity_type": "Chemical", "pos": [238, 250]}], "task": "NER"}
{"text": "Their chemical structures were elucidated on the basis of UV , IR , MS and NMR spectroscopic analyses .", "entity": [], "task": "NER"}
{"text": "In addition , the macrophages respiratory burst ( MRB ) inhibitory activity of the isolated compounds was reported .", "entity": [], "task": "NER"}
{"text": "Compound 2 exhibited considerable MRB inhibitory activity in the test with IC ( 50 ) value of ~ 37 mu M .", "entity": [], "task": "NER"}
{"text": "Two new glycosides from Vitex negundo .", "entity": [], "task": "NER"}
{"text": "Two new glycosides , 2 - methyl pyromeconic acid 3 - O - beta - d - glucopyranoside - 6 ' - ( O - 4 '' - hydroxybenzoate ) ( 1 ) , 6 ' - O - p - hydroxybenzoyl - gardoside ( 2 ) and four known iridoid glycosides ( 3 - 6 ) were isolated from the whole plant of Vitex negundo .", "entity": [{"entity": "2 - methyl pyromeconic acid 3 - O - beta - d - glucopyranoside - 6 ' - ( O - 4 '' - hydroxybenzoate )", "entity_type": "Chemical", "pos": [21, 122]}, {"entity": "6 ' - O - p - hydroxybenzoyl - gardoside", "entity_type": "Chemical", "pos": [131, 171]}, {"entity": "iridoid glycosides", "entity_type": "Chemical", "pos": [193, 211]}], "task": "NER"}
{"text": "Their structures were elucidated on the basis of spectroscopic methods including HR - ESI - MS , 1D and 2D NMR .", "entity": [], "task": "NER"}
{"text": "Identification of alpha - tocopherol and alpha - tocopheryl acetate from the cuticle of soybean pods armyworm ( Spodoptera cosmioides ) .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [18, 36]}, {"entity": "alpha - tocopheryl acetate", "entity_type": "Chemical", "pos": [41, 67]}], "task": "NER"}
{"text": "The chemical composition of the soybean pods armyworm Spodoptera cosmioides ( Walker , 1858 ) ( Lepidoptera : Noctuidae ) and Anticarsia gemmatalis H u bner , 1818 ( Lepidoptera : Erebidae ) larval cuticles was evaluated using gas chromatography coupled to a mass detector ( GC - MS ) .", "entity": [], "task": "NER"}
{"text": "Among the usual lipids found in the insect cuticle , alpha - tocopherol and alpha - tocopheryl acetate were also isolated from S . cosmioides .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [53, 71]}, {"entity": "alpha - tocopheryl acetate", "entity_type": "Chemical", "pos": [76, 102]}], "task": "NER"}
{"text": "On the other hand , no vitamin E derivative was found in A . gemmatalis exuvia .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "This is the first report of vitamin E occurrence in the insect ' s cuticle .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [28, 37]}], "task": "NER"}
{"text": "Bioactives and nutraceutical phytochemicals naturally occurring in virgin olive oil .", "entity": [], "task": "NER"}
{"text": "The case study of the Nocellara del Belice Italian olive cultivar .", "entity": [], "task": "NER"}
{"text": "This work reports on the composition and bionutritional value of organic virgin olive oil from the Nocellara del Belice variety , one cultivated in the olive areas of the Sicily region , Italy .", "entity": [], "task": "NER"}
{"text": "Destoned oils obtained by processing olives with a destoning - based procedure were compared with conventional oils .", "entity": [], "task": "NER"}
{"text": "This innovative technique , consisting in removing the stone from fruits prior to processing , strongly enhanced the already high - quality level of the conventional product .", "entity": [], "task": "NER"}
{"text": "An in - depth analytical investigation from 2008 to 2010 showed how this innovative olive extraction process led to an excellent peculiar final product , mainly attributable to the improved biophenol and volatile composition , as well as higher concentrations of the lipophilic and vitamin antioxidants ( tocopherols and tocotrienols ) .", "entity": [{"entity": "tocopherols", "entity_type": "Chemical", "pos": [305, 316]}, {"entity": "tocotrienols", "entity_type": "Chemical", "pos": [321, 333]}], "task": "NER"}
{"text": "It had higher levels of oleocanthal ( p - HPEA - EDA ) , a nutraceutical compound exerting actions against COX1 and COX2 ( cycloxygenases ) .", "entity": [{"entity": "oleocanthal", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "p - HPEA - EDA", "entity_type": "Chemical", "pos": [38, 52]}], "task": "NER"}
{"text": "Its head - space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the lipoxygenase ( LOX ) - pathway ( one having as precursors the polyunsaturated fatty acids containing a cis - cis - 1 , 4 - pentadiene system ) .", "entity": [{"entity": "polyunsaturated fatty acids", "entity_type": "Chemical", "pos": [178, 205]}, {"entity": "cis - cis - 1 , 4 - pentadiene", "entity_type": "Chemical", "pos": [219, 249]}], "task": "NER"}
{"text": "Among the other bioactives , we highlight its significant levels of trans - beta - carotene and xanthophylls ( lutein , violaxanthin , neoxanthin and other carotenoids ) .", "entity": [{"entity": "trans - beta - carotene", "entity_type": "Chemical", "pos": [68, 91]}, {"entity": "xanthophylls", "entity_type": "Chemical", "pos": [96, 108]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [111, 117]}, {"entity": "violaxanthin", "entity_type": "Chemical", "pos": [120, 132]}, {"entity": "neoxanthin", "entity_type": "Chemical", "pos": [135, 145]}], "task": "NER"}
{"text": "Its enhanced nutritional value was also attributable to the increased intensity of valuable tasting notes .", "entity": [], "task": "NER"}
{"text": "Revealing the excited - state dynamics of the fluorescent protein Dendra2 .", "entity": [], "task": "NER"}
{"text": "Green - to - red photoconversion is a reaction that occurs in a limited number of fluorescent proteins and that is currently mechanistically debated .", "entity": [], "task": "NER"}
{"text": "In this contribution , we report on our investigation of the photoconvertible fluorescent protein Dendra2 by employing a combination of pump - probe , up - conversion and single photon timing spectroscopic techniques .", "entity": [], "task": "NER"}
{"text": "Our findings indicate that upon excitation of the neutral green state an excited state proton transfer proceeds with a time constant of 3 . 4 ps between the neutral green and the anionic green states .", "entity": [], "task": "NER"}
{"text": "In concentrated solution we detected resonance energy transfer ( 25 ps time constant ) between green and red monomers .", "entity": [], "task": "NER"}
{"text": "The time - resolved emission spectra suggest also the formation of a super - red species , first observed for DsRed ( a red fluorescent protein from the corallimorph species Discosoma ) and consistent with peculiar structural details present in both proteins .", "entity": [], "task": "NER"}
{"text": "Improvement of p - cymene antinociceptive and anti - inflammatory effects by inclusion in beta - cyclodextrin .", "entity": [{"entity": "p - cymene", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [90, 109]}], "task": "NER"}
{"text": "Previously , we have demonstrated the analgesic - like property of p - cymene in rodents .", "entity": [{"entity": "p - cymene", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Short half - life is a limitation for p - cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes , including the employment of drug - delivery systems .", "entity": [{"entity": "p - cymene", "entity_type": "Chemical", "pos": [38, 48]}, {"entity": "monoterpenes", "entity_type": "Chemical", "pos": [139, 151]}], "task": "NER"}
{"text": "Here , we used p - cymene / beta - cyclodextrin ( beta - CD ) complex and p - cymene ( PC ) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene .", "entity": [{"entity": "p - cymene", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [28, 47]}, {"entity": "beta - CD", "entity_type": "Chemical", "pos": [50, 59]}, {"entity": "p - cymene", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "monoterpene", "entity_type": "Chemical", "pos": [202, 213]}], "task": "NER"}
{"text": "Male mice ( 26 - 30g ) were pretreated with PC / beta - CD ( 20 or 40mg / kg , p . o . ) , PC ( 20 or 40mg / kg , p . o . ) or vehicle ( distilled water ) , 0 . 5h before painful tests and antinociceptive effect was evaluated at times : 0 . 5 , 1 , 2 , 4 , 8 , and 16h after treatment .", "entity": [{"entity": "beta - CD", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "We evaluated the analgesic - like effect of PC / beta - CD and PC in acetic acid - induced abdominal writhes , hot - plate , carrageenan - induced paw edema and in rota - rod apparatus .", "entity": [{"entity": "beta - CD", "entity_type": "Chemical", "pos": [49, 58]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [69, 80]}], "task": "NER"}
{"text": "Our results demonstrated that acute treatment with complex PC / beta - CD produced an antinocicepitve effect ( p < 0 . 01 or p < 0 . 001 ) for 8h followed whereas isolated PC produced the same effect for 2h .", "entity": [{"entity": "beta - CD", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "Similar results were obtained in hot - plate test , PC / beta - CD , in all doses , significantly reduces ( p < 0 . 01 or p < 0 . 001 ) nociceptive behavior for 8h while isolated PC for 1h , did so only in higher dose .", "entity": [{"entity": "beta - CD", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "Such results were unlikely to be caused by motor abnormality .", "entity": [], "task": "NER"}
{"text": "Systemic pretreatment with PC / beta - CD and PC inhibited the development paw edema by carrageenan 1 % , but PC / beta - CD did so during a longer period when compared with isolated monoterpene alone .", "entity": [{"entity": "beta - CD", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "beta - CD", "entity_type": "Chemical", "pos": [115, 124]}, {"entity": "monoterpene", "entity_type": "Chemical", "pos": [183, 194]}], "task": "NER"}
{"text": "Our results provide evidence to propose that the complex with beta - CD improved analgesic and anti - inflammatory effects of p - cymene .", "entity": [{"entity": "beta - CD", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "p - cymene", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "Towards the validation of a lung tumorigenesis model with mainstream cigarette smoke inhalation using the A / J mouse .", "entity": [], "task": "NER"}
{"text": "A generally accepted and validated laboratory model for smoking - associated pulmonary tumorigenesis would be useful for both basic and applied research applications , such as the development of early diagnostic endpoints or the evaluation of modified risk tobacco products , respectively .", "entity": [], "task": "NER"}
{"text": "The A / J mouse is susceptible for developing both spontaneous and induced lung adenomas and adenocarcinomas , and increased lung tumor multiplicities were also observed in previous cigarette smoke inhalation studies .", "entity": [], "task": "NER"}
{"text": "The present study was designed to collect data useful towards the validation of an 18 - month mainstream smoke ( MS ) inhalation model .", "entity": [], "task": "NER"}
{"text": "Male and female A / J mice were exposed whole - body at three MS concentration levels for 6h / day , and the results were compared to a previous study in the same laboratory and with a similar design .", "entity": [], "task": "NER"}
{"text": "A linear MS concentration - dependent increase in lung tumorigenesis was observed with similar slopes for both sexes and both studies and a maximal 5 - fold increase in multiplicity beyond sham control .", "entity": [], "task": "NER"}
{"text": "The minimal detectable difference in lung tumor multiplicity for the current study was 37 % .", "entity": [], "task": "NER"}
{"text": "In the larynx , papillomas were detectable in all MS - exposed groups in a non - concentration dependent manner .", "entity": [], "task": "NER"}
{"text": "No other extra - pulmonary MS - dependent neoplastic lesions were found .", "entity": [], "task": "NER"}
{"text": "Gene expression signatures of lung tumor tissues allowed a clear differentiation of sham - and high dose MS - exposed mice .", "entity": [], "task": "NER"}
{"text": "In combination with data from previous smoke inhalation studies with A / J mice , the current data suggest that this model for MS inhalation - induced pulmonary tumorigenesis is reliable and relevant , two crucial requirements towards validation of such a model .", "entity": [], "task": "NER"}
{"text": "Dichloro - dihydro - fluorescein diacetate ( DCFH - DA ) assay : a quantitative method for oxidative stress assessment of nanoparticle - treated cells .", "entity": [{"entity": "Dichloro - dihydro - fluorescein diacetate", "entity_type": "Chemical", "pos": [0, 42]}, {"entity": "DCFH - DA", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "No consensus exists on how to address possible toxicity of nanomaterials as they interfere with most in vitro screening tests based on colorimetric and fluorimetric probes such as the dichloro - dihydro - fluorescein diacetate ( DCFH - DA ) assay for detection of oxidative species .", "entity": [{"entity": "dichloro - dihydro - fluorescein diacetate", "entity_type": "Chemical", "pos": [184, 226]}, {"entity": "DCFH - DA", "entity_type": "Chemical", "pos": [229, 238]}], "task": "NER"}
{"text": "In the present research , nanomaterial interaction with DCFH - DA was studied in relation to its nature and / or assay conditions ( cell - based and time exposure ) by incubating Rhodamine ( Rhd ) - labeled 25nm and 50nm silica ( SiO2 ) , naked and oleic acid coated magnetite , ( Fe3O4 ) and maghemite ( Fe2O3 ) iron oxide , titanium dioxide ( TiO2 ) and poly ( ethylene oxide ) - poly ( lactide / glycolide ) acid ( PLGA - PEO ) nanoparticles ( NPs ) with metabolically active rat hepatocytes for 4 and 24 - h periods .", "entity": [{"entity": "DCFH - DA", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "Rhodamine", "entity_type": "Chemical", "pos": [179, 188]}, {"entity": "Rhd", "entity_type": "Chemical", "pos": [191, 194]}, {"entity": "silica", "entity_type": "Chemical", "pos": [221, 227]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [230, 234]}, {"entity": "oleic acid coated magnetite", "entity_type": "Chemical", "pos": [249, 276]}, {"entity": "Fe3O4", "entity_type": "Chemical", "pos": [281, 286]}, {"entity": "maghemite", "entity_type": "Chemical", "pos": [293, 302]}, {"entity": "Fe2O3", "entity_type": "Chemical", "pos": [305, 310]}, {"entity": "iron oxide", "entity_type": "Chemical", "pos": [313, 323]}, {"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [326, 342]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [345, 349]}, {"entity": "poly ( ethylene oxide ) - poly ( lactide / glycolide ) acid", "entity_type": "Chemical", "pos": [356, 415]}, {"entity": "PLGA - PEO", "entity_type": "Chemical", "pos": [418, 428]}], "task": "NER"}
{"text": "Data indicated that nanoparticle uptake correlated with quenching of dye fluorescence emission .", "entity": [], "task": "NER"}
{"text": "In spite of their masking effect , the oxidative potential of NPs could be detected at a limited threshold concentration when exposed for periods of time longer than those frequently used for this test .", "entity": [], "task": "NER"}
{"text": "However , changes in the experimental conditions did not systematically result in free radical formation for all nanomaterials tested .", "entity": [], "task": "NER"}
{"text": "Overall data indicate that despite the quenching effect of nanoparticles on DCFH - DA assay , it can be considered as a useful tool for quantitative measurement of NPs - induced oxidative stress by minor modifications of standardized protocols .", "entity": [{"entity": "DCFH - DA", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Formation of mainstream cigarette smoke constituents prioritized by the World Health Organization - - yield patterns observed in market surveys , clustering and inverse correlations .", "entity": [], "task": "NER"}
{"text": "The WHO TobReg proposed mandating ceilings on selected smoke constituents determined from the market - specific median of nicotine - normalized yield distributions .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [122, 130]}], "task": "NER"}
{"text": "Data validating this regulatory concept were obtained from essentially single - blend surveys .", "entity": [], "task": "NER"}
{"text": "This process is strongly impacted by inverse correlations among yields .", "entity": [], "task": "NER"}
{"text": "In the present study , 18 priority WHO smoke constituent yields ( nicotine - normalized ) were determined ( using two smoking regimens ) from 262 commercial brands including American , Virginia and local blends from 13 countries .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "Principal Component Analysis was used to identify yields patterns , clustering of blend types and the inverse correlations causing these clusters .", "entity": [], "task": "NER"}
{"text": "Three principal components explain about 75 % of total data variability .", "entity": [], "task": "NER"}
{"text": "PC1 was sensitive to the relative levels of gas - and particle - phase compounds .", "entity": [], "task": "NER"}
{"text": "PC2 and PC3 cluster American - and Virginia - blends , revealing inverse correlations : Nitrogen oxides and amino - or nitroso - aromatic compounds inversely correlate to either formaldehyde and acrolein , or benzo ( a ) pyrene and di - hydroxybenzenes .", "entity": [{"entity": "Nitrogen oxides", "entity_type": "Chemical", "pos": [88, 103]}, {"entity": "amino", "entity_type": "Chemical", "pos": [108, 113]}, {"entity": "nitroso", "entity_type": "Chemical", "pos": [119, 126]}, {"entity": "formaldehyde", "entity_type": "Chemical", "pos": [178, 190]}, {"entity": "acrolein", "entity_type": "Chemical", "pos": [195, 203]}, {"entity": "benzo ( a ) pyrene", "entity_type": "Chemical", "pos": [209, 227]}, {"entity": "di - hydroxybenzenes", "entity_type": "Chemical", "pos": [232, 252]}], "task": "NER"}
{"text": "These results can be explained by reviewing the processes determining each components smoke delivery .", "entity": [], "task": "NER"}
{"text": "Regulatory initiatives simultaneously targeting selected smoke constituents in markets with mixed blend styles will be strongly impacted by the inverse correlations described .", "entity": [], "task": "NER"}
{"text": "It is difficult to predict the ultimate impact of such regulations on public health , considering the complex chemistry of cigarette smoke formation .", "entity": [], "task": "NER"}
{"text": "The association between daily calcium intake and sarcopenia in older , non - obese Korean adults : the fourth Korea national health and nutrition examination survey ( KNHANES IV ) 2009 .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Recent data suggest that variations in calcium intake may influence body weight and composition ; however , the relationship between daily calcium intake and muscle mass has not been well established .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "The objective of this study was to assess the relationship between daily calcium intake and sarcopenia .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [73, 80]}], "task": "NER"}
{"text": "We analyzed data for older adults ( over 60 years ) from the fourth Korea National Health and Nutrition Examination Survey ( KNHANES ) conducted in 2009 .", "entity": [], "task": "NER"}
{"text": "A total of 1339 Non - Obese ( BMI between 18 . 5 and 25 kg / m ( 2 ) ) , older adults ( 592 men and 707 women ) were enrolled .", "entity": [], "task": "NER"}
{"text": "Dietary variables were assessed using a nutrition survey that used a 24 - hour recall method .", "entity": [], "task": "NER"}
{"text": "Daily calcium intake based on the consumption of each food item was calculated .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [6, 13]}], "task": "NER"}
{"text": "Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight less than 2 SD below the sex - specific mean for young adults .", "entity": [], "task": "NER"}
{"text": "We found that daily calcium intake was negatively correlated with total body fat percentage and positively correlated with appendicular skeletal mass ( p < 0 . 001 ) .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [20, 27]}], "task": "NER"}
{"text": "Participants with sarcopenia appear to have significantly lower daily calcium intakes than participants without sarcopenia ( p < 0 . 001 ) .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "The unadjusted prevalence of sarcopenia according to daily calcium intake tertiles were 6 . 3 % , 4 . 3 % , and 2 . 7 % in tertiles 1 , 2 , and 3 , respectively .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "After adjustment for age , sex , BMI , total energy intake , and lifestyle factors , compared with those in the lowest tertile of daily calcium intake , participants in the highest tertile had an odds ratio for sarcopenia of 0 . 295 ( 95 % confidence interval , 0 . 087 - 0 . 768 ; p for trend = 0 . 014 ) .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [136, 143]}], "task": "NER"}
{"text": "We found that daily calcium intake , corrected for total energy intake and serum 25 ( OH ) D status , was significantly lower in subjects with sarcopenia than in those without .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [81, 92]}], "task": "NER"}
{"text": "Our results suggest a strong inverse association between daily calcium intake and sarcopenia in non - obese , older Korean adults .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast .", "entity": [{"entity": "dieldrin", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [80, 87]}], "task": "NER"}
{"text": "Exposure to organochlorinated pesticides such as dieldrin has been linked to Parkinson ' s and Alzheimer ' s diseases , endocrine disruption , and cancer , but the cellular and molecular mechanisms of toxicity behind these effects remain largely unknown .", "entity": [{"entity": "dieldrin", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Here we demonstrate , using a functional genomics approach in the model eukaryote Saccharomyces cerevisiae , that dieldrin alters leucine availability .", "entity": [{"entity": "dieldrin", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [130, 137]}], "task": "NER"}
{"text": "This model is supported by multiple lines of congruent evidence : ( 1 ) mutants defective in amino acid signaling or transport are sensitive to dieldrin , which is reversed by the addition of exogenous leucine ; ( 2 ) dieldrin sensitivity of wild - type or mutant strains is dependent upon leucine concentration in the media ; ( 3 ) overexpression of proteins that increase intracellular leucine confer resistance to dieldrin ; ( 4 ) leucine uptake is inhibited in the presence of dieldrin ; and ( 5 ) dieldrin induces the amino acid starvation response .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [93, 103]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [144, 152]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [202, 209]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [218, 226]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [290, 297]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [388, 395]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [417, 425]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [434, 441]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [481, 489]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [502, 510]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [523, 533]}], "task": "NER"}
{"text": "Additionally , we demonstrate that appropriate negative regulation of the Ras / protein kinase A pathway , along with an intact pyruvate dehydrogenase complex , is required for dieldrin tolerance .", "entity": [{"entity": "pyruvate", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "dieldrin", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "Many yeast genes described in this study have human orthologs that may modulate dieldrin toxicity in humans .", "entity": [{"entity": "dieldrin", "entity_type": "Chemical", "pos": [80, 88]}], "task": "NER"}
{"text": "Brain hemispheric differences in the neurochemical effects of lead , prenatal stress , and the combination and their amelioration by behavioral experience .", "entity": [], "task": "NER"}
{"text": "Brain lateralization , critical to mediation of cognitive functions and to \" multitasking , \" is disrupted in conditions such as attention deficit disorder and schizophrenia .", "entity": [], "task": "NER"}
{"text": "Both low - level lead ( Pb ) exposure and prenatal stress ( PS ) have been associated with mesocorticolimbic system - mediated executive - function cognitive and attention deficits .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [24, 26]}], "task": "NER"}
{"text": "Mesocorticolimbic systems demonstrate significant laterality .", "entity": [], "task": "NER"}
{"text": "Thus , altered brain lateralization could play a role in this behavioral toxicity .", "entity": [], "task": "NER"}
{"text": "This study examined laterality of mesocorticolimbic monoamines ( frontal cortex , nucleus accumbens , striatum , midbrain ) and amino acids ( frontal cortex ) in male and female rats subjected to lifetime Pb exposure ( 0 or 50 ppm in drinking water ) , PS ( restraint stress on gestational days 16 - 17 ) , or the combination with and without repeated learning behavioral experience .", "entity": [{"entity": "monoamines", "entity_type": "Chemical", "pos": [52, 62]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [128, 139]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [205, 207]}], "task": "NER"}
{"text": "Control males exhibited prominent laterality , particularly in midbrain and also in frontal cortex and striatum ; females exhibited less laterality , and this was primarily striatal .", "entity": [], "task": "NER"}
{"text": "Lateralized Pb +/- PS induced neurotransmitter changes were assessed only in males because of limited sample sizes of Pb + PS females .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [12, 14]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [118, 120]}], "task": "NER"}
{"text": "In males , Pb +/- PS changes occurred in left hemisphere of frontal cortex and right hemisphere of midbrain .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [11, 13]}], "task": "NER"}
{"text": "Behavioral experience modified the laterality of Pb +/- PS - induced neurotransmitter changes in a region - dependent manner .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [49, 51]}], "task": "NER"}
{"text": "Notably , behavioral experience eliminated Pb +/- PS neurotransmitter changes in males .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [43, 45]}], "task": "NER"}
{"text": "These findings underscore the critical need to evaluate both sexes and brain hemispheres for the mechanistic understanding of sex - dependent differences in neuro - and behavioral toxicity .", "entity": [], "task": "NER"}
{"text": "Furthermore , assessment of central nervous system mechanisms in the absence of behavioral experience , shown here for males , may constitute less relevant models of human health effects .", "entity": [], "task": "NER"}
{"text": "Transcriptome alterations following developmental atrazine exposure in zebrafish are associated with disruption of neuroendocrine and reproductive system function , cell cycle , and carcinogenesis .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Atrazine , a herbicide commonly applied to agricultural areas and a common contaminant of potable water supplies , is implicated as an endocrine - disrupting chemical ( EDC ) and potential carcinogen .", "entity": [{"entity": "Atrazine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Studies show that EDCs can cause irreversible changes in tissue formation , decreased reproductive potential , obesity , and cancer .", "entity": [], "task": "NER"}
{"text": "The U . S .", "entity": [], "task": "NER"}
{"text": "Environmental Protection Agency considers an atrazine concentration of <= 3 ppb in drinking water safe for consumption .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "The specific adverse human health effects associated with a developmental atrazine exposure and the underlying genetic mechanisms of these effects are not well defined .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "In this study , zebrafish embryos were exposed to a range of atrazine concentrations to establish toxicity .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "Morphological , transcriptomic , and protein alterations were then assessed at 72h postfertilization following developmental atrazine exposure at 0 , 0 . 3 , 3 , or 30 ppb .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [125, 133]}], "task": "NER"}
{"text": "A significant increase in head length was observed in all three atrazine treatments .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "Transcriptomic profiles revealed 21 , 62 , and 64 genes with altered expression in the 0 . 3 , 3 , and 30 ppb atrazine treatments , respectively .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [110, 118]}], "task": "NER"}
{"text": "Altered genes were associated with neuroendocrine and reproductive system development , function , and disease ; cell cycle control ; and carcinogenesis .", "entity": [], "task": "NER"}
{"text": "There was a significant overlap ( 42 genes ) between the 3 and 30 ppb differentially expressed gene lists , with two of these genes ( CYP17A1 and SAMHD1 ) present in all three atrazine treatments .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [176, 184]}], "task": "NER"}
{"text": "Increased transcript levels were translated to significant upregulation in protein expression .", "entity": [], "task": "NER"}
{"text": "Overall , this study identifies genetic and molecular targets altered in response to a developmental atrazine exposure to further define the biological pathways and mechanisms of toxicity .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "Integrative Analysis of miRNA and inflammatory gene expression after acute particulate matter exposure .", "entity": [], "task": "NER"}
{"text": "MicroRNAs ( miRNAs ) are environmentally sensitive inhibitors of gene expression that may mediate the effects of metal - rich particulate matter ( PM ) and toxic metals on human individuals .", "entity": [], "task": "NER"}
{"text": "Previous environmental miRNA studies have investigated a limited number of candidate miRNAs and have not yet evaluated the functional effects on gene expression .", "entity": [], "task": "NER"}
{"text": "In this study , we wanted to identify PM - sensitive miRNAs using microarray profiling on matched baseline and postexposure RNA from foundry workers with well - characterized exposure to metal - rich PM and to characterize miRNA relations with expression of candidate inflammatory genes .", "entity": [], "task": "NER"}
{"text": "We applied microarray analysis of 847 human miRNAs and real - time PCR analysis of 18 candidate inflammatory genes on matched blood samples collected from foundry workers at baseline and after 3 days of work ( postexposure ) .", "entity": [], "task": "NER"}
{"text": "We identified differentially expressed miRNAs ( fold change [ FC ] > 2 and p < 0 . 05 ) and correlated their expression with the inflammatory associated genes .", "entity": [], "task": "NER"}
{"text": "We performed in silico network analysis in MetaCore v6 . 9 to characterize the biological pathways connecting miRNA - mRNA pairs .", "entity": [], "task": "NER"}
{"text": "Microarray analysis identified four miRNAs that were differentially expressed in postexposure compared with baseline samples , including miR - 421 ( FC = 2 . 81 , p < 0 . 001 ) , miR - 146a ( FC = 2 . 62 , p = 0 . 007 ) , miR - 29a ( FC = 2 . 91 , p < 0 . 001 ) , and let - 7g ( FC = 2 . 73 , p = 0 . 019 ) .", "entity": [], "task": "NER"}
{"text": "Using false discovery date adjustment for multiple comparisons , we found 11 miRNA - mRNA correlated pairs involving the 4 differentially expressed miRNAs and candidate inflammatory genes .", "entity": [], "task": "NER"}
{"text": "In silico network analysis with MetaCore database identified biological interactions for all the 11 miRNA - mRNA pairs , which ranged from direct mRNA targeting to complex interactions with multiple intermediates .", "entity": [], "task": "NER"}
{"text": "Acute PM exposure may affect gene regulation through PM - responsive miRNAs that directly or indirectly control inflammatory gene expression .", "entity": [], "task": "NER"}
{"text": "Molecular mechanisms of central leptin resistance in obesity .", "entity": [], "task": "NER"}
{"text": "The rapidly increasing prevalence of obesity confers a huge health burden globally .", "entity": [], "task": "NER"}
{"text": "The hypothalamus plays a central role in the regulation of energy homeostasis by integrating multiple metabolic signals from peripheral organs and modulating feeding behavior and energy metabolism .", "entity": [], "task": "NER"}
{"text": "Leptin , a key appetite - regulating hormone derived from the white adipose tissue , primarily acts on hypothalamic neurons to activate catabolic pathway and inhibit anabolic pathway , which can result in anorexia and weight reduction .", "entity": [], "task": "NER"}
{"text": "Despite striking obesity resulting from leptin deficiency , treatment with this hormone in human obesity has been unsuccessful due to leptin resistance .", "entity": [], "task": "NER"}
{"text": "In this review , we describe recent researches extending our understanding of obesity - associated hypothalamic leptin resistance .", "entity": [], "task": "NER"}
{"text": "Evaluation of Current Eligibility Criteria for Bariatric Surgery : Diabetes prevention and risk factor changes in the Swedish Obese Subjects ( SOS ) study .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE Patients with a BMI < 35 kg / m ( 2 ) and patients with a BMI between 35 and 40 kg / m ( 2 ) without comorbidities are noneligible by current eligibility criteria for bariatric surgery .", "entity": [], "task": "NER"}
{"text": "We used Swedish obese subjects ( SOS ) to explore long - term outcomes in noneligible versus eligible patients .", "entity": [], "task": "NER"}
{"text": "RESEARCH DESIGN AND METHODS The SOS study involved 2 , 010 obese patients who underwent bariatric surgery ( 68 % vertical - banded gastroplasty , 19 % banding , and 13 % gastric bypass ) and 2 , 037 contemporaneously matched obese controls receiving usual care .", "entity": [], "task": "NER"}
{"text": "At inclusion , the participant age was 37 - 60 years and BMI was >= 34 kg / m ( 2 ) in men and >= 38 kg / m ( 2 ) in women .", "entity": [], "task": "NER"}
{"text": "The effect of surgery was assessed in patients that do ( n = 3 , 814 ) and do not ( n = 233 ) meet current eligibility criteria .", "entity": [], "task": "NER"}
{"text": "The date of analysis was 1 January 2012 .", "entity": [], "task": "NER"}
{"text": "The follow - up time was up to 20 years , with a median of 10 years .", "entity": [], "task": "NER"}
{"text": "RESULTS Cardiovascular risk factors were significantly improved both in noneligible and eligible individuals after 10 years of follow - up .", "entity": [], "task": "NER"}
{"text": "Surgery reduced the diabetes incidence in both the noneligible ( adjusted hazard ratio 0 . 33 [ 95 % CI 0 . 13 - 0 . 82 ] , P = 0 . 017 ) and eligible ( 0 . 27 [ 0 . 22 - 0 . 33 ] , P < 0 . 001 ) groups .", "entity": [], "task": "NER"}
{"text": "We could not detect a difference in the effect of surgery between the groups ( adjusted interaction P value = 0 . 713 ) .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS Bariatric surgery drastically reduced the incidence of type 2 diabetes both in noneligible and eligible patients and improved cardiovascular risk factors in both groups .", "entity": [], "task": "NER"}
{"text": "Our results show that strict BMI cutoffs are of limited use for bariatric surgery prioritization if the aim is to prevent diabetes and improve cardiovascular risk factors .", "entity": [], "task": "NER"}
{"text": "GLP - 1 Action and Glucose Tolerance in Subjects With Remission of Type 2 Diabetes Mellitus After Gastric Bypass Surgery .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "OBJECTIVEGlucagon like peptide - 1 ( GLP - 1 ) has been suggested as a major factor for the improved glucose tolerance ensuing after Roux - en - Y Gastric Bypass ( RYGBP ) surgery .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "We examined the effect of blocking endogenous GLP - 1 action on glucose tolerance in subjects with sustained remission of type 2 diabetes ( T2DM ) present before RYGBP . RESEARCH DESIGN AND METHODSBlood glucose , insulin , C - peptide , glucagon , GLP - 1 , and glucose - dependent insulinotropic peptide levels were measured after a meal challenge with either exendin - ( 9 - 39 ) ( a GLP - 1r antagonist ) or saline infusion in eight subjects with sustained remission of T2DM after RYGBP and seven healthy controls . RESULTSInfusion of exendin - ( 9 - 39 ) resulted in marginal deterioration of the 2 - h plasma glucose after meal intake in RYGBP subjects ( saline 78 . 4 +/- 15 . 1 mg / dL compared with exendin - ( 9 - 39 ) 116 . 5 +/- 22 . 3 mg / dL ; P < 0 . 001 ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [203, 210]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [262, 269]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [614, 621]}], "task": "NER"}
{"text": "Furthermore , glucose response to meal intake was similarly enlarged in the two study groups ( percent change in the area under the curve of glucose exendin - ( 9 - 39 ) - infusion versus saline - infusion : controls 10 . 84 +/- 8 . 8 % versus RYGBP 9 . 94 +/- 8 . 4 % ; P = 0 . 884 ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [141, 148]}], "task": "NER"}
{"text": "In the RYGBP group , the blockade of the enlarged GLP - 1 response to meal intake resulted in reduced insulin ( P = 0 . 001 ) and C - peptide ( P < 0 . 001 ) , but no change in glucagon ( P = 0 . 258 ) responses . CONCLUSIONThe limited deterioration of glucose tolerance on blockade of GLP - 1 action in our study suggests the resolution of T2DM after RYGBP may be explained by mechanisms beyond enhancement of GLP - 1 action .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [253, 260]}], "task": "NER"}
{"text": "Case study of the Swiss flora for prior phytochemical and biological investigations .", "entity": [], "task": "NER"}
{"text": "Estimates in the literature as to what extent the world ' s higher plant species have been studied chemically or for bioactivity are contradictory and range from 0 . 5 % to > 12 % .", "entity": [], "task": "NER"}
{"text": "In this survey , a model to make credible estimates of the extent of their study is proposed and is exemplified by applying it in a case study of plants native to Switzerland .", "entity": [], "task": "NER"}
{"text": "Using a widely available database ( SciFinder Scholar ) , 454 535 literature references for the 2677 native Swiss plant species were retrieved .", "entity": [], "task": "NER"}
{"text": "It was determined that 55 % of these species have been investigated phytochemically and 28 % for biological activity .", "entity": [], "task": "NER"}
{"text": "The influence of factors such as commonness , growth form , habitat , medicinal use , and reported toxicity on the extent to which different plant groups have been studied is analyzed .", "entity": [], "task": "NER"}
{"text": "The predictive value of random sampling of subsets of plants is compared to the study of the entire Swiss flora , to show that a credible estimate of the extent of prior studies can be achieved with just 5 % of these species .", "entity": [], "task": "NER"}
{"text": "Bioactive sesterterpenoids from a Korean sponge Monanchora sp .", "entity": [{"entity": "sesterterpenoids", "entity_type": "Chemical", "pos": [10, 26]}], "task": "NER"}
{"text": "Chemical investigation of a Korean marine sponge , Monanchora sp . , yielded nine new sesterterpenoids ( 1 - 9 ) along with phorbaketals A - C ( 10 - 12 ) .", "entity": [{"entity": "sesterterpenoids", "entity_type": "Chemical", "pos": [86, 102]}, {"entity": "phorbaketals A - C", "entity_type": "Chemical", "pos": [124, 142]}], "task": "NER"}
{"text": "The planar structures were established on the basis of NMR and MS analysis , and the absolute configurations of 1 - 9 were defined using the modified Mosher ' s method and CD spectroscopic data analysis .", "entity": [], "task": "NER"}
{"text": "Compounds 1 - 8 , designated as phorbaketals D - K , possess a spiroketal - modified benzopyran moiety such as phorbaketal A , and their structural variations are due to oxidation and / or reduction of the tricyclic core or the side chain .", "entity": [{"entity": "phorbaketals D - K", "entity_type": "Chemical", "pos": [32, 50]}, {"entity": "spiroketal", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "benzopyran", "entity_type": "Chemical", "pos": [85, 95]}, {"entity": "phorbaketal A", "entity_type": "Chemical", "pos": [111, 124]}], "task": "NER"}
{"text": "Compound 9 , designated as phorbin A , has a monocyclic structure and is proposed to be a possible biogenetic precursor of the phorbaketals .", "entity": [{"entity": "phorbin A", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "phorbaketals", "entity_type": "Chemical", "pos": [127, 139]}], "task": "NER"}
{"text": "Compounds 1 - 9 were evaluated for cytotoxicity against four human cancer cell lines ( A498 , ACHN , MIA - paca , and PANC - 1 ) , and a few of them were found to exhibit cytotoxic activity .", "entity": [], "task": "NER"}
{"text": "Modulation of cytochrome P450 enzymes in response to continuous or intermittent high - fat diet in pigs .", "entity": [], "task": "NER"}
{"text": "To date , no information has been available on the modulation of cytochrome P450 enzymes ( CYPs ) following the administration of a hyperlipidemic diet in pigs .", "entity": [], "task": "NER"}
{"text": "We investigated the potential modulation of xenobiotic - metabolizing CYPs in liver , heart and duodenum of pigs subjected to a high - fat / high - cholesterol diet for 2 months continuously ( C - HFD ) or on alternate weeks ( A - HFD ) .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [148, 159]}], "task": "NER"}
{"text": "The administration of the high - fat diet resulted in considerably increased plasma cholesterol levels although the animals were still able to manage the lipid overload efficiently , and no sign of effective tissue inflammation occurred in livers .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [84, 95]}], "task": "NER"}
{"text": "Plasma lipid profile and liver histology indicated a better adaptive response of the A - HFD pigs compared to the C - HFD group .", "entity": [], "task": "NER"}
{"text": "We showed a post - transcriptional induction of hepatic CYP2E1 activity in C - HFD pigs and a transcriptional induction of hepatic CYP3As - especially in the A - HFD group .", "entity": [], "task": "NER"}
{"text": "No further CYP modulation was observed in either liver or extra - hepatic tissues .", "entity": [], "task": "NER"}
{"text": "In conclusion , the administration of a high - fat diet in pigs resulted in limited effects on the drug metabolism system .", "entity": [], "task": "NER"}
{"text": "The better adaptive response of A - HFD pigs compared to C - HFD pigs is a very interesting observation since the intermittent administration of the diet reflects the mode of human behavior more closely .", "entity": [], "task": "NER"}
{"text": "Therapeutic potential of targeting lipid aldehydes and lipoxidation end - products in the treatment of ocular disease .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [41, 50]}], "task": "NER"}
{"text": "Lipoxidation reactions and the subsequent accumulation of advanced lipoxidation end products ( ALEs ) have been implicated in the pathogenesis of many of the leading causes of visual impairment .", "entity": [], "task": "NER"}
{"text": "Here , we begin by outlining some of the major lipid aldehydes produced through lipoxidation reactions , the ALEs formed upon their reaction with proteins , and the endogenous aldehyde metabolizing enzymes involved in protecting cells against lipoxidation mediated damage .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [53, 62]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [176, 184]}], "task": "NER"}
{"text": "Discussions are subsequently focused on the clinical and experimental evidence supporting the contribution of lipid aldehydes and ALEs in the development of ocular diseases .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [116, 125]}], "task": "NER"}
{"text": "From these discussions , it is clear that inhibition of lipoxidation reactions and ALE formation could represent a new therapeutic avenue for the treatment of a broad range of ocular disorders .", "entity": [], "task": "NER"}
{"text": "Current and emerging pharmacological strategies to prevent or neutralize the effects of lipid aldehydes and ALEs are therefore considered , with particular emphasis on the potential of these drugs for treatment of diseases of the eye .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [94, 103]}], "task": "NER"}
{"text": "Exploring a new frontier in cancer treatment : targeting the ubiquitin and ubiquitin - like activating enzymes .", "entity": [], "task": "NER"}
{"text": "The labeling of proteins with small ubiquitin ( Ub ) and ubiquitin - like ( Ubl ) modifiers regulates a plethora of activities within the cell , such as protein recycling , cell cycle modifications , and protein translocation .", "entity": [], "task": "NER"}
{"text": "These processes are often overactive in diseased cells , leading to unregulated cell growth and disease progression .", "entity": [], "task": "NER"}
{"text": "Therefore , in systems where Ub / Ubl protein labeling is dysregulated , the development of drugs to selectively and potently disrupt Ub / Ubl protein labeling offers a targeted molecular approach for sensitizing these diseased cells .", "entity": [], "task": "NER"}
{"text": "This Perspective outlines the progress that has been made in the context of inhibitor development for targeting Ub / Ubl pathways .", "entity": [], "task": "NER"}
{"text": "Parallel nanometric 3D tracking of intracellular gold nanorods using multifocal two - photon microscopy .", "entity": [], "task": "NER"}
{"text": "We report a novel technique for long - term parallel three dimensional ( 3D ) - tracking of gold nanorods in live cells with nanometer resolution .", "entity": [], "task": "NER"}
{"text": "Gold nanorods feature a strong plasmon - enhanced two - photon luminescence , can be easily functionalized , and have been shown to be nontoxic .", "entity": [], "task": "NER"}
{"text": "These properties make gold nanorods very suitable for in vivo two - photon luminescence microscopy .", "entity": [], "task": "NER"}
{"text": "By rapid multifocal scanning , we combine the advantages of 3D molecular tracking methods using wide - field imaging with the advantages of two - photon microscopy .", "entity": [], "task": "NER"}
{"text": "Isolated gold nanorods can be localized with a resolution of 4 nm in the xy - plane and 8 nm in the z - direction .", "entity": [], "task": "NER"}
{"text": "The polarization - dependence of the two - photon luminescence signal can be used to resolve the angular orientation , even when two gold nanorods are separated by less than the diffraction limit .", "entity": [], "task": "NER"}
{"text": "Individual nanorods in live U2OS cells could be followed in 3 dimensions for over 30 min , with a photon noise limited accuracy , and a time resolution of 50 ms in 2D and 500 ms in 3D .", "entity": [], "task": "NER"}
{"text": "Discovery of a potent and isoform - selective targeted covalent inhibitor of the lipid kinase PI3K alpha .", "entity": [], "task": "NER"}
{"text": "PI3K alpha has been identified as an oncogene in human tumors .", "entity": [], "task": "NER"}
{"text": "By use of rational drug design , a targeted covalent inhibitor 3 ( CNX - 1351 ) was created that potently and specifically inhibits PI3K alpha .", "entity": [{"entity": "CNX - 1351", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "We demonstrate , using mass spectrometry and X - ray crystallography , that the selective inhibitor covalently modifies PI3K alpha on cysteine 862 ( C862 ) , an amino acid unique to the alpha isoform , and that PI3K beta , - gamma , and - delta are not covalently modified .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [134, 142]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [161, 171]}], "task": "NER"}
{"text": "3 is able to potently ( EC ( 50 ) < 100 nM ) and specifically inhibit signaling in PI3K alpha - dependent cancer cell lines , and this leads to a potent antiproliferative effect ( GI ( 50 ) < 100 nM ) .", "entity": [], "task": "NER"}
{"text": "A covalent probe , 8 ( CNX - 1220 ) , which selectively bonds to PI3K alpha , was used to investigate the duration of occupancy of 3 with PI3K alpha in vivo .", "entity": [{"entity": "CNX - 1220", "entity_type": "Chemical", "pos": [23, 33]}], "task": "NER"}
{"text": "This is the first report of a PI3K alpha - selective inhibitor , and these data demonstrate the biological impact of selectively targeting PI3K alpha .", "entity": [], "task": "NER"}
{"text": "Synthesis and Structure - Activity Relationships of N - Methyl - 5 , 6 , 7 - trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents .", "entity": [{"entity": "N - Methyl - 5 , 6 , 7 - trimethoxylindoles", "entity_type": "Chemical", "pos": [52, 95]}], "task": "NER"}
{"text": "Several new series of 5 , 6 , 7 - trimethoxyindole derivatives were synthesized and their structure - activity relationships ( SARs ) were studied .", "entity": [{"entity": "5 , 6 , 7 - trimethoxyindole", "entity_type": "Chemical", "pos": [22, 50]}], "task": "NER"}
{"text": "Some of these compounds exhibited strong antiproliferative activities in the submicromolar range .", "entity": [], "task": "NER"}
{"text": "N - Methyl - 5 , 6 , 7 - trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities , with IC ( 50 ) values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells ( HUVECs ) .", "entity": [{"entity": "N - Methyl - 5 , 6 , 7 - trimethoxylindoles", "entity_type": "Chemical", "pos": [0, 43]}], "task": "NER"}
{"text": "In addition to vascular disrupting activity verified by in vitro assays , compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA - 4 .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [187, 197]}, {"entity": "combretastatinA - 4", "entity_type": "Chemical", "pos": [202, 221]}], "task": "NER"}
{"text": "The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2 / M phase after treatment with 21 and 31 .", "entity": [], "task": "NER"}
{"text": "It was showed that 21 disrupted tumor vasculature by use of in vivo assay .", "entity": [], "task": "NER"}
{"text": "Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents .", "entity": [], "task": "NER"}
{"text": "Bisphenol A activates the Nrf1 / 2 - antioxidant response element pathway in HEK 293 cells .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is used in the production of polycarbonate plastics and epoxy resins for baby bottles , liners of canned food , and many other consumer products .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "polycarbonate", "entity_type": "Chemical", "pos": [49, 62]}], "task": "NER"}
{"text": "Previously , BPA has been shown to reduce the activity of several antioxidant enzymes , which may contribute to oxidative stress .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [13, 16]}], "task": "NER"}
{"text": "However , the underlying mechanism of the BPA - mediated effect upon antioxidant enzyme activity is unknown .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [42, 45]}], "task": "NER"}
{"text": "Antioxidant and phase II metabolizing enzymes protect cells from oxidative stress and are transcriptionally activated by Nrf1 and Nrf2 factors through their cis - regulatory antioxidant response elements ( AREs ) .", "entity": [], "task": "NER"}
{"text": "In this work , we have assessed the effect of BPA on the Nrf1 / 2 - ARE pathway in cultured human embryonic kidney ( HEK ) 293 cells .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "Surprisingly , glutathione and reactive oxygen species ( ROS ) assays revealed that BPA application created a more reduced intracellular environment in cultured HEK 293 cells .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [15, 26]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [40, 46]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Furthermore , BPA increased the transactivation activity of ectopic Nrf1 and Nrf2 and increased the expression of ARE - target genes ho - 1 and nqo1 at high ( 100 - 200 mu M ) BPA concentrations only .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [176, 179]}], "task": "NER"}
{"text": "Our study suggests that BPA activates the Nrf1 / 2 - ARE pathway at high ( > 10 mu M ) micromolar concentrations .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [24, 27]}], "task": "NER"}
{"text": "Organoselenium compounds modulate extracellular redox by induction of extracellular cysteine and cell surface thioredoxin reductase .", "entity": [{"entity": "Organoselenium", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "The effect of selenium compounds on extracellular redox modulating capacity was studied in murine macrophage RAW 264 . 7 cells and differentiated human THP - 1 monocytes .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [14, 22]}], "task": "NER"}
{"text": "The arylselenium compounds benzeneselenol ( PhSeH ) , dibenzyl diselenide ( DBDSe ) , diphenyl diselenide ( DPDSe ) , and ebselen were capable of inducing extracellular cysteine accumulation via a cystine - and glucose - dependent process .", "entity": [{"entity": "arylselenium", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "benzeneselenol", "entity_type": "Chemical", "pos": [27, 41]}, {"entity": "PhSeH", "entity_type": "Chemical", "pos": [44, 49]}, {"entity": "dibenzyl diselenide", "entity_type": "Chemical", "pos": [54, 73]}, {"entity": "DBDSe", "entity_type": "Chemical", "pos": [76, 81]}, {"entity": "diphenyl diselenide", "entity_type": "Chemical", "pos": [86, 105]}, {"entity": "DPDSe", "entity_type": "Chemical", "pos": [108, 113]}, {"entity": "ebselen", "entity_type": "Chemical", "pos": [122, 129]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [169, 177]}, {"entity": "cystine", "entity_type": "Chemical", "pos": [197, 204]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [211, 218]}], "task": "NER"}
{"text": "Extracellular cysteine production was dose - dependently inhibited by glutamate , an inhibitor of cystine / glutamate antiporter ( Xc ( - ) transporter ) , supporting the involvement of Xc ( - ) transporter for cystine uptake in the above process .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [70, 79]}, {"entity": "cystine", "entity_type": "Chemical", "pos": [98, 105]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "cystine", "entity_type": "Chemical", "pos": [211, 218]}], "task": "NER"}
{"text": "These arylselenium compounds also induced cellular thioredoxin reductase ( TrxR ) expression , particularly at the exofacial surface of cells .", "entity": [{"entity": "arylselenium", "entity_type": "Chemical", "pos": [6, 18]}], "task": "NER"}
{"text": "TrxR1 knockdown using small interfering RNA attenuated TrxR increases and cysteine efflux induced in cells by DPDSe .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [74, 82]}, {"entity": "DPDSe", "entity_type": "Chemical", "pos": [110, 115]}], "task": "NER"}
{"text": "Sodium selenite ( Na2SeO3 ) , selenomethionine ( SeMet ) , seleno - l - cystine ( SeCySS ) , and Se - methylselenocysteine ( MeSeCys ) did not have these effects on macrophages under the same treatment conditions .", "entity": [{"entity": "Sodium selenite", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "Na2SeO3", "entity_type": "Chemical", "pos": [18, 25]}, {"entity": "selenomethionine", "entity_type": "Chemical", "pos": [30, 46]}, {"entity": "SeMet", "entity_type": "Chemical", "pos": [49, 54]}, {"entity": "seleno - l - cystine", "entity_type": "Chemical", "pos": [59, 79]}, {"entity": "SeCySS", "entity_type": "Chemical", "pos": [82, 88]}, {"entity": "Se - methylselenocysteine", "entity_type": "Chemical", "pos": [97, 122]}, {"entity": "MeSeCys", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "The effects of organoselenium compounds on extracellular redox may contribute to the known , but inadequately understood , biological effects of selenium compounds .", "entity": [{"entity": "organoselenium", "entity_type": "Chemical", "pos": [15, 29]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [145, 153]}], "task": "NER"}
{"text": "A nonribosomal peptide synthetase - derived iron ( III ) complex from the pathogenic fungus Aspergillus fumigatus .", "entity": [{"entity": "iron ( III )", "entity_type": "Chemical", "pos": [44, 56]}], "task": "NER"}
{"text": "Small molecules ( SMs ) play central roles as virulence factors of pathogenic fungi and bacteria ; however , genomic analyses suggest that the majority of microbial SMs have remained uncharacterized .", "entity": [], "task": "NER"}
{"text": "Based on microarray analysis followed by comparative metabolomics of overexpression / knockout mutants , we identified a tryptophan - derived iron ( III ) - complex , hexadehydro - astechrome ( HAS ) , as the major product of the cryptic has nonribosomal peptide synthetase ( NRPS ) gene cluster in the human pathogen Aspergillus fumigatus .", "entity": [{"entity": "tryptophan", "entity_type": "Chemical", "pos": [121, 131]}, {"entity": "iron ( III )", "entity_type": "Chemical", "pos": [142, 154]}, {"entity": "hexadehydro - astechrome", "entity_type": "Chemical", "pos": [167, 191]}, {"entity": "HAS", "entity_type": "Chemical", "pos": [194, 197]}], "task": "NER"}
{"text": "Activation of the has cluster created a highly virulent A . fumigatus strain that increased mortality of infected mice .", "entity": [], "task": "NER"}
{"text": "Comparative metabolomics of different mutant strains allowed to propose a pathway for HAS biosynthesis and further revealed cross - talk with another NRPS pathway producing the anticancer fumitremorgins .", "entity": [{"entity": "HAS", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "fumitremorgins", "entity_type": "Chemical", "pos": [188, 202]}], "task": "NER"}
{"text": "Intracellular drug concentrations .", "entity": [], "task": "NER"}
{"text": "Many drug targets are intracellular .", "entity": [], "task": "NER"}
{"text": "To access them , a drug molecule must pass through the cell membrane , a process often facilitated or impeded by transporters .", "entity": [], "task": "NER"}
{"text": "Once in the cytoplasm , basic molecules may become concentrated in organelles .", "entity": [], "task": "NER"}
{"text": "To predict the pharmacologic effect accurately , there must be data concerning the concentration at the target , which is difficult to measure .", "entity": [], "task": "NER"}
{"text": "Techniques that combine mass spectrometry and imaging techniques ( matrix - assisted laser desorption / ionization , secondary ion mass spectrometry ( SIMS ) , and nanoSIMS ) have promise in addressing this problem .", "entity": [], "task": "NER"}
{"text": "Emerging lymphae for the fountain of life .", "entity": [], "task": "NER"}
{"text": "The lymphatic system is indispensable for the collection and cycling of tissue - extravasated fluids , macromolecules and immune cells into the bloodstream .", "entity": [], "task": "NER"}
{"text": "Different mechanisms , including sprouting , ballooning and budding of lymphatic endothelial cells from the cardinal vein , have been proposed for lymphatic vessel formation during mammalial embryogenesis .", "entity": [], "task": "NER"}
{"text": "H a gerling et al ( 2013 ) now provide a cell - scale model of lymphoangiogenesis by applying selective plane illumination - based ultramicroscopy ( Becker et al , 2008 ) to wholemount - immunostained mouse embryos .", "entity": [], "task": "NER"}
{"text": "They describe VEGFR - 3 , VEGF - C and CCBE1 as key regulators of lymphatic endothelial cell budding and migration at the early emergence of lymphatics from venous endothelium .", "entity": [], "task": "NER"}
{"text": "Narrow bandgap colloidal metal chalcogenide quantum dots : synthetic methods , heterostructures , assemblies , electronic and infrared optical properties .", "entity": [], "task": "NER"}
{"text": "The chemistry , material processing and fundamental understanding of colloidal semiconductor nanocrystals ( quantum dots ) are advancing at an astounding rate , bringing the prospects of widespread commercialization of these novel and exciting materials ever closer .", "entity": [], "task": "NER"}
{"text": "Interest in narrow bandgap nanocrystals in particular has intensified in recent years , and the results of research worldwide point to the realistic prospects of applications for these materials in solar cells , infrared optoelectronics ( e . g . lasers , optical modulators , photodetectors and photoimaging devices ) , low cost / large format microelectronics , and in biological imaging and biosensor systems to name only some technologies .", "entity": [], "task": "NER"}
{"text": "Improvements in fundamental understanding and material quality are built on a vast body of experience spread over many different methods of colloidal synthetic growth , each with their own strengths and weaknesses for different materials and sometimes with regard to particular applications .", "entity": [], "task": "NER"}
{"text": "The nanocrystal growth expertise is matched by a rapidly expanding , and highly interdisciplinary , understanding of how best to assemble these materials into films or hybrid composites and thereby into useful devices , and again there are many different strategies that can be adopted .", "entity": [], "task": "NER"}
{"text": "In this review we have attempted to survey and compare the recent work on colloidal synthesis , film and nanocrystal composite material fabrication , concentrating on narrow bandgap chalcogenide materials and some of their topical applications in the solar energy and biological fields .", "entity": [{"entity": "chalcogenide", "entity_type": "Chemical", "pos": [182, 194]}], "task": "NER"}
{"text": "Since these applications are attracting rising interest across a wide range of disciplines , from the biological sciences , device engineering , and materials processing fields as well as the physics and synthetic chemistry communities , we have endeavoured to make the review of these narrow bandgap nanomaterials both comprehensive and accessible to newcomers to the area .", "entity": [], "task": "NER"}
{"text": "Identification of a small - molecule inhibitor of HIV - 1 assembly that targets the phosphatidylinositol ( 4 , 5 ) - bisphosphate binding site of the HIV - 1 matrix protein .", "entity": [{"entity": "phosphatidylinositol ( 4 , 5 ) - bisphosphate", "entity_type": "Chemical", "pos": [84, 129]}], "task": "NER"}
{"text": "The development of drug resistance remains a critical problem for current HIV - 1 antiviral therapies , creating a need for new inhibitors of HIV - 1 replication .", "entity": [], "task": "NER"}
{"text": "We previously reported on a novel anti - HIV - 1 compound , N ( 2 ) - ( phenoxyacetyl ) - N - [ 4 - ( 1 - piperidinylcarbonyl ) benzyl ] glycinamide ( 14 ) , that binds to the highly conserved phosphatidylinositol ( 4 , 5 ) - bisphosphate ( PI ( 4 , 5 ) P ( 2 ) ) binding pocket of the HIV - 1 matrix ( MA ) protein .", "entity": [{"entity": "N ( 2 ) - ( phenoxyacetyl ) - N - [ 4 - ( 1 - piperidinylcarbonyl ) benzyl ] glycinamide", "entity_type": "Chemical", "pos": [60, 148]}, {"entity": "phosphatidylinositol ( 4 , 5 ) - bisphosphate", "entity_type": "Chemical", "pos": [193, 238]}, {"entity": "PI ( 4 , 5 ) P ( 2 )", "entity_type": "Chemical", "pos": [241, 261]}], "task": "NER"}
{"text": "In this study , we re - evaluate the hits from the virtual screen used to identify compound 14 and test them directly in an HIV - 1 replication assay using primary human peripheral blood mononuclear cells .", "entity": [], "task": "NER"}
{"text": "This study resulted in the identification of three new compounds with antiviral activity ; 2 - ( 4 - { [ 3 - ( 4 - fluorophenyl ) - 1 , 2 , 4 - oxadiazol - 5 - yl ] methyl } ) - 1 - piperazinyl ) - N - ( 4 - methylphenyl ) acetamide ( 7 ) , 3 - ( 2 - ethoxyphenyl ) - 5 - [ [ 4 - ( 4 - nitrophenyl ) piperazin - 1 - yl ] methyl ] - 1 , 2 , 4 - oxadiazole ( 17 ) , and N - [ 4 - ethoxy - 3 - ( 1 - piperidinylsulfonyl ) phenyl ] - 2 - ( imidazo [ 2 , 1 - b ] [ 1 , 3 ] thiazol - 6 - yl ) acetamide ( 18 ) , with compound 7 being the most potent of these hits .", "entity": [{"entity": "2 - ( 4 - { [ 3 - ( 4 - fluorophenyl ) - 1 , 2 , 4 - oxadiazol - 5 - yl ] methyl } ) - 1 - piperazinyl ) - N - ( 4 - methylphenyl ) acetamide", "entity_type": "Chemical", "pos": [91, 232]}, {"entity": "3 - ( 2 - ethoxyphenyl ) - 5 - [ [ 4 - ( 4 - nitrophenyl ) piperazin - 1 - yl ] methyl ] - 1 , 2 , 4 - oxadiazole", "entity_type": "Chemical", "pos": [241, 354]}, {"entity": "N - [ 4 - ethoxy - 3 - ( 1 - piperidinylsulfonyl ) phenyl ] - 2 - ( imidazo [ 2 , 1 - b ] [ 1 , 3 ] thiazol - 6 - yl ) acetamide", "entity_type": "Chemical", "pos": [368, 496]}], "task": "NER"}
{"text": "Mechanistic studies on 7 demonstrated that it directly interacts with and functions through HIV - 1 MA .", "entity": [], "task": "NER"}
{"text": "In accordance with our drug target , compound 7 competes with PI ( 4 , 5 ) P ( 2 ) for MA binding and , as a result , diminishes the production of new virus .", "entity": [{"entity": "PI ( 4 , 5 ) P ( 2 )", "entity_type": "Chemical", "pos": [62, 82]}], "task": "NER"}
{"text": "Mutation of residues within the PI ( 4 , 5 ) P ( 2 ) binding site of MA decreased the antiviral effect of compound 7 .", "entity": [{"entity": "PI ( 4 , 5 ) P ( 2 )", "entity_type": "Chemical", "pos": [32, 52]}], "task": "NER"}
{"text": "Additionally , compound 7 displays a broadly neutralizing anti - HIV activity , with IC ( 50 ) values of 7 . 5 - 15 . 6 mu M for the group M isolates tested .", "entity": [], "task": "NER"}
{"text": "Taken together , these results point towards a novel chemical probe that can be used to more closely study the biological role of MA and could , through further optimization , lead to a new class of anti - HIV - 1 therapeutics .", "entity": [], "task": "NER"}
{"text": "CrbpI regulates mammary retinoic acid homeostasis and the mammary microenvironment .", "entity": [{"entity": "retinoic acid", "entity_type": "Chemical", "pos": [24, 37]}], "task": "NER"}
{"text": "Cellular retinol - binding protein , type I ( CrbpI ) , encoded by retinol - binding protein , type 1 ( Rbp1 ) , is a chaperone of vitamin A ( retinol ) that is epigenetically silenced in ~ 25 % of human breast cancers .", "entity": [{"entity": "retinol", "entity_type": "Chemical", "pos": [9, 16]}, {"entity": "retinol", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "vitamin A", "entity_type": "Chemical", "pos": [131, 140]}, {"entity": "retinol", "entity_type": "Chemical", "pos": [143, 150]}], "task": "NER"}
{"text": "CrbpI delivers vitamin A to enzymes for metabolism into an active metabolite , all - trans retinoic acid ( atRA ) , where atRA is essential to cell proliferation , apoptosis , differentiation , and migration .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "all - trans retinoic acid", "entity_type": "Chemical", "pos": [79, 104]}, {"entity": "atRA", "entity_type": "Chemical", "pos": [107, 111]}, {"entity": "atRA", "entity_type": "Chemical", "pos": [122, 126]}], "task": "NER"}
{"text": "Here , we show the effect of CrbpI loss on mammary atRA homeostasis using the Rbp1 ( - / - ) mouse model .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "Rbp1 ( - / - ) mouse mammary tissue has disrupted retinoid homeostasis that results in 40 % depleted endogenous atRA .", "entity": [{"entity": "retinoid", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "atRA", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "CrbpI loss and atRA depletion precede defects in atRA biosynthesis enzyme expression .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "atRA", "entity_type": "Chemical", "pos": [49, 53]}], "task": "NER"}
{"text": "Compensation by CrbpIII as a retinoid chaperone does not functionally replace CrbpI .", "entity": [{"entity": "retinoid", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Mammary subcellular fractions isolated from Rbp1 ( - / - ) mice have altered retinol dehydrogenase / reductase ( Rdh ) enzyme activity that results in 24 - 42 % less atRA production .", "entity": [{"entity": "retinol", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "atRA", "entity_type": "Chemical", "pos": [166, 170]}], "task": "NER"}
{"text": "Rbp1 ( - / - ) mammary tissue has epithelial hyperplasia , stromal hypercellularity , increased collagen , and increased oxidative stress characteristic of atRA deficiency and early tissue dysfunction that precedes tumor formation .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [156, 160]}], "task": "NER"}
{"text": "Consistent with the findings from the Rbp1 ( - / - ) mouse , tumorigenic epithelial cells lacking CrbpI expression produce 51 % less atRA .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "Together , these data show that CrbpI loss disrupts atRA homeostasis in mammary tissue , resulting in microenvironmental defects similar to those observed at the early stages of tumorigenesis . - Pierzchalski , K . , Yu , J . , Norman , V . , Kane , M .", "entity": [{"entity": "atRA", "entity_type": "Chemical", "pos": [52, 56]}], "task": "NER"}
{"text": "Small - molecule - mediated axonal branching in Caenorhabditis elegans .", "entity": [], "task": "NER"}
{"text": "An in vivo system for monitoring small - molecule - mediated neuronal branching has been developed by using C . elegans .", "entity": [], "task": "NER"}
{"text": "Growth - promoting compounds can be detected by visual inspection of GFPlabeled cholinergic neurons , as axonal branching occurs following treatment with neurotrophic agents .", "entity": [], "task": "NER"}
{"text": "Investigation of the structure - activity relationship of the neurotrophic natural product clovanemagnolol ( 1 ) led us to a comparable chemically edited derivative .", "entity": [{"entity": "clovanemagnolol", "entity_type": "Chemical", "pos": [91, 106]}], "task": "NER"}
{"text": "Multifarious roles of intrinsic disorder in proteins illustrate its broad impact on plant biology .", "entity": [], "task": "NER"}
{"text": "Intrinsically disordered proteins ( IDPs ) are highly abundant in eukaryotic proteomes .", "entity": [], "task": "NER"}
{"text": "Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs .", "entity": [], "task": "NER"}
{"text": "Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein - protein interactions .", "entity": [], "task": "NER"}
{"text": "Short interaction - prone segments within IDPs , termed molecular recognition features , represent potential binding sites that can undergo disorder - to - order transition upon binding to their partners .", "entity": [], "task": "NER"}
{"text": "In this review , we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs .", "entity": [], "task": "NER"}
{"text": "Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology , including abiotic stress , transcriptional regulation , light perception , and development .", "entity": [], "task": "NER"}
{"text": "Based on the roles of disorder in the protein - protein interactions , we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways .", "entity": [], "task": "NER"}
{"text": "Mutations in the putative dimer - dimer interfaces of the measles virus hemagglutinin head domain affect membrane fusion triggering .", "entity": [], "task": "NER"}
{"text": "Measles virus ( MV ) , an enveloped RNA virus belonging to the Paramyxoviridae family , enters the cell through membrane fusion mediated by two viral envelope proteins , an attachment protein hemagglutinin ( H ) and a fusion ( F ) protein .", "entity": [], "task": "NER"}
{"text": "The crystal structure of the receptor - binding head domain of MV - H bound to its cellular receptor revealed that the MV - H head domain forms a tetrameric assembly ( dimer of dimers ) , which occurs in two forms ( forms I and II ) .", "entity": [], "task": "NER"}
{"text": "In this study , we show that mutations in the putative dimer - dimer interface of the head domain in either form inhibit the ability of MV - H to support membrane fusion , without greatly affecting its cell surface expression , receptor binding , and interaction with the F protein .", "entity": [], "task": "NER"}
{"text": "Notably , some anti - MV - H neutralizing monoclonal antibodies are directed to the region around the dimer - dimer interface in form I rather than receptor - binding sites .", "entity": [], "task": "NER"}
{"text": "These observations suggest that the dimer - dimer interactions of the MV - H head domain , especially that in form I , contribute to triggering membrane fusion , and that conformational shift of head domain tetramers plays a role in the process .", "entity": [], "task": "NER"}
{"text": "Furthermore , our results indicate that although the stalk and transmembrane regions may be mainly responsible for the tetramer formation of MV - H , the head domain alone can form tetramers , albeit at a low efficiency .", "entity": [], "task": "NER"}
{"text": "Sialylneolacto - N - tetraose c ( LSTc ) - bearing liposomal decoys capture influenza A virus .", "entity": [{"entity": "Sialylneolacto - N - tetraose c", "entity_type": "Chemical", "pos": [0, 31]}, {"entity": "LSTc", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "Influenza is a severe disease in humans and animals with few effective therapies available .", "entity": [], "task": "NER"}
{"text": "All strains of influenza virus are prone to developing drug resistance due to the high mutation rate in the viral genome .", "entity": [], "task": "NER"}
{"text": "A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of influenza .", "entity": [], "task": "NER"}
{"text": "Influenza uses many individually weak ligand binding interactions for a high avidity multivalent attachment to sialic acid - bearing cells .", "entity": [{"entity": "sialic acid", "entity_type": "Chemical", "pos": [111, 122]}], "task": "NER"}
{"text": "Polymerized sialic acid analogs can form multivalent interactions with influenza but are not ideal therapeutics due to solubility and toxicity issues .", "entity": [{"entity": "sialic acid", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "We used liposomes as a novel means for delivery of the glycan sialylneolacto - N - tetraose c ( LSTc ) .", "entity": [{"entity": "sialylneolacto - N - tetraose c", "entity_type": "Chemical", "pos": [62, 93]}, {"entity": "LSTc", "entity_type": "Chemical", "pos": [96, 100]}], "task": "NER"}
{"text": "LSTc - bearing decoy liposomes form multivalent , polymer - like interactions with influenza virus .", "entity": [{"entity": "LSTc", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Decoy liposomes competitively bind influenza virus in hemagglutination inhibition assays and inhibit infection of target cells in a dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "Inhibition is specific for influenza virus , as inhibition of Sendai virus and respiratory syncytial virus is not observed .", "entity": [], "task": "NER"}
{"text": "In contrast , monovalent LSTc does not bind influenza virus or inhibit infectivity .", "entity": [{"entity": "LSTc", "entity_type": "Chemical", "pos": [25, 29]}], "task": "NER"}
{"text": "LSTc decoy liposomes prevent the spread of influenza virus during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus .", "entity": [{"entity": "LSTc", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "LSTc decoy liposomes co - localize with fluorescently tagged influenza virus , whereas control liposomes do not .", "entity": [{"entity": "LSTc", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high avidity interactions with influenza hemagglutinin , our decoy liposomes have potential as a new therapeutic agent against emerging influenza strains .", "entity": [], "task": "NER"}
{"text": "Evidence for metal - surface interactions and their role in stabilizing well - defined immobilized Ru - NHC alkene metathesis catalysts .", "entity": [{"entity": "Ru - NHC alkene", "entity_type": "Chemical", "pos": [99, 114]}], "task": "NER"}
{"text": "Secondary interactions are demonstrated to direct the stability of well - defined Ru - NHC - based heterogeneous alkene metathesis catalysts .", "entity": [{"entity": "Ru - NHC", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "alkene", "entity_type": "Chemical", "pos": [113, 119]}], "task": "NER"}
{"text": "By providing key stabilization of the active sites , higher catalytic performance is achieved .", "entity": [], "task": "NER"}
{"text": "Specifically , they can be described as interactions between the metal center ( active site ) and the surface functionality of the support , and they have been detected by surface - enhanced ( 1 ) H - ( 29 ) Si NMR spectroscopy of the ligand and ( 31 ) P solid - state NMR of the catalyst precursor .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [191, 198]}, {"entity": "( 29 ) Si", "entity_type": "Chemical", "pos": [201, 210]}, {"entity": "( 31 ) P", "entity_type": "Chemical", "pos": [246, 254]}], "task": "NER"}
{"text": "They are present only when the metal center is attached to the surface via a flexible linker ( a propyl group ) , which allows the active site to either react with the substrate or relax , reversibly , to the surface , thus providing stability .", "entity": [{"entity": "propyl", "entity_type": "Chemical", "pos": [97, 103]}], "task": "NER"}
{"text": "In contrast , the use of a rigid linker ( here mesitylphenyl ) leads to a well - defined active site far away from the surface , stabilized only by a phosphine ligand which under reaction conditions leaves probably irreversibly , leading to faster decomposition and deactivation of the catalysts .", "entity": [{"entity": "mesitylphenyl", "entity_type": "Chemical", "pos": [47, 60]}, {"entity": "phosphine", "entity_type": "Chemical", "pos": [150, 159]}], "task": "NER"}
{"text": "Intercalation pathway in many - particle LiFePO4 electrode revealed by nanoscale state - of - charge mapping .", "entity": [{"entity": "LiFePO4", "entity_type": "Chemical", "pos": [41, 48]}], "task": "NER"}
{"text": "The intercalation pathway of lithium iron phosphate ( LFP ) in the positive electrode of a lithium - ion battery was probed at the ~ 40 nm length scale using oxidation - state - sensitive X - ray microscopy .", "entity": [{"entity": "lithium iron phosphate", "entity_type": "Chemical", "pos": [29, 51]}, {"entity": "LFP", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [91, 98]}], "task": "NER"}
{"text": "Combined with morphological observations of the same exact locations using transmission electron microscopy , we quantified the local state - of - charge of approximately 450 individual LFP particles over nearly the entire thickness of the porous electrode .", "entity": [{"entity": "LFP", "entity_type": "Chemical", "pos": [186, 189]}], "task": "NER"}
{"text": "With the electrode charged to 50 % state - of - charge in 0 . 5 h , we observed that the overwhelming majority of particles were either almost completely delithiated or lithiated .", "entity": [], "task": "NER"}
{"text": "Specifically , only ~ 2 % of individual particles were at an intermediate state - of - charge .", "entity": [], "task": "NER"}
{"text": "From this small fraction of particles that were actively undergoing delithiation , we conclude that the time needed to charge a particle is ~ 1 / 50 the time needed to charge the entire particle ensemble .", "entity": [], "task": "NER"}
{"text": "Surprisingly , we observed a very weak correlation between the sequence of delithiation and the particle size , contrary to the common expectation that smaller particles delithiate before larger ones .", "entity": [], "task": "NER"}
{"text": "Our quantitative results unambiguously confirm the mosaic ( particle - by - particle ) pathway of intercalation and suggest that the rate - limiting process of charging is initiating the phase transformation by , for example , a nucleation - like event .", "entity": [], "task": "NER"}
{"text": "Therefore , strategies for further enhancing the performance of LFP electrodes should not focus on increasing the phase - boundary velocity but on the rate of phase - transformation initiation .", "entity": [{"entity": "LFP", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Pharmacological chaperones as therapeutics for lysosomal storage diseases .", "entity": [], "task": "NER"}
{"text": "Lysosomal enzymes are responsible for the degradation of a wide variety of glycolipids , oligosaccharides , proteins , and glycoproteins .", "entity": [], "task": "NER"}
{"text": "Inherited mutations in the genes that encode these proteins can lead to reduced stability of newly synthesized lysosomal enzymes .", "entity": [], "task": "NER"}
{"text": "While often catalytically competent , the mutated enzymes are unable to efficiently pass the quality control mechanisms of the endoplasmic reticulum , resulting in reduced lysosomal trafficking , substrate accumulation , and cellular dysfunction .", "entity": [], "task": "NER"}
{"text": "Pharmacological chaperones ( PCs ) are small molecules that bind and stabilize mutant lysosomal enzymes , thereby allowing proper cellular translocation .", "entity": [], "task": "NER"}
{"text": "Such compounds have been shown to increase enzyme activity and reduce substrate burden in a number of preclinical models and clinical studies .", "entity": [], "task": "NER"}
{"text": "In this Perspective , we review several of the lysosomal diseases for which PCs have been studied and the SAR of the various classes of molecules .", "entity": [], "task": "NER"}
{"text": "In vitro study of injury on human bronchial epithelial cells caused by gunpowder smog .", "entity": [], "task": "NER"}
{"text": "Smog inhalation is associated with acute respiratory symptoms in exposed victims .", "entity": [], "task": "NER"}
{"text": "However , despite the evidence from cell injury caused by smog , a stable and practical apparatus used to treat cells with smog is necessary .", "entity": [], "task": "NER"}
{"text": "The aim of this study is to develop a cell research platform of smoke inhalation injury .", "entity": [], "task": "NER"}
{"text": "In the smog - generation device , a wireless electromagnetic heater was used to ignite gunpowder and generate smog .", "entity": [], "task": "NER"}
{"text": "The quality of black powder was checked by the black powder burn rate , and experimental smog was indirectly checked by the amount of cell damage .", "entity": [], "task": "NER"}
{"text": "The temperature and humidity were set at 37 degrees C +/- 1 degrees C and >= 95 % in the smog - cells reaction chamber , respectively .", "entity": [], "task": "NER"}
{"text": "Factors including gunpowder dosages , smog - exposure time , the cell density , modes of exposure , volumes of smog , test durations , volumes of the cell culture medium and combustion velocity were measured .", "entity": [], "task": "NER"}
{"text": "Coefficient variation of different batches of gunpowder and smog were less than 4 % and 9 % , respectively .", "entity": [], "task": "NER"}
{"text": "With larger gunpowder dosage and longer exposure time , cell injury appeared to increase .", "entity": [], "task": "NER"}
{"text": "When cells were cultured in 4 x 10 ( 4 ) / well density in culture medium ( 1 mL / well ) , exposed to more than 10 L smog with filter screens above plates , detected after 24 h culture in cell incubator and gunpowder burned out within 5 s , smog had the best effect on cell injury .", "entity": [], "task": "NER"}
{"text": "In conclusion , the experimental device can produce test smog stably and safely .", "entity": [], "task": "NER"}
{"text": "The apparatus treating cells with smog can induce cell injury effectively , and the injury is positively correlated with smog concentration and exposure time .", "entity": [], "task": "NER"}
{"text": "Computationally assisted assignment of kahalalide Y configuration using an NMR - constrained conformational search .", "entity": [{"entity": "kahalalide Y", "entity_type": "Chemical", "pos": [39, 51]}], "task": "NER"}
{"text": "Assignment of the absolute configuration of cyclic peptides frequently yields challenges , leaving one or more stereogenic centers unassigned due to small quantities of sample and the limited utility of Marfey ' s or other methods for assigning amino or hydroxy acids .", "entity": [{"entity": "amino or hydroxy acids", "entity_type": "Chemical", "pos": [245, 267]}], "task": "NER"}
{"text": "Here , we report isolation of kahalalide Y ( 1 ) from Bryopsis pennata for the first time ; in addition , the application of a combination of molecular modeling and NOE distance constraint calculations was utilized to determine the conformation of 1 and the absolute configuration of the final stereogenic center of 1 .", "entity": [{"entity": "kahalalide Y", "entity_type": "Chemical", "pos": [30, 42]}], "task": "NER"}
{"text": "Using the Schr o dinger suite , the structure of 1 was sketched in Maestro and minimized using the OPLS2005 force field in Macromodel .", "entity": [], "task": "NER"}
{"text": "A conformational search was performed separately for structures having an R or S configuration at C - 3 of the beta - hydroxy fatty acid subunit that completes the cyclic scaffold of 1 , after which multiple minimizations for all generated conformers were carried out .", "entity": [{"entity": "beta - hydroxy fatty acid", "entity_type": "Chemical", "pos": [111, 136]}], "task": "NER"}
{"text": "The lowest energy conformers of R and S stereoisomers were then subjected to B3LYP geometry optimizations including solvent effects .", "entity": [], "task": "NER"}
{"text": "The S stereoisomer was shown to be in excellent agreement with the NOE - derived distance constraints and hydrogen - bonding stability studies .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "Surfactant adsorption and interfacial tension investigations on cyclopentane hydrate .", "entity": [{"entity": "cyclopentane hydrate", "entity_type": "Chemical", "pos": [64, 84]}], "task": "NER"}
{"text": "Gas hydrates represent an unconventional methane resource and a production / safety risk to traditional oil and gas flowlines .", "entity": [{"entity": "methane", "entity_type": "Chemical", "pos": [41, 48]}], "task": "NER"}
{"text": "In both systems , hydrate may share interfaces with both aqueous and hydrocarbon fluids .", "entity": [{"entity": "hydrocarbon", "entity_type": "Chemical", "pos": [69, 80]}], "task": "NER"}
{"text": "To accurately model macroscopic properties , such as relative permeability in unconventional systems or dispersion viscosity in traditional systems , knowledge of hydrate interfacial properties is required .", "entity": [], "task": "NER"}
{"text": "This work presents hydrate cohesive force results measured on a micromechanical force apparatus , and complementary water - hydrocarbon interfacial tension data .", "entity": [{"entity": "hydrocarbon", "entity_type": "Chemical", "pos": [124, 135]}], "task": "NER"}
{"text": "By combining a revised cohesive force model with experimental data , two interfacial properties of cyclopentane hydrate were estimated : hydrate - water and hydrate - cyclopentane interfacial tension values at 0 . 32 +/- 0 . 05 mN / m and 47 +/- 5 mN / m , respectively .", "entity": [{"entity": "cyclopentane hydrate", "entity_type": "Chemical", "pos": [99, 119]}, {"entity": "cyclopentane", "entity_type": "Chemical", "pos": [167, 179]}], "task": "NER"}
{"text": "These fundamental physiochemical properties have not been estimated or measured for cyclopentane hydrate to date .", "entity": [{"entity": "cyclopentane hydrate", "entity_type": "Chemical", "pos": [84, 104]}], "task": "NER"}
{"text": "The addition of surfactants in the cyclopentane phase significantly reduced the cyclopentane hydrate cohesive force ; we hypothesize this behavior to be the result of surfactant adsorption on the hydrate - oil interface .", "entity": [{"entity": "cyclopentane", "entity_type": "Chemical", "pos": [35, 47]}, {"entity": "cyclopentane hydrate", "entity_type": "Chemical", "pos": [80, 100]}], "task": "NER"}
{"text": "Surface excess quantities were estimated for hydrate - oil and water - oil interfaces using four carboxylic and sulfonic acids .", "entity": [{"entity": "carboxylic and sulfonic acids", "entity_type": "Chemical", "pos": [97, 126]}], "task": "NER"}
{"text": "The results suggest the density of adsorbed surfactant may be 2 x larger for the hydrate - oil interface than the water - oil interface .", "entity": [], "task": "NER"}
{"text": "Additionally , hydrate - oil interfacial tension was observed to begin decreasing from the baseline value at significantly lower surfactant concentrations ( 1 - 3 orders of magnitude ) than those for the water - oil interfacial tension .", "entity": [], "task": "NER"}
{"text": "Neurotoxic potential and cellular uptake of T - 2 toxin in human astrocytes in primary culture .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [44, 55]}], "task": "NER"}
{"text": "The trichothecene mycotoxin T - 2 toxin , which is produced by fungi of the Fusarium species , is a worldwide occurring contaminant of cereal based food and feed .", "entity": [{"entity": "trichothecene", "entity_type": "Chemical", "pos": [4, 17]}, {"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "The cytotoxic properties of T - 2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "However , only few data on neurotoxic properties of T - 2 toxin are reported so far , but in vivo studies showed different effects of T - 2 toxin on behavior as well as on levels of brain amines in animals .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [134, 145]}, {"entity": "amines", "entity_type": "Chemical", "pos": [188, 194]}], "task": "NER"}
{"text": "To further investigate the cytotoxic properties of T - 2 toxin on cells derived from brain tissue , normal human astrocytes in primary culture ( NHA ) were used in this study .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [51, 62]}], "task": "NER"}
{"text": "Besides studies of cytotoxicity , apoptosis ( caspase - 3 - activation , Annexin V ) and necrosis ( LDH - release ) , the cellular uptake and metabolism of T - 2 toxin in NHA was analyzed and compared to the uptake in an established human cell line ( HT - 29 ) .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [156, 167]}], "task": "NER"}
{"text": "The results show that human astrocytes were highly sensitive to the cytotoxic properties of T - 2 toxin , and apoptosis , induced at low concentrations , was identified for the first time as the mechanism of toxic action in NHA .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [92, 103]}], "task": "NER"}
{"text": "Furthermore , a strong accumulation of T - 2 toxin in NHA and HT - 29 cells was detected , and T - 2 toxin was subjected to metabolism leading to HT - 2 toxin , a commonly found metabolite after T - 2 toxin incubation in both cell types .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [95, 106]}, {"entity": "HT - 2 toxin", "entity_type": "Chemical", "pos": [146, 158]}, {"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [195, 206]}], "task": "NER"}
{"text": "This formation seems to occur within the cells since incubations of T - 2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [68, 79]}], "task": "NER"}
{"text": "The results of this study emphasize the neurotoxic potential of T - 2 toxin in human astrocytes at low concentrations after short incubation times .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [64, 75]}], "task": "NER"}
{"text": "Direct atomic - level observation and chemical analysis of ZnSe synthesized by in situ high - throughput reactive fiber drawing .", "entity": [{"entity": "ZnSe", "entity_type": "Chemical", "pos": [59, 63]}], "task": "NER"}
{"text": "We demonstrate a high - throughput method for synthesizing zinc selenide ( ZnSe ) in situ during fiber drawing .", "entity": [{"entity": "zinc selenide", "entity_type": "Chemical", "pos": [59, 72]}, {"entity": "ZnSe", "entity_type": "Chemical", "pos": [75, 79]}], "task": "NER"}
{"text": "Central to this method is a thermally activated chemical reaction occurring across multiple interfaces between alternately layered elemental zinc - ( Zn - ) and selenium - ( Se - ) rich films embedded in a preform and drawn into meters of fiber at a temperature well below the melting temperature of either Zn or ZnSe .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [141, 145]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [150, 152]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [161, 169]}, {"entity": "Se", "entity_type": "Chemical", "pos": [174, 176]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [307, 309]}, {"entity": "ZnSe", "entity_type": "Chemical", "pos": [313, 317]}], "task": "NER"}
{"text": "By depositing 50 nm thick layers of Zn interleaved between 1 mu m thick Se layers , a controlled breakup of the Zn sheet is achieved , thereby enabling a complete and controlled chemical reaction .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [36, 38]}, {"entity": "Se", "entity_type": "Chemical", "pos": [72, 74]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [112, 114]}], "task": "NER"}
{"text": "The thermodynamics and kinetics of this synthesis process are studied using thermogravimetric analysis and differential scanning calorimetry , and the in - fiber compound is analyzed by a multiplicity of materials characterization tools , including transmission electron microscopy , Raman microscopy , energy - dispersive X - ray spectroscopy , and X - ray diffraction , all resulting in unambiguous identification of ZnSe as the compound produced from the reactive fiber draw .", "entity": [{"entity": "ZnSe", "entity_type": "Chemical", "pos": [419, 423]}], "task": "NER"}
{"text": "Furthermore , we characterize the in - fiber ZnSe / Se97S3 heterojunction to demonstrate the prospect of ZnSe - based fiber optoelectronic devices .", "entity": [{"entity": "ZnSe", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "ZnSe", "entity_type": "Chemical", "pos": [105, 109]}], "task": "NER"}
{"text": "The ability to synthesize new compounds during fiber drawing at nanometer scale precision and to characterize them at the atomic - level extends the architecture and materials selection compatible with multimaterial fiber drawing , thus paving the way toward more complex and sophisticated functionality .", "entity": [], "task": "NER"}
{"text": "Zinc - dependent lysosomal enlargement in TRPML1 - deficient cells involves MTF - 1 transcription factor and ZnT4 ( Slc30a4 ) transporter .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Zinc is critical for a multitude of cellular processes , including gene expression , secretion and enzymatic activities .", "entity": [{"entity": "Zinc", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Cellular zinc is controlled by zinc - chelating proteins and by zinc transporters .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [9, 13]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [64, 68]}], "task": "NER"}
{"text": "The recent identification of zinc permeability of the lysosomal ion channel TRPML1 ( transient receptor potential mucolipin 1 ) , and the evidence of abnormal zinc levels in cells deficient in TRPML1 , suggested a role for TRPML1 in zinc transport .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [159, 163]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [233, 237]}], "task": "NER"}
{"text": "In the present study we provide new evidence for such a role and identify additional cellular components responsible for it .", "entity": [], "task": "NER"}
{"text": "In agreement with the previously published data , an acute siRNA ( small interfering RNA ) - driven TRPML1 KD ( knockdown ) leads to the build - up of large cytoplasmic vesicles positive for LysoTracker (TM) and zinc staining , when cells are exposed to high concentrations of zinc .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [212, 216]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [277, 281]}], "task": "NER"}
{"text": "We now show that lysosomal enlargement and zinc build - up in TRPML1 - KD cells exposed to zinc are ameliorated by KD of the zinc - sensitive transcription factor MTF - 1 ( metal - regulatory - element - binding transcription factor - 1 ) or the zinc transporter ZnT4 .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [91, 95]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [125, 129]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [246, 250]}], "task": "NER"}
{"text": "TRPML1 KD is associated with a build - up of cytoplasmic zinc and with enhanced transcriptional response of mRNA for MT2a ( metallothionein 2a ) .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "TRPML1 KD did not suppress lysosomal secretion , but it did delay zinc leak from the lysosomes into the cytoplasm .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [66, 70]}], "task": "NER"}
{"text": "These results underscore a role for TRPML1 in zinc metabolism .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "Furthermore , they suggest that TRPML1 works in concert with ZnT4 to regulate zinc translocation between the cytoplasm and lysosomes .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [78, 82]}], "task": "NER"}
{"text": "Hydrogenated ZnO core - shell nanocables for flexible supercapacitors and self - powered systems .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [13, 16]}], "task": "NER"}
{"text": "Although MnO2 is a promising material for supercapacitors ( SCs ) due to its excellent electrochemical performance and natural abundance , its wide application is limited by poor electrical conductivity .", "entity": [{"entity": "MnO2", "entity_type": "Chemical", "pos": [9, 13]}], "task": "NER"}
{"text": "Inspired by our results that the electrochemical activity and electrical conductivity of ZnO nanowires were greatly improved after hydrogenation , we designed and fabricated hydrogenated single - crystal ZnO @ amorphous ZnO - doped MnO2 core - shell nanocables ( HZM ) on carbon cloth as SC electrodes , showing excellent performance such as areal capacitance of 138 . 7 mF / cm ( 2 ) and specific capacitance of 1260 . 9 F / g .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [204, 207]}, {"entity": "ZnO - doped MnO2", "entity_type": "Chemical", "pos": [220, 236]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [272, 278]}], "task": "NER"}
{"text": "Highly flexible all - solid - state SCs were subsequently assembled with these novel HZM electrodes using polyvinyl alcohol / LiCl electrolyte .", "entity": [{"entity": "polyvinyl alcohol", "entity_type": "Chemical", "pos": [106, 123]}, {"entity": "LiCl", "entity_type": "Chemical", "pos": [126, 130]}], "task": "NER"}
{"text": "The working devices achieved very high total areal capacitance of 26 mF / cm ( 2 ) and retained 87 . 5 % of the original capacitance even after 10 000 charge / discharge cycles .", "entity": [], "task": "NER"}
{"text": "An integrated power pack incorporating series - wound SCs and dye - sensitized solar cells was demonstrated for stand - alone self - powered systems .", "entity": [], "task": "NER"}
{"text": "Influence of chain length and double bond on the aqueous behavior of choline carboxylate soaps .", "entity": [{"entity": "choline carboxylate", "entity_type": "Chemical", "pos": [69, 88]}], "task": "NER"}
{"text": "In preceding studies , we demonstrated that choline carboxylates ChC ( m ) with alkyl chain lengths of m = 12 - 18 are highly water - soluble ( for m = 12 , soluble up to 93 wt % soap and 0 degrees C ) .", "entity": [{"entity": "choline carboxylates", "entity_type": "Chemical", "pos": [44, 64]}, {"entity": "ChC ( m )", "entity_type": "Chemical", "pos": [65, 74]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [80, 85]}], "task": "NER"}
{"text": "In addition , choline soaps are featured by an extraordinary lyotropic phase behavior .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "With decreasing water concentration , the following phases were found : micellar phase ( L ( 1 ) ) , discontinuous cubic phase ( I ( 1 ) ' and I ( 1 ) \" ) , hexagonal phase ( H ( 1 ) ) , bicontinuous cubic phase ( V ( 1 ) ) , and lamellar phase ( L ( alpha ) ) .", "entity": [], "task": "NER"}
{"text": "The present work is also focused on the lyotropic phase behavior of choline soaps but with shorter alkyl chains or different alkyl chain properties .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [99, 104]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [125, 130]}], "task": "NER"}
{"text": "We have investigated the aqueous phase behavior of choline soaps with C ( 8 ) and C ( 10 ) chain - lengths ( choline octanoate and choline decanoate ) and with a C ( 18 ) chain - length with a cis - double bond ( choline oleate ) .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [51, 58]}, {"entity": "C ( 8 )", "entity_type": "Chemical", "pos": [70, 77]}, {"entity": "C ( 10 )", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "choline octanoate", "entity_type": "Chemical", "pos": [109, 126]}, {"entity": "choline decanoate", "entity_type": "Chemical", "pos": [131, 148]}, {"entity": "C ( 18 )", "entity_type": "Chemical", "pos": [162, 170]}, {"entity": "choline oleate", "entity_type": "Chemical", "pos": [213, 227]}], "task": "NER"}
{"text": "We found that choline decanoate follows the lyotropic phase behavior of the longer - chain homologues mentioned above .", "entity": [{"entity": "choline decanoate", "entity_type": "Chemical", "pos": [14, 31]}], "task": "NER"}
{"text": "Choline octanoate in water shows no discontinuous cubic phases , but an extended , isotropic micellar solution phase .", "entity": [{"entity": "Choline octanoate", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "In addition , choline octanoate is at the limit between a surfactant and a hydrotrope .", "entity": [{"entity": "choline octanoate", "entity_type": "Chemical", "pos": [14, 31]}], "task": "NER"}
{"text": "The double bond in choline oleate leads also to a better solubility in water and a decrease of the solubilization temperature .", "entity": [{"entity": "choline oleate", "entity_type": "Chemical", "pos": [19, 33]}], "task": "NER"}
{"text": "It also influences the Gaussian curvature of the aggregates which results in a loss of discontinuous cubic phases in the binary phase diagram .", "entity": [], "task": "NER"}
{"text": "The different lyotropic mesophases were identified by the penetration scan technique with polarizing light microscope and visual observations .", "entity": [], "task": "NER"}
{"text": "To clarify the structural behavior small ( SAXS ) and wide ( WAXS ) angle X - ray scattering were performed .", "entity": [], "task": "NER"}
{"text": "To further characterize the extended , isotropic micellar solution phase in the binary phase diagram of choline octanoate viscosity and conductivity measurements were also carried out .", "entity": [{"entity": "choline octanoate", "entity_type": "Chemical", "pos": [104, 121]}], "task": "NER"}
{"text": "Preparation , characterization , in vivo biodistribution and pharmacokinetic studies of donepezil - loaded PLGA nanoparticles for brain targeting .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [88, 97]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "Abstract Objective : Alzheimer ' s disease ( AD ) is a progressive neurodegenerative disorder manifested by cognitive , memory deterioration and variety of neuropsychiatric symptoms .", "entity": [], "task": "NER"}
{"text": "Donepezil is a reversible cholinesterase inhibitor used for the treatment of AD .", "entity": [{"entity": "Donepezil", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The purpose of this work is to prepare a nanoparticulate drug delivery system of donepezil using poly ( lactic - co - glycolic acid ) ( PLGA ) for sustained release and efficient brain targeting .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "poly ( lactic - co - glycolic acid )", "entity_type": "Chemical", "pos": [97, 133]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [136, 140]}], "task": "NER"}
{"text": "Materials and methods : PLGA nanoparticles ( NPs ) were prepared by the solvent emulsification diffusion - evaporation technique and characterized for particle size , particle - size distribution , zeta potential , entrapment efficiency , drug loading and interaction studies and in vivo studies using gamma scintigraphy techniques .", "entity": [{"entity": "PLGA", "entity_type": "Chemical", "pos": [24, 28]}], "task": "NER"}
{"text": "Results and discussion : The size of drug - loaded NPs ( drug polymer ratio 1 : 1 ) was found to be 89 . 67 +/- 6 . 43 nm .", "entity": [], "task": "NER"}
{"text": "The TEM and SEM images of the formulation suggested that particle size was within 20 - 100 nm and spherical in shape , smooth morphology and coating of Tween - 80 on the NPs was clearly observed .", "entity": [{"entity": "Tween - 80", "entity_type": "Chemical", "pos": [152, 162]}], "task": "NER"}
{"text": "The release behavior of donepezil exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous sustained release .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [24, 33]}], "task": "NER"}
{"text": "The biodistribution studies of donepezil - loaded PLGA NPs and drug solution via intravenous route revealed higher percentage of radioactivity per gram in the brain for the nanoparticulate formulation as compared with the drug solution ( p < 0 . 05 ) .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "Conclusion : The high concentrations of donepezil uptake in brain due to coated NPs may help in a significant improvement for treating AD .", "entity": [{"entity": "donepezil", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "But further , more extensive clinical studies are needed to check and confirm the efficacy of the prepared drug delivery system .", "entity": [], "task": "NER"}
{"text": "Synthesis and biological evaluation of nucleoside analogues than contain silatrane on the basis of the structure of acyclovir ( ACV ) as novel inhibitors of hepatitis B virus ( HBV ) .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "silatrane", "entity_type": "Chemical", "pos": [73, 82]}, {"entity": "acyclovir", "entity_type": "Chemical", "pos": [116, 125]}, {"entity": "ACV", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "Hepatitis B virus ( HBV ) infection causes major public health problems worldwide .", "entity": [], "task": "NER"}
{"text": "Acyclovir ( ACV ) is mainly used to inhibit herpes simplex virus ( HSV ) rather than HBV .", "entity": [{"entity": "Acyclovir", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ACV", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "In this study , we used the combination principle to design and synthesize nucleoside analogues that contain silatrane on the basis of the structure of ACV .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [75, 85]}, {"entity": "silatrane", "entity_type": "Chemical", "pos": [109, 118]}, {"entity": "ACV", "entity_type": "Chemical", "pos": [152, 155]}], "task": "NER"}
{"text": "We found that the compounds were effective inhibitors of HBV , both in vitro and in vivo .", "entity": [], "task": "NER"}
{"text": "All of the compounds showed suppressive activity on the expression of HBV surface antigen ( HBsAg ) and HBV e antigen ( HBeAg ) in the HepG2 . 2 . 15 cell line with low cytotoxicity .", "entity": [], "task": "NER"}
{"text": "One of compounds was studied in HBV transgenic mice model , and the test results showed its ability to reduce the levels of HBsAg , HBeAg and HBV DNA by ELASE and qPCR .", "entity": [], "task": "NER"}
{"text": "Furthermore , significant improvement of T lymphocyte was observed after treatment , as evaluated by flow cytometry ( FCM ) .", "entity": [], "task": "NER"}
{"text": "Serum amyloid A upsurge precedes standard biomarkers of hepatotoxicity in ritodrine - injected mice .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "The tocolytic agent ritodrine acts on the beta 2 - adrenoceptor and is an effective treatment option for preterm labor .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [20, 29]}], "task": "NER"}
{"text": "However , several adverse effects of ritodrine therapy , including liver damage , have been noted .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [37, 46]}], "task": "NER"}
{"text": "To elucidate the underlying mechanisms of ritodrine - induced adverse effects , development of sensitive biomarkers of these adverse events is necessary .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [42, 51]}], "task": "NER"}
{"text": "Here , we report the development and analysis of an animal model of ritodrine - induced liver damage .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "Female mice received daily ritodrine injections for 2 weeks ; liver samples were then collected and subjected to DNA microarray analysis .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "Ritodrine significantly altered the expression of genes related to steroid and lipid metabolism , as well as the metabolism of ritodrine itself .", "entity": [{"entity": "Ritodrine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "ritodrine", "entity_type": "Chemical", "pos": [127, 136]}], "task": "NER"}
{"text": "Importantly , expression of the acute - phase reactant serum amyloid A ( SAA ) significantly increased after ritodrine injection , with values indicating the largest fold - change .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [109, 118]}], "task": "NER"}
{"text": "This large increase in blood SAA levels serves as a more sensitive biomarker than conventional liver enzymes , such as aspartate aminotransferase and alanine aminotransferase .", "entity": [{"entity": "aspartate", "entity_type": "Chemical", "pos": [119, 128]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [150, 157]}], "task": "NER"}
{"text": "The increase in SAA expression is specific to ritodrine - induced liver damage , because SAA expression was not induced by other hepatotoxic drugs such as acetaminophen , valproic acid , or metformin .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [46, 55]}, {"entity": "acetaminophen", "entity_type": "Chemical", "pos": [155, 168]}, {"entity": "valproic acid", "entity_type": "Chemical", "pos": [171, 184]}, {"entity": "metformin", "entity_type": "Chemical", "pos": [190, 199]}], "task": "NER"}
{"text": "Our in vitro studies showed that cyclic adenosine 3 ' , 5 ' - monophosphate ( cAMP ) accumulation was not a primary cause of the ritodrine - induced SAA increase .", "entity": [{"entity": "cyclic adenosine 3 ' , 5 ' - monophosphate", "entity_type": "Chemical", "pos": [33, 75]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [78, 82]}, {"entity": "ritodrine", "entity_type": "Chemical", "pos": [129, 138]}], "task": "NER"}
{"text": "Instead , SAA expression was enhanced by indirect phosphorylation of the signal transducer and activator of transcription - 3 ( STAT3 ) mediated by interleukin - 6 .", "entity": [], "task": "NER"}
{"text": "Therefore , our study provides a method for sensitive and early detection of hepatic injury , and may thus help preclude serious liver damage due to ritodrine use in preterm labor .", "entity": [{"entity": "ritodrine", "entity_type": "Chemical", "pos": [149, 158]}], "task": "NER"}
{"text": "L - type voltage - dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2 - induced neuronal apoptosis .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "Snake venom group IA secretory phospholipase A2 ( sPLA2 - IA ) is known as a neurotoxin .", "entity": [], "task": "NER"}
{"text": "Snake venom sPLA2s are neurotoxic in vivo and in vitro , causing synergistic neurotoxicity to cortical cultures when applied with toxic concentrations of glutamate .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [154, 163]}], "task": "NER"}
{"text": "However , it has not yet been cleared sufficiently how sPLA2 - IA exerts neurotoxicity .", "entity": [], "task": "NER"}
{"text": "Here , we found sPLA2 - IA induced neuronal cell death in a concentration - dependent manner .", "entity": [], "task": "NER"}
{"text": "This death was a delayed response requiring a latent time for 6h .", "entity": [], "task": "NER"}
{"text": "sPLA2 - IA - induced neuronal cell death was accompanied with apoptotic blebbing , condensed chromatin , and fragmented DNA , exhibiting apoptotic features .", "entity": [], "task": "NER"}
{"text": "NMDA receptor blockers suppressed the neurotoxicity of sPLA2 - IA , but an AMPA receptor blocker did not .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [75, 79]}], "task": "NER"}
{"text": "Interestingly , L - type voltage - dependent Ca ( 2 + ) channel ( L - VDCC ) blocker significantly protected neurons from the sPLA2 - IA - induced apoptosis .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [45, 55]}], "task": "NER"}
{"text": "On the other hand , neither N - VDCC blockers nor P / Q - VDCC blocker did .", "entity": [], "task": "NER"}
{"text": "In conclusion , we demonstrated that sPLA2 - IA induced neuronal cell death via apoptosis .", "entity": [], "task": "NER"}
{"text": "Furthermore , the present study suggests that not only NMDA receptor but also L - VDCC contributed to the neurotoxicity of snake venom sPLA2 - IA .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [55, 59]}], "task": "NER"}
{"text": "Chemo - responsive , self - oscillating gels that undergo biomimetic communication .", "entity": [], "task": "NER"}
{"text": "Species ranging from single - cell organisms to social insects can undergo auto - chemotaxis , where the entities move towards a chemo - attractant that they themselves emit .", "entity": [], "task": "NER"}
{"text": "Polymer gels undergoing the self - oscillating Belousov - Zhabotinsky ( BZ ) reaction exhibit autonomous , periodic pulsations , which produce chemical species collectively referred to as the activator .", "entity": [], "task": "NER"}
{"text": "The diffusion of this activator into the surrounding solution affects the dynamic behavior of neighboring BZ gels and hence , the BZ gels not only emit , but also respond to self - generated chemical gradients .", "entity": [], "task": "NER"}
{"text": "This review describes recent experimental and computational studies that reveal how this biomimetic behavior effectively allows neighboring BZ gels to undergo cooperative , self - propelled motion .", "entity": [], "task": "NER"}
{"text": "These distinctive properties of the BZ gels provide a route for creating reconfigurable materials that autonomously communicate with neighboring units and thereby actively participate in constructing the desired structures .", "entity": [], "task": "NER"}
{"text": "Mitogen - activated protein kinases as therapeutic targets for rheumatoid arthritis .", "entity": [], "task": "NER"}
{"text": "Rheumatoid arthritis ( RA ) is a chronic autoimmune disease in which imbalances in pro - and anti - inflammatory cytokines promote the induction of autoimmunity , inflammation and joint destruction .", "entity": [], "task": "NER"}
{"text": "Methotrexate , the standard disease - modifying anti - rheumatic drug ( DMARD ) , has shown a gradual loss of efficacy in a significant proportion of patients , probably due to the onset of drug resistance , and thus it was hoped that the development of biologics would revolutionise RA management .", "entity": [{"entity": "Methotrexate", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Even though biologics have improved the therapy of patients refractive to DMARDs , they require parenteral administration and may leave patients open to serious infection and cancer .", "entity": [], "task": "NER"}
{"text": "Therefore , attention has also been focused on inhibitors of mitogen - activated protein kinases ( MAPKs ) , signalling enzymes that play key roles in pathogenic cytokine production , and their downstream effector pathways , in order to create safe and effective oral drugs .", "entity": [], "task": "NER"}
{"text": "This article therefore provides an overview of the structure and function of MAPKs and their role in the pathogenesis of RA as context to describing the advances in the development of specific , druggable MAPK inhibitors .", "entity": [], "task": "NER"}
{"text": "Their potential as therapies in the management of RA is also discussed .", "entity": [], "task": "NER"}
{"text": "Genotoxicity and carcinogenicity of the light emitted by artificial illumination systems .", "entity": [], "task": "NER"}
{"text": "The light delivered by artificial illumination systems , and in particular by halogen quartz bulbs , contains UVA , UVB , and UVC radiation , is genotoxic to both bacterial and human cells and is potently carcinogenic to hairless mice .", "entity": [{"entity": "halogen", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "quartz", "entity_type": "Chemical", "pos": [86, 92]}], "task": "NER"}
{"text": "Since IARC has classified UV radiation in Group 1 , any source of UV light poses a carcinogenic hazard to humans .", "entity": [], "task": "NER"}
{"text": "Suitable regulations would be needed in order to control the safety of the light emitted by artificial light sources .", "entity": [], "task": "NER"}
{"text": "Impaired social behavior in chicks exposed to sodium valproate during the last week of embryogenesis .", "entity": [{"entity": "sodium valproate", "entity_type": "Chemical", "pos": [46, 62]}], "task": "NER"}
{"text": "RATIONALE AND OBJECTIVES : To evaluate direct exposure to sodium valproate ( VPA ) during embryogenesis , we administered VPA to chick embryos and examined their social behaviors after hatching .", "entity": [{"entity": "sodium valproate", "entity_type": "Chemical", "pos": [58, 74]}, {"entity": "VPA", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "VPA", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "METHODS AND RESULTS : Embryos treated with VPA ( 35 mu mol / egg ) on day 14 were similar to controls for hatching date ( day 21 ) and hatchlings ' abilities , such as motor , imprinting , and surface righting .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "However , these VPA chicks on posthatching day 3 scored significantly low in the chick ' s social separation stress ( SSS ) test as follows .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [16, 19]}], "task": "NER"}
{"text": "Aggregation test evaluated the speed of four chicks , individually isolated by a cardboard in a box , to aggregate upon removal of the cardboards .", "entity": [], "task": "NER"}
{"text": "Belongingness test evaluated the speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner .", "entity": [], "task": "NER"}
{"text": "Vocalization test for each chick was performed in an isolated corner by using a sound level meter .", "entity": [], "task": "NER"}
{"text": "The results demonstrated that compared with controls , VPA chicks were significantly slow in aggregation ( 12 . 7 +/- 2 . 5 s vs . 2 . 9 +/- 0 . 9 s , p = 0 . 006 ) and belongingness ( 3 . 6 +/- 0 . 28 s / 40 cm vs . 2 . 6 +/- 0 . 14 s / 40 cm , P = 0 . 003 ) and weak in vocalization ( 13 . 4 +/- 2 . 8 dB / 30 s vs . 26 . 7 +/- 1 . 3 dB / 30 s , P = 0 . 001 ) , respectively .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "Weight of cerebellum of VAP chick was 15 % lighter than controls ( P = 0 . 004 ) .", "entity": [{"entity": "VAP", "entity_type": "Chemical", "pos": [24, 27]}], "task": "NER"}
{"text": "CONCLUSIONS : Chick embryos exposed to VPA during the last week of embryogenesis had impaired social behaviors in spite of normal mortar and imprinting ability .", "entity": [{"entity": "VPA", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "The present method will be a useful animal model for assessing the effects of environment during embryogenesis on social behaviors in later life .", "entity": [], "task": "NER"}
{"text": "Abstinence from repeated amphetamine treatment induces depressive - like behaviors and oxidative damage in rat brain .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [25, 36]}], "task": "NER"}
{"text": "RATIONALE : Amphetamine has a significant potential for abuse and addiction .", "entity": [{"entity": "Amphetamine", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Among prolonged abusers , amphetamine withdrawal - induced depressive symptoms are common ; however , their pathophysiological mechanism is not fully understood .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [26, 37]}], "task": "NER"}
{"text": "Previously , we found that repeated treatment with amphetamine for 2 weeks induced oxidative stress in rat brain .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [51, 62]}], "task": "NER"}
{"text": "OBJECTIVES : The purpose of the current study is to analyze whether abstinence from repeated amphetamine treatment in rats induces depressive - like behaviors and if oxidative damage in the brain continues during abstinence .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "METHODS : Rats were given repeated treatment with amphetamine once daily at 1 , 2 , or 4 mg / kg for 14 days .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "From 10 to 14 days after final amphetamine treatment , behavioral changes were monitored using open field test , novel object recognition test , and forced swim test .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [31, 42]}], "task": "NER"}
{"text": "Oxidative damage in the medial frontal cortex and hippocampus was analyzed by immunohistochemistry .", "entity": [], "task": "NER"}
{"text": "RESULTS : We found that drug abstinence after repeated amphetamine stimulation decreased locomotor activity and exploratory behavior in the open field test , increased immobility in the forced swim test , and had no significant effect on the recognition index in the novel object recognition test .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "We also found that amphetamine abstinence increased levels of 4 - hydroxynonenal - protein adducts and 8 - hydroxyguanosine in rat medial frontal cortex and in CA3 and dentate gyrus regions of the hippocampus .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "4 - hydroxynonenal", "entity_type": "Chemical", "pos": [62, 80]}, {"entity": "8 - hydroxyguanosine", "entity_type": "Chemical", "pos": [103, 123]}], "task": "NER"}
{"text": "CONCLUSIONS : These results suggest that amphetamine abstinence displays depressive - like behaviors in rats and induces oxidative damage to lipids and RNA in rat brain .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [41, 52]}], "task": "NER"}
{"text": "Our findings indicate that the process of oxidative stress may play a role in pathophysiological changes during drug abstinence from repeated amphetamine stimulation .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [142, 153]}], "task": "NER"}
{"text": "Oroxylin A improves attention deficit hyperactivity disorder - like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro .", "entity": [{"entity": "Oroxylin A", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "In previous studies we have demonstrated that the gamma - aminobutryic acid - A ( GABA - A ) receptor antagonist oroxylin A has an awakening effect and it also represses ADHD - like behaviors ( hyperactivity , impulsivity and inattention ) in the spontaneously hypertensive rat ( SHR ) model of attention - deficit hyperactivity disorder ( ADHD ) .", "entity": [{"entity": "gamma - aminobutryic acid", "entity_type": "Chemical", "pos": [50, 75]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [82, 86]}, {"entity": "oroxylin A", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "We hypothesized that the effects of oroxylin A were exerted via the GABA - A receptor given the important role of the GABAergic system in ADHD .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "However , it is possible that aside from the GABAergic system , oroxylin A may influence other systems especially those implicated in ADHD ( e . g . DAergic , etc . ) .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [64, 74]}], "task": "NER"}
{"text": "To test this hypothesis , we evaluated the effects of GABA agonist , or dopamine ( DA ) antagonist in oroxylin A - induced alleviation of ADHD - like behaviors in SHR .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [72, 80]}, {"entity": "oroxylin A", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "SHR showed inattention and impulsivity as measured by the Y - maze and the electro - foot shock aversive water drinking tests , respectively .", "entity": [], "task": "NER"}
{"text": "Oroxylin A significantly improved these behaviors , furthermore , its effect on SHR impulsivity was attenuated by haloperidol , a DA antagonist , but not by baicalein , an agonist of the GABA - A receptor .", "entity": [{"entity": "Oroxylin A", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "haloperidol", "entity_type": "Chemical", "pos": [114, 125]}, {"entity": "baicalein", "entity_type": "Chemical", "pos": [157, 166]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [187, 191]}], "task": "NER"}
{"text": "In vitro studies showed that oroxylin A inhibited DA uptake similar to methylphenidate , a dopamine transporter blocker , but did not influence norepinephrine uptake unlike atomoxetine , a selective NE reuptake inhibitor .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [29, 39]}, {"entity": "methylphenidate", "entity_type": "Chemical", "pos": [71, 86]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "norepinephrine", "entity_type": "Chemical", "pos": [144, 158]}, {"entity": "atomoxetine", "entity_type": "Chemical", "pos": [173, 184]}], "task": "NER"}
{"text": "Collectively , the present findings suggest that oroxylin A improves ADHD - like behaviors in SHR via enhancement of DA neurotransmission and not modulation of GABA pathway as previously reported .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [49, 59]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [160, 164]}], "task": "NER"}
{"text": "Importantly , the present study indicates the potential therapeutic value of oroxylin A in the treatment of ADHD .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [77, 87]}], "task": "NER"}
{"text": "The toxicity of a ternary biocide mixture to two consecutive earthworm ( Eisenia fetida ) Generations .", "entity": [], "task": "NER"}
{"text": "The aim of the present study was to determine the toxicity of a mixture containing the biocides picoxystrobin , esfenvalerate , and triclosan to the reproduction and adult survival of two consecutive generations of Eisenia fetida ( Savigny , 1826 ) .", "entity": [{"entity": "picoxystrobin", "entity_type": "Chemical", "pos": [96, 109]}, {"entity": "esfenvalerate", "entity_type": "Chemical", "pos": [112, 125]}, {"entity": "triclosan", "entity_type": "Chemical", "pos": [132, 141]}], "task": "NER"}
{"text": "Concentration addition and independent action were used to predict mixture toxicity .", "entity": [], "task": "NER"}
{"text": "Due to degradation of mixture components during the course of the experiment , predictions were based both on the mixture composition at the beginning and the end of the exposure period .", "entity": [], "task": "NER"}
{"text": "As degradations were dose - dependent , none of the calculated predictions were precise for the entire concentration range , although combining both predictions led us to conclude that lethal toxicity was well predicted by concentration addition and sublethal toxicity by independent action .", "entity": [], "task": "NER"}
{"text": "Reproduction of the F1 generation was inhibited more ( p < 0 . 0001 ) than reproduction of the F0 generation .", "entity": [], "task": "NER"}
{"text": "Adult survival did not differ between generations .", "entity": [], "task": "NER"}
{"text": "The accuracy of the mixture toxicity predictions thus depended on both the time - dependent mixture composition and the earthworm generation .", "entity": [], "task": "NER"}
{"text": "The results of this study underline the need for more advanced mixture toxicity prediction models that consider degradation kinetics and changes in toxic effects over time .", "entity": [], "task": "NER"}
{"text": "Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health - related quality of life - a Brazilian multicentre study .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [11, 24]}], "task": "NER"}
{"text": "This study aimed to verify the impact of levothyroxine replacement on health - related quality of life ( HRQoL ) in a Brazilian sample of primary hypothyroidism patients .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [41, 54]}], "task": "NER"}
{"text": "A cross - sectional study was performed with 2 , 057 consecutive primary hypothyroidism patients on levothyroxine ( LT4 ) replacement at four referral centers in Brazil ( median age = 53 ; 25th percentile = 43 ; 75th percentile = 61 years ) .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [100, 113]}, {"entity": "LT4", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "Patient biochemical data were acquired from medical records , and patients completed a questionnaire on socioeconomic issues and clinical signs and symptoms of hypothyroidism .", "entity": [], "task": "NER"}
{"text": "HRQoL was assessed using the SF - 36v2 .", "entity": [], "task": "NER"}
{"text": "Patients were divided into three groups according to TSH levels : overtreated ( OvT ; TSH < 0 . 4 mU / L ) , appropriately treated ( AT ; TSH between 0 . 4 and 4 . 0 mU / L ) , and undertreated ( UnT ; TSH > 4 . 0 mU / L ) .", "entity": [], "task": "NER"}
{"text": "Patients were also analyzed by TSH and FT4 serum levels : overt hyperthyroidism ( OHyper ; TSH < 0 . 4 mU / L and FT4 > 1 . 9 ng / dL ) , subclinical hyperthyroidism ( SHyper ; TSH < 0 . 4 mU / L and FT4 0 . 8 - 1 . 9 ng / dL ) , subclinical hypothyroidism ( SHypo ; TSH > 4 . 0 mU / L and FT4 0 . 8 - 1 . 9 ng / dL ) , and overt hypothyroidism ( OHypo ; TSH > 4 . 0 mU / L and FT4 < 0 . 8 ng / dL ) .", "entity": [], "task": "NER"}
{"text": "A total of 14 . 4 % of patients were OvT , with 13 . 0 % SHyper and 1 . 4 % OHyper .", "entity": [], "task": "NER"}
{"text": "The prevalence of UnT was 25 . 9 % , with 21 . 5 % SHypo and 4 . 4 % OHypo .", "entity": [], "task": "NER"}
{"text": "Overtreatment was not associated with HRQoL impairment .", "entity": [], "task": "NER"}
{"text": "UnT patients had worse HRQoL than AT patients , especially for physical and emotional aspects , independent of SHypo or OHypo status .", "entity": [], "task": "NER"}
{"text": "Hypothyroidism undertreatment is associated with poor patient HRQoL .", "entity": [], "task": "NER"}
{"text": "Therefore , adequate LT4 therapy should be given to maintain serum TSH within the reference range .", "entity": [{"entity": "LT4", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "Novel locus including FGF21 is associated with dietary macronutrient intake .", "entity": [], "task": "NER"}
{"text": "Dietary intake of macronutrients ( carbohydrate , protein , and fat ) has been associated with risk of chronic conditions such as obesity and diabetes .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [35, 47]}], "task": "NER"}
{"text": "Family studies have reported a moderate contribution of genetics to variation in macronutrient intake .", "entity": [], "task": "NER"}
{"text": "In a genome - wide meta - analysis of a population - based discovery cohort ( n = 33 533 ) , rs838133 in FGF21 ( 19q13 . 33 ) , rs197273 near TRAF family member - associated NF - kappa - B activator ( TANK ) ( 2p24 . 2 ) , and rs10163409 in FTO ( 16q12 . 2 ) were among the top associations ( P < 10 ( - 5 ) ) for percentage of total caloric intake from protein and carbohydrate .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [366, 378]}], "task": "NER"}
{"text": "rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium ( CHARGE ) Nutrition Working Group ( n = 38 360 ) and attained genome - wide significance in combined analysis ( Pjoint = 7 . 9 x 10 ( - 9 ) ) .", "entity": [], "task": "NER"}
{"text": "A cytokine involved in cellular metabolism , FGF21 is a potential susceptibility gene for obesity and type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Our results highlight the potential of genetic variation for determining dietary macronutrient intake .", "entity": [], "task": "NER"}
{"text": "Effect of phospholipid composition and phase on nanodisc films at the solid - liquid interface as studied by neutron reflectivity .", "entity": [], "task": "NER"}
{"text": "Nanodiscs are disc - like self - assembled structures formed by phospholipids and amphipatic proteins .", "entity": [], "task": "NER"}
{"text": "The proteins wrap like a belt around the hydrophobic part of the lipids , basically producing nanometer - sized patches of lipid bilayers .", "entity": [], "task": "NER"}
{"text": "The bilayer in the nanodisc constitutes a native - like model of the cell membrane and can act as a nanometer - sized container for functional single membrane proteins .", "entity": [], "task": "NER"}
{"text": "In this study , we present a general nanodisc - based system , intended for structural and functional studies of membrane proteins .", "entity": [], "task": "NER"}
{"text": "In this method , the nanodiscs are aligned at a solid surface , providing the ability to determine the average structure of the film along an axis perpendicular to the interface as measured by neutron reflectivity .", "entity": [], "task": "NER"}
{"text": "The nanodisc film was optimized in terms of nanodisc coverage , reduced film roughness , and stability for time - consuming studies .", "entity": [], "task": "NER"}
{"text": "This was achieved by a systematic variation of the lipid phase , charge , and length of lipid tails .", "entity": [], "task": "NER"}
{"text": "Herein , we show that , although all studied nanodiscs align with their lipid bilayer parallel to the interface , gel - phase DMPC nanodiscs form the most suitable film for future membrane protein studies since they yield a dense irreversibly adsorbed film with low roughness and high stability over time .", "entity": [{"entity": "DMPC", "entity_type": "Chemical", "pos": [126, 130]}], "task": "NER"}
{"text": "This may be explained by the appropriate matching between the thickness of the hydrophobic lipid core of gel phase DMPC and the height of the belt protein .", "entity": [{"entity": "DMPC", "entity_type": "Chemical", "pos": [115, 119]}], "task": "NER"}
{"text": "Moreover , once formed the gel - phase DMPC nanodiscs film can be heated up to melt the lipid bilayer , thus providing a more biologically friendly environment for membrane proteins .", "entity": [{"entity": "DMPC", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "The GABA A receptor subunits heterologously expressed in Xenopus oocytes .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [4, 8]}], "task": "NER"}
{"text": "The gamma - aminobutyric acid ( GABA ) A receptor is composed of a variety of subunits and combinations and shows a characteristic distribution in the CNS .", "entity": [{"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [4, 29]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "To date , 20 subunits of the GABA A receptor have been cloned : alpha 1 - 6 , beta 1 - 4 , gamma 1 - 3 , delta , pi , epsilon , Theta , and rho 1 - 3 .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "Oocyte of Xenopus laevis is one of the most frequently used heterologous expression systems , which are used to design and analyze specific combinations of GABA A receptor subunits .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [156, 160]}], "task": "NER"}
{"text": "In oocytes , a certain GABA A receptor function is studied only by comparing the amplitude of the response to GABA and other drugs by physiological and pharmacological methods .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [23, 27]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [110, 114]}], "task": "NER"}
{"text": "According to the studies on Xenopus laevis oocytes , the alpha 1 beta 2 gamma 2S receptor combination is mostly used .", "entity": [], "task": "NER"}
{"text": "The alpha 1 - containing receptors mediate sedative and anticonvulsant acts .", "entity": [], "task": "NER"}
{"text": "The results of studies on oocytes show that PKA , NKCC1 , P2X3 receptors , and GABA A receptor - associated protein , etc . , are existing systems that show different reactivity to the GABA A receptors .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [79, 83]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [185, 189]}], "task": "NER"}
{"text": "The GABA A receptor subunits contain distinct binding sites for BZDs , neurosteroids , general anesthetics , etc . , which are responsible for the numerous functions of the GABA A receptor .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [4, 8]}, {"entity": "BZDs", "entity_type": "Chemical", "pos": [64, 68]}, {"entity": "neurosteroids", "entity_type": "Chemical", "pos": [71, 84]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [173, 177]}], "task": "NER"}
{"text": "A variety of other drugs , such as topiramate , TG41 , ( + ) - and ( - ) - borneol , apigenin , and 6 - methylflavone could also have modulatory effects on the GABA A receptors .", "entity": [{"entity": "topiramate", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "TG41", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "( + ) - and ( - ) - borneol", "entity_type": "Chemical", "pos": [55, 82]}, {"entity": "apigenin", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "6 - methylflavone", "entity_type": "Chemical", "pos": [100, 117]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [160, 164]}], "task": "NER"}
{"text": "Some of the different models and hypotheses on GABA A receptor structure and function have been achieved by using the two - electrode voltage clamp method in oocytes .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [47, 51]}], "task": "NER"}
{"text": "Bioactive natural products from the antarctic and arctic organisms .", "entity": [], "task": "NER"}
{"text": "Polar regions are remote and challenging areas on the earth .", "entity": [], "task": "NER"}
{"text": "In view of the unique environment and the severe competition in polar regions , it ' s considered that the ecological system might be the producer of new compounds with diversity biological activities .", "entity": [], "task": "NER"}
{"text": "This review is an attempt to consolidate the studies about 97 natural products isolated from Antarctic and Arctic organisms including microbes , algae , sponges , bryozoans , and tunicates and so on published in the recent years .", "entity": [], "task": "NER"}
{"text": "The emphasis is mainly about the new compounds , source organisms and biological activities , which signifies the immense competence of Antarctic and Arctic organisms as bioactive natural products producers .", "entity": [], "task": "NER"}
{"text": "Taxol : efficacy against oral squamous cell carcinoma .", "entity": [{"entity": "Taxol", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "In medicinal chemistry , one of the most studied molecules in recent history is taxol .", "entity": [{"entity": "taxol", "entity_type": "Chemical", "pos": [80, 85]}], "task": "NER"}
{"text": "Taxol is a versatile natural product that is used in various cancer treatment regimens .", "entity": [{"entity": "Taxol", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "It is administered to patients with breast , lung , and ovarian cancers , and is currently being studied for the treatment of squamous cell carcinoma of the oral cavity and tongue .", "entity": [], "task": "NER"}
{"text": "Taxol has been tested in a number of research and clinical phase trials to determine feasibility , toxicity , and cytotoxicity against oral squamous cell carcinoma as a single drug regimen and as a contributing drug component in treatment plans .", "entity": [{"entity": "Taxol", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "This paper reviews over forty articles that examine cell lines , murine models , and human results for the response of taxol against squamous cell carcinoma ( SCC ) of the oral cavity and the tongue .", "entity": [{"entity": "taxol", "entity_type": "Chemical", "pos": [119, 124]}], "task": "NER"}
{"text": "The evolution of drugs on schistosoma treatment : looking to the past to improve the future .", "entity": [], "task": "NER"}
{"text": "Schistosomiasis is a devastating worldwide widespread tropical disease that currently affects more than 230 million people , making it an issue of great socioeconomic and public health importance .", "entity": [], "task": "NER"}
{"text": "Unfortunatelly there is a single drug for the treatment of all forms of schistosomiasis , praziquantel , which was introduced in therapy in 1980 .", "entity": [{"entity": "praziquantel", "entity_type": "Chemical", "pos": [90, 102]}], "task": "NER"}
{"text": "The article goes by antimony compounds , emetine , hydantoin , nitrofurans , lucanthone , hycanthone , oxamniquine derivatives and organophosphates until it finally gets to praziquantel derivatives .", "entity": [{"entity": "emetine", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "hydantoin", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "nitrofurans", "entity_type": "Chemical", "pos": [63, 74]}, {"entity": "lucanthone", "entity_type": "Chemical", "pos": [77, 87]}, {"entity": "hycanthone", "entity_type": "Chemical", "pos": [90, 100]}, {"entity": "oxamniquine", "entity_type": "Chemical", "pos": [103, 114]}, {"entity": "organophosphates", "entity_type": "Chemical", "pos": [131, 147]}, {"entity": "praziquantel", "entity_type": "Chemical", "pos": [173, 185]}], "task": "NER"}
{"text": "The intent of this review is to provide a panorama of drugs that were and are being used in human chemotherapy looking to the past to improve rational design drugs in the future .", "entity": [], "task": "NER"}
{"text": "Not only clinical used compounds will be shown but also synthesized and tested compounds in vitro and in vivo in animal models which haven ' t yet to be used in humans .", "entity": [], "task": "NER"}
{"text": "Prospects for drug discovery and vaccines to be used in the treatment and prevention of schistosomiasis , clinical trials , concerns about the resistance / decreased effectiveness of the treatment , and patent database will also be discussed .", "entity": [], "task": "NER"}
{"text": "At the end of the review the reader will notice that much has been done but much still needs to be done yet .", "entity": [], "task": "NER"}
{"text": "Electrochemiluminescence biosensor based on conducting poly ( 5 - formylindole ) for sensitive detection of Ramos cells .", "entity": [{"entity": "poly ( 5 - formylindole )", "entity_type": "Chemical", "pos": [55, 80]}], "task": "NER"}
{"text": "A signal - on electrochemiluminescence ( ECL ) biosensor devoted to the detection of Ramos cells was fabricated based on a novel conducting polymer , poly ( 5 - formylindole ) ( P5FIn ) , which was synthesized electrochemically by direct anodic oxidation of 5 - formylindole ( 5FIn ) .", "entity": [{"entity": "poly ( 5 - formylindole )", "entity_type": "Chemical", "pos": [150, 175]}, {"entity": "P5FIn", "entity_type": "Chemical", "pos": [178, 183]}, {"entity": "5 - formylindole", "entity_type": "Chemical", "pos": [258, 274]}, {"entity": "5FIn", "entity_type": "Chemical", "pos": [277, 281]}], "task": "NER"}
{"text": "This ECL platform was presented by covalently coupling the 18 - mer amino - substituted oligonucleotide ( ODN ) probes with aldehyde groups that are strongly reactive toward a variety of nucleophiles on the surface of solid substrates .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "The specific identification and high - affinity between aptamers and target cells , gold nanoparticles ( AuNPs ) enhanced ECL nanoprobes , along with P5FIn induced ECL quenching contributed greatly to the sensitivity and selectivity .", "entity": [{"entity": "P5FIn", "entity_type": "Chemical", "pos": [150, 155]}], "task": "NER"}
{"text": "The ECL signals were logarithmically linear with the concentration of Ramos cells in a wide determination range from 500 to 1 . 0 x 10 ( 5 ) cells mL ( - 1 ) , and the corresponding detection limit was 300 cells mL ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "How the quantum efficiency of a highly emissive binuclear copper complex is enhanced by changing the processing solvent .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [58, 64]}], "task": "NER"}
{"text": "Polymorphism is often linked to the choice of processing solvents .", "entity": [], "task": "NER"}
{"text": "Packing effects or the preference of one certain conformer as possible causes of this phenomenon are strongly dependent on solvents and especially on their polarity .", "entity": [], "task": "NER"}
{"text": "Even in amorphous solids , the microstructure can be controlled by the choice of solvents .", "entity": [], "task": "NER"}
{"text": "Polymorphs or amorphous solids featuring different packing densities can exhibit different properties in terms of stability or optical effects .", "entity": [], "task": "NER"}
{"text": "The influence of these effects on a binuclear , strongly luminescent copper ( I ) complex was investigated .", "entity": [{"entity": "copper ( I )", "entity_type": "Chemical", "pos": [69, 81]}], "task": "NER"}
{"text": "Many possible applications for luminescent , amorphous coordination compounds , such as organic light - emitting diodes , sensors , and organic lasers , rely on photophysical properties like quantum efficiency to be repeatable .", "entity": [], "task": "NER"}
{"text": "The effect of processing solvents in this context is often underestimated , but very relevant for utilization in device manufacturing and should therefore be understood more deeply .", "entity": [], "task": "NER"}
{"text": "In this work , theoretical derivations , DFT calculations , X - ray - diffraction , photoluminescence spectroscopy , and the time - dependent single - photon - counting - technique ( TDSPC ) were used to understand this phenomenon more deeply .", "entity": [], "task": "NER"}
{"text": "The influence of five different solvents on Cu2I2 ( MePyrPHOS ) 3 was probed .", "entity": [{"entity": "Cu2I2 ( MePyrPHOS ) 3", "entity_type": "Chemical", "pos": [44, 65]}], "task": "NER"}
{"text": "This resulted in a modulation of the photoluminescence quantum yield phi between 0 . 5 and 0 . 9 in amorphous solid state .", "entity": [], "task": "NER"}
{"text": "A new polymorph of the material with slightly reduced values for phi has been identified .", "entity": [], "task": "NER"}
{"text": "The reduced efficiency could be correlated with a higher porosity and a reduced packing density .", "entity": [], "task": "NER"}
{"text": "Dense packing reduces nonradiative decay by geometrical fixation and thus increases the quantum efficiency .", "entity": [], "task": "NER"}
{"text": "The existence of similar effects on aluminum and iridium compounds has been confirmed by application of different processing solvents on Alq3 and Ir ( ppy ) 3 .", "entity": [{"entity": "aluminum", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "iridium", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "Alq3", "entity_type": "Chemical", "pos": [137, 141]}, {"entity": "Ir ( ppy ) 3", "entity_type": "Chemical", "pos": [146, 158]}], "task": "NER"}
{"text": "These results show that a tuning of the efficiency of a emissive metal complexes by choosing a proper processing solvent is possible .", "entity": [], "task": "NER"}
{"text": "If highly efficient materials for practical applications are desired , an evaluation of multiple solvents has to be considered .", "entity": [], "task": "NER"}
{"text": "Heavy - enzyme kinetic isotope effects on proton transfer in alanine racemase .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [61, 68]}], "task": "NER"}
{"text": "The catalytic effects of perdeuterating the pyridoxal phosphate - dependent enzyme alanine racemase from Geobacillus stearothermophilus are reported .", "entity": [{"entity": "pyridoxal phosphate", "entity_type": "Chemical", "pos": [44, 63]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "The mass of the heavy perdeuterated form is ~ 5 . 5 % greater than that of the protiated form , causing kinetic isotope effects ( KIEs ) of ~ 1 . 3 on k ( cat ) and k ( cat ) / K ( M ) for both L - and D - alanine .", "entity": [{"entity": "L - and D - alanine", "entity_type": "Chemical", "pos": [194, 213]}], "task": "NER"}
{"text": "These values increase when C alpha - deuterated alanine is used as the substrate .", "entity": [{"entity": "C alpha - deuterated alanine", "entity_type": "Chemical", "pos": [27, 55]}], "task": "NER"}
{"text": "The heavy - enzyme KIEs of ~ 3 on k ( cat ) / K ( M ) with deuterated substrates are greater than the product of the individual heavy - enzyme and primary substrate KIEs .", "entity": [], "task": "NER"}
{"text": "This breakdown of the rule of the geometric mean is likely due to coupled motion between the protein and the proton - transfer reaction coordinate in the rate - limiting step .", "entity": [], "task": "NER"}
{"text": "These data implicate a direct role for protein vibrational motions in barrier crossing for proton - transfer steps in alanine racemase .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "Gene copy - number alterations : a cost - benefit analysis .", "entity": [], "task": "NER"}
{"text": "Changes in DNA copy number , whether confined to specific genes or affecting whole chromosomes , have been identified as causes of diseases and developmental abnormalities and as sources of adaptive potential .", "entity": [], "task": "NER"}
{"text": "Here , we discuss the costs and benefits of DNA copy - number alterations .", "entity": [], "task": "NER"}
{"text": "Changes in DNA copy number are largely detrimental .", "entity": [], "task": "NER"}
{"text": "Amplifications or deletions of specific genes can elicit discrete defects .", "entity": [], "task": "NER"}
{"text": "Large - scale changes in DNA copy number can also cause detrimental phenotypes that are due to the cumulative effects of copy - number alterations of many genes simultaneously .", "entity": [], "task": "NER"}
{"text": "On the other hand , studies in microorganisms show that DNA copy - number alterations can be beneficial , increasing survival under selective pressure .", "entity": [], "task": "NER"}
{"text": "As DNA copy - number alterations underlie many human diseases , we will end with a discussion of gene copy - number changes as therapeutic targets .", "entity": [], "task": "NER"}
{"text": "Conformational coupling across the plasma membrane in activation of the EGF receptor .", "entity": [], "task": "NER"}
{"text": "How the epidermal growth factor receptor ( EGFR ) activates is incompletely understood .", "entity": [], "task": "NER"}
{"text": "The intracellular portion of the receptor is intrinsically active in solution , and to study its regulation , we measured autophosphorylation as a function of EGFR surface density in cells .", "entity": [], "task": "NER"}
{"text": "Without EGF , intact EGFR escapes inhibition only at high surface densities .", "entity": [], "task": "NER"}
{"text": "Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities , the intracellular module is inactivated when tethered on its own to the plasma membrane , and fluorescence cross - correlation shows that it fails to dimerize .", "entity": [], "task": "NER"}
{"text": "NMR and functional data indicate that activation requires an N - terminal interaction between the transmembrane helices , which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "We conclude that EGF binding removes steric constraints in the extracellular module , promoting activation through N - terminal association of the transmembrane helices .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [115, 116]}], "task": "NER"}
{"text": "LBR and lamin A / C sequentially tether peripheral heterochromatin and inversely regulate differentiation .", "entity": [], "task": "NER"}
{"text": "Eukaryotic cells have a layer of heterochromatin at the nuclear periphery .", "entity": [], "task": "NER"}
{"text": "To investigate mechanisms regulating chromatin distribution , we analyzed heterochromatin organization in different tissues and species , including mice with mutations in the lamin B receptor ( Lbr ) and lamin A ( Lmna ) genes that encode nuclear envelope ( NE ) proteins .", "entity": [], "task": "NER"}
{"text": "We identified LBR - and lamin - A / C - dependent mechanisms tethering heterochromatin to the NE .", "entity": [], "task": "NER"}
{"text": "The two tethers are sequentially used during cellular differentiation and development : first the LBR - and then the lamin - A / C - dependent tether .", "entity": [], "task": "NER"}
{"text": "The absence of both LBR and lamin A / C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior .", "entity": [], "task": "NER"}
{"text": "Myoblast transcriptome analyses indicated that selective disruption of the LBR - or lamin - A - dependent heterochromatin tethers have opposite effects on muscle gene expression , either increasing or decreasing , respectively .", "entity": [], "task": "NER"}
{"text": "These results show how changes in NE composition contribute to regulating heterochromatin positioning , gene expression , and cellular differentiation during development .", "entity": [], "task": "NER"}
{"text": "Vitamin D metabolism in human bone marrow stromal ( mesenchymal stem ) cells .", "entity": [{"entity": "Vitamin D", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "There are many human extra - renal tissues and cells that biosynthesize 1 alpha , 25 - dihydroxyvitamin D ( 1 alpha , 25 ( OH ) ( 2 ) D ) by the action of CYP27B1 / 1 alpha - hydroxylase .", "entity": [{"entity": "1 alpha , 25 - dihydroxyvitamin D", "entity_type": "Chemical", "pos": [72, 105]}, {"entity": "1 alpha , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [108, 135]}], "task": "NER"}
{"text": "Human marrow stromal cells ( hMSCs ) , also known as mesenchymal stem cells , were isolated from marrow discarded from well - characterized , consented subjects during common orthopedic procedures .", "entity": [], "task": "NER"}
{"text": "Human MSCs can give rise to osteoblasts , chondrocytes , adipocytes , and other lineages .", "entity": [], "task": "NER"}
{"text": "Their in vitro differentiation to osteoblasts is stimulated by 1 alpha , 25 ( OH ) ( 2 ) D , and recent evidence indicates that they have the capacity to metabolize vitamin D in a regulated manner .", "entity": [{"entity": "1 alpha , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [63, 90]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [165, 174]}], "task": "NER"}
{"text": "Human MSCs express the vitamin D receptor , 25 - hydroxylases , 1 alpha - hydroxylase , and 24 - hydroxylase ; stimulation of in vitro osteoblastogenesis by 25 ( OH ) D depends on the activity of CYP27B1 / 1 alpha - hydroxylase .", "entity": [{"entity": "vitamin D", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [157, 168]}], "task": "NER"}
{"text": "The finding that hMSCs are a both a producer and target of 1 alpha , 25 ( OH ) ( 2 ) D suggests a potential autocrine / paracrine role of vitamin D metabolism in osteoblast differentiation .", "entity": [{"entity": "1 alpha , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [59, 86]}, {"entity": "vitamin D", "entity_type": "Chemical", "pos": [138, 147]}], "task": "NER"}
{"text": "Expression and enzyme activity of CYP27B1 / 1 alpha - hydroxylase are upregulated by substrate 25 ( OH ) D and Parathyroid Hormone ( PTH ) and are downregulated by 1 alpha , 25 ( OH ) ( 2 ) D .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [95, 106]}, {"entity": "1 alpha , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [164, 191]}], "task": "NER"}
{"text": "With subject age , there are decreases in basal osteoblast potential and in stimulation of osteoblastogenesis by 1 alpha , 25 ( OH ) ( 2 ) D , 25 ( OH ) D , and PTH .", "entity": [{"entity": "1 alpha , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [113, 140]}, {"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [143, 154]}], "task": "NER"}
{"text": "In vitro treatment with a combination of 25 ( OH ) D and PTH rejuvenated osteoblastogenesis with hMSCs from elders ; this was attributable to increases in CYP27B1 / 1 alpha - hydroxylase and in receptor for each hormone by the reciprocal factor .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [41, 52]}], "task": "NER"}
{"text": "Other clinical variables beside age , i . e . low serum 25 ( OH ) D or low estimated glomerular filtration rate , are correlated with reduced osteoblastogenesis .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [56, 67]}], "task": "NER"}
{"text": "These studies suggest that osteoblastogenesis may not be optimal unless there is sufficient serum 25 ( OH ) D substrate for hMSCs to synthesize and respond to local 1 alpha , 25 ( OH ) ( 2 ) D .", "entity": [{"entity": "25 ( OH ) D", "entity_type": "Chemical", "pos": [98, 109]}, {"entity": "1 alpha , 25 ( OH ) ( 2 ) D", "entity_type": "Chemical", "pos": [165, 192]}], "task": "NER"}
{"text": "Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [15, 26]}], "task": "NER"}
{"text": "OBJECTIVE : To identify novel biomarkers through metabolomic profiles that distinguish metabolically well ( MW ) from metabolically unwell ( MUW ) individuals , independent of body mass index ( BMI ) .", "entity": [], "task": "NER"}
{"text": "MATERIALS / METHODS : This study was conducted as part of the Measurement to Understand the Reclassification of Disease of Cabarrus / Kannapolis ( MURDOCK ) project .", "entity": [], "task": "NER"}
{"text": "Individuals from 3 cohorts were classified as lean ( BMI < 25kg / m ( 2 ) ) , overweight ( BMI >= 25kg / m ( 2 ) , BMI < 30kg / m ( 2 ) ) or obese ( BMI >= 30kg / m ( 2 ) ) .", "entity": [], "task": "NER"}
{"text": "Cardiometabolic abnormalities were defined as : ( 1 ) impaired fasting glucose ( >= 100mg / dL and <= 126mg / dL ) ; ( 2 ) hypertension ; ( 3 ) triglycerides >= 150mg / dL ; ( 4 ) HDL - C < 40mg / dL in men , < 50mg / dL in women ; and ( 5 ) insulin resistance ( calculated Homeostatic Model Assessment ( HOMA - IR ) index of > 5 . 13 ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [71, 78]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [144, 157]}], "task": "NER"}
{"text": "MW individuals were defined as having < 2 cardiometabolic abnormalities and MUW individuals had >= two cardiometabolic abnormalities .", "entity": [], "task": "NER"}
{"text": "Targeted profiling of 55 metabolites used mass - spectroscopy - based methods .", "entity": [], "task": "NER"}
{"text": "Principal components analysis ( PCA ) was used to reduce the large number of correlated metabolites into clusters of fewer uncorrelated factors .", "entity": [], "task": "NER"}
{"text": "RESULTS : Of 1872 individuals , 410 were lean , 610 were overweight , and 852 were obese .", "entity": [], "task": "NER"}
{"text": "Of lean individuals , 67 % were categorized as MUW , whereas 80 % of overweight and 87 % of obese individuals were MUW .", "entity": [], "task": "NER"}
{"text": "PCA - derived factors with levels that differed the most between MW and MUW groups were factors 4 ( branched chain amino acids [ BCAA ] ) [ p < . 0001 ] , 8 ( various metabolites ) [ p < . 0001 ] , 9 ( C4 / Ci4 , C3 , C5 acylcarnitines ) [ p < . 0001 ] and 10 ( amino acids ) [ p < . 0002 ] .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [115, 126]}, {"entity": "C4 / Ci4 , C3 , C5 acylcarnitines", "entity_type": "Chemical", "pos": [202, 235]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [262, 273]}], "task": "NER"}
{"text": "Further , Factor 4 , distinguishes MW from MUW individuals independent of BMI .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : BCAA and related metabolites are promising biomarkers that may aid in understanding cardiometabolic health independent of BMI category .", "entity": [], "task": "NER"}
{"text": "Critical role of a methyl group on the gamma - lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I .", "entity": [{"entity": "methyl", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "gamma - lactone", "entity_type": "Chemical", "pos": [39, 54]}, {"entity": "acetogenins", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "C34 - epi and C34 - epi - C35 - trifluoro analogues of solamin , a mono - THF annonaceous acetogenin , were synthesized .", "entity": [{"entity": "C34 - epi - C35 - trifluoro", "entity_type": "Chemical", "pos": [14, 41]}, {"entity": "solamin", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "mono - THF", "entity_type": "Chemical", "pos": [67, 77]}, {"entity": "acetogenin", "entity_type": "Chemical", "pos": [90, 100]}], "task": "NER"}
{"text": "Their inhibitory activity , along with previously synthesized analogues ( C35 - fluoro , C35 - difluoro , and C35 - trifluorosolamins ) , against bovine mitochondrial NADH - ubiquinone oxidoreductase ( complex I ) was determined .", "entity": [{"entity": "C35 - fluoro , C35 - difluoro , and C35 - trifluorosolamins", "entity_type": "Chemical", "pos": [74, 133]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [167, 171]}, {"entity": "ubiquinone", "entity_type": "Chemical", "pos": [174, 184]}], "task": "NER"}
{"text": "The present study revealed that the methyl group on the gamma - lactone moiety is critical to the potent inhibition of complex I by natural acetogenins .", "entity": [{"entity": "methyl", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "gamma - lactone", "entity_type": "Chemical", "pos": [56, 71]}, {"entity": "acetogenins", "entity_type": "Chemical", "pos": [140, 151]}], "task": "NER"}
{"text": "Synthesis and antibacterial activity of 9 - oxime ether non - ketolides , and novel binding mode of alkylides with bacterial rRNA .", "entity": [{"entity": "9 - oxime", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "ether", "entity_type": "Chemical", "pos": [50, 55]}, {"entity": "ketolides", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "alkylides", "entity_type": "Chemical", "pos": [100, 109]}], "task": "NER"}
{"text": "We report a series of new 9 - oxime ether non - ketolides , including 3 - hydroxyl , 3 - O - acyl and 3 - O - alkyl clarithromycin derivatives , and thiophene - containing ketolides 1b - 1d .", "entity": [{"entity": "9 - oxime", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "ether", "entity_type": "Chemical", "pos": [36, 41]}, {"entity": "ketolides", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "3 - hydroxyl , 3 - O - acyl and 3 - O - alkyl clarithromycin", "entity_type": "Chemical", "pos": [70, 130]}, {"entity": "thiophene", "entity_type": "Chemical", "pos": [149, 158]}, {"entity": "ketolides", "entity_type": "Chemical", "pos": [172, 181]}], "task": "NER"}
{"text": "Unlike previously reported ketolide 1a , none of them is comparable to telithromycin .", "entity": [{"entity": "ketolide", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "telithromycin", "entity_type": "Chemical", "pos": [71, 84]}], "task": "NER"}
{"text": "A molecular modeling study was performed to gain insight into the binding mode of alkylides 17 - 20 with bacterial rRNA and to rationalize the great disparity of their SAR .", "entity": [{"entity": "alkylides", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "The 3 - O - sidechains of 19 and 20 point to the so - called hydrophilic side of the macrolide ring , as seen in clarithromycin .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [8, 9]}, {"entity": "macrolide", "entity_type": "Chemical", "pos": [85, 94]}, {"entity": "clarithromycin", "entity_type": "Chemical", "pos": [113, 127]}], "task": "NER"}
{"text": "In contrast , the 3 - O - sidechains of 17 and 18 bend to the backside , the so - called hydrophobic side of the macrolide ring .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [22, 23]}], "task": "NER"}
{"text": "The results clearly indicated the alkylides with improved antibacterial activity might possess a novel binding mode , which is different from clarithromycin and the alkylides with poor activity .", "entity": [{"entity": "alkylides", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "clarithromycin", "entity_type": "Chemical", "pos": [142, 156]}, {"entity": "alkylides", "entity_type": "Chemical", "pos": [165, 174]}], "task": "NER"}
{"text": "Influence of GluN2 subunit identity on NMDA receptor function .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "N - methyl - d - aspartate receptors ( NMDARs ) are ligand - gated ion channels ( ' ionotropic ' receptors ) activated by the major excitatory neurotransmitter , l - glutamate .", "entity": [{"entity": "N - methyl - d - aspartate", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "l - glutamate", "entity_type": "Chemical", "pos": [162, 175]}], "task": "NER"}
{"text": "While the term ' the NMDAR ' is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar .", "entity": [], "task": "NER"}
{"text": "This heterogeneity was evident from early electrophysiological , pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate , it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system .", "entity": [], "task": "NER"}
{"text": "In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs , consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes , examine the evidence that NMDAR subtypes differentially contribute to the induction of long - term potentiation and long - term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype - dependency of physiological and pathophysiological signalling .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' GluR - dep synaptic plasticity ' .", "entity": [], "task": "NER"}
{"text": "Arsenic induced neuronal apoptosis in guinea pigs is Ca2 + dependent and abrogated by chelation therapy : role of voltage gated calcium channels .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "Ca2 +", "entity_type": "Chemical", "pos": [53, 58]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [128, 135]}], "task": "NER"}
{"text": "Arsenic contaminated drinking water has affected more than 200 million people globally .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Chronic arsenicism has also been associated with numerous neurological diseases .", "entity": [], "task": "NER"}
{"text": "One of the prime mechanisms postulated for arsenic toxicity is reactive oxygen species ( ROS ) mediated oxidative stress .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [43, 50]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [72, 78]}], "task": "NER"}
{"text": "In this study , we explored the kinetic relationship of ROS with calcium and attempted to dissect the calcium ion channels responsible for calcium imbalance after arsenic exposure .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [65, 72]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [102, 109]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [139, 146]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "We also explored if mono - or combinational chelation therapy prevents arsenic - induced ( 25ppm in drinking water for 4 months ) neuronal apoptosis in a guinea pig animal model .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "Results indicate that chronic arsenic exposure caused a significant increase in ROS followed by NO and calcium influx .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "NO", "entity_type": "Chemical", "pos": [96, 98]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "This calcium influx is mainly dependent on L - type voltage gated channels that disrupt mitochondrial membrane potential , increase bax / bcl2 levels and caspase 3 activity leading to apoptosis .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [5, 12]}], "task": "NER"}
{"text": "Interestingly , blocking of ROS could completely reduce calcium influx whereas calcium blockage partially reduced ROS increase .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "While in general mono - and combinational chelation therapies were effective in reversing arsenic induced alteration , combinational therapy of DMSA and MiADMSA was most effective .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [90, 97]}, {"entity": "DMSA", "entity_type": "Chemical", "pos": [144, 148]}, {"entity": "MiADMSA", "entity_type": "Chemical", "pos": [153, 160]}], "task": "NER"}
{"text": "Our results provide evidence for the role of L - type calcium channels in regulating arsenic - induced calcium influx and DMSA + MiADMSA combinational therapy may be a better protocol than monotherapy in mitigating chronic arsenicosis .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [103, 110]}, {"entity": "DMSA", "entity_type": "Chemical", "pos": [122, 126]}, {"entity": "MiADMSA", "entity_type": "Chemical", "pos": [129, 136]}], "task": "NER"}
{"text": "Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF - kappa B and MAPKs activation via the phosphatidylinositol 3 - kinase signaling .", "entity": [{"entity": "Gastrodin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [139, 159]}], "task": "NER"}
{"text": "The phenolic glucoside gastrodin , a main constituent of a Chinese traditional herbal medicine , has been known to display several biological and pharmacological properties .", "entity": [{"entity": "phenolic glucoside", "entity_type": "Chemical", "pos": [4, 22]}, {"entity": "gastrodin", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "However , the role and precise molecular mechanisms explaining how gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown .", "entity": [{"entity": "gastrodin", "entity_type": "Chemical", "pos": [67, 76]}], "task": "NER"}
{"text": "To study this , rat H9c2 cardiomyocytes were treated with gastrodin and / or lipopolysaccharide ( LPS ) .", "entity": [{"entity": "gastrodin", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "Our results showed that gastrodin treatment strongly suppressed nuclear factor - kappa B ( NF - kappa B ) and mitogen - activated protein kinases ( MAPKs ) family activation and upregulation of the expression of inducible nitric oxide synthase ( iNOS ) , cyclooxygenase - 2 ( COX - 2 ) , tumor necrosis factor - alpha ( TNF - alpha ) , and interleukin - 6 ( IL - 6 ) in LPS - stimulated H9c2 cardiomyocytes .", "entity": [{"entity": "gastrodin", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [222, 234]}], "task": "NER"}
{"text": "Simultaneously , gastrodin obviously upregulated the phosphatidylinositol 3 - kinase ( PI3 - K ) / Akt signaling in a dose - dependent manner .", "entity": [{"entity": "gastrodin", "entity_type": "Chemical", "pos": [17, 26]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [53, 73]}], "task": "NER"}
{"text": "However , wortmannin , a specific PI3 - K inhibitor , blocked the inhibitory effects of gastrodin on LPS - stimulated H9c2 cardiomyocytes .", "entity": [{"entity": "wortmannin", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "gastrodin", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "Furthermore , PI3 - K / Akt inhibition partially abolished the inhibitory effects of gastrodin on the phosphorylation of inhibitor kappa B - alpha ( I kappa B - alpha ) , extracellular signal - regulated kinase 1 / 2 ( ERK1 / 2 ) , c - Jun N - terminal protein kinase ( JNK ) , and p38 mitogen - activated protein kinase ( p38 MAPK ) , and activity of NF - kappa B .", "entity": [{"entity": "gastrodin", "entity_type": "Chemical", "pos": [85, 94]}, {"entity": "N", "entity_type": "Chemical", "pos": [240, 241]}], "task": "NER"}
{"text": "Here we report activation of the PI3 - K / Akt signaling by gastrodin and that inhibition of this pathway reverses the inhibitory effects of gastrodin on NF - kappa B and MAPKs activation in H9c2 cardiomyocytes .", "entity": [{"entity": "gastrodin", "entity_type": "Chemical", "pos": [60, 69]}, {"entity": "gastrodin", "entity_type": "Chemical", "pos": [141, 150]}], "task": "NER"}
{"text": "Catalytic - site conformational equilibrium in nerve - agent adducts of acetylcholinesterase : Possible implications for the HI - 6 antidote substrate specificity .", "entity": [{"entity": "HI - 6", "entity_type": "Chemical", "pos": [125, 131]}], "task": "NER"}
{"text": "Nerve agents such as tabun , cyclosarin and Russian VX inhibit the essential enzyme acetylcholinesterase ( AChE ) by organophosphorylating the catalytic serine residue .", "entity": [{"entity": "tabun", "entity_type": "Chemical", "pos": [21, 26]}, {"entity": "cyclosarin", "entity_type": "Chemical", "pos": [29, 39]}, {"entity": "Russian VX", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "serine", "entity_type": "Chemical", "pos": [153, 159]}], "task": "NER"}
{"text": "Nucleophiles , such as oximes , are used as antidotes as they can reactivate and restore the function of the inhibited enzyme .", "entity": [{"entity": "oximes", "entity_type": "Chemical", "pos": [23, 29]}], "task": "NER"}
{"text": "The oxime HI - 6 shows a notably low activity on tabun adducts but can effectively reactivate adducts of cyclosarin and Russian VX .", "entity": [{"entity": "oxime", "entity_type": "Chemical", "pos": [4, 9]}, {"entity": "HI - 6", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [49, 54]}, {"entity": "cyclosarin", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "Russian VX", "entity_type": "Chemical", "pos": [120, 130]}], "task": "NER"}
{"text": "To examine the structural basis for the pronounced substrate specificity of HI - 6 , we determined the binary crystal structures of Mus musculus AChE ( mAChE ) conjugated by cyclosarin and Russian VX and found a conformational mobility of the side chains of Phe338 and His447 .", "entity": [{"entity": "HI - 6", "entity_type": "Chemical", "pos": [76, 82]}, {"entity": "cyclosarin", "entity_type": "Chemical", "pos": [174, 184]}, {"entity": "Russian VX", "entity_type": "Chemical", "pos": [189, 199]}, {"entity": "Phe338", "entity_type": "Chemical", "pos": [258, 264]}, {"entity": "His447", "entity_type": "Chemical", "pos": [269, 275]}], "task": "NER"}
{"text": "The interaction between HI - 6 and tabun - adducts of AChE were subsequently investigated using a combination of time resolved fluorescence spectroscopy and X - ray crystallography .", "entity": [{"entity": "HI - 6", "entity_type": "Chemical", "pos": [24, 30]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [35, 40]}], "task": "NER"}
{"text": "Our findings show that HI - 6 binds to tabun inhibited Homo sapiens AChE ( hAChE ) with an IC50 value of 300 mu M and suggest that the reactive nucleophilic moiety of HI - 6 is excluded from the phosphorus atom of tabun .", "entity": [{"entity": "HI - 6", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "HI - 6", "entity_type": "Chemical", "pos": [167, 173]}, {"entity": "phosphorus", "entity_type": "Chemical", "pos": [195, 205]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [214, 219]}], "task": "NER"}
{"text": "We propose that a conformational mobility of the side - chains of Phe338 and His447 is a common feature in nerve - agent adducts of AChE .", "entity": [{"entity": "Phe338", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "His447", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "We also suggest that the conformational mobility allow HI - 6 to reactivate conjugates of cyclosarin and Russian VX while a reduced mobility in tabun conjugated AChE results in steric hindrance that prevents efficient reactivation .", "entity": [{"entity": "HI - 6", "entity_type": "Chemical", "pos": [55, 61]}, {"entity": "cyclosarin", "entity_type": "Chemical", "pos": [90, 100]}, {"entity": "Russian VX", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "tabun", "entity_type": "Chemical", "pos": [144, 149]}], "task": "NER"}
{"text": "Hepatocytes display a compensatory survival response against cadmium toxicity by a mechanism mediated by EGFR and Src .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [61, 68]}], "task": "NER"}
{"text": "Although the liver is a cadmium - target organ , hepatocyte response involved in its toxicity is not yet elucidated .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [24, 31]}], "task": "NER"}
{"text": "A link between this heavy metal treatment and Stat3 signaling pathways was examined in primary mouse hepatocytes .", "entity": [], "task": "NER"}
{"text": "We provided evidence of a novel link among NADPH oxidase and Stat3 signaling , mediated by Src , EGFR , and Erk1 / 2 .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [43, 48]}], "task": "NER"}
{"text": "Cadmium activates NADPH oxidase .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [18, 23]}], "task": "NER"}
{"text": "ROS produced by this oxidase activates Src , enable that in turn , transactivates EGFR that activates Stat3 in tyrosine , allowing its dimerization .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "Also , ROS from NADPH oxidase favors ERK1 / 2 activation that phosphorylates Stat3 in serine , resulting in a compensatory or adaptive survival response such as production of metallothionein - II in short Cd exposure times .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [16, 21]}, {"entity": "serine", "entity_type": "Chemical", "pos": [86, 92]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [205, 207]}], "task": "NER"}
{"text": "However , after 12h CdCl2 treatment , cell viability diminished in 50 % , accompanied by a drastic decrease of metallothionein - II production , and an increase in p53 activation and the pro - apoptotic protein Bax .", "entity": [{"entity": "CdCl2", "entity_type": "Chemical", "pos": [20, 25]}], "task": "NER"}
{"text": "Catalpol suppresses advanced glycation end - products - induced inflammatory responses through inhibition of reactive oxygen species in human monocytic THP - 1 cells .", "entity": [{"entity": "Catalpol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [118, 124]}], "task": "NER"}
{"text": "Advanced glycation end - products ( AGEs ) play a pivotal role in the development of diabetic complications by inducing inflammation .", "entity": [], "task": "NER"}
{"text": "We previously reported that the fresh roots of Rehmannia glutinosa Libosch . , which have been used for the treatment of diabetes in traditional Korean medicine , also have the potential to suppress AGE - mediated inflammatory response in THP - 1 cells .", "entity": [], "task": "NER"}
{"text": "In the present study , we isolated catalpol from R . glutinosa , and examined whether it has anti - inflammatory effects on AGE - stimulated THP - 1 cells .", "entity": [{"entity": "catalpol", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "Catalpol reduced the expression of pro - inflammatory mediates , such as monocyte chemotactic protein - 1 ( MCP - 1 ) , tumor necrosis factor - alpha ( TNF - alpha ) , inducible NO synthase ( iNOS ) , and receptor for AGE ( RAGE ) .", "entity": [{"entity": "Catalpol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "NO", "entity_type": "Chemical", "pos": [178, 180]}], "task": "NER"}
{"text": "Promoter and electromobility shift assays showed that transcriptional activation of NF - kappa B was significantly reduced by catalpol treatment , while AP - 1 was not .", "entity": [{"entity": "catalpol", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "Catalpol also suppressed AGE - induced phosphorylation of mitogen activated protein ( MAP ) kinases , degradation of I kappa B alpha and the nuclear localization of NF - kappa B .", "entity": [{"entity": "Catalpol", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Moreover , the production of intracellular reactive oxygen species ( ROS ) elicited by AGE was also suppressed by catalpol treatment , through dual action of reducing ROS itself and inhibiting NADPH oxidase activity .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [52, 58]}, {"entity": "catalpol", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [193, 198]}], "task": "NER"}
{"text": "Our findings indicate that catalpol suppresses AGE - mediated inflammation by inhibiting ROS production and NF - kappa B activity .", "entity": [{"entity": "catalpol", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "We suggest that catalpol , a major constituent of the fresh roots of R . glutinosa , contributes to the prevention of AGE - mediated diabetic complications .", "entity": [{"entity": "catalpol", "entity_type": "Chemical", "pos": [16, 24]}], "task": "NER"}
{"text": "New insights toward the discovery of antibacterial agents : multi - tasking QSBER model for the simultaneous prediction of anti - tuberculosis activity and toxicological profiles of drugs .", "entity": [], "task": "NER"}
{"text": "Tuberculosis ( TB ) constitutes one of the most dangerous and serious health problems around the world .", "entity": [], "task": "NER"}
{"text": "It is a very lethal disease caused by microorganisms of the genus mycobacterium , principally Mycobacterium tuberculosis ( MTB ) which affects humans .", "entity": [], "task": "NER"}
{"text": "A very active field for the search of more efficient anti - TB chemotherapies is the use in silico methodologies for the discovery of potent anti - TB agents .", "entity": [], "task": "NER"}
{"text": "The battle against MTB by using antimicrobial chemotherapies will depend on the design of new chemicals with high anti - TB activity and low toxicity as possible .", "entity": [], "task": "NER"}
{"text": "Multi - target methodologies focused on quantitative - structure activity relationships ( mt - QSAR ) have played a very important role for the rationalization of drug design , providing a better understanding about the molecular patterns related with diverse pharmacological profiles including antimicrobial activity .", "entity": [], "task": "NER"}
{"text": "Nowadays , almost all mt - QSAR models have considered the study of biological activity or toxicity separately .", "entity": [], "task": "NER"}
{"text": "In the present study , we develop by the first time , a unified multitasking model based on quantitative - structure biological effect relationships ( mtk - QSBER ) for the simultaneous prediction of anti - TB activity and toxicity against Mus musculus and Rattus norvegicus .", "entity": [], "task": "NER"}
{"text": "The mtk - QSBER model was created by using linear discriminant analysis ( LDA ) for the classification of compounds as positive ( high biological activity and / or low toxicity ) or negative ( otherwise ) under many experimental conditions .", "entity": [], "task": "NER"}
{"text": "Our mtk - QSBER model , correctly classified more than 90 % of the case in the whole database ( more than 12 , 000 cases ) , serving as a powerful tool for the computer - assisted screening of potent and safe anti - TB drugs .", "entity": [], "task": "NER"}
{"text": "Excessive ethanol consumption under exposure to lead intensifies disorders in bone metabolism : A study in a rat model .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [10, 17]}], "task": "NER"}
{"text": "It was investigated whether ethanol ( Et ) modifies the damaging impact of lead ( Pb ) on bone metabolism in a rat model reflecting excessive alcohol consumption by humans exposed to relatively high levels of this metal .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [82, 84]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [142, 149]}], "task": "NER"}
{"text": "For this purpose , markers of bone formation ( osteocalcin , procollagen I , osteoprotegerin , alkaline phosphatase ) and resorption ( telopeptides of collagen I , soluble receptor activator of nuclear factor - kappa B ligand ) , calciotropic hormones ( parathormone , calcitonin , 25 - hydroxyvitamin D and 1 , 25 - dihydroxyvitamin D ) in the serum , and the femur content of mineral ( including calcium - Ca and inorganic phosphorus - Pi ) and organic components were estimated in the rats exposed to 500mg Pb / l ( in drinking water ) or / and Et ( 5g / kg b . wt . / 24h , by oral gavage ) for 12weeks .", "entity": [{"entity": "25 - hydroxyvitamin D", "entity_type": "Chemical", "pos": [282, 303]}, {"entity": "1 , 25 - dihydroxyvitamin D", "entity_type": "Chemical", "pos": [308, 335]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [398, 405]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [408, 410]}, {"entity": "phosphorus", "entity_type": "Chemical", "pos": [425, 435]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [510, 512]}], "task": "NER"}
{"text": "Moreover , Ca and Pi in the serum and urine , alkaline phosphatase in the bone tissue and Pb in the blood and femur were determined .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [11, 13]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [90, 92]}], "task": "NER"}
{"text": "The exposure to Pb or / and Et decreased bone formation and increased its resorption resulting in the bone demineralization .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [16, 18]}], "task": "NER"}
{"text": "These effects were accompanied by destroying the hormonal regulation of mineral metabolism , and Ca and Pi imbalance .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [97, 99]}], "task": "NER"}
{"text": "The co - exposure to Pb and Et - induced disorders in bone metabolism were more advanced than those caused by Pb alone .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [110, 112]}], "task": "NER"}
{"text": "Et co - administration increased Pb concentration in the blood and decreased its accumulation in the bone .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [33, 35]}], "task": "NER"}
{"text": "This paper is the first report providing evidence that consumption of Et under exposure to Pb intensifies disorders in bone metabolism and that destroying of the receptor activator nuclear factor - kappa B ( RANK ) / RANK ligand / osteoprotegerin system is involved in the mechanisms of interactive action of these xenobiotics on the skeleton .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [91, 93]}], "task": "NER"}
{"text": "The modifying impact of Et may be an effect of its independent osteotropic action and interaction with Pb .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [103, 105]}], "task": "NER"}
{"text": "Based on the results it can be concluded that alcohol abuse by subjects excessively exposed to Pb considerably increases the risk of bone damage .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [95, 97]}], "task": "NER"}
{"text": "Cellular mechanisms of the cytotoxic effects of the zearalenone metabolites alpha - zearalenol and beta - zearalenol on RAW264 . 7 macrophages .", "entity": [{"entity": "zearalenone", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "alpha - zearalenol", "entity_type": "Chemical", "pos": [76, 94]}, {"entity": "beta - zearalenol", "entity_type": "Chemical", "pos": [99, 116]}], "task": "NER"}
{"text": "Zearalenone ( ZEN ) and its metabolites are commonly found in many food commodities and are known to cause reproductive disorders and genotoxic effects .", "entity": [{"entity": "Zearalenone", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "ZEN", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "The major ZEN metabolites are alpha - zearalenol ( alpha - ZOL ) and beta - zearalenol ( beta - ZOL ) .", "entity": [{"entity": "ZEN", "entity_type": "Chemical", "pos": [10, 13]}, {"entity": "alpha - zearalenol", "entity_type": "Chemical", "pos": [30, 48]}, {"entity": "alpha - ZOL", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "beta - zearalenol", "entity_type": "Chemical", "pos": [69, 86]}, {"entity": "beta - ZOL", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "Although many studies have demonstrated the cytotoxic effects of these metabolites , the mechanisms by which alpha - ZOL or beta - ZOL mediates their cytotoxic effects appear to differ according to cell type and the exposed toxins .", "entity": [{"entity": "alpha - ZOL", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "beta - ZOL", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "We evaluated the toxicity of alpha - ZOL and beta - ZOL on RAW264 . 7 macrophages and investigated the underlying mechanisms .", "entity": [{"entity": "alpha - ZOL", "entity_type": "Chemical", "pos": [29, 40]}, {"entity": "beta - ZOL", "entity_type": "Chemical", "pos": [45, 55]}], "task": "NER"}
{"text": "beta - ZOL not only more strongly reduced the viability of cells than did alpha - ZOL , but it also induced cell death mainly by apoptosis rather than necrosis .", "entity": [{"entity": "beta - ZOL", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "alpha - ZOL", "entity_type": "Chemical", "pos": [74, 85]}], "task": "NER"}
{"text": "The ZEN metabolites induced loss of mitochondrial membrane potential ( MMP ) , mitochondrial changes in Bcl - 2 and Bax proteins , and cytoplasmic release of cytochrome c and apoptosis - inducing factor ( AIF ) .", "entity": [{"entity": "ZEN", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "Use of an inhibitor specific to c - Jun N - terminal kinase ( JNK ) , p38 kinase or p53 , but not pan - caspase or caspase - 8 , decreased the toxin - induced generation of reactive oxygen species ( ROS ) and also attenuated the alpha - ZOL - or beta - ZOL - induced decrease of cell viability .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [40, 41]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [182, 188]}, {"entity": "alpha - ZOL", "entity_type": "Chemical", "pos": [229, 240]}, {"entity": "beta - ZOL", "entity_type": "Chemical", "pos": [246, 256]}], "task": "NER"}
{"text": "Antioxidative enzyme or compounds such as catalase , acteoside , and ( E ) - 1 - ( 3 , 4 - dihydroxyphenethyl ) - 3 - ( 4 - hydroxystyryl ) urea suppressed the ZEN metabolite - mediated reduction of cell viability .", "entity": [{"entity": "acteoside", "entity_type": "Chemical", "pos": [53, 62]}, {"entity": "( E ) - 1 - ( 3 , 4 - dihydroxyphenethyl ) - 3 - ( 4 - hydroxystyryl ) urea", "entity_type": "Chemical", "pos": [69, 144]}, {"entity": "ZEN", "entity_type": "Chemical", "pos": [160, 163]}], "task": "NER"}
{"text": "Further , knockdown of AIF via siRNA transfection diminished the ZEN metabolite - induced cell death .", "entity": [{"entity": "ZEN", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "Collectively , these results suggest that the activation of p53 , JNK or p38 kinase by ZEN metabolites is the main upstream signal required for the mitochondrial alteration of Bcl - 2 / Bax signaling pathways and intracellular ROS generation , while MMP loss and nuclear translocation of AIF are the critical downstream events for ZEN metabolite - mediated apoptosis in macrophages .", "entity": [{"entity": "ZEN", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "ZEN", "entity_type": "Chemical", "pos": [331, 334]}], "task": "NER"}
{"text": "Sodium arsenite induces cyclooxygenase - 2 expression in human uroepithelial cells through MAPK pathway activation and reactive oxygen species induction .", "entity": [{"entity": "Sodium arsenite", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [29, 35]}], "task": "NER"}
{"text": "Arsenic can induce reactive oxygen species ( ROS ) leading to oxidative stress and carcinogenesis .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [28, 34]}], "task": "NER"}
{"text": "Bladder is one of the major target organs of arsenic , and cyclooxygenase - 2 ( COX - 2 ) may play an important role in arsenic - induced bladder cancer .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [45, 52]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [120, 127]}], "task": "NER"}
{"text": "However , the mechanism by which arsenic induces COX - 2 in bladder cells remains unclear .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [33, 40]}], "task": "NER"}
{"text": "This study aimed at investigating arsenic - mediated intracellular redox status and signaling cascades leading to COX - 2 induction in human uroepithelial cells ( SV - HUC - 1 ) .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [34, 41]}], "task": "NER"}
{"text": "SV - HUC - 1 cells were exposed to sodium arsenite and COX - 2 expression , mitogen - activated protein kinase ( MAPK ) phosphorylation , glutathione ( GSH ) levels , ROS induction and Nrf2 expression were quantified .", "entity": [{"entity": "sodium arsenite", "entity_type": "Chemical", "pos": [35, 50]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [138, 149]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [152, 155]}], "task": "NER"}
{"text": "Our results demonstrate that arsenite ( 1 - 10 mu M ) elevates COX - 2 expression , GSH levels , ROS and Nrf2 expression .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Arsenite treatment for 24h stimulates phosphorylation of ERK and p38 , but not JNK in SV - HUC - 1 cells .", "entity": [{"entity": "Arsenite", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Induction of Cox - 2 mRNA levels by arsenite was attenuated by inhibitors of ERK , p38 and JNK .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Arsenite - induced ROS generation and COX - 2 expression were significantly attenuated by treatment with melatonin ( a ROS scavenger ) , but enhanced by DL - buthionine - ( S , R ) - sulfoximine ( BSO , an inhibitor of gamma - glutamylcysteine synthetase ( gamma - GCS ) resulting in lower GSH and increased ROS levels ) .", "entity": [{"entity": "Arsenite", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "melatonin", "entity_type": "Chemical", "pos": [105, 114]}, {"entity": "DL - buthionine - ( S , R ) - sulfoximine", "entity_type": "Chemical", "pos": [153, 194]}, {"entity": "BSO", "entity_type": "Chemical", "pos": [197, 200]}, {"entity": "gamma - glutamylcysteine", "entity_type": "Chemical", "pos": [219, 243]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [290, 293]}], "task": "NER"}
{"text": "These data indicate that arsenite promotes an induction of ROS , which results in an induction of COX - 2 expression through activation of the MAPK pathway .", "entity": [{"entity": "arsenite", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility .", "entity": [], "task": "NER"}
{"text": "8 - Oxoguanine DNA glycosylase 1 ( OGG1 ) plays an important role in repairing oxidative DNA damage induced by chemical agents , such as tobacco .", "entity": [{"entity": "8 - Oxoguanine", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking , alone or combined , on sperm oxidative DNA damage and the risk of male infertility .", "entity": [], "task": "NER"}
{"text": "A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study .", "entity": [], "task": "NER"}
{"text": "Sperm 8 - hydroxydeoxyguanine ( 8 - OHdG ) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip - based Taq - Man genotyping technology .", "entity": [{"entity": "8 - hydroxydeoxyguanine", "entity_type": "Chemical", "pos": [6, 29]}, {"entity": "8 - OHdG", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8 - OHdG levels .", "entity": [{"entity": "8 - OHdG", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "Individuals with variant Cys / Cys homozygote showed higher levels of sperm 8 - OHdG than wide - type homozygote carriers ( Ser / Ser ) .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "8 - OHdG", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [130, 133]}], "task": "NER"}
{"text": "Stratified analysis found that the association between OGG1 polymorphism and sperm 8 - OHdG levels was only observed among smokers with pack - years >= 5 but not among those subjects with pack - years < 5 ( pack - years = packs smoked per day x years as a smoker ) .", "entity": [{"entity": "8 - OHdG", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "Further analysis based on the case - control study revealed that variant allele ( Cys ) of OGG1 was significantly associated with male infertility risk in a dominant model ( OR = 1 . 35 , 95 % CI : 1 . 01 - 1 . 82 ; trend P < 0 . 001 ) .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "Furthermore , we found a significant gene - environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk ( Pinteration = 0 . 0003 ) .", "entity": [], "task": "NER"}
{"text": "These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk .", "entity": [], "task": "NER"}
{"text": "Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity .", "entity": [{"entity": "Lycorine hydrochloride", "entity_type": "Chemical", "pos": [0, 22]}], "task": "NER"}
{"text": "Uncontrolled tumor cell proliferation and robust neovascularization are prominent features of aggressive ovarian cancers .", "entity": [], "task": "NER"}
{"text": "Although great efforts in anti - ovarian cancer therapy have been made in the past 4 decades , the 5 - year survival rates for ovarian cancer patients are still poor , and effective drugs to cure ovarian cancer patients are absent .", "entity": [], "task": "NER"}
{"text": "In this study , we evaluated the anti - cancer effects of lycorine hydrochloride ( LH ) , a novel anti - ovarian cancer agent , using the highly - invasive ovarian cancer cell line , Hey1B , as a model .", "entity": [{"entity": "lycorine hydrochloride", "entity_type": "Chemical", "pos": [58, 80]}], "task": "NER"}
{"text": "Our data showed that LH effectively inhibited mitotic proliferation of Hey1B cells ( half maximal inhibitory concentration = 1 . 2 mu M ) with very low toxicity , resulting in cell cycle arrest at the G2 / M transition through enhanced expression of the cell cycle inhibitor p21 and marked down - regulation of cyclin D3 expression .", "entity": [], "task": "NER"}
{"text": "Moreover , LH suppressed both the formation of capillary - like tubes by Hey1B cells cultured in vitro and the ovarian cancer cell - dominant neovascularization in vivo when administered to Hey1B - xenotransplanted mice .", "entity": [], "task": "NER"}
{"text": "LH also suppressed the expression of several key angiogenic genes , including VE - cadherin , vascular endothelial growth factor , and Sema4D , and reduced Akt phosphorylation in Hey1B cells .", "entity": [], "task": "NER"}
{"text": "These results suggest that LH selectively inhibits ovarian cancer cell proliferation and neovascularization and is a potential drug candidate for anti - ovarian cancer therapy .", "entity": [], "task": "NER"}
{"text": "Catechins are not major components responsible for the beneficial effect of Camellia sinensis on the ovarian delta - ALA - D activity inhibited by cadmium .", "entity": [{"entity": "Catechins", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "delta - ALA", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [147, 154]}], "task": "NER"}
{"text": "Cadmium has been associated with a wide spectrum of deleterious effects on the reproductive tissues , including ovary .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "This investigation evaluated the protective role of Camellia sinensis ( green , white and red teas ) in the cadmium - induced inhibition of ovarian delta - aminolevulinate dehydratase ( delta - ALA - D ) activity in vitro and ex vivo .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [108, 115]}, {"entity": "delta - aminolevulinate", "entity_type": "Chemical", "pos": [148, 171]}, {"entity": "delta - ALA", "entity_type": "Chemical", "pos": [186, 197]}], "task": "NER"}
{"text": "This study demonstrated that green and white teas restored the cow ovary delta - ALA - D activity inhibited by cadmium whereas red tea had no effect in vitro .", "entity": [{"entity": "delta - ALA", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [111, 118]}], "task": "NER"}
{"text": "In addition , green tea was able to restore enzyme activity inhibited after acute cadmium exposure in mice ovary .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [82, 89]}], "task": "NER"}
{"text": "Teas infusions composition was assessed by HPLC in a quantitative assay for catechins , purine alkaloids and gallic acid as well as total polyphenol content .", "entity": [{"entity": "catechins", "entity_type": "Chemical", "pos": [76, 85]}, {"entity": "purine alkaloids", "entity_type": "Chemical", "pos": [88, 104]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "polyphenol", "entity_type": "Chemical", "pos": [138, 148]}], "task": "NER"}
{"text": "The greatest effect of green tea observed in vitro as well as the protective role presented in the ex vivo study could be attributed to the major content of phenols , but not catechins .", "entity": [{"entity": "phenols", "entity_type": "Chemical", "pos": [157, 164]}, {"entity": "catechins", "entity_type": "Chemical", "pos": [175, 184]}], "task": "NER"}
{"text": "In fact , catechins were not able to restore enzyme activity inhibited by cadmium , demonstrating that these compounds are not major components responsible for the beneficial effect of green tea observed in this study .", "entity": [{"entity": "catechins", "entity_type": "Chemical", "pos": [10, 19]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "This study demonstrated the helpful effect of green tea infusion in ameliorating a marker protein of cadmium intoxication in ovarian tissue .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "4 - Nerolidylcatechol and its synthetic analogues : Antioxidant activity and toxicity evaluation .", "entity": [{"entity": "4 - Nerolidylcatechol", "entity_type": "Chemical", "pos": [0, 21]}], "task": "NER"}
{"text": "4 - Nerolidylcatechol ( 1 ) is a secondary metabolite of plants and is described as a promising anti - inflammatory , antimalarial , antiulcerogenic , analgesic and cytotoxic compound possibly due to its antioxidant profile .", "entity": [{"entity": "4 - Nerolidylcatechol", "entity_type": "Chemical", "pos": [0, 21]}], "task": "NER"}
{"text": "In this study , we evaluated the pharmacologic activity and the antioxidant and toxicological profiles of compound ( 1 ) and its synthetic analogues ( 2 - 6 ) .", "entity": [], "task": "NER"}
{"text": "The synthetic analogues were designed from the lead compound , ( 1 ) , using a molecular - simplification strategy .", "entity": [], "task": "NER"}
{"text": "Compound 5 showed , by 1 , 1 - diphenyl - 2 - picrylhydrazyl ( DPPH ) and beta - carotene systems , similar antioxidant activity when compared to compound ( 1 ) .", "entity": [{"entity": "1 , 1 - diphenyl - 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [23, 60]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "beta - carotene", "entity_type": "Chemical", "pos": [74, 89]}], "task": "NER"}
{"text": "The oxidative stress in erythrocyte membrane demonstrated the highly protective effect of compounds ( 4 ) , ( 5 ) and ( 6 ) and high antioxidant / pro - oxidant activity in relation to the concentrations of compounds ( 1 ) and ( 3 ) .", "entity": [], "task": "NER"}
{"text": "Compounds ( 2 ) , ( 4 ) , ( 5 ) and ( 6 ) were haemobiocompatible .", "entity": [], "task": "NER"}
{"text": "All compounds ( 1 - 6 ) showed cytotoxic effects in 3T3 cells , but compounds ( 2 ) and ( 6 ) were highly cytotoxic in this lineage when compared to compound ( 1 ) .", "entity": [], "task": "NER"}
{"text": "Compound ( 5 ) had a lower myelosuppressive effect in haematopoietic progenitor cells compared to ( 1 ) .", "entity": [], "task": "NER"}
{"text": "Both compounds , ( 1 ) and ( 5 ) , showed low genotoxic effects in vitro , on human lymphocyte cells .", "entity": [], "task": "NER"}
{"text": "In addition , these compounds also showed low - toxicity in vivo as defined a LD50 > 2000 mg / kg .", "entity": [], "task": "NER"}
{"text": "In this assay , we did not observe death in the animals exposed to treatment with ( 1 ) and ( 5 ) compound .", "entity": [], "task": "NER"}
{"text": "In conclusion , the structural design of the analogues as validated once compound ( 5 ) was found to have an antioxidant profile that was as potent as the lead compound ( 1 ) .", "entity": [], "task": "NER"}
{"text": "In addition , considering the safety profile , these compounds are promising as preventive and / or therapeutic agents against oxidative damage .", "entity": [], "task": "NER"}
{"text": "Isolation of a flavonoid , apigenin 7 - O - glucoside , from Mentha longifolia ( L . ) Hudson subspecies longifolia and its genotoxic potency .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "apigenin 7 - O - glucoside", "entity_type": "Chemical", "pos": [27, 53]}], "task": "NER"}
{"text": "Mentha is a medicinal and aromatic plant belonging to the Lamiaceae family , which is widely used in food , flavor , cosmetic and pharmaceutical industries .", "entity": [], "task": "NER"}
{"text": "Recently , it has been found that the use of Mentha as a pharmaceutical source is based on its phytochemical constituents that have far been identified as tannins , saponins , phenolic acids and flavonoids .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [155, 162]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [165, 173]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [176, 190]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [195, 205]}], "task": "NER"}
{"text": "This study was designed to evaluate the mutagenic and antimutagenic activities of apigenin 7 - O - glucoside ( A7G ) , a flavonoid isolated from Mentha longifolia ( L . ) Hudson subspecies longifolia ( ML ) .", "entity": [{"entity": "apigenin 7 - O - glucoside", "entity_type": "Chemical", "pos": [82, 108]}, {"entity": "A7G", "entity_type": "Chemical", "pos": [111, 114]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [121, 130]}], "task": "NER"}
{"text": "The possible antimutagenic potential of A7G was examined against mutagens ethyl methanesulfonate and acridine in an eukaryotic cell system Saccharomyces cerevisiae and sodium azide in Salmonella typhimurium TA1535 and 9 - aminoacridine in S . typhimurium TA1537 .", "entity": [{"entity": "A7G", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "ethyl methanesulfonate", "entity_type": "Chemical", "pos": [74, 96]}, {"entity": "acridine", "entity_type": "Chemical", "pos": [101, 109]}, {"entity": "sodium azide", "entity_type": "Chemical", "pos": [168, 180]}, {"entity": "9 - aminoacridine", "entity_type": "Chemical", "pos": [218, 235]}], "task": "NER"}
{"text": "According to our findings , any concentrations of the A7G used did not show mutagenic activity but exerted strong antimutagenic activities at tested concentrations .", "entity": [{"entity": "A7G", "entity_type": "Chemical", "pos": [54, 57]}], "task": "NER"}
{"text": "The inhibition rates for the Ames test ranged from 27 . 2 % ( S . typhimurium TA1535 : 0 . 4 mu M / plate ) to 91 . 1 % ( S . typhimurium TA1537 : 0 . 2 mu M / plate ) and for the yeast deletion assay from 4 % to 57 . 7 % .", "entity": [], "task": "NER"}
{"text": "This genotoxicological study suggests that a flavonoid from ML owing to antimutagenic properties is of great pharmacological importance and might be beneficial to industries producing food additives , cosmetics and pharmaceuticals products .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "Influence of pesticide exposure on carbonic anhydrase II from sheep stomach .", "entity": [], "task": "NER"}
{"text": "Carbonic anhydrase ( CA ) is a widely distributed enzyme and has a crucial role in the cells , tissues and organs of living organisms .", "entity": [], "task": "NER"}
{"text": "It is found that CA - II is one of the most abundant CA isoenzymes in the gastrointestinal system .", "entity": [], "task": "NER"}
{"text": "It plays an important role in the gastric acid secretion in stomach .", "entity": [], "task": "NER"}
{"text": "In this study , we purified CA - II isoenzyme from sheep stomach with a 615 . 2 purification fold , 78 % purification yield and 5562 . 02 specific activity .", "entity": [], "task": "NER"}
{"text": "Moreover , the in vitro effects of some commonly used pesticides including chlorpyrifos , cypermethrin , dichlorvos , glyphosate isopropylamine and lambda cyhalomethrin on the enzyme activity were investigated .", "entity": [{"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [75, 87]}, {"entity": "cypermethrin", "entity_type": "Chemical", "pos": [90, 102]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "glyphosate isopropylamine", "entity_type": "Chemical", "pos": [118, 143]}, {"entity": "lambda cyhalomethrin", "entity_type": "Chemical", "pos": [148, 168]}], "task": "NER"}
{"text": "Of these compounds , glyphosate isopropylamine and dichlorvos showed an inhibition on CA - II esterase activity .", "entity": [{"entity": "glyphosate isopropylamine", "entity_type": "Chemical", "pos": [21, 46]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [51, 61]}], "task": "NER"}
{"text": "They have IC ( 50 ) values of 0 . 155 micro M and 2 . 690 micro M and K ( i ) values of 0 . 329 micro M and 3 . 654 micro M , respectively .", "entity": [], "task": "NER"}
{"text": "Both glyphosate isopropylamine and dichlorvos inhibited CA - II isoenzyme in a noncompetitive manner .", "entity": [{"entity": "glyphosate isopropylamine", "entity_type": "Chemical", "pos": [5, 30]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [35, 45]}], "task": "NER"}
{"text": "Trim24 - repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA .", "entity": [], "task": "NER"}
{"text": "Trim24 ( Tif1 alpha ) and Trim33 ( Tif1 gamma ) interact to form a co - repressor complex that suppresses murine hepatocellular carcinoma .", "entity": [], "task": "NER"}
{"text": "Here we show that Trim24 and Trim33 cooperatively repress retinoic acid receptor - dependent activity of VL30 - class endogenous retroviruses ( ERVs ) in liver .", "entity": [{"entity": "retinoic acid", "entity_type": "Chemical", "pos": [58, 71]}], "task": "NER"}
{"text": "In Trim24 - knockout hepatocytes , VL30 derepression leads to accumulation of reverse - transcribed VL30 cDNA in the cytoplasm that correlates with activation of the viral - defense interferon responses mimicking the preneoplastic inflammatory state seen in human liver following exogenous viral infection .", "entity": [], "task": "NER"}
{"text": "Furthermore , upon derepression , VL30 long terminal repeats ( LTRs ) act as promoter and enhancer elements deregulating expression of neighboring genes and generating enhancer RNAs that are required for LTR enhancer activity in hepatocytes in vivo .", "entity": [], "task": "NER"}
{"text": "These data reinforce the role of the TRIM family of proteins in retroviral restriction and antiviral defense and provide an example of an ERV - derived oncogenic regulatory network .", "entity": [], "task": "NER"}
{"text": "Association between bisphenol A and abnormal free thyroxine level in men .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [20, 31]}, {"entity": "thyroxine", "entity_type": "Chemical", "pos": [50, 59]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is a chemical that is used in a variety of consumer products , and exposure to BPA is widespread among the general population .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [99, 102]}], "task": "NER"}
{"text": "Recent studies have suggested that BPA may affect the thyroid and related pathways .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [35, 38]}], "task": "NER"}
{"text": "However , human studies are still limited .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine the relationship between BPA exposure and thyroid function .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "We obtained survey data and blood samples from The Thai National Health Examination Survey IV 2009 , a nationally representative cross - sectional survey using a multistage , stratified sampling of the Thai population .", "entity": [], "task": "NER"}
{"text": "A total of 2 , 340 subjects aged 18 - 94 years were sampled for the present study .", "entity": [], "task": "NER"}
{"text": "Serum BPA , TSH , FT ( 4 ) , and related covariates were measured .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [6, 9]}], "task": "NER"}
{"text": "BPA was log - transformed prior to analysis .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "BPA was detected in 52 . 8 % of serum samples with a median concentration of 0 . 33 ( range 0 - 66 . 91 ) ng / mL .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "We excluded subjects who tested positive for thyroid autoantibody and then stratified the remaining subjects by gender ; the analysis showed a significantly negative correlation between serum BPA and FT ( 4 ) levels in males ( r = - 0 . 14 , P < 0 . 001 ) .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [192, 195]}], "task": "NER"}
{"text": "In contrast , no association was observed in females .", "entity": [], "task": "NER"}
{"text": "BPA was not associated with TSH in either gender .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "This gender - related discrepancy is possibly related to androgen - related differences in the metabolism of BPA .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [57, 65]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [109, 112]}], "task": "NER"}
{"text": "Our preliminary results provide evidence of a negative association between BPA and FT ( 4 ) levels .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [75, 78]}], "task": "NER"}
{"text": "Additional detailed studies are needed to investigate the temporal relationship and potential public health implications of such an association .", "entity": [], "task": "NER"}
{"text": "Genetics of type 2 diabetes and potential clinical implications .", "entity": [], "task": "NER"}
{"text": "Type 2 diabetes ( T2DM ) is a common complex metabolic disorder that has a strong genetic component .", "entity": [], "task": "NER"}
{"text": "Recent advances in genome - wide association studies have revolutionized our knowledge regarding the genetics of T2DM .", "entity": [], "task": "NER"}
{"text": "There are at least 64 common genetic variants that are strongly associated with T2DM .", "entity": [], "task": "NER"}
{"text": "However , the pathophysiologic roles of these variants are mostly unknown and require further functional characterization .", "entity": [], "task": "NER"}
{"text": "The variants identified so far have a small effect size and their added effect explains less than 10 % of the T2DM heritability .", "entity": [], "task": "NER"}
{"text": "The current ongoing whole exome and whole genome studies of T2DM are focused on identifying functionally important rare variants that have a stronger effect .", "entity": [], "task": "NER"}
{"text": "Through these efforts , we will have a better understanding of the genetic architecture of T2DM and its pathophysiology .", "entity": [], "task": "NER"}
{"text": "The potential clinical applications of genetic studies of T2DM include risk prediction , identification of novel therapeutic targets , genetic prediction of efficacy and toxicity of anti - diabetic medications , and eventually optimization of patient care through personalized genomic medicine .", "entity": [], "task": "NER"}
{"text": "We hope further research in genetics of T2DM could aid patient care and improve outcomes of T2DM patients .", "entity": [], "task": "NER"}
{"text": "Acute viral infections of the central nervous system in immunocompetent adults : diagnosis and management .", "entity": [], "task": "NER"}
{"text": "Patients with viral infections of the central nervous system ( CNS ) may present with a variety of neurological symptoms , most commonly dominated by either encephalitis or meningitis .", "entity": [], "task": "NER"}
{"text": "The aetiological panorama varies in different parts of the world as well as over time .", "entity": [], "task": "NER"}
{"text": "Thus , virological first - line diagnostics must be adapted to the current epidemiological situation and to the individual patient history , including recent travels .", "entity": [], "task": "NER"}
{"text": "This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective .", "entity": [], "task": "NER"}
{"text": "Effective vaccines are available for viruses such as poliovirus and tick - borne encephalitis virus ( TBEV ) and for the childhood diseases morbilli ( measles ) , rubella ( German measles ) , parotitis ( mumps ) and varicella ( chickenpox ) .", "entity": [], "task": "NER"}
{"text": "However , cases do appear due to suboptimal immunization rates .", "entity": [], "task": "NER"}
{"text": "In viral CNS infections , epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses .", "entity": [], "task": "NER"}
{"text": "Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital .", "entity": [], "task": "NER"}
{"text": "A positive cerebral spinal fluid ( CSF ) polymerase chain reaction ( PCR ) finding is usually reliable for aetiological diagnosis .", "entity": [], "task": "NER"}
{"text": "The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease , hitherto sufficiently evaluated in herpes simplex encephalitis ( HSE ) and tick - borne encephalitis ( TBE ) .", "entity": [], "task": "NER"}
{"text": "Despite improved virological and differential diagnostic methods , aetiology remains unknown in about half of the cases with suspected viral encephalitis .", "entity": [], "task": "NER"}
{"text": "Antiviral treatment is available chiefly for infections caused by herpesviruses , and acyclovir ( aciclovir ) is the drug of choice for empirical therapy in suspected viral encephalitis .", "entity": [{"entity": "acyclovir", "entity_type": "Chemical", "pos": [86, 95]}, {"entity": "aciclovir", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "However , randomized , controlled antiviral trials have only been conducted for HSE , while such studies are lacking in other viral CNS infections .", "entity": [], "task": "NER"}
{"text": "Viral cytolysis and immune - mediated mechanisms may contribute to varying extents to neurological damage .", "entity": [], "task": "NER"}
{"text": "Although the brain damage is believed to depend , to a varying degree , on the intrathecal host immune response , the use of corticosteroids in viral CNS infections is scarcely studied , as is specific treatment for neuroinflammation .", "entity": [{"entity": "corticosteroids", "entity_type": "Chemical", "pos": [125, 140]}], "task": "NER"}
{"text": "Improved antiviral and immunomodulating treatment is desirable .", "entity": [], "task": "NER"}
{"text": "Since neurological sequelae are still abundant , follow - up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan .", "entity": [], "task": "NER"}
{"text": "Sediment - associated pesticides in an urban stream in guangzhou , china : implication of a shift in pesticide use patterns .", "entity": [], "task": "NER"}
{"text": "Pesticide use patterns in China have changed in recent years ; however , the study of the environmental fate of current - use pesticides ( CUPs ) and their ecotoxicological significance in aquatic ecosystems is limited .", "entity": [], "task": "NER"}
{"text": "In the present study , sediments were collected from an urban stream in the Chinese city of Guangzhou .", "entity": [], "task": "NER"}
{"text": "Sediment - associated legacy organochlorine pesticides and CUPs - including organophosphates , pyrethroids , fipronil , and abamectin - were analyzed .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [29, 43]}, {"entity": "organophosphates", "entity_type": "Chemical", "pos": [76, 92]}, {"entity": "pyrethroids", "entity_type": "Chemical", "pos": [95, 106]}, {"entity": "fipronil", "entity_type": "Chemical", "pos": [109, 117]}, {"entity": "abamectin", "entity_type": "Chemical", "pos": [124, 133]}], "task": "NER"}
{"text": "Additionally , the relative toxicity of the sediments was evaluated with 10 - d bioassays using Chironomus dilutus .", "entity": [], "task": "NER"}
{"text": "Fifteen of 16 sediments collected from the stream were acutely toxic to C . dilutus , with 81 % of the samples causing 100 % mortality .", "entity": [], "task": "NER"}
{"text": "Abamectin , fipronil , and pyrethroids ( mainly cypermethrin ) were identified as the principal contributors to the noted toxicity in the midges , with median predicted toxic units of 1 . 63 , 1 . 63 , and 1 . 03 , respectively .", "entity": [{"entity": "Abamectin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "fipronil", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "pyrethroids", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "cypermethrin", "entity_type": "Chemical", "pos": [48, 60]}], "task": "NER"}
{"text": "Sediments taken from downstream sites , where residential and industrial regions were located , had elevated CUP concentrations and sediment toxicity compared with upstream sites .", "entity": [], "task": "NER"}
{"text": "The present study is the first of its kind to link sediment CUPs , fipronil , and abamectin concentrations with toxicity in urban streams in China with a focus on shifting pesticide usage patterns .", "entity": [{"entity": "fipronil", "entity_type": "Chemical", "pos": [67, 75]}, {"entity": "abamectin", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "Environ .", "entity": [], "task": "NER"}
{"text": "Toxicol .", "entity": [], "task": "NER"}
{"text": "Chem .", "entity": [], "task": "NER"}
{"text": "2013 ; 32 : 1040 - 1047 .", "entity": [], "task": "NER"}
{"text": "(c) 2013 SETAC .", "entity": [], "task": "NER"}
{"text": "Pancreatic beta - Cell Dysfunction and Risk of New - Onset Diabetes After Kidney Transplantation .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEChronic exposure to calcineurin inhibitors and corticosteroids poses renal transplant recipients ( RTR ) at high risk for development of new - onset diabetes after transplantation ( NODAT ) .", "entity": [], "task": "NER"}
{"text": "Pancreatic beta - cell dysfunction may be crucial to the pathophysiology of NODAT and specific markers for beta - cell dysfunction may have additive value for predicting NODAT in this population .", "entity": [], "task": "NER"}
{"text": "Therefore , we prospectively investigated whether proinsulin , as a marker of pancreatic beta - cell dysfunction , is associated with future development of NODAT and improves prediction of it . RESEARCH DESIGN AND METHODSAll RTR between 2001 and 2003 with a functioning graft for >= 1 year were considered eligible for inclusion , except for subjects with diabetes at baseline who were excluded .", "entity": [], "task": "NER"}
{"text": "We recorded incidence of NODAT until April 2012 . RESULTSA total of 487 RTR ( age 50 +/- 12 years , 55 % men ) participated at a median time of 6 . 0 ( interquartile range [ IQR ] , 2 . 6 - 11 . 5 ) years after transplantation .", "entity": [], "task": "NER"}
{"text": "Median fasting proinsulin levels were 16 . 6 ( IQR , 11 . 0 - 24 . 2 ) pmol / L .", "entity": [], "task": "NER"}
{"text": "During median follow - up for 10 . 1 ( IQR , 9 . 1 - 10 . 4 ) years , 42 ( 35 % ) RTR had development of NODAT in the highest quartile of the distribution of proinsulin versus 34 ( 9 % ) in the lowest three quartiles ( P < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "In Cox regression analyses , proinsulin ( hazard ratio , 2 . 29 ; 95 % confidence interval , 1 . 85 - 2 . 83 ; P < 0 . 001 ) was strongly associated with NODAT development .", "entity": [], "task": "NER"}
{"text": "This was independent of age , sex , calcineurine inhibitors , prednisolone use , components of the metabolic syndrome , or homeostasis model assessment . CONCLUSIONSIn conclusion , fasting proinsulin is strongly associated with NODAT development in RTR .", "entity": [{"entity": "prednisolone", "entity_type": "Chemical", "pos": [62, 74]}], "task": "NER"}
{"text": "Our results highlight the role of beta - cell dysfunction in the pathophysiology of NODAT and indicate the potential value of proinsulin for identification of RTR at increased risk for NODAT .", "entity": [], "task": "NER"}
{"text": "Glycation Gap Is Associated With Macroproteinuria but Not With Other Complications in Patients With Type 2 Diabetes .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEWe investigated whether glycation gap ( G - Gap ) , an index of intracellular glycation of proteins , was associated with diabetes complications . RESEARCH DESIGN AND METHODSWe measured concomitantly HbA ( 1c ) and fructosamine in 925 patients with type 2 diabetes to calculate the G - Gap , defined as the difference between measured HbA ( 1c ) , and fructosamine - based predicted HbA ( 1c ) .", "entity": [{"entity": "fructosamine", "entity_type": "Chemical", "pos": [224, 236]}, {"entity": "fructosamine", "entity_type": "Chemical", "pos": [361, 373]}], "task": "NER"}
{"text": "Patients were explored for retinopathy , nephropathy , peripheral neuropathy , cardiac autonomic neuropathy ( n = 512 ) , and silent myocardial ischemia ( n = 506 ) . RESULTSMacroproteinuria was the only complication that was associated with G - Gap ( prevalence in the first , second , and third tertile of G - Gap : 2 . 9 , 6 . 2 , and 11 . 0 % , respectively ; P < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "The G - Gap was higher in patients with macroproteinuria than in those without ( 1 . 06 +/- 1 . 62 vs . 0 . 03 +/- 1 . 30 % ; P < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "Because HbA ( 1c ) was associated with both G - Gap ( HbA ( 1c ) 7 . 0 +/- 1 . 4 , 7 . 9 +/- 1 . 4 , and 10 . 1 +/- 1 . 8 % in the first , second , and third G - Gap tertile , respectively ; P < 0 . 0001 ) and macroproteinuria ( HbA ( 1c ) 8 . 8 +/- 2 . 2 % if macroproteinuria , 8 . 3 +/- 2 . 0 % if none ; P < 0 . 05 ) , and because it could have been a confounder , we matched 54 patients with macroproteinuria and 200 patients without for HbA ( 1c ) .", "entity": [], "task": "NER"}
{"text": "Because macroproteinuria was associated with lower serum albumin and fructosamine levels , which might account for higher G - Gap , we calculated in this subpopulation albumin - indexed fructosamine and G - Gap ; macroproteinuria was independently associated with male gender ( odds ratio [ OR ] , 3 . 2 ; 95 % CI , 1 . 5 - 6 . 7 ; P < 0 . 01 ) , hypertension ( 2 . 9 ; [ 1 . 1 - 7 . 5 ] ; P < 0 . 05 ) , and the third tertile of albumin - indexed G - Gap ( 2 . 3 ; [ 1 . 1 - 4 . 4 ] ; P < 0 . 05 ) in multivariate analysis . CONCLUSIONIn type 2 diabetic patients , G - Gap was associated with macroproteinuria , independently of HbA ( 1c ) , albumin levels , and confounding factors , suggesting a specific role of intracellular glycation susceptibility on kidney glomerular changes .", "entity": [{"entity": "fructosamine", "entity_type": "Chemical", "pos": [69, 81]}, {"entity": "fructosamine", "entity_type": "Chemical", "pos": [186, 198]}], "task": "NER"}
{"text": "Activation of the anti - cancer agent upamostat by the mARC enzyme system .", "entity": [{"entity": "upamostat", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "Upamostat ( Mesupron (R) ) is a new small molecule serine protease inhibitor .", "entity": [{"entity": "Upamostat", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Mesupron", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "serine", "entity_type": "Chemical", "pos": [51, 57]}], "task": "NER"}
{"text": "The drug candidate was developed to inhibit the urokinase - type plasminogen activator ( uPA ) system , which plays a major role in tumor invasion and metastasis .", "entity": [], "task": "NER"}
{"text": "Upamostat is currently in clinical development as an anti - metastatic and non - cytotoxic agent against pancreatic and breast cancer .", "entity": [{"entity": "Upamostat", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Upamostat is the orally available amidoxime - ( i . e . hydroxyamidine - ) prodrug of the pharmacologically active form , WX - UK1 .", "entity": [{"entity": "Upamostat", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "amidoxime", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "hydroxyamidine", "entity_type": "Chemical", "pos": [56, 70]}, {"entity": "WX - UK1", "entity_type": "Chemical", "pos": [122, 130]}], "task": "NER"}
{"text": "In this study , the reductive enzymatic activation of upamostat to its corresponding amidine WX - UK1 was analyzed .", "entity": [{"entity": "upamostat", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "WX - UK1", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "The recently discovered molybdenum enzyme \" mitochondrial Amidoxime Reducing Component \" ( mARC ) catalyses together with its electron transport proteins cytochrome b ( 5 ) and NADH cytochrome b ( 5 ) reductase the reduction of N - hydroxylated prodrugs .", "entity": [{"entity": "molybdenum", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "Amidoxime", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [177, 181]}, {"entity": "N", "entity_type": "Chemical", "pos": [228, 229]}], "task": "NER"}
{"text": "In vitro biotransformation assays with porcine subcellular fractions and the reconstituted human enzymes demonstrate an mARC - dependent N - reduction of upamostat .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [137, 138]}, {"entity": "upamostat", "entity_type": "Chemical", "pos": [154, 163]}], "task": "NER"}
{"text": "Nuclease - resistant DNA via high - density packing in polymeric micellar nanoparticle coronas .", "entity": [], "task": "NER"}
{"text": "Herein , we describe a polymeric micellar nanoparticle capable of rendering nucleic acids resistant to nuclease digestion .", "entity": [], "task": "NER"}
{"text": "This approach relies on utilizing DNA as the polar headgroup of a DNA - polymer amphiphile in order to assemble well - defined , discrete nanoparticles .", "entity": [], "task": "NER"}
{"text": "Dense packing of DNA in the micelle corona allows for hybridization of complementary oligonucleotides while prohibiting enzymatic degradation .", "entity": [], "task": "NER"}
{"text": "We demonstrate the preparation , purification , and characterization of the nanoparticles , then describe their resistance to treatment with endo - and exonucleases including snake - venom phosphodiesterase ( SVP ) , a common , general DNA digestion enzyme .", "entity": [], "task": "NER"}
{"text": "Diversification in a biodiversity hot spot : landscape correlates of phylogeographic patterns in the African spotted reed frog .", "entity": [], "task": "NER"}
{"text": "The Eastern Afromontane Biodiversity Hotspot is known for microendemism and exceptional population genetic structure .", "entity": [], "task": "NER"}
{"text": "The region ' s landscape heterogeneity is thought to limit gene flow between fragmented populations and create opportunities for regional adaptation , but the processes involved are poorly understood .", "entity": [], "task": "NER"}
{"text": "Using a combination of phylogeographic analyses and circuit theory , I investigate how characteristics of landscape heterogeneity including regional distributions of slope , rivers and streams , habitat and hydrological basins ( drainages ) impact genetic distance among populations of the endemic spotted reed frog ( Hyperolius substriatus ) , identifying corridors of connectivity as well as barriers to dispersal .", "entity": [], "task": "NER"}
{"text": "Results show that genetic distance among populations is most strongly correlated to regional and local hydrologic structure and the distribution of suitable habitat corridors , not isolation by distance .", "entity": [], "task": "NER"}
{"text": "Contrary to expectations , phylogeographic structure is not coincident with the two montane systems , but instead corresponds to the split between the region ' s two major hydrological basins ( Zambezi and East Central Coastal ) .", "entity": [], "task": "NER"}
{"text": "This results in a paraphyletic relationship for the Malawian Highlands populations with respect to the Eastern Arc Mountains and implies that the northern Malawian Highlands are the diversity centre for H . substriatus .", "entity": [], "task": "NER"}
{"text": "Although the Malawian Highlands collectively hold the greatest genetic diversity , individual populations have lower diversity than their Eastern Arc counterparts , with an overall pattern of decreasing population diversity from north to south .", "entity": [], "task": "NER"}
{"text": "Through the study of intraspecific differentiation across a mosaic of ecosystem and geographic heterogeneity , we gain insight into the processes of diversification and a broader understanding of the role of landscape in evolution .", "entity": [], "task": "NER"}
{"text": "Multifunctional conducting fibres with electrically controlled release of ciprofloxacin .", "entity": [{"entity": "ciprofloxacin", "entity_type": "Chemical", "pos": [74, 87]}], "task": "NER"}
{"text": "We hereby present a new method of producing coaxial conducting polymer fibres loaded with an antibiotic drug that can then be subsequently released ( or sustained ) in response to electrical stimulation .", "entity": [], "task": "NER"}
{"text": "The method involves wet - spinning of poly ( 3 , 4 - ethylenedioxythiophene ) poly ( styrenesulfonate ) ( PEDOT : PSS ) fibre , which served as the inner core to the electropolymerised outer shell layer of polypyrrole ( Ppy ) .", "entity": [{"entity": "poly ( 3 , 4 - ethylenedioxythiophene )", "entity_type": "Chemical", "pos": [38, 77]}, {"entity": "poly ( styrenesulfonate )", "entity_type": "Chemical", "pos": [78, 103]}, {"entity": "PEDOT", "entity_type": "Chemical", "pos": [106, 111]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [114, 117]}, {"entity": "polypyrrole", "entity_type": "Chemical", "pos": [206, 217]}, {"entity": "Ppy", "entity_type": "Chemical", "pos": [220, 223]}], "task": "NER"}
{"text": "Ciprofloxacin hydrochloride ( Cipro ) was selected as the model drug and as the dopant in the Ppy synthesis .", "entity": [{"entity": "Ciprofloxacin", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "hydrochloride", "entity_type": "Chemical", "pos": [14, 27]}, {"entity": "Cipro", "entity_type": "Chemical", "pos": [30, 35]}, {"entity": "Ppy", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "The release of Cipro in phosphate buffered saline ( PBS ) from the fibres was controlled by switching the redox state of Ppy . Cipro layer .", "entity": [{"entity": "Cipro", "entity_type": "Chemical", "pos": [15, 20]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "Ppy", "entity_type": "Chemical", "pos": [121, 124]}, {"entity": "Cipro", "entity_type": "Chemical", "pos": [127, 132]}], "task": "NER"}
{"text": "Released Cipro under passive and stimulated conditions were tested against Gram positive ( Streptococcus pyogenes ) and Gram negative ( Escherichia coli ) bacteria .", "entity": [{"entity": "Cipro", "entity_type": "Chemical", "pos": [9, 14]}], "task": "NER"}
{"text": "Significant inhibition of bacterial growth was observed against both strains tested .", "entity": [], "task": "NER"}
{"text": "These results confirm that Cipro retains antibacterial properties during fibre fabrication and electrochemically controlled release .", "entity": [{"entity": "Cipro", "entity_type": "Chemical", "pos": [27, 32]}], "task": "NER"}
{"text": "In vitro cytotoxicity testing utilising the neural B35 cell line confirmed the cytocompatibility of the drug loaded conducting fibres .", "entity": [], "task": "NER"}
{"text": "Electrical conductivity , cytocompatibility and tuning release profile from this flexible fibre can lead to promising bionic applications such as neuroprosthetics and localised drug delivery .", "entity": [], "task": "NER"}
{"text": "DNA delivery with hyperbranched polylysine : A comparative study with linear and dendritic polylysine .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [32, 42]}, {"entity": "polylysine", "entity_type": "Chemical", "pos": [91, 101]}], "task": "NER"}
{"text": "PEI and polylysine are among the most investigated synthetic polymeric carriers for DNA delivery .", "entity": [{"entity": "PEI", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "polylysine", "entity_type": "Chemical", "pos": [8, 18]}], "task": "NER"}
{"text": "Apart from their practical use , these 2 classes of polymers are also of interest from a fundamental point of view as they both can be prepared in different architectures ( linear and branched / dendritic ) and in a wide range of molecular weights , which is attractive to establish basic structure - activity relationships .", "entity": [], "task": "NER"}
{"text": "This manuscript reports the results of an extensive study on the influence of molecular weight and architecture of a library of polylysine variants that includes linear , dendritic and hyperbranched polylysine .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [128, 138]}, {"entity": "polylysine", "entity_type": "Chemical", "pos": [199, 209]}], "task": "NER"}
{"text": "Hyperbranched polylysine is a new polylysine - based carrier that is structurally related to dendritic polylysine but possesses a randomly branched structure .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "polylysine", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "polylysine", "entity_type": "Chemical", "pos": [103, 113]}], "task": "NER"}
{"text": "Hyperbranched polylysine is attractive as it can be prepared in a one - step process on a large scale .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "The performance of these 3 classes of polylysine analogs was evaluated by assessing eGFP and IgG production in transient gene expression experiments with CHO DG44 cells , which revealed that protein production generally increased with increasing molecular weight and that at comparable molecular weight , the hyperbranched analogs were superior as compared to the dendritic and linear polylysines .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [38, 48]}, {"entity": "polylysines", "entity_type": "Chemical", "pos": [385, 396]}], "task": "NER"}
{"text": "To understand the differences between the gene delivery properties of the hyperbranched polylysine analogs on the one hand and the dendritic and linear polylysines on the other hand , the uptake and trafficking of the corresponding polyplexes were investigated .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [88, 98]}, {"entity": "polylysines", "entity_type": "Chemical", "pos": [152, 163]}], "task": "NER"}
{"text": "These experiments allowed us to identify ( i ) polyplex - external cell membrane binding , ( ii ) free , unbound polylysine coexisting with polyplexes as well as ( iii ) polymer buffer capacity as three possible factors that may contribute to the superior transfection properties of the hyperbranched polylysines as compared to their linear and dendritic analogs .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [113, 123]}, {"entity": "polylysines", "entity_type": "Chemical", "pos": [301, 312]}], "task": "NER"}
{"text": "Altogether , the results of this study indicate that hyperbranched polylysine is an interesting , alternative synthetic gene carrier .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Hyperbranched polylysine can be produced at low costs and in large quantities , is partially biodegradable , which may help to prevent cumulative cytotoxicity , and possesses transfection properties that can approach those of PEI .", "entity": [{"entity": "polylysine", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [226, 229]}], "task": "NER"}
{"text": "Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells .", "entity": [{"entity": "Titanium dioxide", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Atherosclerosis is a chronic inflammatory disease that remains the leading cause of death in the United States .", "entity": [], "task": "NER"}
{"text": "Numerous risk factors for endothelial cell inflammation and the development of atherosclerosis have been identified , including inhalation of ultrafine particles .", "entity": [], "task": "NER"}
{"text": "Recently , engineered nanoparticles ( NPs ) such as titanium ( TiO2 ) NPs have attracted much attention due to their wide range of applications .", "entity": [{"entity": "titanium", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [63, 67]}], "task": "NER"}
{"text": "However , there are also great concerns surrounding potential adverse health effects in vascular systems .", "entity": [], "task": "NER"}
{"text": "Although TiO2 NPs are known to induce oxidative stress and inflammation , the associated signaling pathways have not been well studied .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [9, 13]}], "task": "NER"}
{"text": "The focus of this work , therefore , deals with examination of the cellular signaling pathways responsible for TiO2 NP - induced endothelial oxidative stress and inflammation .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [111, 115]}], "task": "NER"}
{"text": "In this study , primary vascular endothelial cells were treated with TiO2 NPs for 2 - 16h at concentrations of 0 - 50 mu g / mL .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [69, 73]}], "task": "NER"}
{"text": "TiO2 NP exposure increased cellular oxidative stress and DNA binding of NF - kappa B .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Further , phosphorylation of Akt , ERK , JNK and p38 was increased in cells exposed to TiO2 NPs .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [87, 91]}], "task": "NER"}
{"text": "TiO2 NPs also significantly increased induction of mRNA and protein levels of vascular cell adhesion molecule - 1 ( VCAM - 1 ) and mRNA levels of monocyte chemoattractant protein - 1 ( MCP - 1 ) .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Pretreatment with inhibitors for NF - kappa B ( pyrrolidine dithiocarbamate ) , oxidative stress ( epigallocatechin gallate and apocynin ) , Akt ( LY294002 ) , ERK ( PD98059 ) , JNK ( SP600125 ) and p38 ( SB203580 ) significantly attenuated TiO2 NP - induced MCP - 1 and VCAM - 1 gene expression .", "entity": [{"entity": "pyrrolidine dithiocarbamate", "entity_type": "Chemical", "pos": [48, 75]}, {"entity": "epigallocatechin gallate", "entity_type": "Chemical", "pos": [99, 123]}, {"entity": "apocynin", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "LY294002", "entity_type": "Chemical", "pos": [147, 155]}, {"entity": "PD98059", "entity_type": "Chemical", "pos": [166, 173]}, {"entity": "SP600125", "entity_type": "Chemical", "pos": [184, 192]}, {"entity": "SB203580", "entity_type": "Chemical", "pos": [205, 213]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [241, 245]}], "task": "NER"}
{"text": "These data indicate that TiO2 NPs can induce endothelial inflammatory responses via redox - sensitive cellular signaling pathways .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [25, 29]}], "task": "NER"}
{"text": "Cinnamic acid derivatives as inhibitors for chorismatases and isochorismatases .", "entity": [{"entity": "Cinnamic acid", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Chorismatases and isochorismatases catalyse the hydrolysis of chorismate or isochorismate leading to unsaturated cyclohexenoic acid derivatives .", "entity": [{"entity": "chorismate", "entity_type": "Chemical", "pos": [62, 72]}, {"entity": "isochorismate", "entity_type": "Chemical", "pos": [76, 89]}, {"entity": "unsaturated cyclohexenoic acid", "entity_type": "Chemical", "pos": [101, 131]}], "task": "NER"}
{"text": "Based on simplification of the physiological substrates , two cinnamic acid - derived compounds , differing in the saturation of the side chain , were developed .", "entity": [{"entity": "cinnamic acid", "entity_type": "Chemical", "pos": [62, 75]}], "task": "NER"}
{"text": "In contrast to earlier inhibitor studies , the compounds described here do not have an ether bond and therefore can be synthesised very easily in one or two steps without the need for protective groups .", "entity": [], "task": "NER"}
{"text": "Both substances demonstrate inhibition of the isochorismatase EntB from Escherichia coli and the chorismatases FkbO and Hyg5 from Streptomyces .", "entity": [], "task": "NER"}
{"text": "For chorismatases , the unsaturated compound shows IC ( 50 ) values in the millimolar range , while the saturated compound is the better inhibitor with IC ( 50 ) values in the micromolar / low millimolar range ; for the isochorismatase tested both compounds inhibit in the micromolar range .", "entity": [], "task": "NER"}
{"text": "Further , an analysis of the apparent K ( m ) values for FkbO and EntB was performed , showing that both inhibitors act in a competitive manner .", "entity": [], "task": "NER"}
{"text": "Due to the ease of modifying these new inhibitors they are a suitable starting point for exploring further functionalised derivatives .", "entity": [], "task": "NER"}
{"text": "Carbon monoxide protects against ovariectomy - induced bone loss by inhibiting osteoclastogenesis .", "entity": [{"entity": "Carbon monoxide", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Carbon monoxide ( CO ) has been shown to have remarkable therapeutic value at low dosage by suppressing inflammation via inhibitory effects on macrophages , which are also precursors of osteoclasts ( OC ) .", "entity": [{"entity": "Carbon monoxide", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "CO", "entity_type": "Chemical", "pos": [18, 20]}], "task": "NER"}
{"text": "The objective of the present study was to determine whether CO limits bone loss through its effects on osteoclastogenesis .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [60, 62]}], "task": "NER"}
{"text": "Intraperitoneal injection of CO - releasing molecule 2 ( CORM2 ) into mice with reduced bone mass due to ovariectomy ( OVX ) resulted in significantly elevated bone mass .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [29, 31]}], "task": "NER"}
{"text": "Increased serum levels of collagen - type I fragments , tartrate - resistant acid phosphatase 5b , and reactive oxygen species ( ROS ) due to OVX were also decreased when treated with CORM2 .", "entity": [{"entity": "tartrate", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [112, 118]}], "task": "NER"}
{"text": "In vitro , CORM2 inhibited receptor activator of nuclear factor - kappa B ligand ( RANKL ) - induced OC formation without affecting bone resorption .", "entity": [], "task": "NER"}
{"text": "CORM2 reduced long - lasting ROS levels and nuclear factor - kappa B ( NF - kappa B ) activation in response to RANKL .", "entity": [], "task": "NER"}
{"text": "Inhibition of NADPH oxidase partially reduced the inhibitory effect of CO .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [14, 19]}, {"entity": "CO", "entity_type": "Chemical", "pos": [71, 73]}], "task": "NER"}
{"text": "CO induced increase of peroxiredoxin 1 ( PRX1 ) in BMM .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Down - regulation of PRX1 reduced the inhibitory effect of CO on OC formation and sustained the ROS levels induced by RANKL , suggesting that CO reduces generation of ROS and scavenges ROS to inhibit osteoclastogenesis .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [59, 61]}, {"entity": "CO", "entity_type": "Chemical", "pos": [142, 144]}], "task": "NER"}
{"text": "These data suggest that the inhibitory effect of CO on osteoclastogenesis is caused by impaired RANKL signaling through defective NF - kappa B activation and reduced levels of long - lasting ROS .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [49, 51]}], "task": "NER"}
{"text": "These changes result in decreased bone loss .", "entity": [], "task": "NER"}
{"text": "Our data highlight the potential utility of CO for ameliorating bone loss induced by loss of ovarian function .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [44, 46]}], "task": "NER"}
{"text": "Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness .", "entity": [], "task": "NER"}
{"text": "Hearing impairment is the most common sensory disorder , with congenital hearing impairment present in approximately 1 in 1 , 000 newborns .", "entity": [], "task": "NER"}
{"text": "Hereditary deafness is often mediated by the improper development or degeneration of cochlear hair cells .", "entity": [], "task": "NER"}
{"text": "Until now , it was not known whether such congenital failures could be mitigated by therapeutic intervention .", "entity": [], "task": "NER"}
{"text": "Here we show that hearing and vestibular function can be rescued in a mouse model of human hereditary deafness .", "entity": [], "task": "NER"}
{"text": "An antisense oligonucleotide ( ASO ) was used to correct defective pre - mRNA splicing of transcripts from the USH1C gene with the c . 216G > A mutation , which causes human Usher syndrome , the leading genetic cause of combined deafness and blindness .", "entity": [], "task": "NER"}
{"text": "Treatment of neonatal mice with a single systemic dose of ASO partially corrects Ush1c c . 216G > A splicing , increases protein expression , improves stereocilia organization in the cochlea , and rescues cochlear hair cells , vestibular function and low - frequency hearing in mice .", "entity": [], "task": "NER"}
{"text": "These effects were sustained for several months , providing evidence that congenital deafness can be effectively overcome by treatment early in development to correct gene expression and demonstrating the therapeutic potential of ASOs in the treatment of deafness .", "entity": [], "task": "NER"}
{"text": "Formation of polymersomes with double bilayers templated by quadruple emulsions .", "entity": [], "task": "NER"}
{"text": "Polymersomes , vesicles composed of bilayer membranes of amphiphilic block - copolymers , are promising delivery vehicles for long - term storage and controlled release of bioactives ; enhanced stability of the membrane makes polymersomes potentially useful in a wide range of biological delivery applications by comparison with liposomes .", "entity": [], "task": "NER"}
{"text": "However , unilamellar structure is intrinsically fragile when subjected to external stress .", "entity": [], "task": "NER"}
{"text": "Here , we report a microfluidic approach to produce polymersomes with double bilayers , providing higher stability and lower permeability than unilamellar polymersomes .", "entity": [], "task": "NER"}
{"text": "To achieve this , we developed a new design of a capillary microfluidic device to produce quadruple - emulsion drops which serve as a template for the polymersomes - in - polymersomes .", "entity": [], "task": "NER"}
{"text": "When two bilayers are attracted by depletion in polymersomes - in - polymersomes , the inner polymersomes protrude and bud , forming double bilayers .", "entity": [], "task": "NER"}
{"text": "We confirm these structures are indeed double bilayers using microaspiration and selective doping of the leaflets with nanoparticles .", "entity": [], "task": "NER"}
{"text": "The resultant polymersomes have great potential as highly stable and biocompatible microcarriers for robust encapsulation and storage of bioactives such as drugs , cosmetics and nutrients .", "entity": [], "task": "NER"}
{"text": "Kocurin , the true structure of PM181104 , an anti - methicillin - resistant Staphylococcus aureus ( MRSA ) thiazolyl peptide from the marine - derived bacterium Kocuria palustris .", "entity": [{"entity": "Kocurin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "PM181104", "entity_type": "Chemical", "pos": [32, 40]}, {"entity": "methicillin", "entity_type": "Chemical", "pos": [53, 64]}, {"entity": "thiazolyl", "entity_type": "Chemical", "pos": [108, 117]}], "task": "NER"}
{"text": "A new thiazolyl peptide , kocurin ( 1 ) , was isolated from culture broths of a marine - derived Kocuria palustris .", "entity": [{"entity": "thiazolyl", "entity_type": "Chemical", "pos": [6, 15]}, {"entity": "kocurin", "entity_type": "Chemical", "pos": [26, 33]}], "task": "NER"}
{"text": "Its structural elucidation was accomplished using a combination of spectroscopic and chemical methods , including HRMS , extensive 1D and 2D NMR analysis , MS / MS fragmentation , and chemical degradation and Marfey ' s analysis of the resulting amino acid residues .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [246, 256]}], "task": "NER"}
{"text": "The structure herein reported corrects that previously assigned to PM181104 ( 3 ) .", "entity": [{"entity": "PM181104", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "Kocurin displayed activity against methicillin - resistant Staphylococcus aureus ( MRSA ) , with MIC values in the submicromolar range .", "entity": [{"entity": "Kocurin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "methicillin", "entity_type": "Chemical", "pos": [35, 46]}], "task": "NER"}
{"text": "Anisole hydrolysis in high temperature water .", "entity": [{"entity": "Anisole", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "We investigated the hydrolysis of anisole to phenol in high - temperature water with and without water - tolerant Lewis acid catalysis .", "entity": [{"entity": "anisole", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [45, 51]}, {"entity": "Lewis acid", "entity_type": "Chemical", "pos": [114, 124]}], "task": "NER"}
{"text": "With no catalyst present , anisole hydrolyzes to phenol in 97 % yield after 24 hours at 365 degrees C , our experimentally determined optimal temperature and time .", "entity": [{"entity": "anisole", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [49, 55]}], "task": "NER"}
{"text": "Experiments with varied water density and analysis of comparable literature data suggest that anisole hydrolysis is almost third order in water , when the S ( N ) 2 mechanism dominates .", "entity": [{"entity": "anisole", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Of the water - tolerant Lewis acid catalysts studied , In ( OTf ) ( 3 ) offered the best phenol yield .", "entity": [{"entity": "Lewis acid", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "In ( OTf ) ( 3 )", "entity_type": "Chemical", "pos": [55, 71]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "Anisole hydrolysis was first order in catalyst and first order in substrate .", "entity": [{"entity": "Anisole", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Introducing In ( OTf ) ( 3 ) catalysis lowered the activation energy for anisole hydrolysis to 31 +/- 1 kcal mol ( - 1 ) .", "entity": [{"entity": "In ( OTf ) ( 3 )", "entity_type": "Chemical", "pos": [12, 28]}, {"entity": "anisole", "entity_type": "Chemical", "pos": [73, 80]}], "task": "NER"}
{"text": "Anisole hydrolysis in high - temperature water with In ( OTf ) ( 3 ) catalysis is competitive with other techniques in the literature based on rate and yield .", "entity": [{"entity": "Anisole", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "In ( OTf ) ( 3 )", "entity_type": "Chemical", "pos": [52, 68]}], "task": "NER"}
{"text": "In the presence of 5 mol % In ( OTf ) ( 3 ) catalyst , anisole hydrolyzes to phenol in 97 % yield after 90 minutes at 300 degrees C .", "entity": [{"entity": "In ( OTf ) ( 3 )", "entity_type": "Chemical", "pos": [27, 43]}, {"entity": "anisole", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "Application of MCD spectroscopy and TD - DFT to endohedral metallofullerenes for characterization of their electronic transitions .", "entity": [{"entity": "metallofullerenes", "entity_type": "Chemical", "pos": [59, 76]}], "task": "NER"}
{"text": "We describe , for the first time , the application of magnetic circular dichroism ( MCD ) spectroscopy and time - dependent density functional theory ( TD - DFT ) calculations using B3LYP and M06 - 2X functionals to characterize the electronic transitions of endohedral metallofullerenes ( EMFs ) .", "entity": [], "task": "NER"}
{"text": "Results revealed that the electronic transitions of La @ C ( 2v ) - C ( 82 ) , La ( 2 ) @ I ( h ) - C ( 80 ) , and Sc ( 3 ) N @ I ( h ) - C ( 80 ) can be assigned using these techniques .", "entity": [{"entity": "La", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "C ( 82 )", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "La ( 2 )", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "C ( 80 )", "entity_type": "Chemical", "pos": [100, 108]}, {"entity": "Sc ( 3 ) N", "entity_type": "Chemical", "pos": [115, 125]}, {"entity": "C ( 80 )", "entity_type": "Chemical", "pos": [138, 146]}], "task": "NER"}
{"text": "Particularly , a difference in the electronic transitions between La ( 2 ) @ I ( h ) - C ( 80 ) and Sc ( 3 ) N @ I ( h ) - C ( 80 ) , which is invisible in absorption spectra , was observed clearly in MCD spectra .", "entity": [{"entity": "La ( 2 )", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "C ( 80 )", "entity_type": "Chemical", "pos": [87, 95]}, {"entity": "Sc ( 3 ) N", "entity_type": "Chemical", "pos": [100, 110]}, {"entity": "C ( 80 )", "entity_type": "Chemical", "pos": [123, 131]}], "task": "NER"}
{"text": "The observed MCD bands agree well with the oscillator strengths calculated using the B3LYP functional .", "entity": [], "task": "NER"}
{"text": "In addition , the MCD bands of La ( 2 ) @ I ( h ) - C ( 80 ) were altered upon [ 5 , 6 ] - addition , demonstrating that the MCD spectroscopy is sensitive to chemical functionalization of EMFs , and that it is therefore powerful to distinguish [ 5 , 6 ] - adducts from pristine La ( 2 ) @ I ( h ) - C ( 80 ) , although no marked difference exists in their absorption spectra .", "entity": [{"entity": "La ( 2 )", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "C ( 80 )", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "La ( 2 )", "entity_type": "Chemical", "pos": [278, 286]}, {"entity": "C ( 80 )", "entity_type": "Chemical", "pos": [299, 307]}], "task": "NER"}
{"text": "Properties and mechanisms of action of naturally occurring antifungal peptides .", "entity": [], "task": "NER"}
{"text": "Antimicrobial peptides are a vital component of the innate immune system of all eukaryotic organisms and many of these peptides have potent antifungal activity .", "entity": [], "task": "NER"}
{"text": "They have potential application in the control of fungal pathogens that are a serious threat to both human health and food security .", "entity": [], "task": "NER"}
{"text": "Development of antifungal peptides as therapeutics requires an understanding of their mechanism of action on fungal cells .", "entity": [], "task": "NER"}
{"text": "To date , most research on antimicrobial peptides has focused on their activity against bacteria .", "entity": [], "task": "NER"}
{"text": "Several antimicrobial peptides specifically target fungal cells and are not active against bacteria .", "entity": [], "task": "NER"}
{"text": "Others with broader specificity often have different mechanisms of action against bacteria and fungi .", "entity": [], "task": "NER"}
{"text": "This review focuses on the mechanism of action of naturally occurring antifungal peptides from a diverse range of sources including plants , mammals , amphibians , insects , crabs , spiders , and fungi .", "entity": [], "task": "NER"}
{"text": "While antimicrobial peptides were originally proposed to act via membrane permeabilization , the mechanism of antifungal activity for these peptides is generally more complex and often involves entry of the peptide into the cell .", "entity": [], "task": "NER"}
{"text": "Bayesian methods for pharmacokinetic / pharmacodynamic modeling of pazopanib - induced increases in blood pressure and transaminases .", "entity": [{"entity": "pazopanib", "entity_type": "Chemical", "pos": [67, 76]}], "task": "NER"}
{"text": "Relationships between plasma pazopanib concentrations and the probability of elevations in blood pressure , a marker of vascular endothelial growth factor receptor inhibition , and alanine aminotransferase ( ALT ) were investigated with logistic regression models .", "entity": [{"entity": "pazopanib", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "Data from a Phase I dose - escalation study in cancer patients ( n = 57 ) were examined to determine the relationship between steady - state trough plasma pazopanib concentrations ( C tau ) and a clinically significant blood pressure increase , using a Bayesian logistic regression model .", "entity": [{"entity": "pazopanib", "entity_type": "Chemical", "pos": [155, 164]}], "task": "NER"}
{"text": "Data from 5 monotherapy studies in cancer patients ( n = 344 ) were pooled to investigate the relationship between C tau and maximum ALT >= 3 x the upper limit of normal ( ULN ) , using a Bayesian logistic regression model incorporating an asymptote .", "entity": [], "task": "NER"}
{"text": "Both models were fit using WinBUGS .", "entity": [], "task": "NER"}
{"text": "The median ( 95 % credible interval , CrI ) C tau at which the probability of a clinically significant increase in blood pressure was 50 % ( EC50 ) was 12 . 3 mu g / mL ( 6 . 12 , 18 . 4 ) .", "entity": [], "task": "NER"}
{"text": "The median ( 95 % CrI ) EC50 for the maximum probability of ALT >= 3 x ULN was 15 . 4 mu g / mL ( 3 . 8 , 41 . 2 ) and the median ( 95 % CrI ) maximum probability of ALT >= 3 x ULN was 21 % ( 14 . 5 , 43 . 1 ) .", "entity": [], "task": "NER"}
{"text": "Results suggest that dose adjustments could be useful in managing the potential for hepatotoxicity .", "entity": [], "task": "NER"}
{"text": "Clopidogrel , CYP2C19 , and a Black Box .", "entity": [{"entity": "Clopidogrel", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "It has been presumed that CYP2C19 has a major role in the metabolism of clopidogrel .", "entity": [{"entity": "clopidogrel", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "This presumption has been based on in vitro drug metabolism studies using microsomes from baculovirus infected insect cells ( BD - Supersomes (TM) ) .", "entity": [], "task": "NER"}
{"text": "If clopidogrel were primarily a CYP2C19 substrate , a drug / drug interaction with CYP2C19 inhibitors , such as proton pump inhibitors ( PPIs ) , for example , omeprazole and lansoprazole would be anticipated .", "entity": [{"entity": "clopidogrel", "entity_type": "Chemical", "pos": [3, 14]}, {"entity": "omeprazole", "entity_type": "Chemical", "pos": [160, 170]}, {"entity": "lansoprazole", "entity_type": "Chemical", "pos": [175, 187]}], "task": "NER"}
{"text": "Several ex vivo studies , using ADP stimulated platelet aggregation , suggested that there was such an interaction .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "The data from these studies served as a basis for FDA to provide a \" Black Box \" warning for the clopidogrel label in March of 2010 .", "entity": [{"entity": "clopidogrel", "entity_type": "Chemical", "pos": [97, 108]}], "task": "NER"}
{"text": "However , a prospective clinical study , COGENT , and several large meta - analyses have failed to demonstrate a negative effect on major adverse cardiovascular events ( MACE ) , with concomitant administration of clopidogrel and PPIs .", "entity": [{"entity": "clopidogrel", "entity_type": "Chemical", "pos": [214, 225]}], "task": "NER"}
{"text": "The in vitro work using \" Supersomes \" was revisited .", "entity": [], "task": "NER"}
{"text": "In vitro metabolism using hepatosomes , which resemble the native cytochrome P - 450 enzyme expression , has confirmed the earlier work that clopidogrel is primarily a CYP3A substrate .", "entity": [{"entity": "clopidogrel", "entity_type": "Chemical", "pos": [141, 152]}], "task": "NER"}
{"text": "This result correlates better with clinical findings .", "entity": [], "task": "NER"}
{"text": "The absence of an increase in MACE by concomitant administration of PPIs , which are CYP2C19 inhibitors , to a regimen including clopidogrel , is therefore not surprising .", "entity": [{"entity": "clopidogrel", "entity_type": "Chemical", "pos": [129, 140]}], "task": "NER"}
{"text": "A hypothesis is offered to explain why subjects , who carry two reduced function alleles of CYP2C19 , may have more reactive platelets .", "entity": [], "task": "NER"}
{"text": "A decision - analysis tool for benefit - risk assessment of nonprescription drugs .", "entity": [], "task": "NER"}
{"text": "A decision analysis tool is proposed for regulatory assessment of nonprescription drugs .", "entity": [], "task": "NER"}
{"text": "The tool is based on evaluation of each of the drug ' s potential benefit and risk attributes identified using a value - tree framework .", "entity": [], "task": "NER"}
{"text": "The decision tool is designed as two - factor , two - stage instrument .", "entity": [], "task": "NER"}
{"text": "Each attribute is independently assessed based on both the frequency of occurrence and clinical impact of the attribute .", "entity": [], "task": "NER"}
{"text": "Frequency and clinical impact are scored on a 0 - 3 scale where a 0 score means no occurrence or no clinical impact , and a 3 means high frequency of occurrence or high clinical impact .", "entity": [], "task": "NER"}
{"text": "The tool is initially used early in drug development to facilitate communication amongst stakeholders and to identify important data gaps .", "entity": [], "task": "NER"}
{"text": "After new data are generated during the development program the tool is used again across the same attributes to yield a final benefit - risk assessment .", "entity": [], "task": "NER"}
{"text": "In both the early assessment and subsequent evaluation use of the Group - Delphi technique and a benefit - risk trade - off heuristic may yield more consistent and coherent outputs .", "entity": [], "task": "NER"}
{"text": "The tool allows regulators to maintain flexibility with respect to how final decisions are made , yet allows specificity and transparency during the evaluation .", "entity": [], "task": "NER"}
{"text": "Further modifications can be incorporated to address drug - specific requirements or regulatory preferences .", "entity": [], "task": "NER"}
{"text": "Ultralow reflection from a - Si nanograss / Si nanofrustum double layers .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "Si", "entity_type": "Chemical", "pos": [44, 46]}], "task": "NER"}
{"text": "A double - layer nanostructure comprising amorphous Si nanograss on top of Si nanofrustums ( NFs ) with a total height of 680 nm exhibits ultralow reflection .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "Si", "entity_type": "Chemical", "pos": [75, 77]}], "task": "NER"}
{"text": "Almost near - unity absorption and near - zero reflectance result in this layered nanostructure , over a broad range of wavelengths and a wide range of angles of incidence , due to the low packing density of a - Si and the smooth transition of the refractive index from the air to the Si substrate across both the nanograss and NF layers .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [212, 214]}, {"entity": "Si", "entity_type": "Chemical", "pos": [285, 287]}], "task": "NER"}
{"text": "A high - confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex .", "entity": [], "task": "NER"}
{"text": "Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1 , a comprehensive analysis of SIRT1 binding proteins yielding a high - confidence interaction map has not been established .", "entity": [], "task": "NER"}
{"text": "Using a comparative statistical analysis of binding partners , we have assembled a high - confidence SIRT1 interactome .", "entity": [], "task": "NER"}
{"text": "Employing this method , we identified the deubiquitinating enzyme ubiquitin - specific protease 22 ( USP22 ) , a component of the deubiquitinating module ( DUBm ) of the SAGA transcriptional coactivating complex , as a SIRT1 - interacting partner .", "entity": [], "task": "NER"}
{"text": "We found that this interaction is highly specific , requires the ZnF - UBP domain of USP22 , and is disrupted by the inactivating H363Y mutation within SIRT1 .", "entity": [{"entity": "ZnF", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "Moreover , we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine ( K129 ) within the ZnF - UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [56, 62]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [104, 110]}, {"entity": "ZnF", "entity_type": "Chemical", "pos": [131, 134]}], "task": "NER"}
{"text": "Furthermore , USP22 - mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components .", "entity": [], "task": "NER"}
{"text": "Our results indicate an important role of SIRT1 - mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex .", "entity": [], "task": "NER"}
{"text": "Mammalian myosin - 18A , a highly divergent myosin .", "entity": [], "task": "NER"}
{"text": "The Mus musculus myosin - 18A gene is expressed as two alternatively spliced isoforms , alpha and beta , with reported roles in Golgi localization , in maintenance of cytoskeleton , and as receptors for immunological surfactant proteins .", "entity": [], "task": "NER"}
{"text": "Both myosin - 18A isoforms feature a myosin motor domain , a single predicted IQ motif , and a long coiled - coil reminiscent of myosin - 2 .", "entity": [], "task": "NER"}
{"text": "The myosin - 18A alpha isoform , additionally , has an N - terminal PDZ domain .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [55, 56]}], "task": "NER"}
{"text": "Recombinant heavy meromyosin - and subfragment - 1 ( S1 ) - like constructs for both myosin - 18A alpha and - 18 beta species were purified from the baculovirus / Sf9 cell expression system .", "entity": [], "task": "NER"}
{"text": "These constructs bound both essential and regulatory light chains , indicating an additional noncanonical light chain binding site in the neck .", "entity": [], "task": "NER"}
{"text": "Myosin - 18A alpha - S1 and - 18A beta - S1 molecules bound actin weakly with Kd values of 4 . 9 and 54 mu m , respectively .", "entity": [], "task": "NER"}
{"text": "The actin binding data could be modeled by assuming an equilibrium between two myosin conformations , a competent and an incompetent form to bind actin .", "entity": [], "task": "NER"}
{"text": "Actin binding was unchanged by presence of nucleotide .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "Both myosin - 18A isoforms bound N - methylanthraniloyl - nucleotides , but the rate of ATP hydrolysis was very slow ( < 0 . 002 s ( - 1 ) ) and not significantly enhanced by actin .", "entity": [{"entity": "N - methylanthraniloyl - nucleotides", "entity_type": "Chemical", "pos": [33, 69]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "Phosphorylation of the regulatory light chain had no effect on ATP hydrolysis , and neither did the addition of tropomyosin or of GOLPH3 , a myosin - 18A binding partner .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "Electron microscopy of myosin - 18A - S1 showed that the lever is strongly angled with respect to the long axis of the motor domain , suggesting a pre - power stroke conformation regardless of the presence of ATP .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [209, 212]}], "task": "NER"}
{"text": "These data lead us to conclude that myosin - 18A does not operate as a traditional molecular motor in cells .", "entity": [], "task": "NER"}
{"text": "Supervillin - mediated suppression of p53 protein enhances cell survival .", "entity": [], "task": "NER"}
{"text": "Integrin - based adhesions promote cell survival as well as cell motility and invasion .", "entity": [], "task": "NER"}
{"text": "We show here that the adhesion regulatory protein supervillin increases cell survival by decreasing levels of the tumor suppressor protein p53 and downstream target genes .", "entity": [], "task": "NER"}
{"text": "RNAi - mediated knockdown of a new splice form of supervillin ( isoform 4 ) or both isoforms 1 and 4 increases the amount of p53 and cell death , whereas p53 levels decrease after overexpression of either supervillin isoform .", "entity": [], "task": "NER"}
{"text": "Cellular responses to DNA damage induced by etoposide or doxorubicin include down - regulation of endogenous supervillin coincident with increases in p53 .", "entity": [{"entity": "etoposide", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [57, 68]}], "task": "NER"}
{"text": "In DNA - damaged supervillin knockdown cells , p53 knockdown or inhibition partially rescues the loss of cell metabolic activity , a measure of cell proliferation .", "entity": [], "task": "NER"}
{"text": "Knockdown of the p53 deubiquitinating enzyme USP7 / HAUSP also reverses the supervillin phenotype , blocking the increase in p53 levels seen after supervillin knockdown and accentuating the decrease in p53 levels triggered by supervillin overexpression .", "entity": [], "task": "NER"}
{"text": "Conversely , supervillin overexpression decreases the association of USP7 and p53 and attenuates USP7 - mediated p53 deubiquitination .", "entity": [], "task": "NER"}
{"text": "USP7 binds directly to the supervillin N terminus and can deubiquitinate and stabilize supervillin .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [39, 40]}], "task": "NER"}
{"text": "Supervillin also is stabilized by derivatization with the ubiquitin - like protein SUMO1 .", "entity": [], "task": "NER"}
{"text": "These results show that supervillin regulates cell survival through control of p53 levels and suggest that supervillin and its interaction partners at sites of cell - substrate adhesion constitute a locus for cross - talk between survival signaling and cell motility pathways .", "entity": [], "task": "NER"}
{"text": "Menopause , estrogens and frailty .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [12, 21]}], "task": "NER"}
{"text": "Abstract The controversy surrounding the results from the Women ' s Health Initiative ( WHI ) trials published a decade ago caused a significant decline in the use of menopausal hormone replacement therapy .", "entity": [], "task": "NER"}
{"text": "However , these results have been vehemently contested and several lines of evidence suggest that in perimenopausal and non - obese women , estrogen therapy may indeed be of benefit .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [140, 148]}], "task": "NER"}
{"text": "There is ample proof that menopause causes a loss of musculoskeletal tissue mass and quality , thereby causing a loss of health and quality of life .", "entity": [], "task": "NER"}
{"text": "There is also solid evidence that hormone replacement therapy in itself prevents most of these effects in connective tissue in it self .", "entity": [], "task": "NER"}
{"text": "Besides the independent , direct effects on the musculoskeletal tissues , estrogen deficiency also reduces the ability to adequately respond and adapt to external mechanical and metabolic stressors , e . g . exercise , which are otherwise the main stimuli that should maintain musculoskeletal integrity and metabolic function .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "Thus , normophysiological estrogen levels appear to exert a permissive effect on musculoskeletal adaptations to loading , thereby likely improving the outcome of rehabilitation following critical illness , musculoskeletal trauma or orthopedic surgical therapy .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "These effects add to the evidence supporting the use of estrogen therapy , particularly accelerated gain of functional capacity and independence following musculoskeletal disuse .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [56, 64]}], "task": "NER"}
{"text": "Isolation of a mixed valence diiron hydride : evidence for a spectator hydride in hydrogen evolution catalysis .", "entity": [{"entity": "diiron hydride", "entity_type": "Chemical", "pos": [29, 43]}, {"entity": "hydride", "entity_type": "Chemical", "pos": [71, 78]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "The mixed - valence diiron hydrido complex ( mu - H ) Fe2 ( pdt ) ( CO ) 2 ( dppv ) 2 ( [ H1 ] ( 0 ) , where pdt = 1 , 3 - propanedithiolate and dppv = cis - 1 , 2 - C2H2 ( PPh2 ) 2 ) , was generated by reduction of the differous hydride [ H1 ] ( + ) using decamethylcobaltocene .", "entity": [{"entity": "diiron", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "hydrido", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "( mu - H ) Fe2 ( pdt ) ( CO ) 2 ( dppv ) 2", "entity_type": "Chemical", "pos": [43, 85]}, {"entity": "H1", "entity_type": "Chemical", "pos": [90, 92]}, {"entity": "pdt", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "1 , 3 - propanedithiolate", "entity_type": "Chemical", "pos": [115, 140]}, {"entity": "dppv", "entity_type": "Chemical", "pos": [145, 149]}, {"entity": "cis - 1 , 2 - C2H2 ( PPh2 ) 2", "entity_type": "Chemical", "pos": [152, 181]}, {"entity": "hydride", "entity_type": "Chemical", "pos": [230, 237]}, {"entity": "[ H1 ] ( + )", "entity_type": "Chemical", "pos": [238, 250]}, {"entity": "decamethylcobaltocene", "entity_type": "Chemical", "pos": [257, 278]}], "task": "NER"}
{"text": "Crystallographic analysis shows that [ H1 ] ( 0 ) retains the stereochemistry of its precursor , where one dppv ligand spans two basal sites and the other spans apical and basal positions .", "entity": [{"entity": "H1", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "dppv", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "The Fe - - - Fe bond elongates to 2 . 80 from 2 . 66 A , but the Fe - P bonds only change subtly .", "entity": [{"entity": "Fe - - - Fe", "entity_type": "Chemical", "pos": [4, 15]}, {"entity": "Fe - P", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "Although the Fe - H distances are indistinguishable in the precursor , they differ by 0 . 2 A in [ H1 ] ( 0 ) .", "entity": [{"entity": "Fe - H", "entity_type": "Chemical", "pos": [13, 19]}, {"entity": "H1", "entity_type": "Chemical", "pos": [99, 101]}], "task": "NER"}
{"text": "The X - band electron paramagnetic resonance ( EPR ) spectrum reveals the presence of two stereoisomers , the one characterized crystallographically and a contribution of about 10 % from a second symmetrical ( sym ) isomer wherein both dppv ligands occupy apical - basal sites .", "entity": [{"entity": "dppv", "entity_type": "Chemical", "pos": [236, 240]}], "task": "NER"}
{"text": "The unsymmetrical ( unsym ) arrangement of the dppv ligands is reflected in the values of A ( ( 31 ) P ) , which range from 31 MHz for the basal phosphines to 284 MHz for the apical phosphine .", "entity": [{"entity": "dppv", "entity_type": "Chemical", "pos": [47, 51]}, {"entity": "( 31 ) P", "entity_type": "Chemical", "pos": [94, 102]}, {"entity": "phosphines", "entity_type": "Chemical", "pos": [145, 155]}, {"entity": "phosphine", "entity_type": "Chemical", "pos": [182, 191]}], "task": "NER"}
{"text": "Density functional theory calculations were employed to rationalize the electronic structure of [ H1 ] ( 0 ) and to facilitate spectral simulation and assignment of EPR parameters including ( 1 ) H and ( 31 ) P hyperfine couplings .", "entity": [{"entity": "H1", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [190, 197]}, {"entity": "( 31 ) P", "entity_type": "Chemical", "pos": [202, 210]}], "task": "NER"}
{"text": "The EPR spectra of [ H1 ] ( 0 ) and [ D1 ] ( 0 ) demonstrate that the singly occupied molecular orbital is primarily localized on the Fe center with the longer bond to H , that is , Fe ( II ) - H . . . Fe ( I ) .", "entity": [{"entity": "H1", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [134, 136]}, {"entity": "H", "entity_type": "Chemical", "pos": [168, 169]}, {"entity": "Fe ( II ) - H", "entity_type": "Chemical", "pos": [182, 195]}, {"entity": "Fe ( I )", "entity_type": "Chemical", "pos": [202, 210]}], "task": "NER"}
{"text": "The coupling to the hydride is A ( ( 1 ) H ) = 55 and 74 MHz for unsym - amd sym - [ H1 ] ( 0 ) , respectively .", "entity": [{"entity": "hydride", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "H1", "entity_type": "Chemical", "pos": [85, 87]}], "task": "NER"}
{"text": "Treatment of [ H1 ] ( 0 ) with H ( + ) gives 0 . 5 equiv of H2 and [ H1 ] ( + ) .", "entity": [{"entity": "H1", "entity_type": "Chemical", "pos": [15, 17]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "H2", "entity_type": "Chemical", "pos": [60, 62]}, {"entity": "[ H1 ] ( + )", "entity_type": "Chemical", "pos": [67, 79]}], "task": "NER"}
{"text": "Reduction of D ( + ) affords D2 , leaving the hydride ligand intact .", "entity": [{"entity": "D ( + )", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "D2", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "hydride", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "These experiments demonstrate that the bridging hydride ligand in this complex is a spectator in the hydrogen evolution reaction .", "entity": [{"entity": "hydride", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "Femtosecond Dynamics of Excitons and Hole - Polarons in Composite P3HT / PCBM Nanoparticles .", "entity": [{"entity": "P3HT", "entity_type": "Chemical", "pos": [66, 70]}, {"entity": "PCBM", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "The dynamics of charge separation in aqueous suspensions of regioregular P3HT nanoparticles containing PCBM were investigated for the first time using femtosecond transient absorption spectroscopy .", "entity": [{"entity": "P3HT", "entity_type": "Chemical", "pos": [73, 77]}, {"entity": "PCBM", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "This investigation is supported by the recently reported use of regioregular P3HT / PCBM nanoparticles as charge trapping and storage devices .", "entity": [{"entity": "P3HT", "entity_type": "Chemical", "pos": [77, 81]}, {"entity": "PCBM", "entity_type": "Chemical", "pos": [84, 88]}], "task": "NER"}
{"text": "In this study , the presence of excited - state and charge - separated species , including singlet excitons , polymer polarons and free charges , generated in rr - P3HT / PCBM nanoparticles was identified through visible pump and visible / near - infrared probe femtosecond transient absorption spectroscopy at a range of electron acceptor concentrations .", "entity": [{"entity": "P3HT", "entity_type": "Chemical", "pos": [164, 168]}, {"entity": "PCBM", "entity_type": "Chemical", "pos": [171, 175]}], "task": "NER"}
{"text": "The decrease of the singlet exciton lifetime by charge transfer to PCBM is well described by a one - dimensional diffusion model with a P3HT domain size of approximately 5 nm for 5 - 50 wt % PCBM .", "entity": [{"entity": "PCBM", "entity_type": "Chemical", "pos": [67, 71]}, {"entity": "P3HT", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "PCBM", "entity_type": "Chemical", "pos": [191, 195]}], "task": "NER"}
{"text": "This model also indicates that bimolecular recombination is the dominant charge recombination mechanism at 20 wt % PCBM and above .", "entity": [{"entity": "PCBM", "entity_type": "Chemical", "pos": [115, 119]}], "task": "NER"}
{"text": "Surface behavior of malonic acid adsorption at the air / water interface .", "entity": [{"entity": "malonic acid", "entity_type": "Chemical", "pos": [20, 32]}], "task": "NER"}
{"text": "The presence of organic materials adsorbed to the surfaces of aerosol particles has been demonstrated to be a determining factor in relevant atmospheric processes .", "entity": [], "task": "NER"}
{"text": "Malonic acid is a small , water - soluble organic acid that is common in aerosols and is surface - active .", "entity": [{"entity": "Malonic acid", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "A comprehensive investigation of the adsorption of malonic acid to the air / water interface was accomplished using vibrational sum frequency spectroscopy ( VSFS ) and surface tension measurements as functions of concentration and pH .", "entity": [{"entity": "malonic acid", "entity_type": "Chemical", "pos": [51, 63]}], "task": "NER"}
{"text": "Malonic acid was found to be weakly solvated at the air / water interface , and its orientation as a function of concentration was explored through different VSFS polarization schemes .", "entity": [{"entity": "Malonic acid", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "pH - dependent experiments revealed that the surface - active species is the fully protonated species .", "entity": [], "task": "NER"}
{"text": "Computational analyses were used to obtain depth - specific geometries of malonic acid at the air / water interface that confirm and enrich the experimental results .", "entity": [{"entity": "malonic acid", "entity_type": "Chemical", "pos": [74, 86]}], "task": "NER"}
{"text": "Development of quantitative structure - metabolism ( QSMR ) relationships for substituted anilines based on computational chemistry .", "entity": [{"entity": "anilines", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "A novel stepwise classification approach for predicting the metabolic fate of substituted anilines , based on calculated physicochemical parameters of the parent anilines , was developed .", "entity": [{"entity": "anilines", "entity_type": "Chemical", "pos": [90, 98]}, {"entity": "anilines", "entity_type": "Chemical", "pos": [162, 170]}], "task": "NER"}
{"text": "Based on multivariate pattern recognition methods ( PLS - DA or soft independent modelling of class analogy [ SIMCA ] ) , these models allowed prediction of N - acetylation and subsequent N - oxanilic acid formation .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [157, 158]}, {"entity": "N - oxanilic acid", "entity_type": "Chemical", "pos": [188, 205]}], "task": "NER"}
{"text": "These classification methods provided an improved classification success when compared with existing quantitative structure - metabolism relationship models for substituted anilines .", "entity": [{"entity": "anilines", "entity_type": "Chemical", "pos": [173, 181]}], "task": "NER"}
{"text": "Modelling the physicochemical properties of the N - acetylated compounds was considered as an addition to the stepwise model .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [48, 49]}], "task": "NER"}
{"text": "Inclusion of parameters describing the N - acetyl moiety had little effect on the predictive ability of a stepwise parent to N - acetyl to N - oxanilic acid PLS - DA model , and had a negative impact on that of SIMCA models .", "entity": [{"entity": "N - acetyl", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "N - acetyl", "entity_type": "Chemical", "pos": [125, 135]}, {"entity": "N - oxanilic acid", "entity_type": "Chemical", "pos": [139, 156]}], "task": "NER"}
{"text": "This was attributed to the relatively small contribution to the total parameter variance caused by differences arising as a result of N - acetylation compared to the contribution made by the substituent effects .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [134, 135]}], "task": "NER"}
{"text": "Calculation of physicochemical properties incorporating the effect of solvation using ab initio methods improved the classification model in terms of both the visual separation in multivariate projections and prediction accuracy .", "entity": [], "task": "NER"}
{"text": "Frequency - multiplication high - output triboelectric nanogenerator for sustainably powering biomedical microsystems .", "entity": [], "task": "NER"}
{"text": "An attractive method to response the current energy crisis and produce sustainable nonpolluting power source is harvesting energy from our living environment .", "entity": [], "task": "NER"}
{"text": "However , the energy in our living environment always exists in low - frequency form , which is very difficult to be utilized directly .", "entity": [], "task": "NER"}
{"text": "Here , we demonstrated a novel sandwich - shape triboelectric nanogenerator to convert low - frequency mechanical energy to electric energy with double frequency .", "entity": [], "task": "NER"}
{"text": "An aluminum film was placed between two polydimethylsiloxane ( PDMS ) membranes to realize frequency multiplication by twice contact electrifications within one cycle of external force .", "entity": [{"entity": "aluminum", "entity_type": "Chemical", "pos": [3, 11]}, {"entity": "polydimethylsiloxane", "entity_type": "Chemical", "pos": [40, 60]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [63, 67]}], "task": "NER"}
{"text": "The working mechanism was studied by finite element simulation .", "entity": [], "task": "NER"}
{"text": "Additionally , the well - designed micro / nano dual - scale structures ( i . e . , pyramids and V - shape grooves ) fabricated atop PDMS surface was employed to enhance the device performance .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "The output peak voltage , current density , and energy volume density achieved 465 V , 13 . 4 mu A / cm ( 2 ) , and 53 . 4 mW / cm ( 3 ) , respectively .", "entity": [], "task": "NER"}
{"text": "This novel nanogenerator was systematically investigated and also demonstrated as a reliable power source , which can be directly used to not only lighten five commercial light - emitting diodes ( LEDs ) but also drive an implantable 3 - D microelectrode array for neural prosthesis without any energy storage unit or rectification circuit .", "entity": [], "task": "NER"}
{"text": "This is the first demonstration of the nanogenerator for directly driving biomedical microsystems , which extends the application fields of the nanogenerator and drives it closer to practical applications .", "entity": [], "task": "NER"}
{"text": "The salicylate 1 , 2 - dioxygenase as a model for a conventional gentisate 1 , 2 - dioxygenase : crystal structures of the G106A mutant and its adducts with gentisate and salicylate .", "entity": [{"entity": "salicylate", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "gentisate", "entity_type": "Chemical", "pos": [65, 74]}, {"entity": "gentisate", "entity_type": "Chemical", "pos": [157, 166]}, {"entity": "salicylate", "entity_type": "Chemical", "pos": [171, 181]}], "task": "NER"}
{"text": "The salicylate 1 , 2 - dioxygenase ( SDO ) from the bacterium Pseudaminobacter salicylatoxidans BN12 is a versatile gentisate 1 , 2 - dioxygenase ( GDO ) that converts both gentisate ( 2 , 5 - dihydroxybenzoate ) and various monohydroxylated substrates .", "entity": [{"entity": "salicylate", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "gentisate", "entity_type": "Chemical", "pos": [116, 125]}, {"entity": "gentisate", "entity_type": "Chemical", "pos": [173, 182]}, {"entity": "2 , 5 - dihydroxybenzoate", "entity_type": "Chemical", "pos": [185, 210]}], "task": "NER"}
{"text": "Several variants of this enzyme were rationally designed based on the previously determined enzyme structure and sequence differences between the SDO and the ' conventional ' GDO from Corynebacterium glutamicum .", "entity": [], "task": "NER"}
{"text": "This was undertaken in order to define the structural elements that give the SDO its unique ability to dioxygenolytically cleave ( substituted ) salicylates .", "entity": [{"entity": "salicylates", "entity_type": "Chemical", "pos": [145, 156]}], "task": "NER"}
{"text": "SDO variants M103L , G106A , G111A , R113G , S147R and F159Y were constructed and it was found that G106A oxidized only gentisate ; 1 - hydroxy - 2 - naphthoate and salicylate were not converted .", "entity": [{"entity": "gentisate", "entity_type": "Chemical", "pos": [120, 129]}, {"entity": "1 - hydroxy - 2 - naphthoate", "entity_type": "Chemical", "pos": [132, 160]}, {"entity": "salicylate", "entity_type": "Chemical", "pos": [165, 175]}], "task": "NER"}
{"text": "This indicated that this enzyme variant behaves like previously known ' conventional ' GDOs .", "entity": [], "task": "NER"}
{"text": "Crystals of the G106A SDO variant and its complexes with salicylate and gentisate were obtained under anaerobic conditions , and the structures were solved and analyzed .", "entity": [{"entity": "salicylate", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "gentisate", "entity_type": "Chemical", "pos": [72, 81]}], "task": "NER"}
{"text": "The amino acid residue Gly106 is located inside the SDO active site cavity but does not directly interact with the substrates .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "Gly106", "entity_type": "Chemical", "pos": [23, 29]}], "task": "NER"}
{"text": "Crystal structures of G106A SDO complexes with gentisate and salicylate showed a different binding mode for salicylate when compared with the wild - type enzyme .", "entity": [{"entity": "gentisate", "entity_type": "Chemical", "pos": [47, 56]}, {"entity": "salicylate", "entity_type": "Chemical", "pos": [61, 71]}, {"entity": "salicylate", "entity_type": "Chemical", "pos": [108, 118]}], "task": "NER"}
{"text": "Thus , salicylate coordinated in the G106A variant with the catalytically active Fe ( II ) ion in an unusual and unproductive manner because of the inability of salicylate to displace a hydrogen bond that was formed between Trp104 and Asp174 in the G106A variant .", "entity": [{"entity": "salicylate", "entity_type": "Chemical", "pos": [7, 17]}, {"entity": "Fe ( II )", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "salicylate", "entity_type": "Chemical", "pos": [161, 171]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [186, 194]}, {"entity": "Trp104", "entity_type": "Chemical", "pos": [224, 230]}, {"entity": "Asp174", "entity_type": "Chemical", "pos": [235, 241]}], "task": "NER"}
{"text": "It is proposed that this type of unproductive substrate binding might generally limit the substrate spectrum of ' conventional ' GDOs .", "entity": [], "task": "NER"}
{"text": "DATABASE : Structural data are available in the Protein Data Bank databases under the accession numbers 3NST , 3NWA , 3NVC .", "entity": [], "task": "NER"}
{"text": "Three - dimensional high - resolution rotational tracking with superlocalization reveals conformations of surface - bound anisotropic nanoparticles .", "entity": [], "task": "NER"}
{"text": "The ability to directly follow three - dimensional rotational movement of anisotropic nanoparticles will greatly enhance our understanding of the way nanoparticles interact with surfaces .", "entity": [], "task": "NER"}
{"text": "Herein , we demonstrate dual - color total internal reflection scattering microscopy as a tool to probe the interactions of plasmonic gold nanorods with functional surfaces .", "entity": [], "task": "NER"}
{"text": "By taking advantage of both the short and long axis surface plasmon resonance scattering enhancement , we are able to decipher both in - plane and out - of - plane gold nanorod motion relative to the sample surface with equally high resolution .", "entity": [], "task": "NER"}
{"text": "In combination with superlocalization through point spread function fitting , we overcome the four - quadrant angular degeneracy of gold nanorods in the focal plane of the objective and resolve conformations of surface - bound anisotropic nanoparticles in unprecedented detail .", "entity": [], "task": "NER"}
{"text": "The transferrin receptor - 1 membrane stub undergoes intramembrane proteolysis by signal peptide peptidase - like 2b .", "entity": [], "task": "NER"}
{"text": "The successive events of shedding and regulated intramembrane proteolysis are known to comprise a fundamental biological process of type I and II membrane proteins ( e . g . amyloid precursor protein , Notch receptor and pro - tumor necrosis factor - alpha ) .", "entity": [], "task": "NER"}
{"text": "Some of the resulting fragments were shown to be involved in important intra - and extracellular signalling events .", "entity": [], "task": "NER"}
{"text": "Although shedding of the human transferrin receptor - 1 ( TfR1 ) has been known for > 30 years and soluble TfR1 is an accepted diagnostic marker , the fate of the remaining N - terminal fragment ( NTF ) remains unknown .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [173, 174]}], "task": "NER"}
{"text": "In the present study , we demonstrate for the first time that TfR1 - NTF is subject to regulated intramembrane proteolysis and , using MALDI - TOF - TOF - MS , we have identified the cleavage site as being located C - terminal from Gly - 84 .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [214, 215]}, {"entity": "Gly", "entity_type": "Chemical", "pos": [232, 235]}], "task": "NER"}
{"text": "We showed that the resulting C - terminal peptide is extracellularly released after regulated intramembrane proteolysis and it was detected as a monomer with an internal disulfide bridge .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [29, 30]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [170, 179]}], "task": "NER"}
{"text": "We further identified signal peptide peptidase - like 2a and mainly signal peptide peptidase - like 2b as being responsible for the intramembrane proteolysis of TfR1 - NTF .", "entity": [], "task": "NER"}
{"text": "Northern contaminant mixtures induced morphological and functional changes in human coronary artery endothelial cells under culture conditions typifying high fat / sugar diet and ethanol exposure .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [164, 169]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "It has been reported that Northern populations are exposed to mixtures of various environmental contaminants unique to the Arctic ( Northern contaminant mixtures - NCM ) at a large range of concentrations , depending on their geological location , age , lifestyle and dietary habits .", "entity": [], "task": "NER"}
{"text": "To determine if these contaminants may contribute to a cardiovascular health risk , especially when combined with a high fat and sugar diet and ethanol exposure , we treated human coronary artery endothelial cells ( HCAEC ) with two mixtures of 4 organic ( NCM1 ) or 22 organic and inorganic ( NCM2 ) chemicals detected in Northerners ' blood during 2004 - 2005 in the presence or absence of low - density lipoprotein ( 1 . 5mg / ml ) , very - low - density lipoprotein ( 1 . 0mg / ml ) and glucose ( 10mmol / L ) ( LVG ) , and in the absence or presence of 0 . 1 % ethanol .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [129, 134]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [144, 151]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [491, 498]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [566, 573]}], "task": "NER"}
{"text": "After 24h of exposure , cell morphology and markers of cytotoxicity and endothelial function were examined .", "entity": [], "task": "NER"}
{"text": "NCM1 treatment did not affect cell viability , but increased cell size , disrupted cell membrane integrity , and decreased cell density , uptake of small peptides , release of endothelin - 1 ( ET - 1 ) and plasminogen activator inhibitor ( PAI ) , while causing no changes in endothelial nitric oxide synthase ( eNOS ) protein expression and nitric oxide ( NO ) release .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [288, 300]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [342, 354]}, {"entity": "NO", "entity_type": "Chemical", "pos": [357, 359]}], "task": "NER"}
{"text": "In contrast , NCM2 decreased cell viability , total protein yield , uptake of small peptides , eNOS protein expression , and NO release and caused membrane damage , but caused no changes in the secretion of ET - 1 , prostacyclin and PAI .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [96, 98]}, {"entity": "prostacyclin", "entity_type": "Chemical", "pos": [216, 228]}], "task": "NER"}
{"text": "The presence of LVG and / or alcohol did or did not influence the effects of NCM1 or NCM2 depending on the endpoint and the mixture examined .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "These results suggested that the effects of one or one group of contaminants may be altered by the presence of other contaminants , and that with or without the interaction of high fat and sugar diet and / or ethanol exposure , NCMs at the concentrations used caused endothelial dysfunction in vitro .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [189, 194]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [209, 216]}], "task": "NER"}
{"text": "It remains to be investigated if these effects of NCMs also occur in vivo .", "entity": [], "task": "NER"}
{"text": "Epigenetic modifications in rheumatoid arthritis , a review .", "entity": [], "task": "NER"}
{"text": "Rheumatoid arthritis is an autoimmune disease characterized by chronic joint inflammation and progressive destruction of cartilage and bone which leads to ultimately loss of function and pain .", "entity": [], "task": "NER"}
{"text": "Activated synovial fibroblasts are key effector cells in the pathogenesis of rheumatoid arthritis .", "entity": [], "task": "NER"}
{"text": "In the recent years , epigenetic changes including DNA methylation , histone acetylation and other histone modifications were identified that are associated with an intrinsic activation and the aggressive phenotype of these cells .", "entity": [], "task": "NER"}
{"text": "So far , no therapies targeting rheumatoid arthritis synovial fibroblasts exist .", "entity": [], "task": "NER"}
{"text": "This review comprises recent research efforts that propose epigenetic mechanisms behind the activation of rheumatoid arthritis synovial fibroblasts and other cell types .", "entity": [], "task": "NER"}
{"text": "Antitumor drug delivery in multicellular spheroids by electropermeabilization .", "entity": [], "task": "NER"}
{"text": "Electrochemotherapy ( ECT ) is a physical technique that allows cytotoxic molecules to be efficiently released in tumor cells by inducing transient cell plasma membrane permeabilization .", "entity": [], "task": "NER"}
{"text": "The main antitumoral drugs used in ECT are nonpermeant bleomycin and low permeant cisplatin .", "entity": [{"entity": "bleomycin", "entity_type": "Chemical", "pos": [55, 64]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "The method is nowadays applied in clinics as a palliative treatment .", "entity": [], "task": "NER"}
{"text": "In order to improve it , we took advantage of a human 3D multicellular tumor spheroid as a model of tumor to visually and molecularly assess the effect of ECT .", "entity": [], "task": "NER"}
{"text": "We used bleomycin and cisplatin to confirm its relevance and doxorubicin to show its potential to screen new antitumor drug candidates for ECT .", "entity": [{"entity": "bleomycin", "entity_type": "Chemical", "pos": [8, 17]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [61, 72]}], "task": "NER"}
{"text": "Confocal microscopy was used to visualize the topological distribution of permeabilized cells in 3D spheroids subjected to electric pulses .", "entity": [], "task": "NER"}
{"text": "Our results revealed that all cells were efficiently permeabilized , whatever their localization in the spheroid , even those in the core .", "entity": [], "task": "NER"}
{"text": "The combination of antitumor drugs and electric pulses ( ECT ) led to changes in spheroid macroscopic morphology and cell cohesion , to tumor spheroid growth arrest and finally to its complete apoptosis - mediated dislocation , mimicking previously observed in vivo situations .", "entity": [], "task": "NER"}
{"text": "Taken together , these results indicate that the spheroid model is relevant for the study and optimization of electromediated drug delivery protocols .", "entity": [], "task": "NER"}
{"text": "Transdermal delivery of human epidermal growth factor facilitated by a peptide chaperon .", "entity": [], "task": "NER"}
{"text": "Peptide chaperon TD1 was discovered to facilitate several proteins ' transdermal delivery via topical co - administration .", "entity": [], "task": "NER"}
{"text": "To design a practical , safe system for advanced transdermal peptide , a novel method was carried out .", "entity": [], "task": "NER"}
{"text": "Human epidermal growth factor ( hEGF ) was selected as the model biological agent and a fusion protein : TD1 - hEGF was designed .", "entity": [], "task": "NER"}
{"text": "Study showed that TD1 - hEGF not only had the similar bioactivity with native hEGF , but also possessed considerable higher transdermal ability than hEGF and a co - administration of TD1 and hEGF .", "entity": [], "task": "NER"}
{"text": "These results provided convincing evidence for the advantages of TD1 - hEGF in cosmetic and medical applications .", "entity": [], "task": "NER"}
{"text": "Moreover , the fusion pattern between the cargoes and TD1 offered a new approach to facilitate other hydrophilic drugs ' transdermal delivery for therapeutic application .", "entity": [], "task": "NER"}
{"text": "New pyrazole derivatives containing 1 , 2 , 4 - triazoles and benzoxazoles as potent antimicrobial and analgesic agents .", "entity": [{"entity": "pyrazole", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "1 , 2 , 4 - triazoles", "entity_type": "Chemical", "pos": [36, 57]}, {"entity": "benzoxazoles", "entity_type": "Chemical", "pos": [62, 74]}], "task": "NER"}
{"text": "Azole class of compounds are well known for their excellent therapeutic properties .", "entity": [{"entity": "Azole", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Present paper describes about the synthesis of three series of new 1 , 2 , 4 - triazole and benzoxazole derivatives containing substituted pyrazole moiety ( 11a - d , 12a - d and 13a - d ) .", "entity": [{"entity": "1 , 2 , 4 - triazole", "entity_type": "Chemical", "pos": [67, 87]}, {"entity": "benzoxazole", "entity_type": "Chemical", "pos": [92, 103]}, {"entity": "pyrazole", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "The newly synthesized compounds were characterized by spectral studies and also by C , H , N analyses .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [83, 84]}, {"entity": "H", "entity_type": "Chemical", "pos": [87, 88]}, {"entity": "N", "entity_type": "Chemical", "pos": [91, 92]}], "task": "NER"}
{"text": "All the synthesized compounds were screened for their analgesic activity by the tail flick method .", "entity": [], "task": "NER"}
{"text": "The antimicrobial activity of the new derivatives was also performed by Minimum Inhibitory Concentration ( MIC ) by the serial dilution method .", "entity": [], "task": "NER"}
{"text": "The results revealed that the compound 11c having 2 , 5 - dichlorothiophene substituent on pyrazole moiety and a triazole ring showed significant analgesic and antimicrobial activity .", "entity": [{"entity": "2 , 5 - dichlorothiophene", "entity_type": "Chemical", "pos": [50, 75]}, {"entity": "pyrazole", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "triazole", "entity_type": "Chemical", "pos": [113, 121]}], "task": "NER"}
{"text": "Transcriptional Analysis of Hair Follicle - Derived Keratinocytes from Donors with Atopic Dermatitis Reveals Enhanced Induction of IL32 Gene by IFN - gamma .", "entity": [], "task": "NER"}
{"text": "We cultured human hair follicle - derived keratinocytes ( FDKs ) from plucked hairs .", "entity": [], "task": "NER"}
{"text": "To gain insight into gene expression signatures that can distinguish atopic dermatitis from non - atopic controls without skin biopsies , we undertook a comparative study of gene expression in FDKs from adult donors with atopic dermatitis and non - atopic donors .", "entity": [], "task": "NER"}
{"text": "FDK primary cultures ( atopic dermatitis , n = 11 ; non - atopic controls , n = 7 ) before and after interferon gamma ( IFN - gamma ) treatment were used for microarray analysis and quantitative RT - PCR .", "entity": [], "task": "NER"}
{"text": "Comparison of FDKs from atopic and non - atopic donors indicated that the former showed activated pathways with innate immunity and decreased pathways of cell growth , as indicated by increased NLRP2 expression and decreased DKK1 expression , respectively .", "entity": [], "task": "NER"}
{"text": "Treatment with IFN - gamma induced the enhanced expression of IL32 , IL1B , IL8 , and CXCL1 in the cells from atopic donors compared to that in cells from non - atopic donors at 24 h after treatment .", "entity": [], "task": "NER"}
{"text": "IL1B expression in FDKs after IFN - gamma treatment correlated with IL32 expression .", "entity": [], "task": "NER"}
{"text": "We hypothesized that overexpression of IL32 in hair follicle keratinocytes of patients with atopic dermatitis would lead to the excessive production of pro - IL1 beta and that the activation of IL1 beta from pro - IL1 beta by inflammasome complex , in which NLRP2 protein might be involved , would be augmented .", "entity": [], "task": "NER"}
{"text": "This is the first report to show enhanced induction of cytokine / chemokine genes by IFN - gamma in atopic dermatitis using cultured FDKs .", "entity": [], "task": "NER"}
{"text": "Selenite and tellurite form mixed seleno - and tellurotrisulfides with CstR from Staphylococcus aureus .", "entity": [{"entity": "Selenite", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "tellurite", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "seleno - and tellurotrisulfides", "entity_type": "Chemical", "pos": [34, 65]}], "task": "NER"}
{"text": "Staphylococcus aureus CstR ( CsoR - like sulfur transferase repressor ) is a member of the CsoR family of transition metal sensing metalloregulatory proteins .", "entity": [{"entity": "sulfur", "entity_type": "Chemical", "pos": [41, 47]}, {"entity": "transition metal", "entity_type": "Chemical", "pos": [106, 122]}], "task": "NER"}
{"text": "Unlike CsoR , CstR does not form a stable complex with transition metals but instead reacts with sulfite to form a mixture of di - and trisulfide species , CstR2 ( RS - SR ' ) and CstR2 ( RS - S - SR ' ) n ) n = 1 or 2 , respectively .", "entity": [{"entity": "transition metals", "entity_type": "Chemical", "pos": [55, 72]}, {"entity": "sulfite", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "di - and trisulfide", "entity_type": "Chemical", "pos": [126, 145]}, {"entity": "RS - SR '", "entity_type": "Chemical", "pos": [164, 173]}, {"entity": "RS - S - SR '", "entity_type": "Chemical", "pos": [188, 201]}], "task": "NER"}
{"text": "Here , we investigate if CstR performs similar chemistry with related chalcogen oxyanions selenite and tellurite .", "entity": [{"entity": "chalcogen oxyanions", "entity_type": "Chemical", "pos": [70, 89]}, {"entity": "selenite", "entity_type": "Chemical", "pos": [90, 98]}, {"entity": "tellurite", "entity_type": "Chemical", "pos": [103, 112]}], "task": "NER"}
{"text": "In this work we show by high resolution tandem mass spectrometry that CstR is readily modified by selenite ( SeO3 ( 2 - ) ) or tellurite ( TeO3 ( 2 - ) ) to form a mixture of intersubunit disulfides and selenotrisulfides or tellurotrisulfides , respectively , between Cys31 and Cys60 ' .", "entity": [{"entity": "selenite", "entity_type": "Chemical", "pos": [98, 106]}, {"entity": "SeO3 ( 2 - )", "entity_type": "Chemical", "pos": [109, 121]}, {"entity": "tellurite", "entity_type": "Chemical", "pos": [127, 136]}, {"entity": "TeO3 ( 2 - )", "entity_type": "Chemical", "pos": [139, 151]}, {"entity": "disulfides", "entity_type": "Chemical", "pos": [188, 198]}, {"entity": "selenotrisulfides", "entity_type": "Chemical", "pos": [203, 220]}, {"entity": "tellurotrisulfides", "entity_type": "Chemical", "pos": [224, 242]}, {"entity": "Cys31", "entity_type": "Chemical", "pos": [268, 273]}, {"entity": "Cys60", "entity_type": "Chemical", "pos": [278, 283]}], "task": "NER"}
{"text": "Analogous studies with S . aureus CsoR reveals no reaction with selenite and minimal reaction with tellurite .", "entity": [{"entity": "selenite", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "tellurite", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "All cross - linked forms of CstR exhibit reduced DNA binding affinity .", "entity": [], "task": "NER"}
{"text": "We show that Cys31 initiates the reaction with sulfite through the formation of S - sulfocysteine ( RS - SO3 ( 2 - ) ) and Cys60 is required to fully derivatize CstR to CstR2 ( RS - SR ' ) and CstR2 ( RS - S - SR ' ) .", "entity": [{"entity": "Cys31", "entity_type": "Chemical", "pos": [13, 18]}, {"entity": "sulfite", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "S - sulfocysteine", "entity_type": "Chemical", "pos": [80, 97]}, {"entity": "RS - SO3 ( 2 - )", "entity_type": "Chemical", "pos": [100, 116]}, {"entity": "Cys60", "entity_type": "Chemical", "pos": [123, 128]}, {"entity": "RS - SR '", "entity_type": "Chemical", "pos": [177, 186]}, {"entity": "RS - S - SR '", "entity_type": "Chemical", "pos": [201, 214]}], "task": "NER"}
{"text": "The modification of Cys31 also drives an allosteric switch that negatively regulates DNA binding while derivatization of Cys60 alone has no effect on DNA binding .", "entity": [{"entity": "Cys31", "entity_type": "Chemical", "pos": [20, 25]}, {"entity": "Cys60", "entity_type": "Chemical", "pos": [121, 126]}], "task": "NER"}
{"text": "These results highlight the differences between CstRs and CsoRs in chemical reactivity and metal ion selectivity and establish Cys31 as the functionally important cysteine residue in CstRs .", "entity": [{"entity": "Cys31", "entity_type": "Chemical", "pos": [127, 132]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [163, 171]}], "task": "NER"}
{"text": "Study of Environmental and Antimicrobial Agents Impact on Features of Bacterial Growth .", "entity": [], "task": "NER"}
{"text": "Continuous , real - time observation of bacterial growth has a great advantage for studying the mechanisms of interactions of various compounds with the bacterial cell membrane .", "entity": [], "task": "NER"}
{"text": "With the use of physical methods , which are specific for assessment of continuous changes in turbidity over time , we have shown that bacterial growth was affected by not only on types of antibiotics and phages , but also by their concentration in media .", "entity": [], "task": "NER"}
{"text": "Low concentration of antibiotics and bacteriophages in media has no effect on the bacterial growth process .", "entity": [], "task": "NER"}
{"text": "Our research has shown that if bacterial cell membrane is not completely saturated with antibiotics membrane sensitive sites ( MSS ) , or bacteriophages free unbounded receptors are remained , bacterial growth continues unimpeded .", "entity": [], "task": "NER"}
{"text": "Manganese - exposed developing rats display motor deficits and striatal oxidative stress that are reversed by Trolox .", "entity": [{"entity": "Manganese", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "While manganese ( Mn ) is essential for proper central nervous system ( CNS ) development , excessive Mn exposure may lead to neurotoxicity .", "entity": [{"entity": "manganese", "entity_type": "Chemical", "pos": [6, 15]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [102, 104]}], "task": "NER"}
{"text": "Mn preferentially accumulates in the basal ganglia , and in adults it may cause Parkinson ' s disease - like disorder .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Compared to adults , younger individuals accumulate greater Mn levels in the CNS and are more vulnerable to its toxicity .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [60, 62]}], "task": "NER"}
{"text": "Moreover , the mechanisms mediating developmental Mn - induced neurotoxicity are not completely understood .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [50, 52]}], "task": "NER"}
{"text": "The present study investigated the developmental neurotoxicity elicited by Mn exposure ( 5 , 10 and 20 mg / kg ; i . p . ) from postnatal day 8 to PN27 in rats .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [75, 77]}], "task": "NER"}
{"text": "Neurochemical analyses were carried out on PN29 , with a particular focus on striatal alterations in intracellular signaling pathways ( MAPKs , Akt and DARPP - 32 ) , oxidative stress generation and cell death .", "entity": [], "task": "NER"}
{"text": "Motor alterations were evaluated later in life at 3 , 4 or 5 weeks of age .", "entity": [], "task": "NER"}
{"text": "Mn exposure ( 20 mg / kg ) increased p38 ( MAPK ) and Akt phosphorylation , but decreased DARPP - 32 - Thr - 34 phosphorylation .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Mn ( 10 and 20 mg / kg ) increased caspase activity and F ( 2 ) - isoprostane production ( a biological marker of lipid peroxidation ) .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "F ( 2 ) - isoprostane", "entity_type": "Chemical", "pos": [56, 77]}], "task": "NER"}
{"text": "Paralleling the changes in striatal biochemical parameters , Mn ( 20 mg / kg ) also caused motor impairment , evidenced by increased falling latency in the rotarod test , decreased distance traveled and motor speed in the open - field test .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [61, 63]}], "task": "NER"}
{"text": "Notably , the antioxidant Trolox (TM) reversed the Mn ( 20 mg / kg ) - dependent augmentation in p38 ( MAPK ) phosphorylation and reduced the Mn ( 20 mg / kg ) - induced caspase activity and F ( 2 ) - isoprostane production .", "entity": [{"entity": "Trolox", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [142, 144]}, {"entity": "F ( 2 ) - isoprostane", "entity_type": "Chemical", "pos": [191, 212]}], "task": "NER"}
{"text": "Trolox (TM) also reversed the Mn - induced motor coordination deficits .", "entity": [{"entity": "Trolox", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [30, 32]}], "task": "NER"}
{"text": "These findings are the first to show that long - term exposure to Mn during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers , p38 ( MAPK ) phosphorylation and caspase activity in the striatum .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [66, 68]}], "task": "NER"}
{"text": "Moreover , we establish Trolox (TM) as a potential neuroprotective agent given its efficacy in reversing the Mn - induced neurodevelopmental effects .", "entity": [{"entity": "Trolox", "entity_type": "Chemical", "pos": [24, 30]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [109, 111]}], "task": "NER"}
{"text": "Dose finding by concentration - response versus dose - response : a simulation - based comparison .", "entity": [], "task": "NER"}
{"text": "AIM : The investigations reported here aimed to evaluate the incremental benefit for dose finding by concentration - response analysis versus dose - response analysis .", "entity": [], "task": "NER"}
{"text": "METHODS : Trials were simulated using an Emax model for a range of scenarios of drug properties , trial design options and target response levels .", "entity": [], "task": "NER"}
{"text": "The simulated data were analysed by concentration - response and dose - response modelling ; a dose was then chosen to target a specific response level in a confirmatory trial .", "entity": [], "task": "NER"}
{"text": "The two approaches were compared in terms of the quality of model parameter estimation and the success rate for the confirmatory trial .", "entity": [], "task": "NER"}
{"text": "RESULTS : While the accuracy for ED50 estimation was comparably good with both approaches , the precision was up to 90 % higher with concentration - response approach .", "entity": [], "task": "NER"}
{"text": "The difference was most notable when clearance was highly variable between subjects and the top dose was relatively low .", "entity": [], "task": "NER"}
{"text": "The higher precision by the concentration - response analysis lead to better dose selection and up to 20 % higher success rate for the subsequent confirmatory trial .", "entity": [], "task": "NER"}
{"text": "The relatively small difference in success rate translated into a remarkable difference in sample size requirement .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : By customising these parameters , the approach and the findings can be applied to assessing the value of pharmacokinetic sampling in particular trial situations .", "entity": [], "task": "NER"}
{"text": "Refining the UGT1A haplotype associated with irinotecan - induced hematological toxicity in metastatic colorectal cancer patients treated with 5 - fluorouracil / irinotecan - based regimens .", "entity": [{"entity": "irinotecan", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [143, 159]}, {"entity": "irinotecan", "entity_type": "Chemical", "pos": [162, 172]}], "task": "NER"}
{"text": "Despite the importance of UDP - glucuronosyltransferase ( UGT ) 1A1 * 28 in irinotecan pharmacogenetics , our capability to predict drug - induced severe toxicity remains limited .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "irinotecan", "entity_type": "Chemical", "pos": [76, 86]}], "task": "NER"}
{"text": "We aimed at identifying novel genetic markers that would improve prediction of irinotecan toxicity and response in advanced colorectal cancer patients treated with folic acid ( leucovorin ) , fluorouracil ( 5 - FU ) , and irinotecan ( camptosar ) - based regimens .", "entity": [{"entity": "irinotecan", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "folic acid", "entity_type": "Chemical", "pos": [164, 174]}, {"entity": "leucovorin", "entity_type": "Chemical", "pos": [177, 187]}, {"entity": "fluorouracil", "entity_type": "Chemical", "pos": [192, 204]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [207, 213]}, {"entity": "irinotecan", "entity_type": "Chemical", "pos": [222, 232]}, {"entity": "camptosar", "entity_type": "Chemical", "pos": [235, 244]}], "task": "NER"}
{"text": "The relationships between UGT1A candidate markers across the gene ( n = 21 ) and toxicity were prospectively evaluated in 167 patients .", "entity": [], "task": "NER"}
{"text": "We included variants in the 3 ' untranscribed region ( 3 ' UTR ) of the UGT1A locus , not studied in this context yet .", "entity": [], "task": "NER"}
{"text": "These genetic markers were further investigated in 250 Italian FOLFIRI - treated patients .", "entity": [{"entity": "FOLFIRI", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "Several functional UGT1A variants , including UGT1A1 * 28 , significantly influenced risk of severe hematologic toxicity .", "entity": [], "task": "NER"}
{"text": "As previously reported in the Italian cohort , a 5 - marker risk haplotype [ haplotype II ( HII ) ; UGTs 1A9 / 1A7 / 1A1 ] was associated with severe neutropenia in our cohort [ odds ratio ( OR ) = 2 . 43 ; P = 0 . 004 ] .", "entity": [], "task": "NER"}
{"text": "The inclusion of a 3 ' UTR single - nucleotide polymorphism ( SNP ) permitted refinement of the previously defined HI , in which HIa was associated with the absence of severe neutropenia in combined cohorts ( OR = 0 . 55 ; P = 0 . 038 ) .", "entity": [], "task": "NER"}
{"text": "Among all tested UGT1A variations and upon multivariate analyses , no UGT1A1 SNPs remained significant , whereas three SNPs located in the central region of UGT1A were linked to neutropenia grade 3 - 4 .", "entity": [], "task": "NER"}
{"text": "Haplotype analyses of these markers with the 3 ' UTR SNP allowed the identification of a protective HI ( OR = 0 . 50 ; P = 0 . 048 ) and two risk haplotypes , HII and HIII , characterized by 2 and 3 unfavorable alleles , respectively , revealing a dosage effect ( ORs of 2 . 15 and 5 . 28 ; P <= 0 . 030 ) .", "entity": [], "task": "NER"}
{"text": "Our results suggest that specific SNPs in UGT1A , other than UGT1A1 * 28 , may influence irinotecan toxicity and should be considered to refine pharmacogenetic testing .", "entity": [{"entity": "irinotecan", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "Structural and Optoelectronic Characterization of RF Sputtered ZnSnN2 .", "entity": [{"entity": "ZnSnN2", "entity_type": "Chemical", "pos": [63, 69]}], "task": "NER"}
{"text": "ZnSnN2 , a new earth - abundant semiconductor , is synthesized and characterized for use as a photovoltaic absorber material .", "entity": [{"entity": "ZnSnN2", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Results confirm the predicted orthorhombic Pna21 crystal structure in RF sputtered thin films .", "entity": [], "task": "NER"}
{"text": "Additionally , optical measurements reveal a direct bandgap of about 2 eV , which is larger than our calculated bandgap of 1 . 42 eV due to the Burstein - Moss effect .", "entity": [], "task": "NER"}
{"text": "PHI : A powerful new program for the analysis of anisotropic monomeric and exchange - coupled polynuclear d - and f - block complexes .", "entity": [], "task": "NER"}
{"text": "A new program , PHI , with the ability to calculate the magnetic properties of large spin systems and complex orbitally degenerate systems , such as clusters of d - block and f - block ions , is presented .", "entity": [{"entity": "d - block", "entity_type": "Chemical", "pos": [161, 170]}, {"entity": "f - block", "entity_type": "Chemical", "pos": [175, 184]}], "task": "NER"}
{"text": "The program can intuitively fit experimental data from multiple sources , such as magnetic and spectroscopic data , simultaneously .", "entity": [], "task": "NER"}
{"text": "PHI is extensively parallelized and can operate under the symmetric multiprocessing , single process multiple data , or GPU paradigms using a threaded , MPI or GPU model , respectively .", "entity": [], "task": "NER"}
{"text": "For a given problem PHI is been shown to be almost 12 times faster than the well - known program MAGPACK , limited only by available hardware .", "entity": [], "task": "NER"}
{"text": "Androgen Receptor mRNA Measured by Quantitative Real Time PCR is Decreased in the Urethral Mucosa of Patients with Middle Idiopathic Hypospadias .", "entity": [{"entity": "Androgen", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Androgen action is exerted through the androgen receptor .", "entity": [{"entity": "Androgen", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "The normal 46 , XY genital virilization depends on androgen receptor gene expression , which is tissue specific , and requires normal androgen receptor mRNA levels in androgen sensitive tissues .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [134, 142]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [167, 175]}], "task": "NER"}
{"text": "Hypospadias is a frequent male genital abnormality , potentially related to reduced androgen sensitivity in genital tissues .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "The aim of this study was to compare , by quantitative real time PCR , the amount of androgen receptor mRNA in cells obtained from the urethral mucosa of patients with middle idiopathic hypospadias with the androgen receptor mRNA levels observed in control phimosis subjects with eutopic urethral opening .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [207, 215]}], "task": "NER"}
{"text": "Prepubertal individuals were studied , including 41 controls and 17 hypospadias patients with mean ( SD ) ages of 4 . 7 ( 2 . 1 ) years and 4 . 0 ( 3 . 0 ) years , respectively .", "entity": [], "task": "NER"}
{"text": "We observed significantly less androgen receptor mRNA in the urethral mucosa of patients with hypospadias than in the controls ( p = 0 . 002 ) .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [31, 39]}], "task": "NER"}
{"text": "The correlation between the level of androgen receptor mRNA expression and the penile size was almost statistically significant only in hypospadias patients ( r = 0 . 47 ; p = 0 . 053 ) .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "We also established the number of CAG repeats in exon 1 of the androgen receptor gene by GeneScan analysis .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "No significant difference was observed in the number of CAG repeats when patients and controls were compared .", "entity": [], "task": "NER"}
{"text": "A negative correlation between the CAG repeats and penile size was detected in patients with hypospadias , but not in controls .", "entity": [], "task": "NER"}
{"text": "Our data suggest that a critical lower level of androgen receptor mRNA expression could be a determining factor in the development of middle hypospadias .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton .", "entity": [{"entity": "diterpene", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "Digging up skeletons : We report the identification and the functional characterization of two terpene cyclases ( DtcycA and DtcycB ) that were mined from the genome of Streptomyces sp .", "entity": [{"entity": "terpene", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "SANK 60404 .", "entity": [], "task": "NER"}
{"text": "DtcycA and DtcycB are novel bacterial diterpene cyclases for the synthesis of the cembrane skeleton .", "entity": [{"entity": "diterpene", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "A case - based approach to the practical application of dexmedetomidine in critically ill adults .", "entity": [{"entity": "dexmedetomidine", "entity_type": "Chemical", "pos": [56, 71]}], "task": "NER"}
{"text": "Dexmedetomidine is a selective alpha ( 2 ) - adrenoceptor agonist that offers unique sedation because patients are readily awakened while administration continues and the drug does not suppress the respiratory center .", "entity": [{"entity": "Dexmedetomidine", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Limitations of use include higher acquisition cost , inability to produce deep sedation , and bradycardia and hypotension .", "entity": [], "task": "NER"}
{"text": "Using a case - based approach , the purpose of this review was to qualitatively assess the role of dexmedetomidine in the care of the critically ill and in the management of alcohol withdrawal , and to formulate recommendations regarding its clinical application .", "entity": [{"entity": "dexmedetomidine", "entity_type": "Chemical", "pos": [99, 114]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [174, 181]}], "task": "NER"}
{"text": "Sixty - six studies were identified that investigated dexmedetomidine for the provision of sedation .", "entity": [{"entity": "dexmedetomidine", "entity_type": "Chemical", "pos": [54, 69]}], "task": "NER"}
{"text": "These studies were heterogeneous in design and patient populations ; most investigated patients did not require heavy sedation , and few used propofol as the comparator .", "entity": [{"entity": "propofol", "entity_type": "Chemical", "pos": [142, 150]}], "task": "NER"}
{"text": "In general , though , the aggregate results of all studies demonstrate that dexmedetomidine provides comfort , possibly shortens the duration of mechanical ventilation to facilitate extubation , reduces the occurrence of acute brain dysfunction , and facilitates communication , but the drug is associated with hemodynamic instability and requires the supplemental use of traditional sedative and analgesic agents .", "entity": [{"entity": "dexmedetomidine", "entity_type": "Chemical", "pos": [76, 91]}], "task": "NER"}
{"text": "These outcomes need to be substantiated in additional studies that include assessments of cost - effectiveness .", "entity": [], "task": "NER"}
{"text": "Dexmedetomidine should be considered when patients require mild to moderate levels of sedation of short to intermediate time frames , and they qualify for daily awakenings with traditional sedative therapies .", "entity": [{"entity": "Dexmedetomidine", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "The data for dexmedetomidine in relation to alcohol withdrawal are limited to 12 retrospective reports representing a total of 127 patients .", "entity": [{"entity": "dexmedetomidine", "entity_type": "Chemical", "pos": [13, 28]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "Its role for this indication requires further study , but it may be considered as adjunctive therapy when clinicians are concerned about respiratory suppression associated with escalating doses of gamma - aminobutyric acid agonists .", "entity": [{"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [197, 222]}], "task": "NER"}
{"text": "Regardless of the indication for dexmedetomidine , the practitioner must closely monitor patient comfort and the occurrence of hemodynamic deviations with the realization that as - needed administration of traditional sedatives and analgesics will be required and some degree of bradycardia and hypotension expected but intervention rarely required .", "entity": [{"entity": "dexmedetomidine", "entity_type": "Chemical", "pos": [33, 48]}], "task": "NER"}
{"text": "The Sec7 Guanine Nucleotide Exchange Factor GBF1 Regulates Membrane Recruitment of BIG1 and BIG2 Guanine Nucleotide Exchange Factors to the Trans - Golgi Network ( TGN ) .", "entity": [{"entity": "Guanine", "entity_type": "Chemical", "pos": [9, 16]}, {"entity": "Nucleotide", "entity_type": "Chemical", "pos": [17, 27]}, {"entity": "Guanine", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "Nucleotide", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "Three Sec7 guanine nucleotide exchange factors ( GEFs ) activate ADP - ribosylation factors ( ARFs ) to facilitate coating of transport vesicles within the secretory and endosomal pathways .", "entity": [{"entity": "guanine", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [19, 29]}, {"entity": "ADP", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "GBF1 recruits COPI to pre - Golgi and Golgi compartments , whereas BIG1 and BIG2 recruit AP1 and GGA clathrin adaptors to the trans - Golgi network ( TGN ) and endosomes .", "entity": [], "task": "NER"}
{"text": "Here , we report a functional cascade between these GEFs by showing that GBF1 - activated ARFs ( ARF4 and ARF5 , but not ARF3 ) facilitate BIG1 and BIG2 recruitment to the TGN .", "entity": [], "task": "NER"}
{"text": "We localize GBF1 ultrastructurally to the pre - Golgi , the Golgi , and also the TGN .", "entity": [], "task": "NER"}
{"text": "Our findings suggest a model in which GBF1 localized within pre - Golgi and Golgi compartments mediates ARF activation to facilitate recruitment of COPI to membranes , whereas GBF1 localized at the TGN mediates ARF activation that leads to the recruitment of BIG1 and BIG2 to the TGN .", "entity": [], "task": "NER"}
{"text": "Membrane - associated BIG1 / 2 then activates ARFs that recruit clathrin adaptors .", "entity": [], "task": "NER"}
{"text": "In this cascade , an early acting GEF ( GBF1 ) activates ARFs that mediate recruitment of late acting GEFs ( BIG1 / 2 ) to coordinate coating events within the pre - Golgi / Golgi / TGN continuum .", "entity": [], "task": "NER"}
{"text": "Such coordination may optimize the efficiency and / or selectivity of cargo trafficking through the compartments of the secretory pathway .", "entity": [], "task": "NER"}
{"text": "Investigating the enteroenteric recirculation of apixaban , a factor Xa inhibitor : administration of activated charcoal to bile duct - cannulated rats and dogs receiving an intravenous dose and use of drug transporter knockout rats .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "The study described here investigated the impact of intestinal excretion ( IE ; excretion of drug directly from circulation to intestinal lumen ) , enteroenteric recirculation ( EER ) , and renal tubule recirculation ( RTR ) on apixaban pharmacokinetics and disposition .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [228, 236]}], "task": "NER"}
{"text": "The experimental approaches involve integrating apixaban elimination pathways with pharmacokinetic profiles obtained from bile duct - cannulated ( BDC ) rats and dogs receiving i . v . doses together with oral administration of activated charcoal ( AC ) .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "charcoal", "entity_type": "Chemical", "pos": [238, 246]}], "task": "NER"}
{"text": "Additionally , the role of P - gp ( P - glycoprotein ; abcb1 ) and BCRP ( breast cancer resistance protein ; abcg2 ) in apixaban disposition was evaluated in experiments using transporter inhibitors and transporter knockout ( KO ) rats .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [120, 128]}], "task": "NER"}
{"text": "Approximately 20 - 50 % of an apixaban i . v . dose was found in feces of BDC rats and dogs , suggesting IE leading to fecal elimination and intestinal clearance ( IC ) .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "The fecal elimination , IC , and systemic clearance of apixaban were increased upon AC administration in both BDC rats and dogs and were decreased in BDC rats dosed with GF - 120918 , a dual BCRP and P - gp inhibitor ) .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "GF - 120918", "entity_type": "Chemical", "pos": [170, 181]}], "task": "NER"}
{"text": "BCRP appeared to play a more important role for absorption and intestinal and renal elimination of apixaban than P - gp in transporter - KO rats after oral and i . v . dosing , which led to a higher level of active renal excretion in rat than other species .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [99, 107]}], "task": "NER"}
{"text": "These data demonstrate that apixaban undergoes IE , EER , and RTR that are facilitated by efflux transporters .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [28, 36]}], "task": "NER"}
{"text": "Intestinal reabsorption of apixaban could be interrupted by AC even at 3 hours post - drug dose in dogs ( late charcoal effect ) .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "charcoal", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "This study demonstrates that the intestine is an organ for direct clearance and redistribution of apixaban .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [98, 106]}], "task": "NER"}
{"text": "The IE , EER , and RTR contribute to overall pharmacokinetic profiles of apixaban .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "IE as a clearance pathway , balanced with metabolism and renal excretion , helps decrease the impacts of intrinsic ( renal or hepatic impairment ) and extrinsic ( drug - drug interactions ) factors on apixaban disposition .", "entity": [{"entity": "apixaban", "entity_type": "Chemical", "pos": [201, 209]}], "task": "NER"}
{"text": "Removal of molecular adsorbates on gold nanoparticles using sodium borohydride in water .", "entity": [{"entity": "sodium borohydride", "entity_type": "Chemical", "pos": [60, 78]}], "task": "NER"}
{"text": "The mechanism of sodium borohydride removal of organothiols from gold nanoparticles ( AuNPs ) was studied using an experimental investigation and computational modeling .", "entity": [{"entity": "sodium borohydride", "entity_type": "Chemical", "pos": [17, 35]}, {"entity": "organothiols", "entity_type": "Chemical", "pos": [47, 59]}], "task": "NER"}
{"text": "Organothiols and other AuNP surface adsorbates such as thiophene , adenine , rhodamine , small anions ( Br ( - ) and I ( - ) ) , and a polymer ( PVP , poly ( N - vinylpyrrolidone ) ) can all be rapidly and completely removed from the AuNP surfaces .", "entity": [{"entity": "Organothiols", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "thiophene", "entity_type": "Chemical", "pos": [55, 64]}, {"entity": "adenine", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "rhodamine", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "Br ( - )", "entity_type": "Chemical", "pos": [104, 112]}, {"entity": "I ( - )", "entity_type": "Chemical", "pos": [117, 124]}, {"entity": "PVP", "entity_type": "Chemical", "pos": [145, 148]}, {"entity": "poly ( N - vinylpyrrolidone )", "entity_type": "Chemical", "pos": [151, 180]}], "task": "NER"}
{"text": "A computational study showed that hydride derived from sodium borohydride has a higher binding affinity to AuNPs than organothiols .", "entity": [{"entity": "hydride", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "sodium borohydride", "entity_type": "Chemical", "pos": [55, 73]}, {"entity": "organothiols", "entity_type": "Chemical", "pos": [118, 130]}], "task": "NER"}
{"text": "Thus , it can displace organothiols and all the other adsorbates tested from AuNPs .", "entity": [{"entity": "organothiols", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "Sodium borohydride may be used as a hazard - free , general - purpose detergent that should find utility in a variety of AuNP applications including catalysis , biosensing , surface enhanced Raman spectroscopy , and AuNP recycle and reuse .", "entity": [{"entity": "Sodium borohydride", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "Synthesis of MoS2 and MoSe2 films with vertically aligned layers .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [13, 17]}, {"entity": "MoSe2", "entity_type": "Chemical", "pos": [22, 27]}], "task": "NER"}
{"text": "Layered materials consist of molecular layers stacked together by weak interlayer interactions .", "entity": [], "task": "NER"}
{"text": "They often crystallize to form atomically smooth thin films , nanotubes , and platelet or fullerene - like nanoparticles due to the anisotropic bonding .", "entity": [{"entity": "fullerene", "entity_type": "Chemical", "pos": [90, 99]}], "task": "NER"}
{"text": "Structures that predominately expose edges of the layers exhibit high surface energy and are often considered unstable .", "entity": [], "task": "NER"}
{"text": "In this communication , we present a synthesis process to grow MoS2 and MoSe2 thin films with vertically aligned layers , thereby maximally exposing the edges on the film surface .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "MoSe2", "entity_type": "Chemical", "pos": [72, 77]}], "task": "NER"}
{"text": "Such edge - terminated films are metastable structures of MoS2 and MoSe2 , which may find applications in diverse catalytic reactions .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [58, 62]}, {"entity": "MoSe2", "entity_type": "Chemical", "pos": [67, 72]}], "task": "NER"}
{"text": "We have confirmed their catalytic activity in a hydrogen evolution reaction ( HER ) , in which the exchange current density correlates directly with the density of the exposed edge sites .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "Nevirapine bioactivation and covalent binding in the skin .", "entity": [{"entity": "Nevirapine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Nevirapine ( NVP ) treatment is associated with serious skin rashes that appear to be immune - mediated .", "entity": [{"entity": "Nevirapine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "NVP", "entity_type": "Chemical", "pos": [13, 16]}], "task": "NER"}
{"text": "We previously developed a rat model of this skin rash that is immune - mediated and is very similar to the rash in humans .", "entity": [], "task": "NER"}
{"text": "Treatment of rats with the major NVP metabolite , 12 - OH - NVP , also caused the rash .", "entity": [{"entity": "NVP", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "12 - OH - NVP", "entity_type": "Chemical", "pos": [50, 63]}], "task": "NER"}
{"text": "Most idiosyncratic drug reactions are caused by reactive metabolites ; 12 - OH - NVP forms a benzylic sulfate , which was detected in the blood of animals treated with NVP or 12 - OH - NVP .", "entity": [{"entity": "12 - OH - NVP", "entity_type": "Chemical", "pos": [71, 84]}, {"entity": "benzylic sulfate", "entity_type": "Chemical", "pos": [93, 109]}, {"entity": "NVP", "entity_type": "Chemical", "pos": [168, 171]}, {"entity": "12 - OH - NVP", "entity_type": "Chemical", "pos": [175, 188]}], "task": "NER"}
{"text": "This sulfate is presumably formed in the liver ; however , the skin also has significant sulfotransferase activity .", "entity": [{"entity": "sulfate", "entity_type": "Chemical", "pos": [5, 12]}], "task": "NER"}
{"text": "In this study , we used a serum against NVP to detect covalent binding in the skin of rats .", "entity": [{"entity": "NVP", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "There was a large artifact band in immunoblots of whole skin homogenates that interfered with detection of covalent binding ; however , when the skin was separated into dermal and epidermal fractions , covalent binding was clearly present in the epidermis , which is also the location of sulfotransferases .", "entity": [], "task": "NER"}
{"text": "In contrast to rats , treatment of mice with NVP did not result in covalent binding in the skin or skin rash .", "entity": [{"entity": "NVP", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "Although the reaction of 12 - OH - NVP sulfate with nucleophiles such as glutathione is slow , incubation of this sulfate with homogenized human and rat skin led to extensive covalent binding .", "entity": [{"entity": "12 - OH - NVP sulfate", "entity_type": "Chemical", "pos": [25, 46]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "sulfate", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "Incubations of 12 - OH - NVP with the soluble fraction from a 9 , 000g centrifugation ( S9 ) of rat or human skin homogenate in the presence of 3 ' - phosphoadenosine - 5 ' - phosphosulfate ( PAPS ) produced extensive covalent binding , but no covalent binding was detected with mouse skin S9 , which suggests that the reason mice do not develop a rash is that they lack the required sulfotransferase .", "entity": [{"entity": "12 - OH - NVP", "entity_type": "Chemical", "pos": [15, 28]}, {"entity": "3 ' - phosphoadenosine - 5 ' - phosphosulfate", "entity_type": "Chemical", "pos": [144, 189]}, {"entity": "PAPS", "entity_type": "Chemical", "pos": [192, 196]}], "task": "NER"}
{"text": "This is the first study to report covalent binding of NVP to rat and human skin .", "entity": [{"entity": "NVP", "entity_type": "Chemical", "pos": [54, 57]}], "task": "NER"}
{"text": "These data provide strong evidence that covalent binding of NVP in the skin is due to 12 - OH - NVP sulfate , which is likely responsible for NVP - induced skin rash .", "entity": [{"entity": "NVP", "entity_type": "Chemical", "pos": [60, 63]}, {"entity": "12 - OH - NVP sulfate", "entity_type": "Chemical", "pos": [86, 107]}, {"entity": "NVP", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "Sulfation may represent a bioactivation pathway for other drugs that cause a skin rash .", "entity": [], "task": "NER"}
{"text": "Development of Bacteriostatic DNA Aptamers for Salmonella .", "entity": [], "task": "NER"}
{"text": "Salmonella is one of the most dangerous and common food - borne pathogens .", "entity": [], "task": "NER"}
{"text": "The overuse of antibiotics for disease prevention has led to the development of multidrug resistant Salmonella .", "entity": [], "task": "NER"}
{"text": "Now , more than ever , there is a need for new antimicrobial drugs to combat these resistant bacteria .", "entity": [], "task": "NER"}
{"text": "Aptamers have grown in popularity since their discovery , and their properties make them attractive candidates for therapeutic use .", "entity": [], "task": "NER"}
{"text": "In this work , we describe the selection of highly specific DNA aptamers to S . enteritidis and S . typhimurium .", "entity": [], "task": "NER"}
{"text": "To evolve species - specific aptamers , twelve rounds of selection to live S . enteritidis and S . typhimurium were performed , alternating with a negative selection against a mixture of related pathogens .", "entity": [], "task": "NER"}
{"text": "Studies have shown that synthetic pools combined from individual aptamers have the capacity to inhibit growth of S . enteritidis and S . typhimurium in bacterial cultures ; this was the result of a decrease in their membrane potential .", "entity": [], "task": "NER"}
{"text": "Minimal peptide motif for non - covalent peptide - heparin hydrogels .", "entity": [], "task": "NER"}
{"text": "Reduction of complexity of the extracellular matrix ( ECM ) to a non - covalent structure with minimal chemically defined components represents an attractive avenue for understanding the biology of the ECM .", "entity": [], "task": "NER"}
{"text": "The resulting system could lead to the design of tailor - made biomaterials that incorporate varying functionalities .", "entity": [], "task": "NER"}
{"text": "Negatively charged glycosaminoglycans are the major components of the ECM .", "entity": [], "task": "NER"}
{"text": "Their interaction with positively charged proteins is important for dynamic three - dimensional scaffold formation and function .", "entity": [], "task": "NER"}
{"text": "We designed and screened minimal peptide motifs whose conjugates with polyethylene glycol interact with heparin to form non - covalent hydrogels .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [70, 89]}], "task": "NER"}
{"text": "Here we show the structure / function relationship of the ( RA ) ( n ) and ( KA ) ( n ) motifs and determined that both basic residues and the heparin - induced alpha - helix formation are important for the assembly process .", "entity": [], "task": "NER"}
{"text": "Simple rules allowed us to tune various aspects of the matrix system such as the gelation rates , biodegradability , rheological properties , and biofunctionality .", "entity": [], "task": "NER"}
{"text": "The hydrogels can encapsulate cells and support cell survival .", "entity": [], "task": "NER"}
{"text": "Natural products as a source for treating neglected parasitic diseases .", "entity": [], "task": "NER"}
{"text": "Infectious diseases caused by parasites are a major threat for the entire mankind , especially in the tropics .", "entity": [], "task": "NER"}
{"text": "More than 1 billion people world - wide are directly exposed to tropical parasites such as the causative agents of trypanosomiasis , leishmaniasis , schistosomiasis , lymphatic filariasis and onchocerciasis , which represent a major health problem , particularly in impecunious areas .", "entity": [], "task": "NER"}
{"text": "Unlike most antibiotics , there is no \" general \" antiparasitic drug available .", "entity": [], "task": "NER"}
{"text": "Here , the selection of antiparasitic drugs varies between different organisms .", "entity": [], "task": "NER"}
{"text": "Some of the currently available drugs are chemically de novo synthesized , however , the majority of drugs are derived from natural sources such as plants which have subsequently been chemically modified to warrant higher potency against these human pathogens .", "entity": [], "task": "NER"}
{"text": "In this review article we will provide an overview of the current status of plant derived pharmaceuticals and their chemical modifications to target parasite - specific peculiarities in order to interfere with their proliferation in the human host .", "entity": [], "task": "NER"}
{"text": "Oxidative Stress and DNA Damage in Human Gastric Carcinoma : 8 - Oxo - 7 ' 8 - dihydro - 2 ' - deoxyguanosine ( 8 - oxo - dG ) as a Possible Tumor Marker .", "entity": [{"entity": "8 - Oxo - 7 ' 8 - dihydro - 2 ' - deoxyguanosine", "entity_type": "Chemical", "pos": [61, 109]}, {"entity": "8 - oxo - dG", "entity_type": "Chemical", "pos": [112, 124]}], "task": "NER"}
{"text": "We characterized the oxidative stress ( OS ) status by the levels of reduced / oxidized glutathione ( GSH / GSSG ) , malondialdehyde ( MDA ) and the mutagenic base 8 - oxo - 7 ' 8 - dihydro - 2 ' - deoxyguanosine ( 8 - oxo - dG ) in human gastric carcinoma ( HGC ) samples and compared the results with normal tissue from the same patients .", "entity": [{"entity": "reduced / oxidized glutathione", "entity_type": "Chemical", "pos": [69, 99]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [108, 112]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [117, 132]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [135, 138]}, {"entity": "8 - oxo - 7 ' 8 - dihydro - 2 ' - deoxyguanosine", "entity_type": "Chemical", "pos": [164, 212]}, {"entity": "8 - oxo - dG", "entity_type": "Chemical", "pos": [215, 227]}], "task": "NER"}
{"text": "We also analyzed 8 - oxo - dG in peripheral mononuclear cells ( PMNC ) and urine from healthy control subjects and in affected patients in the basal state and one , three , six , nine and twelve months after tumor resection .", "entity": [{"entity": "8 - oxo - dG", "entity_type": "Chemical", "pos": [17, 29]}], "task": "NER"}
{"text": "The levels of DNA repair enzyme mRNA expression ( hOGG1 , RAD51 , MUYTH and MTH1 ) were determined in tumor specimens and compared with normal mucosa .", "entity": [], "task": "NER"}
{"text": "Tumor specimens exhibited increased levels of MDA and 8 - oxo - dG compared with normal gastric tissue .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "8 - oxo - dG", "entity_type": "Chemical", "pos": [54, 66]}], "task": "NER"}
{"text": "GSH levels were also increased , while GSSG levels remained stable .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "DNA repair enzyme mRNA expression was induced in the tumor tissues .", "entity": [], "task": "NER"}
{"text": "Levels of 8 - oxo - dG were significantly elevated in both urine and PMNC of gastric cancer patients compared with healthy controls .", "entity": [{"entity": "8 - oxo - dG", "entity_type": "Chemical", "pos": [10, 22]}], "task": "NER"}
{"text": "After gastrectomy , the levels of the damaged base in urine and PMNC decreased progressively to values close to those found in the healthy population .", "entity": [], "task": "NER"}
{"text": "The high levels of 8 - oxo - dG in urine may be related to the increased induction of DNA repair activity in tumor tissue , and the changes observed after tumor resection support its potential use as a tumor marker .", "entity": [{"entity": "8 - oxo - dG", "entity_type": "Chemical", "pos": [19, 31]}], "task": "NER"}
{"text": "Process engineering with planetary ball mills .", "entity": [], "task": "NER"}
{"text": "Planetary ball mills are well known and used for particle size reduction on laboratory and pilot scales for decades while during the last few years the application of planetary ball mills has extended to mechanochemical approaches .", "entity": [], "task": "NER"}
{"text": "Processes inside planetary ball mills are complex and strongly depend on the processed material and synthesis and , thus , the optimum milling conditions have to be assessed for each individual system .", "entity": [], "task": "NER"}
{"text": "The present review focuses on the insight into several parameters like properties of grinding balls , the filling ratio or revolution speed .", "entity": [], "task": "NER"}
{"text": "It gives examples of the aspects of grinding and illustrates some general guidelines to follow for modelling processes in planetary ball mills in terms of refinement , synthesis ' yield and contamination from wear .", "entity": [], "task": "NER"}
{"text": "The amount of energy transferred from the milling tools to the powder is significant and hardly measurable for processes in planetary ball mills .", "entity": [], "task": "NER"}
{"text": "Thus numerical simulations based on a discrete - element - method are used to describe the energy transfer to give an adequate description of the process by correlation with experiments .", "entity": [], "task": "NER"}
{"text": "The simulations illustrate the effect of the geometry of planetary ball mills on the energy entry .", "entity": [], "task": "NER"}
{"text": "In addition the imaging of motion patterns inside a planetary ball mill from simulations and video recordings is shown .", "entity": [], "task": "NER"}
{"text": "Cloning , characterization and heterologous expression of the indolocarbazole biosynthetic gene cluster from marine - derived Streptomyces sanyensis FMA .", "entity": [{"entity": "indolocarbazole", "entity_type": "Chemical", "pos": [62, 77]}], "task": "NER"}
{"text": "The indolocarbazole ( ICZ ) alkaloids have attracted much attention due to their unique structures and potential therapeutic applications .", "entity": [{"entity": "indolocarbazole", "entity_type": "Chemical", "pos": [4, 19]}, {"entity": "ICZ", "entity_type": "Chemical", "pos": [22, 25]}], "task": "NER"}
{"text": "A series of ICZs were recently isolated and identified from a marine - derived actinomycete strain , Streptomyces sanyensis FMA .", "entity": [{"entity": "ICZs", "entity_type": "Chemical", "pos": [12, 16]}], "task": "NER"}
{"text": "To elucidate the biosynthetic machinery associated with ICZs production in S . sanyensis FMA , PCR using degenerate primers was carried out to clone the FAD - dependent monooxygenase gene fragment for ICZ ring formation , which was used as a probe to isolate the 34 . 6 - kb DNA region containing the spc gene cluster .", "entity": [{"entity": "ICZs", "entity_type": "Chemical", "pos": [56, 60]}, {"entity": "FAD", "entity_type": "Chemical", "pos": [153, 156]}, {"entity": "ICZ", "entity_type": "Chemical", "pos": [201, 204]}], "task": "NER"}
{"text": "Sequence analysis revealed genes for ICZ ring formation ( spcO , D , P , C ) , sugar unit formation ( spcA , B , E , K , J , I ) , glycosylation ( spcN , G ) , methylation ( spcMA , MB ) , as well as regulation ( spcR ) .", "entity": [{"entity": "ICZ", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [79, 84]}], "task": "NER"}
{"text": "Their involvement in ICZ biosynthesis was confirmed by gene inactivation and heterologous expression in Streptomyces coelicolor M1152 .", "entity": [{"entity": "ICZ", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "This work represents the first cloning and characterization of an ICZ gene cluster isolated from a marine - derived actinomycete strain and would be helpful for thoroughly understanding the biosynthetic mechanism of ICZ glycosides .", "entity": [{"entity": "ICZ", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "ICZ glycosides", "entity_type": "Chemical", "pos": [216, 230]}], "task": "NER"}
{"text": "Antimicrobial N - halamine polymers and coatings : a review of their synthesis , characterization , and applications .", "entity": [{"entity": "N - halamine polymers", "entity_type": "Chemical", "pos": [14, 35]}], "task": "NER"}
{"text": "Antimicrobial N - halamine polymers and coatings have been studied extensively over the past decade thanks to their numerous qualities such as effectiveness toward a broad spectrum of microorganisms , long - term stability , regenerability , safety to humans and environment and low cost .", "entity": [{"entity": "N - halamine polymers", "entity_type": "Chemical", "pos": [14, 35]}], "task": "NER"}
{"text": "In this review , recent developments are described by emphasizing the synthesis of polymers and / or coatings having N - halamine moieties .", "entity": [{"entity": "N - halamine", "entity_type": "Chemical", "pos": [117, 129]}], "task": "NER"}
{"text": "Actually , three main approaches of preparation are given in detail : polymerization , generation by electrochemical route with proteins as monomers and grafting with precursor monomers .", "entity": [], "task": "NER"}
{"text": "Identification and characterization of the formation of the N - halamine bonds ( > N - X with X = Cl or Br or I ) by physical techniques such as Fourier transform infrared spectroscopy ( FTIR ) , nuclear magnetic resonance spectroscopy ( NMR ) , energy - dispersive X - ray spectroscopy ( EDX ) , X - ray photoelectron spectroscopy ( XPS ) , and by chemical reactions are described .", "entity": [{"entity": "N - halamine", "entity_type": "Chemical", "pos": [60, 72]}, {"entity": "N", "entity_type": "Chemical", "pos": [83, 84]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "Br", "entity_type": "Chemical", "pos": [104, 106]}, {"entity": "I", "entity_type": "Chemical", "pos": [110, 111]}], "task": "NER"}
{"text": "In order to check the antimicrobial activity of the N - halamine compounds , bacterial tests are also described .", "entity": [{"entity": "N - halamine", "entity_type": "Chemical", "pos": [52, 64]}], "task": "NER"}
{"text": "Finally , some examples of application of these N - halamines in the water treatment , paints , healthcare equipment , and textile industries are presented and discussed .", "entity": [{"entity": "N - halamines", "entity_type": "Chemical", "pos": [48, 61]}], "task": "NER"}
{"text": "Hollow block copolymer nanoparticles through a spontaneous one - step structural reorganization .", "entity": [], "task": "NER"}
{"text": "The spontaneous one - step synthesis of hollow nanocages and nanotubes from spherical and cylindrical micelles based on poly ( acrylic acid ) - b - polylactide ( P ( AA ) - b - P ( LA ) ) block copolymers ( BCPs ) has been achieved .", "entity": [{"entity": "poly ( acrylic acid ) - b - polylactide", "entity_type": "Chemical", "pos": [120, 159]}, {"entity": "P ( AA ) - b - P ( LA )", "entity_type": "Chemical", "pos": [162, 185]}], "task": "NER"}
{"text": "This structural reorganization , which occurs simply upon drying of the samples , was elucidated by transmission electron microscopy ( TEM ) and atomic force microscopy ( AFM ) .", "entity": [], "task": "NER"}
{"text": "We show that it was necessary to use stain - free imaging to examine these nanoscale assemblies , as the hollow nature of the particles was obscured by application of a heavy metal stain .", "entity": [], "task": "NER"}
{"text": "Additionally , the internal topology of the P ( AA ) - b - P ( LA ) particles could be tuned by manipulating the drying conditions to give solid or compartmentalized structures .", "entity": [{"entity": "P ( AA ) - b - P ( LA )", "entity_type": "Chemical", "pos": [44, 67]}], "task": "NER"}
{"text": "Upon resuspension , these reorganized nanoparticles retain their hollow structure and display significantly enhanced loading of a hydrophobic dye compared to the original solid cylinders .", "entity": [], "task": "NER"}
{"text": "Photoelectrochemical properties of nanomultiple CaFe2O4 / ZnFe2O4 pn junction photoelectrodes .", "entity": [{"entity": "CaFe2O4", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "ZnFe2O4", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "Nanomultiple CaFe2O4 / ZnFe2O4pn junctions are prepared by a pulsed laser deposition method to explore their photoelectrochemical properties as the photoelectrodes .", "entity": [{"entity": "CaFe2O4", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "ZnFe2O4pn", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "It is demonstrated that the multiple - pn - junction structure is favorable to enhancing the photocurrent density and the onset potential of the photoelectrode .", "entity": [], "task": "NER"}
{"text": "Furthermore , the 20 - junction photoelectrode - based PEC cell yields a high open circuit photovoltage of up to 0 . 97 V , which is much higher than that for a single pn junction photoelectrode PEC cell that yields an open circuit photovoltage of 0 . 13 V .", "entity": [], "task": "NER"}
{"text": "A multiple - junction band structure model is assumed to describe the behavior of the CaFe2O4 / ZnFe2O4 multiple - junction photoelectrodes .", "entity": [{"entity": "CaFe2O4", "entity_type": "Chemical", "pos": [86, 93]}, {"entity": "ZnFe2O4", "entity_type": "Chemical", "pos": [96, 103]}], "task": "NER"}
{"text": "It is suggested that the open circuit photovoltage is dominated by the number of pn junctions in a multiple - junction photoelectrode and the carrier transfer inside the photoelectrode is improved by narrowing the single - layer thickness .", "entity": [], "task": "NER"}
{"text": "These findings provide a new approach to designing the multiple - junction structure to improve the PEC properties of the photoelectrodes .", "entity": [], "task": "NER"}
{"text": "Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug .", "entity": [], "task": "NER"}
{"text": "Abstract Background : Organic porous material is a promising carrier for enhancing the dissolution of poorly water soluble drug .", "entity": [], "task": "NER"}
{"text": "The aim of the present study was to enhance dissolution and oral bioavailability of lovastatin ( LV ) by preparing a porous starch microsphere foam ( PSM ) using a novel method , meanwhile , looking into the mechanism of improving dissolution of LV .", "entity": [{"entity": "lovastatin", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "Methods : PSM was prepared by the W / O emulsion - freeze thawing method .", "entity": [], "task": "NER"}
{"text": "The porous structure of PSM was characterized by scanning electron microscopy ( SEM ) and nitrogen adsorption / desorption analysis .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "The adsorption role of nanopores on the drug dissolution and physical state of LV was systematically studied by instrumental analysis , and in vitro and in vivo drug dissolution studies .", "entity": [], "task": "NER"}
{"text": "3 - ( 4 , 5 - Dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyltetrazolium bromide ( MTT ) assay was used to evaluate carrier cytotoxicity .", "entity": [{"entity": "3 - ( 4 , 5 - Dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyltetrazolium bromide", "entity_type": "Chemical", "pos": [0, 78]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Results : The SEM images of PSM showed nanometer - sized pores .", "entity": [], "task": "NER"}
{"text": "Physical state characterization indicated that porous structure effectively limited the degree of crystallinity of LV .", "entity": [], "task": "NER"}
{"text": "The results of in vitro and in vivo tests testified that PSM accelerated the release of LV and enhanced its oral bioavailability in comparison with crude LV and commercial capsules .", "entity": [], "task": "NER"}
{"text": "The loaded PSM powder indicated a good physical stability under storage for 12 months .", "entity": [], "task": "NER"}
{"text": "MTT assay shows PSM has no toxicity for Caco - 2 cell .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Conclusion : The preparation was a promising method to produce small and uniform PSM with markedly enhanced dissolution rate and oral bioavailability due to the spatial confinement effect of porous structure .", "entity": [], "task": "NER"}
{"text": "The present work demonstrates the significant potential for the use of PSM as a novel delivery system for poorly water soluble drugs .", "entity": [], "task": "NER"}
{"text": "Different pharmacokinetics of the two structurally similar dammarane sapogenins , protopanaxatriol and protopanaxadiol , in rats .", "entity": [{"entity": "dammarane sapogenins", "entity_type": "Chemical", "pos": [59, 79]}, {"entity": "protopanaxatriol", "entity_type": "Chemical", "pos": [82, 98]}, {"entity": "protopanaxadiol", "entity_type": "Chemical", "pos": [103, 118]}], "task": "NER"}
{"text": "Dammarane Sapogenins ( DS ) , with main ingredients of protopanaxatriol ( PPT , 33 % ) and protopanaxadiol ( PPD , 16 % ) , is an alkaline hydrolyzed product of ginsenosides and had significant activities in improving learning and memory and decreasing chemotherapy - induced myelosuppression .", "entity": [{"entity": "Dammarane Sapogenins", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "protopanaxatriol", "entity_type": "Chemical", "pos": [55, 71]}, {"entity": "PPT", "entity_type": "Chemical", "pos": [74, 77]}, {"entity": "protopanaxadiol", "entity_type": "Chemical", "pos": [91, 106]}, {"entity": "PPD", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "ginsenosides", "entity_type": "Chemical", "pos": [161, 173]}], "task": "NER"}
{"text": "In the present study , the pharmacokinetics and oral bioavailabilities of PPT and PPD were investigated when a single dose of DS was administrated orally ( 75mg / kg ) and intravenously ( i . v . , 30mg / kg ) to rats .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [74, 77]}, {"entity": "PPD", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "Their in vitro stabilities in the GI tract were also investigated .", "entity": [], "task": "NER"}
{"text": "PPT and PPD concentrations were measured by LC - MS .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "PPD", "entity_type": "Chemical", "pos": [8, 11]}], "task": "NER"}
{"text": "The results showed that PPT was eliminated rapidly from the body with an average t1 / 2 , lambda z value of 0 . 80h and CL of 4 . 27l / h / kg after i . v . administration , while PPD was eliminated relatively slowly with a t1 / 2 , lambda z of 6 . 25h and CL of 0 . 98l / h / kg .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "PPD", "entity_type": "Chemical", "pos": [180, 183]}], "task": "NER"}
{"text": "After oral administration , both PPD and PPT could be absorbed into the body , but their systemic exposures were quite different .", "entity": [{"entity": "PPD", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "PPT", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "PPT was absorbed into the body quickly , with a Tmax of 0 . 58h and a Cmax of 0 . 13 mu g / ml , while PPD was absorbed relatively slowly with a Tmax of 1 . 82h and a Cmax of 1 . 04 mu g / ml .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "PPD", "entity_type": "Chemical", "pos": [103, 106]}], "task": "NER"}
{"text": "The absolute bioavailabilities of PPT and PPD were estimated as 3 . 69 % and 48 . 12 % , respectively .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "PPD", "entity_type": "Chemical", "pos": [42, 45]}], "task": "NER"}
{"text": "The stability test found that PPT was instable in the stomach with 40 % degradation after 4h incubation at 37 degrees C , both in pH1 . 2 buffer and in the stomach content solution .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "The instability in the stomach might be one of the reasons for PPT ' s poor bioavailability .", "entity": [{"entity": "PPT", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "Image - guided percutaneous ablation therapies for local recurrences of thyroid tumors .", "entity": [], "task": "NER"}
{"text": "The incidence of thyroid carcinoma has increased steadily over the last few decades .", "entity": [], "task": "NER"}
{"text": "Most differentiated thyroid carcinomas ( DTC ) are cured thanks to the initial treatment with surgery and radioiodine therapy .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [106, 117]}], "task": "NER"}
{"text": "Nevertheless , neck lymph node metastases are found in a few of these patients during their long - term clinical and ultrasound follow - up .", "entity": [], "task": "NER"}
{"text": "In some of these cases radioiodine treatment may not be effective in eradicating nodal metastases due to scant 131 - I uptake .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "131 - I", "entity_type": "Chemical", "pos": [111, 118]}], "task": "NER"}
{"text": "Additionally , a few of these patients undergo repeated neck explorations and / or resections .", "entity": [], "task": "NER"}
{"text": "Based on these considerations and on the frequently indolent course of DTC neck metastases , a non - surgical therapeutic approach should be considered to control small local foci of DTC .", "entity": [], "task": "NER"}
{"text": "There is increasing interest in mini - invasive image - guided procedures that can be performed under local anesthesia which do not affect the performance status of the patient .", "entity": [], "task": "NER"}
{"text": "Image - guided minimally invasive ablative therapies delivered by using needle - like applicators include both thermal and non - thermal source techniques .", "entity": [], "task": "NER"}
{"text": "Over the past 25 years , these therapies have gained widespread attention and , in many cases , broad clinical acceptance as methods for treating focal malignancies .", "entity": [], "task": "NER"}
{"text": "In an attempt to overcome the limitations of treating certain unresectable tumor types not amenable to a further surgical treatment , a few investigators have reported successfully combining percutaneous therapies with other oncologic treatment strategies ( combined treatments ) .", "entity": [], "task": "NER"}
{"text": "In this review , we reported mini - invasive techniques more commonly employed in selected cases to ameliorate local compressive symptoms , control hormonal production , and reduce the volume of neoplastic tissue prior to traditional palliative treatment .", "entity": [], "task": "NER"}
{"text": "Impact of Baseline Insulin Regimen on Glycemic Response to a Group Medical Clinic Intervention .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEGroup medical clinics ( GMC ) combine medication management and self - management training , and may improve diabetes outcomes .", "entity": [], "task": "NER"}
{"text": "It remains unclear which patients benefit most from GMC .", "entity": [], "task": "NER"}
{"text": "This secondary analysis examined the impact of baseline insulin regimen on GMC response . RESEARCH DESIGN AND METHODSWe analyzed a trial of 239 veterans with type 2 diabetes randomized to GMC or usual care ( UC ) .", "entity": [], "task": "NER"}
{"text": "We categorized baseline insulin regimen as the following : no insulin ; basal insulin only ; or complex insulin ( basal - prandial or mixed regimens ) .", "entity": [], "task": "NER"}
{"text": "Using linear mixed models adjusted for clustering within GMC , we evaluated the differential impact of GMC relative to UC on hemoglobin A ( 1c ) ( HbA ( 1c ) ) and self - efficacy among patients on different baseline insulin regimens . RESULTSFrom linear mixed models , the effect of GMC on HbA ( 1c ) differed by baseline insulin regimen versus UC ( P = 0 . 05 ) ; there was no differential effect on self - efficacy ( P = 0 . 29 ) .", "entity": [], "task": "NER"}
{"text": "Among those using complex insulin regimens at baseline , GMC reduced HbA ( 1c ) by study end compared with UC ( - 1 . 0 % ; 95 % CI - 1 . 8 to - 0 . 2 ; P = 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "We found no such HbA ( 1c ) difference between GMC and UC patients using no insulin ( P = 0 . 65 ) or basal insulin only ( P = 0 . 71 ) .", "entity": [], "task": "NER"}
{"text": "There were no clinically significant differences in hypoglycemia by baseline insulin regimen and intervention group . CONCLUSIONSWe found that compared with UC , GMC lowered HbA ( 1c ) specifically among patients using complex insulin regimens at study baseline , which may relate to this group ' s demanding medication and self - management requirements .", "entity": [], "task": "NER"}
{"text": "Implementing GMC among patients using complex insulin regimens may maximize this care delivery strategy ' s potential .", "entity": [], "task": "NER"}
{"text": "Polymer - coated echogenic lipid nanoparticles with dual release triggers .", "entity": [], "task": "NER"}
{"text": "Although lipid nanoparticles are promising drug delivery vehicles , passive release of encapsulated contents at the target site is often slow .", "entity": [], "task": "NER"}
{"text": "Herein , we report contents release from targeted , polymer - coated , echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound .", "entity": [], "task": "NER"}
{"text": "The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross - linker .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [73, 82]}], "task": "NER"}
{"text": "In the presence of cytosolic concentrations of glutathione , the lipid nanoparticles released 76 % of encapsulated contents .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [47, 58]}], "task": "NER"}
{"text": "Plasma concentrations of glutathione failed to release the encapsulated contents .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [25, 36]}], "task": "NER"}
{"text": "Application of 3 MHz ultrasound for 2 min simultaneously with the reducing agent enhanced the release to 96 % .", "entity": [], "task": "NER"}
{"text": "Folic acid conjugated , doxorubicin - loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor ( compared to the control ) .", "entity": [{"entity": "Folic acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "folate", "entity_type": "Chemical", "pos": [141, 147]}], "task": "NER"}
{"text": "With further developments , these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging .", "entity": [], "task": "NER"}
{"text": "Discovery of 4 - { 4 - [ ( 3R ) - 3 - Methylmorpholin - 4 - yl ] - 6 - [ 1 - ( methylsulfonyl ) cyclopropyl ] pyrimidin - 2 - yl } - 1H - indole ( AZ20 ) : a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity .", "entity": [{"entity": "4 - { 4 - [ ( 3R ) - 3 - Methylmorpholin - 4 - yl ] - 6 - [ 1 - ( methylsulfonyl ) cyclopropyl ] pyrimidin - 2 - yl } - 1H - indole", "entity_type": "Chemical", "pos": [13, 144]}, {"entity": "AZ20", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo - or radiation sensitizers or as monotherapy in tumors addicted to particular DNA - repair pathways .", "entity": [], "task": "NER"}
{"text": "We describe the discovery and synthesis of a series of sulfonylmorpholinopyrimidines that show potent and selective ATR inhibition .", "entity": [{"entity": "sulfonylmorpholinopyrimidines", "entity_type": "Chemical", "pos": [55, 84]}], "task": "NER"}
{"text": "Optimization from a high quality screening hit within tight SAR space led to compound 6 ( AZ20 ) which inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 of 50 nM .", "entity": [{"entity": "AZ20", "entity_type": "Chemical", "pos": [90, 94]}], "task": "NER"}
{"text": "Compound 6 potently inhibits the growth of LoVo colorectal adenocarcinoma tumor cells in vitro and has high free exposure in mouse following moderate oral doses .", "entity": [], "task": "NER"}
{"text": "At well tolerated doses 6 leads to significant growth inhibition of LoVo xenografts grown in nude mice .", "entity": [], "task": "NER"}
{"text": "Compound 6 is a useful compound to explore ATR pharmacology in vivo .", "entity": [], "task": "NER"}
{"text": "Surface structures of PDMS incorporated with quaternary ammonium salts designed for antibiofouling and fouling release applications .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [22, 26]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [56, 64]}], "task": "NER"}
{"text": "Poly ( dimethylsiloxane ) ( PDMS ) materials have been extensively shown to function as excellent fouling - release ( FR ) coatings in the marine environment .", "entity": [{"entity": "Poly ( dimethylsiloxane )", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "The incorporation of biocide moieties , such as quaternary ammonium salts ( QAS ) , can impart additional antibiofouling properties to PDMS - based FR coating systems .", "entity": [{"entity": "ammonium", "entity_type": "Chemical", "pos": [59, 67]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "In this study , the molecular surface structures of two different types of QAS - incorporated PDMS systems were investigated in different chemical environments using sum frequency generation vibrational spectroscopy ( SFG ) .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "Specifically , a series of PDMS coatings containing either a QAS with a single ammonium salt group per molecule or a quaternary ammonium - functionalized polyhedral oligomeric silsesquioxane ( Q - POSS ) were measured with SFG in air , water , and artificial seawater ( ASW ) to investigate the relationships between the interfacial surface structures of these materials and their antifouling properties .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "ammonium", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "polyhedral oligomeric silsesquioxane", "entity_type": "Chemical", "pos": [154, 190]}, {"entity": "POSS", "entity_type": "Chemical", "pos": [197, 201]}], "task": "NER"}
{"text": "Although previous studies have shown that the above - mentioned materials are promising contact - active antifouling coatings , slight variations of the QAS structure can lead to substantial differences in the antifouling performance .", "entity": [], "task": "NER"}
{"text": "Indeed , the SFG results presented here indicated that the surface structures of these materials depend on several factors , such as the extent of quaternization , the molecular weight of the PDMS component , and the functional groups of the QAS used for incorporation into the PDMS matrix .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [192, 196]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [278, 282]}], "task": "NER"}
{"text": "It was concluded that in aqueous environments a lower extent of Q - POSS quaternization and the use of ethoxy ( instead of methoxy ) functional groups for QAS incorporation facilitated the extension of the alkyl chains away from the nitrogen atom of the QAS on the surface .", "entity": [{"entity": "POSS", "entity_type": "Chemical", "pos": [68, 72]}, {"entity": "ethoxy", "entity_type": "Chemical", "pos": [103, 109]}, {"entity": "methoxy", "entity_type": "Chemical", "pos": [123, 130]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [233, 241]}], "task": "NER"}
{"text": "The SFG results correlated well with the antifouling activity studies that indicated that the coatings exhibiting a lower concentration of longer alkyl chains protruding out of the surface can neutralize microorganisms more effectively , ultimately leading to better antifouling performance .", "entity": [], "task": "NER"}
{"text": "Furthermore , the results of this study provide additional evidence that incorporated QAS exert their antimicrobial activity through a two - step interaction .", "entity": [], "task": "NER"}
{"text": "The first step is the adsorption of the bacteria on the surface as a result of the electrostatic attraction between the negatively charged microorganisms and the positively charged QAS nitrogen atoms on the surface .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [185, 193]}], "task": "NER"}
{"text": "The second step is the disruption of the cell membranes by the penetration of the QAS long , extended alkyl chains .", "entity": [], "task": "NER"}
{"text": "Glargine safety , diabetes and cancer .", "entity": [], "task": "NER"}
{"text": "INTRODUCTION : In 2009 , several epidemiological studies suggested a higher frequency of malignancy in insulin glargine - treated patients .", "entity": [], "task": "NER"}
{"text": "A number of follow - up epidemiological population studies as well as two randomized , controlled clinical studies , one a 5000 - patient retinopathy study and the other a 12 , 000 - patient cardiovascular outcomes trial ( ORIGIN ) , found no higher frequency of malignancy in glargine - treated patients .", "entity": [], "task": "NER"}
{"text": "AREAS COVERED : We reviewed the existing literature as well as U . S .", "entity": [], "task": "NER"}
{"text": "FDA records to investigate the association of cancer , diabetes , and insulin .", "entity": [], "task": "NER"}
{"text": "There is a 20 - 40 % higher incidence of malignancy in type 2 diabetes patients .", "entity": [], "task": "NER"}
{"text": "Certain cancers are more common , including hepatocellular and pancreatic carcinoma , colorectal cancer , renal cancer , and breast and endometrial cancer , and non - Hodgkin ' s lymphoma .", "entity": [], "task": "NER"}
{"text": "There are numerous inter - related factors which may promote both diabetes and malignancy , including dietary patterns , obesity , insulin resistance , and alcoholism .", "entity": [], "task": "NER"}
{"text": "Patients who receive insulin treatment are typically older and \" sicker \" than those who receive oral agents .", "entity": [], "task": "NER"}
{"text": "EXPERT OPINION : It is very difficult to prove causal associations between diabetes and cancer due to the host of confounding factors .", "entity": [], "task": "NER"}
{"text": "The hypothesis that hyperinsulinemia and IGF - 1 receptor activation promote cancer is strong , but confounded by the association of hyperinsulinemia with obesity , which separately promotes malignancy .", "entity": [], "task": "NER"}
{"text": "Although statistical techniques to adjust for confounding variables can improve epidemiological comparisons , the lesson of the glargine cancer controversy is that controlled clinical trials are the only means to definitely prove hypotheses .", "entity": [], "task": "NER"}
{"text": "Transforming drug discovery and development through innovation : past , present and future .", "entity": [], "task": "NER"}
{"text": "This annual meeting began in 1998 and was the first industry - led event to focus on the specific needs of industry researchers .", "entity": [], "task": "NER"}
{"text": "The goal of Clinical and Pharmaceutical Solutions Through Analysis ( CPSA ) is to provide an in - depth review of innovative technology and industry practices through open discussion of industry - related issues and needs .", "entity": [], "task": "NER"}
{"text": "Education and specialized training are the foundation of all CPSA events .", "entity": [], "task": "NER"}
{"text": "As the industry has evolved so has CPSA .", "entity": [], "task": "NER"}
{"text": "Thus , the year the name was changed from Chemical and Pharmaceutical Structural Analysis to CPSA was to reflect the growing focus on clinical applications and the emergence of personalized medicine .", "entity": [], "task": "NER"}
{"text": "Most importantly , the CPSA annual meeting has retained the same high - quality scientific content , open interaction from industry opinion leaders and a collegial environment .", "entity": [], "task": "NER"}
{"text": "Personalized medicine for targeted and platinum - based chemotherapy of lung and bladder cancer .", "entity": [{"entity": "platinum", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "The personalized medicine revolution is occurring for cancer chemotherapy .", "entity": [], "task": "NER"}
{"text": "Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors , and are being linked to the selection of treatment protocols .", "entity": [], "task": "NER"}
{"text": "This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum - based chemotherapy .", "entity": [{"entity": "platinum", "entity_type": "Chemical", "pos": [146, 154]}], "task": "NER"}
{"text": "Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA .", "entity": [{"entity": "Platinum", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Platinum - DNA adduct levels in patient tissues have been correlated to response and survival .", "entity": [{"entity": "Platinum", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications , termed diagnostic microdosing , prior to the initiation of full - dose therapy .", "entity": [], "task": "NER"}
{"text": "The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications .", "entity": [], "task": "NER"}
{"text": "Fbxl10 / Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [57, 60]}], "task": "NER"}
{"text": "Polycomb repressive complex 1 ( PRC1 ) catalyzes lysine 119 monoubiquitylation on H2A ( H2AK119ub1 ) and regulates pluripotency in embryonic stem cells ( ESCs ) .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [49, 55]}], "task": "NER"}
{"text": "However , the mechanisms controlling the binding of PRC1 to genomic sites and its catalytic activity are poorly understood .", "entity": [], "task": "NER"}
{"text": "Here , we show that Fbxl10 interacts with Ring1B and Nspc1 , forming a noncanonical PRC1 that is required for H2AK119ub1 in mouse ESCs .", "entity": [], "task": "NER"}
{"text": "Genome - wide analyses reveal that Fbxl10 preferentially binds to CpG islands and colocalizes with Ring1B on Polycomb target genes .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [66, 69]}], "task": "NER"}
{"text": "Notably , Fbxl10 depletion causes a decrease in Ring1B binding to target genes and a major loss of H2AK119ub1 .", "entity": [], "task": "NER"}
{"text": "Furthermore , genetic analyses demonstrate that Fbxl10 DNA binding capability and integration into PRC1 are required for H2AK119 ubiquitylation .", "entity": [], "task": "NER"}
{"text": "ESCs lacking Fbxl10 , like previously characterized Polycomb mutants , cannot differentiate properly .", "entity": [], "task": "NER"}
{"text": "These results demonstrate that Fbxl10 has a key role in regulating Ring1B recruitment to its target genes and H2AK119 ubiquitylation in ESCs .", "entity": [], "task": "NER"}
{"text": "Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [26, 28]}], "task": "NER"}
{"text": "Nitric oxide ( NO ) produced by the endothelial NO synthase ( eNOS ) is an antihypertensive , antithrombotic and anti - atherosclerotic molecule .", "entity": [{"entity": "Nitric oxide", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "NO", "entity_type": "Chemical", "pos": [15, 17]}, {"entity": "NO", "entity_type": "Chemical", "pos": [48, 50]}], "task": "NER"}
{"text": "Hypercholesterolemia leads to a reduction in vascular NO bioavailability .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "This is attributed to a dysfunction of the eNOS enzyme and a reduced eNOS activity .", "entity": [], "task": "NER"}
{"text": "NADPH oxidase - mediated oxidative stress leads to oxidation of tetrahydrobiopterin ( BH4 ) , the essential cofactor of eNOS .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "tetrahydrobiopterin", "entity_type": "Chemical", "pos": [64, 83]}, {"entity": "BH4", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "In BH4 deficiency , oxygen reduction uncouples from NO synthesis , thereby converting eNOS to a superoxide - producing enzyme .", "entity": [{"entity": "BH4", "entity_type": "Chemical", "pos": [3, 6]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "NO", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [96, 106]}], "task": "NER"}
{"text": "As a consequence of eNOS uncoupling , NO production is reduced and the pre - existing oxidative stress is enhanced , which contribute significantly to atherogenesis .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [21, 23]}], "task": "NER"}
{"text": "Therefore , pharmacological approaches that prevent eNOS uncoupling and enhance eNOS activity are of therapeutic interest .", "entity": [], "task": "NER"}
{"text": "Angiotensin - converting enzyme inhibitors , AT1 receptor blockers , statins , nebivolol and resveratrol have been shown to reverse eNOS uncoupling and to stimulate eNOS activity concurrently .", "entity": [{"entity": "nebivolol", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "Molecular mechanisms of the aforementioned drugs / compounds on eNOS functionality is summarized and discussed in this review .", "entity": [], "task": "NER"}
{"text": "How sugar tunes your clock .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [4, 9]}], "task": "NER"}
{"text": "While cellular circadian clocks are set by the light / dark cycle , these clocks can be reset by what we eat .", "entity": [], "task": "NER"}
{"text": "Two papers in this issue of Cell Metabolism reveal that O - GlcNAcylation of clock proteins , which is dependent on nutrients , adjusts our circadian clock ( Kaasik et al . , 2013 ; Li et al . , 2013 ) .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [56, 57]}], "task": "NER"}
{"text": "Synthesis and characterization of novel quick - release propofol prodrug via lactonization .", "entity": [{"entity": "propofol", "entity_type": "Chemical", "pos": [56, 64]}], "task": "NER"}
{"text": "The water - soluble derivatives of propofol have gained attention as a method to increase solubility of propofol .", "entity": [{"entity": "propofol", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "According to the principle of lactonization , the lead compound HX0969 was synthesized first and then the pharmacological features of HX0969 were evaluated in a comparison with those of propofol in the SD rats .", "entity": [{"entity": "HX0969", "entity_type": "Chemical", "pos": [64, 70]}, {"entity": "HX0969", "entity_type": "Chemical", "pos": [134, 140]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [186, 194]}], "task": "NER"}
{"text": "Then , HX0969 disodium phosphate monoester ( HX0969W ) and glycine ester trifluoroacetic acid salt ( HX101230 ) were synthesized , and their pharmacological features were compared with those of Lusedra (R) , which has been recognized and marketed as a water - soluble prodrug of propofol since 2008 .", "entity": [{"entity": "HX0969 disodium phosphate monoester", "entity_type": "Chemical", "pos": [7, 42]}, {"entity": "HX0969W", "entity_type": "Chemical", "pos": [45, 52]}, {"entity": "glycine ester trifluoroacetic acid salt", "entity_type": "Chemical", "pos": [59, 98]}, {"entity": "HX101230", "entity_type": "Chemical", "pos": [101, 109]}, {"entity": "Lusedra", "entity_type": "Chemical", "pos": [194, 201]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [279, 287]}], "task": "NER"}
{"text": "The results showed that HX0969 could produce an anesthetic effect within a few seconds ( 3 . 6 +/- 3 . 0s ) and its therapeutic index was 4 . 66 in the SD rat .", "entity": [{"entity": "HX0969", "entity_type": "Chemical", "pos": [24, 30]}], "task": "NER"}
{"text": "The pharmacodynamic characteristics of HX0969W were similar to those of the Lusedra (R) .", "entity": [{"entity": "HX0969W", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "Lusedra", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "HX101230 could still produce an anesthetic effect within 60s in the rats though its therapeutic index was not so high ( TI = 2 . 96 ) .", "entity": [{"entity": "HX101230", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Therefore , our study has indicated that HX0969 is a potentially useful lead compound of propofol derivative .", "entity": [{"entity": "HX0969", "entity_type": "Chemical", "pos": [41, 47]}, {"entity": "propofol", "entity_type": "Chemical", "pos": [89, 97]}], "task": "NER"}
{"text": "Its rapid anesthetic effect is probably associated with lactonization .", "entity": [], "task": "NER"}
{"text": "Chemical probes of a trisubstituted pyrrole to identify its protein target ( s ) in Plasmodium sporozoites .", "entity": [{"entity": "pyrrole", "entity_type": "Chemical", "pos": [36, 43]}], "task": "NER"}
{"text": "Malaria is a disease that has a major impact in many developing nations , especially on the African continent .", "entity": [], "task": "NER"}
{"text": "There is a need to develop new therapeutics and prophylactic treatments against it .", "entity": [], "task": "NER"}
{"text": "A trisubstituted pyrrole was recently found to inhibit infection of mammalian hepatocytes by Plasmodium sporozoites , but the target of this agent is not known .", "entity": [{"entity": "pyrrole", "entity_type": "Chemical", "pos": [17, 24]}], "task": "NER"}
{"text": "In this study trisubstituted pyrrole derivatives with different substituents on a piperidinyl nitrogen were prepared .", "entity": [{"entity": "pyrrole", "entity_type": "Chemical", "pos": [29, 36]}, {"entity": "piperidinyl nitrogen", "entity_type": "Chemical", "pos": [82, 102]}], "task": "NER"}
{"text": "We determined if modifications of the piperidinyl nitrogen would accommodate a drug - biotin linking strategy for affinity purification of the trisubstituted pyrrole ' s target protein ( s ) .", "entity": [{"entity": "piperidinyl nitrogen", "entity_type": "Chemical", "pos": [38, 58]}, {"entity": "biotin", "entity_type": "Chemical", "pos": [86, 92]}, {"entity": "pyrrole", "entity_type": "Chemical", "pos": [158, 165]}], "task": "NER"}
{"text": "Growth factor delivery from hydrogel particle aggregates to promote tubular regeneration after acute kidney injury .", "entity": [], "task": "NER"}
{"text": "Local delivery of growth factors ( GFs ) can accelerate regeneration of injured tissue , but for many medical applications , injectable GF delivery systems are required for clinical success .", "entity": [], "task": "NER"}
{"text": "Viscoelastic , injectable aggregates of micrometer - sized hydrogel particles made of multiarmed polyethylene glycol ( starPEG ) and heparin were prepared and tested for site - specific paracrine stimulation of tissue regeneration .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [97, 116]}], "task": "NER"}
{"text": "Heparin was used as it binds , protects and releases numerous GFs .", "entity": [], "task": "NER"}
{"text": "Hydrogel based delivery of basic fibroblast growth factor ( bFGF ) and murine epidermal growth factor ( EGF ) was monitored utilizing enzyme - linked immunosorbent assay ( ELISA ) .", "entity": [], "task": "NER"}
{"text": "bFGF was released slowly because of its high affinity to the heparin while the significantly higher release of the non - specific binding EGF was controlled by diffusion only .", "entity": [], "task": "NER"}
{"text": "To investigate GF delivery in vivo , a hydrogel loaded with murine EGF or bFGF was injected subcapsularly into the left kidney of mice with experimental acute kidney injury caused by glycerol induced rhabdomyolysis .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [183, 191]}], "task": "NER"}
{"text": "Visual examination confirmed sustained stability of the injected gel aggregates during the timescale of the experiment .", "entity": [], "task": "NER"}
{"text": "The number of proliferating kidney tubular epithelial cells was quantified both in the injected kidney and the non - injected contralateral kidney .", "entity": [], "task": "NER"}
{"text": "bFGF delivery from hydrogels induced a significant increase in cell proliferation in the injected kidney , although small effects were also seen in the non - injected kidney due to a systemic effect .", "entity": [], "task": "NER"}
{"text": "EGF delivery strongly increased cell proliferation for both kidneys , but also showed a local effect on the injected kidney .", "entity": [], "task": "NER"}
{"text": "The hydrogel without loaded GFs was used as a control and showed no increase in cell proliferation .", "entity": [], "task": "NER"}
{"text": "Our results suggest that this novel starPEG - heparin hydrogel system can be an effective approach to deliver GFs locally .", "entity": [], "task": "NER"}
{"text": "Ozonolysis efficiency and safety evaluation of aflatoxin B1 in peanuts .", "entity": [{"entity": "aflatoxin B1", "entity_type": "Chemical", "pos": [47, 59]}], "task": "NER"}
{"text": "Ozonolysis efficiency of aflatoxin - contaminated peanuts ( ACPs ) was investigated , and the safety of ACPs untreated / treated by ozone was evaluated after 28 - day intragastrically administration in male and female Wistar rats .", "entity": [{"entity": "aflatoxin", "entity_type": "Chemical", "pos": [25, 34]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [132, 137]}], "task": "NER"}
{"text": "89 . 40 % of aflatoxin B1 ( AFB1 ) in peanuts was decomposed by ozone with a concentration of 50mg / L , flow rate of 5L / min for 60h .", "entity": [{"entity": "aflatoxin B1", "entity_type": "Chemical", "pos": [13, 25]}, {"entity": "AFB1", "entity_type": "Chemical", "pos": [28, 32]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [64, 69]}], "task": "NER"}
{"text": "After 60h , the ozonolysis efficiency of AFB1 was not further improved .", "entity": [{"entity": "AFB1", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "In the subchronic toxicity experiment , all rats did not have unusual changes in behavior , and no signs of intoxication were observed except for several dead rats due to inappropriate gavage or anesthesia .", "entity": [], "task": "NER"}
{"text": "The results of subchronic toxicity indicated that rats fed on ACPs alone had significantly decreased in body weight gain and feed conversion efficiency .", "entity": [], "task": "NER"}
{"text": "Most serum biochemical indexes of rats had apparently changed compared with those in the negative control , and gender difference significantly affected most indexes of subchronic toxicity except for the ratios of organ to body weight and histopathological observation .", "entity": [], "task": "NER"}
{"text": "Rats fed on ACPs treated by ozone showed significant beneficial health effects .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [28, 33]}], "task": "NER"}
{"text": "All the results suggested that the deleterious effects of AFB1 could be highly reduced by ozone , and ozone itself did not show any toxic effects on animals in this processing .", "entity": [{"entity": "AFB1", "entity_type": "Chemical", "pos": [58, 62]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [90, 95]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [102, 107]}], "task": "NER"}
{"text": "Elevation of 4 - hydroxynonenal and malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1 - bromopropane .", "entity": [{"entity": "4 - hydroxynonenal", "entity_type": "Chemical", "pos": [13, 31]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [36, 51]}, {"entity": "1 - bromopropane", "entity_type": "Chemical", "pos": [141, 157]}], "task": "NER"}
{"text": "1 - Bromopropane ( 1 - BP ) , an alternative to ozone - depleting solvents ( ODS ) , exhibits central nervous system ( CNS ) toxicity in animals and humans .", "entity": [{"entity": "1 - Bromopropane", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "1 - BP", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [48, 53]}], "task": "NER"}
{"text": "This study was designed to relate CNS damage by Morris water maze ( MWM ) test and oxidative stress to 1 - BP exposure in the rat .", "entity": [{"entity": "1 - BP", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "Male Wistar rats were randomly divided into 4 groups ( n = 10 ) , and treated with 0 , 200 , 400 and 800mg / kgbw 1 - BP for consecutive 12 days , respectively .", "entity": [{"entity": "1 - BP", "entity_type": "Chemical", "pos": [114, 120]}], "task": "NER"}
{"text": "From day 8 to day 12 of the experiment , MWM test was employed to assess the cognitive function of rats .", "entity": [], "task": "NER"}
{"text": "The cerebral cortex of rats was obtained immediately following the 24h after MWM test conclusion .", "entity": [], "task": "NER"}
{"text": "Glutathione ( GSH ) , oxidized glutathione ( GSSG ) and total thiol ( total - SH ) content , GSH reductase ( GR ) and GSH peroxidase ( GSH - Px ) activities , malondialdehyde ( MDA ) level , as well as 4 - hydroxynonenal ( 4 - HNE ) and MDA modified proteins in homogenates of cerebral cortex were measured .", "entity": [{"entity": "Glutathione", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "oxidized glutathione", "entity_type": "Chemical", "pos": [22, 42]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [62, 67]}, {"entity": "SH", "entity_type": "Chemical", "pos": [78, 80]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [118, 121]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [135, 138]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [159, 174]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [177, 180]}, {"entity": "4 - hydroxynonenal", "entity_type": "Chemical", "pos": [202, 220]}, {"entity": "4 - HNE", "entity_type": "Chemical", "pos": [223, 230]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [237, 240]}], "task": "NER"}
{"text": "The obtained results showed that 1 - BP led to cognitive dysfunction of rats , which was evidenced by delayed escape latency time and swimming distances in MWM performance .", "entity": [{"entity": "1 - BP", "entity_type": "Chemical", "pos": [33, 39]}], "task": "NER"}
{"text": "GSH and total - SH content , GSH / GSSG ratio , GR activity significantly decreased in cerebral cortex of rats , coupling with the increase of MDA level .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "SH", "entity_type": "Chemical", "pos": [16, 18]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [35, 39]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [143, 146]}], "task": "NER"}
{"text": "4 - HNE and MDA modified protein levels obviously elevated after 1 - BP exposure .", "entity": [{"entity": "4 - HNE", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "1 - BP", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "GSH - Px activities in cerebral cortex of rats also increased .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "These data suggested that 1 - BP resulted in enhanced lipid peroxidation of brain , which might play an important role in CNS damage induced by 1 - BP .", "entity": [{"entity": "1 - BP", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "1 - BP", "entity_type": "Chemical", "pos": [144, 150]}], "task": "NER"}
{"text": "RNA polymerase II acts as an RNA - dependent RNA polymerase to extend and destabilize a non - coding RNA .", "entity": [], "task": "NER"}
{"text": "RNA polymerase II ( Pol II ) is a well - characterized DNA - dependent RNA polymerase , which has also been reported to have RNA - dependent RNA polymerase ( RdRP ) activity .", "entity": [], "task": "NER"}
{"text": "Natural cellular RNA substrates of mammalian Pol II , however , have not been identified and the cellular function of the Pol II RdRP activity is unknown .", "entity": [], "task": "NER"}
{"text": "We found that Pol II can use a non - coding RNA , B2 RNA , as both a substrate and a template for its RdRP activity .", "entity": [], "task": "NER"}
{"text": "Pol II extends B2 RNA by 18 nt on its 3 ' - end in an internally templated reaction .", "entity": [], "task": "NER"}
{"text": "The RNA product resulting from extension of B2 RNA by the Pol II RdRP can be removed from Pol II by a factor present in nuclear extracts .", "entity": [], "task": "NER"}
{"text": "Treatment of cells with alpha - amanitin or actinomycin D revealed that extension of B2 RNA by Pol II destabilizes the RNA .", "entity": [{"entity": "alpha - amanitin", "entity_type": "Chemical", "pos": [24, 40]}, {"entity": "actinomycin D", "entity_type": "Chemical", "pos": [44, 57]}], "task": "NER"}
{"text": "Our studies provide compelling evidence that mammalian Pol II acts as an RdRP to control the stability of a cellular RNA by extending its 3 ' - end .", "entity": [], "task": "NER"}
{"text": "Effect of repeated dosing on rifampin exposure in BALB / c mice .", "entity": [{"entity": "rifampin", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "The discovery of novel therapeutics for the treatment of tuberculosis involves routine testing in a mouse model over four weeks of daily dosing with test compounds .", "entity": [], "task": "NER"}
{"text": "In this model , daily oral administration of rifampin ( 10mg / kg ) showed significantly lower plasma exposure on day 5 compared to day 1 .", "entity": [{"entity": "rifampin", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "The absence of PXR - mediated induction of mouse Cyp3a isoforms was confirmed in the present study by incubating liver microsomes prepared from control and rifampin treated mice with probe substrates of CYP3A .", "entity": [{"entity": "rifampin", "entity_type": "Chemical", "pos": [156, 164]}], "task": "NER"}
{"text": "To test whether the reduction in exposure was due to Pgp - mediated efflux , verapamil , a known Pgp inhibitor , was dosed to the rifampin pre - treated mice which led to an increase in exposure to that obtained after a single dose of rifampin , suggesting the role of Pgp induction in reducing exposure to rifampin .", "entity": [{"entity": "verapamil", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [235, 243]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [307, 315]}], "task": "NER"}
{"text": "To further confirm Pgp induction in rifampin treated mice , digoxin , a known substrate of Pgp , was administered to the rifampin pre - treated mice , and a significant drop in the digoxin exposure was observed compared to the control group .", "entity": [{"entity": "rifampin", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "digoxin", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [121, 129]}, {"entity": "digoxin", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "Collectively , our results show that repeated administration of rifampin in mice leads to a reduction in oral exposure due to induction of Pgp - mediated efflux of rifampin , and not via induction of CYP3A isoforms .", "entity": [{"entity": "rifampin", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "rifampin", "entity_type": "Chemical", "pos": [164, 172]}], "task": "NER"}
{"text": "Mini - review : Foldosome regulation of androgen receptor action in prostate cancer .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "Steroid hormone receptors play diverse roles in many aspects of human physiology including cell division , apoptosis and homeostasis , tissue differentiation , sexual development and response to stress .", "entity": [{"entity": "Steroid hormone", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "These ligand - activated transcription factors require the functional activity of numerous chaperone and chaperone - associated proteins , collectively termed the foldosome , at the crucial step of ligand recognition and binding .", "entity": [], "task": "NER"}
{"text": "Since the initial isolation of foldosome components and pioneering research by Pratt , Toft and colleagues we understand much regarding cytosolic receptor function .", "entity": [], "task": "NER"}
{"text": "The classical view , that the role of foldosome components is restricted to the cytosol , has been modified over recent years by research highlighting additional roles of chaperone proteins in nuclear translocation and target gene expression .", "entity": [], "task": "NER"}
{"text": "Further , dysregulation of chaperone activity and expression has been implicated in various cancers , including breast and prostate cancer .", "entity": [], "task": "NER"}
{"text": "Consequently , the foldosome provides an attractive therapeutic target in steroid hormone receptor - driven malignancies .", "entity": [{"entity": "steroid hormone", "entity_type": "Chemical", "pos": [74, 89]}], "task": "NER"}
{"text": "This review summarises current knowledge of how the foldosome impacts upon androgen receptor signalling , which is the key therapeutic target on prostate cancer , and how foldosome components may be used as biomarkers or therapeutic targets in this disease .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "Interspecies extrapolation based on the RepDose database - - a probabilistic approach .", "entity": [], "task": "NER"}
{"text": "Repeated dose toxicity studies from the RepDose database ( DB ) were used to determine interspecies differences for rats and mice .", "entity": [], "task": "NER"}
{"text": "NOEL ( no observed effect level ) ratios based on systemic effects were investigated for three different types of exposure : inhalation , oral food / drinking water and oral gavage .", "entity": [], "task": "NER"}
{"text": "Furthermore , NOEL ratios for local effects in inhalation studies were evaluated .", "entity": [], "task": "NER"}
{"text": "On the basis of the NOEL ratio distributions , interspecies assessment factors ( AF ) are evaluated .", "entity": [], "task": "NER"}
{"text": "All data sets were best described by a lognormal distribution .", "entity": [], "task": "NER"}
{"text": "No difference was seen between inhalation and oral exposure for systemic effects .", "entity": [], "task": "NER"}
{"text": "Rats and mice were on average equally sensitive at equipotent doses with geometric mean ( GM ) values of 1 and geometric standard deviation ( GSD ) values ranging from 2 . 30 to 3 . 08 .", "entity": [], "task": "NER"}
{"text": "The local AF based on inhalation exposure resulted in a similar distribution with GM values of 1 and GSD values between 2 . 53 and 2 . 70 .", "entity": [], "task": "NER"}
{"text": "Our analysis confirms former analyses on interspecies differences , including also dog and human data .", "entity": [], "task": "NER"}
{"text": "Furthermore it supports the principle of allometric scaling according to caloric demand in the case that body doses are applied .", "entity": [], "task": "NER"}
{"text": "In conclusion , an interspecies distribution animal / human with a GM equal to allometric scaling and a GSD of 2 . 5 was derived .", "entity": [], "task": "NER"}
{"text": "Molecular dissection of botulinum neurotoxin reveals interdomain chaperone function .", "entity": [], "task": "NER"}
{"text": "Clostridium botulinum neurotoxin ( BoNT ) is a multi - domain protein made up of the approximately 100 kDa heavy chain ( HC ) and the approximately 50 kDa light chain ( LC ) .", "entity": [], "task": "NER"}
{"text": "The HC can be further subdivided into two halves : the N - terminal translocation domain ( TD ) and the C - terminal Receptor Binding Domain ( RBD ) .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [55, 56]}, {"entity": "C", "entity_type": "Chemical", "pos": [104, 105]}], "task": "NER"}
{"text": "We have investigated the minimal requirements for channel activity and LC translocation .", "entity": [], "task": "NER"}
{"text": "We utilize a cellular protection assay and a single channel / single molecule LC translocation assay to characterize in real time the channel and chaperone activities of BoNT / A truncation constructs in Neuro 2A cells .", "entity": [], "task": "NER"}
{"text": "The unstructured , elongated belt region of the TD is demonstrated to be dispensable for channel activity , although may be required for productive LC translocation .", "entity": [], "task": "NER"}
{"text": "We show that the RBD is not necessary for channel activity or LC translocation , however it dictates the pH threshold of channel insertion into the membrane .", "entity": [], "task": "NER"}
{"text": "These findings indicate that each domain functions as a chaperone for the others in addition to their individual functions , working in concert to achieve productive intoxication .", "entity": [], "task": "NER"}
{"text": "Photochemical activation of TRPA1 channels in neurons and animals .", "entity": [], "task": "NER"}
{"text": "Optogenetics is a powerful research tool because it enables high - resolution optical control of neuronal activity .", "entity": [], "task": "NER"}
{"text": "However , current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors .", "entity": [], "task": "NER"}
{"text": "Here , we identify optovin , a small molecule that enables repeated photoactivation of motor behaviors in wild - type zebrafish and mice .", "entity": [{"entity": "optovin", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "To our surprise , optovin ' s behavioral effects are not visually mediated .", "entity": [{"entity": "optovin", "entity_type": "Chemical", "pos": [18, 25]}], "task": "NER"}
{"text": "Rather , photodetection is performed by sensory neurons expressing the cation channel TRPA1 .", "entity": [], "task": "NER"}
{"text": "TRPA1 is both necessary and sufficient for the optovin response .", "entity": [{"entity": "optovin", "entity_type": "Chemical", "pos": [47, 54]}], "task": "NER"}
{"text": "Optovin activates human TRPA1 via structure - dependent photochemical reactions with redox - sensitive cysteine residues .", "entity": [{"entity": "Optovin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "In animals with severed spinal cords , optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination .", "entity": [{"entity": "optovin", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "These studies identify a light - based strategy for controlling endogenous TRPA1 receptors in vivo , with potential clinical and research applications in nontransgenic animals , including humans .", "entity": [], "task": "NER"}
{"text": "Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin : molecular mechanisms unveiled by gene expression profiling .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [72, 81]}], "task": "NER"}
{"text": "Previously we reported that liposomal cisplatin ( CDDP ) overcomes CDDP resistance of ovarian A2780cis cancer cells ( Krieger et al . , Int . J . Pharm . 389 , 2010 , 10 - 17 ) .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [54, 58]}], "task": "NER"}
{"text": "This suggests that the mode of action of liposomal CDDP is different from the free drug .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "To gain insight into mechanisms of liposomal CDDP activity , we performed a transcriptome analysis of untreated A2780cis cells , and A2780cis cells in response to exposure with IC50 values of free or liposomal CDDP .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [210, 214]}], "task": "NER"}
{"text": "A process network analysis of upregulated genes showed that liposomal CDDP induced a highly different gene expression profile in comparison to the free drug .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "p53 was identified as a key player directing transcriptional responses to free or liposomal CDDP .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [92, 96]}], "task": "NER"}
{"text": "The free drug induced expression of essential genes of the intrinsic ( mitochondrial ) apoptosis pathway ( BAX , BID , CASP9 ) most likely through p38MAPK activation .", "entity": [], "task": "NER"}
{"text": "In contrast , liposomal CDDP induced expression of genes from DNA damage pathways and several genes of the extrinsic pathway of apoptosis ( TNFRSF10B - DR5 , CD70 - TNFSF7 ) .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [24, 28]}], "task": "NER"}
{"text": "It thus appears that liposomal CDDP overcomes CDDP resistance by inducing DNA damage and in consequence programmed cell death by the extrinsic pathway .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "Predictions from gene expression data with respect to apoptosis activation were confirmed at the protein level by an apoptosis antibody array .", "entity": [], "task": "NER"}
{"text": "This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal CDDP as promising strategy for the treatment of CDDP resistant ovarian carcinomas .", "entity": [{"entity": "CDDP", "entity_type": "Chemical", "pos": [91, 95]}, {"entity": "CDDP", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "Protective effect of Codium fragile against UVB - induced pro - inflammatory and oxidative damages in HaCaT cells and BALB / c mice .", "entity": [], "task": "NER"}
{"text": "Acute exposure to ultraviolet ( UV ) radiation causes pro - inflammatory responses via diverse mechanisms including oxidative stress .", "entity": [], "task": "NER"}
{"text": "Codium fragile is a green alga of Codiales family and has been reported to exhibit anti - edema , anti - allergic , anti - protozoal and anti - mycobacterial activities .", "entity": [], "task": "NER"}
{"text": "In this study , we have investigated a novel anti - inflammatory potential of C . fragile using in vitro cell culture as well as in vivo animal models .", "entity": [], "task": "NER"}
{"text": "In HaCaT cells , buthanol and ethylacetate fractions of 80 % methanol C . fragile extract ( CFB or CFE ) and a single compound , clerosterol ( CLS ) isolated from CFE attenuated UVB ( 60mJ / cm ( 2 ) ) - induced cytotoxicity and reduced expression of pro - inflammatory proteins including cyclooxygenase - 2 ( COX - 2 ) , inducible nitric oxide synthase ( iNOS ) , and tumor necrosis factor - alpha ( TNF - alpha ) .", "entity": [{"entity": "buthanol", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "ethylacetate", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "clerosterol", "entity_type": "Chemical", "pos": [129, 140]}, {"entity": "CLS", "entity_type": "Chemical", "pos": [143, 146]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [332, 344]}], "task": "NER"}
{"text": "Moreover , CFB , CFE and CLS effectively suppressed UVB - induced production of pro - inflammatory mediators such as prostaglandin E2 ( PGE2 ) and nitric oxide ( NO ) .", "entity": [{"entity": "CLS", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "prostaglandin E2", "entity_type": "Chemical", "pos": [117, 133]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [147, 159]}, {"entity": "NO", "entity_type": "Chemical", "pos": [162, 164]}], "task": "NER"}
{"text": "In another experiment , topical application of CFB , CFE or CLS prior to UVB irradiation ( 200mJ / cm ( 2 ) ) on BALB / c mice , inhibited the UVB - elevated protein levels of COX - 2 , iNOS , and TNF - alpha .", "entity": [{"entity": "CLS", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "Furthermore , CFB , CFE and CLS suppressed oxidative damages caused by UVB irradiation for example lipid peroxidation and / or protein carbonylation , which seemed to be mediated by up - regulation of antioxidant defense enzymes .", "entity": [{"entity": "CLS", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "These results suggest that C . fragile could be an effective therapeutic agent providing protection against UVB - induced inflammatory and oxidative skin damages .", "entity": [], "task": "NER"}
{"text": "Involvement of organic anion - transporting polypeptides in the hepatic uptake of dioscin in rats and humans .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [82, 89]}], "task": "NER"}
{"text": "The objective of this study was to clarify the mechanism underlying hepatic uptake of dioscin ( diosgenyl 2 , 4 - di - O - a - L - rhamnopyranosyl - p - D - glucopyranoside ) , an herbal ingredient with antihepatitis activity , in rats and humans .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [86, 93]}, {"entity": "diosgenyl 2 , 4 - di - O - a - L - rhamnopyranosyl - p - D - glucopyranoside", "entity_type": "Chemical", "pos": [96, 172]}], "task": "NER"}
{"text": "The liver uptake index ( LUI ) in vivo , perfused rat liver in situ , rat liver slices , isolated rat hepatocytes , and human organic anion - transporting polypeptide ( OATP ) - transfected cells in vitro were used to evaluate hepatic uptake of dioscin .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [245, 252]}], "task": "NER"}
{"text": "Values of 11 . 9 % +/- 1 . 6 % and 15 . 0 % +/- 0 . 9 % of dose for uptake of dioscin were observed by LUI in vivo and perfused rat livers in situ , respectively .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [78, 85]}], "task": "NER"}
{"text": "The time course of dioscin uptake by rat liver slices was temperature - dependent .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "Uptake of dioscin by rat liver slices and isolated rat hepatocytes was inhibited significantly by Oatp modulators , such as ibuprofen ( Oatp1a1 inhibitor ) , digoxin ( Oatp1a4 substrate ) , and glycyrrhizic acid ( Oatp1b2 inhibitor ) , but not by TEA or p - aminohippurate .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [10, 17]}, {"entity": "ibuprofen", "entity_type": "Chemical", "pos": [124, 133]}, {"entity": "digoxin", "entity_type": "Chemical", "pos": [158, 165]}, {"entity": "glycyrrhizic acid", "entity_type": "Chemical", "pos": [194, 211]}, {"entity": "TEA", "entity_type": "Chemical", "pos": [247, 250]}, {"entity": "p - aminohippurate", "entity_type": "Chemical", "pos": [254, 272]}], "task": "NER"}
{"text": "Uptake of dioscin in rat hepatocytes and OATP1B3 - human embryonic kidney ( HEK ) 293 cells indicated a saturable process with a Km of 3 . 75 +/- 0 . 51 mu M and 2 . 08 +/- 0 . 27 mu M , respectively .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [10, 17]}], "task": "NER"}
{"text": "( - ) - Epigallocatechin gallate , cyclosporin A , rifampicin , and telmisartan inhibited transport of dioscin in OATP1B3 - HEK293 cells .", "entity": [{"entity": "( - ) - Epigallocatechin gallate", "entity_type": "Chemical", "pos": [0, 32]}, {"entity": "cyclosporin A", "entity_type": "Chemical", "pos": [35, 48]}, {"entity": "rifampicin", "entity_type": "Chemical", "pos": [51, 61]}, {"entity": "telmisartan", "entity_type": "Chemical", "pos": [68, 79]}, {"entity": "dioscin", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "However , transcellular transport of dioscin in OATP1B1 - or OATP1B1 / multidrug resistance - associated protein 2 - Madin - Darby canine kidney strain II cells was not observed .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [37, 44]}], "task": "NER"}
{"text": "These results indicate that hepatic uptake of dioscin is involved in OATP1B3 in humans , and multiple Oatps might participate in this process in rats .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Study of PcaV from Streptomyces coelicolor yields new insights into ligand - responsive MarR family transcription factors .", "entity": [], "task": "NER"}
{"text": "MarR family proteins constitute a group of > 12 000 transcriptional regulators encoded in bacterial and archaeal genomes that control gene expression in metabolism , stress responses , virulence and multi - drug resistance .", "entity": [], "task": "NER"}
{"text": "There is much interest in defining the molecular mechanism by which ligand binding attenuates the DNA - binding activities of these proteins .", "entity": [], "task": "NER"}
{"text": "Here , we describe how PcaV , a MarR family regulator in Streptomyces coelicolor , controls transcription of genes encoding beta - ketoadipate pathway enzymes through its interaction with the pathway substrate , protocatechuate .", "entity": [{"entity": "protocatechuate", "entity_type": "Chemical", "pos": [212, 227]}], "task": "NER"}
{"text": "This transcriptional repressor is the only MarR protein known to regulate this essential pathway for aromatic catabolism .", "entity": [], "task": "NER"}
{"text": "In in vitro assays , protocatechuate and other phenolic compounds disrupt the PcaV - DNA complex .", "entity": [{"entity": "protocatechuate", "entity_type": "Chemical", "pos": [21, 36]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [47, 55]}], "task": "NER"}
{"text": "We show that PcaV binds protocatechuate in a 1 : 1 stoichiometry with the highest affinity of any MarR family member .", "entity": [{"entity": "protocatechuate", "entity_type": "Chemical", "pos": [24, 39]}], "task": "NER"}
{"text": "Moreover , we report structures of PcaV in its apo form and in complex with protocatechuate .", "entity": [{"entity": "protocatechuate", "entity_type": "Chemical", "pos": [76, 91]}], "task": "NER"}
{"text": "We identify an arginine residue that is critical for ligand coordination and demonstrate that it is also required for binding DNA .", "entity": [{"entity": "arginine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "We propose that interaction of ligand with this arginine residue dictates conformational changes that modulate DNA binding .", "entity": [{"entity": "arginine", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "Our results provide new insights into the molecular mechanism by which ligands attenuate DNA binding in this large family of transcription factors .", "entity": [], "task": "NER"}
{"text": "Arylamine organic dyes for dye - sensitized solar cells .", "entity": [{"entity": "Arylamine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Arylamine organic dyes with donor ( D ) , pi - bridge ( pi ) and acceptor ( A ) moieties for dye - sensitized solar cells ( DSCs ) have received great attention in the last decade because of their high molar absorption coefficient , low cost and structural variety .", "entity": [{"entity": "Arylamine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "In the early stages , the efficiency of DSCs with arylamine organic dyes with D - pi - A character was far behind that of DSCs with ruthenium ( II ) complexes partly due to the lack of information about the relationship between the chemical structures and the photovoltaic performance .", "entity": [{"entity": "arylamine", "entity_type": "Chemical", "pos": [50, 59]}, {"entity": "ruthenium ( II )", "entity_type": "Chemical", "pos": [132, 148]}], "task": "NER"}
{"text": "However , exciting progress has been recently made , and power conversion efficiencies over 10 % were obtained for DSCs with arylamine organic dyes .", "entity": [{"entity": "arylamine", "entity_type": "Chemical", "pos": [125, 134]}], "task": "NER"}
{"text": "It is thus that the recent research and development in the field of arylamine organic dyes employing an iodide / triiodide redox couple or polypyridyl cobalt redox shuttles as the electrolytes for either DSCs or solid - state DSCs has been summarized .", "entity": [{"entity": "arylamine", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [104, 110]}, {"entity": "triiodide", "entity_type": "Chemical", "pos": [113, 122]}, {"entity": "polypyridyl cobalt", "entity_type": "Chemical", "pos": [139, 157]}], "task": "NER"}
{"text": "The cell performance of the arylamine organic dyes are compared , providing a comprehensive overview of arylamine organic dyes , demonstrating the advantages / disadvantages of each class , and pointing out the field that needs to reinforce the research direction in the further application of DSCs .", "entity": [{"entity": "arylamine", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "arylamine", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "Impaired cliff avoidance reaction in dopamine transporter knockout mice .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "RATIONALE : Impulsivity is a key feature of disorders that include attention - deficit / hyperactivity disorder ( ADHD ) .", "entity": [], "task": "NER"}
{"text": "The cliff avoidance reaction ( CAR ) assesses maladaptive impulsive rodent behavior .", "entity": [], "task": "NER"}
{"text": "Dopamine transporter knockout ( DAT - KO ) mice display features of ADHD and are candidates in which to test other impulsive phenotypes .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "OBJECTIVES : Impulsivity of DAT - KO mice was assessed in the CAR paradigm .", "entity": [], "task": "NER"}
{"text": "For comparison , attentional deficits were also assessed in prepulse inhibition ( PPI ) in which DAT - KO mice have been shown to exhibit impaired sensorimotor gating .", "entity": [], "task": "NER"}
{"text": "RESULTS : DAT - KO mice exhibited a profound CAR impairment compared to wild - type ( WT ) mice .", "entity": [], "task": "NER"}
{"text": "As expected , DAT - KO mice showed PPI deficits compared to WT mice .", "entity": [], "task": "NER"}
{"text": "Furthermore , the DAT - KO mice with the most impaired CAR exhibited the most severe PPI deficits .", "entity": [], "task": "NER"}
{"text": "Treatment with methylphenidate or nisoxetine ameliorated CAR impairments in DAT - KO mice .", "entity": [{"entity": "methylphenidate", "entity_type": "Chemical", "pos": [15, 30]}, {"entity": "nisoxetine", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "CONCLUSION : These results suggest that DAT - KO mice exhibit impulsive CAR behavior that correlates with their PPI deficits .", "entity": [], "task": "NER"}
{"text": "Blockade of monoamine transporters , especially the norepinephrine transporter ( NET ) in the prefrontal cortex ( PFC ) , may contribute to pharmacological improvement of impulsivity in these mice .", "entity": [{"entity": "monoamine", "entity_type": "Chemical", "pos": [12, 21]}, {"entity": "norepinephrine", "entity_type": "Chemical", "pos": [52, 66]}], "task": "NER"}
{"text": "The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post - weaning social isolation in rats .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [27, 38]}], "task": "NER"}
{"text": "RATIONALE : Rearing rats in isolation from weaning is an established preclinical neurodevelopmental model which induces behavioural deficits with apparent translational relevance to some core symptoms of schizophrenia .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : This study evaluated the ability of the atypical antipsychotic risperidone to reverse behavioural deficits induced by post - weaning social isolation of rat pups and to further characterise the predictive validity of this model .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "METHOD : Forty - five male Lister hooded rats were housed in groups of 3 - 4 ( n = 16 ) or singly ( n = 29 ) for 4 weeks immediately after weaning on postnatal day ( PND ) 22 - 24 .", "entity": [], "task": "NER"}
{"text": "On PND 51 , novel cage - induced locomotor activity ( LMA ) was assessed to subdivide rats into groups balanced for behavioural response .", "entity": [], "task": "NER"}
{"text": "On PNDs 58 , 59 , 65 and 72 , rats received either vehicle ( 1 ml / kg ; i . p . ) or risperidone ( 0 . 2 or 0 . 5 mg / kg ; i . p . ) 30 min prior to testing in LMA , novel object discrimination ( NOD ) , prepulse inhibition ( PPI ) of acoustic startle and conditioned emotional response ( CER ) learning paradigms , respectively .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [86, 97]}], "task": "NER"}
{"text": "RESULTS : Isolation rearing had no effect on PPI , but produced LMA hyperactivity and impaired NOD and CER compared to group - housed controls .", "entity": [], "task": "NER"}
{"text": "Risperidone caused a dose - dependent reduction in LMA , irrespective of rearing condition , but selectively reversed the NOD deficit in isolation - reared rats .", "entity": [{"entity": "Risperidone", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Risperidone did not reverse the isolation rearing - induced CER deficit .", "entity": [{"entity": "Risperidone", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "CONCLUSIONS : Similar to its clinical profile , risperidone only partially reverses the schizophrenic symptomology ; since it reversed some , but not all , of the learning and memory deficits induced by post - weaning isolation , the isolation rearing model may be useful to predict antipsychotic activity of novel therapeutic agents .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [48, 59]}], "task": "NER"}
{"text": "Impaired function of prejunctional adenosine A1 receptors expressed by perivascular sympathetic nerves in DOCA - salt hypertensive rats .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "DOCA", "entity_type": "Chemical", "pos": [106, 110]}], "task": "NER"}
{"text": "Increased sympathetic nervous system activity contributes to deoxycorticosterone acetate ( DOCA ) - salt hypertension in rats .", "entity": [{"entity": "deoxycorticosterone acetate", "entity_type": "Chemical", "pos": [61, 88]}, {"entity": "DOCA", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "ATP and norepinephrine ( NE ) are coreleased from perivascular sympathetic nerves .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "norepinephrine", "entity_type": "Chemical", "pos": [8, 22]}], "task": "NER"}
{"text": "NE acts at prejunctional alpha 2 - adrenergic receptors ( alpha 2ARs ) to inhibit NE release , and alpha 2AR function is impaired in DOCA - salt rats .", "entity": [{"entity": "DOCA", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "Adenosine , an enzymatic ATP degradation product , acts at prejunctional A1 adenosine receptors ( A1Rs ) to inhibit NE release .", "entity": [{"entity": "Adenosine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "We tested the hypothesis that prejunctional A1R function is impaired in sympathetic nerves supplying mesenteric arteries ( MAs ) and veins ( MVs ) of DOCA - salt rats .", "entity": [{"entity": "DOCA", "entity_type": "Chemical", "pos": [150, 154]}], "task": "NER"}
{"text": "Electrically evoked NE release and constrictions of blood vessels were studied in vitro with use of amperometry to measure NE oxidation currents and video microscopy , respectively .", "entity": [], "task": "NER"}
{"text": "Immunohistochemical methods were used to localize tyrosine hydroxylase ( TH ) and A1Rs in perivascular sympathetic nerves .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "TH and A1Rs colocalized to perivascular sympathetic nerves .", "entity": [], "task": "NER"}
{"text": "Adenosine and N ( 6 ) - cyclopentyl - adenosine ( CPA , A1R agonist ) constricted MVs but not MAs .", "entity": [{"entity": "Adenosine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "N ( 6 ) - cyclopentyl - adenosine", "entity_type": "Chemical", "pos": [14, 47]}, {"entity": "CPA", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "Adenosine and CPA ( 0 . 001 - 10 micro M ) inhibited neurogenic constrictions and NE release in MAs and MVs .", "entity": [{"entity": "Adenosine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "CPA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "DOCA - salt arteries were resistant to adenosine and CPA - mediated inhibition of NE release and constriction .", "entity": [{"entity": "DOCA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [39, 48]}, {"entity": "CPA", "entity_type": "Chemical", "pos": [53, 56]}], "task": "NER"}
{"text": "The A2A adenosine receptor agonist CGS21680 ( C23H29N7O6 . HCl . xH2O ) ( 0 . 001 - 0 . 1 mu M ) did not alter NE oxidation currents .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [8, 17]}, {"entity": "CGS21680", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "C23H29N7O6 . HCl . xH2O", "entity_type": "Chemical", "pos": [46, 69]}], "task": "NER"}
{"text": "We conclude that there are prejunctional A1Rs in arteries and both pre - and postjunctional A1Rs in veins ; thus , adenosine selectively constricts the veins .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "Prejunctional A1R function is impaired in arteries , but not veins , from DOCA - salt rats .", "entity": [{"entity": "DOCA", "entity_type": "Chemical", "pos": [74, 78]}], "task": "NER"}
{"text": "Sympathetic autoreceptor dysfunction is not specific to alpha 2ARs , but there is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release in DOCA - salt hypertension .", "entity": [{"entity": "DOCA", "entity_type": "Chemical", "pos": [188, 192]}], "task": "NER"}
{"text": "Temperature Effects of Sputtering of Langmuir - Blodgett Multilayers .", "entity": [], "task": "NER"}
{"text": "Time - of - flight secondary ion mass spectrometry ( TOF - SIMS ) and atomic force microscopy ( AFM ) are employed to characterize a wedge - shaped crater eroded by a 40 keV C ( 60 ) ( + ) cluster ion beam on an organic thin film of 402 nm of barium arachidate ( AA ) multilayers prepared by the Langmuir - Blodgett ( LB ) technique .", "entity": [{"entity": "C ( 60 ) ( + )", "entity_type": "Chemical", "pos": [174, 188]}, {"entity": "barium arachidate", "entity_type": "Chemical", "pos": [243, 260]}], "task": "NER"}
{"text": "Sample cooling to 90 K was used to help reduce chemical damage , improve depth resolution and maintain constant erosion rate during depth profiling .", "entity": [], "task": "NER"}
{"text": "The film was characterized at 90 K , 135 K , 165 K , 205 K , 265 K and 300 K .", "entity": [], "task": "NER"}
{"text": "It is shown that sample cooling to 205 K or lower helps to inhibit erosion rate decay , whereas at 300 K and 265 K the erosion rate continues to drop after 250 nm of erosion , reaching about half of the initial value after removal of the entire film .", "entity": [], "task": "NER"}
{"text": "Depth profiles are acquired from the SIMS images of the eroded wedge crater .", "entity": [], "task": "NER"}
{"text": "The results suggest that sample cooling only slightly improves the altered layer thickness , but eliminates the decrease in erosion rate observed above 265 K .", "entity": [], "task": "NER"}
{"text": "Lipid Efflux Mediated by Alkylphospholipids in HepG2 Cells .", "entity": [], "task": "NER"}
{"text": "Antitumoural alkylphospholipid ( APL ) analogues alter cholesterol homoeostasis in HepG2 cells by interfering with cholesterol transport from the plasma membrane to the endoplasmic reticulum ( ER ) and at the same time stimulating the release of considerable quantities of membrane cholesterol .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [55, 66]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [115, 126]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [282, 293]}], "task": "NER"}
{"text": "The capacity of APLs to stimulate cholesterol efflux is suppressed when cells are incubated simultaneously with APLs and serum whilst the inhibition of cholesterol transport to the ER ( measured in terms of the synthesis of esterified cholesterol ) persists , indicating that both effects are independent of each other .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [34, 45]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [152, 163]}, {"entity": "esterified cholesterol", "entity_type": "Chemical", "pos": [224, 246]}], "task": "NER"}
{"text": "Interestingly , our results suggest that both raft and non - raft membrane domains contribute to the cholesterol released to APLs .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [101, 112]}], "task": "NER"}
{"text": "In addition , a marked efflux of choline - bearing phospholipids ( phosphatidylcholine ( PC ) and sphingomyelins ( SM ) ) was found to be related to this release of cholesterol .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [33, 40]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [67, 86]}, {"entity": "sphingomyelins", "entity_type": "Chemical", "pos": [98, 112]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [165, 176]}], "task": "NER"}
{"text": "Finally , we observed that APL micelles composed of cholesterol might act as donor / acceptor cholesterol systems .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "Thus , the findings of this study clearly demonstrate that antitumoural APLs act as extracellular acceptors , stimulating cholesterol and phospholipid efflux , although they may also play a role as cholesterol donors .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [122, 133]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [198, 209]}], "task": "NER"}
{"text": "Prolactin and sex steroids levels in congenital lifetime isolated GH deficiency .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "Growth hormone ( GH ) and prolactin share similarities in structure and function .", "entity": [], "task": "NER"}
{"text": "We have previously shown that women with congenital isolated GH deficiency ( IGHD ) caused by a homozygous mutation in the GHRH receptor gene ( GHRHR ) ( MUT / MUT ) have a short reproductive life , with anticipated climacteric .", "entity": [], "task": "NER"}
{"text": "At climacteric , they have lower prolactin levels than normal controls ( N / N ) .", "entity": [], "task": "NER"}
{"text": "Because they are able to breast feed , we hypothesized that this prolactin reduction is limited to climacteric , as result of lower estradiol exposure of the lactotrophs .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [132, 141]}], "task": "NER"}
{"text": "The purposes of this work were to assess prolactin levels in broader age adults homozygous and heterozygous ( MUT / N ) for the mutation and in normal controls ( N / N ) , and to correlate them to sex steroids levels .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [201, 209]}], "task": "NER"}
{"text": "We enrolled 24 GH - na i ve MUT / MUT ( 12 female ) , 25 MUT / N ( 14 female ) , and 25 N / N ( 11 female ) subjects , aged 25 - 65 years .", "entity": [], "task": "NER"}
{"text": "Anthropometric data and serum prolactin , estradiol , total testosterone , and sex hormone binding globulin ( SHBG ) were measured .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [60, 72]}], "task": "NER"}
{"text": "Free testosterone was calculated .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [5, 17]}], "task": "NER"}
{"text": "Prolactin levels were similar in the three groups .", "entity": [], "task": "NER"}
{"text": "In males , testosterone and SHBG levels were higher in MUT / MUT in comparison to N / N .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [11, 23]}], "task": "NER"}
{"text": "There was no difference in free testosterone among groups .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [32, 44]}], "task": "NER"}
{"text": "In all 74 individuals , prolactin correlated inversely with age ( p < 0 . 0001 ) and directly with serum estradiol ( p = 0 . 018 ) .", "entity": [{"entity": "estradiol", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "Prolactin levels in subjects with IGHD due to a homozygous GHRHR mutation are similar to heterozygous and normal homozygous , but total testosterone and SHBG are higher in male MUT / MUT , with no difference in free testosterone .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [136, 148]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [216, 228]}], "task": "NER"}
{"text": "The reduced prolactin level is limited to climacteric period , possibly due to reduced estrogen exposure .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Lithium / sulfur batteries with high specific energy : old challenges and new opportunities .", "entity": [{"entity": "Lithium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [10, 16]}], "task": "NER"}
{"text": "In this review , we begin with a brief discussion of the operating principles and scientific / technical challenges faced by the development of lithium / sulfur cells .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [144, 151]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "We then introduce some recent progress in exploring cathodes , anodes , and electrolytes for lithium / sulfur cells .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [93, 100]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "In particular , several effective strategies used to enhance energy / power density , obtain good efficiencies , and prolong cycle life will be highlighted .", "entity": [], "task": "NER"}
{"text": "We also discuss recent advancements in techniques for investigating electrode reactions in real time and monitoring structural / morphological changes of electrode materials under cell operating conditions to gain a better understanding of the mechanistic details of electrode processes .", "entity": [], "task": "NER"}
{"text": "Finally , the opportunities and perspective for future research directions will be discussed .", "entity": [], "task": "NER"}
{"text": "Monitoring of deiodinase deficiency based on transcriptomic responses in SH - SY5Y cells .", "entity": [], "task": "NER"}
{"text": "Iodothyronine deiodinase types I , II , and III ( D1 , D2 , and D3 , respectively ) , which constitute a family of selenoenzymes , activate and inactivate thyroid hormones through the removal of specific iodine moieties from thyroxine and its derivatives .", "entity": [{"entity": "Iodothyronine", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [204, 210]}, {"entity": "thyroxine", "entity_type": "Chemical", "pos": [225, 234]}], "task": "NER"}
{"text": "These enzymes are important in the biological effects mediated by thyroid hormones .", "entity": [], "task": "NER"}
{"text": "The expression of activating and inactivating deiodinases plays a critical role in a number of cell systems , including the neuronal system , during development as well as in adult vertebrates .", "entity": [], "task": "NER"}
{"text": "To investigate deiodinase - disrupting chemicals based on transcriptomic responses , we examined differences in gene expression profiles between T3 - treated and deiodinase - knockdown SH - SY5Y cells using microarray analysis and quantitative real - time RT - PCR .", "entity": [], "task": "NER"}
{"text": "A total of 1 , 558 genes , consisting of 755 upregulated and 803 downregulated genes , were differentially expressed between the T3 - treated and deiodinase - knockdown cells .", "entity": [], "task": "NER"}
{"text": "The expression levels of 10 of these genes ( ID2 , ID3 , CCL2 , TBX3 , TGOLN2 , C1orf71 , ZNF676 , GULP1 , KLF9 , and ITGB5 ) were altered by deiodinase - disrupting chemicals ( 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin , polychlorinated biphenyls , propylthiouracil , iodoacetic acid , methylmercury , beta - estradiol , methimazole , 3 - methylcholanthrene , aminotriazole , amiodarone , cadmium chloride , dimethoate , fenvalerate , octylmethoxycinnamate , iopanoic acid , methoxychlor , and 4 - methylbenzylidene - camphor ) .", "entity": [{"entity": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [178, 225]}, {"entity": "polychlorinated biphenyls", "entity_type": "Chemical", "pos": [228, 253]}, {"entity": "propylthiouracil", "entity_type": "Chemical", "pos": [256, 272]}, {"entity": "iodoacetic acid", "entity_type": "Chemical", "pos": [275, 290]}, {"entity": "methylmercury", "entity_type": "Chemical", "pos": [293, 306]}, {"entity": "beta - estradiol", "entity_type": "Chemical", "pos": [309, 325]}, {"entity": "methimazole", "entity_type": "Chemical", "pos": [328, 339]}, {"entity": "3 - methylcholanthrene", "entity_type": "Chemical", "pos": [342, 364]}, {"entity": "aminotriazole", "entity_type": "Chemical", "pos": [367, 380]}, {"entity": "amiodarone", "entity_type": "Chemical", "pos": [383, 393]}, {"entity": "cadmium chloride", "entity_type": "Chemical", "pos": [396, 412]}, {"entity": "dimethoate", "entity_type": "Chemical", "pos": [415, 425]}, {"entity": "fenvalerate", "entity_type": "Chemical", "pos": [428, 439]}, {"entity": "octylmethoxycinnamate", "entity_type": "Chemical", "pos": [442, 463]}, {"entity": "iopanoic acid", "entity_type": "Chemical", "pos": [466, 479]}, {"entity": "methoxychlor", "entity_type": "Chemical", "pos": [482, 494]}, {"entity": "4 - methylbenzylidene - camphor", "entity_type": "Chemical", "pos": [501, 532]}], "task": "NER"}
{"text": "These genes are potential biomarkers for detecting deiodinase deficiency and predicting their effects on thyroid hormone production .", "entity": [], "task": "NER"}
{"text": "Treatment of pretibial myxedema with dexamethazone injected subcutaneously by mesotherapy needles .", "entity": [{"entity": "dexamethazone", "entity_type": "Chemical", "pos": [37, 50]}], "task": "NER"}
{"text": "Pretibial myxedema ( PTM ) is a rare extrathyroidal manifestation of Graves ' disease that requires treatment when the clinical picture is markedly evident .", "entity": [], "task": "NER"}
{"text": "In addition to topical treatment with steroid ointments , there have been previous reports of subcutaneous injections of steroids .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "steroids", "entity_type": "Chemical", "pos": [121, 129]}], "task": "NER"}
{"text": "This procedure may cause nodular degeneration of the skin due to fat atrophy when standard needles are used .", "entity": [], "task": "NER"}
{"text": "In the present study , we have tried a novel modality of treatment of PTM by injecting a solution of dexamethasone in the subcutaneous tissue using needles employed for mesotherapy .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [101, 114]}], "task": "NER"}
{"text": "These needles are <= 4 mm long and deliver the medication within the dermis or the first layer of the subcutaneous fat .", "entity": [], "task": "NER"}
{"text": "We have treated five patients , four with diffuse and one with elephanthiasic PTM .", "entity": [], "task": "NER"}
{"text": "We utilized multiple injections of a solution of dexamethasone , lidocaine , and saline in the PTM plaque and in the pretibial area , both in the PTM plaque and in the area surrounding the lesions , once a week for three consecutive weeks .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [49, 62]}, {"entity": "lidocaine", "entity_type": "Chemical", "pos": [65, 74]}], "task": "NER"}
{"text": "Two patients with a more severe form of PTM underwent another two cycles four to six weeks after initial treatment .", "entity": [], "task": "NER"}
{"text": "Patients were studied before and after treatment by clinical assessment and ultrasound of the pretibial skin .", "entity": [], "task": "NER"}
{"text": "The treatment was well - tolerated , with only moderate pain upon injection of the solution .", "entity": [], "task": "NER"}
{"text": "One month after treatment , all patients showed improvement of PTM at clinical assessment and a reduction of the thickness of the lesions at ultrasound of ~ 15 % , involving mostly the dermis .", "entity": [], "task": "NER"}
{"text": "Moreover , all patients reported amelioration of the leg appearance .", "entity": [], "task": "NER"}
{"text": "The present study , although preliminary , shows that intralesion steroid injection with mesotherapy needles in PTM is effective and well tolerated , and does not cause undesired long - term modifications of the skin .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [66, 73]}], "task": "NER"}
{"text": "More studies are warranted to standardize such treatment in larger groups of patients .", "entity": [], "task": "NER"}
{"text": "Predicting temperature - dependent solid vapor pressures of explosives and related compounds using a quantum mechanical continuum solvation model .", "entity": [], "task": "NER"}
{"text": "Temperature - dependent vapor pressures of solid explosives and their byproducts are calculated to an accuracy of 0 . 32 log units using a modified form of the conductor - like screening model for real solvents ( COSMO - RS ) .", "entity": [], "task": "NER"}
{"text": "Accurate predictions for solids within COSMO - RS require correction for the free energy of fusion as well as other effects such as van der Waals interactions .", "entity": [], "task": "NER"}
{"text": "Limited experimental data on explosives is available to determine these corrections , and thus we have extended the COSMO - RS model by introducing a quantitative structure - property relationship to estimate a lumped correction factor using only information from standard quantum chemistry calculations .", "entity": [], "task": "NER"}
{"text": "This modification improves the COSMO - RS estimate of ambient vapor pressure by more than 1 order of magnitude for a range of nitrogen - rich explosives and their derivatives , bringing the theoretical predictions to within typical experimental error bars for vapor pressure measurements .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "The estimated temperature dependence of these vapor pressures also agrees well with available experimental data , which is particularly important for estimating environmental transport and gas evolution for buried explosives or environmentally contaminated locations .", "entity": [], "task": "NER"}
{"text": "This technique is then used to predict vapor pressures for a number of explosives and degradation products for which experimental data is not readily available .", "entity": [], "task": "NER"}
{"text": "Inductive tuning of Fano - resonant metasurfaces using plasmonic response of graphene in the mid - infrared .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [77, 85]}], "task": "NER"}
{"text": "Graphene is widely known for its anomalously strong broadband optical absorptivity of 2 . 3 % that enables seeing its single - atom layer with the naked eye .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "However , in the mid - infrared part of the spectrum graphene represents a quintessential lossless zero - volume plasmonic material .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [53, 61]}], "task": "NER"}
{"text": "We experimentally demonstrate that , when integrated with Fano - resonant plasmonic metasurfaces , single - layer graphene ( SLG ) can be used to tune their mid - infrared optical response .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [114, 122]}], "task": "NER"}
{"text": "SLG ' s plasmonic response is shown to induce large blue shifts of the metasurface ' s resonance without reducing its spectral sharpness .", "entity": [], "task": "NER"}
{"text": "This effect is explained by a generalized perturbation theory of SLG - metamaterial interaction that accounts for two unique properties of the SLG that set it apart from all other plasmonic materials : its anisotropic response and zero volume .", "entity": [], "task": "NER"}
{"text": "These results pave the way to using gated SLG as a platform for dynamical spectral tuning of infrared metamaterials and metasurfaces .", "entity": [], "task": "NER"}
{"text": "SiO2 @ Au core - shell nanospheres self - assemble to form colloidal crystals that can be sintered and surface modified to produce pH - controlled membranes .", "entity": [{"entity": "SiO2", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "Au", "entity_type": "Chemical", "pos": [7, 9]}], "task": "NER"}
{"text": "We prepared colloidal crystals by self - assembly of gold - coated silica nanospheres , and free - standing nanoporous membranes by sintering these colloidal crystals .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [67, 73]}], "task": "NER"}
{"text": "We modified the nanopore surface with ionizable functional groups , by forming a monolayer of L - cysteine or by surface - initiated polymerization of methacrylic acid .", "entity": [{"entity": "L - cysteine", "entity_type": "Chemical", "pos": [94, 106]}, {"entity": "methacrylic acid", "entity_type": "Chemical", "pos": [151, 167]}], "task": "NER"}
{"text": "Diffusion experiments for the cationic dye Rhodamine B through L - cysteine - modified membranes showed a decrease in flux upon addition of an acid due to the nanopore surface becoming positively charged .", "entity": [{"entity": "Rhodamine B", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "L - cysteine", "entity_type": "Chemical", "pos": [63, 75]}], "task": "NER"}
{"text": "Diffusion experiments for the neutral dye , ferrocenecarboxaldehyde , through the PMAA - modified membranes showed a 13 - fold increase in flux upon addition of an acid resulting from the protonated polymer collapsing onto the nanopore surface leading to larger pore size .", "entity": [{"entity": "ferrocenecarboxaldehyde", "entity_type": "Chemical", "pos": [44, 67]}, {"entity": "PMAA", "entity_type": "Chemical", "pos": [82, 86]}], "task": "NER"}
{"text": "Our results demonstrate that SiO2 @ Au core - shell nanospheres can self - assemble into colloidal crystals and that transport through the corresponding surface - modified Au - coated colloidal membranes can be controlled by pH .", "entity": [{"entity": "SiO2", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "Au", "entity_type": "Chemical", "pos": [36, 38]}, {"entity": "Au", "entity_type": "Chemical", "pos": [172, 174]}], "task": "NER"}
{"text": "Mexican antidiabetic herbs : valuable sources of inhibitors of alpha - glucosidases .", "entity": [], "task": "NER"}
{"text": "Type II - diabetes mellitus ( TII - DM ) has been regarded as one of the most important public health problems in all nations in the 21st century .", "entity": [], "task": "NER"}
{"text": "Although allopathic therapies remain the most important for the initial management of TII - DM , herbal remedies have gained wide acceptance for treating this condition .", "entity": [], "task": "NER"}
{"text": "These alternative therapies are particularly valued in countries such as Mexico , rich in medicinal plants strongly attached to the cultural values of the population .", "entity": [], "task": "NER"}
{"text": "Medicinal plants are prized sources of alpha - glucosidase inhibitors , which delay the liberation of glucose from complex carbohydrates , retarding glucose absorption , and thus controlling the characteristic hyperglycemia of TII - DM .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [102, 109]}, {"entity": "carbohydrates", "entity_type": "Chemical", "pos": [123, 136]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [149, 156]}], "task": "NER"}
{"text": "Among the plant species used for treating diabetes in Mexico only 38 have been analyzed for their inhibitory activity of alpha - glucosidases .", "entity": [], "task": "NER"}
{"text": "Most of these studies , reviewed in the present work , have focused on the evaluation of different types of extracts on the activity of alpha - glucosidases from diverse sources .", "entity": [], "task": "NER"}
{"text": "Four species have been thoroughly analyzed in order to discover novel alpha - glucosidase inhibitors , namely , Hintonia latiflora and Hintonia standleyana ( Rubiaceae ) , Ligusticum porteri ( Apiaceae ) , and Brickellia cavanillesii ( Asteraceae ) .", "entity": [], "task": "NER"}
{"text": "Their ethnomedical uses , pharmacological and toxicological studies , chemical composition , and antihyperglycemic principles with alpha - glucosidase inhibitory activity are summarized .", "entity": [], "task": "NER"}
{"text": "Lessons in microcapsule assembly from imaging delivery of a bioluminescent enzyme .", "entity": [], "task": "NER"}
{"text": "Layer - by - layer assembled microcapsules have potential applications as delivery and biosensing systems , which make them attractive tools for use in various aspects of nanomedicine .", "entity": [], "task": "NER"}
{"text": "We examined the effect of microcapsule location on activity of the bioluminescent enzyme luciferase in both intact capsules and following cell uptake .", "entity": [], "task": "NER"}
{"text": "In intact capsules , the rate of reaction of luciferase was greatest for luciferase in the outer layer and least in the core .", "entity": [], "task": "NER"}
{"text": "Following cell uptake , luciferase in the outer layer was rapidly reactive , and a similar rate of reaction and activity was observed for luciferase placed in capsule interior ( core ) .", "entity": [], "task": "NER"}
{"text": "By contrast , there was minimal activity detected when microcapsules with luciferase sandwiched between polyelectrolytes in a middle layer were delivered to cells .", "entity": [], "task": "NER"}
{"text": "This study informs us of the availability of bioactive molecules located in different positions within microcapsules and will enable better microcapsule construction in line with the intended application , particularly delivery of functional proteins to cells .", "entity": [], "task": "NER"}
{"text": "Magnetoelectric control of superparamagnetism .", "entity": [], "task": "NER"}
{"text": "Here we demonstrate electric - field induced magnetic anisotropy in a multiferroic composite containing nickel nanocrystals strain coupled to a piezoelectric substrate .", "entity": [{"entity": "nickel", "entity_type": "Chemical", "pos": [104, 110]}], "task": "NER"}
{"text": "This system can be switched between a superparamagnetic state and a single - domain ferromagnetic state at room temperature .", "entity": [], "task": "NER"}
{"text": "The nanocrystals show a shift in the blocking temperature of 40 K upon electric poling .", "entity": [], "task": "NER"}
{"text": "We believe this is the first example of a system where an electric field can be used to switch on and off a permanent magnetic moment .", "entity": [], "task": "NER"}
{"text": "Daily physical activity assessment with accelerometers : new insights and validation studies .", "entity": [], "task": "NER"}
{"text": "The field of application of accelerometry is diverse and ever expanding .", "entity": [], "task": "NER"}
{"text": "Because by definition all physical activities lead to energy expenditure , the doubly labelled water ( DLW ) method as gold standard to assess total energy expenditure over longer periods of time is the method of choice to validate accelerometers in their ability to assess daily physical activities .", "entity": [], "task": "NER"}
{"text": "The aim of this paper was to provide a systematic overview of all recent ( 2007 - 2011 ) accelerometer validation studies using DLW as the reference .", "entity": [], "task": "NER"}
{"text": "The PubMed Central database was searched using the following keywords : doubly or double labelled or labeled water in combination with accelerometer , accelerometry , motion sensor , or activity monitor .", "entity": [], "task": "NER"}
{"text": "Limits were set to include articles from 2007 to 2011 , as earlier publications were covered in a previous review .", "entity": [], "task": "NER"}
{"text": "In total , 38 articles were identified , of which 25 were selected to contain sufficient new data .", "entity": [], "task": "NER"}
{"text": "Eighteen different accelerometers were validated .", "entity": [], "task": "NER"}
{"text": "There was a large variability in accelerometer output and their validity to assess daily physical activity .", "entity": [], "task": "NER"}
{"text": "Activity type recognition has great potential to improve the assessment of physical activity - related health outcomes .", "entity": [], "task": "NER"}
{"text": "So far , there is little evidence that adding other physiological measures such as heart rate significantly improves the estimation of energy expenditure .", "entity": [], "task": "NER"}
{"text": "Increased PD - 1 on CD4 ( + ) CD28 ( - ) T cell and soluble PD - 1 ligand - 1 in patients with T2DM : Association with atherosclerotic macrovascular diseases .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : To study the role of the programmed death - 1 ( PD - 1 ) / programmed death - 1 ligand 1 ( PD - L1 ) coinhibitory pathway in regulating CD4 ( + ) CD28 ( - ) T cells , and to explore the association of soluble PD - L1 ( sPD - L1 ) in the development of T2DM with atherosclerotic macrovascular diseases .", "entity": [], "task": "NER"}
{"text": "METHODS : The percentage of CD4 ( + ) CD28 ( - ) T lymphocyte subsets from peripheral blood mononuclear cells ( PBMCs ) and the expression of PD - 1 / PD - L1 on lymphocytes were analyzed by immunostaining and flow cytometry , respectively .", "entity": [], "task": "NER"}
{"text": "The serum levels of sPD - L1 and IFN - gamma were determined by ELISA system .", "entity": [], "task": "NER"}
{"text": "T cell proliferation was determined by cocultivation and WST - 8 incorporation .", "entity": [], "task": "NER"}
{"text": "RESULTS : In 125 T2DM patients and 48 healthy donors , CD4 ( + ) CD28 ( - ) T cells from patients with T2DM expressed higher PD - 1 than that of the cells from healthy individuals , and the proliferation response of CD4 ( + ) CD28 ( - ) T cells could be enhanced by advanced glycation end products ( AGEs ) .", "entity": [], "task": "NER"}
{"text": "The levels of sPD - L1 in patients were also much higher than those of healthy donors , and the increase was displayed in an exacerbation - dependent manner in the T2DM with atherosclerotic macrovascular patients especially with acute coronary syndrome ( ACS ) .", "entity": [], "task": "NER"}
{"text": "The production of sPD - L1 was significantly positively correlated with the level of IFN - gamma and could enhance T cell proliferation .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : Both the upregulation of PD - 1 and the increase of sPD - L1 were closely associated with the severity of diabetic atherosclerotic macrovascular diseases .", "entity": [], "task": "NER"}
{"text": "sPD - L1 may contribute to the continuous T cell activation and development of diabetic macrovascular diseases .", "entity": [], "task": "NER"}
{"text": "Synthesis and biological evaluation of guanidino analogues of roscovitine .", "entity": [{"entity": "guanidino", "entity_type": "Chemical", "pos": [39, 48]}, {"entity": "roscovitine", "entity_type": "Chemical", "pos": [62, 73]}], "task": "NER"}
{"text": "A series of 2 , 9 - substituted 6 - guanidinopurines , structurally related to the cyclin - dependent kinase ( CDK ) inhibitors olomoucine and roscovitine , has been synthesized and characterized .", "entity": [{"entity": "2 , 9 - substituted 6 - guanidinopurines", "entity_type": "Chemical", "pos": [12, 52]}, {"entity": "olomoucine", "entity_type": "Chemical", "pos": [128, 138]}, {"entity": "roscovitine", "entity_type": "Chemical", "pos": [143, 154]}], "task": "NER"}
{"text": "A new copper - catalyzed method for the synthesis of 2 - substituted 6 - guanidino - 9 - isopropylpurines under mild reaction conditions has been developed .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [6, 12]}, {"entity": "2 - substituted 6 - guanidino - 9 - isopropylpurines", "entity_type": "Chemical", "pos": [53, 105]}], "task": "NER"}
{"text": "All prepared compounds were screened for their CDK1 and CDK2 inhibitory activities , cytotoxicity and antiproliferative effects in the breast cancer - derived cell line MCF7 .", "entity": [], "task": "NER"}
{"text": "The most active derivative 16g possessed an identical side chain in the C2 position to roscovitine ; this compound displayed approximately five fold higher inhibitory activity towards CDK2 / cyclin E and more than ten fold increase in cytotoxicity in MCF7 cells .", "entity": [{"entity": "roscovitine", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Interestingly and in contrast to previously described findings , ( S ) - 6 - guanidinopurine derivatives were generally more active than their ( R ) - counterparts .", "entity": [{"entity": "( S ) - 6 - guanidinopurine", "entity_type": "Chemical", "pos": [65, 92]}], "task": "NER"}
{"text": "Kinase selectivity profiling of ( R ) - and ( S ) - enantiomers 16e and 16g , respectively , revealed that introduction of a guanidino group at the C6 position of the purine moiety decreased selectivity towards protein kinases compared to roscovitine .", "entity": [{"entity": "guanidino", "entity_type": "Chemical", "pos": [125, 134]}, {"entity": "purine", "entity_type": "Chemical", "pos": [167, 173]}, {"entity": "roscovitine", "entity_type": "Chemical", "pos": [239, 250]}], "task": "NER"}
{"text": "Nevertheless , increased inhibitory activity and decreased selectivity offer a good starting point for further development of new protein kinase inhibitors .", "entity": [], "task": "NER"}
{"text": "Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice : a role for imidazoline receptors .", "entity": [{"entity": "Agmatine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "imidazoline", "entity_type": "Chemical", "pos": [116, 127]}], "task": "NER"}
{"text": "The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference ( CPP ) and its modulation by imidazoline agents .", "entity": [{"entity": "agmatine", "entity_type": "Chemical", "pos": [45, 53]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "imidazoline", "entity_type": "Chemical", "pos": [154, 165]}], "task": "NER"}
{"text": "Swiss albino mice were treated intraperitoneally with saline or agmatine ( 20 - 40 mg / kg ) before injection of ethanol ( 1 . 25 mg / kg ) during conditioning days or on a test day ( 20 - 120 mg / kg ) , to observe the effect on acquisition or expression of CPP , respectively .", "entity": [{"entity": "agmatine", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [113, 120]}], "task": "NER"}
{"text": "Agmatine inhibited the acquisition but not the expression of ethanol CPP .", "entity": [{"entity": "Agmatine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [61, 68]}], "task": "NER"}
{"text": "Furthermore , both the I ( 1 ) receptor antagonist , efaroxan ( 9 mg / kg ) and the I ( 2 ) receptor antagonist , BU224 ( 5 mg / kg ) attenuated the agmatine - induced inhibition of the ethanol CPP acquisition .", "entity": [{"entity": "efaroxan", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "BU224", "entity_type": "Chemical", "pos": [114, 119]}, {"entity": "agmatine", "entity_type": "Chemical", "pos": [149, 157]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [186, 193]}], "task": "NER"}
{"text": "In contrast , the I ( 2 ) receptor agonist , 2 - BFI ( 5 mg / kg ) and I ( 1 ) receptor agonist , moxonidine ( 0 . 4 mg / kg ) alone , or a combination of their subeffective doses , significantly attenuated the effect of agmatine ( 20 mg / kg ) on acquisition of ethanol CPP .", "entity": [{"entity": "2 - BFI", "entity_type": "Chemical", "pos": [45, 52]}, {"entity": "moxonidine", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "agmatine", "entity_type": "Chemical", "pos": [221, 229]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [263, 270]}], "task": "NER"}
{"text": "Agmatine or imidazoline agents alone produced neither place preference nor aversion , and at the doses used in the present study did not affect locomotor activity .", "entity": [{"entity": "Agmatine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "imidazoline", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Thus , agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline ( I ( 1 ) or I ( 2 ) ) receptors .", "entity": [{"entity": "agmatine", "entity_type": "Chemical", "pos": [7, 15]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "imidazoline", "entity_type": "Chemical", "pos": [78, 89]}], "task": "NER"}
{"text": "In future studies , agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence .", "entity": [{"entity": "agmatine", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "imidazoline", "entity_type": "Chemical", "pos": [53, 64]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [128, 135]}], "task": "NER"}
{"text": "The critical effect of polarization on the dynamical structure of guanine quadruplex DNA .", "entity": [{"entity": "guanine", "entity_type": "Chemical", "pos": [66, 73]}], "task": "NER"}
{"text": "Guanine quadruplex DNA ( G - DNA ) , found in eukaryotic telomeres and recently in non - telomeric genomic DNA , plays important biological roles and their structures are being explored as potential targets for therapeutic intervention .", "entity": [{"entity": "Guanine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Since the quadruplex structure of G - DNA is stabilized by cations , electrostatic interaction is expected to play important roles in the dynamical structure of G - DNA .", "entity": [], "task": "NER"}
{"text": "In current work , MD simulation was carried out to study the dynamical structure of a special G - DNA ( with sequence d ( G ( 4 ) T ( 4 ) G ( 4 ) ) ) complexed with five K ( + ) ions .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [170, 177]}], "task": "NER"}
{"text": "In order to properly include polarization in MD simulation , a new set of polarized nucleic acid specific charge based on fragment quantum chemistry calculation was developed for G - DNA .", "entity": [], "task": "NER"}
{"text": "Our study showed that polarization of the nucleobases by K ( + ) enhanced electrostatic attraction between the base and ions .", "entity": [{"entity": "nucleobases", "entity_type": "Chemical", "pos": [42, 53]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "This increased attractive interaction is critical to stabilizing the stem - loop junction ions in G - DNA .", "entity": [], "task": "NER"}
{"text": "Without this polarization effect , as in MD simulation using a standard ( nonpolarizable ) force field , the top and bottom cations escaped into the solvent within just a few nanoseconds .", "entity": [], "task": "NER"}
{"text": "Furthermore , an incorrect bifurcated bonding geometry of G - DNA , found in previous MD simulation study under a standard force field but not observed in experiments , disappeared in the present stimulation using the new polarized force field .", "entity": [], "task": "NER"}
{"text": "The current study bridged an important gap between the simulation study and experimental observation on the dynamical structure of G - DNA .", "entity": [], "task": "NER"}
{"text": "Chemically - synthesised , atomically - precise gold clusters deposited and activated on titania .", "entity": [{"entity": "titania", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "Synchrotron XPS was used to investigate a series of chemically - synthesised , atomically - precise gold clusters Au ( n ) ( PPh ( 3 ) ) ( y ) ( n = 8 , 9 , 11 and 101 , with y depending on cluster size ) immobilized on titania nanoparticles .", "entity": [{"entity": "Au ( n ) ( PPh ( 3 ) ) ( y )", "entity_type": "Chemical", "pos": [114, 142]}, {"entity": "titania", "entity_type": "Chemical", "pos": [220, 227]}], "task": "NER"}
{"text": "The gold clusters were washed with toluene at 100 degrees C or calcined at 200 degrees C to remove the organic ligand .", "entity": [{"entity": "toluene", "entity_type": "Chemical", "pos": [35, 42]}], "task": "NER"}
{"text": "From the position of the Au 4f ( 7 / 2 ) peak it is concluded that cluster size is not altered through the deposition .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [25, 27]}], "task": "NER"}
{"text": "From the analysis of the phosphorous spectra , it can be concluded that the applied heat treatment removes the organic ligands .", "entity": [{"entity": "phosphorous", "entity_type": "Chemical", "pos": [25, 36]}], "task": "NER"}
{"text": "Washing and calcination leads to partial oxidation and partial agglomeration of the clusters .", "entity": [], "task": "NER"}
{"text": "Oxidation of the clusters is most likely due to the interaction of the cluster core with the oxygen of the titania surface after removal of ligands .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [93, 99]}, {"entity": "titania", "entity_type": "Chemical", "pos": [107, 114]}], "task": "NER"}
{"text": "The position of the Au 4f ( 7 / 2 ) peak indicates that the size of the agglomerated clusters is still smaller than that of Au ( 101 ) .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [20, 22]}, {"entity": "Au ( 101 )", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "Population pharmacokinetic / pharmacodynamic modeling to assist dosing schedule selection for dovitinib .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [94, 103]}], "task": "NER"}
{"text": "Dovitinib is an oral multitargeted kinase inhibitor with potent activity against receptors for vascular endothelial growth factor , platelet - derived growth factor , and basic fibroblast growth factor .", "entity": [{"entity": "Dovitinib", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Initial phase 1 to 2 studies of dovitinib using a continuous daily dosing schedule has shown that dovitinib exhibits a prolonged and overproportional increase in dose and exposure relationship above 400 mg / d .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "dovitinib", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "To address this , intermittent dosing schedules were explored using a model - based approach .", "entity": [], "task": "NER"}
{"text": "A semi - mechanistic population pharmcokinetic / pharmacodynamic ( PD ) model was developed from 4 dovitinib phase 1 studies with daily dosing schedules .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "Autoinduction of cytochrome P450 1A ( CYP1A ) responsible for dovitinib metabolism was described using an indirect response model .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [62, 71]}], "task": "NER"}
{"text": "Simulation of dovitinib plasma concentration profiles following 4 intermittent dosing schedules suggested that intermittent dosing could prevent prolonged drug accumulation .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Based on the simulated plasma profiles , PD response , and patient compliance , a 5 - days - on / 2 - days - off intermittent dosing schedule was selected for a phase 1 to 2 clinical study .", "entity": [], "task": "NER"}
{"text": "The observed dovitinib plasma concentrations in this study confirmed the model predictions .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [13, 22]}], "task": "NER"}
{"text": "Furthermore , dovitinib was well tolerated , and antitumor activity was observed as well in this new study .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "The 5 - days - on / 2 - days - off dosing schedule is currently used in a dovitinib registration trial and other clinical trials .", "entity": [{"entity": "dovitinib", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "Effects of amlodipine on the oral bioavailability of cephalexin and cefuroxime axetil in healthy volunteers .", "entity": [{"entity": "amlodipine", "entity_type": "Chemical", "pos": [11, 21]}, {"entity": "cephalexin", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "cefuroxime axetil", "entity_type": "Chemical", "pos": [68, 85]}], "task": "NER"}
{"text": "In this study , the authors compared the effects of amlodipine ( AML ) on the bioavailability of cephalexin ( LEX ) and cefuroxime axetil ( CXM ) .", "entity": [{"entity": "amlodipine", "entity_type": "Chemical", "pos": [52, 62]}, {"entity": "AML", "entity_type": "Chemical", "pos": [65, 68]}, {"entity": "cephalexin", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "LEX", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "cefuroxime axetil", "entity_type": "Chemical", "pos": [120, 137]}, {"entity": "CXM", "entity_type": "Chemical", "pos": [140, 143]}], "task": "NER"}
{"text": "Twenty - four healthy men were randomized to 4 treatments according to a crossover design with a 14 - day washout .", "entity": [], "task": "NER"}
{"text": "After an overnight fast , they were administered orally LEX 500 mg alone , LEX 500 mg 2 hours after oral administration of AML 5 mg , CXM 500 mg alone , and CXM 500 mg 2 hours after oral administration of AML 5 mg .", "entity": [{"entity": "LEX", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "LEX", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "AML", "entity_type": "Chemical", "pos": [123, 126]}, {"entity": "CXM", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "CXM", "entity_type": "Chemical", "pos": [157, 160]}, {"entity": "AML", "entity_type": "Chemical", "pos": [205, 208]}], "task": "NER"}
{"text": "All participants completed the whole study without side effects being observed .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic data were analyzed by noncompartmental modeling with WinNonlin software .", "entity": [], "task": "NER"}
{"text": "The geometric mean ( GM ) ratios were 1 . 38 ( 90 % confidence interval [ CI ] , 1 . 32 - 1 . 45 ) for the area under the concentration - time curve ( AUC ) for LEX and 1 . 27 ( 1 . 18 - 1 . 36 ) for the maximum concentration of drug in serum ( C ( max ) ) for LEX followed by AML versus alone .", "entity": [{"entity": "LEX", "entity_type": "Chemical", "pos": [161, 164]}, {"entity": "LEX", "entity_type": "Chemical", "pos": [261, 264]}, {"entity": "AML", "entity_type": "Chemical", "pos": [277, 280]}], "task": "NER"}
{"text": "In contrast , no significant differences were found in the pharmacokinetic parameters of CXM between treatments ( P < . 05 ) .", "entity": [{"entity": "CXM", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "They authors conclude that AML possesses an enhancement effect in beta - lactam antibiotic bioavailability ( in this case , LEX ) , and this interaction may be specific to the peptidomimetic beta - lactam antibiotics .", "entity": [{"entity": "AML", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "beta - lactam", "entity_type": "Chemical", "pos": [66, 79]}, {"entity": "LEX", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "beta - lactam", "entity_type": "Chemical", "pos": [191, 204]}], "task": "NER"}
{"text": "Correlation between carbapenem consumption and antimicrobial resistance rates of Acinetobacter baumannii in a university - affiliated hospital in China .", "entity": [{"entity": "carbapenem", "entity_type": "Chemical", "pos": [20, 30]}], "task": "NER"}
{"text": "To investigate the correlation between carbapenem consumption and rates of antimicrobial resistance in Acinetobacter baumannii , carbapenem consumption was expressed as defined daily dose based on the World Health Organization ( WHO ) anatomical therapeutic chemical classification index .", "entity": [{"entity": "carbapenem", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "carbapenem", "entity_type": "Chemical", "pos": [129, 139]}], "task": "NER"}
{"text": "Clinical isolates from 2001 - 2009 were collected and analyzed using WHONET 5 . 4 software .", "entity": [], "task": "NER"}
{"text": "Results show that the consumption of imipenem / cilastatin , meropenem , and total carbapenem is significantly correlated with imipenem resistance in A baumannii ( r = 0 . 818 , P = . 007 ; r = 0 . 817 , P = . 007 ; r = 0 . 827 , P = . 006 ) .", "entity": [{"entity": "imipenem", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "cilastatin", "entity_type": "Chemical", "pos": [48, 58]}, {"entity": "meropenem", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "carbapenem", "entity_type": "Chemical", "pos": [83, 93]}, {"entity": "imipenem", "entity_type": "Chemical", "pos": [127, 135]}], "task": "NER"}
{"text": "Furthermore , total carbapenem consumption is significantly correlated with meropenem resistance in A baumannii ( r = 0 . 900 , P = . 037 ) .", "entity": [{"entity": "carbapenem", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "meropenem", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "In addition , consumption of imipenem / cilastatin , meropenem , and total carbapenem is associated with A baumannii resistance to piperacillin - tazobactam , ceftazidime , cefepime , amikacin , and levofloxacin .", "entity": [{"entity": "imipenem", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "cilastatin", "entity_type": "Chemical", "pos": [40, 50]}, {"entity": "meropenem", "entity_type": "Chemical", "pos": [53, 62]}, {"entity": "carbapenem", "entity_type": "Chemical", "pos": [75, 85]}, {"entity": "piperacillin", "entity_type": "Chemical", "pos": [131, 143]}, {"entity": "tazobactam", "entity_type": "Chemical", "pos": [146, 156]}, {"entity": "ceftazidime", "entity_type": "Chemical", "pos": [159, 170]}, {"entity": "cefepime", "entity_type": "Chemical", "pos": [173, 181]}, {"entity": "amikacin", "entity_type": "Chemical", "pos": [184, 192]}, {"entity": "levofloxacin", "entity_type": "Chemical", "pos": [199, 211]}], "task": "NER"}
{"text": "These drugs are mainly beta - lactams , aminoglycosides , and fluoroquinolones .", "entity": [{"entity": "beta - lactams", "entity_type": "Chemical", "pos": [23, 37]}, {"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [40, 55]}, {"entity": "fluoroquinolones", "entity_type": "Chemical", "pos": [62, 78]}], "task": "NER"}
{"text": "The imipenem and meropenem resistance rates are significantly correlated with resistance rates to numerous antimicrobial drugs ( eg , beta - lactams , aminoglycosides , and fluoroquinolones ) in A baumannii .", "entity": [{"entity": "imipenem", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "meropenem", "entity_type": "Chemical", "pos": [17, 26]}, {"entity": "beta - lactams", "entity_type": "Chemical", "pos": [134, 148]}, {"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [151, 166]}, {"entity": "fluoroquinolones", "entity_type": "Chemical", "pos": [173, 189]}], "task": "NER"}
{"text": "Therefore , increased consumption of carbapenem may contribute to the development of resistance in A baumannii to imipenem , meropenem , and other antimicrobial drugs .", "entity": [{"entity": "carbapenem", "entity_type": "Chemical", "pos": [37, 47]}, {"entity": "imipenem", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "meropenem", "entity_type": "Chemical", "pos": [125, 134]}], "task": "NER"}
{"text": "Cross - resistance possibly occurs among imipenem / cilastatin and meropenem , as well as with beta - lactams , aminoglycosides , and fluoroquinolones .", "entity": [{"entity": "imipenem", "entity_type": "Chemical", "pos": [41, 49]}, {"entity": "cilastatin", "entity_type": "Chemical", "pos": [52, 62]}, {"entity": "meropenem", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "beta - lactams", "entity_type": "Chemical", "pos": [95, 109]}, {"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [112, 127]}, {"entity": "fluoroquinolones", "entity_type": "Chemical", "pos": [134, 150]}], "task": "NER"}
{"text": "Environmental fate of three novel brominated flame retardants in aquatic mesocosms .", "entity": [], "task": "NER"}
{"text": "Currently , little is known about the environmental fate and persistence of novel brominated flame retardants ( NBFRs ) .", "entity": [], "task": "NER"}
{"text": "The recent detection of NBFRs in sediment cores and air samples provides insight into their persistence and potential for transport .", "entity": [], "task": "NER"}
{"text": "Limited numbers of laboratory studies have examined the fate and behavior of these compounds , but field - based fate studies have been especially lacking .", "entity": [], "task": "NER"}
{"text": "The authors conducted an aquatic mesocosm experiment to assess the behavior of three NBFRs : bis ( tribromophenoxy ) ethane ( BTBPE ) , tetrabromobisphenol A bis ( 2 , 3 - dibromopropyl ether ; TBBPA - DBPE ) , and Firemaster BZ - 54 , a commercial mixture containing bis ( 2 - ethylhexyl ) tetrabromophthalate ( BEHTBP ) and 2 - ethylhexyl - 2 , 3 , 4 , 5 - tetrabromobenzoate ( EHTeBB ) in a ratio of 1 : 4 .", "entity": [{"entity": "bis ( tribromophenoxy ) ethane", "entity_type": "Chemical", "pos": [93, 123]}, {"entity": "BTBPE", "entity_type": "Chemical", "pos": [126, 131]}, {"entity": "tetrabromobisphenol A bis ( 2 , 3 - dibromopropyl ether", "entity_type": "Chemical", "pos": [136, 191]}, {"entity": "TBBPA", "entity_type": "Chemical", "pos": [194, 199]}, {"entity": "DBPE", "entity_type": "Chemical", "pos": [202, 206]}, {"entity": "Firemaster BZ - 54", "entity_type": "Chemical", "pos": [215, 233]}, {"entity": "bis ( 2 - ethylhexyl ) tetrabromophthalate", "entity_type": "Chemical", "pos": [268, 310]}, {"entity": "BEHTBP", "entity_type": "Chemical", "pos": [313, 319]}, {"entity": "2 - ethylhexyl - 2 , 3 , 4 , 5 - tetrabromobenzoate", "entity_type": "Chemical", "pos": [326, 377]}, {"entity": "EHTeBB", "entity_type": "Chemical", "pos": [380, 386]}], "task": "NER"}
{"text": "Analysis by gas chromatography - mass spectrometry , operated in the electron capture negative ionization mode , revealed partitioning between the particulate and sediment phases , with BTBPE , TBBPA - DBPE , and BEHTBP identified as being environmentally persistent in both the particulate and the sediment compartments .", "entity": [{"entity": "BTBPE", "entity_type": "Chemical", "pos": [186, 191]}, {"entity": "TBBPA", "entity_type": "Chemical", "pos": [194, 199]}, {"entity": "DBPE", "entity_type": "Chemical", "pos": [202, 206]}, {"entity": "BEHTBP", "entity_type": "Chemical", "pos": [213, 219]}], "task": "NER"}
{"text": "The median dissipation times ( DT50 ) differed in each compartment , with more rapid disappearance in the particulate ( 9 - 30 d ) compared with the sediment compartment ( > 100 d ) for each compound .", "entity": [], "task": "NER"}
{"text": "The degradation products were more concentrated in the particulate compartment and corresponded to known photodegradation products .", "entity": [], "task": "NER"}
{"text": "The ratio of EHTeBB to BEHTBP differed in the mesocosm compartments compared with the technical product used for treatment , indicating increased degradation of EHTeBB relative to BETHBP .", "entity": [{"entity": "EHTeBB", "entity_type": "Chemical", "pos": [13, 19]}, {"entity": "BEHTBP", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "EHTeBB", "entity_type": "Chemical", "pos": [161, 167]}, {"entity": "BETHBP", "entity_type": "Chemical", "pos": [180, 186]}], "task": "NER"}
{"text": "2013 ; 32 : 1060 - 1068 .", "entity": [], "task": "NER"}
{"text": "Acute exposure to DE - 71 causes alterations in visual behavior in zebrafish larvae .", "entity": [], "task": "NER"}
{"text": "Polybrominated diphenyl ethers ( PBDEs ) cause neurobehavioral toxicity , but their effects on visual behavior remain unknown .", "entity": [{"entity": "Polybrominated diphenyl ethers", "entity_type": "Chemical", "pos": [0, 30]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [33, 38]}], "task": "NER"}
{"text": "In the present study , the impact of PBDEs on visual behavior was examined using optokinetic responses and phototaxis in zebrafish larvae .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [37, 42]}], "task": "NER"}
{"text": "Zebrafish embryos were exposed to pentabrominated diphenyl ethers mixture ( DE - 71 ) at concentrations of 0 , 0 . 32 , 3 . 58 , and 31 . 0 micro g / L until 15 d postfertilization .", "entity": [{"entity": "pentabrominated diphenyl ethers", "entity_type": "Chemical", "pos": [34, 65]}], "task": "NER"}
{"text": "The authors then assessed photoreceptor opsin expression , retinal histology , and visual behavior of the larvae .", "entity": [], "task": "NER"}
{"text": "The results showed that the transcriptions of the opsin genes , zfrho and zfgr1 , were significantly upregulated .", "entity": [], "task": "NER"}
{"text": "Western blotting further demonstrated a significant increase in rhodopsin protein expression after exposure of the larvae to DE - 71 .", "entity": [], "task": "NER"}
{"text": "Histological examination revealed the following morphological alterations in the retina : increased area of inner nuclear layer , decreased area of inner plexiform layer , and decreased density of ganglion cells .", "entity": [], "task": "NER"}
{"text": "Tests of optokinetic and phototactic behavior showed hyperactive responses on exposure to DE - 71 , including increased saccadic eye movements and phototactic response .", "entity": [], "task": "NER"}
{"text": "The present study is the first to demonstrate that the acute exposure of zebrafish larvae to DE - 71 causes biochemical and structural changes in the eye that lead to behavioral alterations .", "entity": [], "task": "NER"}
{"text": "Analysis of these visual behavioral paradigms may be useful in predicting the adverse effects of toxicants on visual function in fish .", "entity": [], "task": "NER"}
{"text": "Environ Toxicol Chem 2013 ; 32 : 1370 - 1375 .", "entity": [], "task": "NER"}
{"text": "Rash associated with dabigatran etexilate .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [21, 41]}], "task": "NER"}
{"text": "Patients experiencing atrial fibrillation are at an increased risk for thromboembolic events .", "entity": [], "task": "NER"}
{"text": "Therefore , anticoagulation therapy is imperative to prevent thrombus formation and stroke .", "entity": [], "task": "NER"}
{"text": "Dabigatran etexilate was approved by the Food and Drug Administration in 2010 as anticoagulant prophylaxis for patients with nonvalvular atrial fibrillation .", "entity": [{"entity": "Dabigatran etexilate", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "The frequency of dermatologic reactions to dabigatran etexilate is estimated in the product labeling to be less than 0 . 1 % .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [43, 63]}], "task": "NER"}
{"text": "To date , five cases of dabigatran etexilate - associated rash have reported , including three published cases .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [24, 44]}], "task": "NER"}
{"text": "We describe the sixth reported case of dabigatran etexilate - associated rash , in a 59 - year - old man with a history of atrial fibrillation who received dabigatran etexilate 150 mg twice / day for atrial flutter before cardioversion .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [39, 59]}, {"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [156, 176]}], "task": "NER"}
{"text": "The patient had taken dabigatran etexilate for 5 days before the rash was noted on hospital admission .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [22, 42]}], "task": "NER"}
{"text": "He had no known previous drug allergies , and his platelet count , serum creatinine concentration , and hepatic function were normal .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [73, 83]}], "task": "NER"}
{"text": "The rash resolved 7 days after the discontinuation of dabigatran etexilate , and the patient was stabilized on warfarin therapy .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [54, 74]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship ( score of 5 ) between the patient ' s development of the rash and dabigatran etexilate therapy .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [160, 180]}], "task": "NER"}
{"text": "Clinicians should be aware of this adverse effect of dabigatran etexilate and monitor for dermatologic reactions during follow - up visits .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [53, 73]}], "task": "NER"}
{"text": "Relaxin : New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein .", "entity": [], "task": "NER"}
{"text": "Human relaxin - 2 ( hereafter simply defined as \" relaxin \" ) is a 6 - kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes .", "entity": [], "task": "NER"}
{"text": "This factor can also be involved in the pathophysiology of arterial hypertension and heart failure , in the molecular pathways of fibrosis and cancer , and in angiogenesis and bone remodeling .", "entity": [], "task": "NER"}
{"text": "It belongs to the relaxin peptide family , whose members comprehensively exert numerous effects through interaction with different types of receptors , classified as relaxin family peptide ( RXFP ) receptors ( RXFP1 , RXFP2 , RXFP3 , RXFP4 ) .", "entity": [], "task": "NER"}
{"text": "Research looks toward the in - depth examination and complete understanding of relaxin in its various pleiotropic actions .", "entity": [], "task": "NER"}
{"text": "The intent is to evaluate the likelihood of employing this substance for therapeutic purposes , for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms , also avoiding any adverse effect .", "entity": [], "task": "NER"}
{"text": "Relaxin is already being considered as a promising drug , especially in acute heart failure .", "entity": [], "task": "NER"}
{"text": "A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future .", "entity": [], "task": "NER"}
{"text": "Quantum Dot - Based Thermal Spectroscopy and Imaging of Optically Trapped Microspheres and Single Cells .", "entity": [], "task": "NER"}
{"text": "Laser - induced thermal effects in optically trapped microspheres and single cells are investigated by quantum dot luminescence thermometry .", "entity": [], "task": "NER"}
{"text": "Thermal spectroscopy has revealed a non - localized temperature distribution around the trap that extends over tens of micrometers , in agreement with previous theoretical models besides identifying water absorption as the most important heating source .", "entity": [], "task": "NER"}
{"text": "The experimental results of thermal loading at a variety of wavelengths reveal that an optimum trapping wavelength exists for biological applications close to 820 nm .", "entity": [], "task": "NER"}
{"text": "This is corroborated by a simultaneous analysis of the spectral dependence of cellular heating and damage in human lymphocytes during optical trapping .", "entity": [], "task": "NER"}
{"text": "This quantum dot luminescence thermometry demonstrates that optical trapping with 820 nm laser radiation produces minimum intracellular heating , well below the cytotoxic level ( 43 degrees C ) , thus , avoiding cell damage .", "entity": [], "task": "NER"}
{"text": "A self - organized anisotropic liquid - crystal plasmonic metamaterial .", "entity": [], "task": "NER"}
{"text": "A composite material that leads to self organization of mesogen - coated gold nanospheres is synthesized and shows enhanced anisotropic optical properties due to synergistic effects of the mesogens intrinsic birefringence and its ability to drive the self - assembly process into highly anisotropic architectures with densely packed nanospheres .", "entity": [], "task": "NER"}
{"text": "Such nanoengineered matter sustains a response beyond that achievable by its individual constituents , i . e . , a metamaterial .", "entity": [], "task": "NER"}
{"text": "Nonribosomal assembly of natural lipocyclocarbamate lipoprotein - associated phospholipase inhibitors .", "entity": [], "task": "NER"}
{"text": "EXPANDING OUR KNOWLEDGE : Natural lipocyclocarbamate natural products have provided the inspiration for the first - in - class synthetic phospholipase inhibitor darapladib , currently in phase III clinical trials for the treatment of atherosclerosis .", "entity": [{"entity": "darapladib", "entity_type": "Chemical", "pos": [161, 171]}], "task": "NER"}
{"text": "Here , we discuss their biosynthesis by a nonribosomal peptide synthetase .", "entity": [], "task": "NER"}
{"text": "Engineering new protein - protein interactions on the beta - propeller fold by yeast cell surface display .", "entity": [], "task": "NER"}
{"text": "REINVENTING THE WHEEL : The beta - propeller domain folds like a wheel to provide key protein - protein interactions in the cell .", "entity": [], "task": "NER"}
{"text": "Here we used high - throughput yeast sorting to \" invent \" beta - propellers of new binding specificities with cellular targets .", "entity": [], "task": "NER"}
{"text": "Joining Copper Oxide Nanotube Arrays Driven by the Nanoscale Kirkendall effect .", "entity": [{"entity": "Copper Oxide", "entity_type": "Chemical", "pos": [8, 20]}], "task": "NER"}
{"text": "Various annealing conditions ( environment , temperature , and duration ) are applied to study the nanoscale Kirkendall effect of copper ( Cu ) nanowire ( NW ) arrays on a Si substrate .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [130, 136]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [139, 141]}, {"entity": "Si", "entity_type": "Chemical", "pos": [172, 174]}], "task": "NER"}
{"text": "The results show that an appropriate amount of oxygen supply is crucial for uniform transformation from Cu NWs ( average diameter ~ 50 nm ) into Cu oxide nanotube arrays .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [47, 53]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [104, 106]}, {"entity": "Cu oxide", "entity_type": "Chemical", "pos": [145, 153]}], "task": "NER"}
{"text": "An annealing duration of 30 min at 200 degrees C in a low vacuum environment reveals that the voids are not uniformly distributed at the Cu / Cu oxide interface .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [137, 139]}, {"entity": "Cu oxide", "entity_type": "Chemical", "pos": [142, 150]}], "task": "NER"}
{"text": "This suggests that void growth is due to surface diffusion of Cu along void surfaces .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [62, 64]}], "task": "NER"}
{"text": "Annealing above 200 degrees C for 60 min resulted in complete transformation from Cu NWs into Cu oxide nanotubes .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [82, 84]}, {"entity": "Cu oxide", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "X - ray photoelectron spectroscopy characterization indicates that the Cu oxides formed at 200 degrees C and 300 degrees C are Cu ( 2 ) O and CuO , respectively .", "entity": [{"entity": "Cu oxides", "entity_type": "Chemical", "pos": [71, 80]}, {"entity": "Cu ( 2 ) O", "entity_type": "Chemical", "pos": [127, 137]}, {"entity": "CuO", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "It is demonstrated that the transformation from Cu NW arrays into Cu oxide nanotube arrays can be combined with the joining of stacked Si chips in a single - process step with reasonable joint shear strength .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [48, 50]}, {"entity": "Cu oxide", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "Si", "entity_type": "Chemical", "pos": [135, 137]}], "task": "NER"}
{"text": "Transmission electron microscopy - electron energy loss spectroscopy elemental mapping analysis reveals that the joint interface is Cu oxide .", "entity": [{"entity": "Cu oxide", "entity_type": "Chemical", "pos": [132, 140]}], "task": "NER"}
{"text": "The outward diffusion of Cu driven by the nanoscale Kirkendall effect is believed to enhance the joining process .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [25, 27]}], "task": "NER"}
{"text": "By controlling the environment , temperature , and duration , joined Cu ( 2 ) O or CuO nanotube stacked chips can be achieved , which serve as a platform for the further development of nanostructured , stacked devices .", "entity": [{"entity": "Cu ( 2 ) O", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "CuO", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Protein - Carbohydrate Complex Reveals Circulating Metastatic Cells in a Microfluidic Assay .", "entity": [{"entity": "Carbohydrate", "entity_type": "Chemical", "pos": [10, 22]}], "task": "NER"}
{"text": "Advances in carbohydrate sequencing technologies reveal the tremendous complexity of the glycome and the role that glycomics might have to bring insight into the biological functions .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [12, 24]}], "task": "NER"}
{"text": "Carbohydrate - protein interactions , in particular , are known to be crucial to most mammalian physiological processes as mediators of cell adhesion and metastasis , signal transducers , and organizers of protein interactions .", "entity": [{"entity": "Carbohydrate", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "An assay is developed here to mimic the multivalency of biological complexes that selectively and sensitively detect carbohydrate - protein interactions .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [117, 129]}], "task": "NER"}
{"text": "The binding of beta - galactosides and galectin - 3 - a protein that is correlated to the progress of tumor and metastasis - is examined .", "entity": [{"entity": "beta - galactosides", "entity_type": "Chemical", "pos": [15, 34]}], "task": "NER"}
{"text": "The efficiency of the assay is related to the expression of the receptor while anchoring to the interaction ' s strength .", "entity": [], "task": "NER"}
{"text": "Comparative binding experiments reveal molecular binding preferences .", "entity": [], "task": "NER"}
{"text": "This study establishes that the assay is robust to isolate metastatic cells from colon affected patients and paves the way to personalized medicine .", "entity": [], "task": "NER"}
{"text": "Modulation of photophysics and pKa shift of the anti - cancer drug camptothecin in the nanocavities of supramolecular hosts .", "entity": [{"entity": "camptothecin", "entity_type": "Chemical", "pos": [67, 79]}], "task": "NER"}
{"text": "This article reports the pK ( a ) shift of an anti - cancer drug , 20 ( S ) - camptothecin ( CPT ) , upon encapsulation into the nanocavity of a cucurbit [ 7 ] uril ( CB7 ) macrocycle .", "entity": [{"entity": "20 ( S ) - camptothecin", "entity_type": "Chemical", "pos": [67, 90]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "cucurbit [ 7 ] uril", "entity_type": "Chemical", "pos": [145, 164]}, {"entity": "CB7", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "Steady - state , time - resolved fluorescence and electrospray ionisation mass spectrometry ( ESI - MS ) studies provide evidence for the formation of both 1 : 1 and 2 : 1 ( CB7 . CPT ) stoichiometries .", "entity": [{"entity": "CB7", "entity_type": "Chemical", "pos": [174, 177]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [180, 183]}], "task": "NER"}
{"text": "Astonishingly , we have found that protonation of CPT takes place at a higher concentration of macrocycle ( >= 50 mu M ) when the 2 : 1 stoichiometric complex develops .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "However , we did not find any proof for protonation of CPT when it is encased by a beta - cyclodextrin cavity , which has a cavity size almost the same as that of CB7 .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "beta - cyclodextrin", "entity_type": "Chemical", "pos": [83, 102]}, {"entity": "CB7", "entity_type": "Chemical", "pos": [163, 166]}], "task": "NER"}
{"text": "Hence , we conclude that electron - rich carbonyl portals of CB7 have an important role in protonation of the drug in the 2 : 1 inclusion complex .", "entity": [{"entity": "carbonyl", "entity_type": "Chemical", "pos": [41, 49]}, {"entity": "CB7", "entity_type": "Chemical", "pos": [61, 64]}], "task": "NER"}
{"text": "Docking and semi - empirical quantum chemical calculations have been employed to gain an insight into the molecular picture of orientation of CPT in the inclusion complexes .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "It is clearly seen from the optimised structure of the 2 : 1 ( CB7 . CPT ) inclusion complex that the quinoline nitrogen of CPT does not reside within either of the CB7 cavities , rather it is almost sandwiched between two CB7 rings , and therefore , it experiences huge electron density exerted by both carbonyl portals of the macrocycles .", "entity": [{"entity": "CB7", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "quinoline nitrogen", "entity_type": "Chemical", "pos": [102, 120]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "CB7", "entity_type": "Chemical", "pos": [165, 168]}, {"entity": "CB7", "entity_type": "Chemical", "pos": [223, 226]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [304, 312]}], "task": "NER"}
{"text": "As a result , the pK ( a ) of CPT shifts from 1 . 2 to 6 . 2 .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "Finally , controlled release of the drug has been achieved through the introduction of NaCl , which is rich in cells , as an external stimulus .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [87, 91]}], "task": "NER"}
{"text": "We hope this recognition - mediated binding and release mechanism can be useful for activation of the drug and controlled release of the drug in therapeutic uses .", "entity": [], "task": "NER"}
{"text": "Species difference in the mechanism of nonlinear pharmacokinetics of e2074 , a novel sodium channel inhibitor , in rats , dogs , and monkeys .", "entity": [{"entity": "e2074", "entity_type": "Chemical", "pos": [69, 74]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [85, 91]}], "task": "NER"}
{"text": "New chemical entities often exhibit nonlinear pharmacokinetics ( PK ) profiles in experimental animals .", "entity": [], "task": "NER"}
{"text": "However , the number of studies that have focused on species differences in nonlinear PK is very limited ; thus , the aim of this study was to clarify the mechanism of the nonlinear PK of E2074 ( 2 - [ ( 2R ) - 2 - fluoro - 3 - { ( 3r ) - [ ( 3 - fluorobenzyl ) oxy ] - 8 - azabicyclo [ 3 . 2 . 1 ] oct - 8 - yl } propyl ] - 4 , 5 - dimethyl - 2 , 4 - dihydro - 3H - 1 , 2 , 4 - triazol - 3 - one ) , a novel sodium channel inhibitor , in rats , dogs , and monkeys .", "entity": [{"entity": "E2074", "entity_type": "Chemical", "pos": [188, 193]}, {"entity": "2 - [ ( 2R ) - 2 - fluoro - 3 - { ( 3r ) - [ ( 3 - fluorobenzyl ) oxy ] - 8 - azabicyclo [ 3 . 2 . 1 ] oct - 8 - yl } propyl ] - 4 , 5 - dimethyl - 2 , 4 - dihydro - 3H - 1 , 2 , 4 - triazol - 3 - one", "entity_type": "Chemical", "pos": [196, 396]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [409, 415]}], "task": "NER"}
{"text": "Nonlinear PK profiles with more than dose - proportional increases of Cmax and area under the plasma concentration curve were observed in all species after oral administration .", "entity": [], "task": "NER"}
{"text": "The Michaelis - Menten constant ( Km ) values of hepatic microsomal metabolism were 7 . 23 and 0 . 41 mu M in rats and dogs in vitro , respectively , which were lower than the unbound maximum plasma concentrations after oral administration in vivo , indicating that the nonlinear PK in rats and dogs was attributable to the saturation of hepatic metabolism .", "entity": [], "task": "NER"}
{"text": "However , we do not believe that the saturation of hepatic metabolism was the mechanism of nonlinearity in monkeys because of the high Km value ( 42 . 44 mu M ) observed in liver microsomes .", "entity": [], "task": "NER"}
{"text": "Intestinal metabolism was observed in monkey intestinal microsomes but not in rats and dogs , and the nonlinear PK in monkeys was diminished by inhibition of intestinal metabolism with a concomitant oral dose of ketoconazole .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [212, 224]}], "task": "NER"}
{"text": "These results suggest that saturation of the intestinal metabolism is the potential mechanism of nonlinearity in monkeys .", "entity": [], "task": "NER"}
{"text": "P - glycoprotein was not involved in the nonlinear PK profiles in any species .", "entity": [], "task": "NER"}
{"text": "In conclusion , the mechanism of the nonlinear PK of E2074 is species dependent , with the saturation of hepatic metabolism in rats and dogs and that of intestinal metabolism in monkeys being the primary cause .", "entity": [{"entity": "E2074", "entity_type": "Chemical", "pos": [53, 58]}], "task": "NER"}
{"text": "Interaction of silymarin flavonolignans with organic anion - transporting polypeptides .", "entity": [{"entity": "flavonolignans", "entity_type": "Chemical", "pos": [25, 39]}], "task": "NER"}
{"text": "Organic anion - transporting polypeptides ( OATPs ) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption and elimination , including the intestine and liver .", "entity": [], "task": "NER"}
{"text": "Silymarin is a popular herbal supplement often used by patients with chronic liver disease ; higher oral doses than those customarily used ( 140 mg three times / day ) are being evaluated clinically .", "entity": [], "task": "NER"}
{"text": "The present study examined the effect of silymarin flavonolignans on OATP1B1 - , OATP1B3 - , and OATP2B1 - mediated transport in cell lines stably expressing these transporters and in human hepatocytes .", "entity": [{"entity": "flavonolignans", "entity_type": "Chemical", "pos": [51, 65]}], "task": "NER"}
{"text": "In overexpressing cell lines , OATP1B1 - and OATP1B3 - mediated estradiol - 17 beta - glucuronide uptake and OATP2B1 - mediated estrone - 3 - sulfate uptake were inhibited by most of the silymarin flavonolignans investigated .", "entity": [{"entity": "estradiol - 17 beta - glucuronide", "entity_type": "Chemical", "pos": [64, 97]}, {"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [128, 149]}, {"entity": "flavonolignans", "entity_type": "Chemical", "pos": [197, 211]}], "task": "NER"}
{"text": "OATP1B1 - , OATP1B3 - , and OATP2B1 - mediated substrate transport was inhibited efficiently by silymarin ( IC50 values of 1 . 3 , 2 . 2 and 0 . 3 micro M , respectively ) , silybin A ( IC50 values of 9 . 7 , 2 . 7 and 4 . 5 micro M , respectively ) , silybin B ( IC50 values of 8 . 5 , 5 . 0 and 0 . 8 micro M , respectively ) , and silychristin ( IC50 values of 9 . 0 , 36 . 4 , and 3 . 6 micro M , respectively ) .", "entity": [{"entity": "silybin A", "entity_type": "Chemical", "pos": [174, 183]}, {"entity": "silybin B", "entity_type": "Chemical", "pos": [252, 261]}, {"entity": "silychristin", "entity_type": "Chemical", "pos": [334, 346]}], "task": "NER"}
{"text": "Furthermore , silymarin , silybin A , and silybin B ( 100 micro M ) significantly inhibited OATP - mediated estradiol - 17 beta - glucuronide and rosuvastatin uptake into human hepatocytes .", "entity": [{"entity": "silybin A", "entity_type": "Chemical", "pos": [26, 35]}, {"entity": "silybin B", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "estradiol - 17 beta - glucuronide", "entity_type": "Chemical", "pos": [108, 141]}, {"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [146, 158]}], "task": "NER"}
{"text": "Calculation of the maximal unbound portal vein concentrations / IC50 values indicated a low risk for silymarin - drug interactions in hepatic uptake with a customary silymarin dose .", "entity": [], "task": "NER"}
{"text": "The extent of silymarin - drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport .", "entity": [{"entity": "flavonolignans", "entity_type": "Chemical", "pos": [102, 116]}], "task": "NER"}
{"text": "Higher than customary doses of silymarin , or formulations with improved bioavailability , may increase the risk of flavonolignan interactions with OATP substrates in patients .", "entity": [{"entity": "flavonolignan", "entity_type": "Chemical", "pos": [116, 129]}], "task": "NER"}
{"text": "Thiolates chemically induce redox activation of BTZ043 and related potent nitroaromatic anti - tuberculosis agents .", "entity": [{"entity": "Thiolates", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "BTZ043", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "nitroaromatic", "entity_type": "Chemical", "pos": [74, 87]}], "task": "NER"}
{"text": "The development of multidrug resistant ( MDR ) and extensively drug resistant ( XDR ) forms of tuberculosis ( TB ) has stimulated research efforts globally to expand the new drug pipeline .", "entity": [], "task": "NER"}
{"text": "Nitroaromatic compounds , including 1 , 3 - benzothiazin - 4 - ones ( BTZs ) and related agents , are a promising new class for the treatment of TB .", "entity": [{"entity": "Nitroaromatic", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "1 , 3 - benzothiazin - 4 - ones", "entity_type": "Chemical", "pos": [36, 67]}, {"entity": "BTZs", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "Research has shown that the nitroso intermediates of BTZs that are generated in vivo cause suicide inhibition of decaprenylphosphoryl - beta - D - ribose 2 ' oxidase ( DprE1 ) , which is responsible for cell wall arabinogalactan biosynthesis .", "entity": [{"entity": "nitroso", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "BTZs", "entity_type": "Chemical", "pos": [53, 57]}, {"entity": "decaprenylphosphoryl - beta - D - ribose", "entity_type": "Chemical", "pos": [113, 153]}], "task": "NER"}
{"text": "We have designed and synthesized novel anti - TB agents inspired from BTZs and other nitroaromatic compounds .", "entity": [{"entity": "BTZs", "entity_type": "Chemical", "pos": [70, 74]}, {"entity": "nitroaromatic", "entity_type": "Chemical", "pos": [85, 98]}], "task": "NER"}
{"text": "Computational studies indicated that the unsubstituted aromatic carbons of BTZ043 and related nitroaromatic compounds are the most electron - deficient and might be prone to nucleophilic attack .", "entity": [{"entity": "carbons", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "BTZ043", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "nitroaromatic", "entity_type": "Chemical", "pos": [94, 107]}], "task": "NER"}
{"text": "Our chemical studies on BTZ043 and the additional nitroaromatic compounds synthesized by us and others confirmed the postulated reactivity .", "entity": [{"entity": "BTZ043", "entity_type": "Chemical", "pos": [24, 30]}, {"entity": "nitroaromatic", "entity_type": "Chemical", "pos": [50, 63]}], "task": "NER"}
{"text": "The results indicate that nucleophiles such as thiolates , cyanide , and hydride induce nonenzymatic reduction of the nitro groups present in these compounds to the corresponding nitroso intermediates by addition at the unsubstituted electron - deficient aromatic carbon present in these compounds .", "entity": [{"entity": "thiolates", "entity_type": "Chemical", "pos": [47, 56]}, {"entity": "cyanide", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "hydride", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "nitro", "entity_type": "Chemical", "pos": [118, 123]}, {"entity": "nitroso", "entity_type": "Chemical", "pos": [179, 186]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [264, 270]}], "task": "NER"}
{"text": "Furthermore , we demonstrate here that these compounds are good candidates for the classical von Richter reaction .", "entity": [], "task": "NER"}
{"text": "These chemical studies offer an alternate hypothesis for the mechanism of action of nitroaromatic anti - TB agents , in that the cysteine thiol ( ate ) or a hydride source at the active site of DprE1 may trigger the reduction of the nitro groups in a manner similar to the von Richter reaction to the nitroso intermediates , to initiate the inhibition of DprE1 .", "entity": [{"entity": "nitroaromatic", "entity_type": "Chemical", "pos": [84, 97]}, {"entity": "cysteine thiol ( ate )", "entity_type": "Chemical", "pos": [129, 151]}, {"entity": "hydride", "entity_type": "Chemical", "pos": [157, 164]}, {"entity": "nitro", "entity_type": "Chemical", "pos": [233, 238]}, {"entity": "nitroso", "entity_type": "Chemical", "pos": [301, 308]}], "task": "NER"}
{"text": "A low - overpotential potassium - oxygen battery based on potassium superoxide .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [34, 40]}, {"entity": "potassium superoxide", "entity_type": "Chemical", "pos": [58, 78]}], "task": "NER"}
{"text": "Li - O ( 2 ) battery is regarded as one of the most promising energy storage systems for future applications .", "entity": [{"entity": "Li - O ( 2 )", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "However , its energy efficiency is greatly undermined by the large overpotentials of the discharge ( formation of Li ( 2 ) O ( 2 ) ) and charge ( oxidation of Li ( 2 ) O ( 2 ) ) reactions .", "entity": [{"entity": "Li ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [114, 130]}, {"entity": "Li ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [159, 175]}], "task": "NER"}
{"text": "The parasitic reactions of electrolyte and carbon electrode induced by the high charging potential cause the decay of capacity and limit the battery life .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [43, 49]}], "task": "NER"}
{"text": "Here , a K - O ( 2 ) battery is report that uses K ( + ) ions to capture O ( 2 ) ( - ) to form the thermodynamically stable KO ( 2 ) product .", "entity": [{"entity": "K - O ( 2 )", "entity_type": "Chemical", "pos": [9, 20]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "O ( 2 ) ( - )", "entity_type": "Chemical", "pos": [73, 86]}, {"entity": "KO ( 2 )", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "This allows for the battery to operate through the one - electron redox process of O ( 2 ) / O ( 2 ) ( - ) .", "entity": [{"entity": "O ( 2 )", "entity_type": "Chemical", "pos": [83, 90]}, {"entity": "O ( 2 ) ( - )", "entity_type": "Chemical", "pos": [93, 106]}], "task": "NER"}
{"text": "Our studies confirm the formation and removal of KO ( 2 ) in the battery cycle test .", "entity": [{"entity": "KO ( 2 )", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Furthermore , without the use of catalysts , the battery shows a low discharge / charge potential gap of less than 50 mV at a modest current density , which is the lowest one that has ever been reported in metal - oxygen batteries .", "entity": [{"entity": "metal - oxygen", "entity_type": "Chemical", "pos": [206, 220]}], "task": "NER"}
{"text": "A membrane vesicle - based assay to enable prediction of human biliary excretion .", "entity": [], "task": "NER"}
{"text": "Prediction of biliary excretion is a challenge due to the lack of in vitro assays .", "entity": [], "task": "NER"}
{"text": "Our laboratory previously demonstrated a highly significant correlation between in vitro IC ( 50 ) values against mrp2 using rat canalicular liver plasma membrane vesicles and in vivo biliary excretion ( Colombo et al . , 2012 ) .", "entity": [], "task": "NER"}
{"text": "This study explores the possibility of predicting in vivo biliary excretion in human using membrane vesicles prepared from MDCKII cells transfected with human ABCC2 .", "entity": [], "task": "NER"}
{"text": "In vitro MRP2 activity was determined by measuring the ATP - dependent uptake of 5 ( 6 ) - carboxy - 2 ' , 7 ' - dichlorofluorescein ( CDCF ) in inside - out membrane vesicles isolated from MDCK - ABCC2 cells .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "5 ( 6 ) - carboxy - 2 ' , 7 ' - dichlorofluorescein", "entity_type": "Chemical", "pos": [81, 132]}, {"entity": "CDCF", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "CDCF uptake was time - and concentration - dependent ( K ( m ) of 4 . 0 +/- 1 . 2 micro M and a V ( max ) of 7 . 8 +/- 0 . 9 pmol / mg / min ) and inhibited by benzbromarone and MK - 571 with IC ( 50 ) values of 1 . 2 and 7 . 6 micro M , respectively .", "entity": [{"entity": "CDCF", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "benzbromarone", "entity_type": "Chemical", "pos": [160, 173]}, {"entity": "MK - 571", "entity_type": "Chemical", "pos": [178, 186]}], "task": "NER"}
{"text": "A significant linear correlation ( r ( 2 ) = 0 . 790 ) between the in vitro IC ( 50 ) values from the described MRP2 assay and in vivo biliary excretion in humans was observed using 11 well - documented drugs covering low to high biliary excretions .", "entity": [], "task": "NER"}
{"text": "This study demonstrates , for the first time , that inhibition of CDCF uptake in MDCKII - ABCC2 vesicles not only provides a screening assay to assess MRP2 drug - drug interaction potential , but is also predictive of human MRP2 - mediated biliary excretion .", "entity": [{"entity": "CDCF", "entity_type": "Chemical", "pos": [66, 70]}], "task": "NER"}
{"text": "Effects of hydrogen bonding on internal conversion of GFP - like chromophores .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "The meta - amino systems .", "entity": [{"entity": "meta - amino", "entity_type": "Chemical", "pos": [4, 16]}], "task": "NER"}
{"text": "To rationalize the efficient quenching of the fluorescence and the Z --> E photoisomerization of m - ABDI , the meta - amino analogue of the green fluorescent protein ( GFP ) chromophore , in protic solvents , the femtosecond time - resolved fluorescence and transient infrared ( TRIR ) spectra of m - ABDI in CD3CN , CH3OH , and CD3OD are determined .", "entity": [{"entity": "m - ABDI", "entity_type": "Chemical", "pos": [97, 105]}, {"entity": "meta - amino", "entity_type": "Chemical", "pos": [112, 124]}, {"entity": "m - ABDI", "entity_type": "Chemical", "pos": [298, 306]}, {"entity": "CD3CN", "entity_type": "Chemical", "pos": [310, 315]}, {"entity": "CH3OH", "entity_type": "Chemical", "pos": [318, 323]}, {"entity": "CD3OD", "entity_type": "Chemical", "pos": [330, 335]}], "task": "NER"}
{"text": "For solutions in CD3CN , the fluorescence decay lifetime is ~ 7 . 9 ns and IR absorption lines near 1513 , 1531 , 1557 , and 1613 cm ( - 1 ) of m - ABDI in its electronically excited state were observed with a decay time > 5 ns .", "entity": [{"entity": "CD3CN", "entity_type": "Chemical", "pos": [17, 22]}, {"entity": "m - ABDI", "entity_type": "Chemical", "pos": [144, 152]}], "task": "NER"}
{"text": "For solutions in CH3OH , the fluorescence decay is double exponential with time constants of ~ 16 and 62 ps .", "entity": [{"entity": "CH3OH", "entity_type": "Chemical", "pos": [17, 22]}], "task": "NER"}
{"text": "In addition to IR absorption lines of m - ABDI in its electronically excited state with a decay time of ~ 16 ps , new features near 1513 , 1532 , 1554 , and 1592 cm ( - 1 ) were observed to have a rise time of ~ 19 ps and a decay constant of ~ 58 ps , indicating formation of an intermediate .", "entity": [{"entity": "m - ABDI", "entity_type": "Chemical", "pos": [38, 46]}], "task": "NER"}
{"text": "The assignments for the IR spectra of the ground and excited states were assisted with DFT and TDDFT calculations , respectively .", "entity": [], "task": "NER"}
{"text": "We conclude that the torsion of the exocyclic C = C bond ( the tau torsion ) is responsible for the nonradiative decay of electronically excited m - ABDI in CD3CN .", "entity": [{"entity": "C = C", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "m - ABDI", "entity_type": "Chemical", "pos": [145, 153]}, {"entity": "CD3CN", "entity_type": "Chemical", "pos": [157, 162]}], "task": "NER"}
{"text": "However , in CH3OH and CD3OD , the solute - solvent hydrogen bonding ( SSHB ) interactions diminish significantly the barrier of the tau torsion and induce a new pathway that competes successfully with the tau torsion , consistent with the efficient fluorescence quenching and the diminished yield for Z --> E photoisomerization .", "entity": [{"entity": "CH3OH", "entity_type": "Chemical", "pos": [13, 18]}, {"entity": "CD3OD", "entity_type": "Chemical", "pos": [23, 28]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "The new pathway is likely associated with excited - state proton transfer ( ESPT ) from the solvent to m - ABDI , particularly the carbonyl group , and generates an intermediate ( ESPT * ) that is weakly fluorescent .", "entity": [{"entity": "m - ABDI", "entity_type": "Chemical", "pos": [103, 111]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "Oxidation of tertiary amine - derivatized surfaces to control protein adhesion .", "entity": [{"entity": "tertiary amine", "entity_type": "Chemical", "pos": [13, 27]}], "task": "NER"}
{"text": "Selective oxidation of omega - tertiary amine self - assembled thiol monolayers to tertiary amine N - oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them .", "entity": [{"entity": "omega - tertiary amine", "entity_type": "Chemical", "pos": [23, 45]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [63, 68]}, {"entity": "tertiary amine N - oxides", "entity_type": "Chemical", "pos": [83, 108]}], "task": "NER"}
{"text": "Efficient preparation of both secondary and tertiary linker amides as judged by X - ray photoelectron spectroscopy ( XPS ) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance ( QCM ) sensors using 2 - ( 1H - 7 - azabenzotriazol - 1 - yl ) - 1 , 1 , 3 , 3 - tetramethyl hexafluorophosphate methanaminium uronium ( HATU ) .", "entity": [{"entity": "secondary and tertiary linker amides", "entity_type": "Chemical", "pos": [30, 66]}, {"entity": "amide", "entity_type": "Chemical", "pos": [185, 190]}, {"entity": "quartz", "entity_type": "Chemical", "pos": [214, 220]}, {"entity": "2 - ( 1H - 7 - azabenzotriazol - 1 - yl ) - 1 , 1 , 3 , 3 - tetramethyl hexafluorophosphate methanaminium uronium", "entity_type": "Chemical", "pos": [264, 377]}, {"entity": "HATU", "entity_type": "Chemical", "pos": [380, 384]}], "task": "NER"}
{"text": "Oxidation with hydrogen peroxide was similarly assessed , and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [15, 32]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [103, 112]}], "task": "NER"}
{"text": "Tertiary amine - functionalized sensors adsorbed multilayers of aggregated lysozyme , whereas tertiary amine N - oxides and triethylene glycol - terminated monolayers are consistent with small protein aggregates .", "entity": [{"entity": "Tertiary amine", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "tertiary amine N - oxides", "entity_type": "Chemical", "pos": [94, 119]}, {"entity": "triethylene glycol", "entity_type": "Chemical", "pos": [124, 142]}], "task": "NER"}
{"text": "The surface containing a dimethylamine N - oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins .", "entity": [{"entity": "dimethylamine N - oxide", "entity_type": "Chemical", "pos": [25, 48]}, {"entity": "ethyl secondary amide", "entity_type": "Chemical", "pos": [63, 84]}], "task": "NER"}
{"text": "Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques .", "entity": [{"entity": "tertiary amine", "entity_type": "Chemical", "pos": [13, 27]}], "task": "NER"}
{"text": "Innate immune response and programmed cell death following carrier - mediated delivery of unmodified mRNA to respiratory cells .", "entity": [], "task": "NER"}
{"text": "In this report we show that carrier - mediated delivery of mRNA may activate TLR3 signaling in respiratory cells .", "entity": [], "task": "NER"}
{"text": "This activation of the innate immune system was accompanied with a massive production of type 1 interferons and other immunostimulating cytokines .", "entity": [], "task": "NER"}
{"text": "The recognition of mRNA by the innate immune system was also associated with cell death , which proceeded in human respiratory cells via pyroptosis , a form of programmed cell death mediated by substantial overexpression of caspase - 1 .", "entity": [], "task": "NER"}
{"text": "This indicated that the delivered mRNA is most likely also recognized by NOD - like receptors which regulate caspase - 1 production .", "entity": [], "task": "NER"}
{"text": "The viability of murine respiratory cells was less affected by mRNA transfection , which is in line with the lower transfection efficiency , lower innate immune response and the absence of a massive caspase - 1 upregulation in these cells .", "entity": [], "task": "NER"}
{"text": "Finally , we also demonstrated that the recognition of the delivered mRNA by the innate immune system had a negative effect on mRNA translation .", "entity": [], "task": "NER"}
{"text": "Sexually dimorphic behavior after developmental exposure to characterize endocrine - mediated effects of different non - dioxin - like PCBs in rats .", "entity": [{"entity": "dioxin", "entity_type": "Chemical", "pos": [121, 127]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "Many chemicals are known to exhibit endocrine activity and affect reproductive functions in vertebrates and invertebrates .", "entity": [], "task": "NER"}
{"text": "Endocrine effects include influences on sexual differentiation of the brain during development and reproductive and non - reproductive behavior in adult offspring .", "entity": [], "task": "NER"}
{"text": "We previously demonstrated that developmental exposure to a mixture of polychlorinated biphenyls ( PCBs ) which was reconstituted according to the congener pattern found in human breast milk caused feminization of sweet preference as a sexually dimorphic behavior in adult male rats , following decreases in aromatase activity in the brain of newborn male pups .", "entity": [{"entity": "polychlorinated biphenyls", "entity_type": "Chemical", "pos": [71, 96]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [99, 103]}], "task": "NER"}
{"text": "This result may be due to dioxin - like or non - dioxin - like ( NDL ) PCBs and their respective effects on steroid hormones .", "entity": [{"entity": "dioxin", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "dioxin", "entity_type": "Chemical", "pos": [49, 55]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [71, 75]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [108, 115]}], "task": "NER"}
{"text": "The aim of the present experiments was to determine if exposure to highly purified NDL - PCBs ( to remove Ah receptor active contaminants ) also results in alteration of sweet preference .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [89, 93]}], "task": "NER"}
{"text": "Pregnant rats were orally exposed to PCB52 ( 6 dose groups , total dose of 0 - 3000mg / kg body weight ) or PCB180 ( 6 dose groups , total dose of 0 - 1000mg / kg body weight ) .", "entity": [{"entity": "PCB52", "entity_type": "Chemical", "pos": [37, 42]}, {"entity": "PCB180", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "In a further experiment rat dams were treated with equimolar doses of PCB74 or PCB95 ( total dose , 760 mu mol / kg body weight , corresponding to 229mg / kg or 248mg / kg body weight of PCB74 and PCB95 , respectively ) .", "entity": [{"entity": "PCB74", "entity_type": "Chemical", "pos": [70, 75]}, {"entity": "PCB95", "entity_type": "Chemical", "pos": [79, 84]}, {"entity": "PCB74", "entity_type": "Chemical", "pos": [187, 192]}, {"entity": "PCB95", "entity_type": "Chemical", "pos": [197, 202]}], "task": "NER"}
{"text": "Adult male and female offspring were given a choice between a bottle of saccharin solution ( 0 . 25 % ) and a bottle of tap water on five consecutive days .", "entity": [{"entity": "saccharin", "entity_type": "Chemical", "pos": [72, 81]}], "task": "NER"}
{"text": "Control females consumed approximately twice as much sweetened solution compared with control males , thus , demonstrating sexual dimorphism of this behavior .", "entity": [], "task": "NER"}
{"text": "Only non - significant reduction of sweet preference was found at the top dose level in female offspring after exposure to PCB52 .", "entity": [{"entity": "PCB52", "entity_type": "Chemical", "pos": [123, 128]}], "task": "NER"}
{"text": "Female offspring exposed to PCB180 exhibited signs of supernormal behavior as illustrated by increased saccharin consumption at intermediate dose levels .", "entity": [{"entity": "PCB180", "entity_type": "Chemical", "pos": [28, 34]}, {"entity": "saccharin", "entity_type": "Chemical", "pos": [103, 112]}], "task": "NER"}
{"text": "Decreased sweet preference was observed in females after developmental PCB74 , whereas males were unaffected .", "entity": [{"entity": "PCB74", "entity_type": "Chemical", "pos": [71, 76]}], "task": "NER"}
{"text": "Only PCB95 increased saccharin consumption in exposed males , leading to decreased sexual dimorphism of this behavior and behavioral feminization .", "entity": [{"entity": "PCB95", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "saccharin", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "The results demonstrate that different NDL - PCBs exhibit differential effects on sexually dimorphic behavior and that feminization occurs after removal of Ah receptor active contaminants .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "Comparison with data from the literature reveals little evidence for a relation to anti - androgenic activity of the studied NDL - PCBs .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [131, 135]}], "task": "NER"}
{"text": "Characterization of anti - crotalic antibodies .", "entity": [], "task": "NER"}
{"text": "Crotalus durissus terrificus , C .", "entity": [], "task": "NER"}
{"text": "d . collilineatus , C .", "entity": [], "task": "NER"}
{"text": "d . cascavella and C .", "entity": [], "task": "NER"}
{"text": "d . marajoensis are responsible minor but severe snake bites in Brazil .", "entity": [], "task": "NER"}
{"text": "The venoms of these snakes share the presence of crotoxin , a neurotoxin comprising of two associated components , crotapotin and phospholipase A2 ( PLA2 ) .", "entity": [], "task": "NER"}
{"text": "Treatment of the victims with specific antiserum is the unique effective therapeutic measure .", "entity": [], "task": "NER"}
{"text": "The ability of anti - Crotalus antisera produced by the routine using crude venom to immunize horses or purified crotoxin and PLA2 as individual immunogens was compared .", "entity": [], "task": "NER"}
{"text": "Antisera obtained from horses immunized with C . durissus terrificus crude venom were able to recognize and neutralize not only the toxins presents in C . durissus terrificus , but also the ones present in the venoms from C .", "entity": [], "task": "NER"}
{"text": "d . marajoensis .", "entity": [], "task": "NER"}
{"text": "Antisera from horses immunized with individual crotoxin or PLA2 , although in lesser titers , were also able of recognizing the toxins in all four Crotalus species and neutralize the lethality of the C .", "entity": [], "task": "NER"}
{"text": "d . terrificus venom .", "entity": [], "task": "NER"}
{"text": "Combined effects of organochlorine pesticides heptachlor and hexachlorobenzene on the promotion stage of hepatocarcinogenesis in rats .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [20, 34]}, {"entity": "heptachlor", "entity_type": "Chemical", "pos": [46, 56]}, {"entity": "hexachlorobenzene", "entity_type": "Chemical", "pos": [61, 78]}], "task": "NER"}
{"text": "We aimed to investigate the combined effect of organochlorine pesticides heptachlor ( HEP ) and hexachlorobenzene ( HCB ) by using a medium - term rat liver bioassay .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [47, 61]}, {"entity": "heptachlor", "entity_type": "Chemical", "pos": [73, 83]}, {"entity": "HEP", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "hexachlorobenzene", "entity_type": "Chemical", "pos": [96, 113]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "Male F344 rats were initially administered diethylnitrosamine ( DEN , 200mg / kgi . p . ) ; after a 2 - week non - dosing period , they were given diets containing HEP ( 5 or 25ppm ) , HCB ( 70 or 350ppm ) , or their mixtures ( 5 and 70ppm or 25 and 350ppm ) for 6weeks .", "entity": [{"entity": "diethylnitrosamine", "entity_type": "Chemical", "pos": [43, 61]}, {"entity": "DEN", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "HEP", "entity_type": "Chemical", "pos": [164, 167]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [185, 188]}], "task": "NER"}
{"text": "All rats were subjected to partial hepatectomy at week 3 and killed at week 8 .", "entity": [], "task": "NER"}
{"text": "We observed additive or synergistic effects of HEP and HCB in groups treated with mixtures of these pesticides .", "entity": [{"entity": "HEP", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "Number and area of preneoplastic foci positive for glutathione S - transferase placental form ( GST - P ) were consistently higher in these groups than the sum of individual values in the groups treated with HEP or HCB alone .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "S", "entity_type": "Chemical", "pos": [63, 64]}, {"entity": "HEP", "entity_type": "Chemical", "pos": [208, 211]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [215, 218]}], "task": "NER"}
{"text": "Consistent with these findings , HEP and HCB had additive or synergistic effects on cell proliferation induction within the preneoplastic foci and cytochrome P450 ( CYP ) 2B1 and 3A1 induction , which may lead to more efficient metabolic activation of HEP and HCB .", "entity": [{"entity": "HEP", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "HEP", "entity_type": "Chemical", "pos": [252, 255]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [260, 263]}], "task": "NER"}
{"text": "On the basis of these findings , we conclude that HEP and HCB have additive and synergistic effects on the development of GST - P - positive foci and that higher risks are associated with a combination of residual organochlorine pesticides in foods than with individual residual organochlorine pesticides .", "entity": [{"entity": "HEP", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [58, 61]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [214, 228]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [279, 293]}], "task": "NER"}
{"text": "Monitoring of arsenic levels in some ready - to - use anti - malaria herbal products from drug sales outlets in the Madina area of Accra , Ghana .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "In Ghana anti - malaria herbal medicines or products are used to compliment commercial drugs in treatment and prevention of Plasmodium falciparum infections .", "entity": [], "task": "NER"}
{"text": "In this study , four common aqueous based anti - malaria herbal products ( coded HEB , KFE , MDM and NIB ) which are used by Ghanaian population from pharmacy / herbal stores in the Madina area , Accra were blindly and randomly sampled for cadmium ( Cd ) , arsenic ( As ) and Lead ( Pb ) analysis using Atomic Absorption Spectrophotometry technique .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [240, 247]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [250, 252]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [257, 264]}, {"entity": "As", "entity_type": "Chemical", "pos": [267, 269]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [283, 285]}], "task": "NER"}
{"text": "Arsenic concentrations were 1 . 087 mu g / mL ( 108 . 7 % ) , 1 . 027 mu g / mL ( 102 . 7 % ) , 0 . 330 mu g / mL ( 33 . 0 % ) and 0 . 274 mu g / mL ( 27 . 4 % ) in MDM , KFE , NIB and HEB respectively .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Arsenic concentration determined in MDM and KFE were above the maximum permissible limit of 1 . 0ppm determined by WHO / FAO .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Cadmium concentration in each of the four products as well as lead concentration in KFE , NIB and HEB were below the detection limit of < 0 . 002mg / mL ( Cd ) and < 0 . 005mg / mL ( Pb ) respectively .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [155, 157]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [183, 185]}], "task": "NER"}
{"text": "The maximum permissible limits for Pb and Cd determined by WHO / FAO are 10 . 0ppm and 0 . 3ppm respectively .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [35, 37]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [42, 44]}], "task": "NER"}
{"text": "Thus , random assessment on the safety of some ready - to - use aqueous based anti - malaria herbal products on the market is necessary to prevent public health hazards associated with consuming these plant extracts .", "entity": [], "task": "NER"}
{"text": "Although lead and cadmium concentration in the anti - malaria herbal products were below the maximum permissible limits , their cumulative effect on the health of an individual which consume recommended volume of not less than 1000 mL for effective malaria parasite clearance cannot be ignored .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [18, 25]}], "task": "NER"}
{"text": "Enzymatic catalyzed palm oil hydrolysis under ultrasound irradiation : diacylglycerol synthesis .", "entity": [{"entity": "diacylglycerol", "entity_type": "Chemical", "pos": [71, 85]}], "task": "NER"}
{"text": "Diacylglycerol ( DAG ) rich oils have an organoleptic property like that of regular edible oils , but these oils do not tend to be accumulated as fat .", "entity": [{"entity": "Diacylglycerol", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "DAG", "entity_type": "Chemical", "pos": [17, 20]}], "task": "NER"}
{"text": "Palm oil ranks first in the world in terms of edible oil production owing to its low cost .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to propose a new methodology to produce diacylglycerol by hydrolysis of palm oil using Lipozyme RM IM commercial lipase as a catalyst under ultrasound irradiation .", "entity": [{"entity": "diacylglycerol", "entity_type": "Chemical", "pos": [66, 80]}], "task": "NER"}
{"text": "The reactions were carried out at 55 degrees C with two different methods .", "entity": [], "task": "NER"}
{"text": "First , the reaction system was exposed to ultrasonic waves for the whole reaction time , which led to enzymatic inactivation and water evaporation .", "entity": [], "task": "NER"}
{"text": "Ultrasound was then used to promote emulsification of the water / oil system before the hydrolysis reaction , avoiding contact between the probe and the enzymes .", "entity": [], "task": "NER"}
{"text": "An experimental design was used to optimize the ultrasound - related parameters and maximize the hydrolysis rate , and in these conditions , with a change in equilibrium , DAG production was evaluated .", "entity": [{"entity": "DAG", "entity_type": "Chemical", "pos": [172, 175]}], "task": "NER"}
{"text": "Better reaction conditions were achieved for the second method : 11 . 20 wt . % ( water + oil mass ) water content , 1 . 36 wt . % ( water + oil mass ) enzyme load , 12 h of reaction time , 1 . 2 min and 200 W of exposure to ultrasound .", "entity": [], "task": "NER"}
{"text": "In these conditions diacylglycerol yield was 34 . 17 wt . % .", "entity": [{"entity": "diacylglycerol", "entity_type": "Chemical", "pos": [20, 34]}], "task": "NER"}
{"text": "Clearance and bioavailability study through arterio - venous drug concentrations relationship .", "entity": [], "task": "NER"}
{"text": "Venous plasma drug concentrations are routinely monitored in order to determine pharmacokinetic parameters or to establish relationships with drug pharmacodynamic and clinical effects .", "entity": [], "task": "NER"}
{"text": "Arterial drug concentration is higher than the respective venous concentration during the period where drug input of the substance predominates , whereas venous drug concentration is higher during the long period where drug elimination becomes the main process .", "entity": [], "task": "NER"}
{"text": "This arterial - venous difference responds to current bioavailability and clearance of the drug - individual systems .", "entity": [], "task": "NER"}
{"text": "Following the vein / artery plasma drug concentration ratio at a non - eliminating organ it is possible to monitor both parameters time by time .", "entity": [], "task": "NER"}
{"text": "This way of following up the pharmacokinetic systems allows us to detect any changes in drug absorption or disposition more efficiently , without the need of a long period of time and regardless the duration of such system modification .", "entity": [], "task": "NER"}
{"text": "Spray - dried casein - based micelles as a vehicle for solubilization and controlled delivery of flutamide : Formulation , characterization , and in vivo pharmacokinetics .", "entity": [{"entity": "flutamide", "entity_type": "Chemical", "pos": [97, 106]}], "task": "NER"}
{"text": "Novel casein ( CAS ) - based micelles loaded with the poorly soluble anti - cancer drug , flutamide ( FLT ) , were successfully developed in a powdered form via spray - drying technique .", "entity": [{"entity": "flutamide", "entity_type": "Chemical", "pos": [90, 99]}, {"entity": "FLT", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Genipin ( GNP ) was used to crosslink CAS micelles as demonstrated by color variation of the micelles .", "entity": [{"entity": "Genipin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "GNP", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "Drug solubilization was enhanced by incorporation within the hydrophobic micellar core which was confirmed by solubility study and UV spectra .", "entity": [], "task": "NER"}
{"text": "Spherical core - shell micelles were obtained with a particle size below 100nm and zeta potential around - 30mV .", "entity": [], "task": "NER"}
{"text": "At low drug loading , FLT was totally incorporated within micellar core as revealed by thermal analysis .", "entity": [{"entity": "FLT", "entity_type": "Chemical", "pos": [22, 25]}], "task": "NER"}
{"text": "However , at higher loading , excess non - incorporated drug at micelle surface caused a significant reduction in the surface charge density .", "entity": [], "task": "NER"}
{"text": "Turbidity measurements demonstrated the high physical stability of micelles for 2weeks dependent on GNP - crosslinking degree .", "entity": [{"entity": "GNP", "entity_type": "Chemical", "pos": [100, 103]}], "task": "NER"}
{"text": "In a dry powdered form , the micelles were stable for 6months with no significant changes in drug content or particle size .", "entity": [], "task": "NER"}
{"text": "A sustained drug release from CAS micelles up to 5days was observed .", "entity": [], "task": "NER"}
{"text": "After i . v . administration into rats , CAS micelles exhibited a prolonged plasma circulation of FLT compared to drug solution .", "entity": [{"entity": "FLT", "entity_type": "Chemical", "pos": [98, 101]}], "task": "NER"}
{"text": "Furthermore , a more prolonged drug systemic circulation was observed for GNP - crosslinked micelles .", "entity": [{"entity": "GNP", "entity_type": "Chemical", "pos": [74, 77]}], "task": "NER"}
{"text": "Overall , this study reports the application of spray - dried natural protein - based micelles for i . v . delivery of hydrophobic anti - cancer drugs such as FLT .", "entity": [{"entity": "FLT", "entity_type": "Chemical", "pos": [159, 162]}], "task": "NER"}
{"text": "Neuroprotective effects of mercaptoethylleonurine and mercaptoethylguanidine analogs on hydrogen peroxide - induced apoptosis in human neuronal SH - SY5Y cells .", "entity": [{"entity": "mercaptoethylleonurine", "entity_type": "Chemical", "pos": [27, 49]}, {"entity": "mercaptoethylguanidine", "entity_type": "Chemical", "pos": [54, 76]}, {"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [88, 105]}], "task": "NER"}
{"text": "A series of mercaptoethylleonurine and mercaptoethylguanidine derivatives were designed and synthesized .", "entity": [{"entity": "mercaptoethylleonurine", "entity_type": "Chemical", "pos": [12, 34]}, {"entity": "mercaptoethylguanidine", "entity_type": "Chemical", "pos": [39, 61]}], "task": "NER"}
{"text": "Their neuroprotective effects toward H2O2 - induced apoptosis were investigated in human SH - SY5Y cells .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "The results from these studies identified several potent compounds , with compound 8k emerging as the most effective .", "entity": [], "task": "NER"}
{"text": "Further investigation demonstrated that 8k reduced H2O2 - induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of Bcl - 2 .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "Moreover , the molecular mechanism underlying the observed neuroprotective effects of 8k was exerted via the Akt and JNK pathways .", "entity": [], "task": "NER"}
{"text": "Compound 8k can be a lead compound for further discovery of neuroprotective medicine .", "entity": [], "task": "NER"}
{"text": "Paeoniflorin protects human EA . hy926 endothelial cells against gamma - radiation induced oxidative injury by activating the NF - E2 - related factor 2 / heme oxygenase - 1 pathway .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "heme", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "Pulmonary endothelial cells have been demonstrated to have a critical role in the pathogenesis of radiation - induced lung injury .", "entity": [], "task": "NER"}
{"text": "Our preliminary experiments indicated that Paeoniflorin protected human EA . hy926 endothelial cells from radiation - induced oxidative injury .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [43, 55]}], "task": "NER"}
{"text": "This study was designed to confirm the protective effect of Paeoniflorin against radiation - induced endothelial cellular damage and to elucidate the underlying mechanisms .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [60, 72]}], "task": "NER"}
{"text": "Preincubation of EA . hy926 cells with Paeoniflorin before gamma - radiation resulted in significant inhibition of apoptosis , a decrease in mitochondrial membrane potential and enhanced cell viability .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [39, 51]}], "task": "NER"}
{"text": "In particular , we showed that Paeoniflorin significantly reduced the formation of intracellular reactive oxygen species ( ROS ) , the level of malondialdehyde ( MDA ) and lactate dehydrogenase ( LDH ) leakage , and enhanced production of the endogenous antioxidants , glutathione ( GSH ) and superoxide dismutase ( SOD ) in EA . hy926 cells .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [31, 43]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [106, 112]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [144, 159]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [162, 165]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [172, 179]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [269, 280]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [283, 286]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [293, 303]}], "task": "NER"}
{"text": "Treatment of these cells with Paeoniflorin significantly induced HO - 1 expression .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [30, 42]}], "task": "NER"}
{"text": "Moreover , Paeoniflorin promoted the nuclear translocation of nuclear factor erythroid 2 related factor - 2 ( Nrf - 2 ) .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [11, 23]}], "task": "NER"}
{"text": "The Paeoniflorin - induced HO - 1 expression was abrogated by Nrf2 siRNA .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [4, 16]}], "task": "NER"}
{"text": "Furthermore , inhibition of HO - 1 with zinc protoporphyrin IX ( ZNPP ) significantly reversed the protective effect of Paeoniflorin against radiation - induced damage in EA . hy926 cells .", "entity": [{"entity": "zinc protoporphyrin IX", "entity_type": "Chemical", "pos": [40, 62]}, {"entity": "ZNPP", "entity_type": "Chemical", "pos": [65, 69]}, {"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [120, 132]}], "task": "NER"}
{"text": "Our findings confirmed that Paeoniflorin protected EA . hy926 cells against radiation - induced injury through the Nrf2 / HO - 1 pathway .", "entity": [{"entity": "Paeoniflorin", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "Stimuli - responsive copolymer solution and surface assemblies for biomedical applications .", "entity": [], "task": "NER"}
{"text": "Stimuli - responsive polymeric materials is one of the fastest growing fields of the 21st century , with the annual number of papers published more than quadrupling in the last ten years .", "entity": [], "task": "NER"}
{"text": "The responsiveness of polymer solution assemblies and surfaces to biological stimuli ( e . g . pH , reduction - oxidation , enzymes , glucose ) and externally applied triggers ( e . g . temperature , light , solvent quality ) shows particular promise for various biomedical applications including drug delivery , tissue engineering , medical diagnostics , and bioseparations .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [134, 141]}], "task": "NER"}
{"text": "Furthermore , the integration of copolymer architectures into stimuli - responsive materials design enables exquisite control over the locations of responsive sites within self - assembled nanostructures .", "entity": [], "task": "NER"}
{"text": "The combination of new synthesis techniques and well - defined copolymer self - assembly has facilitated substantial developments in stimuli - responsive materials in recent years .", "entity": [], "task": "NER"}
{"text": "In this tutorial review , we discuss several methods that have been employed to synthesize self - assembling and stimuli - responsive copolymers for biomedical applications , and we identify common themes in the response mechanisms among the targeted stimuli .", "entity": [], "task": "NER"}
{"text": "Additionally , we highlight parallels between the chemistries used for generating solution assemblies and those employed for creating copolymer surfaces .", "entity": [], "task": "NER"}
{"text": "Anatomical connection strength predicts dopaminergic drug effects on fronto - striatal function .", "entity": [], "task": "NER"}
{"text": "RATIONALE : The neurotransmitter dopamine plays a key role in cognitive functions that are associated with fronto - striatal circuitry and has been implicated in many neuropsychiatric disorders .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "However , there is a large variability in the direction and extent of dopaminergic drug effects across individuals .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : We investigated whether individual differences in dopaminergic drug effects on human fronto - striatal functioning are associated with individual differences in white matter tracts .", "entity": [], "task": "NER"}
{"text": "METHODS : The effects of the dopamine receptor agonist bromocriptine were assessed using functional magnetic resonance imaging in 22 healthy volunteers in a placebo - controlled , double - blind , within - subject design .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "bromocriptine", "entity_type": "Chemical", "pos": [55, 68]}], "task": "NER"}
{"text": "Human psychopharmacology and functional neuroimaging were combined with functional connectivity analyses and structural connectivity analyses to establish a link between dopaminergic drug effects on fronto - striatal function and fronto - striatal anatomy .", "entity": [], "task": "NER"}
{"text": "RESULTS : We demonstrate that bromocriptine alters functional signals associated with attention switching in the basal ganglia .", "entity": [{"entity": "bromocriptine", "entity_type": "Chemical", "pos": [30, 43]}], "task": "NER"}
{"text": "Crucially , individual differences in the drug ' s effect on these signals could be predicted from individual differences in fronto - striato - thalamic white matter tracts , as indexed by diffusion tensor imaging .", "entity": [], "task": "NER"}
{"text": "Anatomical fronto - striatal connectivity also predicted drug effects on switch - related functional connectivity between the basal ganglia and the prefrontal cortex .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : These data reinforce the link between dopamine , cognition and the basal ganglia and have implications for the individual tailoring of dopaminergic drug therapy based on anatomical fronto - striatal connection strength .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Management of chemotherapy - induced nausea and vomiting : focus on newer agents and new uses for older agents .", "entity": [], "task": "NER"}
{"text": "Chemotherapy - induced nausea and vomiting ( CINV ) is associated with a significant deterioration in quality of life .", "entity": [], "task": "NER"}
{"text": "The emetogenicity of the chemotherapeutic agents , repeated chemotherapy cycles , and patient risk factors significantly influence CINV .", "entity": [], "task": "NER"}
{"text": "The use of a combination of a serotonin 5 - HT3 receptor antagonist , dexamethasone and a neurokinin 1 ( NK1 ) receptor antagonist has significantly improved the control of acute and delayed emesis in single - day chemotherapy .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [30, 39]}, {"entity": "dexamethasone", "entity_type": "Chemical", "pos": [70, 83]}], "task": "NER"}
{"text": "Palonosetron , a second - generation 5 - HT3 receptor antagonist with a different half - life , a different binding capacity and a different mechanism of action than the first - generation 5 - HT3 receptor antagonists appears to be the most effective agent in its class .", "entity": [{"entity": "Palonosetron", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Aprepitant , the first and only agent clinically available in the NK1 receptor antagonist drug class has been used effectively as an additive agent to the 5 - HT3 receptor antagonists and dexamethasone to control CINV .", "entity": [{"entity": "Aprepitant", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "dexamethasone", "entity_type": "Chemical", "pos": [188, 201]}], "task": "NER"}
{"text": "Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials .", "entity": [{"entity": "Rolapitant", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "netupitant", "entity_type": "Chemical", "pos": [15, 25]}], "task": "NER"}
{"text": "Despite the control of emesis , nausea has not been well controlled by current agents .", "entity": [], "task": "NER"}
{"text": "Olanzapine , a US - FDA approved antipsychotic , has emerged in recent trials as an effective preventative agent for CINV , as well as a very effective agent for the treatment of breakthrough emesis and nausea .", "entity": [{"entity": "Olanzapine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Clinical trials using gabapentin , cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV .", "entity": [{"entity": "gabapentin", "entity_type": "Chemical", "pos": [22, 32]}], "task": "NER"}
{"text": "Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple - day chemotherapy and bone marrow transplantation .", "entity": [], "task": "NER"}
{"text": "Predicting the Optimal Basal Insulin Infusion Pattern in Children and Adolescents on Insulin Pumps .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEWe aimed at developing and cross - validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy ( CSII ) . RESEARCH DESIGN AND METHODSWe used the German / Austrian DPV - Wiss database for quality control and scientific surveys in pediatric diabetology and retrieved all CSII patients < 20 years of age ( November 2009 ) .", "entity": [], "task": "NER"}
{"text": "A total of 1 , 248 individuals from our previous study were excluded ( dataset 1 ) , resulting in 6 , 063 CSII patients ( dataset 2 ) ( mean age 10 . 6 +/- 4 . 3 years ) .", "entity": [], "task": "NER"}
{"text": "Only the most recent basal insulin infusion rates ( BRs ) were considered .", "entity": [], "task": "NER"}
{"text": "BR patterns were identified and corresponding patients sorted by unsupervised clustering .", "entity": [], "task": "NER"}
{"text": "Logistic regression analysis was applied to calculate the probabilities for each BR pattern .", "entity": [], "task": "NER"}
{"text": "Equations were based on both independent datasets separately , and probabilities for BR patterns were cross - validated using typical test patients . RESULTSOf the 6 , 063 children , 5 , 903 clustered in one of four major circadian BR patterns , confirming our previous study .", "entity": [], "task": "NER"}
{"text": "The oldest age - group ( mean age 12 . 8 years ) was represented by 2 , 490 patients ( 42 . 18 % ) with a biphasic dawn - dusk pattern ( BC ) .", "entity": [], "task": "NER"}
{"text": "A broad single insulin maximum at 9 - 10 p . m .", "entity": [], "task": "NER"}
{"text": "( F ) was unveiled by 853 patients ( 14 . 45 % ) ( mean age 6 . 3 years ) .", "entity": [], "task": "NER"}
{"text": "Logistic regression analysis revealed that age , to a lesser extent duration of diabetes , and partly sex predicted BR patterns .", "entity": [], "task": "NER"}
{"text": "Cross - validation revealed almost identical probabilities for BR patterns BC and F in the two datasets but some variation in the remaining two BR patterns . CONCLUSIONSReconfirmation of four key BR patterns in two very large independent cohorts supports that these patterns are realistic approximations of the circadian distribution of insulin needs in children with type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "Prediction of an optimal pattern a priori can improve initiation and clinical follow - up of CSII in children and adolescents .", "entity": [], "task": "NER"}
{"text": "In addition , these BR patterns represent valuable information for insulin - infusion algorithms in closed - loop CSII .", "entity": [], "task": "NER"}
{"text": "Metabolism - Dependent Inhibition of CYP3A4 by Lapatinib : Evidence for Formation of a Metabolic Intermediate Complex with a Nitroso / Oxime Metabolite Formed via a Nitrone Intermediate .", "entity": [{"entity": "Lapatinib", "entity_type": "Chemical", "pos": [47, 56]}, {"entity": "Nitroso", "entity_type": "Chemical", "pos": [125, 132]}, {"entity": "Oxime", "entity_type": "Chemical", "pos": [135, 140]}, {"entity": "Nitrone", "entity_type": "Chemical", "pos": [165, 172]}], "task": "NER"}
{"text": "Metabolism - dependent inhibition ( MDI ) of cytochrome P450 ( P450 ) enzymes has the potential to cause clinically relevant drug - drug interactions .", "entity": [], "task": "NER"}
{"text": "In the case of several alkylamine drugs , MDI of P450 involves formation of a metabolite that binds quasi - irreversibly to the ferrous heme iron to form a metabolic intermediate ( MI ) complex .", "entity": [{"entity": "alkylamine", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "ferrous", "entity_type": "Chemical", "pos": [128, 135]}, {"entity": "heme", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "iron", "entity_type": "Chemical", "pos": [141, 145]}], "task": "NER"}
{"text": "The specific metabolites coordinately bound to ferrous iron and the pathways leading to MI complex formation are the subject of debate .", "entity": [{"entity": "ferrous", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "iron", "entity_type": "Chemical", "pos": [55, 59]}], "task": "NER"}
{"text": "We describe an approach combining heme iron oxidation with potassium ferricyanide and metabolite profiling to probe the mechanism of MI complex - based CYP3A4 inactivation by the secondary alkylamine drug lapatinib .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "iron", "entity_type": "Chemical", "pos": [39, 43]}, {"entity": "potassium ferricyanide", "entity_type": "Chemical", "pos": [59, 81]}, {"entity": "secondary alkylamine", "entity_type": "Chemical", "pos": [179, 199]}, {"entity": "lapatinib", "entity_type": "Chemical", "pos": [205, 214]}], "task": "NER"}
{"text": "Ten metabolites formed from lapatinib by CYP3A4 - mediated heteroatom dealkylation , C - hydroxylation , N - oxygenation with or without further oxidation , or a combination thereof , were detected by accurate mass spectrometry .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [28, 37]}, {"entity": "C", "entity_type": "Chemical", "pos": [41, 42]}, {"entity": "N", "entity_type": "Chemical", "pos": [105, 106]}], "task": "NER"}
{"text": "The abundance of one metabolite , the N - dealkylated nitroso / oxime lapatinib metabolite ( M9 ) , correlated directly with the prevalence or the disruption of the MI complex with CYP3A4 .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [38, 39]}, {"entity": "nitroso", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "oxime", "entity_type": "Chemical", "pos": [64, 69]}, {"entity": "lapatinib", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "Nitroso / oxime metabolite formation from secondary alkylamines has been proposed to occur through two possible pathways : ( 1 ) sequential N - dealkylation , N - hydroxylation , and dehydrogenation ( primary hydroxylamine pathway ) or ( 2 ) N - hydroxylation with dehydrogenation to yield a nitrone followed by N - dealkylation ( secondary hydroxylamine pathway ) .", "entity": [{"entity": "Nitroso", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "oxime", "entity_type": "Chemical", "pos": [10, 15]}, {"entity": "alkylamines", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "N", "entity_type": "Chemical", "pos": [140, 141]}, {"entity": "N", "entity_type": "Chemical", "pos": [159, 160]}, {"entity": "primary hydroxylamine", "entity_type": "Chemical", "pos": [201, 222]}, {"entity": "N", "entity_type": "Chemical", "pos": [242, 243]}, {"entity": "nitrone", "entity_type": "Chemical", "pos": [292, 299]}, {"entity": "N", "entity_type": "Chemical", "pos": [312, 313]}, {"entity": "secondary hydroxylamine", "entity_type": "Chemical", "pos": [331, 354]}], "task": "NER"}
{"text": "All intermediates for the secondary hydroxylamine pathway were detected but the primary N - hydroxylamine intermediate of the primary hydroxylamine pathway was not .", "entity": [{"entity": "secondary hydroxylamine", "entity_type": "Chemical", "pos": [26, 49]}, {"entity": "N", "entity_type": "Chemical", "pos": [88, 89]}, {"entity": "hydroxylamine", "entity_type": "Chemical", "pos": [92, 105]}, {"entity": "primary hydroxylamine", "entity_type": "Chemical", "pos": [126, 147]}], "task": "NER"}
{"text": "Our findings support the mechanism of lapatinib CYP3A4 inactivation as MI complex formation with the nitroso metabolite formed through the secondary hydroxylamine and nitrone pathway , rather than by N - dealkylation to the primary amine followed by N - hydroxylation and dehydrogenation as is usually assumed .", "entity": [{"entity": "lapatinib", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "nitroso", "entity_type": "Chemical", "pos": [101, 108]}, {"entity": "secondary hydroxylamine", "entity_type": "Chemical", "pos": [139, 162]}, {"entity": "nitrone", "entity_type": "Chemical", "pos": [167, 174]}, {"entity": "N", "entity_type": "Chemical", "pos": [200, 201]}, {"entity": "primary amine", "entity_type": "Chemical", "pos": [224, 237]}, {"entity": "N", "entity_type": "Chemical", "pos": [250, 251]}], "task": "NER"}
{"text": "Interpretation of optoelectronic transient and charge extraction measurements in dye - sensitized solar cells .", "entity": [], "task": "NER"}
{"text": "Tools that assess the limitations of dye sensitized solar cells ( DSSCs ) made with new materials are critical for progress .", "entity": [], "task": "NER"}
{"text": "Measuring the transient electrical signals ( voltage or current ) after optically perturbing a DSSC is an approach which can give information about electron concentration , transport and recombination .", "entity": [], "task": "NER"}
{"text": "Here we describe the theory and practice of this class of optoelectronic measurements , illustrated with numerous examples .", "entity": [], "task": "NER"}
{"text": "The measurements are interpreted with the multiple trapping continuum model which describes electrons in a semiconductor with an exponential distribution of trapping states .", "entity": [], "task": "NER"}
{"text": "We review standard small perturbation photocurrent and photovoltage transients , and introduce the photovoltage time of flight measurement which allows the simultaneous derivation of both effective diffusion and recombination coefficients .", "entity": [], "task": "NER"}
{"text": "We then consider the utility of large perturbation measurements such as charge extraction and the current interrupt technique for finding the internal charge and voltage within a device .", "entity": [], "task": "NER"}
{"text": "Combining these measurements allows differences between DSSCs to be understood in terms such as electron collection efficiency , semiconductor conduction band edge shifts and recombination kinetics .", "entity": [], "task": "NER"}
{"text": "Functional UDP - glucuronyltransferase 2B15 polymorphism and bisphenol A concentrations in blood : results from physiologically based kinetic modelling .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [11, 14]}, {"entity": "bisphenol A", "entity_type": "Chemical", "pos": [61, 72]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is a chemical in widespread use that is under scientific discussion due to its endocrine activity .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "Controversies exist about how to interpret reportedly high blood concentrations measured in uncontrolled situations .", "entity": [], "task": "NER"}
{"text": "Physiologically based pharmaco - / toxicokinetic modelling resulted in 10 - 100 - fold lower blood concentrations than those reported .", "entity": [], "task": "NER"}
{"text": "Moreover , in controlled situations , BPA did not exceed the level of detection ( < 0 . 3 ng / ml ) in human blood or urine .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Using a validated human PBK model , this study investigated the influence of functionally relevant polymorphic UGT2B15 , the enzyme mediating BPA metabolism , on the BPA concentration - time profile in human blood .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [142, 145]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [166, 169]}], "task": "NER"}
{"text": "Maximum concentrations ( C ( max ) ) and areas under the curves ( AUCs ) in blood from high and low metabolisers differed by a factor of 4 . 7 and 4 . 6 , respectively ( doses : 1 and 0 . 05 mu g / kg / day ) .", "entity": [], "task": "NER"}
{"text": "Low metabolisers excreted a greater proportion of BPA via the sulphate pathway compared to high metabolisers .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [50, 53]}, {"entity": "sulphate", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "This finding explains why C ( max ) and AUC increased to a smaller extent , as predicted from in vitro data obtained with transfected cells possessing only the UGT2B15 variants .", "entity": [], "task": "NER"}
{"text": "The highest C ( max ) value calculated in the subject with the lowest metabolic clearance was roughly 40 pg / ml , which is far lower than reported high blood concentrations , which in turn cannot be explained by genetically impaired UGT2B15 activity .", "entity": [], "task": "NER"}
{"text": "From the risk assessment perspective , our results indicate that the traditional uncertainty factor is sufficient to account for the variability in the polymorphic glucuronidation of BPA .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [183, 186]}], "task": "NER"}
{"text": "Current - use pesticides in stream water and suspended particles following runoff : Exposure , effects , and mitigation requirements .", "entity": [], "task": "NER"}
{"text": "The European Union ' s directive for sustainable use of pesticides requires implementing risk mitigation measures at streams threatened by pesticide entries .", "entity": [], "task": "NER"}
{"text": "The need for mitigation measures was investigated at 10 stream sites within an intensively used arable region in central Germany by characterizing pesticide exposure following edge - of - field runoff and effects on the aquatic macroinvertebrates .", "entity": [], "task": "NER"}
{"text": "Moreover , the influence of riparian buffer strip width ( as a mitigation measure ) at the sampling sites was considered .", "entity": [], "task": "NER"}
{"text": "Generally , invertebrate fauna was dominated by pesticide - tolerant species , suggesting a high pesticide exposure at almost all sites .", "entity": [], "task": "NER"}
{"text": "This result is also reflected by the elevated levels of suspended particle contamination in terms of toxic units ( logTUMax > - 2 ) , corresponding to one - hundredth of the median lethal concentration ( LC50 ) to Daphnia magna .", "entity": [], "task": "NER"}
{"text": "At two sites that received high aqueous - phase entries of the pyrethroid lambda - cyhalothrin ( logTUMax > - 0 . 6 ) , the abundance and number of sensitive species in terms of the species at risk index decreased during the pesticide application period .", "entity": [{"entity": "lambda - cyhalothrin", "entity_type": "Chemical", "pos": [74, 94]}], "task": "NER"}
{"text": "In contrast , no acute significant negative effects on macroinvertebrates were observed at sites characterised by low water - phase toxicity ( logTUMax < - 3 . 5 ) .", "entity": [], "task": "NER"}
{"text": "An influence of riparian buffer strip width on pesticide exposure was not observed , supposedly because of the presence of erosion rills and ephemeral ditches .", "entity": [], "task": "NER"}
{"text": "In conclusion , results show that mitigation measures ( such as the improvement of currently present riparian buffer strips ) are needed in the study area .", "entity": [], "task": "NER"}
{"text": "Environ Toxicol Chem 2013 ; 32 : 1254 - 1263 .", "entity": [], "task": "NER"}
{"text": "ERK - mediated phosphorylation of fibroblast growth factor receptor 1 on Ser777 inhibits signaling .", "entity": [{"entity": "Ser777", "entity_type": "Chemical", "pos": [73, 79]}], "task": "NER"}
{"text": "Fibroblast growth factor 1 ( FGF1 ) controls cellular activities through the activation of specific cell - surface FGF receptors ( FGFRs ) .", "entity": [], "task": "NER"}
{"text": "Transphosphorylation of tyrosine residues in the kinase domain of FGFRs leads to activation of intracellular signaling cascades , including those mediated by mitogen - activated protein kinases ( MAPKs ) .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [24, 32]}], "task": "NER"}
{"text": "FGFRs also contain a serine - rich C - terminal tail .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "C", "entity_type": "Chemical", "pos": [35, 36]}], "task": "NER"}
{"text": "We identified a regulatory mechanism of FGFR signaling involving phosphorylation of Ser ( 777 ) in the C - terminal region of FGFR1 by the MAPKs extracellular signal - regulated kinase 1 ( ERK1 ) and ERK2 .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "C", "entity_type": "Chemical", "pos": [103, 104]}], "task": "NER"}
{"text": "Prevention of the phosphorylation of Ser ( 777 ) in FGFR1 or mutation of Ser ( 777 ) to alanine enhanced FGF - stimulated receptor tyrosine phosphorylation and increased cell proliferation , cell migration , and axonal growth .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [73, 76]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [88, 95]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "A form of FGFR1 with a phosphomimetic mutation at Ser ( 777 ) exhibited reduced signaling .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "Activation of MAPKs by other receptor tyrosine kinases also resulted in phosphorylation of Ser ( 777 ) in FGFR1 , thereby enabling crosstalk regulation of FGFR activity by other signaling pathways .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [38, 46]}, {"entity": "Ser", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "Our data reveal a negative feedback mechanism that controls FGF signaling and thereby protects the cell from excessive activation of FGFR .", "entity": [], "task": "NER"}
{"text": "Indolizine derivatives as HIV - 1 VIF - ElonginC interaction inhibitors .", "entity": [{"entity": "Indolizine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Compound 1 ( VEC - 5 ) was identified as a potent small molecular HIV - 1 VIF inhibitor that targets the VIF - ElonginC interaction .", "entity": [], "task": "NER"}
{"text": "A structure - activity relationship study was carried out to develop compounds with improved efficacy against HIV - 1 and 49 indolizine derivatives of three categories were designed and synthesized .", "entity": [{"entity": "indolizine", "entity_type": "Chemical", "pos": [125, 135]}], "task": "NER"}
{"text": "We found that 5 compounds exhibited promising anti - HIV - 1 activity and the most active compound 2g had an IC ( 50 ) value of 11 . 0 mu M .", "entity": [], "task": "NER"}
{"text": "These results provide new information to develop highly potent small - molecule HIV - 1 VIF inhibitors .", "entity": [], "task": "NER"}
{"text": "(c) 2013 John Wiley & Sons A / S .", "entity": [], "task": "NER"}
{"text": "Solution structure and in silico binding of a cyclic peptide with hepatitis B surface antigen .", "entity": [], "task": "NER"}
{"text": "A specific ligand targeting the immunodominant region of hepatitis B virus ( HBV ) is desired in neutralizing the infectivity of the virus .", "entity": [], "task": "NER"}
{"text": "In a previous study , a disulfide constrained cyclic peptide cyclo S ( 1 ) , S ( 9 ) Cys - Glu - Thr - Gly - Ala - Lys - Pro - His - Cys ( S ( 1 ) , S ( 9 ) - cyclo - CETGAKPHC ) was isolated from a phage displayed cyclic peptide library using an affinity selection method against HBV surface antigen ( HBsAg ) .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "cyclo S ( 1 ) , S ( 9 ) Cys - Glu - Thr - Gly - Ala - Lys - Pro - His - Cys", "entity_type": "Chemical", "pos": [61, 136]}], "task": "NER"}
{"text": "The cyclic peptide binds tightly to HBsAg with a relative dissociation constant ( K ( D ) ( rel ) ) of 2 . 9 nM .", "entity": [], "task": "NER"}
{"text": "The binding site of the peptide was located at the immunodominant region on HBsAg .", "entity": [], "task": "NER"}
{"text": "Consequently , this study was aimed to elucidate the structure of the cyclic peptide and its interaction with HBsAg in silico .", "entity": [], "task": "NER"}
{"text": "The solution structure of this cyclic peptide was solved using ( 1 ) H , ( 13 ) C and ( 15 ) N NMR spectroscopy and molecular dynamics ( MD ) simulations with NMR - derived distance and torsion angle restraints .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [63, 70]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [73, 81]}, {"entity": "( 15 ) N", "entity_type": "Chemical", "pos": [86, 94]}], "task": "NER"}
{"text": "The cyclic peptide adopted two distinct conformations due to the isomerization of the Pro residue with one structured region in the ETGA sequence .", "entity": [{"entity": "Pro", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "Docking studies of the peptide ensemble with a model structure of HBsAg revealed that the cyclic peptide can potentially be developed as a therapeutic drug that inhibits the virus - host interactions .", "entity": [], "task": "NER"}
{"text": "Adsorption of model perfumes at the air - solution interface by coadsorption with an anionic surfactant .", "entity": [], "task": "NER"}
{"text": "The adsorption of the model perfumes phenyl ethanol , PE , and linalool , LL , at the air - solution interface by coadsorption with the anionic surfactant sodium dodecyl 6 - benezene sulfonate , LAS - 6 , has been studied primarily by neutron reflectivity , NR .", "entity": [{"entity": "phenyl ethanol", "entity_type": "Chemical", "pos": [37, 51]}, {"entity": "linalool", "entity_type": "Chemical", "pos": [63, 71]}, {"entity": "sodium dodecyl 6 - benezene sulfonate", "entity_type": "Chemical", "pos": [155, 192]}, {"entity": "LAS - 6", "entity_type": "Chemical", "pos": [195, 202]}], "task": "NER"}
{"text": "The variation in the mixed surface adsorption with solution composition is highly nonideal , and the more hydrophobic LL is more surface active .", "entity": [], "task": "NER"}
{"text": "At a LAS - 6 concentration of 0 . 5 mM the adsorption of PE and LL is broadly similar but with the LL systematically more surface active , and at 2 mM the LL completes more effectively for the surface than the PE .", "entity": [{"entity": "LAS - 6", "entity_type": "Chemical", "pos": [5, 12]}], "task": "NER"}
{"text": "The variation in surface composition with solution composition and concentration reflect the greater hydrophobicity and hence surface activity of LL , and the greater solubility of PE in aqueous solution .", "entity": [], "task": "NER"}
{"text": "Changing the geometry of the LAS isomer , from the symmetrical LAS - 6 geometry to the more asymmetrical LAS - 4 , results in the LL competing more effectively for the surface due to changes in the packing constraints associated with the hydrophobic region .", "entity": [{"entity": "LAS", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "LAS - 6", "entity_type": "Chemical", "pos": [63, 70]}, {"entity": "LAS - 4", "entity_type": "Chemical", "pos": [105, 112]}], "task": "NER"}
{"text": "The results provide insights into the factors that affect coadsorption that can be more broadly applied to the surface delivery of a wide range of molecules other than perfumes .", "entity": [], "task": "NER"}
{"text": "In vitro polyphenolics erythrocyte model and in vivo chicken embryo model revealed gallic acid to be a potential hemorrhage inducer : physicochemical action mechanisms .", "entity": [{"entity": "polyphenolics", "entity_type": "Chemical", "pos": [9, 22]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "The in vivo chicken embryo model ( CEM ) demonstrated that gallic acid ( GA ) induced dysvascularization and hypoxia .", "entity": [{"entity": "gallic acid", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "Inflammatory edema , Zenker ' s necrosis , hemolysis , and liposis of cervical muscles were the common symptoms .", "entity": [], "task": "NER"}
{"text": "Levels of the gene hif - 1 alpha , HIF - 1 alpha , TNF - alpha , IL - 6 , and NF kappa B in cervical muscles were all significantly upregulated , while the vascular endothelial growth factor ( VEGF ) was downregulated in a dose - responsive manner .", "entity": [], "task": "NER"}
{"text": "Consequently , the cervical muscle inflammation and hemolysis could have been stimulated en route to the tissue TNF - alpha - canonical and the atypical pathways .", "entity": [], "task": "NER"}
{"text": "We hypothesized that GA could deplete the dissolved oxygen ( DO ) at the expense of semiquinone and quinone formation , favoring the reactive oxygen species ( ROS ) production to induce RBC disruption and Fe ( 2 + ) ion release .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [52, 58]}, {"entity": "semiquinone", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "quinone", "entity_type": "Chemical", "pos": [100, 107]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [142, 148]}, {"entity": "Fe ( 2 + )", "entity_type": "Chemical", "pos": [205, 215]}], "task": "NER"}
{"text": "To explore this , the in vitro polyphenolics - erythrocyte model ( PEM ) was established .", "entity": [{"entity": "polyphenolics", "entity_type": "Chemical", "pos": [31, 44]}], "task": "NER"}
{"text": "PEM revealed that the DO was rapidly depleted , leading to the release of a huge amount of Fe ( II ) ions and hydrogen peroxide ( HPO ) in a two - phase kinetic pattern .", "entity": [{"entity": "Fe ( II )", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [110, 127]}, {"entity": "HPO", "entity_type": "Chemical", "pos": [130, 133]}], "task": "NER"}
{"text": "The kinetic coefficients for Fe ( II ) ion release ranged from 0 . 347 h ( - 1 ) to 0 . 774 h ( - 1 ) ; and those for Fe ( III ) ion production were from 6 . 66 x 10 ( - 3 ) h ( - 1 ) to 8 . 93 x 10 ( - 3 ) h ( - 1 ) .", "entity": [{"entity": "Fe ( II )", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "Fe ( III )", "entity_type": "Chemical", "pos": [118, 128]}], "task": "NER"}
{"text": "For phase I HPO production , they ranged from 0 . 236 h ( - 1 ) to 0 . 774 h ( - 1 ) and for phase II HPO production from 0 . 764 h ( - 1 ) to 2 . 560 h ( - 1 ) at GA within 6 mu M to 14 mu M .", "entity": [{"entity": "HPO", "entity_type": "Chemical", "pos": [12, 15]}, {"entity": "HPO", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Thus , evidence obtained from PEM could strongly support the phenomena of CEM .", "entity": [], "task": "NER"}
{"text": "To conclude , GA tends to elicit hypoxia - related inflammation and hemolysis in chicken cervical muscles through its extremely high prooxidant activity .", "entity": [], "task": "NER"}
{"text": "A genetically encoded and gate for cell - targeted metabolic labeling of proteins .", "entity": [], "task": "NER"}
{"text": "We describe a genetic AND gate for cell - targeted metabolic labeling and proteomic analysis in complex cellular systems .", "entity": [], "task": "NER"}
{"text": "The centerpiece of the AND gate is a bisected methionyl - tRNA synthetase ( MetRS ) that charges the Met surrogate azidonorleucine ( Anl ) to tRNA ( Met ) .", "entity": [{"entity": "methionyl", "entity_type": "Chemical", "pos": [46, 55]}, {"entity": "Met", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "azidonorleucine", "entity_type": "Chemical", "pos": [115, 130]}, {"entity": "Anl", "entity_type": "Chemical", "pos": [133, 136]}, {"entity": "Met", "entity_type": "Chemical", "pos": [149, 152]}], "task": "NER"}
{"text": "Cellular protein labeling occurs only upon activation of two different promoters that drive expression of the N - and C - terminal fragments of the bisected MetRS .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [110, 111]}, {"entity": "C", "entity_type": "Chemical", "pos": [118, 119]}], "task": "NER"}
{"text": "Anl - labeled proteins can be tagged with fluorescent dyes or affinity reagents via either copper - catalyzed or strain - promoted azide - alkyne cycloaddition .", "entity": [{"entity": "Anl", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "copper", "entity_type": "Chemical", "pos": [91, 97]}], "task": "NER"}
{"text": "Protein labeling is apparent within 5 min after addition of Anl to bacterial cells in which the AND gate has been activated .", "entity": [{"entity": "Anl", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "This method allows spatial and temporal control of proteomic labeling and identification of proteins made in specific cellular subpopulations .", "entity": [], "task": "NER"}
{"text": "The approach is demonstrated by selective labeling of proteins in bacterial cells immobilized in the center of a laminar - flow microfluidic channel , where they are exposed to overlapping , opposed gradients of inducers of the N - and C - terminal MetRS fragments .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [228, 229]}, {"entity": "C", "entity_type": "Chemical", "pos": [236, 237]}], "task": "NER"}
{"text": "The observed labeling profile is predicted accurately from the strengths of the individual input signals .", "entity": [], "task": "NER"}
{"text": "Improving the second - order nonlinear optical response of fluorescent proteins : the symmetry argument .", "entity": [], "task": "NER"}
{"text": "We have successfully designed and expressed a new fluorescent protein with improved second - order nonlinear optical properties .", "entity": [], "task": "NER"}
{"text": "It is the first time that a fluorescent protein has been rationally altered for this particular characteristic .", "entity": [], "task": "NER"}
{"text": "On the basis of the specific noncentrosymmetry requirements for second - order nonlinear optical effects , we had hypothesized that the surprisingly low first hyperpolarizability ( beta ) of the enhanced yellow fluorescent protein ( eYFP ) could be explained by centrosymmetric stacking of the chromophoric Tyr66 and the neighboring Tyr203 residue .", "entity": [{"entity": "Tyr66", "entity_type": "Chemical", "pos": [307, 312]}, {"entity": "Tyr203", "entity_type": "Chemical", "pos": [333, 339]}], "task": "NER"}
{"text": "The inversion center was removed by mutating Tyr203 into Phe203 , with minor changes in the linear optical properties and even an improved fluorescence quantum yield .", "entity": [{"entity": "Tyr203", "entity_type": "Chemical", "pos": [45, 51]}, {"entity": "Phe203", "entity_type": "Chemical", "pos": [57, 63]}], "task": "NER"}
{"text": "Structure determination by X - ray crystallography as well as linear optical characterization corroborate a correct folding and maturation .", "entity": [], "task": "NER"}
{"text": "Measurement of beta by means of hyper - Rayleigh scattering ( HRS ) as well as their analysis using quantum chemistry calculations validate our hypothesis .", "entity": [], "task": "NER"}
{"text": "This observation can eventually lead to improved red fluorescent proteins for even better performance .", "entity": [], "task": "NER"}
{"text": "On the basis of the specific function ( second - harmonic generation ) , the color of its emission , and in analogy with the \" fruit \" names , we propose SHardonnay as the name for this Tyr203Phe mutant of eYFP .", "entity": [], "task": "NER"}
{"text": "Raman spectra of interchanging beta - lactamase inhibitor intermediates on the millisecond time scale .", "entity": [], "task": "NER"}
{"text": "Rapid mix - rapid freeze is a powerful method to study the mechanisms of enzyme - substrate reactions in solution .", "entity": [], "task": "NER"}
{"text": "Here we report a protocol that combines this method with normal ( non - resonance ) Raman microscopy to enable us to define molecular details of intermediates at early time points .", "entity": [], "task": "NER"}
{"text": "With this combined method , SHV - 1 , a class A beta - lactamase , and tazobactam , a commercially available beta - lactamase inhibitor , were rapidly mixed on the millisecond time scale and then were flash - frozen by injection into an isopentane solution surrounded by liquid nitrogen .", "entity": [{"entity": "tazobactam", "entity_type": "Chemical", "pos": [71, 81]}, {"entity": "isopentane", "entity_type": "Chemical", "pos": [237, 247]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [278, 286]}], "task": "NER"}
{"text": "The \" ice \" was finally freeze - dried and characterized by Raman microscopy .", "entity": [], "task": "NER"}
{"text": "We found that the reaction is almost complete in solution at 25 ms , giving rise to a major population composed of the trans - enamine intermediate .", "entity": [{"entity": "trans - enamine", "entity_type": "Chemical", "pos": [119, 134]}], "task": "NER"}
{"text": "Between 25 and 500 ms , minor populations of protonated imine are detected that have previously been postulated to precede enamine intermediates .", "entity": [{"entity": "imine", "entity_type": "Chemical", "pos": [56, 61]}, {"entity": "enamine", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "However , within 1 s , the imines are converted entirely to enamines .", "entity": [{"entity": "imines", "entity_type": "Chemical", "pos": [27, 33]}, {"entity": "enamines", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "Interestingly , with this method , we can measure directly the turnover number of SHV - 1 and tazobactam .", "entity": [{"entity": "tazobactam", "entity_type": "Chemical", "pos": [94, 104]}], "task": "NER"}
{"text": "The enzyme is completely inhibited at 1 : 4 ratio ( enzyme : inhibitor ) or greater , a number that agrees with the turnover number derived from steady - state kinetic methods .", "entity": [], "task": "NER"}
{"text": "This application , employing non - intensity - enhanced Raman spectroscopy , provides a general and effective route to study the early events in enzyme - substrate reactions .", "entity": [], "task": "NER"}
{"text": "Preparation of lipase - coated , stabilized , hydrophobic magnetic particles for reversible conjugation of biomacromolecules .", "entity": [], "task": "NER"}
{"text": "This Communication presents the development of a novel strategy for the easy conjugation of biomolecules to hydrophobic magnetic microparticles via reversible coating with previously functionalized lipase molecules .", "entity": [], "task": "NER"}
{"text": "First , the ability of lipase to be strongly adsorbed onto hydrophobic surfaces was exploited for the stabilization of microparticles in aqueous medium by the creation of a hydrophilic surface .", "entity": [], "task": "NER"}
{"text": "Second , the surface amino acids of lipase can be tailored to suit biomolecule conjugation .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [21, 32]}], "task": "NER"}
{"text": "This approach has been demonstrated by amino - epoxy activation of lipase , enabling the conjugation of different biomolecules to the magnetic particle ' s surface .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "epoxy", "entity_type": "Chemical", "pos": [47, 52]}], "task": "NER"}
{"text": "For example , it was possible to immobilize 70 % of Escherichia coli proteins on the recovered particles .", "entity": [], "task": "NER"}
{"text": "Furthermore , this strategy could be extended to other lipase chemical modification protocols , enabling fine control of biomolecule coupling .", "entity": [], "task": "NER"}
{"text": "These conjugation techniques constitute a modular methodology that also permits the recycling of the magnetic carrier following use .", "entity": [], "task": "NER"}
{"text": "Exposure to lambda - cyhalothrin , a synthetic pyrethroid , increases reactive oxygen species production and induces genotoxicity in rat peripheral blood .", "entity": [{"entity": "lambda - cyhalothrin", "entity_type": "Chemical", "pos": [12, 32]}, {"entity": "pyrethroid", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "Lambda - cyhalothrin ( LTC ) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control a wide range of insect pests in a variety of applications .", "entity": [{"entity": "Lambda - cyhalothrin", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "LTC", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "pyrethroid", "entity_type": "Chemical", "pos": [44, 54]}], "task": "NER"}
{"text": "However , there is little known about its adverse effects , in particular those related to its genotoxicity in humans .", "entity": [], "task": "NER"}
{"text": "To elucidate the genotoxicity mechanisms of LTC , the micronuclei ( MN ) frequencies , the levels of reactive oxygen species ( ROS ) , erythrocyte osmotic fragility , nitrite ( NO ) formation , protein carbonyl ( PCO ) levels and malondialdehyde ( MDA ) production were evaluated for a period of 7 , 14 and 21 days .", "entity": [{"entity": "LTC", "entity_type": "Chemical", "pos": [44, 47]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [110, 116]}, {"entity": "nitrite", "entity_type": "Chemical", "pos": [167, 174]}, {"entity": "NO", "entity_type": "Chemical", "pos": [177, 179]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [202, 210]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [230, 245]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [248, 251]}], "task": "NER"}
{"text": "Our results show that exposure rat to LTC ( 1 / 10DL50 = 6 . 23 mg / kg ) for a period of 7 , 14 and 21 days induced a noticeable genotoxic effect in rat peripheral blood evidenced by a significant increase in the frequency of MN only at day 21 of treatment .", "entity": [{"entity": "LTC", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Significant differences between the two groups were observed in erythrocyte osmotic fragility .", "entity": [], "task": "NER"}
{"text": "Further , a significant ( p < 0 . 01 ) increase in ROS contents , NO formation , PCO levels and lipid peroxidation in erythrocytes were observed at different times of treatments , suggesting the implication of oxidative stress in its toxicity .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [66, 68]}], "task": "NER"}
{"text": "These results confirm the genotoxic and the pro - oxidant effects of LTC in rat peripheral blood .", "entity": [{"entity": "LTC", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "The periodontal health of lead - exposed children living in a shipyard industrial area .", "entity": [], "task": "NER"}
{"text": "In a cross - sectional design , 292 schoolchildren living around a shipyard area , known to be contaminated with lead from shipyard industry , were examined to verify the association between lead exposure and periodontal health .", "entity": [], "task": "NER"}
{"text": "The probing pocket depth ( PD ) , bleeding on probing , plaque and calculus , and the presence of Aggregatibacter actinomycetemcomitans ( Aa ) in subgingival crevices were recorded .", "entity": [], "task": "NER"}
{"text": "Gingival inflammation was the most common ( 98 % ) among children in the area .", "entity": [], "task": "NER"}
{"text": "No significant difference in gingival inflammation was observed between high blood lead ( PbB ) and low PbB children .", "entity": [], "task": "NER"}
{"text": "The prevalence rate of probing PD of >= 5 mm was 14 % .", "entity": [], "task": "NER"}
{"text": "The high PbB group showed more deep pockets at tooth 16 ( upper right first permanent molar ) and tooth 46 ( lower right first permanent molar ) than the low PbB group .", "entity": [], "task": "NER"}
{"text": "The odds ratios ( ORs ) for having probing PD >= 5 mm after adjusting for other factors were 3 . 63 ( 95 % confidence interval ( CI ) , 1 . 24 - 10 . 61 ; p = 0 . 02 ) for tooth 16 and 3 . 93 ( 95 % CI , 1 . 18 - 13 . 00 ; p = 0 . 02 ) for tooth 46 .", "entity": [], "task": "NER"}
{"text": "The presence of Aa was observed in 17 % of the children and it significantly increased in high PbB compared with low PbB children at tooth 46 ( OR = 5 . 53 , 95 % CI : 1 . 68 - 18 . 15 ; p = 0 . 005 ) .", "entity": [], "task": "NER"}
{"text": "This study may suggest no association between lead exposure and gingival inflammation , yet there was the involvement of deeper periodontal tissue in lead - exposed children .", "entity": [], "task": "NER"}
{"text": "Protective role of L - carnitine and vitamin E on the testis of atherosclerotic rats .", "entity": [{"entity": "L - carnitine", "entity_type": "Chemical", "pos": [19, 32]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [37, 46]}], "task": "NER"}
{"text": "Atherosclerosis is a condition caused by lipid build - up and inflammation in the arteries , so hyperlipidemia is the major reason for atherosclerosis .", "entity": [], "task": "NER"}
{"text": "Testis was found to be negatively affected by hyperlipidemia which leads to its impaired functions .", "entity": [], "task": "NER"}
{"text": "Vitamin E and < sc > l < / sc > - carnitine have well - known lipid - lowering and antioxidative activities .", "entity": [{"entity": "Vitamin E", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [14, 43]}], "task": "NER"}
{"text": "Triton WR 1339 is a non - ionic detergent , which induces severe hyperlipidemia by inhibition of lipoprotein lipase .", "entity": [{"entity": "Triton WR 1339", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "The present study evaluates the protective role of vitamin E and < sc > l < / sc > - carnitine on the testis in atherosclerosis and detects the most effective choice for protection against atherosclerosis ; vitamin E , < sc > l < / sc > - carnitine or a combination of both .", "entity": [{"entity": "vitamin E", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [65, 94]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [207, 216]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [219, 248]}], "task": "NER"}
{"text": "A total of 80 albino male rats were divided into eight groups ( 10 rats for each group ) : control ( G ( 1 ) ) , triton ( G ( 2 ) ) , < sc > l < / sc > - carnitine ( G ( 3 ) ) , triton + < sc > l < / sc > - carnitine ( G ( 4 ) ) , vitamin E ( G ( 5 ) ) , triton + vitamin E ( G ( 6 ) ) , < sc > l < / sc > - carnitine + vitamin E ( G ( 7 ) ) and triton + < sc > l < / sc > - carnitine + vitamin E ( G ( 8 ) ) .", "entity": [{"entity": "triton", "entity_type": "Chemical", "pos": [113, 119]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [134, 163]}, {"entity": "triton", "entity_type": "Chemical", "pos": [178, 184]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [187, 216]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [231, 240]}, {"entity": "triton", "entity_type": "Chemical", "pos": [255, 261]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [264, 273]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [288, 317]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [320, 329]}, {"entity": "triton", "entity_type": "Chemical", "pos": [346, 352]}, {"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [355, 384]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [387, 396]}], "task": "NER"}
{"text": "Data showed a significant increase in the levels of total cholesterol ( TC ) , triglycerides ( TGs ) , low - density lipoprotein cholesterol ( LDL - C ) , 17 beta hydroxysteroid dehydrogenase ( 17 beta HSD ) , testicular catalase and malondialdehyde ( MDA ) in G ( 2 ) when compared with G ( 1 ) , whereas high - density lipoprotein cholesterol ( HDL - C ) , serum testosterone , testicular 17 ketosteroid reductase ( 17 KSR ) , total thiol and glutathione - S - transferase ( GST ) data showed a significant decrease in G ( 2 ) when compared with G ( 1 ) .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [79, 92]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [129, 140]}, {"entity": "17 beta hydroxysteroid", "entity_type": "Chemical", "pos": [155, 177]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [234, 249]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [252, 255]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [333, 344]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [365, 377]}, {"entity": "ketosteroid", "entity_type": "Chemical", "pos": [394, 405]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [435, 440]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [445, 456]}, {"entity": "S", "entity_type": "Chemical", "pos": [459, 460]}], "task": "NER"}
{"text": "Treatment with < sc > l < / sc > - carnitine or / and vitamin E helps in improving the adverse effect of triton ; also the histological changes confirm this finding .", "entity": [{"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [15, 44]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "triton", "entity_type": "Chemical", "pos": [105, 111]}], "task": "NER"}
{"text": "So the present study recommends all people to include < sc > l < / sc > - carnitine and vitamin E in their diet to be protected against atherosclerosis .", "entity": [{"entity": "< sc > l < / sc > - carnitine", "entity_type": "Chemical", "pos": [54, 83]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "Critical parameters in exfoliating graphite into graphene .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Dispersing graphite into few - layers graphene sheets ( GS ) in water is very appealing as an environmental - friendly , low - cost , low - energy method of obtaining graphene .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [38, 46]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [167, 175]}], "task": "NER"}
{"text": "Very high GS concentrations in water ( 0 . 7 mg mL ( - 1 ) ) were obtained by optimizing the nature of dispersant and the type of ultra - sonic generator .", "entity": [], "task": "NER"}
{"text": "We find that a multi - step sonication procedure involving both tip and bath sources considerably enhances the yield of exfoliated GS .", "entity": [], "task": "NER"}
{"text": "Raman and transmission electron microscopy indicate few - layers graphene patches with typical size of ~ 0 . 65 mu m in one dimension and ~ 0 . 35 mu m in the other .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "These were further employed in combination with water - dispersed CNTs to fabricate conductive transparent electrodes for a molecularly - controlled solar - cell with an open - circuit voltage of 0 . 53 V .", "entity": [], "task": "NER"}
{"text": "The CRF ( 1 ) receptor antagonist SSR125543 prevents stress - induced cognitive deficit associated with hippocampal dysfunction : Comparison with paroxetine and D - cycloserine .", "entity": [{"entity": "SSR125543", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "paroxetine", "entity_type": "Chemical", "pos": [146, 156]}, {"entity": "D - cycloserine", "entity_type": "Chemical", "pos": [161, 176]}], "task": "NER"}
{"text": "RATIONALE : The selective CRF ( 1 ) ( corticotropin releasing factor type 1 ) receptor antagonist SSR125543 has been previously shown to attenuate the long - term cognitive deficit produced by traumatic stress exposure .", "entity": [{"entity": "SSR125543", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "Memory disturbances described in post - traumatic stress disorder ( PTSD ) patients are believed to be associated with changes in neuronal activity , in particular at the level of the hippocampus .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The present study aims at investigating whether the effects of SSR125543 ( 10 mg / kg / day for 2 weeks ) on cognitive impairment induced by traumatic stress exposure are associated with changes in hippocampal excitability .", "entity": [{"entity": "SSR125543", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Effects of SSR125543 were compared to those of the 5 - HT reuptake inhibitor , paroxetine ( 10 mg / kg / day ) , and the partial N - methyl - D - aspartate ( NMDA ) receptor agonist , D - cycloserine ( 10 mg / kg / day ) , two compounds which have demonstrated clinical efficacy against PTSD .", "entity": [{"entity": "SSR125543", "entity_type": "Chemical", "pos": [11, 20]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "paroxetine", "entity_type": "Chemical", "pos": [79, 89]}, {"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [129, 155]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [158, 162]}, {"entity": "D - cycloserine", "entity_type": "Chemical", "pos": [184, 199]}], "task": "NER"}
{"text": "METHODS : Mice received two unavoidable electric foot - shocks .", "entity": [], "task": "NER"}
{"text": "Then , 1 or 16 days after stress , they were tested for their memory performance using the object recognition test .", "entity": [], "task": "NER"}
{"text": "Neuronal excitability was recorded during the third week post - stress in the CA1 area of the hippocampus .", "entity": [], "task": "NER"}
{"text": "Drugs were administered from day 1 post - stress to the day preceding the electrophysiological study .", "entity": [], "task": "NER"}
{"text": "RESULTS : Application of electric shocks produced cognitive impairment 16 , but not 1 day after stress , an effect which was associated with a decrease in hippocampal neuronal excitability .", "entity": [], "task": "NER"}
{"text": "Both stress - induced effects were prevented by repeated administration of SSR125543 , paroxetine and D - cycloserine .", "entity": [{"entity": "SSR125543", "entity_type": "Chemical", "pos": [75, 84]}, {"entity": "paroxetine", "entity_type": "Chemical", "pos": [87, 97]}, {"entity": "D - cycloserine", "entity_type": "Chemical", "pos": [102, 117]}], "task": "NER"}
{"text": "CONCLUSIONS : These findings confirm that the CRF ( 1 ) receptor antagonist SSR125543 is able to attenuate the behavioral effects of traumatic stress exposure and indicate that these effects are associated with a normalization of hippocampal neuronal excitability impaired by stress .", "entity": [{"entity": "SSR125543", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Lupenone from Erica multiflora leaf extract stimulates melanogenesis in B16 murine melanoma cells through the inhibition of ERK1 / 2 activation .", "entity": [{"entity": "Lupenone", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Hypopigmentation diseases are usually managed using UVB light which increases the patients ' risk for skin cancer .", "entity": [], "task": "NER"}
{"text": "Here , we evaluated the melanogenesis stimulatory effects of leaf extracts of Erica multiflora , a medicinal plant from the Mediterranean region , and its active component , lup - 20 ( 29 ) - en - 3 - one , as possible therapeutic agents to address hypopigmentation disorders .", "entity": [{"entity": "lup - 20 ( 29 ) - en - 3 - one", "entity_type": "Chemical", "pos": [174, 204]}], "task": "NER"}
{"text": "B16 murine melanoma cells were treated with E . multiflora extracts or its active component lupenone to evaluate their effects on melanin biosynthesis .", "entity": [{"entity": "lupenone", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "The mechanism underlying the observed effects was also determined .", "entity": [], "task": "NER"}
{"text": "Bioactivity - guided fractionation of fifteen ethyl acetate fractions identified fraction 2 to have melanogenesis stimulatory effects due to its ability to decrease mitogen - activated protein kinase phosphorylated extracellular signal - regulated kinases 1 and 2 activation .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [46, 59]}], "task": "NER"}
{"text": "Preparative TLC of ethyl acetate fraction 2 revealed the presence of lup - 20 ( 29 ) - en - 3 - one as the major bioactive component .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [19, 32]}, {"entity": "lup - 20 ( 29 ) - en - 3 - one", "entity_type": "Chemical", "pos": [69, 99]}], "task": "NER"}
{"text": "B16 cells treated with lup - 20 ( 29 ) - en - 3 - one increased melanin content without cytotoxicity .", "entity": [{"entity": "lup - 20 ( 29 ) - en - 3 - one", "entity_type": "Chemical", "pos": [23, 53]}], "task": "NER"}
{"text": "To determine the mechanism for the observed effects of lup - 20 ( 29 ) - en - 3 - one , the tyrosinase enzyme activity , the tyrosinase protein expression , and the activation of phosphorylated extracellular signal - regulated kinases 1 and 2 were determined .", "entity": [{"entity": "lup - 20 ( 29 ) - en - 3 - one", "entity_type": "Chemical", "pos": [55, 85]}], "task": "NER"}
{"text": "In addition , the expression of the tyrosinase mRNA was quantified using real - time PCR .", "entity": [], "task": "NER"}
{"text": "Results showed that lup - 20 ( 29 ) - en - 3 - one has no effect on the tyrosinase enzyme activity but can increase tyrosinase expression at both the transcriptional and translational levels .", "entity": [{"entity": "lup - 20 ( 29 ) - en - 3 - one", "entity_type": "Chemical", "pos": [20, 50]}], "task": "NER"}
{"text": "The increase in the tyrosinase mRNA expression was most likely due to the inhibited mitogen - activated protein kinase phosphorylated extracellular signal - regulated kinases 1 and 2 activation .", "entity": [], "task": "NER"}
{"text": "We report for the first time that E . multiflora ethyl acetate extract and its active compound lup - 20 ( 29 ) - en - 3 - one stimulate melanogenesis by increasing the tyrosinase enzyme expression via mitogen - activated protein kinase phosphorylated extracellular signal - regulated kinases 1 and 2 phosphorylation inhibition , making it a possible treatment for hypopigmentation diseases .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [49, 62]}, {"entity": "lup - 20 ( 29 ) - en - 3 - one", "entity_type": "Chemical", "pos": [95, 125]}], "task": "NER"}
{"text": "Peptide based macrocycles : selective histone deacetylase inhibitors with antiproliferative activity .", "entity": [], "task": "NER"}
{"text": "Histone deacetylase inhibitors ( HDACi ) have been enthusiastically investigated as a novel generation of chemotherapeutics for cancers usually called as epigenetic therapeutics .", "entity": [], "task": "NER"}
{"text": "Histone deacetylases have been found to influence cellular function by catalyzing the removal of acetyl groups from epsilon - N - acetylated lysine residues of several protein substrates including histones , transcription factors , alpha - tubulin , and nuclear importers .", "entity": [{"entity": "acetyl", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "epsilon - N - acetylated lysine", "entity_type": "Chemical", "pos": [116, 147]}], "task": "NER"}
{"text": "Cyclic peptides represent the most structurally complicated and diverse class of histone deacetylase inhibitors .", "entity": [], "task": "NER"}
{"text": "Each subtype of the Histone Deacetylase ( HDAC ) family perform a distinct role in the gene expression and cyclic peptides with their plentiful set of surface contacts , zinc binding group and macrocyclic cap , can target enzyme precisely through adequate modulation of the amino acid configurational and structural assortment .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [170, 174]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [274, 284]}], "task": "NER"}
{"text": "The present article summarizes current status of different peptide based macrocyclic compounds being developed as HDACi for the treatment of cancer .", "entity": [], "task": "NER"}
{"text": "Targeting multiplicity : the key factor for anti - cancer nanoparticles .", "entity": [], "task": "NER"}
{"text": "In this mini - review , we focus on different strategies to bring nanotools specifically to cancer cells .", "entity": [], "task": "NER"}
{"text": "We discuss about a better targeting of tumor , combining the characteristics of tumor environment , the increase in nanoparticles life time , the biomarkers overexpressed on cancer cells and different physical methods for non invasive therapies .", "entity": [], "task": "NER"}
{"text": "Here we detail the necessity of a synergy between passive and active targeting for an actual specificity of cancer cells .", "entity": [], "task": "NER"}
{"text": "Computational models for predicting interactions with membrane transporters .", "entity": [], "task": "NER"}
{"text": "Membrane transporters , including two members : ATP - binding cassette ( ABC ) transporters and solute carrier ( SLC ) transporters are proteins that play important roles to facilitate molecules into and out of cells .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "Consequently , these transporters can be major determinants of the therapeutic efficacy , toxicity and pharmacokinetics of a variety of drugs .", "entity": [], "task": "NER"}
{"text": "Considering the time and expense of bio - experiments taking , research should be driven by evaluation of efficacy and safety .", "entity": [], "task": "NER"}
{"text": "Computational methods arise to be a complementary choice .", "entity": [], "task": "NER"}
{"text": "In this article , we provide an overview of the contribution that computational methods made in transporters field in the past decades .", "entity": [], "task": "NER"}
{"text": "At the beginning , we present a brief introduction about the structure and function of major members of two families in transporters .", "entity": [], "task": "NER"}
{"text": "In the second part , we focus on widely used computational methods in different aspects of transporters research .", "entity": [], "task": "NER"}
{"text": "In the absence of a high - resolution structure of most of transporters , homology modeling is a useful tool to interpret experimental data and potentially guide experimental studies .", "entity": [], "task": "NER"}
{"text": "We summarize reported homology modeling in this review .", "entity": [], "task": "NER"}
{"text": "Researches in computational methods cover major members of transporters and a variety of topics including the classification of substrates and / or inhibitors , prediction of protein - ligand interactions , constitution of binding pocket , phenotype of non - synonymous single - nucleotide polymorphisms , and the conformation analysis that try to explain the mechanism of action .", "entity": [], "task": "NER"}
{"text": "As an example , one of the most important transporters P - gp is elaborated to explain the differences and advantages of various computational models .", "entity": [], "task": "NER"}
{"text": "In the third part , the challenges of developing computational methods to get reliable prediction , as well as the potential future directions in transporter related modeling are discussed .", "entity": [], "task": "NER"}
{"text": "Index of refraction , density , and solubility of ammonium iodide solutions at high pressure .", "entity": [{"entity": "ammonium iodide", "entity_type": "Chemical", "pos": [50, 65]}], "task": "NER"}
{"text": "An asymmetric moissanite anvil cell is used to study aqueous solutions of ammonium iodide at pressures up to 10 kbar .", "entity": [{"entity": "moissanite", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "ammonium iodide", "entity_type": "Chemical", "pos": [74, 89]}], "task": "NER"}
{"text": "The index of refraction is measured using the rotating Fabry - Perot technique , with an accuracy of approximately 1 % .", "entity": [], "task": "NER"}
{"text": "The mass density and molar volume of the solutions are estimated using the measured index values , and the molar volume is used to predict the pressure dependence of the solubility .", "entity": [], "task": "NER"}
{"text": "The solubility derived from the index of refraction measurements is shown to agree with that which is determined by direct observation of the onset of crystallization .", "entity": [], "task": "NER"}
{"text": "Antimalarial activities of 6 - iodouridine and its prodrugs and potential for combination therapy .", "entity": [{"entity": "6 - iodouridine", "entity_type": "Chemical", "pos": [27, 42]}], "task": "NER"}
{"text": "Resistance by Plasmodium falciparum to almost all clinically used antimalarial drugs requires the development of new classes of antimalarials .", "entity": [], "task": "NER"}
{"text": "6 - Iodouridine ( 15 ) , a novel and potent inhibitor of orotidine 5 ' - monophosphate decarboxylase ( ODCase ) , exhibited efficacy in a mouse model infected by P . chabaudi chabaudi .", "entity": [{"entity": "6 - Iodouridine", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "orotidine 5 ' - monophosphate", "entity_type": "Chemical", "pos": [57, 86]}], "task": "NER"}
{"text": "Compound 15 exhibited promising antimalarial activity against P . falciparum , including drug - resistant isolates , and no rapid drug - resistant populations of the parasite were observed when challenged with 15 .", "entity": [], "task": "NER"}
{"text": "Uridine provided options to overcome any toxicity in the host but still suppressing the parasite load when treated with 15 .", "entity": [{"entity": "Uridine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In drug combination studies , compound 15 showed good efficacy in vivo with artemisinin and azithromycin .", "entity": [{"entity": "artemisinin", "entity_type": "Chemical", "pos": [76, 87]}, {"entity": "azithromycin", "entity_type": "Chemical", "pos": [92, 104]}], "task": "NER"}
{"text": "The propionyl ester of 15 exhibited superior antimalarial efficacy .", "entity": [{"entity": "propionyl ester", "entity_type": "Chemical", "pos": [4, 19]}], "task": "NER"}
{"text": "Antimalarial activities of 15 and its prodrugs and potential for combination therapy are discussed in the context of novel strategies .", "entity": [], "task": "NER"}
{"text": "Solution effect on diazonium - modified Au ( 111 ) : reactions and structures .", "entity": [{"entity": "diazonium", "entity_type": "Chemical", "pos": [19, 28]}, {"entity": "Au ( 111 )", "entity_type": "Chemical", "pos": [40, 50]}], "task": "NER"}
{"text": "Surface modifications of a Au ( 111 ) electrode with 4 - bromobenzenediazonium tetrafluoroborate ( BBD ) in acetonitrile ( ACN ) and 0 . 1 M HClO4 have been characterized by scanning tunneling microscopy ( STM ) .", "entity": [{"entity": "Au ( 111 )", "entity_type": "Chemical", "pos": [27, 37]}, {"entity": "4 - bromobenzenediazonium tetrafluoroborate", "entity_type": "Chemical", "pos": [53, 96]}, {"entity": "BBD", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [108, 120]}, {"entity": "ACN", "entity_type": "Chemical", "pos": [123, 126]}, {"entity": "HClO4", "entity_type": "Chemical", "pos": [141, 146]}], "task": "NER"}
{"text": "In ACN , STM results reveal the formation of disordered thin organic films .", "entity": [{"entity": "ACN", "entity_type": "Chemical", "pos": [3, 6]}], "task": "NER"}
{"text": "The involvement of the radical as an intermediate is evidenced by the negative effect of radical scavengers on organic thin film formation .", "entity": [], "task": "NER"}
{"text": "In contrast , the 4 , 4 ' - dibromobiphenyl monolayer is observed when the aqueous solution is used as a medium to carry out the grafting experiment .", "entity": [{"entity": "4 , 4 ' - dibromobiphenyl", "entity_type": "Chemical", "pos": [18, 43]}], "task": "NER"}
{"text": "The biphenyl compound is considered to be generated by a radical - radical coupling reaction .", "entity": [{"entity": "biphenyl", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "Genome - wide integrated analyses of androgen receptor signaling in prostate cancer based on high - throughput technology .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "The androgen receptor ( AR ) is a steroid hormone receptor that functions as a ligand - dependent transcriptional factor , which plays a key role in the development and progression of prostate cancer .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [34, 41]}], "task": "NER"}
{"text": "Recent advancement in high throughput technologies including microarrays and deep - sequencing provides unbiased genome - wide knowledge on the AR signaling including datasets for androgen - regulated gene expression and genomic binding sites for AR .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [180, 188]}], "task": "NER"}
{"text": "In the present review , we will briefly summarize the main features of the AR signaling as well as the individual AR target genes identified by the integration of multiple datasets in prostate cancer .", "entity": [], "task": "NER"}
{"text": "Cap analysis gene expression ( CAGE ) is also featured as a unique transcriptome method , which particularly determines the androgen - dependent transcription start points in prostate cancer .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "Recurrent rearrangements in prostate cancer : causes and therapeutic potential .", "entity": [], "task": "NER"}
{"text": "DNA damage and genetic rearrangements are hallmarks of cancer .", "entity": [], "task": "NER"}
{"text": "However , gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75 % of prostate cancer patients .", "entity": [], "task": "NER"}
{"text": "The discovery of the TMPRSS2 - ERG fusion sparked an onslaught of discovery and innovation resulting in a delineation of prostate cancer via a molecular signature of gene fusion events .", "entity": [], "task": "NER"}
{"text": "The increased commonality of high - throughput sequencing data coupled with improved bioinformatics approaches not only elucidated the molecular underpinnings of prostate cancer progression , but the mechanisms of gene fusion biogenesis .", "entity": [], "task": "NER"}
{"text": "Interestingly , the androgen receptor ( AR ) , already known to play a significant role in prostate cancer tumorigenesis , has recently been implicated in the processes resulting in gene fusions by inducing the spatial proximity of genes involved in rearrangements , promoting the formation of double - strand DNA breaks ( DSB ) , and facilitating the recruitment of proteins for non - homologous end - joining ( NHEJ ) .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "Our increased understanding of the mechanisms inducing genomic instability may lead to improved diagnostic and therapeutic strategies .", "entity": [], "task": "NER"}
{"text": "To date , the majority of prostate cancer patients can be molecularly stratified based on their gene fusion status thereby increasing the potential for tailoring more specific and effective therapies .", "entity": [], "task": "NER"}
{"text": "Targeting the akt kinase to modulate survival , invasiveness and drug resistance of cancer cells .", "entity": [], "task": "NER"}
{"text": "The deregulation of oncogenic signaling pathways which provide survival advantages to tumor cells is mediated by multiple cellular networks .", "entity": [], "task": "NER"}
{"text": "Among them , the PI3K - Akt - mTOR axis , in particular the serine / threonine kinase Akt , is recognized as a key player .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "threonine", "entity_type": "Chemical", "pos": [69, 78]}], "task": "NER"}
{"text": "The kinase is hyperactivated due to a variety of mechanisms including loss of PTEN , mutations in the PI3K catalytic subunit , receptor tyrosine kinase and Ras activation .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Indeed , inappropriate activation of the Akt kinase is a common event in human tumors and Akt appears to be a critical player in cell survival that may also account for the therapeutic resistance and the invasive phenotype of tumors .", "entity": [], "task": "NER"}
{"text": "Inhibition of Akt signalling results in apoptosis and growth inhibition of tumour cells with elevated Akt activity .", "entity": [], "task": "NER"}
{"text": "A functional role in drug resistance is supported by evidence that tumor cells with acquired resistance to antitumor agents may display increased Akt activation and that treatment with molecularly targeted agents can activate feed - back loops involving Akt .", "entity": [], "task": "NER"}
{"text": "This serine / threonine kinase may therefore represent an amenable target for modulation of sensitivity to compounds with different molecular features due to its pleiotropic role in cell survival .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [5, 11]}, {"entity": "threonine", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Different types of Akt inhibitors [ i . e . , ATP mimetics and pleckstrin - homology ( PH ) domain binders ] have been generated and some of them have reached the clinical setting .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "The present review focuses on the i ) mechanisms implicating Akt in increased survival and invasive potential of tumor cells of different tumor types and ii ) on the development of Akt inhibitors as modulators of drug resistance .", "entity": [], "task": "NER"}
{"text": "Emerging Role of Colloidal Drug Delivery Systems ( CDDS ) in NSAID Topical Administration .", "entity": [], "task": "NER"}
{"text": "NSAIDs are the most commonly prescribed category of drugs for the treatment of musculoskeletal pain and inflammation associated with many conditions .", "entity": [], "task": "NER"}
{"text": "Topical administration of these drugs is always the best choice since adverse effects occur commonly with systemic NSAID therapy .", "entity": [], "task": "NER"}
{"text": "Colloidal drug delivery systems ( CDDS ) are interesting systems , which are able to improve the duration of drug residence in the skin and to allow an achievable drug sustained and controlled release compared to conventional topical formulations . This review focuses on micro and nanoemulsions , vesicular carriers and nanoparticles as novel high efficiency delivery systems of NSAIDs in topical applications .", "entity": [], "task": "NER"}
{"text": "Rationally designed multi - targeted agents against neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "Neurodegenerative diseases are complex disorders with several pathoetiological pathways leading to cell death .", "entity": [], "task": "NER"}
{"text": "Rationally designed multi - targeted agents , or \" multi - targeted designed drugs \" ( MTDD ) show significant promise in preclinical studies as neuroprotective and disease - modifying agents .", "entity": [], "task": "NER"}
{"text": "In this review , we highlight the use of chemical scaffolds that lend themselves exquisitely to the development of MTDDs in neurodegeneration .", "entity": [], "task": "NER"}
{"text": "Notably , synthetic polycyclic cage compounds have served as scaffolds for novel voltage - gated calcium channel blockers , NMDA receptor antagonists , and sigma - receptor ligands - attractive targets in neurodegeneration .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [124, 128]}], "task": "NER"}
{"text": "In an entirely different approach , compounds containing the thiazolidinedione moiety ( referred to as glitazones ) alter mitochondrial function through the mitochondrial protein mitoNEET , an attractive new drug target for the treatment of neurodegenerative diseases .", "entity": [{"entity": "thiazolidinedione", "entity_type": "Chemical", "pos": [61, 78]}, {"entity": "glitazones", "entity_type": "Chemical", "pos": [103, 113]}], "task": "NER"}
{"text": "The design strategy for yet another agent , ladostigil , employed the amalgamation of active chemical moieties of the AChE inhibitor rivastigmine , and the monoamine oxidase - B ( MAO - B ) inhibitor rasagiline , leading to a single compound that targets both enzymes simultaneously .", "entity": [{"entity": "ladostigil", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "rivastigmine", "entity_type": "Chemical", "pos": [133, 145]}, {"entity": "monoamine", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "rasagiline", "entity_type": "Chemical", "pos": [200, 210]}], "task": "NER"}
{"text": "Natural products have also served as design templates for several MTDD design studies .", "entity": [], "task": "NER"}
{"text": "In particular , the stilbene scaffold has become popular in particular due to the neuroprotective effects of the non - flavonoid natural product resveratrol .", "entity": [{"entity": "stilbene", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [119, 128]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [145, 156]}], "task": "NER"}
{"text": "Recently , stilbene scaffold - based compounds were developed to reduce - through chelation with metal ions that interact with beta - amyloid - both metal - induced beta - amyloid protein aggregation , and ROS generated from this aggregate .", "entity": [{"entity": "stilbene", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "Other subtle modifications of the stilbene motif led to the creation of reversible , non - competitive MAO inhibitors .", "entity": [{"entity": "stilbene", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "Finally , compounds derived from the xanthine scaffold afford neuroprotection in Parkinson ' s disease through mechanisms that include dual adenosine A2A receptor antagonism and MAO - B inhibition .", "entity": [{"entity": "xanthine", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [140, 149]}], "task": "NER"}
{"text": "Human disease and drug pharmacology , complex as real life .", "entity": [], "task": "NER"}
{"text": "In the past decades drug discovery practice has escaped from the complexity of the formerly used phenotypic screening in animals to focus on assessing drug effects on isolated protein targets in the search for drugs that exclusively and potently hit one selected target , thought to be critical for a given disease , while not affecting at all any other target to avoid the occurrence of side - effects .", "entity": [], "task": "NER"}
{"text": "However , reality does not conform to these expectations , and , conversely , this approach has been concurrent with increased attrition figures in late - stage clinical trials , precisely due to lack of efficacy and safety .", "entity": [], "task": "NER"}
{"text": "In this context , a network biology perspective of human disease and treatment has burst into the drug discovery scenario to bring it back to the consideration of the complexity of living organisms and particularly of the ( patho ) physiological environment where protein targets are ( mal ) functioning and where drugs have to exert their restoring action .", "entity": [], "task": "NER"}
{"text": "Under this perspective , it has been found that usually there is not one but several disease - causing genes and , therefore , not one but several relevant protein targets to be hit , which do not work on isolation but in a highly interconnected manner , and that most known drugs are inherently promiscuous .", "entity": [], "task": "NER"}
{"text": "In this light , the rationale behind the currently prevailing single - target - based drug discovery approach might even seem a Utopia , while , conversely , the notion that the complexity of human disease must be tackled with complex polypharmacological therapeutic interventions constitutes a difficult - torefuse argument that is spurring the development of multitarget therapies .", "entity": [], "task": "NER"}
{"text": "Photothermal tautomerization of a UV sunscreen ( 4 - tert - butyl - 4 ' - methoxydibenzoylmethane ) in acetonitrile studied by steady - state and laser flash photolysis .", "entity": [{"entity": "4 - tert - butyl - 4 ' - methoxydibenzoylmethane", "entity_type": "Chemical", "pos": [49, 97]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [103, 115]}], "task": "NER"}
{"text": "The photothermal tautomerization processes between enol and keto forms of 4 - tert - butyl - 4 ' - methoxydibenzoylmethane ( trade name , Avobenzone ) in acetonitrile have been studied by steady - state and laser flash photolysis .", "entity": [{"entity": "enol", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "keto", "entity_type": "Chemical", "pos": [60, 64]}, {"entity": "4 - tert - butyl - 4 ' - methoxydibenzoylmethane", "entity_type": "Chemical", "pos": [74, 122]}, {"entity": "Avobenzone", "entity_type": "Chemical", "pos": [138, 148]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [154, 166]}], "task": "NER"}
{"text": "The keto form is produced upon photolysis of the enol in only acetonitrile with a quantum yield of 0 . 014 .", "entity": [{"entity": "keto", "entity_type": "Chemical", "pos": [4, 8]}, {"entity": "enol", "entity_type": "Chemical", "pos": [49, 53]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [62, 74]}], "task": "NER"}
{"text": "The molar absorptivity of the keto form was determined .", "entity": [{"entity": "keto", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "Phototautomerization from the keto to the enol form was not seen .", "entity": [{"entity": "keto", "entity_type": "Chemical", "pos": [30, 34]}, {"entity": "enol", "entity_type": "Chemical", "pos": [42, 46]}], "task": "NER"}
{"text": "Laser flash photolysis of the keto form recognized the formation of the triplet state .", "entity": [{"entity": "keto", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "In the dark , the keto form underwent thermal tautomerization to the enol with a lifetime of 5 . 1 h at 295 K .", "entity": [{"entity": "keto", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "enol", "entity_type": "Chemical", "pos": [69, 73]}], "task": "NER"}
{"text": "The enolization rate in acetonitrile was not accelerated by the presence of alcohols and / or water but increased with increasing temperature and followed the Arrhenius expression .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "alcohols", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "The activation energy and the frequency factor were determined for the enolization process from the keto to the enol form .", "entity": [{"entity": "keto", "entity_type": "Chemical", "pos": [100, 104]}, {"entity": "enol", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "On the basis of the energy states of the tautomers and isomers as estimated by DFT calculations , a schematic energy diagram was determined for the photothermal tautomerization processes in acetonitrile .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [190, 202]}], "task": "NER"}
{"text": "Newly observed spontaneous activation of ethephon as a butyrylcholinesterase inhibitor .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [41, 49]}], "task": "NER"}
{"text": "The plant growth regulator ethephon ( 2 - chloroethylphosphonic acid ) inhibits human butyrylcholinesterase ( BChE ) by making a covalent adduct on the active site serine 198 .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "2 - chloroethylphosphonic acid", "entity_type": "Chemical", "pos": [38, 68]}, {"entity": "serine", "entity_type": "Chemical", "pos": [164, 170]}], "task": "NER"}
{"text": "Our goal was to extend earlier studies on ethephon inhibition .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "Addition of freshly prepared ethephon to BChE in buffered medium , at pH 7 . 0 and 22 degrees C , resulted in no inhibition initially .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "However , inhibition developed progressively over 60 min of incubation .", "entity": [], "task": "NER"}
{"text": "Preincubation of ethephon in pH 7 - 9 buffers increased its initial inhibitory potency .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "These observations indicated that ethephon itself was not the inhibitor .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "About 3 % of the initial ethephon could be trapped as a BChE adduct .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "Mass spectral analysis of the active site peptide from inhibited BChE showed that the inhibitor added a mass of 108 Da to the active site serine on peptide FGES198AGAAS .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [138, 144]}], "task": "NER"}
{"text": "This result rules out a previous hypothesis that ethephon adds HPO3 to BChE ( added mass of 80 Da ) .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [49, 57]}, {"entity": "HPO3", "entity_type": "Chemical", "pos": [63, 67]}], "task": "NER"}
{"text": "To accommodate these observations , we propose that in aqueous media at neutral to slightly alkaline pH about 3 % of the ethephon is converted ( t1 / 2 = 9 . 9 h at pH 7 . 0 ) into a cyclic oxaphosphetane which is the actual BChE inhibitor forming the 2 - hydroxyethylphosphonate adduct on BChE at Ser198 while about 97 % of the ethephon breaks down to ethylene ( t1 / 2 = 11 - 48 h at pH 7 . 0 ) which is responsible for plant growth regulation .", "entity": [{"entity": "ethephon", "entity_type": "Chemical", "pos": [121, 129]}, {"entity": "cyclic oxaphosphetane", "entity_type": "Chemical", "pos": [183, 204]}, {"entity": "2 - hydroxyethylphosphonate", "entity_type": "Chemical", "pos": [252, 279]}, {"entity": "Ser198", "entity_type": "Chemical", "pos": [298, 304]}, {"entity": "ethephon", "entity_type": "Chemical", "pos": [329, 337]}, {"entity": "ethylene", "entity_type": "Chemical", "pos": [353, 361]}], "task": "NER"}
{"text": "Neural stem / progenitor cells display a low requirement for oxidative metabolism independent of hypoxia inducible factor - 1alpha expression .", "entity": [], "task": "NER"}
{"text": "Neural stem / progenitor cells ( NSPCs ) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages .", "entity": [], "task": "NER"}
{"text": "Maintenance of NSPC multipotency is promoted by low oxygen tension , although the metabolic underpinnings of this trait have not been described .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [52, 58]}], "task": "NER"}
{"text": "In this study , we investigated the metabolic state of undifferentiated NSPCs in culture , and tested their relative reliance on oxidative versus glycolytic metabolism for survival , as well as their dependence on hypoxia inducible factor - 1alpha ( HIF - 1 alpha ) expression for maintenance of metabolic phenotype .", "entity": [], "task": "NER"}
{"text": "Unlike primary neurons , NSPCs from embryonic and adult mice survived prolonged hypoxia in culture .", "entity": [], "task": "NER"}
{"text": "In addition , NSPCs displayed greater susceptibility to glycolytic inhibition compared with primary neurons , even in the presence of alternative mitochondrial TCA substrates .", "entity": [{"entity": "TCA", "entity_type": "Chemical", "pos": [160, 163]}], "task": "NER"}
{"text": "NSPCs were also more resistant than neurons to mitochondrial cyanide toxicity , less capable of utilizing galactose as an alternative substrate to glucose , and more susceptible to pharmacological inhibition of the pentose phosphate pathway by 6 - aminonicotinamide .", "entity": [{"entity": "cyanide", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "galactose", "entity_type": "Chemical", "pos": [106, 115]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [147, 154]}, {"entity": "pentose phosphate", "entity_type": "Chemical", "pos": [215, 232]}, {"entity": "6 - aminonicotinamide", "entity_type": "Chemical", "pos": [244, 265]}], "task": "NER"}
{"text": "Inducible deletion of exon 1 of the Hif1a gene improved the ability of NSPCs to utilize pyruvate during glycolytic inhibition , but did not alter other parameters of metabolism , including their ability to withstand prolonged hypoxia .", "entity": [{"entity": "pyruvate", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "Taken together , these data indicate that NSPCs have a relatively low requirement for oxidative metabolism for their survival and that hypoxic resistance is not dependent upon HIF - 1 alpha signaling .", "entity": [], "task": "NER"}
{"text": "The in vitro and in vivo effects of nicotine on bone , bone cells and fracture repair .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "INTRODUCTION : Cigarette smoke has negative effects on bone metabolism and fracture repair .", "entity": [], "task": "NER"}
{"text": "However , no study has reviewed effects of nicotine on bone and fracture repair independent of other constituents of cigarette smoke .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "The authors review the existing evidence of the effect of nicotine on ' bone ' and ' bone cells ' and fracture repair , drawing conclusions relevant to clinical practice and future research .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [58, 66]}], "task": "NER"}
{"text": "AREAS COVERED : A literature review was conducted using PRISMA guidelines and PubMed , Cochrane , MEDLINE / OVID , EMBASE , NHS Evidence and Google scholar databases .", "entity": [], "task": "NER"}
{"text": "Articles were included if they specifically investigated the effects of nicotine on ' bone ' or fracture repair in animal or human models or in vitro effects on ' bone cells ' .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "A total of 64 papers were included in this review , of which 15 were human in vitro studies and 49 animal studies wherein 9 were in vitro and 40 in vivo .", "entity": [], "task": "NER"}
{"text": "In vivo studies of the effects of nicotine in animals demonstrated widespread effects on bone including osteoneogenesis , osseointegration , steady - state skeletal bone and genes and cytokines relevant to bone cell physiology and bone homeostasis .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "In these studies , nicotine ' s effects are predominately negative , inhibiting bone cell metabolism and fracture repair , whereas most in vitro studies reported biphasic responses in all bone cells except osteoclastic cells .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [19, 27]}], "task": "NER"}
{"text": "EXPERT OPINION : The review suggests that nicotine has effects on osteoneogenesis , osseointegration and steady - state skeletal bone in animal in vivo models , as well as effects on all ' bone cells ' , via several mechanisms in both animal and human cell in vitro studies .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "The effect of nicotine is dose - dependent , with higher concentrations having predominantly negative effects , whereas at low concentrations a stimulatory effect is seen .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [14, 22]}], "task": "NER"}
{"text": "Stimulatory effects on certain cells may indicate a possible , limited therapeutic role ; advice regarding smoking cessation perioperatively should remain due to the other harmful components of cigarette smoke , but there may be scope for allowing the use of nicotine patches instead of complete abstention .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [259, 267]}], "task": "NER"}
{"text": "Further research into clinical outcomes is required before the exact response of bone and fracture repair in humans to nicotine is known .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "Benchmark dose for estimation of cadmium reference level for osteoporosis in a Chinese female population .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [33, 40]}], "task": "NER"}
{"text": "In this study , the reference level of cadmium in urine and blood related with bone damage was assessed using benchmark dose in a Chinese female population .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "Total of 338 women was recruited , and urine and blood samples were collected from each individual for determination of cadmium in urine ( UCd ) and blood ( BCd ) .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [120, 127]}], "task": "NER"}
{"text": "Bone mineral density was measured by dual energy X - ray absorptiometry .", "entity": [], "task": "NER"}
{"text": "BMD and BMDL were calculated corresponding to additional risk of 5 % and 10 % .", "entity": [], "task": "NER"}
{"text": "With benchmark response ( BMR ) of 5 % / 10 % , the BMD of BCd , UCd related with osteoporosis was 1 . 88 mu g / L / 3 . 23 mu g / L and 5 . 30 mu g / g crea / 9 . 06 mu g / g crea , and the BMDL - 05 was 1 . 39 mu g / L / 2 . 38 mu g / L and 3 . 78 mu g / g crea / 6 . 36 mu g / g crea ; the BMD of BCd , UCd related with low bone mass was 0 . 95 mu g / L / 3 . 12 mu g / L and 3 . 12 mu g / g crea / 5 . 87 mu g / g crea , and the BMDL - 05 was 0 . 72 mu g / L / 1 . 35 mu g / L and 2 . 14 mu g / g crea / 3 . 99 mu g / g crea .", "entity": [], "task": "NER"}
{"text": "The BMD of UCd in people over 60years old was much lower than that of people less than 60years old .", "entity": [], "task": "NER"}
{"text": "BMD value was related with ages and effects biomarkers .", "entity": [], "task": "NER"}
{"text": "Our data showed that BMD of UCd associated with osteoporosis was lower than that previously estimated .", "entity": [], "task": "NER"}
{"text": "DNA damage and oxidative stress in human B lymphoblastoid cells after combined exposure to hexavalent chromium and nickel compounds .", "entity": [{"entity": "hexavalent chromium", "entity_type": "Chemical", "pos": [91, 110]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [115, 121]}], "task": "NER"}
{"text": "In the present study , human B lymphoblastoid cells were exposed to potassium dichromate and / or nickel chloride for 24h or 48h .", "entity": [{"entity": "potassium dichromate", "entity_type": "Chemical", "pos": [68, 88]}, {"entity": "nickel chloride", "entity_type": "Chemical", "pos": [98, 113]}], "task": "NER"}
{"text": "The cell viability and DNA damage induced by these compounds was measured with the CCK - 8 assay and Comet assay , respectively .", "entity": [], "task": "NER"}
{"text": "In addition , the generation of reactive oxygen species ( ROS ) and the levels of malondialdehyde ( MDA ) were measured using commercially available kits .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [41, 47]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [82, 97]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [100, 103]}], "task": "NER"}
{"text": "Our results indicated that potassium dichromate could decrease cell viability and induce DNA damage in human B lymphoblastoid cells in a time - and concentration - dependent manner , but the toxicity of nickel chloride was not so obvious at concentrations used in our study .", "entity": [{"entity": "potassium dichromate", "entity_type": "Chemical", "pos": [27, 47]}, {"entity": "nickel chloride", "entity_type": "Chemical", "pos": [203, 218]}], "task": "NER"}
{"text": "The results of ROS showed that both two compounds could only induce weak elevation of ROS level , but MDA levels were significantly enhanced .", "entity": [{"entity": "MDA", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Antagonistic effects of cytotoxicity were mainly found between Cr ( VI ) and Ni ( II ) , and synergistic effects of DNA damage and oxidative stress were partially found between these two compounds .", "entity": [{"entity": "Cr ( VI )", "entity_type": "Chemical", "pos": [63, 72]}, {"entity": "Ni ( II )", "entity_type": "Chemical", "pos": [77, 86]}], "task": "NER"}
{"text": "Moreover , there were good correlations between the results of comet assay and the results of oxidative stress assays .", "entity": [], "task": "NER"}
{"text": "It is suggested that synergistic DNA damage induced by simultaneously exposure of hexavalent chromium and nickel compounds is possibly related to oxidative stress .", "entity": [{"entity": "hexavalent chromium", "entity_type": "Chemical", "pos": [82, 101]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [106, 112]}], "task": "NER"}
{"text": "Spiro heterocycles as potential inhibitors of SIRT1 : Pd / C - mediated synthesis of novel N - indolylmethyl spiroindoline - 3 , 2 ' - quinazolines .", "entity": [{"entity": "Pd", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "C", "entity_type": "Chemical", "pos": [59, 60]}, {"entity": "N - indolylmethyl spiroindoline - 3 , 2 ' - quinazolines", "entity_type": "Chemical", "pos": [91, 147]}], "task": "NER"}
{"text": "Novel N - indolylmethyl substituted spiroindoline - 3 , 2 ' - quinazolines were designed as potential inhibitiors of SIRT1 .", "entity": [{"entity": "N - indolylmethyl substituted spiroindoline - 3 , 2 ' - quinazolines", "entity_type": "Chemical", "pos": [6, 74]}], "task": "NER"}
{"text": "These compounds were synthesized in good yields by using Pd / C - Cu mediated coupling - cyclization strategy as a key step involving the reaction of 1 - ( prop - 2 - ynyl ) - 1 ' H - spiro [ indoline - 3 , 2 ' - quinazoline ] - 2 , 4 ' ( 3 ' H ) - dione with 2 - iodoanilides .", "entity": [{"entity": "Pd", "entity_type": "Chemical", "pos": [57, 59]}, {"entity": "C - Cu", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "1 - ( prop - 2 - ynyl ) - 1 ' H - spiro [ indoline - 3 , 2 ' - quinazoline ] - 2 , 4 ' ( 3 ' H ) - dione", "entity_type": "Chemical", "pos": [150, 254]}, {"entity": "2 - iodoanilides", "entity_type": "Chemical", "pos": [260, 276]}], "task": "NER"}
{"text": "Some of the compounds synthesized have shown encouraging inhibition of Sir 2 protein ( a yeast homologue of mammalian SIRT1 ) in vitro and three of them showed dose dependent inhibition of Sir 2 .", "entity": [], "task": "NER"}
{"text": "The docking results suggested that the benzene ring of 1 , 2 , 3 , 4 - tetrahydroquinazolin ring system of these molecules occupied the deep hydrophobic pocket of the protein and one of the NH along with the sulfonyl group participated in strong H - bonding interaction with the amino acid residues .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "1 , 2 , 3 , 4 - tetrahydroquinazolin", "entity_type": "Chemical", "pos": [55, 91]}, {"entity": "NH", "entity_type": "Chemical", "pos": [190, 192]}, {"entity": "sulfonyl", "entity_type": "Chemical", "pos": [208, 216]}, {"entity": "H", "entity_type": "Chemical", "pos": [246, 247]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [279, 289]}], "task": "NER"}
{"text": "Effects of salinomycin on human bone marrow - derived mesenchymal stem cells in vitro .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [11, 22]}], "task": "NER"}
{"text": "Various hypotheses on the origin of cancer stem cells ( CSCs ) exist , including that CSCs develop from transformed human bone marrow mesenchymal stem cells ( hBMSC ) .", "entity": [], "task": "NER"}
{"text": "Since the polyether antibiotic salinomycin selectively kills CSCs , the present study aims to elucidate the effects of salinomycin on normal hBMSC .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [31, 42]}, {"entity": "salinomycin", "entity_type": "Chemical", "pos": [119, 130]}], "task": "NER"}
{"text": "The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [35, 46]}], "task": "NER"}
{"text": "The multi - differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining .", "entity": [{"entity": "Oil Red O", "entity_type": "Chemical", "pos": [63, 72]}], "task": "NER"}
{"text": "Cytotoxic effects of salinomycin were monitored by the [ 3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyl tetrazolium bromide ] ( MTT ) assay .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [21, 32]}, {"entity": "3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyl tetrazolium bromide", "entity_type": "Chemical", "pos": [57, 136]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [141, 144]}], "task": "NER"}
{"text": "Furthermore , spheroid formation and migration capacity were assessed .", "entity": [], "task": "NER"}
{"text": "There were no differences in the immunophenotype and multi - differentiation capacity of hBMSC induced by salinomycin treatment .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [106, 117]}], "task": "NER"}
{"text": "Cytotoxic effects were observed at concentrations of 30 mu M and above .", "entity": [], "task": "NER"}
{"text": "Neither the migration capability nor the ability to form spheroids was affected .", "entity": [], "task": "NER"}
{"text": "Essential functional properties of hBMSC were unaffected by salinomycin .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [60, 71]}], "task": "NER"}
{"text": "However , dose - dependent cytotoxicity effects could be observed .", "entity": [], "task": "NER"}
{"text": "Overall , low dose salinomycin showed no negative effects on hBMSC .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [19, 30]}], "task": "NER"}
{"text": "Since mesenchymal stem cells from various sources respond differently , further in vitro studies are needed to clarify the effect of salinomycin on tissue - specific stem cells .", "entity": [{"entity": "salinomycin", "entity_type": "Chemical", "pos": [133, 144]}], "task": "NER"}
{"text": "Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology .", "entity": [], "task": "NER"}
{"text": "For years , scientists from various disciplines have studied the effects of endocrine disrupting chemicals ( EDCs ) on the health and wellbeing of humans and wildlife .", "entity": [], "task": "NER"}
{"text": "Some studies have specifically focused on the effects of low doses , i . e . those in the range that are thought to be safe for humans and / or animals .", "entity": [], "task": "NER"}
{"text": "Others have focused on the existence of non - monotonic dose - response curves .", "entity": [], "task": "NER"}
{"text": "These concepts challenge the way that chemical risk assessment is performed for EDCs .", "entity": [], "task": "NER"}
{"text": "Continued discussions have clarified exactly what controversies and challenges remain .", "entity": [], "task": "NER"}
{"text": "We address several of these issues , including why the study and regulation of EDCs should incorporate endocrine principles ; what level of consensus there is for low dose effects ; challenges to our understanding of non - monotonicity ; and whether EDCs have been demonstrated to produce adverse effects .", "entity": [], "task": "NER"}
{"text": "This discussion should result in a better understanding of these issues , and allow for additional dialog on their impact on risk assessment .", "entity": [], "task": "NER"}
{"text": "Net analyte signal standard addition method for simultaneous determination of sulphadiazine and trimethoprim in bovine milk and veterinary medicines .", "entity": [{"entity": "sulphadiazine", "entity_type": "Chemical", "pos": [78, 91]}, {"entity": "trimethoprim", "entity_type": "Chemical", "pos": [96, 108]}], "task": "NER"}
{"text": "Net analyte signal standard addition method has been used for the simultaneous determination of sulphadiazine and trimethoprim by spectrophotometry in some bovine milk and veterinary medicines .", "entity": [{"entity": "sulphadiazine", "entity_type": "Chemical", "pos": [96, 109]}, {"entity": "trimethoprim", "entity_type": "Chemical", "pos": [114, 126]}], "task": "NER"}
{"text": "The method combines the advantages of standard addition method with the net analyte signal concept which enables the extraction of information concerning a certain analyte from spectra of multi - component mixtures .", "entity": [], "task": "NER"}
{"text": "This method has some advantages such as the use of a full spectrum realisation , therefore it does not require calibration and prediction step and only a few measurements require for the determination .", "entity": [], "task": "NER"}
{"text": "Cloud point extraction based on the phenomenon of solubilisation used for extraction of sulphadiazine and trimethoprim in bovine milk .", "entity": [{"entity": "sulphadiazine", "entity_type": "Chemical", "pos": [88, 101]}, {"entity": "trimethoprim", "entity_type": "Chemical", "pos": [106, 118]}], "task": "NER"}
{"text": "It is based on the induction of micellar organised media by using Triton X - 100 as an extraction solvent .", "entity": [{"entity": "Triton X - 100", "entity_type": "Chemical", "pos": [66, 80]}], "task": "NER"}
{"text": "At the optimum conditions , the norm of NAS vectors increased linearly with concentrations in the range of 1 . 0 - 150 . 0 mu molL ( - 1 ) for both sulphadiazine and trimethoprim .", "entity": [{"entity": "sulphadiazine", "entity_type": "Chemical", "pos": [148, 161]}, {"entity": "trimethoprim", "entity_type": "Chemical", "pos": [166, 178]}], "task": "NER"}
{"text": "The limits of detection ( LOD ) for sulphadiazine and trimethoprim were 0 . 86 and 0 . 92 mu molL ( - 1 ) , respectively .", "entity": [{"entity": "sulphadiazine", "entity_type": "Chemical", "pos": [36, 49]}, {"entity": "trimethoprim", "entity_type": "Chemical", "pos": [54, 66]}], "task": "NER"}
{"text": "Anti - inflammatory effects of an aqueous extract of Welsh onion green leaves in mice .", "entity": [], "task": "NER"}
{"text": "The anti - inflammatory effects of an aqueous extract of Welsh onion green leaves ( WOE ) in mice was investigated .", "entity": [], "task": "NER"}
{"text": "Administration of WOE , in the range of 0 . 25 - 1g / kg , showed a concentration dependent inhibition on paw edema development after carrageenan treatment in mice .", "entity": [], "task": "NER"}
{"text": "The anti - inflammatory effects of WOE were closely attributed to decreased levels of tissue NO and tumor necrosis factor - alpha ( TNF - alpha ) .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [93, 95]}], "task": "NER"}
{"text": "Further evidence for WOE ' s protection is shown in the reduction of lipid oxidation and the increase of antioxidant enzyme activities , including catalase ( CAT ) , superoxide dismutase ( SOD ) , and glutathione peroxidase ( GPX ) in vivo .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [166, 176]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [201, 212]}], "task": "NER"}
{"text": "Further , WOE also decreased the number of acetic acid - induced writhing responses and formalin - induced pain in the late phase in mice .", "entity": [{"entity": "acetic acid", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "Overall , the results showed that WOE might serve as a natural source of anti - inflammatory compounds .", "entity": [], "task": "NER"}
{"text": "Apple polyphenols suppress antigen presentation of ovalbumin by THP - 1 - derived dendritic cells .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [6, 17]}], "task": "NER"}
{"text": "Apple polyphenol extract ( AP ) and procyanidin contained in AP were investigated for their immunomodulatory effects using THP - 1 - derived human dendritic cells ( TDDCs ) .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [6, 16]}, {"entity": "procyanidin", "entity_type": "Chemical", "pos": [36, 47]}], "task": "NER"}
{"text": "The expression levels of HLA - DR ( MHC class II ) and CD86 ( costimulatory molecule ) were measured as an indicator of antigen presentation in TDDCs .", "entity": [], "task": "NER"}
{"text": "A significant decrease in HLA - DR expression was observed in the AP and fractionated procyanidin - treated cells in the presence of ovalbumin ( OVA ) , but no effect on CD86 expression was observed .", "entity": [{"entity": "procyanidin", "entity_type": "Chemical", "pos": [86, 97]}], "task": "NER"}
{"text": "The uptake of OVA was not inhibited by AP treatment , and the gene expression of membrane - associated RING - CH ubiquitin E3 ligase , MARCH1 , was up - regulated by AP treatment .", "entity": [], "task": "NER"}
{"text": "It can therefore be presumed that AP suppresses HLA - DR expression via the ubiquitin - proteasome pathway .", "entity": [], "task": "NER"}
{"text": "Furthermore , the up - regulation of IL - 12 and TNF - alpha was found in the procyanidin trimers - treated cells in the presence of OVA .", "entity": [{"entity": "procyanidin", "entity_type": "Chemical", "pos": [78, 89]}], "task": "NER"}
{"text": "These results suggest that apple polyphenols would be an effective factor for the development of immunomodulatory agents with suppressive effects of antigen presentation .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [33, 44]}], "task": "NER"}
{"text": "Comparison of extraction induced by emulsion breaking , ultrasonic extraction and wet digestion procedures for determination of metals in edible oil samples in Turkey using ICP - OES .", "entity": [], "task": "NER"}
{"text": "The content of elements ( Cd , Cr , Cu , Fe , Mn , Ni , Pb and Zn ) in edible oils ( sunflower , hazelnut , canola , corn and olive oils ) from Turkey was determined using inductively coupled plasma optical emission spectrometry ( ICP - OES ) after ultrasonic extraction , wet digestion , and extraction induced by emulsion breaking procedures ( EIEB ) .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [26, 28]}, {"entity": "Cr", "entity_type": "Chemical", "pos": [31, 33]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [36, 38]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [46, 48]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [63, 65]}], "task": "NER"}
{"text": "In order to evaluate the best sample preparation procedure , EIEB procedure was compared by ultrasonic extraction and wet digestion procedures .", "entity": [], "task": "NER"}
{"text": "The results in the samples ( minimum - maximum in mgkg ( - 1 ) ) were : 0 . 022 - 0 . 058 , Cr 0 . 126 - 7 . 106 , Cu 0 . 570 - 4 . 504 , Fe 8 . 004 - 12 . 588 , Mn 0 . 035 - 0 . 054 , Ni 0 . 908 - 2 . 182 , Pb 0 . 099 - 0 . 134 and Zn 2 . 206 - 8 . 982 .", "entity": [{"entity": "Cr", "entity_type": "Chemical", "pos": [92, 94]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [115, 117]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [138, 140]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [162, 164]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [185, 187]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [208, 210]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [233, 235]}], "task": "NER"}
{"text": "The EIEB procedure was found to be fast , reliable , simple , and excellent in comparison with the other studied procedures .", "entity": [], "task": "NER"}
{"text": "The recovery test was performed by spiking the samples with known amounts of the metals in the form of organometallic standards and applying the EIEB procedure .", "entity": [], "task": "NER"}
{"text": "The recoveries were in the range of 96 - 109 % .", "entity": [], "task": "NER"}
{"text": "Reduction of abdominal fat accumulation in rats by 8 - week ingestion of a newly developed sweetener made from high fructose corn syrup .", "entity": [{"entity": "fructose", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "Many studies have shown that ingestion of high - fructose corn syrup ( HFCS ) may cause an increase in body weight and abdominal fat .", "entity": [{"entity": "fructose", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "We recently developed a new sweetener containing rare sugars ( rare sugar syrup ; RSS ) by slight isomerization of HFCS .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [54, 60]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [68, 73]}], "task": "NER"}
{"text": "Here , the functional effects of RSS on body weight and abdominal fat , and biochemical parameters in Wistar rats were examined .", "entity": [], "task": "NER"}
{"text": "Rats ( n = 30 ) were randomly divided into three groups and maintained for 8 - weeks on starch , starch + HFCS ( 50 : 50 ) , and starch + RSS ( 50 : 50 ) diets .", "entity": [], "task": "NER"}
{"text": "Rats in the Starch and HFCS groups gained significantly more body weight and abdominal fat than the RSS group .", "entity": [], "task": "NER"}
{"text": "Fasting serum insulin in the RSS group was significantly lower than in the Starch and HFCS groups , although serum glucose in the HFCS and RSS groups was significantly lower than that in the Starch group .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [115, 122]}], "task": "NER"}
{"text": "Thus , the substitution of HFCS with RSS prevents obesity induced by the consumption of HFCS .", "entity": [], "task": "NER"}
{"text": "Analysis of the blackening of green pepper ( Piper nigrum Linnaeus ) berries .", "entity": [], "task": "NER"}
{"text": "This paper investigates polyphenol oxidase ( PPO ) activity , reduced weight percentage after sun drying , and the changes in colour and appearance of green pepper ( Piper nigrum Linnaeus ) berries after blanching and sun drying .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [24, 34]}], "task": "NER"}
{"text": "The results show that the degree of reduced weight percentage and browning in green pepper berries after blanching for 10 min is greater at 100 degrees C than at 90 and 80 degrees C .", "entity": [], "task": "NER"}
{"text": "Moreover , the samples blanched at 100 degrees C for 10 min had the fastest water loss , but the lowest PPO activity .", "entity": [], "task": "NER"}
{"text": "Thus , the PPO enzymatic oxidation of polyphenols might not be the only reason for the browning of green pepper berries .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [38, 49]}], "task": "NER"}
{"text": "This result is significantly different from that of Variyar , Pendharkar , Banerjeea , and Bandyopadhyay ( 1988 ) and therefore deserves further study .", "entity": [], "task": "NER"}
{"text": "Nutritional value and antioxidant activity of honeys produced in a European Atlantic area .", "entity": [], "task": "NER"}
{"text": "One hundred eighty - seven honey samples from an Atlantic European area were studied to determine their nutritional compositions and antioxidant capacities , as well as the relationships between them .", "entity": [], "task": "NER"}
{"text": "The results showed that heather , polyfloral , blackberry , and eucalyptus honeys had the highest carbohydrate contents , whereas honeydew and chestnut honeys had the lowest .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [98, 110]}], "task": "NER"}
{"text": "There were some important differences among the honey types , which were related to the presence of minor components .", "entity": [], "task": "NER"}
{"text": "The protein contents were significantly higher in honeydew and chestnut honeys , and the same results were obtained for mineral contents .", "entity": [], "task": "NER"}
{"text": "Related to the presence of several antioxidant compounds , heather honey had the highest phenolic content , whereas honeydew and chestnut honeys had the highest flavonoid contents .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [161, 170]}], "task": "NER"}
{"text": "Multivariate analysis showed that some variables , such as the amounts of flavonoids , minerals , proteins , and phenols , were significantly correlated with antioxidant activity .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "phenols", "entity_type": "Chemical", "pos": [113, 120]}], "task": "NER"}
{"text": "The regression analysis produced a significant model ( R ( 2 ) = 0 . 716 ; F = 154 . 680 ; P < 0 . 001 ) that related the antioxidant activity and the flavonoids , K , and P contents .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [151, 161]}, {"entity": "K", "entity_type": "Chemical", "pos": [164, 165]}, {"entity": "P", "entity_type": "Chemical", "pos": [172, 173]}], "task": "NER"}
{"text": "Assessment of antimicrobial and antiprotozoal activity of the olive oil macerate samples of Hypericum perforatum and their LC - DAD - MS analyses .", "entity": [], "task": "NER"}
{"text": "Twenty - one samples of traditionally - prepared ( home - made ) and ready - made ( commercial ) St .", "entity": [], "task": "NER"}
{"text": "John ' s Wort olive oil macerates were profiled for their in vitro antimicrobial and antiprotozoal activity .", "entity": [], "task": "NER"}
{"text": "Their cytotoxic potential was evaluated on MRC - 5 fibroblasts .", "entity": [], "task": "NER"}
{"text": "In the antiprotozoal assays , ten of the oils inhibited Trypanosoma brucei rhodesiense ( IC ( 50 ) 15 . 9 - 64 . 5 mu g / mL ) , while only one oil exerted antimicrobial activity towards Staphylococcus aureus ( IC ( 50 ) = 88 . 7 mu g / mL ) .", "entity": [], "task": "NER"}
{"text": "LC - DAD - MS data revealed the presence of pseudohypericin ( 0 . 135 - 3 . 280 mu g / g ) and hypericin ( 0 . 277 - 6 . 634 mu g / g ) in all the oils , whereas chlorogenic acid ( 1 . 063 mu g / g ) was detected only in one oil sample .", "entity": [{"entity": "pseudohypericin", "entity_type": "Chemical", "pos": [44, 59]}, {"entity": "hypericin", "entity_type": "Chemical", "pos": [95, 104]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [162, 178]}], "task": "NER"}
{"text": "Hyperforin was detected in four ( 0 . 977 - 2 . 399 mu g / g ) and adhyperforin in six samples ( 0 . 005 - 3 . 165 mu g / g ) .", "entity": [{"entity": "Hyperforin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "adhyperforin", "entity_type": "Chemical", "pos": [67, 79]}], "task": "NER"}
{"text": "Hypericin and pseudohypericin were common in the active oils , whereas hyperforin , adhyperforin , and chlorogenic acid were absent in these samples .", "entity": [{"entity": "Hypericin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "pseudohypericin", "entity_type": "Chemical", "pos": [14, 29]}, {"entity": "hyperforin", "entity_type": "Chemical", "pos": [71, 81]}, {"entity": "adhyperforin", "entity_type": "Chemical", "pos": [84, 96]}, {"entity": "chlorogenic acid", "entity_type": "Chemical", "pos": [103, 119]}], "task": "NER"}
{"text": "Our results indicated that if the correct plant material is used , the infused oils from Hypericum perforatum may contain active components .", "entity": [], "task": "NER"}
{"text": "Classification of Spanish extra virgin olive oils by data fusion of visible spectroscopic fingerprints and chemical descriptors .", "entity": [], "task": "NER"}
{"text": "The potential of visible fingerprints and physical - chemical parameters in combination with multivariate data analysis was examined to classify extra virgin olive oils ( EVOOs ) from different Spanish regions according to their geographical origin .", "entity": [], "task": "NER"}
{"text": "Firstly , spectral and quality parameters matrices were processed separately and subsequently were joined to evaluate the effect of synergy on the information obtained from the different methodologies .", "entity": [], "task": "NER"}
{"text": "Linear discriminant analysis ( LDA ) and partial least squares discriminant analysis ( PLS - DA ) were performed as classification methods .", "entity": [], "task": "NER"}
{"text": "The results revealed a perfect discrimination between the defined categories after performing PLS - DA on the Fused matrix , reaching 100 % of correct classifications and showed a clear improvement in the overall prediction rates ( 92 . 5 % ) , so that the effect of synergy was confirmed .", "entity": [], "task": "NER"}
{"text": "These accurate results emphasise the feasibility of the proposed strategy and encourage the development of similar approaches based on visible spectroscopy in olive oil quality and traceability determination .", "entity": [], "task": "NER"}
{"text": "Anti - inflammatory effects of phenolic crude extracts from five fractions of Corchorus Olitorius L .", "entity": [], "task": "NER"}
{"text": "Corchorus olitorius L .", "entity": [], "task": "NER"}
{"text": "is grown in Taiwan during summer .", "entity": [], "task": "NER"}
{"text": "Tender leaves are crushed and washed by running water before eating .", "entity": [], "task": "NER"}
{"text": "Five fractions including crude phenolic extracts ( using 80 per cent aqueous acetone ) of whole plant , leaf , stem , washed leaf ( WL ) and dried water washing material ( WW ) were used in this study .", "entity": [{"entity": "acetone", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "Linoleic acid autoxidation inhibitions on all fractions were higher than that on alpha - tocopherol .", "entity": [{"entity": "Linoleic acid", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [81, 99]}], "task": "NER"}
{"text": "Except for WL and WW , other fractions also showed DPPH radical scavenging efficiency .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "The effect of all fractions on the regulation of inflammatory responses in lipopolysaccharide ( LPS ) - stimulated J774A . 1 macrophage cells was investigated .", "entity": [], "task": "NER"}
{"text": "All fractions diminished LPS - induced protein expression of inducible nitric oxide synthase ( iNOS ) and cyclooxygenase 2 ( COX - 2 ) .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [71, 83]}], "task": "NER"}
{"text": "Nitric oxide ( NO ) and prostaglandin E2 ( PGE ( 2 ) ) , downstream products , were also suppressed in dose - dependent manners , except for WL and WW .", "entity": [{"entity": "Nitric oxide", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "NO", "entity_type": "Chemical", "pos": [15, 17]}, {"entity": "prostaglandin E2", "entity_type": "Chemical", "pos": [24, 40]}, {"entity": "PGE ( 2 )", "entity_type": "Chemical", "pos": [43, 52]}], "task": "NER"}
{"text": "Oxidative modification and loss of leaf phenolics after kneading and washing greatly affected DPPH radical scavenging and inflammatory responses .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "Storage stability of hen egg white powders in three protein / water dough model systems .", "entity": [], "task": "NER"}
{"text": "In recent years , due to the specific health benefits associated with bioactive peptides and the reduction of protein allergenicity by enzymatic hydrolysis , the utilisation of protein hydrolysates in the intermediate - moisture food ( IMF ) market , such as high protein nutrition bars ( HPNB ) , has significantly increased .", "entity": [], "task": "NER"}
{"text": "Currently , no reported study is related to the storage stability of dried hen egg white ( DEW ) and its hydrolysates ( HEW ) in an IMF matrix .", "entity": [], "task": "NER"}
{"text": "Therefore , three DEW / HEW dough model systems ( 100 % HEW + 0 % DEW , 75 % HEW + 25 % DEW and 50 % HEW + 50 % DEW ) were established using two commercial spray - dried egg white powders to study the effect of temperature and fraction of HEW on these IMF models ( water activity ( a ( w ) ) : ~ 0 . 8 ) .", "entity": [], "task": "NER"}
{"text": "During storage at three different temperatures ( 23 , 35 and 45 degrees C ) for 70 days , the selected physicochemical properties of the dough systems were compared .", "entity": [], "task": "NER"}
{"text": "Overall , kinetic analysis showed an apparent zero - order model fit for the change in the colour ( L ( * ) ) , fluorescence intensity ( FI ) and hardness , as a function of time , for different dough model systems .", "entity": [], "task": "NER"}
{"text": "As expected , the L ( * ) , FI and hardness increased as a function of time mainly due to the Maillard reaction .", "entity": [], "task": "NER"}
{"text": "The amount of free amino groups decreased , with an increase in rate of loss , as temperature increased in the 100 % HEW + 0 % DEW model .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [19, 24]}], "task": "NER"}
{"text": "When DEW was substituted for some HEW , the regeneration of the free amino groups after loss was observed as a function of time .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [69, 74]}], "task": "NER"}
{"text": "Furthermore , when the percentage of HEW was decreased , the incidence of mouldy samples occurred sooner , which indicates that HEW has some antimicrobial ability , especially in the 100 % HEW + 0 % DEW system where mould growth did not occur .", "entity": [], "task": "NER"}
{"text": "Investigation of isotope dilution mass spectrometric ( ID - MS ) method to determine niacin in infant formula , breakfast cereals and multivitamins .", "entity": [{"entity": "niacin", "entity_type": "Chemical", "pos": [85, 91]}], "task": "NER"}
{"text": "An isotope dilution LC / mass spectrometric ( ID - LC / MS ) method was developed as a candidate reference method for the accurate determination of niacin in infant formula , breakfast cereals and multivitamin .", "entity": [{"entity": "niacin", "entity_type": "Chemical", "pos": [148, 154]}], "task": "NER"}
{"text": "After spiking nicotinamide - d ( 4 ) as an internal standard , infant formula and breakfast cereal samples were hydrolysed under alkaline condition .", "entity": [{"entity": "nicotinamide - d ( 4 )", "entity_type": "Chemical", "pos": [14, 36]}], "task": "NER"}
{"text": "Samples were then analysed in SRM mode to detect nicotinic acid and nicotinic acid - d ( 4 ) at m / z 124 --> 80 and 127 --> 84 , respectively .", "entity": [{"entity": "nicotinic acid", "entity_type": "Chemical", "pos": [49, 63]}, {"entity": "nicotinic acid - d ( 4 )", "entity_type": "Chemical", "pos": [68, 92]}], "task": "NER"}
{"text": "In the case of multivitamin sample that contains mainly free nicotinamide , LC / MS monitored nicotinamide and nicotinamide - d ( 4 ) at their SRM channels of m / z 123 --> 80 and m / z 127 --> 84 , respectively , after simple extraction .", "entity": [{"entity": "nicotinamide", "entity_type": "Chemical", "pos": [61, 73]}, {"entity": "nicotinamide", "entity_type": "Chemical", "pos": [94, 106]}, {"entity": "nicotinamide - d ( 4 )", "entity_type": "Chemical", "pos": [111, 133]}], "task": "NER"}
{"text": "The repeatability and reproducibility were tested for the validation of the developed ID / LC - MS method .", "entity": [], "task": "NER"}
{"text": "Additionally , the developed analytical method was applied to determine total niacin contents in homogenised infant formula , homogenised multivitamin , and commercially available products including different types of infant formula , breakfast cereals , and multivitamin tablets .", "entity": [{"entity": "niacin", "entity_type": "Chemical", "pos": [78, 84]}], "task": "NER"}
{"text": "Hypolipidemic and antioxidant activities of thymoquinone and limonene in atherogenic suspension fed rats .", "entity": [{"entity": "thymoquinone", "entity_type": "Chemical", "pos": [44, 56]}, {"entity": "limonene", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "The hypolipidemic and antioxidant actions of thymoquinone ( TQ ) and limonene ( LMN ) were investigated by giving 1 ml of 10mg TQ or 200mg LMN suspension , by gavage in two equal doses ( morning and evening ) of 0 . 5 ml each for 30 days , in rats , fed an atherogenic suspension .", "entity": [{"entity": "thymoquinone", "entity_type": "Chemical", "pos": [45, 57]}, {"entity": "limonene", "entity_type": "Chemical", "pos": [69, 77]}, {"entity": "LMN", "entity_type": "Chemical", "pos": [80, 83]}, {"entity": "LMN", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "These compounds effectively ameliorated all the altered cardiovascular risk parameters via a reduction in HMG - CoA reductase activity , along with an increase in arylesterase activity .", "entity": [{"entity": "HMG - CoA", "entity_type": "Chemical", "pos": [106, 115]}], "task": "NER"}
{"text": "The compounds significantly blocked the shift in buoyancy from less atherogenic lb - LDL to highly atherogenic sd - LDL , restoring the percent distribution of LDL - C and apoB into sd - LDL and lb - LDL to near normal levels .", "entity": [], "task": "NER"}
{"text": "These compounds also blocked basal and maximal formation of CD and malondialdehyde , and lengthened the lag times of LDL , sd - LDL and lb - LDL in the order TQ > LMN .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [67, 82]}, {"entity": "LMN", "entity_type": "Chemical", "pos": [163, 166]}], "task": "NER"}
{"text": "Our results strongly suggest an important therapeutic use of test compounds , especially TQ , in the prevention of cardiovascular disease risks parameters .", "entity": [], "task": "NER"}
{"text": "Effects of sodium caseinate concentration and storage conditions on the oxidative stability of oil - in - water emulsions .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [11, 17]}], "task": "NER"}
{"text": "The oxidative stability of various oils ( sunflower , camelina and fish ) and 20 % oil - in - water ( O / W ) emulsions , were examined .", "entity": [], "task": "NER"}
{"text": "The mean particle size decreased from 1179 to 325 nm as sodium caseinate ( emulsifier ) concentration was increased from 0 . 25 % to 3 % in O / W emulsions ( P < 0 . 05 ) .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [56, 62]}], "task": "NER"}
{"text": "Increasing the microfluidisation pressure from 21 to 138 MPa , resulted in a particle size decrease from 289 to 194 nm ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Emulsified oils had lower detectable lipid hydroperoxide and p - Anisidine values than their corresponding bulk oils ( P < 0 . 05 ) .", "entity": [{"entity": "hydroperoxide", "entity_type": "Chemical", "pos": [43, 56]}, {"entity": "p - Anisidine", "entity_type": "Chemical", "pos": [61, 74]}], "task": "NER"}
{"text": "The lipid hydroperoxide and p - Anisidine values of emulsions generally decreased as sodium caseinate concentration increased , and similarly decreased as microfluidisation pressure increased ( P < 0 . 05 ) .", "entity": [{"entity": "hydroperoxide", "entity_type": "Chemical", "pos": [10, 23]}, {"entity": "p - Anisidine", "entity_type": "Chemical", "pos": [28, 41]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [85, 91]}], "task": "NER"}
{"text": "Increasing storage temperature of the emulsions from 5 to 60 degrees C , resulted in lower detectable lipid oxidation products during storage ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Antioxidant activity and nutritional quality of traditional red - grained rice varieties containing proanthocyanidins .", "entity": [{"entity": "proanthocyanidins", "entity_type": "Chemical", "pos": [100, 117]}], "task": "NER"}
{"text": "Proanthocyanidin - containing rice varieties have been rarely reported .", "entity": [{"entity": "Proanthocyanidin", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Antioxidant capacity , major antioxidant components , and nutritional parameters of eight traditional red - grained rice varieties containing proanthocyanidins grown in Sri Lanka were investigated .", "entity": [{"entity": "proanthocyanidins", "entity_type": "Chemical", "pos": [142, 159]}], "task": "NER"}
{"text": "The tested traditional red varieties , on the average , had over sevenfold higher both total antioxidant capacity and phenolic content than three light brown - grained new - improved rice varieties .", "entity": [], "task": "NER"}
{"text": "Major antioxidant phenolic compounds identified in this study included proanthocyanidins , phenolic acids and gamma - oryzanols ( ferulic acid derivatives ) .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [18, 26]}, {"entity": "proanthocyanidins", "entity_type": "Chemical", "pos": [71, 88]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [91, 105]}, {"entity": "gamma - oryzanols", "entity_type": "Chemical", "pos": [110, 127]}, {"entity": "ferulic acid", "entity_type": "Chemical", "pos": [130, 142]}], "task": "NER"}
{"text": "Proanthocyanidins were detected only in the traditional red varieties , but not found in new - improved ones .", "entity": [{"entity": "Proanthocyanidins", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Most traditional red varieties also contained significantly higher levels of protein with well balanced amino acids and higher contents of fat , fibre and vitamin E ( tocopherols and tocotrienols ) than the new - improved ones .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [104, 115]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [155, 164]}, {"entity": "tocopherols", "entity_type": "Chemical", "pos": [167, 178]}, {"entity": "tocotrienols", "entity_type": "Chemical", "pos": [183, 195]}], "task": "NER"}
{"text": "Great variations in antioxidant capacity , major phenolics , and nutritional parameters were observed among different rice varieties .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [49, 58]}], "task": "NER"}
{"text": "These Sri Lankan traditional red - grained rice varieties containing proanthocyanidins may be used as important genetic sources for rice breeding .", "entity": [{"entity": "proanthocyanidins", "entity_type": "Chemical", "pos": [69, 86]}], "task": "NER"}
{"text": "Hydroxytyrosyl ethyl ether exhibits stronger intestinal anticarcinogenic potency and effects on transcript profiles compared to hydroxytyrosol .", "entity": [{"entity": "Hydroxytyrosyl ethyl ether", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [128, 142]}], "task": "NER"}
{"text": "The anticarcinogenic activity of hydroxytyrosyl ethyl ether ( HTy - Et ) compared to its precursor hydroxytyrosol ( HTy ) has been studied in human Caco - 2 colon adenocarcinoma cells .", "entity": [{"entity": "hydroxytyrosyl ethyl ether", "entity_type": "Chemical", "pos": [33, 59]}, {"entity": "HTy - Et", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [99, 113]}, {"entity": "HTy", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "451 and 977 genes were differentially expressed in Caco - 2 cells exposed to HTy or HTy - Et for 24h , respectively , compared with untreated cells ( P < 0 . 005 ; FDR = 0 ) , using Affymetrix microarrays .", "entity": [{"entity": "HTy", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "HTy - Et", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "Results showed that both HTy and HTy - Et inhibited cell proliferation and arrested the cell cycle by up - regulating p21 and CCNG2 and down - regulating CCNB1 protein expression .", "entity": [{"entity": "HTy", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "HTy - Et", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "HTy and HTy - Et also altered the transcription of specific genes involved in apoptosis , as suggested by the up - regulation of BNIP3 , BNIP3L , PDCD4 and ATF3 and the activation of caspase - 3 .", "entity": [{"entity": "HTy", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "HTy - Et", "entity_type": "Chemical", "pos": [8, 16]}], "task": "NER"}
{"text": "Moreover , these polyphenols up - regulated xenobiotic metabolizing enzymes UGT1A10 and CYP1A1 , enhancing carcinogen detoxification .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [17, 28]}], "task": "NER"}
{"text": "In conclusion , these results highlight that HTy and its derivative HTy - Et modulate molecular mechanisms involved in colon cancer , with HTy - Et being more effective than HTy .", "entity": [{"entity": "HTy", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "HTy - Et", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "HTy - Et", "entity_type": "Chemical", "pos": [139, 147]}, {"entity": "HTy", "entity_type": "Chemical", "pos": [174, 177]}], "task": "NER"}
{"text": "Determination of ethyl carbamate in cacha c a produced from copper stills by HPLC .", "entity": [{"entity": "ethyl carbamate", "entity_type": "Chemical", "pos": [17, 32]}, {"entity": "copper", "entity_type": "Chemical", "pos": [60, 66]}], "task": "NER"}
{"text": "Ethyl carbamate ( EC ) is a common substance in fermented foods and drinks , and its quantification is important because of its carcinogenic nature and its usually presence in alcoholic beverages .", "entity": [{"entity": "Ethyl carbamate", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "The present work involved the development and validation of an analytical method for the evaluation of EC in cacha c a by HPLC - FLD after previous derivatization with xanthydrol .", "entity": [{"entity": "xanthydrol", "entity_type": "Chemical", "pos": [168, 178]}], "task": "NER"}
{"text": "The method presented a mean recovery of 94 . 88 % , an intra - day precision of 4 . 19 % ( 30 . 0 mu gL ( - 1 ) ) and 3 . 32 % ( 75 . 0 mu gL ( - 1 ) ) , a coefficient of determination ( r ( 2 ) ) equal to 0 . 9985 , and limits of detection and quantification equal to 6 . 39 and 21 . 32 mu gL ( - 1 ) , respectively .", "entity": [], "task": "NER"}
{"text": "The results show that the analytical method is accurate , reproducible and linear over the concentration range from 5 . 0 to 160 mu g of EC per litre .", "entity": [], "task": "NER"}
{"text": "The method was applied to the analysis of EC in cacha c a , the analyses being rapid and efficient .", "entity": [], "task": "NER"}
{"text": "Moisture diffusivity in food materials .", "entity": [], "task": "NER"}
{"text": "This paper investigates whether moisture diffusion can be predicted for food materials .", "entity": [], "task": "NER"}
{"text": "We focus especially on mixtures of glucose homopolymers and water .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [35, 42]}], "task": "NER"}
{"text": "The predictions are based on three theories : ( 1 ) the Darken relation , linking the mutual diffusivity to the self diffusivities , ( 2 ) the generalised Stokes - Einstein relation for the solute self diffusivity , and ( 3 ) the free volume theory for water self diffusivity .", "entity": [], "task": "NER"}
{"text": "Using literature data obtained for the whole class of glucose homopolymer , we show that these theories predict the moisture diffusivity for the whole range of volume fractions , from zero to one , and a broad range of temperatures .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [54, 61]}], "task": "NER"}
{"text": "Furthermore , we show that the theories equally holds for other hydrophilic biopolymers one finds in food .", "entity": [], "task": "NER"}
{"text": "In the concentrated regime , all experimental data collapse to a single curve .", "entity": [], "task": "NER"}
{"text": "This universal behaviour arises because these biopolymers form a hydrogen bonded network , where water molecules move via rearrangement of the free volume .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "Investigation of the effect of gelatine , egg albumin and cross - flow microfiltration on the phenolic composition of Pinotage wine .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "The effect of fining and cross - flow microfiltration on the phenolic composition of red wine was investigated .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "Both gelatine ( G ) and egg albumin ( EA ) fining decreased the mean degree of polymerisation ( mDP ) of tannin significantly by 26 . 4 % and 25 . 2 % , respectively , compared to the control ( C ) .", "entity": [{"entity": "tannin", "entity_type": "Chemical", "pos": [105, 111]}], "task": "NER"}
{"text": "Cross - flow microfiltration ( CF ) also decreased the mDP significantly by 25 % .", "entity": [], "task": "NER"}
{"text": "Thus , the fining agents and cross - flow microfiltration selectively removed the highly polymerised phenols .", "entity": [{"entity": "phenols", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "After 3 . 5 months of bottle ageing , differences between the different treatments and the control decreased .", "entity": [], "task": "NER"}
{"text": "CF had the most significant effect on the flavan - 3 - ol and polymeric phenol ( tannin ) content of the wines compared to the control followed by G fining .", "entity": [{"entity": "flavan - 3 - ol", "entity_type": "Chemical", "pos": [42, 57]}, {"entity": "polymeric phenol", "entity_type": "Chemical", "pos": [62, 78]}, {"entity": "tannin", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "CF and EA treatments significantly decreased the total pigment content compared to C .", "entity": [], "task": "NER"}
{"text": "CF was also the only treatment that could be distinguished from the other treatments by sensory analysis .", "entity": [], "task": "NER"}
{"text": "All treatments improved clarity of the wines with cross - flow microfiltration having the largest effect .", "entity": [], "task": "NER"}
{"text": "Iron and zinc bioavailability in Caco - 2 cells : influence of caseinophosphopeptides .", "entity": [{"entity": "Iron", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [9, 13]}], "task": "NER"}
{"text": "A study has been made of the influence of two pools of caseinophosphopeptides ( CPPs ) obtained from alpha ( s ) - and beta - casein ( CN ) fractions , and of three specific CPPs ( beta - CN ( 1 - 25 ) 4P , alpha ( s1 ) - CN ( 64 - 74 ) 4P and alpha ( s2 ) - CN ( 1 - 19 ) 4P ) , on iron bioavailability ( ferritin synthesis ) and zinc bioavailability ( retention , transport and uptake of zinc ) in Caco - 2 cells .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [283, 287]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [331, 335]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [390, 394]}], "task": "NER"}
{"text": "alpha - CPP and beta - CPP pools did not improve ferritin synthesis , but the three specific CPPs showed an increase in ferritin synthesis in Caco - 2 cells versus iron sulphate , beta - CN ( 1 - 25 ) 4P being the most effective .", "entity": [{"entity": "iron sulphate", "entity_type": "Chemical", "pos": [164, 177]}], "task": "NER"}
{"text": "In relation to zinc bioavailability , alpha - CPPs , beta - CPPs , alpha ( s1 ) - CN ( 64 - 74 ) 4P and beta - CN ( 1 - 25 ) 4P increased zinc uptake .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [138, 142]}], "task": "NER"}
{"text": "However , this increase was of the same order as the increase due to the presence of zinc sulphate .", "entity": [{"entity": "zinc sulphate", "entity_type": "Chemical", "pos": [85, 98]}], "task": "NER"}
{"text": "The physical characteristics and emulsification properties of partially dephosphorylated bovine beta - casein .", "entity": [], "task": "NER"}
{"text": "Bovine beta - casein was purified from phosphocasein by rennet coagulation and cold solubilisation from the resultant curd .", "entity": [], "task": "NER"}
{"text": "beta - Casein was then dephosphorylated using potato acid phosphatase .", "entity": [], "task": "NER"}
{"text": "Urea - polyacrylamide gel electrophoresis ( PAGE ) of partially dephosphorylated beta - casein showed a number of bands , depending on the final level of phosphorylation .", "entity": [{"entity": "Urea", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "polyacrylamide", "entity_type": "Chemical", "pos": [7, 21]}], "task": "NER"}
{"text": "Dephosphorylating beta - casein increased its pH of minimum solubility from ~ pH 5 to 5 . 5 and reduced its net negative charge from - 30 . 8 to - 27 . 0 mV .", "entity": [], "task": "NER"}
{"text": "During the acidification of beta - casein solutions , partially dephosphorylated beta - casein failed to form a gel , unlike the phosphorylated ( i . e . , control ) beta - casein .", "entity": [], "task": "NER"}
{"text": "Use of partially dephosphorylated beta - casein to stabilise oil - in - water emulsions resulted in larger fat globules compared to control beta - casein , but such globules were less susceptible to aggregation in the presence of 15 or 30 mM CaCl ( 2 ) .", "entity": [{"entity": "CaCl ( 2 )", "entity_type": "Chemical", "pos": [242, 252]}], "task": "NER"}
{"text": "Overall , the dephosphorylation of beta - casein resulted in a protein similar to human beta - casein in terms of physicochemical functionality , with increased stability against calcium - induced aggregation .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "A rapid determination method for ethylenethiourea in potato and cucumber by modified QuEChERS - high performance liquid chromatography - tandem mass spectrometry .", "entity": [{"entity": "ethylenethiourea", "entity_type": "Chemical", "pos": [33, 49]}], "task": "NER"}
{"text": "A rapid and sensitive analytical method for the determination of ethylenethiourea ( ETU ) in potatoes and cucumbers is developed .", "entity": [{"entity": "ethylenethiourea", "entity_type": "Chemical", "pos": [65, 81]}, {"entity": "ETU", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "This method employs modified QuEChERS followed by high performance liquid chromatography - tandem mass spectrometry ( HPLC - MS / MS ) analysis .", "entity": [], "task": "NER"}
{"text": "ETU was extracted by alkaline acetonitrile ( containing 1 % NH ( 3 ) . H ( 2 ) 0 ) , separated on a ZIC - pHILIC column , confirmed by multiple reaction monitoring ( MRM ) mode with electrospray ionisation source .", "entity": [{"entity": "ETU", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "NH ( 3 ) . H ( 2 ) 0", "entity_type": "Chemical", "pos": [60, 80]}], "task": "NER"}
{"text": "This modified procedure showed satisfactory recovery ( 90 . 6 - 103 . 5 % ) fortified at the range of 0 . 005 - 0 . 05 mg kg ( - 1 ) with relative standard deviation ( RSD ) < 7 % .", "entity": [], "task": "NER"}
{"text": "The limits of detection ( LOD ) and the limits of quantification ( LOQ ) were 0 . 002 mg kg ( - 1 ) and 0 . 005 mg kg ( - 1 ) , respectively .", "entity": [], "task": "NER"}
{"text": "Matrix effect and HILIC retention mechanism were also evaluated .", "entity": [], "task": "NER"}
{"text": "The method was finally applied to detect ETU in potato and cucumber samples collected at harvest period .", "entity": [{"entity": "ETU", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "Residues of ETU were detected in four cucumber samples with the level lower than LOQ .", "entity": [{"entity": "ETU", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "Multiple mutations of the critical amino acid residues for the sweetness of the sweet - tasting protein , brazzein .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [35, 45]}], "task": "NER"}
{"text": "We have previously identified critical residues important for sweetness of the sweet protein brazzein by site - directed mutagenesis ( Yoon , Kong , Jo , & Kong , 2011 ) .", "entity": [], "task": "NER"}
{"text": "In order to elucidate the interaction mechanisms of brazzein with the sweet taste receptor , we made multiple mutations of three residues ( His31 in loop 30 - 33 , Glu36 in beta - strand III , and Glu41 in loop 40 - 43 ) .", "entity": [{"entity": "His31", "entity_type": "Chemical", "pos": [140, 145]}, {"entity": "Glu36", "entity_type": "Chemical", "pos": [164, 169]}, {"entity": "Glu41", "entity_type": "Chemical", "pos": [197, 202]}], "task": "NER"}
{"text": "We found that all double mutations ( H31R / E36D , H31R / E41A and E36D / E41A ) made the molecules sweeter than des - pE1M - brazzein and three single mutants .", "entity": [], "task": "NER"}
{"text": "Moreover , the triple mutation ( H31R / E36D / E41A ) made the molecule significantly sweeter than three double mutants .", "entity": [], "task": "NER"}
{"text": "These results strongly support the hypothesis that brazzein binds to the multisite surface of the sweet taste receptor .", "entity": [], "task": "NER"}
{"text": "Our findings also suggest that mutations reducing the overall negative charge and / or increasing the positive charge favour sweet - tasting protein potency .", "entity": [], "task": "NER"}
{"text": "Characterization of 3 , 4 - DHPEA - EDA oxidation products in virgin olive oil by high performance liquid chromatography coupled with mass spectrometry .", "entity": [{"entity": "3 , 4 - DHPEA - EDA", "entity_type": "Chemical", "pos": [20, 39]}], "task": "NER"}
{"text": "Secoiridoid derivatives are the most important antioxidants of virgin olive oil ( VOO ) , and their oxidation products could be used as molecular markers of VOO freshness to define the VOO autoxidation state .", "entity": [{"entity": "Secoiridoid", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The aim of this research was to characterise the dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol ( 3 , 4 - DHPEA - EDA ) oxidation products to find analytical indicators that could be used as early evaluation index of the VOO autoxidation state .", "entity": [{"entity": "dialdehydic", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "decarboxymethyl elenolic acid", "entity_type": "Chemical", "pos": [69, 98]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [109, 123]}, {"entity": "3 , 4 - DHPEA - EDA", "entity_type": "Chemical", "pos": [126, 145]}], "task": "NER"}
{"text": "3 , 4 - DHPEA - EDA was oxidised by enzymatic and Fenton reactions .", "entity": [{"entity": "3 , 4 - DHPEA - EDA", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "Terpenic structure oxidation products accumulated in VOO during the autoxidation process , thus they may be used as early evaluation index of the VOO autoxidation state before fatty acids oxidation .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [176, 187]}], "task": "NER"}
{"text": "Effects of Azocompost and urea on the herbage yield and contents and compositions of essential oils from two genotypes of dragonhead ( Dracocephalum moldavica L . ) in two regions of Iran .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "Dragonhead is an annual , herbaceous , balm - scented and spicy aromatic member of the family Lamiaceae .", "entity": [], "task": "NER"}
{"text": "We examined effects of different sources of nitrogen on the content and composition of essential oils in two genotypes of dragonhead in two regions of Iran .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "The sources of nitrogen used were 100 % urea ( 70 kg N ha ( - 1 ) ) , 75 % urea ( 52 . 5 kg N ha ( - 1 ) ) + 25 % Azocompost ( 3 . 85 tonha ( - 1 ) ) , 50 % urea ( 35 kg N ha ( - 1 ) ) + 50 % Azocompost ( 7 . 77 tonha ( - 1 ) ) , 25 % urea ( 17 . 5 kg N ha ( - 1 ) ) + 75 % Azocompost ( 11 . 55 tonha ( - 1 ) ) , and 100 % Azocompost ( 15 . 55 tonha ( - 1 ) ) .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "urea", "entity_type": "Chemical", "pos": [40, 44]}, {"entity": "urea", "entity_type": "Chemical", "pos": [75, 79]}, {"entity": "urea", "entity_type": "Chemical", "pos": [157, 161]}, {"entity": "urea", "entity_type": "Chemical", "pos": [235, 239]}], "task": "NER"}
{"text": "Optimal yield and content of essential oil at both locations for both genotypes were obtained by applying 50 % urea + 50 % Azocompost .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [111, 115]}], "task": "NER"}
{"text": "Geraniol , geranial , and geranyl acetate were the most abundant compounds .", "entity": [{"entity": "Geraniol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "geranial", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "geranyl acetate", "entity_type": "Chemical", "pos": [26, 41]}], "task": "NER"}
{"text": "For both genotypes and both locations , application of 50 % urea + 50 % Azocompost increased levels of geraniol and geranial , and application of Azocompost alone increased levels of geranyl acetate .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [60, 64]}, {"entity": "geraniol", "entity_type": "Chemical", "pos": [103, 111]}, {"entity": "geranial", "entity_type": "Chemical", "pos": [116, 124]}, {"entity": "geranyl acetate", "entity_type": "Chemical", "pos": [183, 198]}], "task": "NER"}
{"text": "Overall , we conclude that the application of 50 % urea with 50 % Azocompost is recommended for optimising the content and composition of essential oils in dragonhead .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [51, 55]}], "task": "NER"}
{"text": "In vitro digestibility and starch content , predicted glycemic index and potential in vitro antidiabetic effect of lentil sprouts obtained by different germination techniques .", "entity": [], "task": "NER"}
{"text": "The study focuses on changes in starch content and expected glycemic index ( eGI ) caused by different sprouting methods of lentil .", "entity": [], "task": "NER"}
{"text": "On germination , a decrease was observed in total starch content ( TS ) , alpha - amylase inhibitors activity ( alpha AI ) and eGI values .", "entity": [], "task": "NER"}
{"text": "After elicitation , the highest TS content was determined in 3 - day - old control sprouts ( 100 . 9 mg / gf . m . ) , whereas the lowest was in 4 - day - old sprouts induced with 300 mM NaCl ( 57 . 8 mg / gf . m . ) .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [187, 191]}], "task": "NER"}
{"text": "Resistant starch ( RS ) content was most effectively increased by induction with 600 mM mannitol .", "entity": [{"entity": "mannitol", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "The highest eGI values were determined for 3 - day - old sprouts induced with 300 mM NaCl , whereas the lowest were for 6 - day - old sprouts induced with 100mM NaCl .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [85, 89]}, {"entity": "NaCl", "entity_type": "Chemical", "pos": [161, 165]}], "task": "NER"}
{"text": "In treated sprouts starch digestibility was connected with alpha AI activity and RS content .", "entity": [], "task": "NER"}
{"text": "Sprouting conditions can modify starch content , its potential bioavailability and eGI values .", "entity": [], "task": "NER"}
{"text": "Optimization of this process will allow for the maximum nutritional benefit .", "entity": [], "task": "NER"}
{"text": "Molecular and functional properties of gelatin from the skin of unicorn leatherjacket as affected by extracting temperatures .", "entity": [], "task": "NER"}
{"text": "Gelatins extracted from the skin of unicorn leatherjacket at different temperatures ( 45 , 55 , 65 and 75 degrees C ) in the presence and the absence of soybean trypsin inhibitor ( SBTI ; 100 units / g pretreated skin ) for 12h were characterised .", "entity": [{"entity": "trypsin", "entity_type": "Chemical", "pos": [161, 168]}], "task": "NER"}
{"text": "In general , the addition of SBTI resulted in the lower yield , regardless of extraction temperature .", "entity": [], "task": "NER"}
{"text": "Higher yield was obtained when higher extraction temperature was used ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Gelatin from skin extracted at 75 degrees C in the absence of SBTI showed the highest yield ( 10 . 66 +/- 0 . 41 % ) ( based on dry weight ) .", "entity": [], "task": "NER"}
{"text": "The highest alpha - amino group content was observed in gelatin extracted at 55 degrees C without SBTI incorporated .", "entity": [{"entity": "alpha - amino", "entity_type": "Chemical", "pos": [12, 25]}], "task": "NER"}
{"text": "The band intensity of beta - chain and alpha - chains increased as the extraction temperature increased , particularly above 55 degrees C .", "entity": [], "task": "NER"}
{"text": "Gelatin extracted at 65 degrees C with and without SBTI incorporation exhibited the highest gel strength ( 178 . 00 +/- 7 . 50 g and 170 . 47 +/- 1 . 30 g , respectively ) .", "entity": [], "task": "NER"}
{"text": "FTIR spectra indicated that a greater loss of molecular order of triple helix with a higher degradation was found in gelatin extracted at 55 degrees C in the absence SBTI .", "entity": [], "task": "NER"}
{"text": "Gelatin extracted at 65 degrees C , either with or without SBTI , had the highest EAI and ESI with high foam expansion and stability .", "entity": [], "task": "NER"}
{"text": "Thus , the extraction of gelatin from the skin of unicorn leatherjacket at temperature sufficiently high could render the gelatin with less degradation .", "entity": [], "task": "NER"}
{"text": "Purification and identification of lipolysis - stimulating peptides derived from enzymatic hydrolysis of soy protein .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to purify and identify lipolysis - stimulating peptides derived from Flavourzyme (R) - soy protein isolate ( SPI ) hydrolysate ( F - SPIH ) .", "entity": [], "task": "NER"}
{"text": "Glycerol release was employed as a marker for lipolysis in 3T3 - L1 adipocytes .", "entity": [{"entity": "Glycerol", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "A higher glycerol release represents a better lipolysis - stimulating activity .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [9, 17]}], "task": "NER"}
{"text": "The peptide fraction with highest glycerol release obtained from F - SPIH fractionated by sequential ultrafiltration membranes was further purified using gel filtration chromatography and two steps of reverse - phase high - performance liquid chromatography .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "The peptides were identified using liquid chromatography - tandem mass spectrometry ( LC / MS / MS ) .", "entity": [], "task": "NER"}
{"text": "Three lipolysis - stimulating peptides were obtained , and the amino acid sequences were ILL , LLL and VHVV , respectively .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [63, 73]}], "task": "NER"}
{"text": "The in vitro effect of gastrointestinal proteases on lipolysis - stimulating activity of synthetic ILL , LLL and VHVV , respectively , was also investigated .", "entity": [], "task": "NER"}
{"text": "The result suggested that the gastrointestinal protease did not affect lipolysis - stimulating activity of the three novel peptides , which reveals their potential to act as anti - obesity ingredients .", "entity": [], "task": "NER"}
{"text": "Vitexin - 2 - O - xyloside , raphasatin and ( - ) - epigallocatechin - 3 - gallate synergistically affect cell growth and apoptosis of colon cancer cells .", "entity": [{"entity": "Vitexin - 2 - O - xyloside", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "raphasatin", "entity_type": "Chemical", "pos": [29, 39]}, {"entity": "( - ) - epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [44, 82]}], "task": "NER"}
{"text": "Cytotoxic effects of the combination of the food components vitexin - 2 - O - xyloside ( X ) , raphasatin ( 4 - methylsulphanyl - 3 - butenyl isothiocyanates ; G ) and ( - ) - epigallocatechin - 3 - gallate ( E ) were investigated in colon ( LoVo and CaCo - 2 ) and breast ( MDA - MB - 231 and MCF - 7 ) cancer cells .", "entity": [{"entity": "vitexin - 2 - O - xyloside", "entity_type": "Chemical", "pos": [60, 86]}, {"entity": "raphasatin", "entity_type": "Chemical", "pos": [95, 105]}, {"entity": "4 - methylsulphanyl - 3 - butenyl isothiocyanates", "entity_type": "Chemical", "pos": [108, 157]}, {"entity": "( - ) - epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [168, 206]}], "task": "NER"}
{"text": "Breast cancer cells were more resistant than colon cells to X , G and E inhibition .", "entity": [], "task": "NER"}
{"text": "On the contrary , marked synergistic effects among X , G and E on cell growth were found in both colon cancer cells .", "entity": [], "task": "NER"}
{"text": "Further analysis revealed a G0 / G1 arrest of the phase cell progression and apoptosis , linked to modulation of Bax , Bcl2 , caspase - 9 and poly ( ADP - ribose ) polymerase as well as Reactive Oxygen Species ( ROS ) generation in both colon cancer cells , whereas apoptosis and ROS were not significantly detected in normal human lymphocytes .", "entity": [{"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [142, 163]}, {"entity": "Oxygen", "entity_type": "Chemical", "pos": [195, 201]}], "task": "NER"}
{"text": "We conclude that the X , G and E mixture might act by mitochondrial pathway activation of apoptosis , possibly elicited by ROS and the mixture may be effective in the chemoprevention of colon cancer .", "entity": [], "task": "NER"}
{"text": "Absorption and urinary excretion of A - type procyanidin oligomers from Litchi chinensis pericarp in rats by selected ion monitoring liquid chromatography - mass spectrometry .", "entity": [{"entity": "A - type procyanidin", "entity_type": "Chemical", "pos": [36, 56]}], "task": "NER"}
{"text": "Intervention studies with A - type oligomeric procyanidins from litchi ( Litchi chinensis ) pericarp ( LPOPC ) suggested its protective effect against cardiovascular diseases .", "entity": [{"entity": "procyanidins", "entity_type": "Chemical", "pos": [46, 58]}], "task": "NER"}
{"text": "However , there is no consensus on the absorption and metabolism of LPOPC .", "entity": [], "task": "NER"}
{"text": "It was demonstrated that the main components in LPOPC were ( - ) - epicatechin , A - type procyanidin dimers , trimers and tetramers .", "entity": [{"entity": "( - ) - epicatechin", "entity_type": "Chemical", "pos": [59, 78]}, {"entity": "A - type procyanidin", "entity_type": "Chemical", "pos": [81, 101]}], "task": "NER"}
{"text": "Rats were orally administered different levels of LPOPC ( 150 and 300 mg / kgbw ) , the procyanidins and their microbial metabolites in urine were identified by HPLC - MS / MS analysis 18 h post - administration .", "entity": [{"entity": "procyanidins", "entity_type": "Chemical", "pos": [88, 100]}], "task": "NER"}
{"text": "Data indicated that seven aromatic acid metabolites excreted were significantly increased by 300 mg / kgbw of LPOPC ( P < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "However , only ( - ) - epicatechin and its methylated derivatives were detected in rat plasma 1h after 300 mg / kgbw of LPOPC administration .", "entity": [{"entity": "( - ) - epicatechin", "entity_type": "Chemical", "pos": [15, 34]}], "task": "NER"}
{"text": "The total EC content absorbed in plasma was only 2 . 54 +/- 0 . 53 mu mol / L , indicating that the biological properties of LPOPC should be probably explained by its microbial degraded phenolic acids .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [186, 200]}], "task": "NER"}
{"text": "Phenolics content and antioxidant and anti - inflammatory activities of legume fractions .", "entity": [{"entity": "Phenolics", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Two faba bean ( Vicia faba L . ) subspecies major and minor and lentil seeds grown in Algeria were separated into cotyledons and hulls .", "entity": [], "task": "NER"}
{"text": "These fractions , together with their corresponding whole seeds , were extracted with two solvents , aqueous ( 70 % ) acetone and ( 80 % ) ethanol , and evaluated for antioxidant activity in relation to their phenolic contents .", "entity": [{"entity": "acetone", "entity_type": "Chemical", "pos": [118, 125]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [139, 146]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [209, 217]}], "task": "NER"}
{"text": "Acetone selectively extracted tannins from faba beans .", "entity": [{"entity": "Acetone", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "tannins", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "The hulls always exhibited high antioxidant activity , measured using the reducing power ( RP ) , antiradical activity ( DPPH ) or oxygen radical absorbance capacity ( ORAC ) assays .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [121, 125]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [131, 137]}], "task": "NER"}
{"text": "Aqueous ethanol ( 80 % ) extract of lentil hulls exhibited high antioxidant and anti - inflammatory activities preferentially inhibiting 15 - LOX ( IC ( 50 ) , 55 mu g / ml ) , with moderate COX - 1 ( IC ( 50 ) , 66 mu g / ml ) and COX - 2 ( IC ( 50 ) , 119 mu g / ml ) inhibitory effects on the COX pathway , whereas faba bean hull extracts exerted relatively mild LOX inhibitory activity .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [8, 15]}], "task": "NER"}
{"text": "Microbial metabolites , but not other phenolics derived from grape seed phenolic extract , are transported through differentiated Caco - 2 cell monolayers .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "Grape seed phenolic extract ( GSE ) is predicted to have health benefits , even though its bioavailability , including digestibility , permeability and ultimate metabolism , are still poorly understood .", "entity": [], "task": "NER"}
{"text": "In vitro gastric and pancreatic digestion and in vitro ileal and faecal fermentation were combined with Caco - 2 cell permeability studies for GSE samples .", "entity": [], "task": "NER"}
{"text": "Qualitatively , there was no change in type / number of GSE compounds following gastric and pancreatic digestion and LC - MS analysis .", "entity": [], "task": "NER"}
{"text": "However , the monomers were significantly ( P < 0 . 05 ) increased after gastric digestion , along with a significant ( P < 0 . 05 ) decrease in polymers .", "entity": [], "task": "NER"}
{"text": "In addition , all forms of phenolic compounds decreased following pancreatic digestion .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "However , none of the original GSE phenolic compounds passed the Caco - 2 cell monolayer , since all were recovered in the apical compartment .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "In contrast , the two intestinal microbiota metabolites with deprotonated molecular weights of [ M - H ] - 165 / 121 and 193 / 175 , that were found both in the ileal and faecal fermented samples , passed the Caco - 2 cell monolayer .", "entity": [], "task": "NER"}
{"text": "Enhancing the production of galacto - oligosaccharides by mutagenesis of Sulfolobus solfataricus beta - galactosidase .", "entity": [], "task": "NER"}
{"text": "Galacto - oligosaccharides ( GOS ) , an important class of functional food , are commonly produced from lactose using beta - galactosidase .", "entity": [{"entity": "lactose", "entity_type": "Chemical", "pos": [104, 111]}], "task": "NER"}
{"text": "In the present study , beta - galactosidase ( LacS ) from Sulfolobus solfataricus P2 was cloned and site - directed mutagenesis was performed to obtain two mutants , F359Q and F441Y .", "entity": [], "task": "NER"}
{"text": "All of the wild - type enzyme and mutants were expressed in Escherichia coli BL21 ( DE3 ) and purified to homogeneity .", "entity": [], "task": "NER"}
{"text": "The enzymatic properties and optimal condition for transglycosylation reaction of the enzymes were investigated in detail .", "entity": [], "task": "NER"}
{"text": "Under their individual optimal conditions , yields of GOS could reach 50 . 9 % for wild - type enzyme , 58 . 3 % for F359Q , and 61 . 7 % for F441Y .", "entity": [], "task": "NER"}
{"text": "In addition , the potential mechanism for this enhancement was analysed .", "entity": [], "task": "NER"}
{"text": "Detection of adulteration in honey samples added various sugar syrups with 13C / 12C isotope ratio analysis method .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [57, 62]}, {"entity": "13C", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "12C", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Honey can be adulterated in various ways .", "entity": [], "task": "NER"}
{"text": "One of the adulteration methods is the addition of different sugar syrups during or after honey production .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [61, 66]}], "task": "NER"}
{"text": "Starch - based sugar syrups , high fructose corn syrup ( HFCS ) , glucose syrup ( GS ) and saccharose syrups ( SS ) , which are produced from beet or canes , can be used for adulterating honey .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [15, 20]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "saccharose", "entity_type": "Chemical", "pos": [91, 101]}], "task": "NER"}
{"text": "In this study , adulterated honey samples were prepared with the addition of HFCS , GS and SS ( beet sugar ) at a ratio of 0 % , 10 % , 20 % , 40 % and 50 % by weight .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [101, 106]}], "task": "NER"}
{"text": "( 13 ) C / ( 12 ) C analysis was conducted on these adulterated honey samples using an isotope ratio mass spectrometer in combination with an elemental analyser ( EA - IRMS ) .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "( 12 ) C", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "As a result , adulteration using C ( 4 ) sugar syrups ( HFCS and GS ) could be detected to a certain extent while adulteration of honey using C ( 3 ) sugar syrups ( beet sugar ) could not be detected .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [41, 46]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [150, 155]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [170, 175]}], "task": "NER"}
{"text": "Adulteration by using SS ( beet sugar ) still has a serious detection problem , especially in countries in which beet is used in manufacturing sugar .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [32, 37]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [143, 148]}], "task": "NER"}
{"text": "For this reason , practice and analysis methods are needed to meet this deficit and to detect the adulterations precisely in the studies that will be conducted .", "entity": [], "task": "NER"}
{"text": "Effect of TiO2 photocatalytic activity in a HDPE - based food packaging on the structural and microbiological stability of a short - ripened cheese .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [10, 14]}], "task": "NER"}
{"text": "A high density polyethylene ( HDPE ) / calcium carbonate ( CaCO ( 3 ) ) film containing TiO ( 2 ) was prepared via blown film extrusion process .", "entity": [{"entity": "polyethylene", "entity_type": "Chemical", "pos": [15, 27]}, {"entity": "calcium carbonate", "entity_type": "Chemical", "pos": [39, 56]}, {"entity": "CaCO ( 3 )", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "The photocatalytic properties of this film were evaluated by voltammetric , UV - Vis spectrophotometric and gas chromatographic measurements following the decomposition rate of suitably selected molecular probes , such as 4 - hydroxybenzoic acid and methylene blue .", "entity": [{"entity": "4 - hydroxybenzoic acid", "entity_type": "Chemical", "pos": [222, 245]}, {"entity": "methylene blue", "entity_type": "Chemical", "pos": [250, 264]}], "task": "NER"}
{"text": "The film containing 1 % w / w of TiO ( 2 ) displayed a profitable and reproducible photoinduced degradation activity towards target organic compounds .", "entity": [{"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [33, 42]}], "task": "NER"}
{"text": "The effect of packaging photocatalytic activity on the structural and microbiological stability of a short - ripened cheese was studied .", "entity": [], "task": "NER"}
{"text": "Cheese structure was assessed by dynamic , small deformation rheological tests .", "entity": [], "task": "NER"}
{"text": "A container consisting of a multilayer material , where the layer brought in contact with the food , made from the HDPE + CaCO ( 3 ) + TiO ( 2 ) composite matrix , was able to provide a greater maintenance of the original cheese structure than a rigid container currently used , mainly due to the inhibition of lactic acid bacteria and coliforms .", "entity": [{"entity": "CaCO ( 3 )", "entity_type": "Chemical", "pos": [122, 132]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [135, 144]}, {"entity": "lactic acid", "entity_type": "Chemical", "pos": [311, 322]}], "task": "NER"}
{"text": "Prediction of fatty acid composition in Camellia oleifera oil by near infrared transmittance spectroscopy ( NITS ) .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "Under the serious circumstances of Camellia oleifera adulteration , the accurate examination for quality trait of C . oleifera oil is extremely urgent .", "entity": [], "task": "NER"}
{"text": "For rapid determination of FA composition in C . oleifera oil , the feasibility of NITS was first studied .", "entity": [], "task": "NER"}
{"text": "The quantitative models for FA were built based on PLS regression .", "entity": [], "task": "NER"}
{"text": "NITS spectra is able to accurately predict for oleic , linoleic , and palmitic acids ( R ( cv ) > 0 . 844 , R ( 2 ) > 0 . 886 ) .", "entity": [{"entity": "oleic , linoleic , and palmitic acids", "entity_type": "Chemical", "pos": [47, 84]}], "task": "NER"}
{"text": "R ( cv ) are 0 . 91987 , 0 . 95755 , and 0 . 84447 , and R ( 2 ) are 0 . 9424 , 0 . 9682 , 0 . 8862 for NITS models of oleic , linoleic , and palmitic acids , respectively .", "entity": [{"entity": "oleic , linoleic , and palmitic acids", "entity_type": "Chemical", "pos": [119, 156]}], "task": "NER"}
{"text": "But models for stearic and unsaturated acids are less accurate , with values of R ( cv ) from 0 . 67440 to 0 . 69114 , and R ( 2 ) from 0 . 6834 to 0 . 7587 .", "entity": [{"entity": "stearic and unsaturated acids", "entity_type": "Chemical", "pos": [15, 44]}], "task": "NER"}
{"text": "These results indicate that NITS will have potential to be used in predicting FA composition of C . oleifera oil .", "entity": [], "task": "NER"}
{"text": "Cyto - genotoxic and oxidative effects of a continuous UV - C treatment of liquid egg products .", "entity": [], "task": "NER"}
{"text": "UV - C treatment of food is a promising non - thermal processing technology to improve food safety and preservation .", "entity": [], "task": "NER"}
{"text": "Most of the chemical constituents of food absorb UV - C light that can lead to chemical modifications and quality changes .", "entity": [], "task": "NER"}
{"text": "This work investigated the effects of UV - C treatment of liquid egg products on lipid , protein oxidations and potential cyto - and genotoxic effects on intestinal epithelial cells in vitro .", "entity": [], "task": "NER"}
{"text": "Egg preparations ( egg white , yolk , liquid whole egg ) were treated with UV - C ( 254 nm , volumetric doses between 0 and 115 , 619 J L ( - 1 ) ) using a commercial UV - C processing unit equipped with a Dean Flow reactor .", "entity": [], "task": "NER"}
{"text": "UV - C treatment at high doses ( from 32 , 181 J L ( - 1 ) , about 2 times higher than that needed to inactivate 5 log of relevant microorganisms ) showed an increased lipid oxidation in egg yolk and slight effects in liquid whole eggs ; this was confirmed by slightly but not statistically significant increased peroxide values .", "entity": [{"entity": "peroxide", "entity_type": "Chemical", "pos": [313, 321]}], "task": "NER"}
{"text": "UV - C induced also slight protein damage , characterised by the total sulfhydryl group reduction .", "entity": [{"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [71, 81]}], "task": "NER"}
{"text": "These UV - C - induced oxidative modifications in egg preparations however did not cause any increase in the cyto - or genotoxic ( DNA strand breaks ) effects in intestinal Caco - 2 cells .", "entity": [], "task": "NER"}
{"text": "Purification and characterisation of a novel antioxidant peptide derived from blue mussel ( Mytilus edulis ) protein hydrolysate .", "entity": [], "task": "NER"}
{"text": "Protein derived from blue mussel ( Mytilus edulis ) was hydrolysed using four kinds of proteases ( pepsin , papain , neutrase and alcalase ) , and the neutrase hydrolysate ( BNH ) obtained by 3 - h hydrolysis exhibited the highest 2 , 2 - diphenyl - 1 - picrylhydrazyl ( DPPH ) radical scavenging activity compared to other hydrolysates .", "entity": [{"entity": "2 , 2 - diphenyl - 1 - picrylhydrazyl", "entity_type": "Chemical", "pos": [231, 268]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [271, 275]}], "task": "NER"}
{"text": "By using ultrafiltration , gel filtration chromatography and reversed phase high performance liquid chromatography ( RP - HPLC ) , a novel antioxidant peptide ( BNH - P7 ) was isolated from BNH , and its amino acid sequence was identified as YPPAK ( Tyr - Pro - Pro - Ala - Lys ) with molecular weight of 574 Da .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [204, 214]}, {"entity": "Tyr - Pro - Pro - Ala - Lys", "entity_type": "Chemical", "pos": [250, 277]}], "task": "NER"}
{"text": "BNH - P7 exhibited good scavenging activity on DPPH radical , hydroxyl radical , and superoxide anion radical with EC ( 50 ) of 2 . 62 , 0 . 228 , and 0 . 072 mg / ml , respectively .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [47, 51]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [85, 95]}], "task": "NER"}
{"text": "BNH - P7 was also effectively against lipid peroxidation in a linoleic acid model system .", "entity": [{"entity": "linoleic acid", "entity_type": "Chemical", "pos": [62, 75]}], "task": "NER"}
{"text": "The high activity of BNH - P7 was due to the small size and the presence of antioxidant and hydrophobic amino acid residues ( Tyr and Pro ) within its sequence .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [104, 114]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [126, 129]}, {"entity": "Pro", "entity_type": "Chemical", "pos": [134, 137]}], "task": "NER"}
{"text": "Volatile profiling of high quality hazelnuts ( Corylus avellana L . ) : chemical indices of roasting .", "entity": [], "task": "NER"}
{"text": "The study proposes an investigation strategy to identify sensitive , robust and reliable chemical markers of hazelnut roasting .", "entity": [], "task": "NER"}
{"text": "A fully - automated and validated analytical method , based on Headspace Solid Phase Microextraction ( HS - SPME ) coupled with Gas Chromatography - Mass Spectrometric detection ( GC - MS ) , for effective off - line monitoring of changes in the volatile profile of high - quality hazelnuts was developed .", "entity": [], "task": "NER"}
{"text": "Samples from two different harvests were submitted to roasting , following different time / temperature protocols and different technologies , enabling chemical changes to be correlated with technological processing and sensory quality .", "entity": [], "task": "NER"}
{"text": "Chemical indices , expressed as analyte response ratio , were defined and their trend observed across roasting profiles .", "entity": [], "task": "NER"}
{"text": "Reliability and robustness of chemical indices were also evaluated , in view of their application to on - line monitoring with Mass Spectrometry - based electronic nose technology ( MS - nose ) .", "entity": [], "task": "NER"}
{"text": "Experiments , simulating on - line chemical characterisation of the volatile fraction , were performed through a fully - automated system .", "entity": [], "task": "NER"}
{"text": "The results confirmed : ( a ) the effectiveness of single process indicators of roasting selected by the separative method ( 5 - methylfurfural , 1 ( H ) - pyrrole , furfuryl alcohol , 1 ( H ) - pyrrole - 2 - carboxaldehyde , 1 - hydroxy - 2 - propanone , dihydro - 2 ( 3H ) - furanone , 5 - methyl - ( E ) - 2 - hepten - 4 - one , acetic acid , pyridine , furfural , pyrazine , and several alkyl - pyrazines ) ; and , ( b ) the reliability of proposed chemical indices : 5 - methylfurfural / 2 , 5 - dimethylpyrazine , 5 - methylfurfural / 2 - methylpyrazine , 2 , 5 - dimethylpyrazine / 2 , 3 - dimethylpyrazine ; these maintained a consistent trend versus harvest and sampling / analysis technology .", "entity": [{"entity": "5 - methylfurfural", "entity_type": "Chemical", "pos": [125, 143]}, {"entity": "1 ( H ) - pyrrole", "entity_type": "Chemical", "pos": [146, 163]}, {"entity": "furfuryl alcohol", "entity_type": "Chemical", "pos": [166, 182]}, {"entity": "1 ( H ) - pyrrole - 2 - carboxaldehyde", "entity_type": "Chemical", "pos": [185, 223]}, {"entity": "1 - hydroxy - 2 - propanone", "entity_type": "Chemical", "pos": [226, 253]}, {"entity": "dihydro - 2 ( 3H ) - furanone", "entity_type": "Chemical", "pos": [256, 285]}, {"entity": "5 - methyl - ( E ) - 2 - hepten - 4 - one", "entity_type": "Chemical", "pos": [288, 329]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [332, 343]}, {"entity": "pyridine", "entity_type": "Chemical", "pos": [346, 354]}, {"entity": "furfural", "entity_type": "Chemical", "pos": [357, 365]}, {"entity": "pyrazine", "entity_type": "Chemical", "pos": [368, 376]}, {"entity": "alkyl - pyrazines", "entity_type": "Chemical", "pos": [391, 408]}, {"entity": "5 - methylfurfural", "entity_type": "Chemical", "pos": [472, 490]}, {"entity": "2 , 5 - dimethylpyrazine", "entity_type": "Chemical", "pos": [493, 517]}, {"entity": "5 - methylfurfural", "entity_type": "Chemical", "pos": [520, 538]}, {"entity": "2 - methylpyrazine", "entity_type": "Chemical", "pos": [541, 559]}, {"entity": "2 , 5 - dimethylpyrazine", "entity_type": "Chemical", "pos": [562, 586]}, {"entity": "2 , 3 - dimethylpyrazine", "entity_type": "Chemical", "pos": [589, 613]}], "task": "NER"}
{"text": "Detection , isolation and characterisation of cyclolinopeptides J and K in ageing flax .", "entity": [{"entity": "cyclolinopeptides J and K", "entity_type": "Chemical", "pos": [46, 71]}], "task": "NER"}
{"text": "Methionine sulfone containing peptides CLs J ( 11 ) and K ( 12 ) may be produced from their reduced forms by oxidation but it is not known if these compounds occur in foods that contain flax .", "entity": [{"entity": "Methionine sulfone", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "These compounds have been reported to possess greater immunosuppressive activity than their reduced methionine sulfoxide peptide forms 4 and 6 , respectively .", "entity": [{"entity": "methionine sulfoxide", "entity_type": "Chemical", "pos": [100, 120]}], "task": "NER"}
{"text": "Since 11 and 12 have not been detected in commercial flax oil and milled flax seed , we tested for their presence in flax food products .", "entity": [], "task": "NER"}
{"text": "Here we report that 11 and 12 accumulate in ground flaxseed that is exposed to air and heat ( 100 degrees C ) for more than 4h .", "entity": [], "task": "NER"}
{"text": "Standards of 11 and 12 were prepared , isolated and extensively characterised using HPLC - MS / MS , 1D and 2D NMR methods .", "entity": [], "task": "NER"}
{"text": "We also report the excellent thermal and oxidative stability of these peptides .", "entity": [], "task": "NER"}
{"text": "Due to the harsh conditions required to produce 11 and 12 , it is expected that their levels in flax based foods would be low and therefore their presence could serve as an indicative measure of severe oxidation of a food product .", "entity": [], "task": "NER"}
{"text": "In vitro antioxidant properties of crude extracts and compounds from brown algae .", "entity": [], "task": "NER"}
{"text": "Research on the bioactives from seaweeds has increased in recent years .", "entity": [], "task": "NER"}
{"text": "Antioxidant activity is one of the most studied , due to the interest of these compounds both as preservatives and protectors against oxidation in food and cosmetics and also due to their health implications , mainly in relation to their potential as functional ingredients .", "entity": [], "task": "NER"}
{"text": "Brown algae present higher antioxidant potential in comparison with red and green families and contain compounds not found in terrestrial sources .", "entity": [], "task": "NER"}
{"text": "In vitro antioxidant chemical methods , used as a first approach to evaluate potential agents to protect from lipid oxidation in foods , confirmed that the brown algae crude extracts , fractions and pure components are comparatively similar or superior to synthetic antioxidants .", "entity": [], "task": "NER"}
{"text": "Particular emphasis on the fucoidan and phlorotannin polymeric fractions is given , considering variations associated with the species , collection area , season , and extraction and purification technologies .", "entity": [], "task": "NER"}
{"text": "Concentrations of PCDD / Fs , dioxin - like PCBs , PBDEs , and hexachlorobenzene in fat samples from cattle of different ages and gender in Korea .", "entity": [{"entity": "PCDD / Fs", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "dioxin - like PCBs", "entity_type": "Chemical", "pos": [30, 48]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [51, 56]}, {"entity": "hexachlorobenzene", "entity_type": "Chemical", "pos": [63, 80]}], "task": "NER"}
{"text": "Polychlorinated dibenzo - p - dioxins and dibenzofurans ( PCDD / Fs ) , dioxin - like polychlorinated biphenyls ( DL - PCBs ) , polybrominated diphenyl ethers ( PBDEs ) , and hexachlorobenzene ( HCB ) concentrations were determined in abdominal fat samples from 30 cattle .", "entity": [{"entity": "Polychlorinated dibenzo - p - dioxins and dibenzofurans", "entity_type": "Chemical", "pos": [0, 55]}, {"entity": "PCDD / Fs", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "dioxin - like polychlorinated biphenyls", "entity_type": "Chemical", "pos": [72, 111]}, {"entity": "DL - PCBs", "entity_type": "Chemical", "pos": [114, 123]}, {"entity": "polybrominated diphenyl ethers", "entity_type": "Chemical", "pos": [128, 158]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [161, 166]}, {"entity": "hexachlorobenzene", "entity_type": "Chemical", "pos": [175, 192]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [195, 198]}], "task": "NER"}
{"text": "The relationships between chemicals , age , and gender were investigated .", "entity": [], "task": "NER"}
{"text": "The concentration of PCDD / Fs ranged from 0 . 01 to 1 . 36 pg TEQ g ( - 1 ) fat , DL - PCBs ranged from 0 . 17 to 1 . 64 pg TEQ g ( - 1 ) fat , PBDEs ranged from 135 to 725 pgg ( - 1 ) fat , and HCB ranged from 25 . 5 to 2061 pgg ( - 1 ) fat .", "entity": [{"entity": "PCDD / Fs", "entity_type": "Chemical", "pos": [21, 30]}, {"entity": "DL - PCBs", "entity_type": "Chemical", "pos": [83, 92]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [145, 150]}, {"entity": "HCB", "entity_type": "Chemical", "pos": [196, 199]}], "task": "NER"}
{"text": "A comparison between cattle ' s age and gender vs . the concentration of contaminants revealed higher concentrations of PCDD / Fs and DL - PCBs in cattle aged more than 3 years ; no difference between genders was apparent .", "entity": [{"entity": "PCDD / Fs", "entity_type": "Chemical", "pos": [120, 129]}, {"entity": "DL - PCBs", "entity_type": "Chemical", "pos": [134, 143]}], "task": "NER"}
{"text": "Moreover , the concentrations of PBDEs in cattle fat did not correspond with the age of cattle .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [33, 38]}], "task": "NER"}
{"text": "Relative to cattle 1 . 5 - 2 . 5 years of age , cattle aged 3 and 4 years had higher concentration of HCB but the concentration difference was not clear at age 5 .", "entity": [{"entity": "HCB", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Human exposures to these compounds from beef sources were calculated based on beef consumption .", "entity": [], "task": "NER"}
{"text": "Effects of various pressing programs and yields on the antioxidant activity , antimicrobial activity , phenolic content and colour of pomegranate juices .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "Pomegranate juice ( PJ ) samples were produced with three different pressing programs : ( 1 ) 1 . 2 - 4 . 8 bar for 25 min , ( 2 ) 1 . 2 - 2 . 4 bar for 15 min and ( 3 ) 1 . 2 - 1 . 8 bar for 5 . 5 min .", "entity": [], "task": "NER"}
{"text": "Respective juice yields were 39 . 2 % , 33 . 2 % and 27 . 2 % .", "entity": [], "task": "NER"}
{"text": "Effects of pressing pressure - time and yield on total phenolic ( TP ) content , condensed tannin ( CT ) content , monomeric anthocyanin ( MA ) content , antioxidant activity ( AOA ) and antimicrobial activity ( AMA ) of the samples were determined .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "tannin", "entity_type": "Chemical", "pos": [91, 97]}, {"entity": "anthocyanin", "entity_type": "Chemical", "pos": [125, 136]}], "task": "NER"}
{"text": "Strong positive linear correlations were found between the pressing pressure with AOA ( r = 0 . 973 ) and TP content ( r = 0 . 979 ) , while negative logarithmic correlations were found between pressing pressure with the contents of CT ( r = - 0 . 778 ) and MA ( r = - 0 . 955 ) .", "entity": [], "task": "NER"}
{"text": "Among 12 microorganisms tested , Bacillus megaterium , Bacillus subtilis , Staphyloccocus aureus and Pseudomonas sp . were found to be sensitive to juice samples .", "entity": [], "task": "NER"}
{"text": "However , increasing pressing pressure and yield did not lead to a significant change on the AMAs of the juices .", "entity": [], "task": "NER"}
{"text": "Evolution of flavonoids in Mourat o n berries taken from both bunch halves .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [13, 23]}], "task": "NER"}
{"text": "Galicia ( N . W . Spain ) is a Spanish region with several old - traditional winegrowing areas .", "entity": [], "task": "NER"}
{"text": "There are autochthonous grapevine varieties , such as Vitis vinifera L .", "entity": [], "task": "NER"}
{"text": "cv .", "entity": [], "task": "NER"}
{"text": "Mourat o n , considered a biodiversity resource in viticulture and an opportunity for Galician sustainable wine production .", "entity": [], "task": "NER"}
{"text": "Therefore , it is necessary to assess the potential of traditional cultivars to produce quality red wines .", "entity": [], "task": "NER"}
{"text": "In this work , anthocyanin and flavonol evolution was followed in red berries from V . vinifera L .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [15, 26]}, {"entity": "flavonol", "entity_type": "Chemical", "pos": [31, 39]}], "task": "NER"}
{"text": "Mourat o n .", "entity": [], "task": "NER"}
{"text": "The novelty of this study is that grapes were separately collected from two different positions ( tips and shoulders ) within the cluster , over ripening to examine the effects of berry position within the fruit cluster on the flavonoid compounds .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [227, 236]}], "task": "NER"}
{"text": "Derivatives of five anthocyanins ( malvidin , peonidin , petunidin , delphinidin and cyanidin ) and derivatives of six flavonols ( quercetin , myricetin , kaempherol , laricitrin isorhamnetin and syringetin ) were detected in both positions within the cluster .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [20, 32]}, {"entity": "malvidin", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "peonidin", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "petunidin", "entity_type": "Chemical", "pos": [57, 66]}, {"entity": "delphinidin", "entity_type": "Chemical", "pos": [69, 80]}, {"entity": "cyanidin", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [119, 128]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [131, 140]}, {"entity": "myricetin", "entity_type": "Chemical", "pos": [143, 152]}, {"entity": "kaempherol", "entity_type": "Chemical", "pos": [155, 165]}, {"entity": "laricitrin", "entity_type": "Chemical", "pos": [168, 178]}, {"entity": "isorhamnetin", "entity_type": "Chemical", "pos": [179, 191]}, {"entity": "syringetin", "entity_type": "Chemical", "pos": [196, 206]}], "task": "NER"}
{"text": "Dynamic of anthocyanins ( from 819 mg / kg to 1206 mg / kg in tips ; and from 786 mg / kg to 1077 mg / kg in shoulders ) and dynamic of flavonols ( from 25mg / kg to 41 mg / kg in tips ; and from 18 mg / kg to 21 mg / kg in shoulders ) confirmed their upward trends over ripening .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [11, 23]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [136, 145]}], "task": "NER"}
{"text": "Grapes located inside the shoulder bunch receive less sunlight radiation than those located inside the tip bunch and this fact could explain the different accumulation observed for both positions .", "entity": [], "task": "NER"}
{"text": "These results can be useful for winemakers in order to obtain different final red wine quality .", "entity": [], "task": "NER"}
{"text": "Influences of muscle composition and structure of pork from different breeds on stability and textural properties of cooked meat emulsion .", "entity": [], "task": "NER"}
{"text": "The influences of composition and structure of meats from different pig breeds , including Duroc ( D ) , Large White ( LW ) , Landrace ( LR ) , two - way cross ( LR x LW ) and three - way cross ( D x [ LR x LW ] ) on stability and textural characteristics of cooked meat emulsions were studied by using partial least squares ( PLS ) regression .", "entity": [], "task": "NER"}
{"text": "Compared to other pig breeds , cooked meat emulsion from LW exhibited superior properties as indicated by lower water and fat released as well as higher chewiness , gumminess , cohesiveness , resilience , springiness and hardness .", "entity": [], "task": "NER"}
{"text": "The univariate analyses of those selected properties indicated a significant correlation with higher contents of myofibrillar and sarcoplasmic proteins , smaller muscle fibre diameter and lower myofibril fragmentation of LW meat , as compared to other breeds .", "entity": [], "task": "NER"}
{"text": "Therefore properties of cooked pork emulsion were influenced by composition and structure of meat , which varied according to the pig breeds .", "entity": [], "task": "NER"}
{"text": "A traceability study on the Moscato wine chain .", "entity": [], "task": "NER"}
{"text": "To address the growing interest of consumers for information on the provenance of foodstuffs , the production chain of world renowned Moscato d ' Asti white wine has been studied using the distribution of lanthanides as chemical markers .", "entity": [{"entity": "lanthanides", "entity_type": "Chemical", "pos": [205, 216]}], "task": "NER"}
{"text": "From soil to must , upon every stage of the chain , samples have been taken and analysed with ICP - MS in order to verify whether the original fingerprint of soil is maintained or not along the chain .", "entity": [], "task": "NER"}
{"text": "Results of this traceability study show clearly that lanthanides fingerprint is kept unaltered in the passage soil - grapes - must , while fractionation occurs upon wine clarifying with bentonites .", "entity": [{"entity": "lanthanides", "entity_type": "Chemical", "pos": [53, 64]}, {"entity": "bentonites", "entity_type": "Chemical", "pos": [186, 196]}], "task": "NER"}
{"text": "The second part of the work involves a study on 102 samples of Moscato d ' Asti musts in order to verify how they reflect the features of the different geographical zones where they come from , and to build a basis to be able to identify possible adulterations performed by addition of foreign musts .", "entity": [], "task": "NER"}
{"text": "Development of a standardised human in vitro digestion protocol based on macronutrient digestion using response surface methodology .", "entity": [], "task": "NER"}
{"text": "Bioaccessibility studies should be taken into account when evaluating the physiological effects of ingested compounds at the intestine level .", "entity": [], "task": "NER"}
{"text": "Several in vitro digestion protocols have been described , with a wide range of experimental conditions but no optimised protocol exists .", "entity": [], "task": "NER"}
{"text": "In order to fill in this gap , we evaluated the influence of three continuous factors ( pH , incubation time , and enzyme concentrations ) , in the range of values found in literature , on the digestion of standard macronutrients ( starch , albumin , triolein ) alone or in mixture .", "entity": [{"entity": "triolein", "entity_type": "Chemical", "pos": [251, 259]}], "task": "NER"}
{"text": "Three central composite designs , using response surface methodology , were employed to model the three abiotic steps of pre - colonic digestion .", "entity": [], "task": "NER"}
{"text": "A validated in vitro digestion was eventually set up for the salivary step ( pH 6 . 9 , 5 min , 3 . 9 units alpha - amylase / ml ) , the gastric step ( pH 2 , 90 min , 71 . 2 units pepsin / ml ) , and the abiotic duodenal step ( pH 7 , 150 min , 9 . 2mg pancreatin and 55 . 2mg bile extract / ml ) .", "entity": [], "task": "NER"}
{"text": "Purification , properties and cDNA cloning of glutamate decarboxylase in germinated faba bean ( Vicia faba L . ) .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [46, 55]}], "task": "NER"}
{"text": "Gamma - aminobutyric acid ( GABA ) is a non - protein amino acid with bioactive functions in humans .", "entity": [{"entity": "Gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [28, 32]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [54, 64]}], "task": "NER"}
{"text": "In this work , glutamate decarboxylase ( EC 4 . 1 . 1 . 15 , GAD ) which is key in the GABA bioformation was purified from 5 - day germinated faba beans and characterized .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [87, 91]}], "task": "NER"}
{"text": "A single band was observed at 58 kDa using sodium dodecyl sulphate gel electrophoresis .", "entity": [{"entity": "sodium dodecyl sulphate", "entity_type": "Chemical", "pos": [43, 66]}], "task": "NER"}
{"text": "GAD optimal activity was at pH 6 . 0 at 40 degrees C with a K ( m ) value for glutamic acid ( Glu ) of 2 . 63 mM .", "entity": [{"entity": "glutamic acid", "entity_type": "Chemical", "pos": [78, 91]}, {"entity": "Glu", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "The enzyme was inhibited significantly by Cu ( 2 + ) , Fe ( 3 + ) , Mg ( 2 + ) , Ba ( 2 + ) , aminoxyacetate , EGTA , Na ( 2 ) EDTA , l - cysteine and beta - mercaptoethanol ; and activated at low Ca ( 2 + ) 0 . 2mM .", "entity": [{"entity": "Cu ( 2 + )", "entity_type": "Chemical", "pos": [42, 52]}, {"entity": "Fe ( 3 + )", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [68, 78]}, {"entity": "Ba ( 2 + )", "entity_type": "Chemical", "pos": [81, 91]}, {"entity": "aminoxyacetate", "entity_type": "Chemical", "pos": [94, 108]}, {"entity": "EGTA", "entity_type": "Chemical", "pos": [111, 115]}, {"entity": "Na ( 2 ) EDTA", "entity_type": "Chemical", "pos": [118, 131]}, {"entity": "l - cysteine", "entity_type": "Chemical", "pos": [134, 146]}, {"entity": "beta - mercaptoethanol", "entity_type": "Chemical", "pos": [151, 173]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [197, 207]}], "task": "NER"}
{"text": "Using RT - PCR , the GAD cDNA was sequenced which indicated 1787 bp long , containing a 1527 bp open reading frame ( ORF ) that encoded 509 amino - acid peptides with a calculated molecular weight of 57 . 74 kDa and a pI of 5 . 41 ( GenBank accession number : JX444699 ) .", "entity": [{"entity": "amino - acid", "entity_type": "Chemical", "pos": [140, 152]}], "task": "NER"}
{"text": "Validation of methods for the detection and quantification of engineered nanoparticles in food .", "entity": [], "task": "NER"}
{"text": "The potential impact of nanomaterials on the environment and on human health has already triggered legislation requiring labelling of products containing nanoparticles .", "entity": [], "task": "NER"}
{"text": "However , so far , no validated analytical methods for the implementation of this legislation exist .", "entity": [], "task": "NER"}
{"text": "This paper outlines a generic approach for the validation of methods for detection and quantification of nanoparticles in food samples .", "entity": [], "task": "NER"}
{"text": "It proposes validation of identity , selectivity , precision , working range , limit of detection and robustness , bearing in mind that each \" result \" must include information about the chemical identity , particle size and mass or particle number concentration .", "entity": [], "task": "NER"}
{"text": "This has an impact on testing for selectivity and trueness , which also must take these aspects into consideration .", "entity": [], "task": "NER"}
{"text": "Selectivity must not only be tested against matrix constituents and other nanoparticles , but it shall also be tested whether the methods apply equally well to particles of different suppliers .", "entity": [], "task": "NER"}
{"text": "In trueness testing , information whether the particle size distribution has changed during analysis is required .", "entity": [], "task": "NER"}
{"text": "Results are largely expected to follow normal distributions due to the expected high number of particles .", "entity": [], "task": "NER"}
{"text": "An approach of estimating measurement uncertainties from the validation data is given .", "entity": [], "task": "NER"}
{"text": "Effects of fish protein hydrolysate and freeze - thaw treatment on physicochemical and gel properties of natural actomyosin from Pacific cod .", "entity": [], "task": "NER"}
{"text": "The properties of natural actomyosin ( NAM ) containing 2 % or 8 % fish protein hydrolysate ( FPH - 2 , FPH - 8 ) or 8 % sucrose - sorbitol blend ( SuSo ) were compared to control NAM before and after freeze - thaw treatment .", "entity": [{"entity": "sucrose", "entity_type": "Chemical", "pos": [121, 128]}, {"entity": "sorbitol", "entity_type": "Chemical", "pos": [131, 139]}, {"entity": "SuSo", "entity_type": "Chemical", "pos": [148, 152]}], "task": "NER"}
{"text": "Surface hydrophobicity of control and FPH - 2 increased after freeze - thaw treatment , while that of FPH - 8 did not change , which may be related to greater thermostability of actin and myosin in FPH - 8 as observed by differential scanning calorimetry .", "entity": [], "task": "NER"}
{"text": "The cooked gel of freeze - thawed control had 39 % expressible moisture after an 8 . 5 % cook loss , whereas gels of freeze - thawed SuSo , FPH - 2 and FPH - 8 had significantly lower expressible moisture ( 15 - 22 % ) and no cook loss .", "entity": [{"entity": "SuSo", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "Gels of freeze - thawed FPH - 2 and FPH - 8 were similar to unfrozen control gel in hardness , cohesiveness and gumminess .", "entity": [], "task": "NER"}
{"text": "This study demonstrates that FPH effectively stabilised NAM protein structure and function during freeze - thaw treatment .", "entity": [], "task": "NER"}
{"text": "Rapid quantification of muscle fat content and subcutaneous adipose tissue in fish using MRI .", "entity": [], "task": "NER"}
{"text": "The potentiality of MRI to quantify fat content in flesh and subcutaneous fat in fish cutlets was investigated .", "entity": [], "task": "NER"}
{"text": "Low measurement time was aimed at in a view to handling large number of samples needed in selective breeding programs for example .", "entity": [], "task": "NER"}
{"text": "Results on fresh and frozen - thawed cutlets were compared to assess this way of conservation .", "entity": [], "task": "NER"}
{"text": "As MRI generates unwanted spatial variations of the signal , a correction method was developed enabling the measurement on several cutlets simultaneously in less than 3 min per sample .", "entity": [], "task": "NER"}
{"text": "For subcutaneous fat , the results were compared with vision measurements .", "entity": [], "task": "NER"}
{"text": "High correlations between both techniques were found ( R ( 2 ) = 0 . 77 and 0 . 87 for the ventral and dorsal part ) .", "entity": [], "task": "NER"}
{"text": "Fat in flesh was validated vs NMR measurements .", "entity": [], "task": "NER"}
{"text": "No statistical difference was found between fresh and frozen - thawed cutlets .", "entity": [], "task": "NER"}
{"text": "RMSE was respectively 0 . 8 % and 0 . 89 % .", "entity": [], "task": "NER"}
{"text": "These results confirmed the potentiality of MRI for fat measurement in fish particularly for a large number of samples .", "entity": [], "task": "NER"}
{"text": "Pesticide residues in market foods in Shaanxi Province of China in 2010 .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to investigate the pesticide residues in market vegetables in Shaanxi Province of China .", "entity": [], "task": "NER"}
{"text": "The concentrations of 33 pesticides were determined by gas chromatography ( GC ) in 285 samples .", "entity": [], "task": "NER"}
{"text": "Ten organophosphorus pesticides ( OPs ) were found in concentrations ranging from 0 . 004 to 0 . 257 mg / kg .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [4, 20]}], "task": "NER"}
{"text": "The mean levels of omethoate , phorate , chlorpyrifos , methidathion , ethoprophos in vegetables exceeded the maximum residue limits ( MRLs ) allowed by the Ministry of Health , of China .", "entity": [{"entity": "omethoate", "entity_type": "Chemical", "pos": [19, 28]}, {"entity": "phorate", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "methidathion", "entity_type": "Chemical", "pos": [56, 68]}, {"entity": "ethoprophos", "entity_type": "Chemical", "pos": [71, 82]}], "task": "NER"}
{"text": "Other detectable OP pesticide residues levels were below their MRLs .", "entity": [], "task": "NER"}
{"text": "Dicofol were detectable in green pepper and chives samples .", "entity": [{"entity": "Dicofol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Five pyrethroid pesticides ( PYRs ) were detectable in vegetable samples respectively .", "entity": [{"entity": "pyrethroid", "entity_type": "Chemical", "pos": [5, 15]}], "task": "NER"}
{"text": "The results provide useful information on the current contamination status of a key agricultural area in China , and point to the need for urgent action to control the excessive use of some chemicals .", "entity": [], "task": "NER"}
{"text": "Colour and stability assessment of blue ferric anthocyanin chelates in liquid pectin - stabilised model systems .", "entity": [{"entity": "ferric anthocyanin", "entity_type": "Chemical", "pos": [40, 58]}], "task": "NER"}
{"text": "The formation of blue coloured ferric anthocyanin chelates and their colour stability during storage and thermal treatment were monitored in a pH range relevant to food ( 3 . 6 - 5 . 0 ) .", "entity": [{"entity": "ferric anthocyanin", "entity_type": "Chemical", "pos": [31, 49]}], "task": "NER"}
{"text": "Liquid model systems were composed of different types of Citrus pectins , juices ( J ) and the respective phenolic extracts ( E ) from elderberry ( EB ) , black currant ( BC ) , red cabbage ( RC ) and purple carrot ( PC ) in the presence of ferric ions .", "entity": [{"entity": "ferric", "entity_type": "Chemical", "pos": [241, 247]}], "task": "NER"}
{"text": "For EB , BC and PC , pure blue colours devoid of a violet tint were exclusively observed for the phenolic extracts and at pH values >= 4 . 5 in model systems containing high methoxylated and amidated pectins , respectively .", "entity": [], "task": "NER"}
{"text": "Colour and its stability strongly depended on the amount of ferric ions and the plant source ; however , colour decay could generally be described as a pseudo - first - order kinetics .", "entity": [{"entity": "ferric", "entity_type": "Chemical", "pos": [60, 66]}], "task": "NER"}
{"text": "Despite optimal colour hues for RC - E and RC - J , storage and heat stabilities were poor .", "entity": [], "task": "NER"}
{"text": "Highest colour intensities and best stabilities were observed for model systems containing PC - E at a molar anthocyanin : ferric ion ratio of 1 : 2 .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "ferric", "entity_type": "Chemical", "pos": [123, 129]}], "task": "NER"}
{"text": "Ascorbic and lactic acids interfered with ferric ions , thus significantly affecting blue colour evolution and stability .", "entity": [{"entity": "Ascorbic and lactic acids", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "ferric", "entity_type": "Chemical", "pos": [42, 48]}], "task": "NER"}
{"text": "Colour loss strongly depended on heat exposure with activation energies ranging between 60 . 5 and 78 . 4 kJ / mol .", "entity": [], "task": "NER"}
{"text": "The comprehensive evaluation of the interrelationship of pigment source , pH conditions and pectin type on chelate formation and stability demonstrated that ferric anthocyanin chelates are promising natural blue food colourants .", "entity": [{"entity": "ferric anthocyanin", "entity_type": "Chemical", "pos": [157, 175]}], "task": "NER"}
{"text": "Combined effect of starter culture and temperature on phenolic compounds during fermentation of Taggiasca black olives .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "The influence of two operative parameters on the fermentation process of table olives from Taggiasca cultivar were investigated .", "entity": [], "task": "NER"}
{"text": "Laboratory scale fermentations were performed using Lactobacillus plantarum as the only starter and in combination with Saccharomyces cerevisiae at three different temperatures ( 23 , 30 and 37 degrees C ) .", "entity": [], "task": "NER"}
{"text": "Control tests used for each trial were fermented only by indigenous microflora .", "entity": [], "task": "NER"}
{"text": "pH and phenolic compounds were monitored in the brine and olive flesh during the fermentation .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [7, 15]}], "task": "NER"}
{"text": "Higher temperatures ( 37 degrees C ) enhanced notably the release of phenolic compounds in the brine .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "High performance liquid chromatography ( HPLC ) analysis of brines evidenced the complete hydrolysis of oleuropein after 100 days of fermentation at 37 degrees C for all treatments .", "entity": [{"entity": "oleuropein", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "The antioxidant power of the extracts was linearly correlated to their polyphenol contents .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [71, 81]}], "task": "NER"}
{"text": "The results confirmed the efficiency of treatments compared with the control tests for debittering process of table black olives .", "entity": [], "task": "NER"}
{"text": "Phenolic compounds in the brines can be then extracted and used in food , cosmetic and pharmaceutical industries .", "entity": [{"entity": "Phenolic", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Expression patterns of cell cycle proteins in the livers of rats treated with hepatocarcinogens for 28 days .", "entity": [], "task": "NER"}
{"text": "Some hepatocarcinogens induce cytomegaly , which reflects aberrant cell cycling and increased ploidy , from the early stages of administration to animals .", "entity": [], "task": "NER"}
{"text": "To clarify the regulatory molecular mechanisms behind cell cycle aberrations related to the early stages of hepatocarcinogenesis , we performed gene expression analysis using microarrays and real - time reverse transcription polymerase chain reaction followed by immunohistochemical analysis in the livers of rats treated with the cytomegaly inducing hepatocarcinogens thioacetamide ( TAA ) , fenbendazole , and methyleugenol , the cytomegaly non - inducing hepatocarcinogen piperonyl butoxide ( PBO ) , or the non - carcinogenic hepatotoxicants acetaminophen and alpha - naphthyl isothiocyanate , for 28 days .", "entity": [{"entity": "thioacetamide", "entity_type": "Chemical", "pos": [369, 382]}, {"entity": "TAA", "entity_type": "Chemical", "pos": [385, 388]}, {"entity": "fenbendazole", "entity_type": "Chemical", "pos": [393, 405]}, {"entity": "methyleugenol", "entity_type": "Chemical", "pos": [412, 425]}, {"entity": "piperonyl butoxide", "entity_type": "Chemical", "pos": [475, 493]}, {"entity": "PBO", "entity_type": "Chemical", "pos": [496, 499]}, {"entity": "acetaminophen", "entity_type": "Chemical", "pos": [546, 559]}, {"entity": "alpha - naphthyl isothiocyanate", "entity_type": "Chemical", "pos": [564, 595]}], "task": "NER"}
{"text": "Gene expression profiling showed that cell cycle - related genes , especially those of G ( 2 ) / M phase , were mostly upregulated after TAA treatment .", "entity": [{"entity": "TAA", "entity_type": "Chemical", "pos": [137, 140]}], "task": "NER"}
{"text": "Immunohistochemical analysis was performed on cell cycle proteins that were upregulated by TAA treatment and on related proteins .", "entity": [{"entity": "TAA", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "All hepatocarcinogens , irrespective of their cytomegaly inducing potential , increased liver cells immunoreactive for p21 ( Cip1 ) , which acts on cells arrested in G ( 1 ) phase , and for Aurora B or Incenp , which is suggestive of an increase in a cell population with chromosomal instability caused by overexpression .", "entity": [], "task": "NER"}
{"text": "PBO did not induce cell proliferation after 28 - day treatment .", "entity": [{"entity": "PBO", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Hepatocarcinogens that induced cell proliferation after 28 - day treatment also caused an increase in p53 ( + ) cells in parallel with increased apoptotic cells , as well as increased population of cells expressing M phase - related proteins nuclear Cdc2 , phospho - Histone H3 , and HP1 alpha .", "entity": [], "task": "NER"}
{"text": "These results suggest that hepatocarcinogens may increase cellular populations arrested in G ( 1 ) phase or showing chromosomal instability after 28 - day treatment .", "entity": [], "task": "NER"}
{"text": "Hepatocarcinogens that induce cell cycle facilitation may cause M phase arrest accompanied by apoptosis .", "entity": [], "task": "NER"}
{"text": "End - faced waveguide mediated optical propulsion of microspheres and single cells in a microfluidic device .", "entity": [], "task": "NER"}
{"text": "Single cell transport in microfluidic devices is a topic of interest as their utility is becoming appreciated by cell and molecular biologist .", "entity": [], "task": "NER"}
{"text": "Cell transport should minimize mechanical stress due to friction or pressure gradients .", "entity": [], "task": "NER"}
{"text": "Optical forces have the advantage of applying their forces across the cell volume and not only at the cell membrane and are thus preferable .", "entity": [], "task": "NER"}
{"text": "Optical pushing by scattering force is a suitable candidate so highly dependent on the photon irradiance field inside the propagation capillary which in turn is determined by the waveguide properties delivering the radiation pressure .", "entity": [], "task": "NER"}
{"text": "Here we present a numerical approach to predict the optical scattering force , speed and trajectory of cells as a function of waveguide and propagation capillary geometry .", "entity": [], "task": "NER"}
{"text": "Experimental verification of the simulation approach is demonstrated using polystyrene microspheres and leukemia cells .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "Effects of optical fibre to waveguide alignment , capillary wall angle and temperature on the dynamic viscosity on speed and position of the microspheres and cells inside the propagation capillary are demonstrated .", "entity": [], "task": "NER"}
{"text": "Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms .", "entity": [{"entity": "Adenosine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Activation of the adenosine 2A receptor ( A ( 2A ) R ) reduces inflammation in models of acute injury but contribution in development of chronic abdominal aortic aneurysms ( AAAs ) is unknown .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [18, 27]}], "task": "NER"}
{"text": "Elastase perfusion to induce AAA formation in A ( 2A ) R - knockout ( A ( 2A ) RKO ) and C57BL6 / J wild - type ( WT ) mice resulted in nearly 100 % larger aneurysms in A ( 2A ) RKO compared to WT at d 14 ( P < 0 . 05 ) , with evidence of greater elastin fragmentation , more immune cell infiltration , and increased matrix metallatoproteinase ( MMP ) 9 expression ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Separately , exogenous A ( 2A ) R antagonism in elastase - perfused WT mice also resulted in larger aneurysms ( P < 0 . 05 ) , while A ( 2A ) R agonism limited aortic dilatation ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Activated Thy - 1 . 2 ( + ) T lymphocytes from WT mice treated in vitro with A ( 2A ) R antagonist increased cytokine production , and treatment with A ( 2A ) R agonist decreased cytokine production ( P < 0 . 05 for all ) .", "entity": [], "task": "NER"}
{"text": "Primary activated CD4 ( + ) T lymphocytes from A ( 2A ) RKO mice exhibited greater chemotaxis ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "A ( 2A ) R antagonist increased chemotaxis of activated CD4 ( + ) cells from WT mice in vitro , and A ( 2A ) R agonist reduced this effect ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "A ( 2A ) R activation attenuates AAA formation partly by inhibiting immune cell recruitment and reducing elastin fragmentation .", "entity": [], "task": "NER"}
{"text": "These findings support augmenting A ( 2A ) R signaling as a putative target for limiting aneurysm formation . - Bhamidipati , C .", "entity": [], "task": "NER"}
{"text": "M . , Mehta , G .", "entity": [], "task": "NER"}
{"text": "S . , Moehle , C .", "entity": [], "task": "NER"}
{"text": "W . , Meher , A .", "entity": [], "task": "NER"}
{"text": "K . , Su , G . , Vigneshwar , N .", "entity": [], "task": "NER"}
{"text": "G . , Barbery , C . , Sharma , A .", "entity": [], "task": "NER"}
{"text": "K . , Kron , I .", "entity": [], "task": "NER"}
{"text": "L . , Laubach , V .", "entity": [], "task": "NER"}
{"text": "E . , Owens , G .", "entity": [], "task": "NER"}
{"text": "K . , Upchurch Jr . , G .", "entity": [], "task": "NER"}
{"text": "R . , Ailawadi , G .", "entity": [], "task": "NER"}
{"text": "Spectroscopic characterization and constitutional and rotational isomerism of ClC ( O ) SCN and ClC ( O ) NCS .", "entity": [{"entity": "ClC ( O ) SCN", "entity_type": "Chemical", "pos": [78, 91]}, {"entity": "ClC ( O ) NCS", "entity_type": "Chemical", "pos": [96, 109]}], "task": "NER"}
{"text": "Chlorocarbonylthio - and isothiocyanate ( ClC ( O ) SCN and ClC ( O ) NCS ) have been isolated and characterized by IR ( Ar matrix , gas ) , Raman ( liquid ) , ( 13 ) C NMR and UV - visible spectroscopies .", "entity": [{"entity": "Chlorocarbonylthio - and isothiocyanate", "entity_type": "Chemical", "pos": [0, 39]}, {"entity": "ClC ( O ) SCN", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "ClC ( O ) NCS", "entity_type": "Chemical", "pos": [60, 73]}, {"entity": "Ar", "entity_type": "Chemical", "pos": [121, 123]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [160, 168]}], "task": "NER"}
{"text": "Vibrational and quantum chemical studies suggest the presence of the syn and anti conformers ( SCN group with respect to the C = O bond ) in the gas phase for both constitutional isomers .", "entity": [{"entity": "SCN", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "C = O", "entity_type": "Chemical", "pos": [125, 130]}], "task": "NER"}
{"text": "syn - ClC ( O ) SCN is preferred by Delta H degrees ( anti / syn ) = 1 . 3 ( 0 . 3 ) kcal mol ( - 1 ) .", "entity": [{"entity": "syn - ClC ( O ) SCN", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "The solid - state structure of ClC ( O ) SCN has been determined by single crystal X - ray diffraction analysis at low temperature .", "entity": [{"entity": "ClC ( O ) SCN", "entity_type": "Chemical", "pos": [31, 44]}], "task": "NER"}
{"text": "The crystalline solid consists exclusively of molecules in the syn conformation .", "entity": [], "task": "NER"}
{"text": "On the other hand , the anti form is more stable for the ClC ( O ) NCS isomer .", "entity": [{"entity": "ClC ( O ) NCS", "entity_type": "Chemical", "pos": [57, 70]}], "task": "NER"}
{"text": "The structure of ClC ( O ) NCS and its conformational composition were determined by gas electron diffraction .", "entity": [{"entity": "ClC ( O ) NCS", "entity_type": "Chemical", "pos": [17, 30]}], "task": "NER"}
{"text": "An unusual low syn --> anti interconversion energy barrier of 0 . 98 ( 0 . 15 ) kcal mol ( - 1 ) was detected for ClC ( O ) NCS at cryogenic temperatures .", "entity": [{"entity": "ClC ( O ) NCS", "entity_type": "Chemical", "pos": [114, 127]}], "task": "NER"}
{"text": "The photochemistry of both constitutional isomers isolated in solid argon at 15 K was studied .", "entity": [{"entity": "argon", "entity_type": "Chemical", "pos": [68, 73]}], "task": "NER"}
{"text": "Rearrangement of ClC ( O ) SCN to ClC ( O ) NCS was observed in the neat liquid and under UV - vis irradiation of ClC ( O ) SCN isolated in solid argon .", "entity": [{"entity": "ClC ( O ) SCN", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "ClC ( O ) NCS", "entity_type": "Chemical", "pos": [34, 47]}, {"entity": "ClC ( O ) SCN", "entity_type": "Chemical", "pos": [114, 127]}, {"entity": "argon", "entity_type": "Chemical", "pos": [146, 151]}], "task": "NER"}
{"text": "Properties have been discussed in terms of the valence electronic structure , including the analysis of the He ( I ) photoelectron spectrum of ClC ( O ) SCN .", "entity": [{"entity": "He ( I )", "entity_type": "Chemical", "pos": [108, 116]}, {"entity": "ClC ( O ) SCN", "entity_type": "Chemical", "pos": [143, 156]}], "task": "NER"}
{"text": "Potential - dependent interaction of DOPC liposomes with an octadecanol - covered Au ( 111 ) surface investigated using electrochemical methods coupled with in situ fluorescence microscopy .", "entity": [{"entity": "DOPC", "entity_type": "Chemical", "pos": [37, 41]}, {"entity": "octadecanol", "entity_type": "Chemical", "pos": [60, 71]}, {"entity": "Au ( 111 )", "entity_type": "Chemical", "pos": [82, 92]}], "task": "NER"}
{"text": "The potential - controlled incorporation of DOPC liposomes ( 100 nm diameter ) into an adsorbed octadecanol layer on Au ( 111 ) was studied using electrochemical and in situ fluorescence microscopy .", "entity": [{"entity": "DOPC", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "octadecanol", "entity_type": "Chemical", "pos": [96, 107]}, {"entity": "Au ( 111 )", "entity_type": "Chemical", "pos": [117, 127]}], "task": "NER"}
{"text": "The adsorbed layer of octadecanol included a small amount of a lipophilic fluorophore - octadecanol modified with BODIPY - to enable fluorescence imaging .", "entity": [{"entity": "octadecanol", "entity_type": "Chemical", "pos": [22, 33]}, {"entity": "octadecanol", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "BODIPY", "entity_type": "Chemical", "pos": [114, 120]}], "task": "NER"}
{"text": "The deposited octadecanol layer was found not to allow liposomes to interact unless the potential was less than - 0 . 4 V / SCE , which introduces defects into the adsorbed layer .", "entity": [{"entity": "octadecanol", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Small increases in the capacitance of the adsorbed layer were measured after introducing the defects , allowing the liposomes to interact with the defects and then annealing the defects at 0 V / SCE .", "entity": [], "task": "NER"}
{"text": "A change in the adsorbed layer was also signified by a more positive desorption potential for the liposome - modified adsorbed layer as compared to that for an adsorbed layer that was porated in a similar fashion but without liposomes present in the electrolyte .", "entity": [], "task": "NER"}
{"text": "These subtle changes in capacitance are difficult to interpret , so an in situ spectroscopic study was performed to provide a more direct measure of the interaction .", "entity": [], "task": "NER"}
{"text": "The incorporation of liposomes should result in an increase in the fluorescence measured because the fluorophore should become further separated from the gold surface , reducing the efficiency of fluorescence quenching .", "entity": [], "task": "NER"}
{"text": "No significant increase in the fluorescence of the adsorbed layer was observed during the potential pulses used in the poration procedure in the absence of liposomes .", "entity": [], "task": "NER"}
{"text": "In the presence of liposomes , the fluorescence intensity was found to depend on the potential and time used for poration .", "entity": [], "task": "NER"}
{"text": "At 0 V / SCE , no significant change in the fluorescence was observed for defect - free adsorbed layers .", "entity": [], "task": "NER"}
{"text": "Changing the poration potential to - 0 . 4 V / SCE caused significant increases in the fluorescence and the appearance of new structural features in the adsorbed layers that were more easily observed during the desorption procedure .", "entity": [], "task": "NER"}
{"text": "The extent of fluorescence changes was found to be strongly dependent on the nature of the adsorbed layer under investigation , which suggests that the poration and liposome interaction are dependent on the quality of the adsorbed layer and its ease of poration through changes in the electrode potential .", "entity": [], "task": "NER"}
{"text": "Bifunctional electrophiles cross - link thioredoxins with redox relay partners in cells .", "entity": [], "task": "NER"}
{"text": "Thioredoxin protects cells against oxidative damage by reducing disulfide bonds in improperly oxidized proteins .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "Previously , we found that the baker ' s yeast cytosolic thioredoxin Trx2 undergoes cross - linking to form several protein - protein complexes in cells treated with the bifunctional electrophile divinyl sulfone ( DVSF ) .", "entity": [{"entity": "divinyl sulfone", "entity_type": "Chemical", "pos": [196, 211]}, {"entity": "DVSF", "entity_type": "Chemical", "pos": [214, 218]}], "task": "NER"}
{"text": "Here , we report that the peroxiredoxin Tsa1 and the thioredoxin reductase Trr1 , both of which function in a redox relay network with thioredoxin , become cross - linked in complexes with Trx2 upon DVSF treatment .", "entity": [{"entity": "DVSF", "entity_type": "Chemical", "pos": [199, 203]}], "task": "NER"}
{"text": "Treatment of yeast with other bifunctional electrophiles , including diethyl acetylenedicarboxylate ( DAD ) , mechlorethamine ( HN2 ) , and 1 , 2 , 3 , 4 - diepoxybutane ( DEB ) , resulted in the formation of similar cross - linked complexes .", "entity": [{"entity": "diethyl acetylenedicarboxylate", "entity_type": "Chemical", "pos": [69, 99]}, {"entity": "DAD", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "mechlorethamine", "entity_type": "Chemical", "pos": [110, 125]}, {"entity": "HN2", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "1 , 2 , 3 , 4 - diepoxybutane", "entity_type": "Chemical", "pos": [140, 169]}, {"entity": "DEB", "entity_type": "Chemical", "pos": [172, 175]}], "task": "NER"}
{"text": "Cross - linking of Trx2 and Tsa1 to other proteins by DVSF and DAD is dependent on modification of the active site Cys residues within these proteins .", "entity": [{"entity": "DVSF", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "DAD", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "In addition , the human cytosolic thioredoxin , cytosolic thioredoxin reductase , and peroxiredoxin 2 form cross - linked complexes to other proteins in the presence of DVSF , although each protein shows different susceptibilities to modification by DAD , HN2 , and DEB .", "entity": [{"entity": "DVSF", "entity_type": "Chemical", "pos": [169, 173]}, {"entity": "DAD", "entity_type": "Chemical", "pos": [250, 253]}, {"entity": "HN2", "entity_type": "Chemical", "pos": [256, 259]}, {"entity": "DEB", "entity_type": "Chemical", "pos": [266, 269]}], "task": "NER"}
{"text": "Taken together , our results indicate that bifunctional electrophiles potentially disrupt redox homeostasis in yeast and human cells by forming cross - linked complexes between thioredoxins and their redox partners .", "entity": [], "task": "NER"}
{"text": "Bioanalytical LC separation techniques for quantitative analysis of free amino acids in human plasma .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [73, 84]}], "task": "NER"}
{"text": "The quantitative analysis of free amino acids in human plasma has become an important and essential analysis parameter in different areas of life sciences .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [34, 45]}], "task": "NER"}
{"text": "Free amino acid concentrations in human plasma samples are generally determined by means of GC or LC after chemical derivatization followed by UV , fluorescent or MS detection of the amino acid derivatives .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [5, 15]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [183, 193]}], "task": "NER"}
{"text": "Derivatization of free amino acids is done either pre - or post - column , and the amino acid derivatives obtained posess improved chromatographic behavior , increased detection sensitivity and selectivity compared with non - derivatized free amino acids .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [83, 93]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [243, 254]}], "task": "NER"}
{"text": "This work gives an overview of different chemical derivatization methods applied and their liquid separation techniques in bioanalytical assays for quantitative free amino acid analysis in human plasma samples .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [166, 176]}], "task": "NER"}
{"text": "Important plasma preparation procedures , pre - and post - column derivatization , and different LC separation techniques are presented .", "entity": [], "task": "NER"}
{"text": "Application of the compensated Arrhenius formalism to fluidity data of polar organic liquids .", "entity": [], "task": "NER"}
{"text": "The temperature dependence of viscosity ( the reciprocal of fluidity ) in polar liquids has been studied for over a century , but the available theoretical models have serious limitations .", "entity": [], "task": "NER"}
{"text": "Consequently , the viscosity is often described with empirical equations using adjustable fitting parameters that offer no insight into the molecular mechanism of transport .", "entity": [], "task": "NER"}
{"text": "We have previously reported a novel approach called the compensated Arrhenius formalism ( CAF ) to describe ionic conductivity , self - diffusion , and dielectric relaxation in terms of molecular and system properties .", "entity": [], "task": "NER"}
{"text": "Here the CAF is applied to fluidity data of pure n - acetates , 2 - ketones , n - nitriles , and n - alcohols over the temperature range 5 - 85 degrees C .", "entity": [{"entity": "n - acetates", "entity_type": "Chemical", "pos": [49, 61]}, {"entity": "2 - ketones", "entity_type": "Chemical", "pos": [64, 75]}, {"entity": "n - nitriles", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "n - alcohols", "entity_type": "Chemical", "pos": [97, 109]}], "task": "NER"}
{"text": "The fluidity is represented as an Arrhenius - like expression that includes a static dielectric constant dependence in the exponential prefactor .", "entity": [], "task": "NER"}
{"text": "The dielectric constant dependence results from the dependence of mass and charge transport on the molecular dipole moment and the solvent dipole density .", "entity": [], "task": "NER"}
{"text": "The CAF is the only self - consistent description of fluid transport in polar liquids written solely in terms of molecular and system parameters .", "entity": [], "task": "NER"}
{"text": "A scaling procedure is used to calculate the activation energy for transport .", "entity": [], "task": "NER"}
{"text": "We find that the activation energies for fluidity of the aprotic liquids are comparable in value , whereas a higher average E ( a ) value is observed for the n - alcohol data .", "entity": [{"entity": "n - alcohol", "entity_type": "Chemical", "pos": [158, 169]}], "task": "NER"}
{"text": "Finally , we contrast the molecular description of transport presented here with the conventional hydrodynamic model .", "entity": [], "task": "NER"}
{"text": "Ester hydrolysis by a histidine - containing cavitein .", "entity": [{"entity": "Ester", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "histidine", "entity_type": "Chemical", "pos": [22, 31]}], "task": "NER"}
{"text": "We have used a template - assembled synthetic protein ( TASP ) to investigate catalytic function in ester hydrolysis .", "entity": [{"entity": "ester", "entity_type": "Chemical", "pos": [100, 105]}], "task": "NER"}
{"text": "A histidine - containing cavitein has been found to catalyze ester hydrolysis with a rate increase of 18 times that of background .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [2, 11]}, {"entity": "ester", "entity_type": "Chemical", "pos": [61, 66]}], "task": "NER"}
{"text": "Triazolo and imidazo dihydropyrazolopyrimidine potassium channel antagonists .", "entity": [{"entity": "Triazolo and imidazo dihydropyrazolopyrimidine", "entity_type": "Chemical", "pos": [0, 46]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "Previously disclosed C6 amido and benzimidazole dihydropyrazolopyrimidines were potent and selective blockers of IKur current .", "entity": [{"entity": "amido and benzimidazole dihydropyrazolopyrimidines", "entity_type": "Chemical", "pos": [24, 74]}], "task": "NER"}
{"text": "Syntheses and SAR for C6 triazolo and imidazo dihydropyrazolopyrimidines series are described .", "entity": [{"entity": "triazolo and imidazo dihydropyrazolopyrimidines", "entity_type": "Chemical", "pos": [25, 72]}], "task": "NER"}
{"text": "Trifluoromethylcyclohexyl N ( 1 ) triazole , compound 51 , was identified as a potent and selective Kv1 . 5 inhibitor with an acceptable PK and liability profile .", "entity": [{"entity": "Trifluoromethylcyclohexyl N ( 1 ) triazole", "entity_type": "Chemical", "pos": [0, 42]}], "task": "NER"}
{"text": "Discovery of a novel series of quinolone alpha 7 nicotinic acetylcholine receptor agonists .", "entity": [{"entity": "quinolone", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [59, 72]}], "task": "NER"}
{"text": "High throughput screening led to the identification of a novel series of quinolone alpha 7 nicotinic acetylcholine receptor ( nAChR ) agonists .", "entity": [{"entity": "quinolone", "entity_type": "Chemical", "pos": [73, 82]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [101, 114]}], "task": "NER"}
{"text": "Optimization of an HTS hit ( 1 ) led to 4 - phenyl - 1 - ( quinuclidin - 3 - ylmethyl ) quinolin - 2 ( 1H ) - one , which was found to be potent and selective .", "entity": [{"entity": "4 - phenyl - 1 - ( quinuclidin - 3 - ylmethyl ) quinolin - 2 ( 1H ) - one", "entity_type": "Chemical", "pos": [40, 113]}], "task": "NER"}
{"text": "Poor brain penetrance in this series was attributed to transporter - mediated efflux , which was in turn due to high pKa .", "entity": [], "task": "NER"}
{"text": "A novel 4 - fluoroquinuclidine significantly lowered the pKa of the quinuclidine moiety , reducing efflux as measured by a Caco - 2 assay .", "entity": [{"entity": "4 - fluoroquinuclidine", "entity_type": "Chemical", "pos": [8, 30]}, {"entity": "quinuclidine", "entity_type": "Chemical", "pos": [68, 80]}], "task": "NER"}
{"text": "A genetic program promotes C . elegans longevity at cold temperatures via a thermosensitive TRP channel .", "entity": [], "task": "NER"}
{"text": "Both poikilotherms and homeotherms live longer at lower body temperatures , highlighting a general role of temperature reduction in lifespan extension .", "entity": [], "task": "NER"}
{"text": "However , the underlying mechanisms remain unclear .", "entity": [], "task": "NER"}
{"text": "One prominent model is that cold temperatures reduce the rate of chemical reactions , thereby slowing the rate of aging .", "entity": [], "task": "NER"}
{"text": "This view suggests that cold - dependent lifespan extension is simply a passive thermodynamic process .", "entity": [], "task": "NER"}
{"text": "Here , we challenge this view in C . elegans by showing that genetic programs actively promote longevity at cold temperatures .", "entity": [], "task": "NER"}
{"text": "We find that TRPA - 1 , a cold - sensitive TRP channel , detects temperature drop in the environment to extend lifespan .", "entity": [], "task": "NER"}
{"text": "This effect requires cold - induced , TRPA - 1 - mediated calcium influx and a calcium - sensitive PKC that signals to the transcription factor DAF - 16 / FOXO .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [58, 65]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "Human TRPA1 can functionally substitute for worm TRPA - 1 in promoting longevity .", "entity": [], "task": "NER"}
{"text": "Our results reveal a previously unrecognized function for TRP channels , link calcium signaling to longevity , and , importantly , demonstrate that genetic programs contribute to lifespan extension at cold temperatures .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [78, 85]}], "task": "NER"}
{"text": "Beneficial effect of the non - psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease .", "entity": [{"entity": "cannabigerol", "entity_type": "Chemical", "pos": [62, 74]}], "task": "NER"}
{"text": "Inflammatory bowel disease ( IBD ) is an incurable disease which affects millions of people in industrialized countries .", "entity": [], "task": "NER"}
{"text": "Anecdotal and scientific evidence suggests that Cannabis use may have a positive impact in IBD patients .", "entity": [], "task": "NER"}
{"text": "Here , we investigated the effect of cannabigerol ( CBG ) , a non - psychotropic Cannabis - derived cannabinoid , in a murine model of colitis .", "entity": [{"entity": "cannabigerol", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "CBG", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "Colitis was induced in mice by intracolonic administration of dinitrobenzene sulphonic acid ( DNBS ) .", "entity": [{"entity": "dinitrobenzene sulphonic acid", "entity_type": "Chemical", "pos": [62, 91]}, {"entity": "DNBS", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "Inflammation was assessed by evaluating inflammatory markers / parameters ( colon weight / colon length ratio and myeloperoxidase activity ) , by histological analysis and immunohistochemistry ; interleukin - 1 beta , interleukin - 10 and interferon - gamma levels by ELISA , inducible nitric oxide synthase ( iNOS ) and cyclooxygenase - 2 ( COX - 2 ) by western blot and RT - PCR ; CuZn - superoxide dismutase ( SOD ) activity by a colorimetric assay .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [286, 298]}, {"entity": "CuZn", "entity_type": "Chemical", "pos": [383, 387]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [390, 400]}], "task": "NER"}
{"text": "Murine macrophages and intestinal epithelial cells were used to evaluate the effect of CBG on nitric oxide production and oxidative stress , respectively .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [94, 106]}], "task": "NER"}
{"text": "CBG reduced colon weight / colon length ratio , myeloperoxidase activity , and iNOS expression , increased SOD activity and normalized interleukin - 1 beta , interleukin - 10 and interferon - gamma changes associated to DNBS administration .", "entity": [{"entity": "CBG", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "DNBS", "entity_type": "Chemical", "pos": [220, 224]}], "task": "NER"}
{"text": "In macrophages , CBG reduced nitric oxide production and iNOS protein ( but not mRNA ) expression .", "entity": [{"entity": "CBG", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [29, 41]}], "task": "NER"}
{"text": "Rimonabant ( a CB1 receptor antagonist ) did not change the effect of CBG on nitric oxide production , while SR144528 ( a CB2 receptor antagonist ) further increased the inhibitory effect of CBG on nitric oxide production .", "entity": [{"entity": "Rimonabant", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "CBG", "entity_type": "Chemical", "pos": [70, 73]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [77, 89]}, {"entity": "SR144528", "entity_type": "Chemical", "pos": [109, 117]}, {"entity": "CBG", "entity_type": "Chemical", "pos": [191, 194]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [198, 210]}], "task": "NER"}
{"text": "In conclusion , CBG attenuated murine colitis , reduced nitric oxide production in macrophages ( effect being modulated by the CB2 receptor ) and reduced ROS formation in intestinal epithelial cells .", "entity": [{"entity": "CBG", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [56, 68]}], "task": "NER"}
{"text": "CBG could be considered for clinical experimentation in IBD patients .", "entity": [{"entity": "CBG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "ADAM17 , shedding , TACE as therapeutic targets .", "entity": [], "task": "NER"}
{"text": "ADAM17 has been molecularly cloned as the enzyme responsible for cleavage of the transmembrane protein TNF alpha ( TNF alpha converting enzyme , TACE ) .", "entity": [], "task": "NER"}
{"text": "Later it was realized that ADAM17 was also responsible for the processing of cell adhesion proteins , cytokine and growth factor receptors and many ligands of the EGF receptor .", "entity": [], "task": "NER"}
{"text": "Since TNF alpha is a target of anti - inflammatory therapies , it was speculated that inhibition of ADAM17 might be a therapeutic strategy in the treatment of inflammation or inflammation associated cancer .", "entity": [], "task": "NER"}
{"text": "Meanwhile it has been recognized that ADAM17 governs many vital functions in the body and loss of ADAM17 leads to severe defects in the skin and to high susceptibility of the intestine to inflammation .", "entity": [], "task": "NER"}
{"text": "Here I summarize data on the physiologic role of ADAM17 and the feasibility of specific blockade of this enzyme .", "entity": [], "task": "NER"}
{"text": "11 beta - Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7 - keto - and 7 - hydroxy - oxysterols in vivo .", "entity": [{"entity": "11 beta - Hydroxysteroid", "entity_type": "Chemical", "pos": [0, 24]}, {"entity": "7 - keto - and 7 - hydroxy - oxysterols", "entity_type": "Chemical", "pos": [81, 120]}], "task": "NER"}
{"text": "11 beta - Hydroxysteroid dehydrogenase 1 ( 11 beta HSD1 ; EC 1 . 1 . 1 . 146 ) generates active glucocorticoids from inert 11 - keto metabolites .", "entity": [{"entity": "11 beta - Hydroxysteroid", "entity_type": "Chemical", "pos": [0, 24]}, {"entity": "11 - keto", "entity_type": "Chemical", "pos": [123, 132]}], "task": "NER"}
{"text": "However , it can also metabolize alternative substrates , including 7 beta - hydroxy - and 7 - keto - cholesterol ( 7 beta OHC , 7KC ) .", "entity": [{"entity": "7 beta - hydroxy - and 7 - keto - cholesterol", "entity_type": "Chemical", "pos": [68, 113]}, {"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [116, 126]}, {"entity": "7KC", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "This has been demonstrated in vitro but its consequences in vivo are uncertain .", "entity": [], "task": "NER"}
{"text": "We used genetically modified mice to investigate the contribution of 11 beta HSD1 to the balance of circulating levels of 7KC and 7 beta OHC in vivo , and dissected in vitro the kinetics of the interactions between oxysterols and glucocorticoids for metabolism by the mouse enzyme .", "entity": [{"entity": "7KC", "entity_type": "Chemical", "pos": [122, 125]}, {"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [130, 140]}, {"entity": "oxysterols", "entity_type": "Chemical", "pos": [215, 225]}], "task": "NER"}
{"text": "Circulating levels of 7KC and 7 beta OHC in mice were 91 . 3 +/- 22 . 3 and 22 . 6 +/- 5 . 7nM respectively , increasing to 1240 +/- 220 and 406 +/- 39nM in ApoE ( - / - ) mice receiving atherogenic western diet .", "entity": [{"entity": "7KC", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [30, 40]}], "task": "NER"}
{"text": "Disruption of 11 beta HSD1 in mice increased ( p < 0 . 05 ) the 7KC / 7 beta OHC ratio in plasma ( by 20 % ) and also in isolated microsomes ( 2 fold ) .", "entity": [{"entity": "7KC", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [70, 80]}], "task": "NER"}
{"text": "The 7KC / 7 beta OHC ratio was similarly increased when NADPH generation was restricted by disruption of hexose - 6 - phosphate dehydrogenase .", "entity": [{"entity": "7KC", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [56, 61]}, {"entity": "hexose - 6 - phosphate", "entity_type": "Chemical", "pos": [105, 127]}], "task": "NER"}
{"text": "Reduction and oxidation of 7 - oxysterols by murine 11 beta HSD1 proceeded more slowly and substrate affinity was lower than for glucocorticoids . in vitro 7 beta OHC was a competitive inhibitor of oxidation of corticosterone ( Ki = 0 . 9 mu M ) , whereas 7KC only weakly inhibited reduction of 11 - dehydrocorticosterone .", "entity": [{"entity": "7 - oxysterols", "entity_type": "Chemical", "pos": [27, 41]}, {"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [156, 166]}, {"entity": "corticosterone", "entity_type": "Chemical", "pos": [211, 225]}, {"entity": "7KC", "entity_type": "Chemical", "pos": [256, 259]}, {"entity": "11 - dehydrocorticosterone", "entity_type": "Chemical", "pos": [295, 321]}], "task": "NER"}
{"text": "However , supplementation of 7 - oxysterols in cultured cells , secondary to cholesterol loading , preferentially slowed reduction of glucocorticoids , rather than oxidation .", "entity": [{"entity": "7 - oxysterols", "entity_type": "Chemical", "pos": [29, 43]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [77, 88]}], "task": "NER"}
{"text": "Thus , in mouse , 11 beta HSD1 influenced the abundance and balance of circulating and tissue levels of 7 beta OHC and 7KC , promoting reduction of 7KC .", "entity": [{"entity": "7 beta OHC", "entity_type": "Chemical", "pos": [104, 114]}, {"entity": "7KC", "entity_type": "Chemical", "pos": [119, 122]}, {"entity": "7KC", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "In health , 7 - oxysterols are unlikely to regulate glucocorticoid metabolism .", "entity": [{"entity": "7 - oxysterols", "entity_type": "Chemical", "pos": [12, 26]}], "task": "NER"}
{"text": "However , in hyperlipidaemia , 7 - oxysterols may inhibit glucocorticoid metabolism and modulate signaling through corticosteroid receptors .", "entity": [{"entity": "7 - oxysterols", "entity_type": "Chemical", "pos": [31, 45]}, {"entity": "corticosteroid", "entity_type": "Chemical", "pos": [115, 129]}], "task": "NER"}
{"text": "Amino acid derived quinazolines as Rock / PKA inhibitors .", "entity": [{"entity": "Amino acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "quinazolines", "entity_type": "Chemical", "pos": [19, 31]}], "task": "NER"}
{"text": "SAR and lead optimization studies for Rock inhibitors based on amino acid - derived quinazolines are described .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "quinazolines", "entity_type": "Chemical", "pos": [84, 96]}], "task": "NER"}
{"text": "Studies demonstrated that these amino acid derived quinazolinones were mainly pan - Rock ( I & II ) inhibitors .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [32, 42]}, {"entity": "quinazolinones", "entity_type": "Chemical", "pos": [51, 65]}], "task": "NER"}
{"text": "While selectivity against other kinases could be achieved , selectivity for most of these compounds against PKA was not achieved .", "entity": [], "task": "NER"}
{"text": "This is distinct from Rock inhibitors based on non - amino acid derived quinazolinones , where high selectivity against PKA could be obtained . ( 22 ) The inhibitors presented here in some cases possessed sub - nanomolar inhibition of Rock , nanomolar potency in ppMLC cell based assays , low to fair cytochrome P - 450 inhibition , and good human microsomal stability .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "quinazolinones", "entity_type": "Chemical", "pos": [72, 86]}], "task": "NER"}
{"text": "Aza - BODIPY : improved synthesis and interaction with soluble A beta 1 - 42 oligomers .", "entity": [{"entity": "Aza - BODIPY", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Dye - binding assays that are used to evaluate anti - aggregation ability of small molecule inhibitors towards amyloids are known to be prone to false - positive effects due to spectral overlaps between the dye and the inhibitor .", "entity": [], "task": "NER"}
{"text": "Aza - BODIPY dye , which has both excitation and emission maxima above 600nm , exhibits a significant increase in its fluorescence intensity in the presence of soluble oligomers of A beta 1 - 42 .", "entity": [{"entity": "Aza - BODIPY", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "These results indicate that aza - BODIPY could serve as a near - IR probe for detecting conformational changes of A beta 1 - 42 soluble oligomers in vitro , and it should eliminate false - positive effects that are associated with currently utilized thioflavin T - based dyes .", "entity": [{"entity": "aza - BODIPY", "entity_type": "Chemical", "pos": [28, 40]}, {"entity": "thioflavin T", "entity_type": "Chemical", "pos": [250, 262]}], "task": "NER"}
{"text": "In addition , a facile synthesis of aza - BODIPY has been developed , which might further expand the applications of this dye .", "entity": [{"entity": "aza - BODIPY", "entity_type": "Chemical", "pos": [36, 48]}], "task": "NER"}
{"text": "Effects of lurasidone in behavioral models of depression .", "entity": [{"entity": "lurasidone", "entity_type": "Chemical", "pos": [11, 21]}], "task": "NER"}
{"text": "Role of the 5 - HT7 receptor subtype .", "entity": [], "task": "NER"}
{"text": "Major depression is a common psychiatric disorder associated with high symptomatic and functional burdens .", "entity": [], "task": "NER"}
{"text": "Pharmacological treatment is often effective , but there remain substantial unmet needs in the form of non - responders , delayed onset of clinical effect , and side effects .", "entity": [], "task": "NER"}
{"text": "Recent studies have positioned the serotonin 5 - HT7 receptor as a new target for the treatment of depression .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "Preclinical studies have shown that antagonists induce an antidepressant - like response , a phenotype that can also be observed in mice lacking the receptor .", "entity": [], "task": "NER"}
{"text": "Lurasidone is a new atypical antipsychotic agent with very high affinity for the 5 - HT7 receptor .", "entity": [{"entity": "Lurasidone", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Patients in clinical trials have reported improved scores in depression ratings .", "entity": [], "task": "NER"}
{"text": "We have tested lurasidone in both acute and chronic mouse models of depression .", "entity": [{"entity": "lurasidone", "entity_type": "Chemical", "pos": [15, 25]}], "task": "NER"}
{"text": "In the tail suspension and forced swim tests lurasidone decreased immobility , an antidepressant - like response .", "entity": [{"entity": "lurasidone", "entity_type": "Chemical", "pos": [45, 55]}], "task": "NER"}
{"text": "The effect required functional 5 - HT7 receptors as it was absent in mice lacking the receptor .", "entity": [], "task": "NER"}
{"text": "In the repeated open - space swim test lurasidone was able to reverse the despair induced by repeated swims in a manner similar to the commonly used antidepressant citalopram .", "entity": [{"entity": "lurasidone", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "citalopram", "entity_type": "Chemical", "pos": [164, 174]}], "task": "NER"}
{"text": "The results provide evidence that lurasidone can act as a 5 - HT7 receptor antagonist and provide a possible explanation for the antidepressant effect data currently emerging from lurasidone clinical trials .", "entity": [{"entity": "lurasidone", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "lurasidone", "entity_type": "Chemical", "pos": [180, 190]}], "task": "NER"}
{"text": "Additionally , the results give further support for targeting the 5 - HT7 receptor in the treatment of depression .", "entity": [], "task": "NER"}
{"text": "It will be of interest to clinically evaluate lurasidone as an antidepressant either as monotherapy or as an adjunctive therapy to available drugs .", "entity": [{"entity": "lurasidone", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "Dexamethasone alters epithelium proliferation and survival and suppresses Wnt / beta - catenin signaling in developing cleft palate .", "entity": [{"entity": "Dexamethasone", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Dexamethasone ( Dex ) contributes to a cleft palate , but the cellular and molecular mechanisms responsible for the deleterious effect on the developing palate are unclear .", "entity": [{"entity": "Dexamethasone", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "Dex", "entity_type": "Chemical", "pos": [16, 19]}], "task": "NER"}
{"text": "Wnt signaling is a causal mechanism of Dex - induced osteoporosis , so this study was conducted to determine whether Dex - induced cleft palate may result from altered Wnt signaling .", "entity": [{"entity": "Dex", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "Dex", "entity_type": "Chemical", "pos": [117, 120]}], "task": "NER"}
{"text": "Administration of Dex to mice completely inhibited canonical Wnt / beta - catenin signaling and altered cell proliferation and apoptosis of the craniofacial epithelium in developing embryos .", "entity": [{"entity": "Dex", "entity_type": "Chemical", "pos": [18, 21]}], "task": "NER"}
{"text": "Thus , downregulated Wnt / beta - catenin signaling was associated with Dex - induced cleft palate .", "entity": [{"entity": "Dex", "entity_type": "Chemical", "pos": [72, 75]}], "task": "NER"}
{"text": "Moreover , altered cell fate by Dex responsible for small palates , delaying shelf elevation and unfused palates was a crucial mechanism in cleft palate .", "entity": [{"entity": "Dex", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Our findings help in elucidating the mechanisms of Dex - induced cleft palate .", "entity": [{"entity": "Dex", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "Cysteamine : an old drug with new potential .", "entity": [{"entity": "Cysteamine", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Cysteamine is an amino thiol with the chemical formula HSCH2CH2NH2 .", "entity": [{"entity": "Cysteamine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "amino thiol", "entity_type": "Chemical", "pos": [17, 28]}, {"entity": "HSCH2CH2NH2", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "Endogenously , cysteamine is derived from coenzyme A degradation , although its plasma concentrations are low .", "entity": [{"entity": "cysteamine", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "coenzyme A", "entity_type": "Chemical", "pos": [42, 52]}], "task": "NER"}
{"text": "Most experience with cysteamine as a drug originates from the field of the orphan disease cystinosis , in which cysteamine is prescribed to decrease intralysosomal cystine accumulation .", "entity": [{"entity": "cysteamine", "entity_type": "Chemical", "pos": [21, 31]}, {"entity": "cysteamine", "entity_type": "Chemical", "pos": [112, 122]}, {"entity": "cystine", "entity_type": "Chemical", "pos": [164, 171]}], "task": "NER"}
{"text": "However , over the years , the drug has been used for several other applications both in vitro and in vivo .", "entity": [], "task": "NER"}
{"text": "In this article , we review the different applications of cysteamine , ending with an overview of ongoing clinical trials for new indications , such as neurodegenerative disorders and nonalcoholic fatty liver disease ( NAFLD ) .", "entity": [{"entity": "cysteamine", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "The recent development of an enteric - coated cysteamine formulation makes cysteamine more patient friendly and will extend its applicability for both old and new indications .", "entity": [{"entity": "cysteamine", "entity_type": "Chemical", "pos": [46, 56]}, {"entity": "cysteamine", "entity_type": "Chemical", "pos": [75, 85]}], "task": "NER"}
{"text": "Collaborative virtual organisation and infrastructure for drug discovery .", "entity": [], "task": "NER"}
{"text": "A virtual organisation approach was applied to collaborative drug discovery integrating experimental and computational design approaches .", "entity": [], "task": "NER"}
{"text": "Scientists Against Malaria was formed with the goal of designing novel antimalarial drug candidates .", "entity": [], "task": "NER"}
{"text": "The collaboration of nine founding partners carried out computational and laboratory work that produced significant volumes of data and metadata , the interpretation for the analysis of which , as well as the related decision making , was challenging .", "entity": [], "task": "NER"}
{"text": "During the first phase the partners developed this ' green - field ' project from initiation through to target selection and modelling , computational screening , biological materials and assay preparation , culminating in the completion of initial experimental testing .", "entity": [], "task": "NER"}
{"text": "A support infrastructure involving a semantic collaborative laboratory framework , interoperating with a cloud of web services through an ontology describing the virtual and experimental screening data , was designed and tested .", "entity": [], "task": "NER"}
{"text": "Modulation of melanogenesis and antioxidant defense system in melanocytes by amikacin .", "entity": [{"entity": "amikacin", "entity_type": "Chemical", "pos": [77, 85]}], "task": "NER"}
{"text": "Amikacin is principally used to treat infections caused by microorganisms resistant to other aminoglycosides .", "entity": [{"entity": "Amikacin", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [93, 108]}], "task": "NER"}
{"text": "Ototoxicity is one of the side effects of amikacin , but the causative mechanism of damage to the ear has not been fully established .", "entity": [{"entity": "amikacin", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "Thus , the aim of this work was to examine the impact of amikacin on the melanogenesis and antioxidant defense system in cultured human normal melanocytes ( HEMa - LP ) .", "entity": [{"entity": "amikacin", "entity_type": "Chemical", "pos": [57, 65]}], "task": "NER"}
{"text": "Amikacin induced the concentration - dependent loss in melanocytes viability .", "entity": [{"entity": "Amikacin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The value of EC50 was determined to be ~ 7 . 5 mM .", "entity": [], "task": "NER"}
{"text": "The analyzed antibiotic inhibited melanin biosynthesis in concentration - dependent manner .", "entity": [], "task": "NER"}
{"text": "Increasing the amikacin concentration also resulted in a decrease in cellular tyrosinase activity .", "entity": [{"entity": "amikacin", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "To study the antioxidant defense system in melanocytes , the activities of superoxide dismutase ( SOD ) , catalase ( CAT ) and glutathione peroxidase ( GPx ) in cells exposed to amikacin were determined .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [75, 85]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [127, 138]}, {"entity": "amikacin", "entity_type": "Chemical", "pos": [178, 186]}], "task": "NER"}
{"text": "Significant changes in cellular antioxidant enzymes activities were observed .", "entity": [], "task": "NER"}
{"text": "Modulation of melanogenesis and the antioxidant status of melanocytes resulting from the use of amikacin in vitro may explain a potential role of melanin and melanocytes in the mechanisms of aminoglycosides ototoxic effects in vivo .", "entity": [{"entity": "amikacin", "entity_type": "Chemical", "pos": [96, 104]}, {"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [191, 206]}], "task": "NER"}
{"text": "Bioaccessibility of 12 trace elements in marine molluscs .", "entity": [], "task": "NER"}
{"text": "We conducted a large scale investigation of the bioaccessibility of 12 trace elements from 11 marine mollusc species ( scallop , oyster , clam , abalone , snail , and mussel ) collected from five locations in Chinese coastal waters .", "entity": [], "task": "NER"}
{"text": "The bioaccessibility of all the 12 trace elements was generally high , with the average values ranging from 42 . 5 % to 90 . 7 % .", "entity": [], "task": "NER"}
{"text": "The highest bioaccessibility was observed for As , Cu , Ni and Se , and the lowest for Fe , Co and Pb .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [46, 48]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [51, 53]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "Se", "entity_type": "Chemical", "pos": [63, 65]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [87, 89]}, {"entity": "Co", "entity_type": "Chemical", "pos": [92, 94]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [99, 101]}], "task": "NER"}
{"text": "Steaming decreased the bioaccessibility of all 12 trace elements and thus diminished their risks .", "entity": [], "task": "NER"}
{"text": "No correlation was observed between the bioaccessibility and the total concentration of the 12 elements .", "entity": [], "task": "NER"}
{"text": "However , there was a significant correlation between the bioaccessibility of the 12 elements and their subcellular distribution .", "entity": [], "task": "NER"}
{"text": "For most trace elements , a significantly negative relationship was demonstrated between the bioaccessibility and the elemental partitioning in the metal - rich granule fraction or in the cellular debris fraction , and a significantly positive correlation was observed between the bioaccessibility and the elemental partitioning in the heat - stable protein fraction and in the trophically available fraction .", "entity": [], "task": "NER"}
{"text": "Hence , the elemental subcellular distribution , especially the elemental partitioning in the trophically available fraction , might be a good predictor of the bioaccessibility and risks of trace elements in molluscs .", "entity": [], "task": "NER"}
{"text": "Ameliorating effects of casein glycomacropeptide on obesity induced by high - fat diet in male Sprague - Dawley rats .", "entity": [], "task": "NER"}
{"text": "The effect of casein glycomacropeptide ( GMP ) as a specific regulating mediator in obese rats induced by high - fat ( HF ) diet was investigated .", "entity": [], "task": "NER"}
{"text": "Male obese Sprague - Dawley ( SD ) rats induced by high - fat diet for 8weeks period were fed high - fat , high - fat with GMP of 100mg / kg BW ( HFLG ) , 200mg / kg BW ( HFMG ) and 400mg / kg BW ( HFHG ) for 6weeks .", "entity": [], "task": "NER"}
{"text": "Compared with the high - fat control ( HFC ) group GMP supplementation significantly decreased adipose tissue weight , activity of fatty acid synthase ( FAS ) and glycerol - 3 - phosphate dehydrogenase ( GPDH ) .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [131, 141]}, {"entity": "glycerol - 3 - phosphate", "entity_type": "Chemical", "pos": [163, 187]}], "task": "NER"}
{"text": "Hepatic lipid droplet size , plasma and hepatic lipid levels markedly reduced .", "entity": [], "task": "NER"}
{"text": "Moreover , GMP reduces plasma total cholesterol and low - density lipoprotein ( LDL ) cholesterol as well as hepatic - cholesterol and triglycerides .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [36, 47]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [86, 97]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [119, 130]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [135, 148]}], "task": "NER"}
{"text": "The liver steatosis observed in obese rats was also prevented by GMP supplement .", "entity": [], "task": "NER"}
{"text": "In addition , GMP significantly diminished mitochondrial and liver malondialdehyde ( MDA ) production , and obviously elevated the activities of mitochondrial and hepatic superoxidase dismutase ( SOD ) and glutathione peroxidase ( GSH - Px ) .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [67, 82]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [85, 88]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [206, 217]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [231, 234]}], "task": "NER"}
{"text": "Leptin production and proinflammatory cytokines such as TNF - alpha and IL - 6 secretion decreased .", "entity": [], "task": "NER"}
{"text": "Taken together , GMP can reduce lipid accumulation and enhance antioxidant capability of obese rats .", "entity": [], "task": "NER"}
{"text": "It suggests that GMP can counteract high - fat diet - induced obesity , which might make it a potential ingredient with anti - obesity activity .", "entity": [], "task": "NER"}
{"text": "Central administration of angiotensin IV rapidly enhances novel object recognition among mice .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [26, 40]}], "task": "NER"}
{"text": "Angiotensin IV ( Val ( 1 ) - Tyr ( 2 ) - Ile ( 3 ) - His ( 4 ) - Pro ( 5 ) - Phe ( 6 ) ) has demonstrated potential cognitive - enhancing effects .", "entity": [{"entity": "Angiotensin IV", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "Val ( 1 ) - Tyr ( 2 ) - Ile ( 3 ) - His ( 4 ) - Pro ( 5 ) - Phe ( 6 )", "entity_type": "Chemical", "pos": [17, 86]}], "task": "NER"}
{"text": "The present investigation assessed and characterized : ( 1 ) dose - dependency of angiotensin IV ' s cognitive enhancement in a C57BL / 6J mouse model of novel object recognition , ( 2 ) the time - course for these effects , ( 3 ) the identity of residues in the hexapeptide important to these effects and ( 4 ) the necessity of actions at angiotensin IV receptors for procognitive activity .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [82, 96]}, {"entity": "hexapeptide", "entity_type": "Chemical", "pos": [263, 274]}, {"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [340, 354]}], "task": "NER"}
{"text": "Assessment of C57BL / 6J mice in a novel object recognition task demonstrated that prior administration of angiotensin IV ( 0 . 1 , 1 . 0 , or 10 . 0 , but not 0 . 01 nmol , i . c . v . ) significantly enhanced novel object recognition in a dose - dependent manner .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [107, 121]}], "task": "NER"}
{"text": "These effects were time dependent , with improved novel object recognition observed when angiotensin IV ( 0 . 1 nmol , i . c . v . ) was administered 10 or 20 , but not 30 min prior to the onset of the novel object recognition testing .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [89, 103]}], "task": "NER"}
{"text": "An alanine scan of the angiotensin IV peptide revealed that replacement of the Val ( 1 ) , Ile ( 3 ) , His ( 4 ) , or Phe ( 6 ) residues with Ala attenuated peptide - induced improvements in novel object recognition , whereas Tyr ( 2 ) or Pro ( 5 ) replacement did not significantly affect performance .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [3, 10]}, {"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [23, 37]}, {"entity": "Val", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "Ile", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "His", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "Phe", "entity_type": "Chemical", "pos": [118, 121]}, {"entity": "Ala", "entity_type": "Chemical", "pos": [142, 145]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [226, 229]}, {"entity": "Pro", "entity_type": "Chemical", "pos": [239, 242]}], "task": "NER"}
{"text": "Administration of the angiotensin IV receptor antagonist , divalinal - Ang IV ( 20 nmol , i . c . v . ) , reduced ( but did not abolish ) novel object recognition ; however , this antagonist completely blocked the procognitive effects of angiotensin IV ( 0 . 1 nmol , i . c . v . ) in this task .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [22, 36]}, {"entity": "divalinal - Ang IV", "entity_type": "Chemical", "pos": [59, 77]}, {"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [238, 252]}], "task": "NER"}
{"text": "Rotorod testing demonstrated no locomotor effects with any angiotensin IV or divalinal - Ang IV dose tested .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [59, 73]}, {"entity": "divalinal - Ang IV", "entity_type": "Chemical", "pos": [77, 95]}], "task": "NER"}
{"text": "These data demonstrate that angiotensin IV produces a rapid enhancement of associative learning and memory performance in a mouse model that was dependent on the angiotensin IV receptor .", "entity": [{"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [28, 42]}, {"entity": "angiotensin IV", "entity_type": "Chemical", "pos": [162, 176]}], "task": "NER"}
{"text": "Maternal exposure to airborne particulate matter causes postnatal immunological dysfunction in mice offspring .", "entity": [], "task": "NER"}
{"text": "Evidence suggests that prenatal exposure to air pollution affects the ontogeny and development of the fetal immune system .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to investigate the effect of maternal exposure to airborne particulate matter ( PM ) on immune function in postnatal offspring .", "entity": [], "task": "NER"}
{"text": "Pregnant female ICR mice were intralaryngopharyngeally administered with 30 mu l of phosphate buffered solution ( the control group ) or resuspended PM of Standard Reference Material 1649a at 0 . 09 ( low ) , 0 . 28 ( medium ) , 1 . 85 ( high ) or 6 . 92 ( overdose ) mu g / mu l once every three days from day 0 to 18 of pregnancy ( n = 8 - 10 ) .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [84, 93]}], "task": "NER"}
{"text": "Offspring were sacrificed on postnatal day 30 .", "entity": [], "task": "NER"}
{"text": "Interleukin - 4 and interferon - gamma levels in plasma and splenocytes , splenic lymphocyte proliferation , and expressions of GATA - 3 and T - bet mRNA in the spleen were tested .", "entity": [], "task": "NER"}
{"text": "The spleen and thymus were histopathologically examined .", "entity": [], "task": "NER"}
{"text": "The offspring of the medium , high and overdose PM - exposed dams showed significantly suppressed splenocyte proliferation .", "entity": [], "task": "NER"}
{"text": "Decreased interferon - gamma and increased interleukin - 4 levels in the blood and splenocytes , and lowered T - bet and elevated GATA - 3 mRNA expressions were found in the spleen in the medium , high and overdose groups when compared with the control or low dose group ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Histopathology revealed prominent tissue damage in the spleen and thymus in the overdose group .", "entity": [], "task": "NER"}
{"text": "These results suggest that exposure of pregnant mice to PM modulates the fetal immune system , resulting in postnatal immune dysfunction by exacerbation of Thl / Th2 deviation .", "entity": [], "task": "NER"}
{"text": "This deviation is associated with altered T - bet and GATA - 3 gene expressions .", "entity": [], "task": "NER"}
{"text": "Dexamethasone antagonizes the in vivo myotoxic and inflammatory effects of Bothrops venoms .", "entity": [{"entity": "Dexamethasone", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "In the present work we investigated the toxic activities of two Bothrops snake venoms using in vivo and in vitro experimental protocols in mice and tested the protective effect of dexamethasone ( DEXA ) in different conditions , comparing it with the polyvalent antivenom .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [180, 193]}, {"entity": "DEXA", "entity_type": "Chemical", "pos": [196, 200]}], "task": "NER"}
{"text": "We also expanded the investigations on the antiophidic effect of the Eclipta prostrata ( EP ) crude extract .", "entity": [], "task": "NER"}
{"text": "The administration of Bothrops jararaca and Bothrops jararacussu snake venoms induced muscle damage demonstrated in vivo by the elevation on plasma creatine kinase ( CK ) activity in mice and by the decrease in CK content in the extensor digitorum longus ( EDL ) muscle of these animals , and in vitro by the increase in the rate of CK release from the isolated EDL muscle .", "entity": [{"entity": "creatine", "entity_type": "Chemical", "pos": [148, 156]}], "task": "NER"}
{"text": "We also observed inflammatory response following perimuscular injection of B . jararacussu venom ( 1 . 0 mg / kg ) .", "entity": [], "task": "NER"}
{"text": "Treatment with DEXA ( 1 . 0 mg / kg ) preserved over 50 % of the EDL muscle CK content in vivo when evaluated 24 and 72 h after the injection of B . jararacussu venom in mice , and likewise reduced about 20 % of the edema induced by this venom .", "entity": [{"entity": "DEXA", "entity_type": "Chemical", "pos": [15, 19]}], "task": "NER"}
{"text": "DEXA reduced in 50 % the presence of inflammatory cells and their activity in EDL muscle .", "entity": [{"entity": "DEXA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The EP extract ( 50 mg / kg ) showed similar ability in preventing the induction of edema and the decrease in muscle CK content , and its association with DEXA showed additive effect .", "entity": [{"entity": "DEXA", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "EP reduced over 77 % of the plasma CK activity induced by the B . jararacussu venom .", "entity": [], "task": "NER"}
{"text": "In the in vitro experiments , DEXA was not able to change the rate of CK release from EDL muscles exposed to 25 mu g / mL of B . jararacussu venom , neither to prevent the fall in the amplitude of the indirectly evoked twitch at the phrenic - diaphragm preparation .", "entity": [{"entity": "DEXA", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "EP extract showed otherwise a protective effect on these protocols , reaching up to 100 % of protection when concentrations of 50 . 0 and 100 . 0 mu g / mL were used .", "entity": [], "task": "NER"}
{"text": "Altogether our results show that inflammation is at least in part responsible for the tissue damage induced by Bothrops snake venoms , once the steroidal anti - inflammatory drug dexamethasone was able to decrease the myotoxic effects of these venoms , by reducing the inflammatory response to the venom injection .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [179, 192]}], "task": "NER"}
{"text": "Hypothetical physiological and molecular basis for the effect of acupuncture in the treatment of polycystic ovary syndrome .", "entity": [], "task": "NER"}
{"text": "Clinical and experimental evidence indicates that acupuncture may be a safe alternative or complement in the treatment of endocrine and reproductive function in women with polycystic ovary syndrome ( PCOS ) .", "entity": [], "task": "NER"}
{"text": "This review describes potential etiological factors of PCOS with the aim to support potential mechanism of action of acupuncture to relieve PCOS related symptoms .", "entity": [], "task": "NER"}
{"text": "The theory that increased sympathetic activity contributes to the development and maintenance of PCOS is presented , and that the effects of acupuncture are , at least in part , mediated by modulation of sympathetic outflow .", "entity": [], "task": "NER"}
{"text": "While there are no relevant randomized controlled studies on the use of acupuncture to treat metabolic abnormalities in women with PCOS , a number of experimental studies indicate that acupuncture may improve metabolic dysfunction .", "entity": [], "task": "NER"}
{"text": "For each aspect of PCOS , it is important to pursue new treatment strategies that have fewer negative side effects than drug treatments , as women with PCOS often require prolonged treatment .", "entity": [], "task": "NER"}
{"text": "Analyzing lead absorption by the sycamore tree species in the industrial park of Rasht , Iran .", "entity": [], "task": "NER"}
{"text": "In this study , the subject of heavy metal concentration in soil , rock , sediment , surface water and groundwater , which can be caused by natural or man - posed pollution , was analyzed in the industrial park of Rasht .", "entity": [], "task": "NER"}
{"text": "These concentrations were compared with the standard range of environmental data .", "entity": [], "task": "NER"}
{"text": "Heavy metals are important environmental pollutants that can cause health hazards to humans , plants and microorganisms by entering food chain .", "entity": [], "task": "NER"}
{"text": "This study aimed to investigate the absorption of lead by the leaves of sycamore tree species in the industrial park of Rasht .", "entity": [], "task": "NER"}
{"text": "For this purpose , a sample of 32 sycamore tree species were randomly selected at a specified time , and the concentration of lead were measured using an atomic absorption device .", "entity": [], "task": "NER"}
{"text": "Results showed that the amount of lead absorption by sycamore leaves is remarkable .", "entity": [], "task": "NER"}
{"text": "The highest amount of lead absorption by sycamore leaves was detected at station 1 ( Khazar Steel ) and the lowest amount at station 2 ( control station ) .", "entity": [], "task": "NER"}
{"text": "Transcription forms and remodels supercoiling domains unfolding large - scale chromatin structures .", "entity": [], "task": "NER"}
{"text": "DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication .", "entity": [], "task": "NER"}
{"text": "However , DNA supercoiling at a genomic scale in human cells is uncharacterized .", "entity": [], "task": "NER"}
{"text": "To map supercoiling , we used biotinylated trimethylpsoralen as a DNA structure probe to show that the human genome is organized into supercoiling domains .", "entity": [{"entity": "biotinylated trimethylpsoralen", "entity_type": "Chemical", "pos": [30, 60]}], "task": "NER"}
{"text": "Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC - AT boundaries and CTCF insulator protein - binding sites .", "entity": [], "task": "NER"}
{"text": "Underwound domains are transcriptionally active and enriched in topoisomerase I , ' open ' chromatin fibers and DNase I sites , but they are depleted of topoisomerase II .", "entity": [], "task": "NER"}
{"text": "Furthermore , DNA supercoiling affects additional levels of chromatin compaction as underwound domains are cytologically decondensed , topologically constrained and decompacted by transcription of short RNAs .", "entity": [], "task": "NER"}
{"text": "We suggest that supercoiling domains create a topological environment that facilitates gene activation , providing an evolutionary purpose for clustering genes along chromosomes .", "entity": [], "task": "NER"}
{"text": "Evolution and dynamics of pancreatic cancer progression .", "entity": [], "task": "NER"}
{"text": "Efficient metastasis is believed as the result of multiple genetic , epigenetic and / or post - translational events in the lifetime of a carcinoma .", "entity": [], "task": "NER"}
{"text": "At the genetic level , these events may be categorized into those that occur during carcinogenesis , and those that occur during subclonal evolution .", "entity": [], "task": "NER"}
{"text": "This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs , many features of which can be extrapolated to other solid tumor types .", "entity": [], "task": "NER"}
{"text": "The implications of these findings to personalize genome analyses of an individual patient ' s tumor are also discussed . Oncogene advance online publication , 18 February 2013 ; doi : 10 . 1038 / onc . 2013 . 29 .", "entity": [], "task": "NER"}
{"text": "Hepatic growth hormone resistance after acute injury .", "entity": [], "task": "NER"}
{"text": "Severe injury and infection are often followed by accelerated protein catabolism and acute insulin resistance .", "entity": [], "task": "NER"}
{"text": "This results in several effects that complicate and prolong recovery , including weakness , immobility , impaired wound healing , and organ dysfunction .", "entity": [], "task": "NER"}
{"text": "Recent studies have demonstrated the development of GH resistance during severe inflammation , providing a potential mechanism for the protein loss that follows injury and infection .", "entity": [], "task": "NER"}
{"text": "To understand this GH resistance , we recently developed a murine model of acute injury .", "entity": [], "task": "NER"}
{"text": "Mice were subjected to soft - tissue injury , alone or combined with hemorrhage , and injected iv with GH 30 , 60 , or 90 minutes later .", "entity": [], "task": "NER"}
{"text": "Hepatic GH signaling was measured via Western analysis .", "entity": [], "task": "NER"}
{"text": "GH - induced signal transducer and activator of transcription 5 phosphorylation was decreased immediately after completion of the trauma procedure , and at 30 and 60 minutes , but further decreased by 90 minutes after trauma .", "entity": [], "task": "NER"}
{"text": "Combined trauma and hemorrhage resulted in severely decreased GH - induced signal transducer and activator of transcription 5 phosphorylation compared with trauma alone , and this was true at all time points studied .", "entity": [], "task": "NER"}
{"text": "Western analysis revealed an apparent decrease in the molecular weight of the hepatic GH receptor ( GHR ) after trauma and hemorrhage , but not trauma alone .", "entity": [], "task": "NER"}
{"text": "Additional studies determined that the hemorrhage - induced decrease in receptor size was not due to changes in GHR N - linked glycosylation .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [116, 117]}], "task": "NER"}
{"text": "These results suggest that GH sensitivity is rapidly impaired after acute injury and that trauma combined with hemorrhage results in a more severe form of GH resistance resulting from alteration or inactivation of hepatic GHR .", "entity": [], "task": "NER"}
{"text": "The effects of an environmentally relevant 58 - congener polychlorinated biphenyl ( PCB ) mixture on cardiac development in the chick embryo .", "entity": [{"entity": "polychlorinated biphenyl", "entity_type": "Chemical", "pos": [57, 81]}, {"entity": "PCB", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Chicken ( Gallus domesticus ) embryonic exposure in ovo to a 58 - congener polychlorinated biphenyl ( PCB ) mixture resulted in teratogenic heart defects in chick embryos at critical heart developmental stages Hamburger - Hamilton ( HH ) stages 10 , 16 , and 20 .", "entity": [{"entity": "polychlorinated biphenyl", "entity_type": "Chemical", "pos": [75, 99]}, {"entity": "PCB", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "The 58 - congener mixture contained relative proportions of primary congeners measured in belted sandpiper ( Megaceryle alcyon ) and spotted sandpiper ( Actitis macularia ) eggs collected along the upper Hudson River , New York , USA , and chicken doses were well below observed environmental exposure levels .", "entity": [], "task": "NER"}
{"text": "Embryos were injected with 0 . 08 micro g PCBs / g egg weight and 0 . 50 micro g PCBs / g egg weight ( 0 . 01 and 0 . 064 ng toxic equivalent / g , respectively ) at embryonic day 0 , prior to incubation .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [42, 46]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "Mortality of exposed embryos was increased at all developmental stages , with a marked rise in cardiomyopathies at HH16 and HH20 ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Heart abnormalities occurred across all treatments , including abnormal elongation and expansion of the heart tube at HH10 , improper looping and orientation , indentations in the emerging ventricular wall ( HH16 and HH20 ) , and irregularities in overall heart shape ( HH10 , HH16 , and HH20 ) .", "entity": [], "task": "NER"}
{"text": "Histology was conducted on 2 cardiac proteins critical to embryonic heart development , ventricular myosin heavy chain and titin , to investigate potential mechanistic effects of PCBs on heart development , but no difference was observed in spatiotemporal expression .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [179, 183]}], "task": "NER"}
{"text": "Similarly , cellular apoptosis in the developing heart was not affected by exposure to the PCB mixture .", "entity": [{"entity": "PCB", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "Conversely , cardiomyocyte proliferation rates dramatically declined ( p < 0 . 01 ) at HH16 and HH20 as PCB exposure concentrations increased .", "entity": [{"entity": "PCB", "entity_type": "Chemical", "pos": [104, 107]}], "task": "NER"}
{"text": "Early embryonic cardiomyocyte proliferation contributes to proper formation of the morphology and overall thickness of the ventricular wall .", "entity": [], "task": "NER"}
{"text": "Therefore , in ovo exposure to this 58 - congener PCB mixture at critical stages adversely affects embryonic heart development .", "entity": [{"entity": "PCB", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "Environ Toxicol Chem 2013 ; 32 : 1317 - 1324 .", "entity": [], "task": "NER"}
{"text": "Flock - Based Microfluidics .", "entity": [], "task": "NER"}
{"text": "Flock - based microfluidics are created by depositing hydrophilic microfibers on an adhesive - coated substrate using an electric field .", "entity": [], "task": "NER"}
{"text": "This enables the fabrication of self - powered microfluidics from one or more different kinds of fibers that form 2D and 3D flowpaths , which can wick 40 microliters of liquid per square centimeter .", "entity": [], "task": "NER"}
{"text": "With this approach , large areas of functional wicking materials can be produced at extremely low cost .", "entity": [], "task": "NER"}
{"text": "Hollow Multilayer Microcapsules for pH - / Thermally Responsive Drug Delivery using Aliphatic Poly ( urethane - amine ) as Smart Component .", "entity": [{"entity": "Aliphatic Poly ( urethane - amine )", "entity_type": "Chemical", "pos": [84, 119]}], "task": "NER"}
{"text": "Hollow multilayer microcapsules made of aliphatic poly ( urethane - amine ) ( PUA ) and sodium poly ( styrene sulfonate ) ( PSS ) , templated on PSS - doped CaCO3 particles , are prepared for pH - / thermally responsive drug delivery .", "entity": [{"entity": "aliphatic poly ( urethane - amine )", "entity_type": "Chemical", "pos": [40, 75]}, {"entity": "PUA", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "sodium poly ( styrene sulfonate )", "entity_type": "Chemical", "pos": [88, 121]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [145, 148]}, {"entity": "CaCO3", "entity_type": "Chemical", "pos": [157, 162]}], "task": "NER"}
{"text": "The electrostatic interaction and hydrogen bonding under weak - acid conditions between aliphatic PUA and PSS contribute to the formation of multilayer microcapsules .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [34, 42]}, {"entity": "PUA", "entity_type": "Chemical", "pos": [98, 101]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "Scanning electron microscopy ( SEM ) results demonstrate an obvious variation of the hollow multilayer microcapsules in response to changes in temperature and pH value .", "entity": [], "task": "NER"}
{"text": "Drug - release behaviors using DOX as a model drug demonstrate that the drug release increases on decreasing the pH value because of the interaction weakness between aliphatic PUA and PSS in acidic conditions .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "PUA", "entity_type": "Chemical", "pos": [176, 179]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [184, 187]}], "task": "NER"}
{"text": "Moreover , the drug release is higher at 55 degrees C than that at 37 degrees C for the sake of the shrinkage of aliphatic PUA above its lower critical solution temperature ( LCST ) .", "entity": [{"entity": "PUA", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "BaSnO3 perovskite nanoparticles for high efficiency dye - sensitized solar cells .", "entity": [{"entity": "BaSnO3", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "perovskite", "entity_type": "Chemical", "pos": [7, 17]}], "task": "NER"}
{"text": "The synthesis of highly crystalline perovskite BaSnO3 nanoparticles for use as photoanode materials in dye - sensitized solar cells ( DSSCs ) is reported , and the photovoltaic properties of DSSCs based on BaSnO3 nanoparticles ( BaSnO3 cells ) are demonstrated .", "entity": [{"entity": "perovskite", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "BaSnO3", "entity_type": "Chemical", "pos": [47, 53]}, {"entity": "BaSnO3", "entity_type": "Chemical", "pos": [206, 212]}, {"entity": "BaSnO3", "entity_type": "Chemical", "pos": [229, 235]}], "task": "NER"}
{"text": "The resulting DSSCs exhibit remarkably rapid charge collection and a DSSC fabricated with a BaSnO3 film thickness of 43 micro m leads to a high energy conversion efficiency of 5 . 2 % , which is one of the highest reported for ternary oxide - based DSSCs .", "entity": [{"entity": "BaSnO3", "entity_type": "Chemical", "pos": [92, 98]}, {"entity": "ternary oxide", "entity_type": "Chemical", "pos": [227, 240]}], "task": "NER"}
{"text": "More importantly , the BaSnO3 cells show superior charge collection in nanoparticle films compared to TiO2 cells and could offer a breakthrough in the efficiencies of DSSCs .", "entity": [{"entity": "BaSnO3", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [102, 106]}], "task": "NER"}
{"text": "Incorporating Graphene Oxide and Gold Nanoclusters : A Synergistic Catalyst with Surprisingly High Peroxidase - Like Activity Over a Broad pH Range and its Application for Cancer Cell Detection .", "entity": [{"entity": "Graphene Oxide", "entity_type": "Chemical", "pos": [14, 28]}], "task": "NER"}
{"text": "A synergistic graphene oxide - gold nanocluster ( GO - AuNC ) hybrid has been constructed as an enzyme mimic that is able to show high catalytic activity over a broad pH range , especially at neutral pH .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [14, 28]}], "task": "NER"}
{"text": "Importantly , the target - functionalized hybrid has been applied as a robust nanoprobe for selective , quantitative , and fast colorimetric detection of cancer cells .", "entity": [], "task": "NER"}
{"text": "Synthesis of heterocyclic terpenoids by promiscuous squalene - hopene cyclases .", "entity": [{"entity": "heterocyclic terpenoids", "entity_type": "Chemical", "pos": [13, 36]}, {"entity": "squalene", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "hopene", "entity_type": "Chemical", "pos": [63, 69]}], "task": "NER"}
{"text": "PROMISCUOUS ENZYMES : The substrate promiscuity of squalene - hopene cyclases has been explored and applied in the enzyme - catalyzed synthesis of heterocyclic terpenoids .", "entity": [{"entity": "squalene", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "hopene", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "heterocyclic terpenoids", "entity_type": "Chemical", "pos": [147, 170]}], "task": "NER"}
{"text": "Features of this work include cyclization reactions without pyrophosphate activation , and stereospecific ring closure of substrates of varying chain length and terminal nucleophile .", "entity": [{"entity": "pyrophosphate", "entity_type": "Chemical", "pos": [60, 73]}], "task": "NER"}
{"text": "This provides a biocatalytic alternative to traditional chemical catalysts .", "entity": [], "task": "NER"}
{"text": "Engineered nanomaterials in water and soils : A risk quantification based on probabilistic exposure and effect modeling .", "entity": [], "task": "NER"}
{"text": "The production and use of engineered nanomaterials ( ENMs ) are increasing rapidly , and therefore , the need to assess their environmental exposure and associated risks has become increasingly important .", "entity": [], "task": "NER"}
{"text": "Only a handful of studies have quantified the release and environmental concentrations of ENMs , but much work has been done to investigate the effects of these materials on organisms .", "entity": [], "task": "NER"}
{"text": "The aim of the present study was to quantify probabilistically the environmental risks of ENMs , producing species sensitivity distributions that were then compared with probability distributions of predicted environmental concentrations .", "entity": [], "task": "NER"}
{"text": "Five nanomaterials ( nano - Ag , nano - TiO2 , nano - ZnO , carbon nanotubes [ CNTs ] , and fullerenes ) and 4 environmental compartments ( surface water , sewage treatment plant effluents , soils , and sludge - treated soils ) were considered .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [28, 30]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [40, 44]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "fullerenes", "entity_type": "Chemical", "pos": [92, 102]}], "task": "NER"}
{"text": "From 60 ecotoxicological studies , the authors extracted 112 single values to work with ( 25 values in 13 studies for nano - Ag , 17 values in 10 studies for CNTs , 7 values in 7 studies for fullerenes , 34 values in 23 studies for nano - TiO2 , and 29 values in 17 studies for nano - ZnO ) .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [125, 127]}, {"entity": "fullerenes", "entity_type": "Chemical", "pos": [191, 201]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [239, 243]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [285, 288]}], "task": "NER"}
{"text": "The results indicate there is only a marginal risk for these metal - based nanomaterials in surface water ( 0 . 7 % risk for nano - Ag and < 0 . 1 % for nano - TiO2 ) and some risk in sewage treatment plant effluents ( nano - Ag 39 . 7 % , nano - TiO2 18 . 7 % , and nano - ZnO 1 . 1 % ) .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [132, 134]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [160, 164]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [226, 228]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [247, 251]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [274, 277]}], "task": "NER"}
{"text": "Apart from a marginal value of < 0 . 1 % for nano - TiO2 in sludge - treated soils , no risk from the other evaluated ENMs in terrestrial compartments is currently predicted .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [52, 56]}], "task": "NER"}
{"text": "The discussion of the results considers the influence of the effects of different forms of 1 ENM ( coating , agglomeration state , and mineralogy ) , the test conditions ( dissolution and agglomeration ) , and transformation reactions .", "entity": [], "task": "NER"}
{"text": "Environ Toxicol Chem 2013 ; 32 : 1278 - 1287 .", "entity": [], "task": "NER"}
{"text": "The Prevalence of Meeting A1C , Blood Pressure , and LDL Goals Among People With Diabetes , 1988 - 2010 .", "entity": [], "task": "NER"}
{"text": "OBJECTIVETo determine the prevalence of people with diabetes who meet hemoglobin A ( 1c ) ( A1C ) , blood pressure ( BP ) , and LDL cholesterol ( ABC ) recommendations , and their current statin use , factors associated with goal achievement , and changes in the proportion achieving goals between 1988 and 2010 . RESEARCH AND DESIGN METHODSData were cross - sectional from the National Health and Nutrition Examination Surveys ( NHANES ) from 1988 - 1994 , 1999 - 2002 , 2003 - 2006 , and 2007 - 2010 .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "Participants were 4 , 926 adults aged >= 20 years who self - reported a previous diagnosis of diabetes and completed the household interview and physical examination ( n = 1 , 558 for valid LDL levels ) .", "entity": [], "task": "NER"}
{"text": "Main outcome measures were A1C , BP , and LDL cholesterol , in accordance with the American Diabetes Association recommendations , and current use of statins . RESULTSIn 2007 - 2010 , 52 . 5 % of people with diabetes achieved A1C < 7 . 0 % ( < 53 mmol / mol ) , 51 . 1 % achieved BP < 130 / 80 mmHg , 56 . 2 % achieved LDL < 100 mg / dL , and 18 . 8 % achieved all three ABCs .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [46, 57]}], "task": "NER"}
{"text": "These levels of control were significant improvements from 1988 to 1994 ( all P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Statin use significantly increased between 1988 - 1994 ( 4 . 2 % ) and 2007 - 2010 ( 51 . 4 % , P < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "Compared with non - Hispanic whites , Mexican Americans were less likely to meet A1C and LDL goals ( P < 0 . 03 ) , and non - Hispanic blacks were less likely to meet BP and LDL goals ( P < 0 . 02 ) .", "entity": [], "task": "NER"}
{"text": "Compared with non - Hispanic blacks , Mexican Americans were less likely to meet A1C goals ( P < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "Younger individuals were less likely to meet A1C and LDL goals . CONCLUSIONSDespite significant improvement during the past decade , achieving the ABC goals remains suboptimal among adults with diabetes , particularly in some minority groups .", "entity": [], "task": "NER"}
{"text": "Substantial opportunity exists to further improve diabetes control and , thus , to reduce diabetes - related morbidity and mortality .", "entity": [], "task": "NER"}
{"text": "Simultaneous determination of evodiamine and evodine in Beagle dog plasma using liquid chromatography tandem mass spectrometry .", "entity": [{"entity": "evodiamine", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "A sensitive , rapid , and specific liquid chromatography / tandem mass spectrometry assay has been established and validated for the quantitation of evodiamine and evodine in Beagle dog plasma .", "entity": [{"entity": "evodiamine", "entity_type": "Chemical", "pos": [149, 159]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [164, 171]}], "task": "NER"}
{"text": "Plasma samples of 0 . 2 ml were processed by liquid - liquid extraction with n - hexane / ethyl acetate ( 2 : 1 , v / v ) .", "entity": [{"entity": "n - hexane", "entity_type": "Chemical", "pos": [77, 87]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [90, 103]}], "task": "NER"}
{"text": "Chromatographic separations were done on a Symmetry C ( 18 ) column ( 100 mm x 4 . 6 mm , ID , 5 mu m ) at 35 degrees C with a linear gradient of methanol and 20 mM ammonium formate containing 0 . 2 % formic acid .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [146, 154]}, {"entity": "ammonium formate", "entity_type": "Chemical", "pos": [165, 181]}, {"entity": "formic acid", "entity_type": "Chemical", "pos": [201, 212]}], "task": "NER"}
{"text": "Evodiamine , evodine , and glibenclamide [ internal standard ( IS ) ] were ionized with an electrospray ionization source operated in positive ion mode .", "entity": [{"entity": "Evodiamine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "glibenclamide", "entity_type": "Chemical", "pos": [27, 40]}], "task": "NER"}
{"text": "The MS / MS transitions were m / z 304 . 1 --> 161 . 1 for evodiamine , m / z 471 . 2 --> 425 . 1 for evodine , and m / z 494 . 1 --> 369 . 1 for IS .", "entity": [{"entity": "evodiamine", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "Calibration curves were linear over the concentration range of 0 . 1 - 100 ng / ml for evodiamine and 0 . 5 - 500 ng / ml for evodine .", "entity": [{"entity": "evodiamine", "entity_type": "Chemical", "pos": [87, 97]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "The mean extraction recoveries were 88 . 10 +/- 3 . 21 % for evodiamine and 81 . 24 +/- 4 . 07 % for evodine .", "entity": [{"entity": "evodiamine", "entity_type": "Chemical", "pos": [61, 71]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "The intra - and inter - day precisions were less than 11 . 10 % and 12 . 81 % , and the accuracy was within +/- 11 . 76 % for both analytes .", "entity": [], "task": "NER"}
{"text": "Evodiamine and evodine were stable during storage and analytical periods .", "entity": [{"entity": "Evodiamine", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [15, 22]}], "task": "NER"}
{"text": "The validated method has been successfully applied to a pharmacokinetic study of evodiamine and evodine in beagle dogs after oral administration .", "entity": [{"entity": "evodiamine", "entity_type": "Chemical", "pos": [81, 91]}, {"entity": "evodine", "entity_type": "Chemical", "pos": [96, 103]}], "task": "NER"}
{"text": "New alkaloid from Streptomyces koyangensis residing in Odontotermes formosanus .", "entity": [], "task": "NER"}
{"text": "A new alkaloid was isolated from the ethyl acetate extract of the culture of a termite - associated Streptomyces koyangensis BY - 4 .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [37, 50]}], "task": "NER"}
{"text": "The structure of 1 was elucidated by using MS , NMR , electronic circular dichroism data , and computational approaches .", "entity": [], "task": "NER"}
{"text": "Compound 1 showed weak antimicrobial activities against a panel of test microbes .", "entity": [], "task": "NER"}
{"text": "Two new triterpenoids from the fungus Perenniporia maackiae .", "entity": [{"entity": "triterpenoids", "entity_type": "Chemical", "pos": [8, 21]}], "task": "NER"}
{"text": "Two new triterpenoids , 3 beta - ( 2 - methoxy - oxalyloxy ) - 24 - methylene - lanost - 8 - en - 21 - oic acid ( 1 ) and 3 beta - ( 2 - methoxy - oxalyloxy ) - 15 alpha - hydroxy - 24 - methylene - lanost - 8 - en - 21 - oic acid ( 2 ) , were isolated from cultures of the fungus Perenniporia maackiae , together with two previously known triterpenoids ( 3 and 4 ) .", "entity": [{"entity": "triterpenoids", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "3 beta - ( 2 - methoxy - oxalyloxy ) - 24 - methylene - lanost - 8 - en - 21 - oic acid", "entity_type": "Chemical", "pos": [24, 111]}, {"entity": "3 beta - ( 2 - methoxy - oxalyloxy ) - 15 alpha - hydroxy - 24 - methylene - lanost - 8 - en - 21 - oic acid", "entity_type": "Chemical", "pos": [122, 230]}, {"entity": "triterpenoids", "entity_type": "Chemical", "pos": [340, 353]}], "task": "NER"}
{"text": "Their structures were determined by spectroscopic methods , including 1D and 2D NMR , and MS analyses .", "entity": [], "task": "NER"}
{"text": "All compounds were evaluated for their cytotoxic activities on five tumor cell lines .", "entity": [], "task": "NER"}
{"text": "Three new norlignans from Glechoma longituba .", "entity": [{"entity": "norlignans", "entity_type": "Chemical", "pos": [10, 20]}], "task": "NER"}
{"text": "Three new norlignans , glechomols A - C ( 1 - 3 , respectively ) , together with a known compound , 4 - ethylcatechol ( 4 ) , were isolated from the ethyl acetate extract of Glechoma longituba ( NaKai ) Kupr .", "entity": [{"entity": "norlignans", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "glechomols A - C", "entity_type": "Chemical", "pos": [23, 39]}, {"entity": "4 - ethylcatechol", "entity_type": "Chemical", "pos": [100, 117]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [149, 162]}], "task": "NER"}
{"text": "Their structures were elucidated by the detailed analysis of 1D and 2D NMR and HR - MS data .", "entity": [], "task": "NER"}
{"text": "Glechomols A - C were the first norlignans reported from genus Glechoma , and compound 4 was also isolated from genus Glechoma for the first time .", "entity": [{"entity": "Glechomols A - C", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "norlignans", "entity_type": "Chemical", "pos": [32, 42]}], "task": "NER"}
{"text": "Intracellular antioxidant assays showed that compounds 1 - 4 displayed significant protective effects on H ( 2 ) O ( 2 ) - induced cardiac cell injury .", "entity": [{"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [105, 120]}], "task": "NER"}
{"text": "Heterogeneous vapor bubble nucleation on a rough surface .", "entity": [], "task": "NER"}
{"text": "Vapor bubble nucleation on a microrough surface wetted by a volatile , incompressible liquid has been analyzed .", "entity": [], "task": "NER"}
{"text": "The work of formation of a critical nucleus in a surface cavity has been evaluated .", "entity": [], "task": "NER"}
{"text": "Concave sites of a surface with negative curvature can decrease the height of the activation barrier for the formation of a critical nucleus .", "entity": [], "task": "NER"}
{"text": "The average density of the nucleation sites has been evaluated for a surface whose ( small ) deviation from a plane is specified by a Gaussian random function .", "entity": [], "task": "NER"}
{"text": "Charge screening between anionic and cationic surfactants in ionic liquids .", "entity": [], "task": "NER"}
{"text": "The aggregation and interfacial behavior of mixtures of anionic ( sodium dodecylsulfate , SDS ) and cationic ( dodecylammonium bromide , DTAB ) surfactants were investigated .", "entity": [{"entity": "sodium dodecylsulfate", "entity_type": "Chemical", "pos": [66, 87]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [90, 93]}, {"entity": "dodecylammonium bromide", "entity_type": "Chemical", "pos": [111, 134]}, {"entity": "DTAB", "entity_type": "Chemical", "pos": [137, 141]}], "task": "NER"}
{"text": "A room - temperature ionic liquid ( IL ) was explored as a solvent for the SDS / DTAB system and compared to water .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "DTAB", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "The critical micelle concentration ( cmc ) and composition in mixed micelles were determined for both solvents .", "entity": [], "task": "NER"}
{"text": "Our experiments showed nearly ideal mixing of SDS / DTAB over the entire composition range and suggest that charge screening is prominent in ILs .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [46, 49]}, {"entity": "DTAB", "entity_type": "Chemical", "pos": [52, 56]}], "task": "NER"}
{"text": "This behavior is in sharp contrast to the strong electrostatic attraction and a multiphase composition gap in water .", "entity": [], "task": "NER"}
{"text": "Two models by Clint and Rubingh , which describe ideal and nonideal micellar behavior , respectively , are discussed on the basis of our results .", "entity": [], "task": "NER"}
{"text": "According to Rubingh ' s model , the composition of mixed micelles is gradually changing with the bulk composition in ILs but tends to be a 1 : 1 ratio in water .", "entity": [], "task": "NER"}
{"text": "The results here are further support of the strong charge screening in ionic liquids .", "entity": [], "task": "NER"}
{"text": "Synthesis and characterization of hybrid hyaluronic Acid - gelatin hydrogels .", "entity": [], "task": "NER"}
{"text": "Biomimetic hybrid hydrogels have generated broad interest in tissue engineering and regenerative medicine .", "entity": [], "task": "NER"}
{"text": "Hyaluronic acid ( HA ) and gelatin ( hydrolyzed collagen ) are naturally derived polymers and biodegradable under physiological conditions .", "entity": [], "task": "NER"}
{"text": "Moreover , collagen and HA are major components of the extracellular matrix ( ECM ) in most of the tissues ( e . g . , cardiovascular , cartilage , neural ) .", "entity": [], "task": "NER"}
{"text": "When used as a hybrid material , HA - gelatin hydrogels may enable mimicking the ECM of native tissues .", "entity": [], "task": "NER"}
{"text": "Although HA - gelatin hybrid hydrogels are promising biomimetic substrates , their material properties have not been thoroughly characterized in the literature .", "entity": [], "task": "NER"}
{"text": "Herein , we generated hybrid hydrogels with tunable physical and biological properties by using different concentrations of HA and gelatin .", "entity": [], "task": "NER"}
{"text": "The physical properties of the fabricated hydrogels including swelling ratio , degradation , and mechanical properties were investigated .", "entity": [], "task": "NER"}
{"text": "In addition , in vitro cellular responses in both two and three - dimensional culture conditions were assessed .", "entity": [], "task": "NER"}
{"text": "It was found that the addition of gelatin methacrylate ( GelMA ) into HA methacrylate ( HAMA ) promoted cell spreading in the hybrid hydogels .", "entity": [{"entity": "methacrylate", "entity_type": "Chemical", "pos": [42, 54]}, {"entity": "methacrylate", "entity_type": "Chemical", "pos": [73, 85]}], "task": "NER"}
{"text": "Moreover , the hybrid hydrogels showed significantly improved mechanical properties compared to their single component analogs .", "entity": [], "task": "NER"}
{"text": "The HAMA - GelMA hydrogels exhibited remarkable tunability behavior and may be useful for cardiovascular tissue engineering applications .", "entity": [], "task": "NER"}
{"text": "Laponite nanodisks as an efficient platform for Doxorubicin delivery to cancer cells .", "entity": [{"entity": "Laponite", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [48, 59]}], "task": "NER"}
{"text": "We report a facile approach to using laponite ( LAP ) nanodisks as a platform for efficient delivery of doxorubicin ( DOX ) to cancer cells .", "entity": [{"entity": "laponite", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "LAP", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [104, 115]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "In this study , DOX was encapsulated into the interlayer space of LAP through an ionic exchange process with an exceptionally high loading efficiency of 98 . 3 +/- 0 . 77 % .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "LAP", "entity_type": "Chemical", "pos": [66, 69]}], "task": "NER"}
{"text": "The successful DOX loading was extensively characterized via different methods .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [15, 18]}], "task": "NER"}
{"text": "In vitro drug release study shows that the release of DOX from LAP / DOX nanodisks is pH - dependent , and DOX is released at a quicker rate at acidic pH condition ( pH = 5 . 4 ) than at physiological pH condition .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "LAP", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "Importantly , cell viability assay results reveal that LAP / DOX nanodisks display a much higher therapeutic efficacy in inhibiting the growth of a model cancer cell line ( human epithelial carcinoma cells , KB cells ) than free DOX drug at the same DOX concentration .", "entity": [{"entity": "LAP", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [61, 64]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [229, 232]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [250, 253]}], "task": "NER"}
{"text": "The enhanced antitumor efficacy is primarily due to the much more cellular uptake of the LAP / DOX nanodisks than that of free DOX , which has been confirmed by confocal laser scanning microscope and flow cytometry analysis .", "entity": [{"entity": "LAP", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [127, 130]}], "task": "NER"}
{"text": "The high DOX payload and enhanced antitumor efficacy render LAP nanodisks as a robust carrier system for different biomedical applications .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [9, 12]}, {"entity": "LAP", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "Danshen mediates through estrogen receptors to activate Akt and inhibit apoptosis effect of Leu27IGF - II - induced IGF - II receptor signaling activation in cardiomyoblasts .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "Post - menopausal women show dramatically increased cardiovascular disease morbidity ( CVD ) .", "entity": [], "task": "NER"}
{"text": "Danshen is used widely in China for the treatment of cardiovascular disorders , including coronary heart disease .", "entity": [], "task": "NER"}
{"text": "Danshen possesses lipid - soluble biologically active components with a structure similar to 17 beta - estrodiol ( E2 ) .", "entity": [{"entity": "17 beta - estrodiol", "entity_type": "Chemical", "pos": [93, 112]}], "task": "NER"}
{"text": "This study assesses whether the cardio - protection exerted by Danshen is mediated through the ERs within H9c2 cardiomyoblast cells .", "entity": [], "task": "NER"}
{"text": "Cardiomyoblast cells pretreated with Fulvestrant ( ICI 182 , 780 ) , an estrogen receptor antagonist was applied to investigate the estrogenic activity of Danshen .", "entity": [{"entity": "Fulvestrant", "entity_type": "Chemical", "pos": [37, 48]}, {"entity": "ICI 182 , 780", "entity_type": "Chemical", "pos": [51, 64]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "The Danshen extract preventive effects on Leu27IGF - II - induced IGF - IIR signaling activator and H9c2 cell apoptosis were identified using TUNEL assay , JC - 1 staining and Western blot assay .", "entity": [], "task": "NER"}
{"text": "We found that Danshen extract treatments significantly enhanced phosphorylated Akt through estrogen receptor activation to inhibit Leu27IGF - II - induced calcineurin activation and block H9c2 cell apoptosis .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "Danshen extracts suppressed the IGF - IIR signaling proteins , pro - apoptotic proteins and reversed the mitochondrial membrane instability induced by Leu27IGF - II .", "entity": [], "task": "NER"}
{"text": "However , the cardioprotective properties of Danshen to inhibit Leu27IGF - II - induced cell apoptosis and promote cell survival were attenuated by applying ICI , which suggests that the Danshen cardioprotective effect is mediated through estrogen receptors .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [239, 247]}], "task": "NER"}
{"text": "All our data indicated that Danshen exerts strong estrogenic activity which can be considered a novel selective estrogen receptor modulator ( SERM ) against IGF2R signaling that blocks cardiac apoptosis .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Approach to distribution and accumulation of dibutyl phthalate in rats by immunoassay .", "entity": [{"entity": "dibutyl phthalate", "entity_type": "Chemical", "pos": [45, 62]}], "task": "NER"}
{"text": "Dibutyl phthalate ( DBP ) is mainly taken up by the general population from food intake .", "entity": [{"entity": "Dibutyl phthalate", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [20, 23]}], "task": "NER"}
{"text": "To estimate intake of phthalates , determining distribution and accumulation of DBP in biological materials was a critical need .", "entity": [{"entity": "phthalates", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [80, 83]}], "task": "NER"}
{"text": "In this work , we set up two novel approaches with a monoclonal antibody specific to DBP to determine the distribution and accumulation of DBP in vivo .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [85, 88]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "The contents of DBP in liver , kidney , stomach and testes were detected by immunofluorescence assays and indirect competitive ELISA .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [16, 19]}], "task": "NER"}
{"text": "This data give directly evidence that indicates the distribution and accumulation of DBP in vivo .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [85, 88]}], "task": "NER"}
{"text": "Double - label immunofluorescence assay provides with a visual approach to determination of the distribution and accumulation of DBP .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "It indicated that DBP accumulated in subcutaneous tissue such as sweat gland , hair follicle .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [18, 21]}], "task": "NER"}
{"text": "Both of immunofluorescence assay and ELISA can be used to detect the content of DBP in biological materials .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [80, 83]}], "task": "NER"}
{"text": "Our assays showed that DBP accumulated in viscera being rich in fat , such as liver , kidney and could overcome physiological barriers to penetrate testes .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "The date suggested that the accumulations of DBP exposed through dermal route were less than that of oral route and most of DBP was metabolized in 2 or 3days .", "entity": [{"entity": "DBP", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "DBP", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "Integrating clinical pharmacology concepts in individualized therapy with tyrosine kinase inhibitors .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "Tyrosine kinases have emerged as important tumor targets for the design of potent and selective inhibitors .", "entity": [{"entity": "Tyrosine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Eighteen of these tyrosine kinase inhibitors ( TKIs ) have already been approved for the treatment of diseases that were previously essentially resistant to standard chemotherapy .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "Major efforts are ongoing that focus on the development of companion diagnostics for investigational and approved TKIs , as well as on integrating clinical pharmacology principles in clinical practice to decrease toxicity and improve efficacy .", "entity": [], "task": "NER"}
{"text": "The state of clinical pharmacology today .", "entity": [], "task": "NER"}
{"text": "It has been more than 40 years since a major position paper on clinical pharmacology was published by the World Health Organization ( WHO ) .", "entity": [], "task": "NER"}
{"text": "A recent publication , Clinical Pharmacology in Health Care , Teaching , and Research , provides a current vision of the discipline suitable for the twenty - first century .", "entity": [], "task": "NER"}
{"text": "Uptake , retention and internalization of quantum dots in Daphnia is influenced by particle surface functionalization .", "entity": [], "task": "NER"}
{"text": "Nanomaterials are a diverse group of compounds whose inevitable release into the environment warrants study of the fundamental processes that govern the ingestion , uptake and accumulation in aquatic organisms .", "entity": [], "task": "NER"}
{"text": "Nanomaterials have the ability to transfer to higher trophic levels in aquatic ecosystems , and recent evidence suggests that the surface chemistry of both the nanoparticle and biological membrane can influence uptake kinetics .", "entity": [], "task": "NER"}
{"text": "Therefore , our study investigates the effect of surface functionalization on uptake , internalization and depuration in Daphnia spp .", "entity": [], "task": "NER"}
{"text": "Uncharged ( polyethylene glycol ; PEG ) , positively charged ( amino - terminated : NH2 ) and negatively charged ( carboxyl - modified ; COOH ) cadmium selenide / zinc sulfide quantum dots were used to monitor ingestion , uptake and depuration of nanometals in Daphnia magna and Ceriodaphnia dubia over 24h of exposure .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [12, 31]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "amino", "entity_type": "Chemical", "pos": [63, 68]}, {"entity": "NH2", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [115, 123]}, {"entity": "COOH", "entity_type": "Chemical", "pos": [137, 141]}, {"entity": "cadmium selenide", "entity_type": "Chemical", "pos": [144, 160]}, {"entity": "zinc sulfide", "entity_type": "Chemical", "pos": [163, 175]}], "task": "NER"}
{"text": "These studies demonstrated that particles with higher negative charge ( COOH quantum dots ) were taken up to a greater extent by Daphnia ( 259 . 17 +/- 17 . 70 RFU / 20 Daphnia ) than either the NH2 ( 150 . 01 +/- 18 . 91 ) or PEG quantum dots ( 95 . 17 +/- 9 . 78 ) , however this is likely related to the functional groups attached to the nanoparticles as there were no real differences in zeta potential .", "entity": [{"entity": "COOH", "entity_type": "Chemical", "pos": [72, 76]}, {"entity": "NH2", "entity_type": "Chemical", "pos": [195, 198]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [227, 230]}], "task": "NER"}
{"text": "Whole body fluorescence associates well with fluorescent microscopic images obtained at the 24h timepoint .", "entity": [], "task": "NER"}
{"text": "Confocal and electron microscopic analysis clearly demonstrated that all three types of quantum dots could cross the intestinal epithelial barrier and be translocated to other cells .", "entity": [], "task": "NER"}
{"text": "Upon cessation of exposure , elimination of all three materials was biphasic with rapid initial clearance that likely represents elimination of material remaining in the GI tract followed by a much slower elimination phase that likely represents elimination of internalized material .", "entity": [], "task": "NER"}
{"text": "These studies demonstrate that daphnids can take up intact nanomaterial from the water column and that this uptake is strongly influenced by particle surface functionalization .", "entity": [], "task": "NER"}
{"text": "In addition , the usefulness of using quantum dots as a proxy for other nanometals ( no acute toxicity , clear visualization in electron microscopy ) , in conjunction with several different imaging techniques in assessing uptake and accumulation of nanoparticles in daphnids was demonstrated .", "entity": [], "task": "NER"}
{"text": "A kavalactone derivative inhibits lipopolysaccharide - stimulated iNOS induction and NO production through activation of Nrf2 signaling in BV2 microglial cells .", "entity": [{"entity": "kavalactone", "entity_type": "Chemical", "pos": [2, 13]}, {"entity": "NO", "entity_type": "Chemical", "pos": [67, 69]}], "task": "NER"}
{"text": "Neuroinflammation and oxidative stress are involved in the pathogenesis of neurodegenerative diseases such as Alzheimer ' s diseases and Parkinson ' s disease .", "entity": [], "task": "NER"}
{"text": "Naturally derived kavalactones isolated from Piper methysticum ( Piperaceae ) have been shown to exhibit neuroprotective effects .", "entity": [{"entity": "kavalactones", "entity_type": "Chemical", "pos": [18, 30]}], "task": "NER"}
{"text": "We have previously reported that a chemically synthesized kavalactone derivative , 2 ' , 6 ' - dichloro - 5 - methoxymethyl - 5 , 6 - dehydrokawain ( compound 1 ) protects against oxidative stress - induced neuronal cell death through activation of Nrf2 signaling .", "entity": [{"entity": "kavalactone", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "2 ' , 6 ' - dichloro - 5 - methoxymethyl - 5 , 6 - dehydrokawain", "entity_type": "Chemical", "pos": [83, 147]}], "task": "NER"}
{"text": "In the present study , we examined the effect of compound 1 on neuroinflammation .", "entity": [], "task": "NER"}
{"text": "In BV2 microglial cells , compound 1 strongly inhibited LPS - stimulated iNOS induction and NO production , but did not affect LPS - stimulated induction of COX2 .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [74, 76]}], "task": "NER"}
{"text": "At 6h after LPS challenge , when iNOS induction was not clearly seen , treatment with LPS or compound 1 alone increased expression of heme oxygenase 1 ( HO - 1 ) whose transcription is regulated by Nrf2 .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [134, 138]}], "task": "NER"}
{"text": "When treated with both , compound 1 enhanced LPS - stimulated HO - 1 induction , which was more evident at 24h after LPS treatment .", "entity": [], "task": "NER"}
{"text": "Furthermore , LPS - stimulated activation of Nrf2 signaling and nuclear translocation of Nrf2 were potentiated by compound 1 .", "entity": [], "task": "NER"}
{"text": "The mechanism by which compound 1 activated Nrf2 signaling was supposed to be a covalent modification of the sulfhydryl groups of Keap1 by an alpha , beta - unsaturated carbonyl group present in the compound 1 .", "entity": [{"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [109, 119]}, {"entity": "alpha , beta - unsaturated carbonyl", "entity_type": "Chemical", "pos": [142, 177]}], "task": "NER"}
{"text": "Treatment with hemin , a HO - 1 inducer , and with [ Ru ( CO ) 3Cl2 ] 2 , a CO donor , decreased LPS - stimulated iNOS induction and NO production .", "entity": [{"entity": "hemin", "entity_type": "Chemical", "pos": [15, 20]}, {"entity": "[ Ru ( CO ) 3Cl2 ] 2", "entity_type": "Chemical", "pos": [51, 71]}, {"entity": "CO", "entity_type": "Chemical", "pos": [76, 78]}, {"entity": "NO", "entity_type": "Chemical", "pos": [115, 117]}], "task": "NER"}
{"text": "In contrast , siRNA - mediated knockdown of HO - 1 expression reduced the inhibitory effect of compound 1 on LPS - stimulated iNOS induction and NO production .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [127, 129]}], "task": "NER"}
{"text": "The compound 1 inhibited LPS - stimulated ERK phosphorylation after LPS treatment .", "entity": [], "task": "NER"}
{"text": "Finally , compound 1 suppressed LPS / IFN - gamma - stimulated NO production in primary microglial cells .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [63, 65]}], "task": "NER"}
{"text": "These results suggest that compound 1 is capable of inhibiting LPS - stimulated iNOS induction and NO production via activation of Nrf2 signaling and HO - 1 induction in microglial cells .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [81, 83]}], "task": "NER"}
{"text": "Taken together , compound 1 has a potential to reduce neuroinflammation as well as oxidative stress in neurodegenerative diseases through activation of Nrf2 signaling .", "entity": [], "task": "NER"}
{"text": "The protein corona mediates the impact of nanomaterials and slows amyloid beta fibrillation .", "entity": [], "task": "NER"}
{"text": "Put your coat on : It is well recognized that the surfaces of nanomaterials in biological media are covered by various biomolecules ( e . g . , proteins ) .", "entity": [], "task": "NER"}
{"text": "A ) The protein corona creates a shell over different nanomaterials , regardless of their physicochemical properties ( e . g . , composition and shape ) , resulting in reduced levels of amyloid beta fibril formation .", "entity": [], "task": "NER"}
{"text": "B ) Pristine nanomaterials might have acceleratory effects on the fibrillation of amyloid beta .", "entity": [], "task": "NER"}
{"text": "Effects of phosphate buffer in parenteral drugs on particle formation from glass vials .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [11, 20]}], "task": "NER"}
{"text": "The characteristics of inorganic particles generated in glass vials filled with phosphate buffer solutions were investigated .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [80, 89]}], "task": "NER"}
{"text": "During storage , particles were visually detected in the phosphate buffer solution in particular glass vials which pass compendial tests of containers for injectable drugs .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "These particles were considered to be different from ordinal glass delamination , which has been reported in a number of papers because the particles were mainly composed of Al , P and O , but not Si .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [174, 176]}, {"entity": "P", "entity_type": "Chemical", "pos": [179, 180]}, {"entity": "O", "entity_type": "Chemical", "pos": [185, 186]}, {"entity": "Si", "entity_type": "Chemical", "pos": [197, 199]}], "task": "NER"}
{"text": "The formation of the particles accelerated at higher storage temperatures .", "entity": [], "task": "NER"}
{"text": "Among the surface treatments tested for the glass vials , sulfur treatment showed a protective effect on the particle formation in the vials , whereas the SiO2 coating did not have any protective effects .", "entity": [{"entity": "sulfur", "entity_type": "Chemical", "pos": [58, 64]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "It was found that the elution ratio of Al and Si in the solution stored in the glass vials after the heating was similar to the ratio of Al and Si in borosilicate glass .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "Si", "entity_type": "Chemical", "pos": [46, 48]}, {"entity": "Al", "entity_type": "Chemical", "pos": [137, 139]}, {"entity": "Si", "entity_type": "Chemical", "pos": [144, 146]}, {"entity": "borosilicate", "entity_type": "Chemical", "pos": [150, 162]}], "task": "NER"}
{"text": "However , the Al concentration decreased during storage ( 5 degrees C , 6 months ) , and consequently , particle formation was observed in the solution .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [14, 16]}], "task": "NER"}
{"text": "Adding citrate , which is a chelating agent for Al , effectively suppressed the particle formation in the heated solution .", "entity": [{"entity": "citrate", "entity_type": "Chemical", "pos": [7, 14]}, {"entity": "Al", "entity_type": "Chemical", "pos": [48, 50]}], "task": "NER"}
{"text": "When 50 ppb and higher concentrations of Al ion were added to the phosphate buffer solution , the formation of white particles containing Al , P and O was detected .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [66, 75]}, {"entity": "Al", "entity_type": "Chemical", "pos": [138, 140]}, {"entity": "P", "entity_type": "Chemical", "pos": [143, 144]}, {"entity": "O", "entity_type": "Chemical", "pos": [149, 150]}], "task": "NER"}
{"text": "It is suggested that a phosphate buffer solution in a borosilicate glass vial has the ability to form particles due to interactions with the Al that is eluted from the glass during storage .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "borosilicate", "entity_type": "Chemical", "pos": [54, 66]}, {"entity": "Al", "entity_type": "Chemical", "pos": [141, 143]}], "task": "NER"}
{"text": "Microengineered PEG Hydrogels : 3D Scaffolds for Guided Cell Growth .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [16, 19]}], "task": "NER"}
{"text": "Designing three - dimensional ( 3D ) scaffolds for selective manipulation of cell growth is of high relevance for applications in regenerative medicine .", "entity": [], "task": "NER"}
{"text": "Especially , scaffolds with oriented morphologies bear high potential to guide the restoration of specific tissues .", "entity": [], "task": "NER"}
{"text": "The fabrication of hydrogel scaffolds that support long - term survival , proliferation , and unidirectional growth of embedded cells is presented here .", "entity": [], "task": "NER"}
{"text": "Parallel channel structures are introduced into the bulk hydrogels by uniaxial freezing , providing stable , and uniform porosity suitable for cell invasion ( pore diameters of 5 - 15 micro m ) .", "entity": [], "task": "NER"}
{"text": "In vitro assessment of the scaffolds with murine fibroblasts ( NIH L929 ) shows a remarkable unidirectional movement along the channels , with the cells traveling several millimeters through the hydrogel .", "entity": [], "task": "NER"}
{"text": "Parameterization of a reactive force field using a monte carlo algorithm .", "entity": [], "task": "NER"}
{"text": "Parameterization of a molecular dynamics force field is essential in realistically modeling the physicochemical processes involved in a molecular system .", "entity": [], "task": "NER"}
{"text": "This step is often challenging when the equations involved in describing the force field are complicated as well as when the parameters are mostly empirical .", "entity": [], "task": "NER"}
{"text": "ReaxFF is one such reactive force field which uses hundreds of parameters to describe the interactions between atoms .", "entity": [], "task": "NER"}
{"text": "The optimization of the parameters in ReaxFF is done such that the properties predicted by ReaxFF matches with a set of quantum chemical or experimental data .", "entity": [], "task": "NER"}
{"text": "Usually , the optimization of the parameters is done by an inefficient single - parameter parabolic - search algorithm .", "entity": [], "task": "NER"}
{"text": "In this study , we use a robust metropolis Monte - Carlo algorithm with simulated annealing to search for the optimum parameters for the ReaxFF force field in a high - dimensional parameter space .", "entity": [], "task": "NER"}
{"text": "The optimization is done against a set of quantum chemical data for MgSO4 hydrates .", "entity": [{"entity": "MgSO4 hydrates", "entity_type": "Chemical", "pos": [68, 82]}], "task": "NER"}
{"text": "The optimized force field reproduced the chemical structures , the equations of state , and the water binding curves of MgSO4 hydrates .", "entity": [{"entity": "MgSO4 hydrates", "entity_type": "Chemical", "pos": [120, 134]}], "task": "NER"}
{"text": "The transferability test of the ReaxFF force field shows the extend of transferability for a particular molecular system .", "entity": [], "task": "NER"}
{"text": "This study points out that the ReaxFF force field is not indefinitely transferable .", "entity": [], "task": "NER"}
{"text": "Co - delivery of 10 - Hydroxycamptothecin with Doxorubicin Conjugated Prodrugs for Enhanced Anticancer Efficacy .", "entity": [{"entity": "10 - Hydroxycamptothecin", "entity_type": "Chemical", "pos": [17, 41]}, {"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [47, 58]}], "task": "NER"}
{"text": "Well - defined amphiphilic linear - dendritic prodrugs ( MPEG - b - PAMAM - DOX ) are synthesized by conjugating doxorubicin ( DOX ) , to MPEG - b - PAMAM through the acid - labile hydrazone bond .", "entity": [{"entity": "MPEG - b - PAMAM - DOX", "entity_type": "Chemical", "pos": [57, 79]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [113, 124]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [127, 130]}, {"entity": "MPEG - b - PAMAM", "entity_type": "Chemical", "pos": [138, 154]}, {"entity": "hydrazone", "entity_type": "Chemical", "pos": [181, 190]}], "task": "NER"}
{"text": "The amphiphilic prodrugs form self - assembled nanoparticles in deionized water and encapsulate the hydrophobic anticancer drug 10 - hydroxycamptothecin ( HCPT ) with a high drug loading efficiency .", "entity": [{"entity": "10 - hydroxycamptothecin", "entity_type": "Chemical", "pos": [128, 152]}, {"entity": "HCPT", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "Studies on drug release and cellular uptake of the co - delivery system reveal that both drugs are released in a pH - dependent manner and effectively taken up by MCF - 7 cells .", "entity": [], "task": "NER"}
{"text": "In vitro methyl thiazolyl tetrazolium ( MTT ) assays and drug - induced apoptosis tests demonstrate the HCPT - loaded nanoparticles suppress cancer cell growth more efficiently than the MPEG - b - PAMAM - DOX prodrugs , free HCPT , and physical mixtures of MPEG - b - PAMAM - DOX and HCPT at equivalent DOX or HCPT doses .", "entity": [{"entity": "methyl thiazolyl tetrazolium", "entity_type": "Chemical", "pos": [9, 37]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "HCPT", "entity_type": "Chemical", "pos": [104, 108]}, {"entity": "MPEG - b - PAMAM - DOX", "entity_type": "Chemical", "pos": [186, 208]}, {"entity": "HCPT", "entity_type": "Chemical", "pos": [225, 229]}, {"entity": "MPEG - b - PAMAM - DOX", "entity_type": "Chemical", "pos": [257, 279]}, {"entity": "HCPT", "entity_type": "Chemical", "pos": [284, 288]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [303, 306]}, {"entity": "HCPT", "entity_type": "Chemical", "pos": [310, 314]}], "task": "NER"}
{"text": "Rational Discovery of Dengue Type 2 Non - competitive Inhibitors .", "entity": [], "task": "NER"}
{"text": "Various works have been carried out in developing therapeutics against dengue .", "entity": [], "task": "NER"}
{"text": "However , to date , no effective vaccine or anti - dengue agent has yet been discovered .", "entity": [], "task": "NER"}
{"text": "The development of protease inhibitors is considered as a promising option , but most previous works have involved competitive inhibition .", "entity": [], "task": "NER"}
{"text": "In this study , we focused on rational discovery of potential anti - dengue agents based on non - competitive inhibition of DEN - 2 NS2B / NS3 protease .", "entity": [], "task": "NER"}
{"text": "A homology model of the DEN - 2 NS2B / NS3 protease ( using West Nile Virus NS2B / NS3 protease complex , 2FP7 , as the template ) was used as the target and pinostrobin , a flavanone , was used as the standard ligand .", "entity": [{"entity": "pinostrobin", "entity_type": "Chemical", "pos": [158, 169]}, {"entity": "flavanone", "entity_type": "Chemical", "pos": [174, 183]}], "task": "NER"}
{"text": "Virtual screening was performed involving a total of 13 , 341 small compounds , with the backbone structures of chalcone , flavanone and flavone , available from the ZINC database .", "entity": [{"entity": "chalcone", "entity_type": "Chemical", "pos": [112, 120]}, {"entity": "flavanone", "entity_type": "Chemical", "pos": [123, 132]}, {"entity": "flavone", "entity_type": "Chemical", "pos": [137, 144]}], "task": "NER"}
{"text": "Ranking of the resulting compounds yielded compounds with higher binding affinities compared to the standard ligand .", "entity": [], "task": "NER"}
{"text": "Inhibition assay of the selected top ranking compounds against DEN - 2 NS2B / NS3 proteolytic activity resulted in significantly better inhibition compared to the standard and correlated well with in silico results .", "entity": [], "task": "NER"}
{"text": "In conclusion , via this rational discovery technique , better inhibitors were identified .", "entity": [], "task": "NER"}
{"text": "This method can be used in further work to discover lead compounds for anti - dengue agents .", "entity": [], "task": "NER"}
{"text": "Potential of nanocrystalline cellulose - fibrin nanocomposites for artificial vascular graft applications .", "entity": [], "task": "NER"}
{"text": "The potential of synthesizing new nanocomposites from nanocrystalline cellulose ( NCC ) and fibrin for small - diameter replacement vascular graft ( SDRVG ) application was demonstrated .", "entity": [], "task": "NER"}
{"text": "Periodate oxidation of NCC can augment reactive carbonyl groups on NCC and facilitate its cross - linking with fibrin .", "entity": [{"entity": "carbonyl", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "NCC - fibrin nanocomposites were synthesized , composed of homogeneously dispersed oxidized NCC ( ONCC ) in a fibrin matrix , with fibrin providing elasticity and ONCC providing strength .", "entity": [], "task": "NER"}
{"text": "The maximum strength and elongation of the nanocomposites were determined by Atomic Force Microscopy ( AFM ) and compared with a native blood vessel .", "entity": [], "task": "NER"}
{"text": "The manipulation of degree of oxidation of NCC and the NCC - to - fibrin ratio resulted in the variation of strength and elongation of the nanocomposites , indicating that the nanocomposites can be tailored to conform to the diverse mechanical properties of native blood vessels .", "entity": [], "task": "NER"}
{"text": "A mechanistic understanding of the molecular interactions of ONCC and fibrin was illustrated .", "entity": [], "task": "NER"}
{"text": "This study established fundamental information to utilizing NCC for SDRVG applications .", "entity": [], "task": "NER"}
{"text": "Functional interactions between matrix metalloproteinases and glycosaminoglycans .", "entity": [], "task": "NER"}
{"text": "Similar to most proteinases , matrix metalloproteinases ( MMP ) do not recognize a consensus cleavage site .", "entity": [], "task": "NER"}
{"text": "Thus , it is not surprising that , in a defined in vitro reaction , most MMPs can act on a wide range of proteins , including many extracellular matrix proteins .", "entity": [], "task": "NER"}
{"text": "However , the findings obtained from in vivo studies with genetic models have demonstrated that individual MMPs act on just a few extracellular protein substrates , typically not matrix proteins .", "entity": [], "task": "NER"}
{"text": "The limited , precise functions of an MMP imply that mechanisms have evolved to control the specificity of proteinase : substrate interactions .", "entity": [], "task": "NER"}
{"text": "We discuss the possibility that interactions with the glycosaminoglycan chains of proteoglycans may function as allosteric regulators or accessory factors directing MMP catalysis to specific substrates .", "entity": [], "task": "NER"}
{"text": "We propose that understanding how the activity of specific MMPs is confined to discreet compartments and targeted to defined substrates via interactions with other macromolecules may provide a means of blocking potentially deleterious MMP - mediated processes at the same time as sparing any beneficial functions .", "entity": [], "task": "NER"}
{"text": "The pharmacokinetics and conversion of the lactone to the carboxylate forms of ginkgolide B in rat plasma .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [43, 50]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "ginkgolide B", "entity_type": "Chemical", "pos": [79, 91]}], "task": "NER"}
{"text": "Ginkgolide B consists of three lactone groups , which may undergo hydrolysis , and lead to the rings opening in aqueous solution with different pHs .", "entity": [{"entity": "Ginkgolide B", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "lactone", "entity_type": "Chemical", "pos": [31, 38]}], "task": "NER"}
{"text": "From mechanisms of pharmacological activity in vivo , the lactone appears to be the active form of the drug .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "Pharmacokinetics of lactone form ( GB - lac ) and the total of the lactone and carboxylate form ( GB - tot ) of ginkgolide B were investigated after intravenous administration of a dose of 4 mg / kg ginkgolide B .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "GB - lac", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "lactone", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [79, 90]}, {"entity": "ginkgolide B", "entity_type": "Chemical", "pos": [112, 124]}, {"entity": "ginkgolide B", "entity_type": "Chemical", "pos": [199, 211]}], "task": "NER"}
{"text": "The rate of lactone hydrolysis was also studied in plasma in vitro .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [12, 19]}], "task": "NER"}
{"text": "After intravenous administration , ginkgolide B in the original form was converted to its carboxylate form under simulated physiological conditions .", "entity": [{"entity": "ginkgolide B", "entity_type": "Chemical", "pos": [35, 47]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [90, 101]}], "task": "NER"}
{"text": "The AUC0 - infinity of GB - lac constituted 63 . 5 +/- 17 . 4 % of the AUC0 - infinity of GB - tot .", "entity": [{"entity": "GB - lac", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "The ratio of average cumulation of excretion of lactone to carboxylate reached approximately 1 to 1 in urine .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "From the equilibrium of lactone hydrolysis in rat plasma in vitro , the k obs was - 0 . 0176 min ( - 1 ) and t 1 / 2 was 39 . 38 min .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [24, 31]}], "task": "NER"}
{"text": "In conclusion , the equilibrium existed between lactone of ginkgolide B and its carboxylate form in vivo at physiological pH , which suggested that more attention should be focused on the original and the ionization forms of ginkgolide B and the conversion of the lactone into carboxylate in vivo .", "entity": [{"entity": "lactone", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "ginkgolide B", "entity_type": "Chemical", "pos": [59, 71]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [80, 91]}, {"entity": "ginkgolide B", "entity_type": "Chemical", "pos": [225, 237]}, {"entity": "lactone", "entity_type": "Chemical", "pos": [264, 271]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [277, 288]}], "task": "NER"}
{"text": "Molecular orientation and dynamics of different sized organic radicals included in organic 1D nanochannels .", "entity": [], "task": "NER"}
{"text": "The molecular orientation and dynamics of di - t - butylnitroxide ( DTBN ) and 4 - oxo - 2 , 2 , 6 , 6 - tetramethyl - 1 - piperidinyl - 1 - oxyl ( TEMPONE ) radicals in the organic 1D nanochannels of tris ( o - phenylenedioxy ) cyclotriphosphazene ( TPP ) were investigated by examining inclusion compounds ( ICs ) diluted by the co - inclusion of nonradicals using electron spin resonance ( ESR ) .", "entity": [{"entity": "di - t - butylnitroxide", "entity_type": "Chemical", "pos": [42, 65]}, {"entity": "DTBN", "entity_type": "Chemical", "pos": [68, 72]}, {"entity": "4 - oxo - 2 , 2 , 6 , 6 - tetramethyl - 1 - piperidinyl - 1 - oxyl", "entity_type": "Chemical", "pos": [79, 145]}, {"entity": "TEMPONE", "entity_type": "Chemical", "pos": [148, 155]}, {"entity": "tris ( o - phenylenedioxy ) cyclotriphosphazene", "entity_type": "Chemical", "pos": [201, 248]}, {"entity": "TPP", "entity_type": "Chemical", "pos": [251, 254]}], "task": "NER"}
{"text": "Spectral simulation showed that the axial rotation of DTBN or TEMPONE molecules is excited in TPP nanochannels with activation energies of 3 and 10 kJ mol ( - 1 ) , respectively .", "entity": [{"entity": "DTBN", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "TEMPONE", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "TPP", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "The rotation axes for both DTBN and TEMPONE were determined to be almost parallel to the principal y - axis of the g tensor , which agrees with the result reported for 2 , 2 , 6 , 6 - tetramethyl - 1 - piperidinyl - 1 - oxyl ( TEMPO ) in TPP nanochannels , which has the activation energy of 5 kJ mol ( - 1 ) .", "entity": [{"entity": "DTBN", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "TEMPONE", "entity_type": "Chemical", "pos": [36, 43]}, {"entity": "2 , 2 , 6 , 6 - tetramethyl - 1 - piperidinyl - 1 - oxyl", "entity_type": "Chemical", "pos": [168, 224]}, {"entity": "TEMPO", "entity_type": "Chemical", "pos": [227, 232]}, {"entity": "TPP", "entity_type": "Chemical", "pos": [238, 241]}], "task": "NER"}
{"text": "These results indicate that the molecular orientations of guest nitroxide radicals are almost independent of the molecular sizes of the guest radicals in TPP nanochannels , although the molecular dynamics are dependent on the molecular sizes .", "entity": [{"entity": "nitroxide", "entity_type": "Chemical", "pos": [64, 73]}, {"entity": "TPP", "entity_type": "Chemical", "pos": [154, 157]}], "task": "NER"}
{"text": "Ethnobotanical study on traditional use of medicinal plants in South - Western Serbia , Zlatibor district .", "entity": [], "task": "NER"}
{"text": "Ethnopharmacological relevance : This paper provides significant ethnobotanical information on medicinal plant uses in the Zlatibor district , South - Western Serbia .", "entity": [], "task": "NER"}
{"text": "Materials and methods : A survey was performed using questionnaires with 220 informants ( mean age 47 , 79 % female , 21 % male ) .", "entity": [], "task": "NER"}
{"text": "In addition , the use value and the relative importance of species were determined and the informant consensus factor was calculated for the medicinal plants included in the study .", "entity": [], "task": "NER"}
{"text": "Intended plants usage was compared with previous ethnobotanical literature , with reference to the neighboring areas of Zlatibor district .", "entity": [], "task": "NER"}
{"text": "Results : The informants provided data for 69 medicinal plants belonging to 36 families .", "entity": [], "task": "NER"}
{"text": "Rosaceae , Lamiaceae and Asteraceae were the predominant locally used families .", "entity": [], "task": "NER"}
{"text": "The species with the highest use value were Mentha piperita , Matricaria chamomilla , Hypericum perforatum and Achillea millefolium .", "entity": [], "task": "NER"}
{"text": "The most frequently reported medicinal uses were ones for treating gastrointestinal ailments , respiratory problems and skin diseases .", "entity": [], "task": "NER"}
{"text": "Usually , the administration was primarily oral followed by topical applications .", "entity": [], "task": "NER"}
{"text": "All different plant parts were utilized , however leaves were the most exploited parts of the plants .", "entity": [], "task": "NER"}
{"text": "Conclusions : Folk medicine in South - Western Serbia , Zlatibor district is intended mainly as a mode of primary health care in healing of minor illnesses .", "entity": [], "task": "NER"}
{"text": "The results indicate a slight reduction in the ethnobotanical and medical knowledge in this area , when compared with neighboring regions .", "entity": [], "task": "NER"}
{"text": "Recombinant streptavidin - C3bot for delivery of proteins into macrophages .", "entity": [], "task": "NER"}
{"text": "We demonstrated previously that monocytes and macrophages are target cells for the Rho - modifying Clostridium botulinum C3 ADP - ribosyltransferase .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "Here , we report the construction , expression and characterization of a recombinant streptavidin - C3 fusion protein which allows for delivery of biotin - labelled molecules into the cytosol of macrophages via enzymatically inactive C3bot1E174Q .", "entity": [{"entity": "biotin", "entity_type": "Chemical", "pos": [147, 153]}], "task": "NER"}
{"text": "The enzyme domain of diphtheria toxin was used as cargo to demonstrate proof of principle .", "entity": [], "task": "NER"}
{"text": "This transport system could represent an attractive tool for experimental monocyte / macrophage pharmacology .", "entity": [], "task": "NER"}
{"text": "Cardiovascular disease prevention : matching evidence - based algorithms with individualized care .", "entity": [], "task": "NER"}
{"text": "The appropriate use of statins in primary prevention remains a matter of debate .", "entity": [], "task": "NER"}
{"text": "Although statins reduce cardiovascular events at all levels of baseline risk , they are associated with rare but important side effects including incident diabetes .", "entity": [], "task": "NER"}
{"text": "Herein , we review strategies for statin allocation ranging from strict \" evidence - based \" adherence to randomized controlled clinical trial ( RCT ) entry criteria to more \" personalized \" risk assessment using high - sensitivity C - reactive protein ( hsCRP ) , coronary artery calcification ( CAC ) , or genetic testing .", "entity": [], "task": "NER"}
{"text": "Current guidelines advocate an unusual middle ground between an evidence - based approach and a personalized approach .", "entity": [], "task": "NER"}
{"text": "Hedgehog - Gli Activators Direct Osteo - chondrogenic Function of Bone Morphogenetic Protein toward Osteogenesis in the Perichondrium .", "entity": [], "task": "NER"}
{"text": "Specification of progenitors into the osteoblast lineage is an essential event for skeletogenesis .", "entity": [], "task": "NER"}
{"text": "During endochondral ossification , cells in the perichondrium give rise to osteoblast precursors .", "entity": [], "task": "NER"}
{"text": "Hedgehog ( Hh ) and bone morphogenetic protein ( BMP ) are suggested to regulate the commitment of these cells .", "entity": [], "task": "NER"}
{"text": "However , properties of perichondrial cells and regulatory mechanisms of the specification process are still poorly understood .", "entity": [], "task": "NER"}
{"text": "Here , we investigated the machineries by combining a novel organ culture system and single - cell expression analysis with mouse genetics and biochemical analyses .", "entity": [], "task": "NER"}
{"text": "In a metatarsal organ culture reproducing bone collar formation , activation of BMP signaling enhanced the bone collar formation cooperatively with Hh input , whereas the signaling induced ectopic chondrocyte formation in the perichondrium without Hh input .", "entity": [], "task": "NER"}
{"text": "Similar phenotypes were also observed in compound mutant mice , where signaling activities of Hh and BMP were genetically manipulated .", "entity": [], "task": "NER"}
{"text": "Single - cell quantitative RT - PCR analyses showed heterogeneity of perichondrial cells in terms of natural characteristics and responsiveness to Hh input .", "entity": [], "task": "NER"}
{"text": "In vitro analyses revealed that Hh signaling suppressed BMP - induced chondrogenic differentiation ; Gli1 inhibited the expression of Sox5 , Sox6 , and Sox9 ( SRY box - containing gene 9 ) as well as transactivation by Sox9 .", "entity": [], "task": "NER"}
{"text": "Indeed , ectopic expression of chondrocyte maker genes were observed in the perichondrium of metatarsals in Gli1 ( - / - ) fetuses , and the phenotype was more severe in Gli1 ( - / - ) ; Gli2 ( - / - ) newborns .", "entity": [], "task": "NER"}
{"text": "These data suggest that Hh - Gli activators alter the function of BMP to specify perichondrial cells into osteoblasts ; the timing of Hh input and its target populations are critical for BMP function .", "entity": [], "task": "NER"}
{"text": "A novel mechanism by which SDF - 1 beta protects cardiac cells from palmitate - induced ER stress and apoptosis via CXCR7 and AMPK / p38 MAPK - mediated IL - 6 generation .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "We studied the protective effect of stromal cell - derived factor - 1beta ( SDF - 1 beta ) on cardiac cells from lipotoxicity in vitro and diabetes in vivo .", "entity": [], "task": "NER"}
{"text": "Exposure of cardiac cells to palmitate increased apoptosis by activating NADPH oxidase - associated nitrosative stress and endoplasmic reticulum ( ER ) stress , which abolished by pretreatment with SDF - 1 beta via up - regulation of AMPK - mediated p38 MAPK phosphorylation and IL - 6 production .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [73, 78]}], "task": "NER"}
{"text": "The SDF - 1 beta cardiac protection could be abolished by inhibition of AMPK , p38 MAPK or IL - 6 .", "entity": [], "task": "NER"}
{"text": "Activation of AMPK or addition of recombinant IL - 6 recaptured a similar cardiac protection .", "entity": [], "task": "NER"}
{"text": "SDF - 1 beta receptor CXCR4 antagonist AMD3100 or CXCR4 siRNA could not , but CXCR7 siRNA completely abolish SDF - 1 beta ' s protection from palmitate - induced apoptosis and activation of AMPK and p38 MAPK .", "entity": [{"entity": "AMD3100", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [142, 151]}], "task": "NER"}
{"text": "Administration of SDF - 1 beta to diabetic rats , induced by high - fat - diet feeding with a small dose of streptozotocin , could significantly reduce cardiac apoptosis and increase in AMPK phosphorylation along with a prevention of diabetes - induced cardiac oxidative damage , inflammation , hypertrophy and remodeling .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [108, 122]}], "task": "NER"}
{"text": "These results showed that SDF - 1 beta protects palmitate - induced cardiac apoptosis , which is mediated by NADPH oxidase - activated nitrosative damage and ER stress , via CXCR7 to activate AMPK / p38 MAPK - mediated IL - 6 generation .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [109, 114]}], "task": "NER"}
{"text": "The cardiac protection by SDF - 1 beta from diabetes - induced oxidative damage , cell death and remodeling was also associated with AMPK activation .", "entity": [], "task": "NER"}
{"text": "Modulation of cytochrome P450 1 ( Cyp1 ) by vanadium in hepatic tissue and isolated hepatocyte of C57BL / 6 mice .", "entity": [{"entity": "vanadium", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "The objective of the current study was to investigate the effect of vanadium ( V ( 5 + ) ) on Cyp1 expression and activity in C57BL / 6 mice liver and isolated hepatocytes .", "entity": [{"entity": "vanadium", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [79, 88]}], "task": "NER"}
{"text": "For this purpose , C57BL6 mice were injected intraperitoneally with V ( 5 + ) ( 5 mg / kg ) in the absence and presence of 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) ( 15 mu g / kg ) for 6 and 24 h .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [123, 170]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [173, 177]}], "task": "NER"}
{"text": "Furthermore , isolated hepatocytes from C57BL6 mice were treated with V ( 5 + ) ( 5 , 10 , and 20 mu M ) in the absence and presence of TCDD ( 1 nM ) for 3 , 6 , 12 , and 24 h .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [70, 79]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [136, 140]}], "task": "NER"}
{"text": "In vivo , V ( 5 + ) alone did not significantly alter Cyp1a1 , Cyp1a2 , or Cyp1b1 mRNA , protein , or catalytic activity levels .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [10, 19]}], "task": "NER"}
{"text": "Upon co - exposure to V ( 5 + ) and TCDD , V ( 5 + ) significantly potentiated the TCDD - mediated induction of the Cyp1a1 , Cyp1a2 , and Cyp1b1 mRNA , protein , and catalytic activity levels at 24 h .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [43, 52]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "In vitro , V ( 5 + ) decreased the TCDD - mediated induction of Cyp1a1 mRNA , protein , and catalytic activity levels .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [11, 20]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [35, 39]}], "task": "NER"}
{"text": "Furthermore , V ( 5 + ) significantly inhibited the TCDD - induced AhR - dependent luciferase activity .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [52, 56]}], "task": "NER"}
{"text": "V ( 5 + ) also increased serum hemoglobin ( Hb ) levels in animals treated for 24 h .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Upon treatment of isolated hepatocytes with Hb alone or in the presence of TCDD , there was an increase in the AhR - dependent luciferase activity .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [75, 79]}], "task": "NER"}
{"text": "When isolated hepatocytes were treated for 2 h with V ( 5 + ) in the presence of TCDD , followed by replacement of the medium with new medium containing Hb , there was further potentiation to the TCDD - mediated effect .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [52, 61]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [81, 85]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [196, 200]}], "task": "NER"}
{"text": "The present study demonstrates that there is a differential modulation of Cyp1a1 by V ( 5 + ) in C57BL / 6 mice livers and isolated hepatocytes and demonstrates Hb as an in vivo specific modulator .", "entity": [{"entity": "V ( 5 + )", "entity_type": "Chemical", "pos": [84, 93]}], "task": "NER"}
{"text": "Metabolic dephenylation of the rubber antioxidant N - phenyl - 2 - naphthylamine to carcinogenic 2 - naphthylamine in rats .", "entity": [{"entity": "N - phenyl - 2 - naphthylamine", "entity_type": "Chemical", "pos": [50, 80]}, {"entity": "2 - naphthylamine", "entity_type": "Chemical", "pos": [97, 114]}], "task": "NER"}
{"text": "N - Phenyl - 2 - naphthylamine ( P2NA ) was widely used as oxidation inhibitor , particularly in rubber manufacturing .", "entity": [{"entity": "N - Phenyl - 2 - naphthylamine", "entity_type": "Chemical", "pos": [0, 30]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "Technical - grade P2NA was contaminated with carcinogenic 2 - naphthylamine ( 2NA ) , and bladder cancer risk in exposed workers was attributed to this impurity .", "entity": [{"entity": "P2NA", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "2 - naphthylamine", "entity_type": "Chemical", "pos": [58, 75]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "Investigations in humans and mammalian species revealed that small amounts of 2NA are excreted into urine after exposure to P2NA .", "entity": [{"entity": "2NA", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [124, 128]}], "task": "NER"}
{"text": "However , since 2NA per se is not carcinogenic and main downstream metabolites of 2NA have not been found in urine so far , it remained uncertain if 2NA derived from P2NA dephenylation is further activated to carcinogenic downstream metabolites .", "entity": [{"entity": "2NA", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [149, 152]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [166, 170]}], "task": "NER"}
{"text": "An experimental animal study was therefore designed to indicate if , and if yes to which extent , 2NA from P2NA dephenylation is accessible to the metabolic pathway that is held responsible for the carcinogenicity of 2NA .", "entity": [{"entity": "2NA", "entity_type": "Chemical", "pos": [98, 101]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [107, 111]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [217, 220]}], "task": "NER"}
{"text": "Groups of 5 male and female CD rats were dosed with P2NA ( 2 - 550 mg / kg b . w . ) and 2NA ( 0 . 075 - 75 mg / kg b . w . ) ; 2NA - haemoglobin adducts and urinary 2NA excretion were determined applying GC - MS / MS .", "entity": [{"entity": "P2NA", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [166, 169]}], "task": "NER"}
{"text": "2NA haemoglobin adducts originated dose - dependently after 2NA and P2NA dosing .", "entity": [{"entity": "2NA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [60, 63]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "To induce identical adduct concentrations , an approximately 100 - 200 - fold higher dose of P2NA was necessary compared to 2NA .", "entity": [{"entity": "P2NA", "entity_type": "Chemical", "pos": [93, 97]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "Since haemoglobin adducts are formed by the same pathway ( N - hydroxylation ) as the ultimate carcinogens from 2NA , the comparison of adduct concentrations after 2NA and P2NA dosage permits a quantitative estimate of the carcinogenicity of P2NA .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [59, 60]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [112, 115]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [164, 167]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [172, 176]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [242, 246]}], "task": "NER"}
{"text": "The results show that 2NA derived from dephenylation of P2NA enters the carcinogenic downstream pathway of 2NA in rats .", "entity": [{"entity": "2NA", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "P2NA", "entity_type": "Chemical", "pos": [56, 60]}, {"entity": "2NA", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "Hence , the bladder cancer risk after human exposures to P2NA must be re - evaluated .", "entity": [{"entity": "P2NA", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "Effect of bisphenol - A on insulin signal transduction and glucose oxidation in skeletal muscle of adult male albino rat .", "entity": [{"entity": "bisphenol - A", "entity_type": "Chemical", "pos": [10, 23]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "The estrogenic monomer bisphenol - A ( BPA ) is an endocrine - disrupting chemical used in the production of epoxy resins , plastic food and beverage containers , leading to ubiquitous human exposure .", "entity": [{"entity": "bisphenol - A", "entity_type": "Chemical", "pos": [23, 36]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "epoxy", "entity_type": "Chemical", "pos": [109, 114]}], "task": "NER"}
{"text": "Environmentally relevant doses of BPA have profound effects on mice endocrine pancreas .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "It increases pancreatic insulin content and favors postprandial hyperinsulinemia and insulin resistance in male mice .", "entity": [], "task": "NER"}
{"text": "Skeletal muscle plays a crucial role in maintaining systemic glucose metabolism .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [61, 68]}], "task": "NER"}
{"text": "In the present study , we investigated the possible effects of BPA on insulin - signaling molecules and glucose oxidation in skeletal muscle of male rat .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [104, 111]}], "task": "NER"}
{"text": "Adult male Wistar albino rats were divided into three groups .", "entity": [], "task": "NER"}
{"text": "Group I : control ( vehicle treated ) and groups II and III were administered with BPA orally ( 20 and 200 mg / kg bw / day , respectively ) .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Although there was no change in the levels of insulin receptor ( IR ) , Akt ( protein kinase B ) and glucose transporter - 4 ( GLUT4 ) messenger RNA , BPA significantly decreased the IR , Akt and GLUT4 protein levels ( both plasma membrane and cytosolic fraction ) of the gastrocnemius muscle .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [101, 108]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [151, 154]}], "task": "NER"}
{"text": "There was an increase in serum insulin and decrease in serum testosterone levels but fasting blood glucose level remained unaltered .", "entity": [{"entity": "testosterone", "entity_type": "Chemical", "pos": [61, 73]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "In conclusion , BPA has adverse effects on phosphorylation of Akt , GLUT4 translocation and ( 14 ) C - glucose oxidation .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "( 14 ) C - glucose", "entity_type": "Chemical", "pos": [92, 110]}], "task": "NER"}
{"text": "Effects of the combined artesunate and mefloquine antimalarial drugs on rat embryos .", "entity": [{"entity": "artesunate", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "mefloquine", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "Artemisinins combination therapy ( ACT ) is the first choice therapy for falciparum malaria .", "entity": [{"entity": "Artemisinins", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Data on the safety of ACTs in pregnancy are limited and controversial and the use is not recommended on the first trimester .", "entity": [], "task": "NER"}
{"text": "To evaluate the effects of isolated and combined artesunate ( AS ) / mefloquine ( MQ ) on embryo rats , pregnant rats were treated orally with AS ( 15 and 40 mg / kg body weight ( bwt ) / day ) , MQ ( 30 and 80 mg / kg bwt / day ) and AS / MQ ( 15 / 30 and 40 / 80 mg / kg bwt / day ) on days 9 - 11 post coitum ( pc ) .", "entity": [{"entity": "artesunate", "entity_type": "Chemical", "pos": [49, 59]}, {"entity": "mefloquine", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "The dams were euthanized on day 12 pc and gestational and embryos histological parameters were evaluated .", "entity": [], "task": "NER"}
{"text": "Embryolethality and histopathological anomalies were significant when AS was given alone or combined with MQ .", "entity": [], "task": "NER"}
{"text": "Combination of AS and MQ did not enhance their toxicity compared to their separate administrations ; on the other side , there was a reduction in the toxic effects of the AS when combined with MQ .", "entity": [], "task": "NER"}
{"text": "Isolated MQ did not induce developmental toxicity .", "entity": [], "task": "NER"}
{"text": "Cytotoxic , genotoxic and antigenotoxic potencies of oligorutins .", "entity": [], "task": "NER"}
{"text": "Rutin has been enzymatically oligomerized by laccase from Trametes versicolor .", "entity": [{"entity": "Rutin", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Five fractions of oligomers were obtained from the monomers having high solubility in water , which can reach 351 - times that of rutin .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [130, 135]}], "task": "NER"}
{"text": "Cytotoxicity of rutin and oligorutin fractions was evaluated towards K562 cells .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [16, 21]}], "task": "NER"}
{"text": "Oligorutin fractions showed a lower antiproliferative effect compared with its monomer .", "entity": [], "task": "NER"}
{"text": "The genotoxic potential of rutin and oligorutin fractions was assessed , at the limit of the solubility of each molecule , using the comet test .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [27, 32]}], "task": "NER"}
{"text": "None of the tested concentrations of either rutin or oligorutin fractions has showed a genotoxic effect .", "entity": [{"entity": "rutin", "entity_type": "Chemical", "pos": [44, 49]}], "task": "NER"}
{"text": "Similarly , the antigenotoxic effect of these flavonoids was tested using the same assay .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "The obtained results showed a higher ability of oligorutin fractions to reduce the genotoxicity induced by hydrogen peroxide compared with monomeric rutin .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [107, 124]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [149, 154]}], "task": "NER"}
{"text": "Rheological properties and tunable thermoplasticity of phenolic rich fraction of pyrolysis bio - oil .", "entity": [], "task": "NER"}
{"text": "In this work we report on the preparation , characterization , and properties of a thermally treated lignin - derived , phenolic - rich fraction ( PRF ) of wood pyrolysis bio - oil obtained by ethyl acetate extraction .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [193, 206]}], "task": "NER"}
{"text": "The PRF was characterized for viscoelastic and rheological behavior using dynamic mechanical analysis ( DMA ) and cone and plate rheology .", "entity": [], "task": "NER"}
{"text": "A unique thermoplastic behavior was evidenced .", "entity": [], "task": "NER"}
{"text": "Heat - treated PRFs acquire high modulus but show low temperatures of thermal flow which can be systematically manipulated through the thermal pretreatment .", "entity": [], "task": "NER"}
{"text": "Loss of volatiles , changes in molecular weight , and glass transition temperature ( Tg ) were investigated using thermogravimetric analysis ( TGA ) , mass spectrometry ( MS ) , and differential scanning calorimetry ( DSC ) , respectively .", "entity": [], "task": "NER"}
{"text": "Underlying mechanisms for the thermal and rheological behavior are discussed with regard to interactions between pyrolytic lignin nanoparticles present in the system and the role of volatile materials on determining the properties of the material resembling in several aspects to colloidal suspension systems .", "entity": [], "task": "NER"}
{"text": "Low thermal flow temperatures and reversible thermal effects can be attributed to association of pyrolytic lignin particles due to intermolecular interactions that are easily ruptured at higher temperatures .", "entity": [], "task": "NER"}
{"text": "The thermoplastic behavior of PRF and its low Tg is of particular interest , as it gives opportunities for application of this fraction in several melt processing and adhesive technologies .", "entity": [], "task": "NER"}
{"text": "Accurate semiexperimental structure of 1 , 3 , 4 - oxadiazole by the mixed estimation method .", "entity": [{"entity": "1 , 3 , 4 - oxadiazole", "entity_type": "Chemical", "pos": [39, 61]}], "task": "NER"}
{"text": "In order to determine an accurate equilibrium structure for 1 , 3 , 4 - oxadiazole , microwave transitions and ground - state rotational constants are reported for the parent species and for the ( 18 ) O isotopologue measured in natural abundance .", "entity": [{"entity": "1 , 3 , 4 - oxadiazole", "entity_type": "Chemical", "pos": [60, 82]}, {"entity": "( 18 ) O", "entity_type": "Chemical", "pos": [195, 203]}], "task": "NER"}
{"text": "These rotational constants along with those of the ( 13 ) C , ( 15 ) N , and D1 species were used together with vibration - rotation constants calculated from a cubic force field calculated at the B3LYP / 6 - 311 + G ( 3df , 2pd ) level of theory to derive a semiexperimental equilibrium structure .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "( 15 ) N", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "However , the results of this fit were not satisfactory ; therefore , the structure was later significantly improved by the mixed estimation method .", "entity": [], "task": "NER"}
{"text": "In this method , internal coordinates from good - quality quantum chemical calculations ( with appropriate uncertainties ) are fitted simultaneously with moments of inertia of the full set of isotopologues .", "entity": [], "task": "NER"}
{"text": "The accuracy of this structure has been confirmed by using an extrapolation technique .", "entity": [], "task": "NER"}
{"text": "All elements of the ( 14 ) N nuclear quadrupole coupling tensor have been determined .", "entity": [{"entity": "( 14 ) N", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "Antinociceptive effect of 7 - methoxyflavone isolated from Zornia brasiliensis .", "entity": [{"entity": "7 - methoxyflavone", "entity_type": "Chemical", "pos": [26, 44]}], "task": "NER"}
{"text": "In this study , we investigated the antinociceptive effect of 7 - methoxyflavone ( 7MF ) in mice using the following tests : acetic acid - induced writhing , glutamate - and formalin - induced nociception and hotplate .", "entity": [{"entity": "7 - methoxyflavone", "entity_type": "Chemical", "pos": [62, 80]}, {"entity": "7MF", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [125, 136]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [158, 167]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [174, 182]}], "task": "NER"}
{"text": "7MF ( 30 , 50 , 100 and 300 mu mol / kg , i . p . ) reduced the number of writhes , with ID ( 50 ) = 82 . 5 +/- 11 . 7 mu mol / kg and E ( max ) = 58 . 4 % .", "entity": [{"entity": "7MF", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "7MF treatment ( 100 mu mol / kg , i . p . ) inhibited paw - licking time in the neurogenic phase of the formalin pain response ( 65 . 6 % ) and did not decrease the nociceptive response in the inflammatory phase .", "entity": [{"entity": "7MF", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "In addition , in glutamate - induced nociception , 7MF inhibited 26 % of the nociceptive answer .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [17, 26]}, {"entity": "7MF", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "On the other hand , 7MF did not increase the latency time of the animals in the hotplate test .", "entity": [{"entity": "7MF", "entity_type": "Chemical", "pos": [20, 23]}], "task": "NER"}
{"text": "These results suggest that 7MF has peripheral antinociceptive activity .", "entity": [{"entity": "7MF", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "Directed organization of DNA filaments in a soft matter template .", "entity": [], "task": "NER"}
{"text": "We have developed a noninvasive , all - optical , holographic technique for permanently aligning liquid crystalline DNA filaments in a microperiodic template realized in soft - composite ( polymeric ) materials .", "entity": [], "task": "NER"}
{"text": "By combining optical intensity holography with a selective microfluidic etching process , a channelled microstructure has been realized which enables self - assembly of DNA .", "entity": [], "task": "NER"}
{"text": "The striking chemicophysical properties of the structure immobilize the DNA filaments within the microchannels without the need of any kind of surface chemistry or functionalization .", "entity": [], "task": "NER"}
{"text": "Polarized optical , confocal , and electronic microscopies have been used for characterizing the DNA geometry inside the microchannels in terms of birefringence , fluorescence , and nanoscale organization properties .", "entity": [], "task": "NER"}
{"text": "In particular , observation of a far - field diffraction pattern confirms a periodic organization of the DNA filaments inside the polymeric template .", "entity": [], "task": "NER"}
{"text": "Self - assembly of morphology - tunable architectures from tetraarylmethane derivatives for targeted drug delivery .", "entity": [{"entity": "tetraarylmethane", "entity_type": "Chemical", "pos": [59, 75]}], "task": "NER"}
{"text": "Tetraarylmethane compounds consisting of two pyrogallol and two aniline units , namely , Ar2CAr ' 2 { Ar = 3 , 4 , 5 - C6H2 ( OH ) 3 and Ar ' = 3 , 5 - R2 - 4 - C6H2NH2 [ R = Me ( 1 ) , iPr ( 2 ) ] } exhibit excellent self - assembly behavior .", "entity": [{"entity": "Tetraarylmethane", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "pyrogallol", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "aniline", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "Ar2CAr ' 2", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "3 , 4 , 5 - C6H2 ( OH ) 3", "entity_type": "Chemical", "pos": [107, 132]}, {"entity": "3 , 5 - R2 - 4 - C6H2NH2", "entity_type": "Chemical", "pos": [144, 168]}, {"entity": "iPr", "entity_type": "Chemical", "pos": [186, 189]}], "task": "NER"}
{"text": "Compound 1 yields size - tunable hollow nanospheres ( HNSs ) with a narrow size distribution , and 2 yields various morphologies ranging from microtubules to microrods via self - assembly induced by hydrogen bonding and pi - pi stacking interactions .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [199, 207]}], "task": "NER"}
{"text": "On the basis of the experimental results , a plausible mechanism for morphology tunability was proposed .", "entity": [], "task": "NER"}
{"text": "As a means of utilizing the self - assembled HNSs for targeting controlled drug delivery , folic acid ( FA ) and rhodamine 6G ( Rh6G ) were grafted onto compound 1 to yield the FA - Rh6G - 1 complex .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [91, 101]}, {"entity": "rhodamine 6G", "entity_type": "Chemical", "pos": [113, 125]}, {"entity": "Rh6G", "entity_type": "Chemical", "pos": [128, 132]}, {"entity": "FA - Rh6G - 1", "entity_type": "Chemical", "pos": [177, 190]}], "task": "NER"}
{"text": "The HNSs fabricated with FA - Rh6G - 1 showed low cytotoxicity against human embryonic kidney 293T cells and CT26 colon carcinoma cells and good doxorubicin ( DOX ) loading capacity ( 9 . 6 wt % ) .", "entity": [{"entity": "FA - Rh6G - 1", "entity_type": "Chemical", "pos": [25, 38]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [145, 156]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [159, 162]}], "task": "NER"}
{"text": "The FA receptor - mediated endocytosis of FA - Rh6G - 1 HNSs examined by using a confocal laser scanning microscope and a flow cytometer revealed that the uptake of FA - Rh6G - 1 HNSs into CT26 cells was induced by FA receptor - mediated endocytosis .", "entity": [{"entity": "FA - Rh6G - 1", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "FA - Rh6G - 1", "entity_type": "Chemical", "pos": [165, 178]}], "task": "NER"}
{"text": "In vitro drug delivery tests showed that the DOX molecules were released from the resulting HNSs in a sustainable and pH - dependent manner , demonstrating a potential application for HNSs in targeted drug delivery for cancer therapy .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "Novel microwave assisted chemical synthesis of Nd 2 Fe 1 4 B hard magnetic nanoparticles .", "entity": [{"entity": "Nd 2 Fe 1 4 B", "entity_type": "Chemical", "pos": [47, 60]}], "task": "NER"}
{"text": "The high coercivity and excellent energy product of Nd2Fe14B hard magnets have led to a large number of high value added industrial applications .", "entity": [{"entity": "Nd2Fe14B", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Chemical synthesis of Nd2Fe14B nanoparticles is challenging due to the large reduction potential of Nd ( 3 + ) and the high tendency for Nd2Fe14B oxidation .", "entity": [{"entity": "Nd2Fe14B", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "Nd ( 3 + )", "entity_type": "Chemical", "pos": [100, 110]}, {"entity": "Nd2Fe14B", "entity_type": "Chemical", "pos": [137, 145]}], "task": "NER"}
{"text": "We report the novel synthesis of Nd2Fe14B nanoparticles by a microwave assisted combustion process .", "entity": [{"entity": "Nd2Fe14B", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "The process consisted of Nd - Fe - B mixed oxide preparation by microwave assisted combustion , followed by the reduction of the mixed oxide by CaH2 .", "entity": [{"entity": "Nd - Fe - B", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [43, 48]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [135, 140]}, {"entity": "CaH2", "entity_type": "Chemical", "pos": [144, 148]}], "task": "NER"}
{"text": "This combustion process is fast , energy efficient and offers facile elemental substitution .", "entity": [], "task": "NER"}
{"text": "The coercivity of the resulting powders was ~ 8 . 0 kOe and the saturation magnetization was ~ 40 emu g ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "After removal of CaO by washing , saturation magnetization increased and an energy product of 3 . 57 MGOe was obtained .", "entity": [{"entity": "CaO", "entity_type": "Chemical", "pos": [17, 20]}], "task": "NER"}
{"text": "A range of magnetic properties was obtained by varying the microwave power , reduction temperature and Nd to Fe ratio .", "entity": [{"entity": "Nd", "entity_type": "Chemical", "pos": [103, 105]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [109, 111]}], "task": "NER"}
{"text": "A transition from soft to exchange coupled to hard magnetic properties was obtained by varying the composition of NdxFe1 - xB8 ( x varies from 7 % to 40 % ) .", "entity": [{"entity": "NdxFe1 - xB8", "entity_type": "Chemical", "pos": [114, 126]}], "task": "NER"}
{"text": "This synthesis procedure offers an inexpensive and facile platform to produce exchange coupled hard magnets .", "entity": [], "task": "NER"}
{"text": "Acyl - CoA Synthetase 1 Is Induced by Gram - negative Bacteria and Lipopolysaccharide and Is Required for Phospholipid Turnover in Stimulated Macrophages .", "entity": [{"entity": "Acyl - CoA", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The enzyme acyl - CoA synthetase 1 ( ACSL1 ) is induced by peroxisome proliferator - activated receptor alpha ( PPAR alpha ) and PPAR gamma in insulin target tissues , such as skeletal muscle and adipose tissue , and plays an important role in beta - oxidation in these tissues .", "entity": [{"entity": "acyl - CoA", "entity_type": "Chemical", "pos": [11, 21]}], "task": "NER"}
{"text": "In macrophages , however , ACSL1 mediates inflammatory effects without significant effects on beta - oxidation .", "entity": [], "task": "NER"}
{"text": "Thus , the function of ACSL1 varies in different tissues .", "entity": [], "task": "NER"}
{"text": "We therefore investigated the signals and signal transduction pathways resulting in ACSL1 induction in macrophages as well as the consequences of ACSL1 deficiency for phospholipid turnover in LPS - activated macrophages .", "entity": [], "task": "NER"}
{"text": "LPS , Gram - negative bacteria , IFN - gamma , and TNF alpha all induce ACSL1 expression in macrophages , whereas PPAR agonists do not .", "entity": [], "task": "NER"}
{"text": "LPS - induced ACSL1 expression is dependent on Toll - like receptor 4 ( TLR4 ) and its adaptor protein TRIF ( Toll - like receptor adaptor molecule 1 ) but does not require the MyD88 ( myeloid differentiation primary response gene 88 ) arm of TLR4 signaling ; nor does it require STAT1 ( signal transducer and activator of transcription 1 ) for maximal induction .", "entity": [], "task": "NER"}
{"text": "Furthermore , ACSL1 deletion attenuates phospholipid turnover in LPS - stimulated macrophages .", "entity": [], "task": "NER"}
{"text": "Thus , the regulation and biological function of ACSL1 in macrophages differ markedly from that in insulin target tissues .", "entity": [], "task": "NER"}
{"text": "These results suggest that ACSL1 may have an important role in the innate immune response .", "entity": [], "task": "NER"}
{"text": "Further , these findings illustrate an interesting paradigm in which the same enzyme , ACSL1 , confers distinct biological effects in different cell types , and these disparate functions are paralleled by differences in the pathways that regulate its expression .", "entity": [], "task": "NER"}
{"text": "CYP2C8 * 3 polymorphism and donor age are associated with allograft dysfunction in kidney transplant recipients treated with calcineurin inhibitors .", "entity": [], "task": "NER"}
{"text": "Epoxieicosatrienoic acids ( EETs ) play a protective role against damaging processes in the kidney .", "entity": [{"entity": "Epoxieicosatrienoic acids", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "EETs", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "We have assessed the effect of polymorphisms in EETs - producing enzymes ( CYP2C8 and CYP2J2 ) and other proteins involved in calcineurin inhibitors ( CNIs ) disposition ( CYP3A4 , CYP3A5 , and ABCB1 ) on graft function and clinical outcome in 166 renal transplant recipients treated with CNIs .", "entity": [{"entity": "EETs", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "Both CYP2C8 * 3 and donor age greater than 48 years were associated to a higher incidence of delayed graft function ( DGF ) [ OR = 2 . 01 ( 1 . 1 - 4 . 1 ) , P = . 04 and 5 . 14 ( 2 . 4 - 10 . 9 ) , P < . 0001 ; respectively ] and worse creatinine clearance 1 year after grafting ( P < . 05 and P < . 001 , respectively ) .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [237, 247]}], "task": "NER"}
{"text": "In addition , carrying 4 - 6 variants in the 3 ABCB1 loci and older donor age were individually associated to higher incidence of calcineurin - inhibitor - induced nephrotoxicity [ OR = 2 . 38 ( 1 . 1 - 5 . 4 ) , P = . 03 and OR = 1 . 03 ( 1 . 01 - 1 . 06 ) , P = . 038 ] .", "entity": [], "task": "NER"}
{"text": "Regression analyses confirmed the relevant effect of both CYP2C8 * 3 and donor age on graft dysfunction .", "entity": [], "task": "NER"}
{"text": "Carrying the 2C8 * 3 allele and having a donor older than 48 years was defined as a high - risk status and observed to be highly related to DGF [ OR = 3 . 91 ( 1 . 46 - 10 . 48 ) , P < . 01 ] and worse creatinine clearance ( P = . 033 ) .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [202, 212]}], "task": "NER"}
{"text": "Our results show that genetic and clinical parameters can be combined to identify risk factors for allograft dysfunction in renal transplant recipients .", "entity": [], "task": "NER"}
{"text": "Dissecting the roles of the N - and C - flanking residues of acetyllysine substrates for SIRT1 activity .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [28, 29]}, {"entity": "C", "entity_type": "Chemical", "pos": [36, 37]}, {"entity": "acetyllysine", "entity_type": "Chemical", "pos": [61, 73]}], "task": "NER"}
{"text": "SIRT1 specificity : The multispecific SIRT1 enzyme catalyzes the deacetylation of acetyllysine residues within protein targets .", "entity": [{"entity": "acetyllysine", "entity_type": "Chemical", "pos": [82, 94]}], "task": "NER"}
{"text": "However , little is known regarding the molecular basis for SIRT1 substrate recognition .", "entity": [], "task": "NER"}
{"text": "Kinetic analysis of SIRT1 with a panel of peptide substrates shows the high importance of the region N - flanking the target acetyllysine and its high conservation through evolution .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [101, 102]}, {"entity": "acetyllysine", "entity_type": "Chemical", "pos": [125, 137]}], "task": "NER"}
{"text": "Chromatin Remodeling by Rosuvastatin Normalizes TSC2 - / meth Cell Phenotype through the Expression of Tuberin .", "entity": [{"entity": "Rosuvastatin", "entity_type": "Chemical", "pos": [24, 36]}], "task": "NER"}
{"text": "Tuberous sclerosis complex ( TSC ) is a multi - systemic syndrome caused by mutations in TSC1 or TSC2 gene .", "entity": [], "task": "NER"}
{"text": "In TSC2 - null cells , Rheb , a member of the Ras family of GTPases , is constitutively activated .", "entity": [], "task": "NER"}
{"text": "Statins inhibit 3 - hydroxy - 3 - methylglutaryl coenzyme A reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation .", "entity": [{"entity": "3 - hydroxy - 3 - methylglutaryl coenzyme A", "entity_type": "Chemical", "pos": [16, 59]}, {"entity": "isoprenoid", "entity_type": "Chemical", "pos": [97, 107]}], "task": "NER"}
{"text": "The effects of rosuvastatin on the function of human TSC2 ( - / - ) and TSC2 ( - / meth ) alpha - actin smooth muscle ( ASM ) cells have been investigated .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [15, 27]}], "task": "NER"}
{"text": "The TSC2 ( - / - ) and TSC2 ( - / meth ) ASM cells , previously isolated in our laboratory from the renal angiomyolipoma of two TSC patients , do not express tuberin and bear loss of heterozigosity caused by a double hit on TSC2 and methylation of TSC2 promoter , respectively .", "entity": [], "task": "NER"}
{"text": "Exposure to rosuvastatin affected TSC2 ( - / meth ) ASM cell growth and promoted tuberin expression by acting as a demethylating agent .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [12, 24]}], "task": "NER"}
{"text": "This occurred without changes in interleukin release .", "entity": [], "task": "NER"}
{"text": "Rosuvastatin also reduced RhoA activation in TSC2 ( - / meth ) ASM cells , and it required coadministration with the specific mTOR ( mammalian target of rapamycin ) inhibitor rapamycin to be effective in TSC2 ( - / - ) ASM cells .", "entity": [{"entity": "Rosuvastatin", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [153, 162]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [175, 184]}], "task": "NER"}
{"text": "Rapamycin enhanced rosuvastatin effect in inhibiting cell proliferation in TSC2 ( - / - ) and TSC2 ( - / meth ) ASM cells .", "entity": [{"entity": "Rapamycin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [19, 31]}], "task": "NER"}
{"text": "Rosuvastatin alone did not alter phosphorylation of S6 and extracellular signal - regulated kinase ( ERK ) , and at the higher concentration , rosuvastatin and rapamycin slightly decreased ERK phosphorylation .", "entity": [{"entity": "Rosuvastatin", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [143, 155]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [160, 169]}], "task": "NER"}
{"text": "These results suggest that rosuvastatin may potentially represent a treatment adjunct to the therapy with mTOR inhibitors now in clinical development for TSC .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [27, 39]}], "task": "NER"}
{"text": "In particular , rosuvastatin appears useful when the disease is originated by epigenetic defects .", "entity": [{"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [16, 28]}], "task": "NER"}
{"text": "PtCl2 - Catalyzed Tandem Enyne Cyclization / 1 , 2 Ester Migration Reaction Controlled by Substituent Effects of All - Carbon 1 , 6 - Enynyl Esters .", "entity": [{"entity": "PtCl2", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "Enyne", "entity_type": "Chemical", "pos": [25, 30]}, {"entity": "1 , 2 Ester", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "All - Carbon 1 , 6 - Enynyl Esters", "entity_type": "Chemical", "pos": [113, 147]}], "task": "NER"}
{"text": "On the move : A novel PtCl2 - catalyzed tandem 1 , 6 - enyne cyclization / 1 , 2 - acyloxy migration reaction was developed , which was shown to be controlled by substitution effects .", "entity": [{"entity": "PtCl2", "entity_type": "Chemical", "pos": [22, 27]}, {"entity": "1 , 6 - enyne", "entity_type": "Chemical", "pos": [47, 60]}, {"entity": "1 , 2 - acyloxy", "entity_type": "Chemical", "pos": [75, 90]}], "task": "NER"}
{"text": "Using this method , a series of substituted enol esters containing the cyclopentenyl motif were prepared in moderate to high yields .", "entity": [{"entity": "enol esters", "entity_type": "Chemical", "pos": [44, 55]}, {"entity": "cyclopentenyl", "entity_type": "Chemical", "pos": [71, 84]}], "task": "NER"}
{"text": "Surface Enhanced Raman Scattering on Non - SERS Active Substrates and In Situ Electrochemical Study based on a Single Gold Microshell .", "entity": [], "task": "NER"}
{"text": "A single gold microshell , which was elaborately fabricated to carry numerous hot spots on its own surface , enabled the acquisition of the SERS spectra from the molecules on non - SERS active substrates such as Si / SiO2 , ITO , and glass .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [212, 214]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [217, 221]}, {"entity": "ITO", "entity_type": "Chemical", "pos": [224, 227]}], "task": "NER"}
{"text": "A self - assembled monolayer of 11 - mercaptoundecanols on the gold microshell offered an easy and reliable way to electrically insulate from the underlying flat Pt electrode and accomplish in situ monitoring the electrochemical reaction with minimal interference .", "entity": [{"entity": "11 - mercaptoundecanols", "entity_type": "Chemical", "pos": [32, 55]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [162, 164]}], "task": "NER"}
{"text": "Acute waterborne copper toxicity to the euryhaline copepod Acartia tonsa at different salinities : Influence of natural freshwater and marine dissolved organic matter .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [17, 23]}], "task": "NER"}
{"text": "The influence of natural dissolved organic matter ( DOM ) on acute waterborne Cu toxicity was evaluated in the euryhaline copepod Acartia tonsa at 3 different water salinities .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [78, 80]}], "task": "NER"}
{"text": "Three sources of freshwater DOM ( extracted by reverse osmosis ) and 2 sources of marine DOM ( extracted using a solid - phase technique ) were used .", "entity": [], "task": "NER"}
{"text": "Artificial salt water was used to prepare the experimental media .", "entity": [], "task": "NER"}
{"text": "Different combinations of Cu concentrations and DOM sources and concentrations were tested at salinities of 5 , 15 , and 30 ppt .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [26, 28]}], "task": "NER"}
{"text": "Toxicity data ( 48 - h median lethal concentration [ LC50 ] values ) were calculated based on dissolved Cu concentrations .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [104, 106]}], "task": "NER"}
{"text": "In a broad view , data showed that increasing salinity was protective against the acute waterborne Cu toxicity .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [99, 101]}], "task": "NER"}
{"text": "In general , Cu toxicity was also lower in the presence than in the absence of DOM .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [13, 15]}], "task": "NER"}
{"text": "Toxicity ( 48 - h LC50 ) values from all treatments at the same salinity showed a positive linear relationship with the dissolved organic carbon ( DOC ) .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [138, 144]}], "task": "NER"}
{"text": "Thus , the protective effect of DOM against the acute Cu toxicity seems to be dependent mainly on the DOM concentration .", "entity": [{"entity": "Cu", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "However , it seems also to be dependent to some extent on the source of DOM used .", "entity": [], "task": "NER"}
{"text": "In summary , findings reported in the present study clearly indicate that both salinity and DOM ( source and concentration ) should be taken into account in the development of an estuarine version of the biotic ligand model .", "entity": [], "task": "NER"}
{"text": "Environ Toxicol Chem 2013 ; 32 : 1412 - 1419 .", "entity": [], "task": "NER"}
{"text": "Physical Properties and Erosion Behavior of Poly ( trimethylene carbonate - co - epsilon - caprolactone ) Networks .", "entity": [{"entity": "Poly ( trimethylene carbonate - co - epsilon - caprolactone )", "entity_type": "Chemical", "pos": [44, 105]}], "task": "NER"}
{"text": "Form - stable resorbable networks are prepared by gamma irradiating trimethylene carbonate ( TMC ) - and epsilon - caprolactone ( CL ) - based ( co ) polymer films .", "entity": [{"entity": "trimethylene carbonate", "entity_type": "Chemical", "pos": [68, 90]}, {"entity": "TMC", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "epsilon - caprolactone", "entity_type": "Chemical", "pos": [105, 127]}], "task": "NER"}
{"text": "To evaluate their suitability for biomedical applications , their physical properties and erosion behavior are investigated .", "entity": [], "task": "NER"}
{"text": "Homopolymer and copolymer networks that are amorphous at room temperature are flexible and rubbery with elastic moduli ranging from 1 . 8 +/- 0 . 3 to 5 . 2 +/- 0 . 4 MPa and permanent set values as low as 0 . 9 % strain .", "entity": [], "task": "NER"}
{"text": "The elastic moduli of the semicrystalline networks are higher and range from 61 +/- 3 to 484 +/- 34 MPa .", "entity": [], "task": "NER"}
{"text": "The erosion behavior of ( co ) polymer networks is investigated in vitro using macrophage cultures , and in vivo by subcutaneous implantation in rats .", "entity": [], "task": "NER"}
{"text": "In macrophage cultures , as well as upon implantation , a surface erosion process is observed for the amorphous ( co ) polymer networks , while an abrupt decrease in the rate and a change in the nature of the erosion process are observed with increasing crystallinity .", "entity": [], "task": "NER"}
{"text": "These resorbable and form - stable networks with tuneable properties may find application in a broad range of biomedical applications .", "entity": [], "task": "NER"}
{"text": "Improvement of nanoprecipitation technique for preparation of gelatin nanoparticles and potential macromolecular drug loading .", "entity": [], "task": "NER"}
{"text": "An optimum nanoprecipitation technique for gelatin nanoparticles is established , based on aqueous gelatin solution and ethanolic solution containing stabilizer .", "entity": [], "task": "NER"}
{"text": "Crosslinking with glutaraldehyde results in stable gelatine nanoparticles .", "entity": [{"entity": "glutaraldehyde", "entity_type": "Chemical", "pos": [18, 32]}], "task": "NER"}
{"text": "Several factors such as the surfactant concentration , type of surfactant , type of nonsolvent and gelatin concentration are evaluated .", "entity": [], "task": "NER"}
{"text": "Gelatin nanoparticles with 200 - 300 nm can be produced using 20 - 30 mg mL ( - 1 ) of gelatin and a minimum of 7 % w / v stabilizer ( Poloxamer 407 or 188 ) .", "entity": [], "task": "NER"}
{"text": "Furthermore , methanol and ethanol are good nonsolvents , whereas other nonsolvents such as acetone , isopropyl alcohol , and acetonitrile , result in phase separation and visible precipitates .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "isopropyl alcohol", "entity_type": "Chemical", "pos": [102, 119]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [126, 138]}], "task": "NER"}
{"text": "The entrapment efficiency of fluorescein - isothiocyanate ( FITC ) - dextran as model drug was determined to 50 % with no substantial effect on particle size .", "entity": [{"entity": "fluorescein - isothiocyanate", "entity_type": "Chemical", "pos": [29, 57]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [60, 64]}], "task": "NER"}
{"text": "80 % of the drug is only released after enzymatic digestion .", "entity": [], "task": "NER"}
{"text": "Neural correlates of performance monitoring in chronic cannabis users and cannabis - naive controls .", "entity": [], "task": "NER"}
{"text": "Chronic cannabis use is associated with residual negative effects on measures of executive functioning .", "entity": [], "task": "NER"}
{"text": "However , little previous work has focused specifically on executive processes involved in performance monitoring in frequent cannabis users .", "entity": [], "task": "NER"}
{"text": "The present study investigated event - related potential ( ERP ) correlates of performance monitoring in chronic cannabis users .", "entity": [], "task": "NER"}
{"text": "The error - related negativity ( ERN ) and error positivity ( Pe ) , ERPs sensitive to performance monitoring , were recorded from 30 frequent cannabis users ( mean usage = 5 . 52 days / week ) and 32 cannabis - na i ve control participants during a speeded stimulus discrimination task .", "entity": [], "task": "NER"}
{"text": "The \" oddball \" P3 ERP was recorded as well .", "entity": [], "task": "NER"}
{"text": "Users and controls did not differ on the amplitude or latency of the ERN ; however , Pe amplitude was larger among users .", "entity": [], "task": "NER"}
{"text": "Users also showed increased amplitude and reduced latency of the P3 in response to infrequent stimuli presented during the task .", "entity": [], "task": "NER"}
{"text": "Among users , urinary cannabinoid metabolite levels at testing were unrelated to ERP outcomes .", "entity": [], "task": "NER"}
{"text": "However , total years of cannabis use correlated negatively with P3 latency and positively with P3 amplitude , and age of first cannabis use correlated negatively with P3 amplitude .", "entity": [], "task": "NER"}
{"text": "The results of this study suggest that chronic cannabis use is associated with alterations in neural activity related to the processing of motivationally - relevant stimuli ( P3 ) and errors ( Pe ) .", "entity": [], "task": "NER"}
{"text": "Expansion of Secretin - Like G Protein - Coupled Receptors and Their Peptide Ligands via Local Duplications Before and After Two Rounds of Whole - Genome Duplication .", "entity": [], "task": "NER"}
{"text": "In humans , the secretin - like G protein - coupled receptor ( GPCR ) family comprises 15 members with 18 corresponding peptide ligand genes .", "entity": [], "task": "NER"}
{"text": "Although members have been identified in a large variety of vertebrate and nonvertebrate species , the origin and relationship of these proteins remain unresolved .", "entity": [], "task": "NER"}
{"text": "To address this issue , we employed large - scale genome comparisons to identify genome fragments with conserved synteny and matched these fragments to linkage groups in reconstructed early gnathostome ancestral chromosomes ( GAC ) .", "entity": [], "task": "NER"}
{"text": "This genome comparison revealed that most receptor and peptide genes were clustered in three GAC linkage groups and suggested that the ancestral forms of five peptide subfamilies ( corticotropin - releasing hormone - like , calcitonin - like , parathyroid hormone - like , glucagon - like , and growth hormone - releasing hormone - like ) and their cognate receptor families emerged through tandem local gene duplications before two rounds ( 2R ) of whole - genome duplication .", "entity": [], "task": "NER"}
{"text": "These subfamily genes have , then , been amplified by 2R whole - genome duplication , followed by additional local duplications and gene loss prior to the divergence of land vertebrates and teleosts .", "entity": [], "task": "NER"}
{"text": "This study delineates a possible evolutionary scenario for whole secretin - like peptide and receptor family members and may shed light on evolutionary mechanisms for expansion of a gene family with a large number of paralogs .", "entity": [], "task": "NER"}
{"text": "Decompression - induced crystal polymorphism in a room - temperature ionic liquid , N , N - diethyl - N - methyl - N - ( 2 - methoxyethyl ) ammonium tetrafluoroborate .", "entity": [{"entity": "N , N - diethyl - N - methyl - N - ( 2 - methoxyethyl ) ammonium tetrafluoroborate", "entity_type": "Chemical", "pos": [84, 166]}], "task": "NER"}
{"text": "We explore the phase behavior of room - temperature ionic liquids ( RTILs ) compressed under high pressure to determine whether they crystallize or hold a liquid state .", "entity": [], "task": "NER"}
{"text": "RTILs have attractive supercooling properties compared with ordinary molecular liquids , which easily become a glassy state without crystallizing at ambient pressure .", "entity": [], "task": "NER"}
{"text": "Thus , phase behavior under extreme stress , such as pressure , might yield interesting results .", "entity": [], "task": "NER"}
{"text": "Here , we show that N , N - diethyl - N - methyl - N - ( 2 - methoxyethyl ) ammonium tetrafluoroborate ( [ DEME ] [ BF4 ] ) could be crystallized upon compression , but it usually formed a superpressed liquid .", "entity": [{"entity": "N , N - diethyl - N - methyl - N - ( 2 - methoxyethyl ) ammonium tetrafluoroborate", "entity_type": "Chemical", "pos": [20, 102]}, {"entity": "[ DEME ] [ BF4 ]", "entity_type": "Chemical", "pos": [105, 121]}], "task": "NER"}
{"text": "Alternatively , unusual crystallization could be induced by releasing the pressure on the superpressed liquid .", "entity": [], "task": "NER"}
{"text": "Notably , crystal polymorphism was observed in the decompression process .", "entity": [], "task": "NER"}
{"text": "These facts along with visual observations indicate the possibility of [ DEME ] [ BF4 ] serving as a superpressurized glass .", "entity": [{"entity": "[ DEME ] [ BF4 ]", "entity_type": "Chemical", "pos": [71, 87]}], "task": "NER"}
{"text": "Our findings may facilitate the development of a new range of applications for RTILs that have undergone high - pressure recrystallization .", "entity": [], "task": "NER"}
{"text": "Excitons in conjugated polymers : a tale of two particles .", "entity": [], "task": "NER"}
{"text": "Since the discovery of electroluminescence in the phenyl - based conjugated polymers in 1990 , the field of polymer optoelectronics has matured to the extent that presently a wide class of devices have been commercialized .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [50, 56]}], "task": "NER"}
{"text": "These range from both miniature and wide - area light emitting devices to hybrid photovoltaic devices .", "entity": [], "task": "NER"}
{"text": "Similarly , our understanding of the fundamental processes that determine these optoelectronic properties has also progressed .", "entity": [], "task": "NER"}
{"text": "In particular , owing to insights from both experimental and theoretical investigations , the role of the primary excited states , i . e . , excitons , is now considerably clearer .", "entity": [], "task": "NER"}
{"text": "This review discusses these primary excited states and explains how the three key roles of electron - electron interactions , electron - nuclear coupling , and disorder determine their properties .", "entity": [], "task": "NER"}
{"text": "We show that the properties of an exciton are more readily understood by decomposing it into two effective particles .", "entity": [], "task": "NER"}
{"text": "First , a relative particle that describes the size and binding energy of the electron - hole pair .", "entity": [], "task": "NER"}
{"text": "Second , a center - of - mass particle that describes the extent of the delocalization of the electron - hole pair .", "entity": [], "task": "NER"}
{"text": "Disorder and coupling to the normal modes localizes the center - of - mass particle and provides a quantitative definition of chromophores in conjugated polymers , paving the way for a first - principles theory of exciton diffusion in these systems .", "entity": [], "task": "NER"}
{"text": "Components of the Interleukin - 6 transsignalling system are associated with the metabolic syndrome , endothelial dysfunction and arterial stiffness .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : The metabolic syndrome ( MetS ) is an increasing epidemiologic challenge and cardiovascular risk factor .", "entity": [], "task": "NER"}
{"text": "Interleukin - 6 ( IL - 6 ) is a cytokine that exerts its biological function via a complex orchestration of soluble and membrane bound receptors .", "entity": [], "task": "NER"}
{"text": "We have investigated associations between IL - 6 and its soluble receptors , soluble IL - 6 receptor ( sIL - 6r ) and soluble glycoprotein 130 ( sGP130 ) and the metabolic syndrome .", "entity": [], "task": "NER"}
{"text": "Furthermore , we have investigated possible associations with endothelial dysfunction and arterial stiffness .", "entity": [], "task": "NER"}
{"text": "METHODS : A total of 563 subjects were included in this study .", "entity": [], "task": "NER"}
{"text": "The Adult Treatment Panel III criteria of the National Cholesterol Education Program were used for the definition of MetS .", "entity": [{"entity": "Cholesterol", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "We used commercially available ELISA to analyse circulating levels of the markers .", "entity": [], "task": "NER"}
{"text": "Pulse wave propagation time ( PWP ) was determined to assess arterial stiffness .", "entity": [], "task": "NER"}
{"text": "RESULTS : The criteria for having MetS were filled by 221 subjects .", "entity": [], "task": "NER"}
{"text": "sGP130 , sIL - 6r and IL - 6 levels were elevated in subjects with MetS ( p < 0 . 05 for all markers ) , and are associated with increasing components of MetS .", "entity": [], "task": "NER"}
{"text": "Particularly hypertriglyceridaemia , hypertension and fasting plasma glucose ( FPG ) seem to carry this association .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [69, 76]}], "task": "NER"}
{"text": "sGP130 ( p < 0 . 01 ) , IL - 6 ( p < 0 . 05 ) and partially sIL - 6r ( p < 0 . 05 ) correlated with markers of endothelial function ( E - selectin , I - CAM - 1 , V - CAM - 1 ) and inversely with PWP after adjustment for relevant covariates .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : sGP130 , sIL - 6r and IL - 6 were significantly elevated in subjects with MetS .", "entity": [], "task": "NER"}
{"text": "In addition , sGP130 , IL - 6 and partially sIL - 6r were associated with markers of endothelial function and arterial stiffness .", "entity": [], "task": "NER"}
{"text": "This finding sheds new light on the role of these inflammatory cytokines in subjects with MetS and the development and progression of clinically silent atherosclerosis .", "entity": [], "task": "NER"}
{"text": "Atorvastatin withdrawal elicits oxidative / nitrosative damage in the rat cerebral cortex .", "entity": [{"entity": "Atorvastatin", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Statins are inhibitors of the enzyme 3 - hydroxy - 3 - methylglutaryl coenzyme A reductase , the rate - limiting step in cholesterol biosynthesis .", "entity": [{"entity": "3 - hydroxy - 3 - methylglutaryl coenzyme A", "entity_type": "Chemical", "pos": [37, 80]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "Statins effectively prevent and reduce the risk of coronary artery disease through lowering serum cholesterol , and also exert anti - thrombotic , anti - inflammatory and antioxidant effects independently of changes in cholesterol levels .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [98, 109]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [219, 230]}], "task": "NER"}
{"text": "On the other hand , clinical and experimental evidence suggests that abrupt cessation of statin treatment ( i . e . statin withdrawal ) is associated with a deleterious rebound phenomenon .", "entity": [], "task": "NER"}
{"text": "In fact , statin withdrawal increases the risk of thrombotic vascular events , causes impairment of endothelium - dependent relaxation and facilitates experimental seizures .", "entity": [], "task": "NER"}
{"text": "However , evidence for statin withdrawal - induced detrimental effects to the brain parenchyma is still lacking .", "entity": [], "task": "NER"}
{"text": "In the present study adult male Wistar rats were treated with atorvastatin for seven days ( 10mg / kg / day ) and neurochemical assays were performed in the cerebral cortex 30min ( atorvastatin treatment ) or 24h ( atorvastatin withdrawal ) after the last atorvastatin administration .", "entity": [{"entity": "atorvastatin", "entity_type": "Chemical", "pos": [62, 74]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [181, 193]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [215, 227]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [256, 268]}], "task": "NER"}
{"text": "We found that atorvastatin withdrawal decreased levels of nitric oxide and mitochondrial superoxide dismutase activity , whereas increased NADPH oxidase activity and immunoreactivity for the protein nitration marker 3 - nitrotyrosine in the cerebral cortex .", "entity": [{"entity": "atorvastatin", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [58, 70]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [139, 144]}, {"entity": "3 - nitrotyrosine", "entity_type": "Chemical", "pos": [216, 233]}], "task": "NER"}
{"text": "Catalase , glutathione - S - transferase and xanthine oxidase activities were not altered by atorvastatin treatment or withdrawal , as well as protein carbonyl and 4 - hydroxy - 2 - nonenal immunoreactivity .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [11, 22]}, {"entity": "S", "entity_type": "Chemical", "pos": [25, 26]}, {"entity": "xanthine", "entity_type": "Chemical", "pos": [45, 53]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [93, 105]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [151, 159]}, {"entity": "4 - hydroxy - 2 - nonenal", "entity_type": "Chemical", "pos": [164, 189]}], "task": "NER"}
{"text": "Immunoprecipitation of mitochondrial SOD followed by analysis of 3 - nitrotyrosine revealed increased levels of nitrated mitochondrial SOD , suggesting the mechanism underlying the atorvastatin withdrawal - induced decrease in enzyme activity .", "entity": [{"entity": "3 - nitrotyrosine", "entity_type": "Chemical", "pos": [65, 82]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [181, 193]}], "task": "NER"}
{"text": "Altogether , our results indicate the atorvastatin withdrawal elicits oxidative / nitrosative damage in the rat cerebral cortex , and that changes in NADPH oxidase activity and mitochondrial superoxide dismutase activities may underlie such harmful effects .", "entity": [{"entity": "atorvastatin", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [150, 155]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [191, 201]}], "task": "NER"}
{"text": "Medical therapy of coronary artery disease after percutaneous intervention .", "entity": [], "task": "NER"}
{"text": "Medical therapy following percutaneous coronary intervention aims at preventing first , coronary disease progression and its clinical manifestations , and finally , the two main complications of coronary stenting , stent thrombosis and restenosis .", "entity": [], "task": "NER"}
{"text": "Prevention of in - stent restenosis is restricted to local drug delivery in the form of drug eluting stents ( DES ) .", "entity": [], "task": "NER"}
{"text": "Second generation DES have improved their efficacy and safety profile by innovations in drug coating , the polymer drug - delivery system and stent design .", "entity": [], "task": "NER"}
{"text": "The mainstay of stent thrombosis prevention remains dual anti - platelet therapy with acetylsalicylic acid and a platelet ADP - receptor blocker , traditionally clopidogrel .", "entity": [{"entity": "acetylsalicylic acid", "entity_type": "Chemical", "pos": [86, 106]}, {"entity": "ADP", "entity_type": "Chemical", "pos": [122, 125]}, {"entity": "clopidogrel", "entity_type": "Chemical", "pos": [161, 172]}], "task": "NER"}
{"text": "Two new drugs , prasugrel and ticagrelor , provide faster , greater , and more consistent platelet inhibition than clopidogrel , and have been shown to be more efficacious in preventing ischemic events after PCI in acute coronary syndrome patients .", "entity": [{"entity": "prasugrel", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "ticagrelor", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "clopidogrel", "entity_type": "Chemical", "pos": [115, 126]}], "task": "NER"}
{"text": "Oxysterol - binding proteins : Functions in cell regulation beyond lipid metabolism .", "entity": [{"entity": "Oxysterol", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Oxysterol - binding ( OSBP ) - related proteins ( ORPs ) constitute a family of sterol and phosphoinositide binding / transfer proteins in eukaryotes from yeast to man .", "entity": [{"entity": "Oxysterol", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [80, 86]}, {"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [91, 107]}], "task": "NER"}
{"text": "While their functions have mainly been addressed in cellular lipid metabolism or sterol transport , increasing evidence points to more versatile regulatory roles in a spectrum of cellular regimes .", "entity": [{"entity": "sterol", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "In fact ORPs do not appear to be robust controllers of lipid homeostasis .", "entity": [], "task": "NER"}
{"text": "Several ORPs localize at membrane contacts sites ( MCS ) , where endoplasmic reticulum ( ER ) is apposed with other organelle limiting membranes .", "entity": [], "task": "NER"}
{"text": "Apparently , ORPs have the capacity to control the formation of MCS or activity of enzymatic machineries at these sites .", "entity": [], "task": "NER"}
{"text": "Thereby , ORPs most likely affect organelle membrane lipid compositions , with impacts on signaling and vesicle transport , but also cellular lipid metabolism .", "entity": [], "task": "NER"}
{"text": "Moreover , an increasing number of protein interaction partners of ORPs have been identified , connecting these proteins with various aspects of cell regulation .", "entity": [], "task": "NER"}
{"text": "Small molecular anti - proliferative compounds , ORPphilins , were recently found to target two members of the ORP family , OSBP and ORP4 , revealing an essential function of ORPs in cancer cell proliferation and survival .", "entity": [], "task": "NER"}
{"text": "Further functions assigned for ORPs include regulation of extracellular signal regulated kinase ( ERK ) activity ( OSBP ) , control of ER - late endosome MCS and late endosome motility ( ORP1L ) , regulation of beta 1 - integrin activity ( ORP3 ) , modulation of hepatocyte insulin signaling and macrophage migration ( ORP8 ) , as well as post - Golgi vesicle transport , phosphatidylinositol - 4 - phosphate and target of rapamycin complex 1 signaling and nitrogen sensing ( Saccharomyces cerevisiae Osh4p ) .", "entity": [{"entity": "phosphatidylinositol - 4 - phosphate", "entity_type": "Chemical", "pos": [372, 408]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [423, 432]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [457, 465]}], "task": "NER"}
{"text": "These and other recent observations shed light on the ORPs as integrators of lipid signals with an unforeseen variety of vital cellular processes .", "entity": [], "task": "NER"}
{"text": "Inhibitory effect of dihydroartemisinin against phorbol ester - induced cyclooxygenase - 2 expression in macrophages .", "entity": [{"entity": "dihydroartemisinin", "entity_type": "Chemical", "pos": [21, 39]}, {"entity": "phorbol ester", "entity_type": "Chemical", "pos": [48, 61]}], "task": "NER"}
{"text": "Dihydroartemisinin ( DHA ) , a semi - synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua L . , has recently been shown to possess antitumor activity in various cancer cells .", "entity": [{"entity": "Dihydroartemisinin", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [21, 24]}, {"entity": "artemisinin", "entity_type": "Chemical", "pos": [62, 73]}], "task": "NER"}
{"text": "However , the effect of anti - inflammatory potentials of DHA in murine macrophage RAW 264 . 7 cells has not been studied .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "The present study investigated the effect of COX - 2 and molecular mechanisms by DHA in PMA stimulated RAW 264 . 7 cells .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "PMA", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "DHA dose - dependently decreased PMA - induced COX - 2 expression and PGE2 production , as well as COX - 2 promoter - driven luciferase activity .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "PMA", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "Additionally , DHA decreased luciferase activity of COX - 2 regulation - related transcription factors including NF - kappa B , AP - 1 , C / EBP and CREB .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [15, 18]}], "task": "NER"}
{"text": "DHA also remarkably reduced PMA - induced p65 , C / EBP beta , c - jun and CREB nuclear translocation .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "PMA", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "Furthermore , DHA evidently inhibited PMA - induced phosphorylation of AKT and the MAP Kinases , such as ERK , JNK and p38 .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "PMA", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Taken together , our data indicated that DHA effectively attenuates COX - 2 production via down - regulation of AKT and MAPK pathway , revealing partial molecular basis for the anti - inflammatory properties of DHA .", "entity": [{"entity": "DHA", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [211, 214]}], "task": "NER"}
{"text": "Low - dose bisphenol A and estrogen increase ventricular arrhythmias following ischemia - reperfusion in female rat hearts .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [11, 22]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) is an environmental estrogenic endocrine disruptor that may have adverse health impacts on a range of tissue / systems .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "In previous studies , we reported that BPA rapidly promoted arrhythmias in female rodent hearts through alteration of myocyte calcium handling .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "In the present study we investigated the acute effects of BPA on ventricular arrhythmias and infarction following ischemia - reperfusion in rat hearts .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "Rat hearts were subjected to 20min of global ischemia followed by reperfusion .", "entity": [], "task": "NER"}
{"text": "In female , but not male hearts , acute exposure to 1nM BPA , either alone or combined with 1nM 17 beta - estradiol ( E2 ) , during reperfusion resulted in a marked increase in the duration of sustained ventricular arrhythmias .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [96, 115]}], "task": "NER"}
{"text": "BPA plus E2 increased the duration ventricular fibrillation , and the duration of VF as a fraction of total duration of sustained ventricular arrhythmia .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The pro - arrhythmic effects of estrogens were abolished by MPP combined with PHTPP , suggesting the involvements of both ER alpha and ER beta signaling .", "entity": [{"entity": "estrogens", "entity_type": "Chemical", "pos": [32, 41]}, {"entity": "MPP", "entity_type": "Chemical", "pos": [60, 63]}, {"entity": "PHTPP", "entity_type": "Chemical", "pos": [78, 83]}], "task": "NER"}
{"text": "In contrast to their pro - arrhythmic effects , BPA and E2 reduced infarction size , agreeing with previously described protective effect of estrogen against cardiac infarction .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "In conclusion , rapid exposure to low dose BPA , particularly when combined with E2 , exacerbates ventricular arrhythmia following IR injury in female rat hearts .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "Effects of maternally exposed coloring food additives on receptor expressions related to learning and memory in rats .", "entity": [], "task": "NER"}
{"text": "Exposure to artificial food colors and additives ( AFCAs ) has been implicated in the induction and severity of some childhood behavioral and learning disabilities .", "entity": [], "task": "NER"}
{"text": "N - methyl - D - aspartate receptors ( NMDARs ) and nicotinic acetylcholine receptors ( nACHRs ) are thought to be effective in the learning and memory - generating process .", "entity": [{"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [62, 75]}], "task": "NER"}
{"text": "In this study , we investigated the effects of intrauterine exposure to AFCAs on subunit concentrations of NMDARs and nAChRs isoforms in rats .", "entity": [], "task": "NER"}
{"text": "We administered a mixture of AFCAs ( Eritrosin , Ponceau 4R , Allura Red AC , Sunset Yellow FCF , Tartrazin , Amaranth , Brilliant Blue , Azorubin and Indigotin ) to female rats before and during gestation .", "entity": [{"entity": "Eritrosin", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "Ponceau 4R", "entity_type": "Chemical", "pos": [49, 59]}, {"entity": "Allura Red AC", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "Sunset Yellow FCF", "entity_type": "Chemical", "pos": [78, 95]}, {"entity": "Tartrazin", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "Amaranth", "entity_type": "Chemical", "pos": [110, 118]}, {"entity": "Brilliant Blue", "entity_type": "Chemical", "pos": [121, 135]}, {"entity": "Azorubin", "entity_type": "Chemical", "pos": [138, 146]}, {"entity": "Indigotin", "entity_type": "Chemical", "pos": [151, 160]}], "task": "NER"}
{"text": "The concentration of NR2A and NR2B subunits and nAChR alpha 7 , alpha 4 beta 2 isoforms in their offspring ' s hippocampi were measured by Western Blotting .", "entity": [], "task": "NER"}
{"text": "Expressions of NR2B and nAChR beta 2 were significantly increased ( 17 % and 6 . 70 % , respectively ) , whereas expression of nAChR alpha 4 was significantly decreased ( 5 . 67 % ) in male experimental group compared to the male control group ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "In the female experimental group , AFCAs caused a 14 % decrease in NR2B expression when compared to the female control group ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Our results indicate that exposure to AFCAs during the fetal period may lead to alterations in expressions of NMDARs and nAChRs in adulthood .", "entity": [], "task": "NER"}
{"text": "These alterations were different between male and female genders .", "entity": [], "task": "NER"}
{"text": "Metallothionein 1A polymorphisms may influence urine uric acid and N - acetyl - beta - d - glucosaminidase ( NAG ) excretion in chronic lead - exposed workers .", "entity": [{"entity": "uric acid", "entity_type": "Chemical", "pos": [53, 62]}, {"entity": "N - acetyl", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Lead is a renal toxin , and susceptibility to lead varies between individuals .", "entity": [], "task": "NER"}
{"text": "Metallothionein ( MT ) is known for its metal scavenging role .", "entity": [], "task": "NER"}
{"text": "The aim of the study was to investigate the association of blood lead levels , urinary uric acid ( UA ) and N - acetyl - beta - d - glucosaminidase ( NAG ) in chronic occupational lead - exposed workers , and to study whether the association was influenced by MT1A gene polymorphisms .", "entity": [{"entity": "uric acid", "entity_type": "Chemical", "pos": [87, 96]}, {"entity": "N - acetyl", "entity_type": "Chemical", "pos": [108, 118]}], "task": "NER"}
{"text": "In this cross - sectional study , 412 lead - exposed workers participated .", "entity": [], "task": "NER"}
{"text": "Their annual health examination data and renal function markers were collected after the Institutional Review Broad of Kaohsiung Medical University Hospital approved the study and consent letters were obtained .", "entity": [], "task": "NER"}
{"text": "From the blood samples , DNA was extracted and used for real - time PCR typing of 2 MT1A single nucleotide polymorphisms ( SNPs ) : rs11640851 and rs8052394 on exons 2 and 3 .", "entity": [], "task": "NER"}
{"text": "Descriptive analysis , one - way ANOVA , and multiple linear regressions were performed .", "entity": [], "task": "NER"}
{"text": "There was a significant inverted relationship of creatinine - adjusted urine UA concentrations and the time - weighted index of cumulative blood lead levels ( TWICL ) that may be significantly influenced by the AC genotypes of rs11640851 in exon 2 and rs8052394 in exon 3 .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [49, 59]}], "task": "NER"}
{"text": "After controlling for potential confounding factors , the creatinine - adjusted urine NAG concentrations were shown to be influenced by the GG genotype of rs8052394 in exon 3 , and were weakly increased with TWICL .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "Therefore , we concluded that the variations of MT1A SNPs may influence urine UA and NAG excretion in chronic lead - exposed workers , and urine creatinine - adjusted urine UA as a biomarker of lead toxicity should be considered .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [145, 155]}], "task": "NER"}
{"text": "Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD .", "entity": [{"entity": "Alcohol", "entity_type": "Chemical", "pos": [28, 35]}], "task": "NER"}
{"text": "RATIONALE : Prior research has found that adults with attention - deficit / hyperactivity disorder ( ADHD ) show increased sensitivity to the impairing effects of alcohol ( Weafer et al . , Exp Clin Psychopharmacol 17 : 113 - 121 , 2009 ) .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "However , these studies have focused exclusively on the ascending limb of the blood alcohol concentration ( BAC ) curve , and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "OBJECTIVE : This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "METHODS : Adult social drinkers with ADHD and control adults completed measures of motor coordination , reaction time ( RT ) , and subjective intoxication twice following 0 . 64 g / kg alcohol and placebo .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [185, 192]}], "task": "NER"}
{"text": "The measures were administered during the ascending limb of the BAC curve and again during the descending limb .", "entity": [], "task": "NER"}
{"text": "RESULTS : During the ascending limb , alcohol reduced motor coordination , slowed RT , and increased self - reports of subjective intoxication .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [38, 45]}], "task": "NER"}
{"text": "Those with ADHD displayed greater impairment of motor coordination compared with controls .", "entity": [], "task": "NER"}
{"text": "During the descending limb , controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "Those with ADHD showed reduced subjective intoxication and faster RT during this time , but they did not recover motor control .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group .", "entity": [], "task": "NER"}
{"text": "Effect of chronic ethanol treatment on mu - opioid receptor function , interacting proteins and morphine - induced place preference .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [18, 25]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "RATIONALE : Both the acute and chronic consumption of ethanol have been reported to modify several molecular events in the central nervous system , and the endogenous mu - opioid receptor system is involved in the reinforcing / rewarding effects of ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [249, 256]}], "task": "NER"}
{"text": "OBJECTIVES : The present study was designed to clarify the effects of chronic ethanol treatment on cellular processes involving mu - opioid receptor and the development of morphine - induced rewarding effects .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [172, 180]}], "task": "NER"}
{"text": "METHODS : Male C57BL / 6J mice were continuously treated with a liquid diet containing 3 . 0 w / v ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "The direct involvement of mu - opioid receptor functions in the activation of G - proteins and changes in protein levels in the lower midbrain of mice after chronic treatment with ethanol were investigated by a [ ( 35 ) S ] GTP gamma S binding assay and Western blotting , respectively .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [180, 187]}, {"entity": "[ ( 35 ) S ] GTP gamma S", "entity_type": "Chemical", "pos": [211, 235]}], "task": "NER"}
{"text": "The rewarding effects of morphine ( 5 mg / kg ) under treatment with ethanol were measured by the conditioned place preference paradigm .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [69, 76]}], "task": "NER"}
{"text": "RESULTS : The function of mu - opioid receptor was increased by treatment with ethanol in the lower midbrain using [ ( 35 ) S ] GTP gamma S binding assay .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "[ ( 35 ) S ] GTP gamma S", "entity_type": "Chemical", "pos": [115, 139]}], "task": "NER"}
{"text": "Furthermore , the GRK2 protein level was significantly increased by treatment with ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "Chronic treatment with ethanol enhanced the rewarding effects of morphine .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [23, 30]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "On the other hand , this enhancement of the rewarding effects of morphine by ethanol treatment was significantly inhibited by the GRK2 inhibitor beta - adrenergic receptor kinase 1 inhibitor .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [65, 73]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "CONCLUSIONS : The present study demonstrated that chronic treatment with ethanol enhanced the rewarding effects of morphine by up - regulating functional changes in mu - opioid receptor , mediated by GRK2 .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "Interleukin - 10 promoter variants predict HPV - positive tumors and survival of squamous cell carcinoma of the oropharynx .", "entity": [], "task": "NER"}
{"text": "Interleukin - 10 ( IL - 10 ) plays an important role in a host ' s defense against human papillomavirus ( HPV ) infection .", "entity": [], "task": "NER"}
{"text": "IL - 10 promoter variants may affect its expression level or functional efficiency and , subsequently , susceptibility to and survival of HPV16 - associated squamous cell carcinoma of oropharynx ( SCCOP ) .", "entity": [], "task": "NER"}
{"text": "We determined tumor HPV16 DNA and genotyped three IL - 10 promoter polymorphisms in 309 incident patients with SCCOP .", "entity": [], "task": "NER"}
{"text": "Compared with the patients with corresponding common homozygous genotypes , patients carrying variant genotypes of IL - 10 rs1800871 and rs1800872 were ~ 2 . 5 times more likely to have HPV16 ( + ) tumors among patients with SCCOP .", "entity": [], "task": "NER"}
{"text": "Among HPV16 ( + ) patients with SCCOP only , compared to those with the corresponding variant genotypes , the patients with IL - 10 rs1800871 and rs1800872 CC genotypes had significantly better survival and ~ 70 - 80 % reduced risk of death / recurrence after multivariable adjustment .", "entity": [], "task": "NER"}
{"text": "Additionally , functional relevance of these variants was characterized to explore the genotype - phenotype correlation .", "entity": [], "task": "NER"}
{"text": "Our findings indicate that IL - 10 genetic variants may be associated with tumor HPV16 ( + ) SCCOP and predict survival of HPV16 ( + ) patients with SCCOP .", "entity": [], "task": "NER"}
{"text": "Larger studies are needed to validate our findings . - Jin , L . , Sturgis , E .", "entity": [], "task": "NER"}
{"text": "M . , Cao , X . , Song , X . , Salahuddin , T . , Wei , Q . , Li , G .", "entity": [], "task": "NER"}
{"text": "Effect of Ketoconazole on the Pharmacokinetics of the 11 beta - Hydroxysteroid Dehydrogenase Type 1 Inhibitor ABT - 384 and Its Two Active Metabolites in Healthy Volunteers : Population Analysis of Data from a Drug - Drug Interaction Study .", "entity": [{"entity": "Ketoconazole", "entity_type": "Chemical", "pos": [10, 22]}, {"entity": "11 beta - Hydroxysteroid", "entity_type": "Chemical", "pos": [54, 78]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [110, 119]}], "task": "NER"}
{"text": "ABT - 384 [ 1 - piperazineacetamide , N - [ 5 - ( aminocarbonyl ) tricyclo [ 3 . 3 . 1 . 13 , 7 ] dec - 2 - yl ] - alpha , alpha - dimethyl - 4 - [ 5 - ( trifluoromethyl ) - 2 - pyridinyl ] - , stereoisomer ] is a potent and selective inhibitor of 11 beta - hydroxysteroid dehydrogenase type 1 ( HSD - 1 ) .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "1 - piperazineacetamide , N - [ 5 - ( aminocarbonyl ) tricyclo [ 3 . 3 . 1 . 13 , 7 ] dec - 2 - yl ] - alpha , alpha - dimethyl - 4 - [ 5 - ( trifluoromethyl ) - 2 - pyridinyl ]", "entity_type": "Chemical", "pos": [12, 189]}, {"entity": "11 beta - hydroxysteroid", "entity_type": "Chemical", "pos": [248, 272]}], "task": "NER"}
{"text": "ABT - 384 has been shown to be safe and well tolerated in humans at doses up to 100 mg daily , and to fully inhibit both peripheral and brain HSD - 1 at a dose of 2 mg daily .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The effect of ketoconazole on the pharmacokinetics of ABT - 384 and its two active metabolites , A - 1331480 and A - 847082 , was investigated in healthy volunteers .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "A - 1331480", "entity_type": "Chemical", "pos": [97, 108]}, {"entity": "A - 847082", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "When 10 mg of ABT - 384 was coadministered with ketoconazole , ABT - 384 exposures increased 18 - fold for area under the plasma concentration - time curve from time 0 to infinity and 3 . 5 - fold for Cmax .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [14, 23]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [48, 60]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [63, 72]}], "task": "NER"}
{"text": "The results suggest that ABT - 384 is a sensitive substrate of CYP3A .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [25, 34]}], "task": "NER"}
{"text": "After ketoconazole coadministration , exposures of A - 1331480 and A - 847082 were also greatly increased .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [6, 18]}, {"entity": "A - 1331480", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "A - 847082", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "A population pharmacokinetic model was constructed for ABT - 384 and its metabolites using NonMEM .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "A two - compartment model with three transit absorption compartments best described ABT - 384 data .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [84, 93]}], "task": "NER"}
{"text": "The model predicted a 69 . 3 % decrease in ABT - 384 clearance and 91 . 1 % increase in the volume of distribution of ABT - 384 in the presence of ketoconazole .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [43, 52]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [118, 127]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [147, 159]}], "task": "NER"}
{"text": "A - 1331480 was shown to be formation rate - limited and A - 847082 was elimination rate - limited .", "entity": [{"entity": "A - 1331480", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "A - 847082", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "Both metabolites were characterized by a one - compartment model with first - order rate constants of formation and elimination .", "entity": [], "task": "NER"}
{"text": "Overall the model adequately captured the concentration - time profiles of ABT - 384 , A - 1331480 , and A - 847082 in both ABT - 384 - alone and ketoconazole - coadministration conditions .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [75, 84]}, {"entity": "A - 1331480", "entity_type": "Chemical", "pos": [87, 98]}, {"entity": "A - 847082", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [124, 133]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [146, 158]}], "task": "NER"}
{"text": "Although ABT - 384 exposures were greatly increased in the presence of ketoconazole , coadministration of ABT - 384 with ketoconazole or other strong / moderate CYP3A inhibitors is not expected to contribute to any major clinical safety issues considering the favorable safety profile of ABT - 384 .", "entity": [{"entity": "ABT - 384", "entity_type": "Chemical", "pos": [9, 18]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [71, 83]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [106, 115]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [121, 133]}, {"entity": "ABT - 384", "entity_type": "Chemical", "pos": [288, 297]}], "task": "NER"}
{"text": "Two new sesquiterpenoids from the rhizomes of Nardostachys jatamansi .", "entity": [{"entity": "sesquiterpenoids", "entity_type": "Chemical", "pos": [8, 24]}], "task": "NER"}
{"text": "Phytochemical investigation of CHCl ( 3 ) : MeOH ( 1 : 1 ) extract from the rhizomes of Nardostachys jatamansi led to the isolation of two new sesquiterpenoids ( 5 and 6 ) , along with six known compounds ( 1 - 4 , 7 , and 8 ) .", "entity": [{"entity": "CHCl ( 3 )", "entity_type": "Chemical", "pos": [31, 41]}, {"entity": "MeOH", "entity_type": "Chemical", "pos": [44, 48]}, {"entity": "sesquiterpenoids", "entity_type": "Chemical", "pos": [143, 159]}], "task": "NER"}
{"text": "The structures of two new compounds were established using IR , MS , 1D , and 2D NMR techniques .", "entity": [], "task": "NER"}
{"text": "In addition , all the isolates were tested for their cytotoxicities against the A549 ( lung cancer ) , DU - 145 ( prostate cancer ) , MCF - 7 ( breast cancer ) , and SK - N - SH ( neuroblastoma ) .", "entity": [], "task": "NER"}
{"text": "Transient Receptor Potential ( TRP ) Cation Channels in Diabetes .", "entity": [], "task": "NER"}
{"text": "Transient Receptor Potential ( TRP ) proteins constitute a family of cation channels with very diverse permeation and gating properties .", "entity": [], "task": "NER"}
{"text": "Likewise they have a very diverse role in mammalian physiology ranging from sensory nerve endings , the cardiac muscle to immune cells .", "entity": [], "task": "NER"}
{"text": "Increasing evidence has implicated TRP channels in the pathology of diabetes , both on the level of insulin release from the pancreatic beta cells and in secondary conditions such as diabetic neuropathy , nephropathy and vasculopathy .", "entity": [], "task": "NER"}
{"text": "In this review we summarize these recent findings , which all together indicate that TRP channels are interesting drug targets for the treatment of patients suffering from diabetes .", "entity": [], "task": "NER"}
{"text": "Symmetrical Windowing for Quantum States in Quasi - Classical Trajectory Simulations .", "entity": [], "task": "NER"}
{"text": "A microscopically reversible approach toward computing reaction probabilities via classical trajectory simulation has been developed that bins trajectories symmetrically on the basis of their initial and final classical actions .", "entity": [], "task": "NER"}
{"text": "The symmetrical quasi - classical ( SQC ) approach involves defining a classical action window function centered at integer quantum values of the action , choosing a width parameter that is less than unit quantum width , and applying the window function to both initial reactant and final product vibrational states .", "entity": [], "task": "NER"}
{"text": "Calculations were performed using flat histogram windows and Gaussian windows over a range of width parameters .", "entity": [], "task": "NER"}
{"text": "Use of the Wigner distribution function was also investigated as a possible choice .", "entity": [], "task": "NER"}
{"text": "It was demonstrated for collinear H + H2 reactive scattering on the BKMP2 potential energy surface that reaction probabilities computed via the SQC methodology using a Gaussian window function of 1 / 2 unit width produces good agreement with quantum mechanical results over the 0 . 4 - 0 . 6 eV energy range relevant to the ground vibrational state to the ground vibrational state reactive transition .", "entity": [{"entity": "H", "entity_type": "Chemical", "pos": [34, 35]}, {"entity": "H2", "entity_type": "Chemical", "pos": [38, 40]}], "task": "NER"}
{"text": "Binding of Diverse Environmental Chemicals with Human Cytochromes P450 2A13 , 2A6 , and 1B1 and Enzyme Inhibition .", "entity": [], "task": "NER"}
{"text": "A total of 68 chemicals including derivatives of naphthalene , phenanthrene , fluoranthene , pyrene , biphenyl , and flavone were examined for their abilities to interact with human P450s 2A13 and 2A6 .", "entity": [{"entity": "naphthalene", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "phenanthrene", "entity_type": "Chemical", "pos": [63, 75]}, {"entity": "fluoranthene", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "pyrene", "entity_type": "Chemical", "pos": [93, 99]}, {"entity": "biphenyl", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "flavone", "entity_type": "Chemical", "pos": [117, 124]}], "task": "NER"}
{"text": "Fifty - one of these 68 chemicals induced stronger Type I binding spectra ( iron low - to high - spin state shift ) with P450 2A13 than those seen with P450 2A6 , i . e . , the spectral binding intensities ( Delta Amax / Ks ratio ) determined with these chemicals were always higher for P450 2A13 .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "In addition , benzo [ c ] phenanthrene , fluoranthene , 2 , 3 - dihydroxy - 2 , 3 - dihydrofluoranthene , pyrene , 1 - hydroxypyrene , 1 - nitropyrene , 1 - acetylpyrene , 2 - acetylpyrene , 2 , 5 , 2 ' , 5 ' - tetrachlorobiphenyl , 7 - hydroxyflavone , chrysin , and galangin were found to induce a Type I spectral change only with P450 2A13 .", "entity": [{"entity": "benzo [ c ] phenanthrene", "entity_type": "Chemical", "pos": [14, 38]}, {"entity": "fluoranthene", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "2 , 3 - dihydroxy - 2 , 3 - dihydrofluoranthene", "entity_type": "Chemical", "pos": [56, 103]}, {"entity": "pyrene", "entity_type": "Chemical", "pos": [106, 112]}, {"entity": "1 - hydroxypyrene", "entity_type": "Chemical", "pos": [115, 132]}, {"entity": "1 - nitropyrene", "entity_type": "Chemical", "pos": [135, 150]}, {"entity": "1 - acetylpyrene", "entity_type": "Chemical", "pos": [153, 169]}, {"entity": "2 - acetylpyrene", "entity_type": "Chemical", "pos": [172, 188]}, {"entity": "2 , 5 , 2 ' , 5 ' - tetrachlorobiphenyl", "entity_type": "Chemical", "pos": [191, 230]}, {"entity": "7 - hydroxyflavone", "entity_type": "Chemical", "pos": [233, 251]}, {"entity": "chrysin", "entity_type": "Chemical", "pos": [254, 261]}, {"entity": "galangin", "entity_type": "Chemical", "pos": [268, 276]}], "task": "NER"}
{"text": "Coumarin 7 - hydroxylation , catalyzed by P450 2A13 , was strongly inhibited by 2 ' - methoxy - 5 , 7 - dihydroxyflavone , 2 - ethynylnaphthalene , 2 ' - methoxyflavone , 2 - naphththalene propargyl ether , acenaphthene , acenaphthylene , naphthalene , 1 - acetylpyrene , flavanone , chrysin , 3 - ethynylphenanthrene , flavone , and 7 - hydroxyflavone ; these chemicals induced Type I spectral changes with low Ks values .", "entity": [{"entity": "Coumarin", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "2 ' - methoxy - 5 , 7 - dihydroxyflavone", "entity_type": "Chemical", "pos": [80, 120]}, {"entity": "2 - ethynylnaphthalene", "entity_type": "Chemical", "pos": [123, 145]}, {"entity": "2 ' - methoxyflavone", "entity_type": "Chemical", "pos": [148, 168]}, {"entity": "2 - naphththalene propargyl ether", "entity_type": "Chemical", "pos": [171, 204]}, {"entity": "acenaphthene", "entity_type": "Chemical", "pos": [207, 219]}, {"entity": "acenaphthylene", "entity_type": "Chemical", "pos": [222, 236]}, {"entity": "naphthalene", "entity_type": "Chemical", "pos": [239, 250]}, {"entity": "1 - acetylpyrene", "entity_type": "Chemical", "pos": [253, 269]}, {"entity": "flavanone", "entity_type": "Chemical", "pos": [272, 281]}, {"entity": "chrysin", "entity_type": "Chemical", "pos": [284, 291]}, {"entity": "3 - ethynylphenanthrene", "entity_type": "Chemical", "pos": [294, 317]}, {"entity": "flavone", "entity_type": "Chemical", "pos": [320, 327]}, {"entity": "7 - hydroxyflavone", "entity_type": "Chemical", "pos": [334, 352]}], "task": "NER"}
{"text": "On the basis of the intensities of the spectral changes and inhibition of P450 2A13 , we classified the 68 chemicals into eight groups based on the order of affinities for these chemicals and inhibition of P450 2A13 .", "entity": [], "task": "NER"}
{"text": "The metabolism of chemicals by P450 2A13 during the assays explained why some of the chemicals that bound well were poor inhibitors of P450 2A13 .", "entity": [], "task": "NER"}
{"text": "Finally , we compared the 68 chemicals for their abilities to induce Type I spectral changes of P450 2A13 with the Reverse Type I binding spectra observed with P450 1B1 : 45 chemicals interacted with both P450s 2A13 and 1B1 , indicating that the two enzymes have some similarty of structural features regarding these chemicals .", "entity": [], "task": "NER"}
{"text": "Molecular docking analyses suggest similarities at the active sites of these P450 enzymes .", "entity": [], "task": "NER"}
{"text": "These results indicate that P450 2A13 , as well as Family 1 P450 enzymes , is able to catalyze many detoxication and activation reactions with chemicals of environmental interest .", "entity": [], "task": "NER"}
{"text": "ATP synthase : a molecular therapeutic drug target for antimicrobial and antitumor peptides .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "In this review we discuss the role of ATP synthase as a molecular drug target for natural and synthetic antimicrobial / antitumor peptides .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "We start with an introduction of the universal nature of the ATP synthase enzyme and its role as a biological nanomotor .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [61, 64]}], "task": "NER"}
{"text": "Significant structural features required for catalytic activity and motor functions of ATP synthase are described .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "Relevant details regarding the presence of ATP synthase on the surface of several animal cell types , where it is associated with multiple cellular processes making it a potential drug target with respect to antimicrobial peptides and other inhibitors such as dietary polyphenols , is also reviewed .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [43, 46]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [268, 279]}], "task": "NER"}
{"text": "ATP synthase is known to have about twelve discrete inhibitor binding sites including peptides and other inhibitors located at the interface of alpha / beta subunits on the F1 sector of the enzyme .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Molecular interaction of peptides at the beta DEELSEED site on ATP synthase is discussed with specific examples .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "An inhibitory effect of other natural / synthetic inhibitors on ATP is highlighted to explore the therapeutic roles played by peptides and other inhibitors .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Lastly , the effect of peptides on the inhibition of the Escherichia coli model system through their action on ATP synthase is presented .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [111, 114]}], "task": "NER"}
{"text": "Interlayer breathing and shear modes in few - trilayer MoS2 and WSe2 .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "WSe2", "entity_type": "Chemical", "pos": [64, 68]}], "task": "NER"}
{"text": "Two - dimensional ( 2D ) layered transition metal dichalcogenides ( TMDs ) have recently attracted tremendous interest as potential valleytronic and nanoelectronic materials , in addition to being well - known as excellent lubricants in the bulk .", "entity": [{"entity": "transition metal dichalcogenides", "entity_type": "Chemical", "pos": [33, 65]}, {"entity": "TMDs", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "The interlayer van der Waals ( vdW ) coupling and low - frequency phonon modes and how they evolve with the number of layers are important for both the mechanical and the electrical properties of 2D TMDs .", "entity": [{"entity": "TMDs", "entity_type": "Chemical", "pos": [199, 203]}], "task": "NER"}
{"text": "Here we uncover the ultralow frequency interlayer breathing and shear modes in few - layer MoS2 and WSe2 , prototypical layered TMDs , using both Raman spectroscopy and first principles calculations .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [91, 95]}, {"entity": "WSe2", "entity_type": "Chemical", "pos": [100, 104]}, {"entity": "TMDs", "entity_type": "Chemical", "pos": [128, 132]}], "task": "NER"}
{"text": "Remarkably , the frequencies of these modes can be perfectly described using a simple linear chain model with only nearest - neighbor interactions .", "entity": [], "task": "NER"}
{"text": "We show that the derived in - plane ( shear ) and out - of - plane ( breathing ) force constants from experiment remain the same from two - layer 2D crystals to the bulk materials , suggesting that the nanoscale interlayer frictional characteristics of these excellent lubricants should be independent of the number of layers .", "entity": [], "task": "NER"}
{"text": "Checkpoint protein Rad9 plays an important role in nucleotide excision repair .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [51, 61]}], "task": "NER"}
{"text": "Rad9 , an evolutionarily conserved checkpoint gene with multiple functions for preserving genomic integrity , has been shown to play important roles in homologous recombination repair , base excision repair and mismatch repair .", "entity": [], "task": "NER"}
{"text": "However , whether Rad9 has an impact on nucleotide excision repair remains unknown .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [40, 50]}], "task": "NER"}
{"text": "Here we demonstrated that Rad9 was involved in nucleotide excision repair and loss of Rad9 led to defective removal of the UV - derived photoproduct 6 - 4PP ( 6 , 4 pyrimidine - pyrimidone ) and the BPDE ( anti - benzo ( a ) pyrene - trans - 7 , 8 - dihydrodiol - 9 , 10 - epoxide ) - DNA adducts in mammalian cells .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "6 - 4PP", "entity_type": "Chemical", "pos": [149, 156]}, {"entity": "6 , 4 pyrimidine - pyrimidone", "entity_type": "Chemical", "pos": [159, 188]}, {"entity": "BPDE", "entity_type": "Chemical", "pos": [199, 203]}, {"entity": "benzo ( a ) pyrene - trans - 7 , 8 - dihydrodiol - 9 , 10 - epoxide", "entity_type": "Chemical", "pos": [213, 280]}], "task": "NER"}
{"text": "We also demonstrated that Rad9 could co - localize with XPC in response to local UV irradiation .", "entity": [], "task": "NER"}
{"text": "However , our data showed that Rad9 was not required for the photoproducts recognition step of nucleotide excision repair .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [95, 105]}], "task": "NER"}
{"text": "Further investigation revealed that reduction of Rad9 reduced the UV - induced transcription of the genes of the nucleotide excision repair factors DDB2 , XPC , DDB1 and XPB and DDB2 protein levels in human cells .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "Interestingly , knockdown of one subunit of DNA damage recognition complex , hHR23B impaired Rad9 - loading onto UV - damaged chromatin .", "entity": [], "task": "NER"}
{"text": "Based on these results , we suggest that Rad9 plays an important role in nucleotide excision repair through mechanisms including maintaining DDB2 protein level in human cells .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [73, 83]}], "task": "NER"}
{"text": "LOX - 1 is a novel marker for peripheral artery disease in patients with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : The aim of this study was to investigate whether serum soluble lectin - like oxidized low - density lipoprotein receptor - 1 ( sLOX - 1 ) , which mediates initiation and progression of atherosclerosis in endothelial cells , could be a novel marker for peripheral artery disease ( PAD ) in patients with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "METHODS : We evaluated relationships of serum sLOX - 1 to ankle - brachial index ( ABI ) and examined the association of serum sLOX - 1 with PAD in 410 patients with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "RESULTS : Serum sLOX - 1 was inversely correlated with ABI ( r = - 0 . 197 , P < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "Stepwise regression analysis demonstrated that serum sLOX - 1 ( beta = - 0 . 168 , F = 5 . 571 , P < 0 . 05 ) was independently associated with ABI , and multiple logistic regression analysis demonstrated that serum sLOX - 1 ( 16 . 254 ( 1 . 237 - 213 . 651 ) , P = 0 . 0339 ) was independently associated with PAD .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Serum sLOX - 1 is associated with ABI and it could be a novel marker for PAD in patients with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Discovery of biological evaluation of pyrazole / imidazole amides as mGlu5 receptor negative allosteric modulators .", "entity": [{"entity": "pyrazole / imidazole amides", "entity_type": "Chemical", "pos": [38, 65]}], "task": "NER"}
{"text": "Development of SAR in a 5 - aryl - 3 - acylpyridinyl - pyrazoles and 1 - aryl - 4 - acylpyridinyl imidazoles series of mGlu5 receptor negative allosteric modulators ( mGluR5 NAMs ) using a functional cell - based assay is described in this Letter .", "entity": [{"entity": "5 - aryl - 3 - acylpyridinyl - pyrazoles", "entity_type": "Chemical", "pos": [24, 64]}, {"entity": "1 - aryl - 4 - acylpyridinyl imidazoles", "entity_type": "Chemical", "pos": [69, 108]}], "task": "NER"}
{"text": "Analysis of the Ligand - lipophilic efficiency ( LipE ) of compounds provided new insight for the design of potent mGluR5 negative allosteric modulators with anti - depressant activities .", "entity": [], "task": "NER"}
{"text": "Microwave assisted nano ( ZnO - TiO2 ) catalyzed synthesis of some new 4 , 5 , 6 , 7 - tetrahydro - 6 - ( ( 5 - substituted - 1 , 3 , 4 - oxadiazol - 2 - yl ) methyl ) thieno [ 2 , 3 - c ] pyridine as antimicrobial agents .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [32, 36]}, {"entity": "4 , 5 , 6 , 7 - tetrahydro - 6 - ( ( 5 - substituted - 1 , 3 , 4 - oxadiazol - 2 - yl ) methyl ) thieno [ 2 , 3 - c ] pyridine", "entity_type": "Chemical", "pos": [71, 197]}], "task": "NER"}
{"text": "Combined nano zinc oxide and titanium dioxide [ nano ( ZnO - TiO ( 2 ) ) ] has been reported first time for the synthesis of novel series of 4 , 5 , 6 , 7 - tetrahydro - 6 - ( ( 5 - substituted - 1 , 3 , 4 - oxadiazol - 2 - yl ) methyl ) thieno [ 2 , 3 - c ] pyridine .", "entity": [{"entity": "zinc oxide", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "titanium dioxide", "entity_type": "Chemical", "pos": [29, 45]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "TiO ( 2 )", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "4 , 5 , 6 , 7 - tetrahydro - 6 - ( ( 5 - substituted - 1 , 3 , 4 - oxadiazol - 2 - yl ) methyl ) thieno [ 2 , 3 - c ] pyridine", "entity_type": "Chemical", "pos": [141, 267]}], "task": "NER"}
{"text": "All the synthesized compounds ( 7a - 7m ) are novel and were screened for their antimicrobial activity against four different strains like Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus and Bacillus subtilis and antifungal activity was determined against two strains Candida albicans and Aspergillus niger .", "entity": [], "task": "NER"}
{"text": "SAR for the newly synthesised derivatives has been developed by comparing their MIC values with ampicillin , ciprofloxacin and miconazole for antibacterial and antifungal activities , respectively .", "entity": [{"entity": "ampicillin", "entity_type": "Chemical", "pos": [96, 106]}, {"entity": "ciprofloxacin", "entity_type": "Chemical", "pos": [109, 122]}, {"entity": "miconazole", "entity_type": "Chemical", "pos": [127, 137]}], "task": "NER"}
{"text": "Among the synthesized compounds , 2 , 6 dichlorophenyl analogue ( 7f ) , 4 fluorophenyl analogue ( 7k ) and 2 , 6 dichlorophenyl analogue ( 7l ) shows promising antibacterial as well as antifungal activity whereas thiophene substituted compound ( 7j ) shows promising antibacterial activity .", "entity": [{"entity": "2 , 6 dichlorophenyl", "entity_type": "Chemical", "pos": [34, 54]}, {"entity": "4 fluorophenyl", "entity_type": "Chemical", "pos": [73, 87]}, {"entity": "2 , 6 dichlorophenyl", "entity_type": "Chemical", "pos": [108, 128]}, {"entity": "thiophene", "entity_type": "Chemical", "pos": [214, 223]}], "task": "NER"}
{"text": "Improved guanide compounds which bind the CXCR4 co - receptor and inhibit HIV - 1 infection .", "entity": [{"entity": "guanide", "entity_type": "Chemical", "pos": [9, 16]}], "task": "NER"}
{"text": "The G - protein coupled receptor CXCR4 is a co - receptor for HIV - 1 infection and is involved in signaling cell migration and proliferation .", "entity": [], "task": "NER"}
{"text": "In a previous study of non - peptide , guanide - based CXCR4 - binding compounds , spermine and spermidine phenylguanides inhibited HIV - 1 entry at low micromolar concentrations .", "entity": [{"entity": "guanide", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "spermine and spermidine phenylguanides", "entity_type": "Chemical", "pos": [83, 121]}], "task": "NER"}
{"text": "Subsequently , crystal structures of CXCR4 were used to dock a series of naphthylguanide derivatives of the polyamines spermidine and spermine .", "entity": [{"entity": "naphthylguanide", "entity_type": "Chemical", "pos": [73, 88]}, {"entity": "polyamines", "entity_type": "Chemical", "pos": [108, 118]}, {"entity": "spermidine", "entity_type": "Chemical", "pos": [119, 129]}, {"entity": "spermine", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "Synthesis and evaluation of the naphthylguanide compounds identified our best compound , spermine tris - 1 - naphthylguanide , which bound CXCR4 with an IC ( 50 ) of 40 nM and inhibited the infection of TZM - bl cells with X4 , but not R5 , strains of HIV - 1 with an IC ( 50 ) of 50 - 100 nM .", "entity": [{"entity": "naphthylguanide", "entity_type": "Chemical", "pos": [32, 47]}, {"entity": "spermine tris - 1 - naphthylguanide", "entity_type": "Chemical", "pos": [89, 124]}], "task": "NER"}
{"text": "Advances in the discovery of kinesin spindle protein ( Eg5 ) inhibitors as antitumor agents .", "entity": [], "task": "NER"}
{"text": "Cancer is considered as one of the most serious health problems .", "entity": [], "task": "NER"}
{"text": "Despite the presence of many effective chemotherapeutic agents , their severe side effects together with the appearance of mutant tumors limit the use of these drugs and increase the need for new anticancer agents .", "entity": [], "task": "NER"}
{"text": "Eg5 represents an attractive target for medicinal chemists since Eg5 is overexpressed in many proliferative tissues while almost no Eg5 is detected in nonproliferative tissues .", "entity": [], "task": "NER"}
{"text": "Many Eg5 inhibitors displayed potent anticancer activity against some of the mutant tumors with limited side effects .", "entity": [], "task": "NER"}
{"text": "The present review provides an overview about the progress in the discovery of Eg5 inhibitors especially from 2009 to 2012 as well as the clinical trials conducted on some of these inhibitors .", "entity": [], "task": "NER"}
{"text": "Synthesis , biological evaluation of new oxazolidino - sulfonamides as potential antimicrobial agents .", "entity": [{"entity": "oxazolidino - sulfonamides", "entity_type": "Chemical", "pos": [41, 67]}], "task": "NER"}
{"text": "A number of linezolid - like oxazolidino - sulfonamides ( 7a - y and 8a - b ) were designed and synthesized with a view to develop antimicrobial agents with improved properties .", "entity": [{"entity": "linezolid", "entity_type": "Chemical", "pos": [12, 21]}, {"entity": "oxazolidino - sulfonamides", "entity_type": "Chemical", "pos": [29, 55]}], "task": "NER"}
{"text": "Most of the synthesized compounds showed good to moderate activity against a panel of standard Gram - positive and Gram - negative bacteria and fungal strains .", "entity": [], "task": "NER"}
{"text": "The compounds 7i and 7v exhibited significant activity , with a MIC value of 2 . 0 - 6 . 0 mu g / mL against a panel of Gram - positive and Gram - negative bacteria .", "entity": [], "task": "NER"}
{"text": "These compounds also showed activity against Candida albicans , with a MIC value of 4 . 0 mu g / mL .", "entity": [], "task": "NER"}
{"text": "A correlation of the antimicrobial activity with calculated lipophilicity values ( C log P ) is also presented .", "entity": [], "task": "NER"}
{"text": "Synthesis and cytotoxicity of 3 - aryl acrylic amide derivatives of the simplified saframycin - ecteinascidin skeleton prepared from l - dopa .", "entity": [{"entity": "3 - aryl acrylic amide", "entity_type": "Chemical", "pos": [30, 52]}, {"entity": "saframycin", "entity_type": "Chemical", "pos": [83, 93]}, {"entity": "ecteinascidin", "entity_type": "Chemical", "pos": [96, 109]}, {"entity": "l - dopa", "entity_type": "Chemical", "pos": [133, 141]}], "task": "NER"}
{"text": "Twenty four compounds with diversified 3 - aryl acrylic amide side chains of the simplified saframycin - ecteinascidin pentacyclic skeleton were synthesized via a 14 - step stereospecific route starting from l - dopa .", "entity": [{"entity": "3 - aryl acrylic amide", "entity_type": "Chemical", "pos": [39, 61]}, {"entity": "saframycin", "entity_type": "Chemical", "pos": [92, 102]}, {"entity": "ecteinascidin", "entity_type": "Chemical", "pos": [105, 118]}, {"entity": "l - dopa", "entity_type": "Chemical", "pos": [208, 216]}], "task": "NER"}
{"text": "The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT - 8 , BEL - 7402 , BGC - 803 , A549 , A2780 , MCF - 7 , MX - 1 , and MDA - MB - 231 .", "entity": [], "task": "NER"}
{"text": "Most of these compounds exhibited potent antitumor activity , and a preliminary structure - activity relationship ( SAR ) was discussed .", "entity": [], "task": "NER"}
{"text": "Compound 28 with 3 - thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA - MB - 231 cell line with the IC50 value of 50 nM .", "entity": [{"entity": "3 - thiophenyl acrylic amide", "entity_type": "Chemical", "pos": [17, 45]}], "task": "NER"}
{"text": "The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway .", "entity": [], "task": "NER"}
{"text": "Tumor - associated macrophages ( TAMs ) are correlated with poor prognosis in many human cancers ; however , the mechanism by which TAMs facilitate ovarian cancer cell migration and invasion remains unknown .", "entity": [], "task": "NER"}
{"text": "This study was aimed to examine the function of adrenomedullin ( ADM ) in macrophage polarization and their further effects on the migration of ovarian cancer cells .", "entity": [], "task": "NER"}
{"text": "Exogenous ADM antagonist and small interfering RNA ( siRNA ) specific for ADM expression were treated to macrophages and EOC cell line HO8910 , respectively .", "entity": [], "task": "NER"}
{"text": "Then macrophages were cocultured with HO8910 cells without direct contact .", "entity": [], "task": "NER"}
{"text": "Flow cytometry , Western blot and real - time PCR were used to detect macrophage phenotype and cytokine production .", "entity": [], "task": "NER"}
{"text": "The migration ability and cytoskeleton rearrangement of ovarian cancer cells were determined by Transwell migration assay and phalloidin staining .", "entity": [{"entity": "phalloidin", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "Western blot was performed to evaluate the activity status of signaling molecules in the process of ovarian cancer cell migration .", "entity": [], "task": "NER"}
{"text": "The results showed that ADM induced macrophage phenotype and cytokine production similar to TAMs .", "entity": [], "task": "NER"}
{"text": "Macrophages polarized by ADM promoted the migration and cytoskeleton rearrangement of HO8910 cells .", "entity": [], "task": "NER"}
{"text": "The expression of RhoA and its downstream effector , cofilin , were upregulated in macrophage - induced migration of HO8910 cells .", "entity": [], "task": "NER"}
{"text": "In conclusion , ADM could polarize macrophages similar to TAMs , and then polarized macrophages promote the migration of ovarian cancer cells via activation of RhoA signaling pathway in vitro .", "entity": [], "task": "NER"}
{"text": "Identification of three genes encoding for the late acyltransferases of lipid A in Cronobacter sakazakii .", "entity": [], "task": "NER"}
{"text": "Lipid A , the hydrophobic anchor of lipopolysaccharide , is an essential component in the outer membrane of most Gram - negative bacteria .", "entity": [], "task": "NER"}
{"text": "Food - borne pathogen Cronobacter sakazakii synthesizes two lipid A species , differing by the length of the secondary acyl chain .", "entity": [{"entity": "acyl", "entity_type": "Chemical", "pos": [119, 123]}], "task": "NER"}
{"text": "In this work , we identified three genes ESA02293 , ESA02951 and ESA01386 encoding for the late acyltransferases of lipid A biosynthesis pathway in C . sakazakii .", "entity": [], "task": "NER"}
{"text": "Based on the sequence alignment , proteins YP _ 001438378 . 1 encoded by ESA02293 , YP _ 001439016 . 1 encoded by ESA02951 , and YP _ 001437482 . 1 encoded by ESA01386 are homologous to E . coli LpxL , LpxP and LpxM , respectively .", "entity": [], "task": "NER"}
{"text": "Functions of the three acyltransferases were confirmed by overexpressing the genes in E . coli , isolating lipid As and analyzing their structures using an ESI / MS .", "entity": [], "task": "NER"}
{"text": "C . sakazakii LpxL and LpxM transfer a C14 : 0 secondary acyl chain to the 2 ' - and 3 ' - position of lipid A , respectively .", "entity": [{"entity": "acyl", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "C . sakazakii LpxP can transfer either a C16 : 1 or a C14 : 0 secondary acyl chains to the 2 ' - position of lipid A .", "entity": [{"entity": "acyl", "entity_type": "Chemical", "pos": [72, 76]}], "task": "NER"}
{"text": "A 35kD Phyllanthus niruri protein modulates iron mediated oxidative impairment to hepatocytes via the inhibition of ERKs , p38 MAPKs and activation of PI3k / Akt pathway .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "It has been reported that the herb , Phyllanthus niruri , possess antioxidant , anti - infection , anti - asthmatic , anti - diuretic , anti - soresis and many more beneficial activities .", "entity": [], "task": "NER"}
{"text": "The goal of our present study was to evaluate the protective role of a 35kD protein ( PNP ) isolated from this herb against iron - induced cytotoxicity in murine hepatocytes .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [124, 128]}], "task": "NER"}
{"text": "Exposure of hepatocytes to iron ( FeSO4 ) caused elevation of reactive oxygen species ( ROS ) production , enhanced lipid peroxidation and protein carbonylation , depleted glutathione levels , decreased the antioxidant power ( FRAP ) of the cells and reduced cell viability .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "FeSO4", "entity_type": "Chemical", "pos": [34, 39]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [71, 77]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [172, 183]}], "task": "NER"}
{"text": "Iron mediated cytotoxicity disrupted mitochondrial membrane potential ( Delta psi m ) and thereby caused apoptosis mainly by the intrinsic pathway via the down - regulation of I kappa B alpha with a concomitant up - regulation of NF - kB as well as the phosphorylation of ERKs and p38 MAP kinases .", "entity": [{"entity": "Iron", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "In addition , iron - induced cytotoxicity disrupted the normal balance of Bcl - 2 family proteins in hepatocytes .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "Incubation of hepatocytes with PNP , however , protected the cells from apoptosis by stabilizing the mitochondria and arresting the release of cytochrome c .", "entity": [], "task": "NER"}
{"text": "It also suppressed caspase activation and cleavage of PARP .", "entity": [], "task": "NER"}
{"text": "Moreover , this protein has strong free radical scavenging activity and thereby scavenged ROS extensively .", "entity": [], "task": "NER"}
{"text": "Combining all , results suggest that simultaneous treatment with PNP might suppress the iron - induced cytotoxicity in hepatocytes .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [88, 92]}], "task": "NER"}
{"text": "Hepatic and renal Bcrp transporter expression in mice treated with perfluorooctanoic acid .", "entity": [{"entity": "perfluorooctanoic acid", "entity_type": "Chemical", "pos": [67, 89]}], "task": "NER"}
{"text": "The breast cancer resistance protein ( Bcrp ) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals .", "entity": [], "task": "NER"}
{"text": "Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha ( PPAR alpha ) can up - regulate the hepatic expression of Bcrp .", "entity": [], "task": "NER"}
{"text": "The current study investigated the regulation of hepatic and renal Bcrp mRNA and protein in mice treated with the PPAR alpha agonist perfluorooctanoic acid ( PFOA ) and the ability of PFOA to alter human BCRP function in vitro .", "entity": [{"entity": "perfluorooctanoic acid", "entity_type": "Chemical", "pos": [133, 155]}, {"entity": "PFOA", "entity_type": "Chemical", "pos": [158, 162]}, {"entity": "PFOA", "entity_type": "Chemical", "pos": [184, 188]}], "task": "NER"}
{"text": "Bcrp mRNA and protein expression were quantified in the livers and kidneys of male C57BL / 6 mice treated with vehicle or PFOA ( 1 or 3mg / kg / day oral gavage ) for 7 days .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [122, 126]}], "task": "NER"}
{"text": "PFOA treatment increased liver weights as well as the hepatic mRNA and protein expression of the PPAR alpha target gene , cytochrome P450 4a14 .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Compared to vehicle - treated control mice , PFOA increased hepatic Bcrp mRNA and protein between 1 . 5 - and 3 - fold .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "Immunofluorescent staining confirmed enhanced canalicular Bcrp staining in liver sections from PFOA - treated mice .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "The kidney expression of cytochrome P450 4a14 mRNA , but not Bcrp , was increased in mice treated with PFOA .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "Micromolar concentrations of PFOA decreased human BCRP ATPase activity and inhibited BCRP - mediated transport in inverted membrane vesicles .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "Together , these studies demonstrate that PFOA induces hepatic Bcrp expression in mice and may inhibit human BCRP transporter function at concentrations that exceed levels observed in humans .", "entity": [{"entity": "PFOA", "entity_type": "Chemical", "pos": [42, 46]}], "task": "NER"}
{"text": "Fluctuating charge - density waves in a cuprate superconductor .", "entity": [{"entity": "cuprate", "entity_type": "Chemical", "pos": [40, 47]}], "task": "NER"}
{"text": "Cuprate materials hosting high - temperature superconductivity ( HTS ) also exhibit various forms of charge and spin ordering whose significance is not fully understood .", "entity": [{"entity": "Cuprate", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "So far , static charge - density waves ( CDWs ) have been detected by diffraction probes only at particular doping levels or in an applied external field .", "entity": [], "task": "NER"}
{"text": "However , dynamic CDWs may also be present more broadly and their detection , characterization and relationship with HTS remain open problems .", "entity": [], "task": "NER"}
{"text": "Here we present a method based on ultrafast spectroscopy to detect the presence and measure the lifetimes of CDW fluctuations in cuprates .", "entity": [{"entity": "cuprates", "entity_type": "Chemical", "pos": [129, 137]}], "task": "NER"}
{"text": "In an underdoped La1 . 9Sr0 . 1CuO4 film ( Tc = 26 K ) , we observe collective excitations of CDW that persist up to 100 K .", "entity": [{"entity": "La1 . 9Sr0 . 1CuO4", "entity_type": "Chemical", "pos": [17, 35]}], "task": "NER"}
{"text": "This dynamic CDW fluctuates with a characteristic lifetime of 2 ps at T = 5 K that decreases to 0 . 5 ps at T = 100 K .", "entity": [], "task": "NER"}
{"text": "In contrast , in an optimally doped La1 . 84Sr0 . 16CuO4 film ( Tc = 38 . 5 K ) , we detect no signatures of fluctuating CDWs at any temperature , favouring the competition scenario .", "entity": [{"entity": "La1 . 84Sr0 . 16CuO4", "entity_type": "Chemical", "pos": [36, 56]}], "task": "NER"}
{"text": "This work forges a path for studying fluctuating order parameters in various superconductors and other materials .", "entity": [], "task": "NER"}
{"text": "Modulation of A - type K ( + ) channels by the short - chain cobrotoxin through the protein kinase C - delta isoform decreases membrane excitability in dorsal root ganglion neurons .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [23, 30]}], "task": "NER"}
{"text": "A - type K ( + ) channels are crucial in controlling neuronal excitability , and their regulation in sensory neurons may alter pain sensation .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [9, 16]}], "task": "NER"}
{"text": "In this study , we identified the functional role of cobrotoxin , the short - chain alpha - neurotoxin isolated from Naja atra venom , which acts in the regulation of the transient A - type K ( + ) currents ( IA ) and membrane excitability in dorsal root ganglion ( DRG ) neurons via the activation of the muscarinic M3 receptor ( M3R ) .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [190, 197]}], "task": "NER"}
{"text": "Our results showed that cobrotoxin increased IA in a concentration - dependent manner , whereas the sustained delayed rectifier K ( + ) currents ( IDR ) were not affected .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [128, 135]}], "task": "NER"}
{"text": "Cobrotoxin did not affect the activation of IA markedly , however , it shifted the inactivation curve significantly in the depolarizing direction .", "entity": [], "task": "NER"}
{"text": "The cobrotoxin - induced IA response was blocked by the M3R - selective antagonists DAU - 5884 and 4 - DAMP .", "entity": [{"entity": "DAU - 5884", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "4 - DAMP", "entity_type": "Chemical", "pos": [99, 107]}], "task": "NER"}
{"text": "An siRNA targeting the M3R in small DRG neurons abolished the cobrotoxin - induced IA increase .", "entity": [], "task": "NER"}
{"text": "In addition , dialysis of the cells with the novel protein kinase C - delta isoform ( PKC - delta ) inhibitor delta v1 - 1 or an siRNA targeting PKC - delta abolished the cobrotoxin - induced IA response , whereas inhibition of PKA or classic PKC activity elicited no such effects .", "entity": [], "task": "NER"}
{"text": "Moreover , we observed a significant decrease in the firing rate of the neuronal action potential induced by M3R activation .", "entity": [], "task": "NER"}
{"text": "Pretreatment of the cells with 4 - aminopyridine , a selective blocker of IA , abolished this effect .", "entity": [{"entity": "4 - aminopyridine", "entity_type": "Chemical", "pos": [31, 48]}], "task": "NER"}
{"text": "Taken together , these results suggest that the short - chain cobrotoxin selectively enhances IA via a novel PKC - delta - dependent pathway .", "entity": [], "task": "NER"}
{"text": "This effect occurred via the activation of M3R and might contribute to its neuronal hypoexcitability in small DRG neurons .", "entity": [], "task": "NER"}
{"text": "Molecular aspects of cancer cell resistance to chemotherapy .", "entity": [], "task": "NER"}
{"text": "Cancer cell resistance to chemotherapy is still a heavy burden that impairs treatment of cancer patients .", "entity": [], "task": "NER"}
{"text": "Both intrinsic and acquired resistance results from the numerous genetic and epigenetic changes occurring in cancer cells .", "entity": [], "task": "NER"}
{"text": "Most of the hallmarks of cancer cells provide general mechanisms to sustain stresses such as the ones induced by chemotherapeutic drugs .", "entity": [], "task": "NER"}
{"text": "Moreover , specific changes in the target bring resistance to specific drugs like modification in nucleotide synthesis enzymes upon anti - metabolite exposure , in microtubule composition upon spindle poison treatment , in topoisomerase activity upon topoisomerase inhibitor incubation or in intracellular signaling pathways when targeting tyrosine kinase receptors .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [340, 348]}], "task": "NER"}
{"text": "Finally , the stemness properties of a few cancer cells as well as components of the tumor stroma , like fibroblasts and tumor - associated macrophages but also hypoxia , also help tumor to resist to anticancer agents .", "entity": [], "task": "NER"}
{"text": "These processes provide an additional level of complexity to the understanding of the tumor resistance phenomenon .", "entity": [], "task": "NER"}
{"text": "This review aims to describe the different general mechanisms as well as some examples of specific on target modifications inducing cancer cell resistance to chemotherapy at the molecular level .", "entity": [], "task": "NER"}
{"text": "Perspectives to develop more efficient treatment , using genomic signature or more specific biomarkers to characterize putative resistance mechanisms in patients before choosing the more appropriate treatment , will also be discussed .", "entity": [], "task": "NER"}
{"text": "ATM kinase activity modulates ITCH E3 - ubiquitin ligase activity .", "entity": [], "task": "NER"}
{"text": "Ataxia Telangiectasia Mutated ( ATM ) kinase , a central regulator of the DNA damage response , regulates the activity of several E3 - ubiquitin ligases , and the ubiquitination - proteasome system is a consistent target of ATM .", "entity": [], "task": "NER"}
{"text": "ITCH is an E3 - ubiquitin ligase that modulates the ubiquitination of several targets , therefore participating to the regulation of several cellular responses , such as the DNA damage response , tumor necrosis factor alpha ( TNF alpha ) , Notch and Hedgehog signaling , and the differentiation of ' naive ' lymphocytes into T helper type 2 cells .", "entity": [], "task": "NER"}
{"text": "Here we uncover ATM as a novel positive modulator of ITCH E3 - ubiquitin ligase activity .", "entity": [], "task": "NER"}
{"text": "A single residue on ITCH protein , S161 , which is part of an ATM SQ consensus motif , is required for ATM - dependent activation of ITCH .", "entity": [], "task": "NER"}
{"text": "ATM activity enhances ITCH enzymatic activity , which in turn drives the ubiquitination and degradation of c - FLIP - L and c - Jun , previously identified as ITCH substrates .", "entity": [], "task": "NER"}
{"text": "Importantly , ATM - deficient mice show resistance to hepatocyte cell death , similarly to Itch - deficient animals , providing in vivo genetic evidence for this circuit .", "entity": [], "task": "NER"}
{"text": "Our data identify ITCH as a novel component of the ATM - dependent signaling pathway and suggest that the impairment of the correct functionality of ITCH caused by Atm deficiency may contribute to the complex clinical features linked to Ataxia Telangiectasia . Oncogene advance online publication , 25 February 2013 ; doi : 10 . 1038 / onc . 2013 . 52 .", "entity": [], "task": "NER"}
{"text": "Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins .", "entity": [], "task": "NER"}
{"text": "Parathyroid cancer is a rare , clinically aggressive cause of primary hyperparathyroidism , and whether these malignancies generally evolve from pre - existing benign adenomas or arise de novo is unclear .", "entity": [], "task": "NER"}
{"text": "Furthermore , while inactivation of the CDC73 ( HRPT2 ) tumor suppressor gene , encoding parafibromin , is a major contributor , other genes essential to parathyroid carcinogenesis remain unknown .", "entity": [], "task": "NER"}
{"text": "We sought to identify genomic regions potentially harboring such oncogenes or tumor suppressor genes , and to gain insight into the origins and molecular relationship of malignant versus benign parathyroid tumors .", "entity": [], "task": "NER"}
{"text": "We performed genome - wide copy - number and loss of heterozygosity analysis using Affymetrix 50K SNP mapping arrays and / or comparative genomic hybridization on 16 primary parathyroid carcinomas , local recurrences or distant metastases , and matched normal controls , from 10 individuals .", "entity": [], "task": "NER"}
{"text": "Recurrent regions of allelic loss were observed on chromosomes 1p , 3 , and 13q suggesting that key parathyroid tumor suppressor genes are located in these chromosomal locations .", "entity": [], "task": "NER"}
{"text": "Recurrent allelic gains were seen on chromosomes 1q and 16 , suggesting the presence of parathyroid oncogenes on these chromosomes .", "entity": [], "task": "NER"}
{"text": "Importantly , the most common alteration in benign parathyroid adenomas , loss of 11q , was not found as a recurrent change in the malignant parathyroid tissues .", "entity": [], "task": "NER"}
{"text": "Molecular allelotyping using highly polymorphic microsatellite markers provided further confirmation that the prevalence of 11q loss is markedly and significantly lower in carcinomas as compared with adenomas .", "entity": [], "task": "NER"}
{"text": "Our observations provide molecular support for the concept that sporadic parathyroid cancer usually arises de novo , rather than evolving from a pre - existing typical benign adenoma .", "entity": [], "task": "NER"}
{"text": "Furthermore , these results help direct future investigation to ultimately determine which of the candidate genes in these chromosomal locations make significant contributions to the molecular pathogenesis of parathyroid cancer .", "entity": [], "task": "NER"}
{"text": "Fluorescence spectroscopy of PTCDA molecules on the KCl ( 100 ) surface in the limit of low coverages : site selection and diffusion .", "entity": [{"entity": "PTCDA", "entity_type": "Chemical", "pos": [29, 34]}, {"entity": "KCl", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "We performed fluorescence ( FL ) and fluorescence excitation ( FLE ) spectroscopy on the model molecule perylene - 3 , 4 , 9 , 10 - tetracarboxyl acid dianhydride ( PTCDA ) for very low coverages ( below 1 % of a monolayer ) on thin ( 100 ) oriented KCl films .", "entity": [{"entity": "perylene - 3 , 4 , 9 , 10 - tetracarboxyl acid dianhydride", "entity_type": "Chemical", "pos": [104, 162]}, {"entity": "PTCDA", "entity_type": "Chemical", "pos": [165, 170]}, {"entity": "KCl", "entity_type": "Chemical", "pos": [250, 253]}], "task": "NER"}
{"text": "Two different states of PTCDA molecules can be distinguished in the spectra : an initial state , which is observed directly after deposition of the molecules onto the cold sample at 20 K , and a final state , which is found after intensive optical excitation or thermal annealing of the sample .", "entity": [{"entity": "PTCDA", "entity_type": "Chemical", "pos": [24, 29]}], "task": "NER"}
{"text": "The spectrum of the final state is blue - shifted with respect to that of the initial state by 130 +/- 15 cm ( - 1 ) and exhibits lines with significantly reduced widths .", "entity": [], "task": "NER"}
{"text": "This can be explained by diffusion of molecules from initially populated terrace sites to energetically favoured step edge sites .", "entity": [], "task": "NER"}
{"text": "Polarization dependent spectroscopy reveals the same azimuthal orientation of the molecules on both adsorption sites and leads to a model of the adsorption geometry of PTCDA at the KCl step sites .", "entity": [{"entity": "PTCDA", "entity_type": "Chemical", "pos": [168, 173]}, {"entity": "KCl", "entity_type": "Chemical", "pos": [181, 184]}], "task": "NER"}
{"text": "Our experiment demonstrates how optical spectroscopy can be used to investigate kinetic processes of fluorescent molecules on surfaces .", "entity": [], "task": "NER"}
{"text": "Avoidance behaviour response and esterase inhibition in the earthworm , Lumbricus terrestris , after exposure to chlorpyrifos .", "entity": [{"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [113, 125]}], "task": "NER"}
{"text": "The avoidance response of earthworms to polluted soils has been standardised using a simple and low - cost test , which facilitates soil toxicity screening .", "entity": [], "task": "NER"}
{"text": "In this study , the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos - spiked soils , depending on the pesticide concentration and exposure duration .", "entity": [{"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [81, 93]}], "task": "NER"}
{"text": "The inhibition of acetylcholinesterase ( AChE ) and carboxylesterase ( CbE ) activities was also determined as indirect measures of pesticide bioavailability .", "entity": [], "task": "NER"}
{"text": "The effects of different chlorpyrifos concentrations were examined in a standardised test ( two - chamber system ) with 0 . 6 , 3 and 15 mg / kg chlorpyrifos .", "entity": [{"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [25, 37]}, {"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [145, 157]}], "task": "NER"}
{"text": "A modification of the test involved a pre - exposure step ( 24 , 48 or 72 h ) in soils spiked with 15 mg / kg .", "entity": [], "task": "NER"}
{"text": "In both protocols , earthworms were unable to avoid the contaminated soils .", "entity": [], "task": "NER"}
{"text": "However , the esterase activities showed that all earthworms were exposed to chlorpyrifos .", "entity": [{"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [77, 89]}], "task": "NER"}
{"text": "Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test ( 0 . 58 +/- 0 . 20 U / mg protein , mean +/- SD ; n = 72 ) , whereas the CbE activity was significantly inhibited ( 62 - 87 % inhibition ) in earthworms exposed to 3 and 15 mg / kg .", "entity": [], "task": "NER"}
{"text": "In the modified test , earthworms had greatly inhibited AChE activity ( 0 . 088 +/- 0 . 034 U / mg protein , n = 72 ) , which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime ( 2 - PAM ) .", "entity": [{"entity": "pralidoxime", "entity_type": "Chemical", "pos": [208, 219]}, {"entity": "2 - PAM", "entity_type": "Chemical", "pos": [222, 229]}], "task": "NER"}
{"text": "Similarly , the CbE activity was significantly inhibited in earthworms with all treatments .", "entity": [], "task": "NER"}
{"text": "This study suggests that the avoidance behaviour test for organophosphorus - contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [58, 74]}], "task": "NER"}
{"text": "Impact of childhood - onset type 1 diabetes on schooling : a population - based register study .", "entity": [], "task": "NER"}
{"text": "AIMS / HYPOTHESIS : We investigated the impact of type 1 diabetes on educational achievements in compulsory and upper secondary school , as well as potential long - lasting effects .", "entity": [], "task": "NER"}
{"text": "METHODS : Altogether 2 , 485 individuals with type 1 diabetes , diagnosed at the age of < 15 years and born in 1972 - 1978 , were selected from the Swedish Childhood Diabetes Register , which was linked to national population registers including the Swedish Education Register .", "entity": [], "task": "NER"}
{"text": "For each individual , four controls from the general population , matched for year of birth and residence at the time of diagnosis , were selected by Statistics Sweden ( n = 9 , 940 ) .", "entity": [], "task": "NER"}
{"text": "We analysed the impact of diabetes on final school grades at 16 years ( compulsory school ) and 19 years ( upper secondary school ) and on participation in the labour market at 29 years using linear , logistic , ordered logistic and quantile regression analyses , controlling for demographics and socioeconomic background .", "entity": [], "task": "NER"}
{"text": "RESULTS : Diabetes had a negative effect on mean final grades ( scale of 1 - 5 ) in compulsory school ( - 0 . 07 , p < 0 . 001 ) and theoretical programmes in upper secondary school ( - 0 . 07 , p = 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "Children with early - onset diabetes ( 0 - 4 years ) suffered a greater disadvantage as a result of the disease ( - 0 . 15 , p = 0 . 001 in compulsory school ) .", "entity": [], "task": "NER"}
{"text": "The strongest effect was seen in the lowest deciles of the conditional distribution on mean final grades .", "entity": [], "task": "NER"}
{"text": "At age 29 , individuals with diabetes were less likely to be gainfully employed ( OR 0 . 82 , 95 % CI 0 . 73 , 0 . 91 ) .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS / INTERPRETATION : The small but significant negative effect of type 1 diabetes on schooling could affect opportunities for further education and career development .", "entity": [], "task": "NER"}
{"text": "Attention must be paid in school to the special needs of children with diabetes .", "entity": [], "task": "NER"}
{"text": "Multiple biological properties of macelignan and its pharmacological implications .", "entity": [{"entity": "macelignan", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "Macelignan found in the nutmeg mace of Myristica fragrans obtains increasing attention as a new avenue in treating various diseases .", "entity": [{"entity": "Macelignan", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Macelignan has been shown to possess a spectrum of pharmacological activities , including anti - bacterial , anti - inflammatory , anti - cancer , anti - diabetes , and hepatoprotective activities ; recently , it has also been shown to have neuroprotective activities .", "entity": [{"entity": "Macelignan", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "This review summarizes the current research on the biological effects of macelignan derived from M . fragrans , with emphasis on the importance in understanding and treating complex diseases such as cancer and Alzheimer ' s disease .", "entity": [{"entity": "macelignan", "entity_type": "Chemical", "pos": [73, 83]}], "task": "NER"}
{"text": "Induction of heme oxygenase - 1 protects mouse liver from apoptotic ischemia / reperfusion injury .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [13, 17]}], "task": "NER"}
{"text": "Ischemia / reperfusion ( I / R ) injury is the main cause of primary graft dysfunction of liver allografts .", "entity": [], "task": "NER"}
{"text": "Cobalt - protoporphyrin ( CoPP ) - dependent induction of heme oxygenase ( HO ) - 1 has been shown to protect the liver from I / R injury .", "entity": [{"entity": "Cobalt - protoporphyrin", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "CoPP", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "heme", "entity_type": "Chemical", "pos": [58, 62]}], "task": "NER"}
{"text": "This study analyzes the apoptotic mechanisms of HO - 1 - mediated cytoprotection in mouse liver exposed to I / R injury .", "entity": [], "task": "NER"}
{"text": "HO - 1 induction was achieved by the administration of CoPP ( 1 . 5 mg / kg body weight i . p . ) .", "entity": [{"entity": "CoPP", "entity_type": "Chemical", "pos": [55, 59]}], "task": "NER"}
{"text": "Mice were studied in in vivo model of hepatic segmental ( 70 % ) ischemia for 60 min and reperfusion injury .", "entity": [], "task": "NER"}
{"text": "Mice were randomly allocated to four main experimental groups ( n = 10 each ) : ( 1 ) A control group undergoing sham operation .", "entity": [], "task": "NER"}
{"text": "( 2 ) Similar to group 1 but with the administration of CoPP 72 h before the operation .", "entity": [{"entity": "CoPP", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "( 3 ) Mice undergoing in vivo hepatic I / R .", "entity": [], "task": "NER"}
{"text": "( 4 ) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction .", "entity": [{"entity": "CoPP", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "When compared with the I / R mice group , in the I / R + CoPP mice group , the increased hepatic expression of HO - 1 was associated with a significant reduction in liver enzyme levels , fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase - 3 , there was a decreased mean number of proliferating cells ( positively stained for Ki67 ) , and a reduced hepatic expression of : C / EBP homologous protein ( an index of endoplasmic reticulum stress ) , the NF - kappa B ' s regulated genes ( CIAP2 , MCP - 1 and IL - 6 ) , and increased hepatic expression of I kappa Ba ( the inhibitory protein of NF - kappa B ) .", "entity": [{"entity": "CoPP", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "HO - 1 over - expression plays a pivotal role in reducing the hepatic apoptotic IR injury .", "entity": [], "task": "NER"}
{"text": "HO - 1 may serve as a potential target for therapeutic intervention in hepatic I / R injury during liver transplantation .", "entity": [], "task": "NER"}
{"text": "Myeloperoxidase Activity and Its Corresponding mRNA Expression as well as Gene Polymorphism in the Population Living in the Coal - Burning Endemic Fluorosis Area in Guizhou of China .", "entity": [], "task": "NER"}
{"text": "The myeloperoxidase ( MPO ) activity and its corresponding mRNA expression as well as gene polymorphism were investigated in the population who live in the endemic fluorosis area .", "entity": [], "task": "NER"}
{"text": "In the study , 150 people were selected from the coal - burning endemic fluorosis area and 150 normal persons from the non - fluorosis area in Guizhou province of China .", "entity": [], "task": "NER"}
{"text": "The blood samples were collected from these people .", "entity": [], "task": "NER"}
{"text": "The activity of MPO in the plasma was determined by spectrophotometer ; the expression of MPO mRNA was measured by employing real - time polymerase chain reaction ; DNAs were extracted from the leucocytes in blood and five SNP genotypes of MPO promoter gene detected by a multiplex genotyping method , adapter - ligation - mediated allele - specific amplification .", "entity": [], "task": "NER"}
{"text": "The results showed that the MPO activity and its corresponding mRNA in blood were significantly increased in the population living in the area of fluorosis .", "entity": [], "task": "NER"}
{"text": "The different genotype frequencies of MPO , including - 1228G / A , - 585T / C , - 463G / A , and - 163C / T , and the three haplotypes with higher frequencies , including - 163C - 463G - 585T - 1228G - 1276T , - 163C - 463G - 585T - 1228G - 1276C , and - 163C - 463G - 585T - 1228A - 1276T , were significantly associated with fluorosis .", "entity": [], "task": "NER"}
{"text": "The results indicated that the elevated activity of MPO induced by endemic fluorosis may be connected in mechanism to the stimulated expression of MPO mRNA and the changed gene polymorphism .", "entity": [], "task": "NER"}
{"text": "Microporous carbon nanoplates from regenerated silk proteins for supercapacitors .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [12, 18]}], "task": "NER"}
{"text": "Novel carbon - based microporous nanoplates containing numerous heteroatoms ( H - CMNs ) are fabricated from regenerated silk fibroin by the carbonization and activation of KOH .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [6, 12]}, {"entity": "KOH", "entity_type": "Chemical", "pos": [173, 176]}], "task": "NER"}
{"text": "The H - CMNs exhibit superior electrochemical performance , displaying a specific capacitance of 264 F / g in aqueous electrolytes , a specific energy of 133 Wh / kg , a specific power of 217 kW / kg , and a stable cycle life over 10000 cycles .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic properties of anti - influenza neuraminidase inhibitors .", "entity": [], "task": "NER"}
{"text": "Neuraminidase inhibitors are the mainstay of anti - influenza treatment .", "entity": [], "task": "NER"}
{"text": "Oseltamivir is the most widely used drug but is currently available only as an oral formulation .", "entity": [{"entity": "Oseltamivir", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Resistance spreads rapidly in seasonal H1N1 influenza A viruses , which were universally resistant in 2008 , because of the H275Y mutation in the neuraminidase ( NA ) gene .", "entity": [], "task": "NER"}
{"text": "Oseltamivir is a prodrug for the active carboxylate metabolite .", "entity": [{"entity": "Oseltamivir", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [40, 51]}], "task": "NER"}
{"text": "Ex vivo conversion in blood samples may have confounded early pharmacokinetic studies .", "entity": [], "task": "NER"}
{"text": "Oseltamivir shows dose linear kinetics , and oseltamivir carboxylate has an elimination half - life ( t ( 1 / 2 ) beta ) after oral administration in healthy individuals of approximately 7 . 7 hours .", "entity": [{"entity": "Oseltamivir", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "oseltamivir carboxylate", "entity_type": "Chemical", "pos": [45, 68]}], "task": "NER"}
{"text": "Oseltamivir carboxylate is eliminated primarily by tubular secretion , and both clearance and tissue distribution are reduced by probenecid .", "entity": [{"entity": "Oseltamivir carboxylate", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "probenecid", "entity_type": "Chemical", "pos": [129, 139]}], "task": "NER"}
{"text": "The H275Y mutation in NA confers high - level oseltamivir resistance and intermediate peramivir resistance but does not alter zanamivir susceptibility .", "entity": [{"entity": "oseltamivir", "entity_type": "Chemical", "pos": [46, 57]}, {"entity": "peramivir", "entity_type": "Chemical", "pos": [86, 95]}, {"entity": "zanamivir", "entity_type": "Chemical", "pos": [126, 135]}], "task": "NER"}
{"text": "Zanamivir is available as a powder for inhalation , and a parenteral form is under development .", "entity": [{"entity": "Zanamivir", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Zanamivir distributes in an apparent volume of distribution approximating that of extracellular water and is rapidly eliminated ( t ( 1 / 2 ) beta of approximately 3 . 0 hours ) .", "entity": [{"entity": "Zanamivir", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Peramivir is slowly eliminated ( t ( 1 / 2 ) beta of 7 . 7 - 20 . 8 hours ) and is prescribed as either a once - daily injection or as a single infusion .", "entity": [{"entity": "Peramivir", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Laninamivir is a recently developed slowly eliminated compound for administration by inhalation .", "entity": [{"entity": "Laninamivir", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Comparison of subcutaneous and intravenous administration of trastuzumab : a phase I / Ib trial in healthy male volunteers and patients with HER2 - positive breast cancer .", "entity": [], "task": "NER"}
{"text": "Trastuzumab is a key component of treatment for human epidermal growth factor receptor 2 ( HER2 ) - positive breast cancer in both the early and metastatic settings .", "entity": [], "task": "NER"}
{"text": "It is administered intravenously , with between 17 and 52 infusions in standard regimens over 1 year .", "entity": [], "task": "NER"}
{"text": "Intravenous administration of trastuzumab requires substantial time commitments for patients and health care professionals and can result in patient discomfort .", "entity": [], "task": "NER"}
{"text": "A subcutaneous formulation of trastuzumab , containing recombinant human hyaluronidase to overcome subcutaneous absorption barriers , would reduce the administration duration and remove the need to establish intravenous access , thus improving the overall convenience of trastuzumab administration .", "entity": [], "task": "NER"}
{"text": "This open - label , 2 - part , phase I / Ib study ( NCT00800436 ) was undertaken in healthy male volunteers and female patients with HER2 - positive early breast cancer to identify the dose of subcutaneous trastuzumab that resulted in exposure comparable with the approved intravenous trastuzumab dose .", "entity": [], "task": "NER"}
{"text": "A subcutaneous trastuzumab dose of 8 mg / kg was found to result in exposure comparable with the intravenous trastuzumab dose of 6 mg / kg .", "entity": [], "task": "NER"}
{"text": "The subcutaneous formulation was well tolerated , with a trend toward fewer adverse events versus intravenous administration ; most adverse events were mild in intensity .", "entity": [], "task": "NER"}
{"text": "These results support an ongoing phase III efficacy and safety study comparing a fixed subcutaneous trastuzumab dose with intravenous trastuzumab administration .", "entity": [], "task": "NER"}
{"text": "Inhibitory effect of ketoconazole on the pharmacokinetics of a multireceptor tyrosine kinase inhibitor BMS - 690514 in healthy participants : assessing the mechanism of the interaction with physiologically - based pharmacokinetic simulations .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [21, 33]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [103, 115]}], "task": "NER"}
{"text": "BMS - 690514 , a selective inhibitor of the ErbB and vascular endothelial growth factor receptors , has shown antitumor activity in early clinical development .", "entity": [{"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "The compound is metabolized by multiple enzymes , with CYP3A4 responsible for the largest fraction ( 34 % ) of metabolism .", "entity": [], "task": "NER"}
{"text": "It is also a substrate of P - glycoprotein ( P - gp ) in vitro .", "entity": [], "task": "NER"}
{"text": "To assess the effect of ketoconazole on BMS - 690514 pharmacokinetics , 17 healthy volunteers received 200 mg BMS - 690514 alone followed by 100 mg BMS - 690514 with ketoconazole ( 400 mg once daily for 4 days ) .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [40, 52]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [110, 122]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [148, 160]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [166, 178]}], "task": "NER"}
{"text": "The AUC ( infinity ) of 100 mg BMS - 690514 concomitantly administered with ketoconazole was similar to that of 200 mg BMS - 690514 alone .", "entity": [{"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [31, 43]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [76, 88]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [119, 131]}], "task": "NER"}
{"text": "The dose - normalized C ( max ) and AUC ( infinity ) of BMS - 690514 from the 100 - mg BMS - 690514 / 400 - mg ketoconazole treatment increased by 55 % and 127 % , respectively , relative to those from 200 mg BMS - 690514 alone .", "entity": [{"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [56, 68]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [87, 99]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [111, 123]}, {"entity": "BMS - 690514", "entity_type": "Chemical", "pos": [209, 221]}], "task": "NER"}
{"text": "Prediction of the drug - drug interaction ( DDI ) using a population - based simulator ( Simcyp ) indicated that , in addition to CYP3A4 inhibition , the inhibition of P - gp by ketoconazole in the intestine , liver , and kidneys must be invoked to fully account for the DDI observed .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [178, 190]}], "task": "NER"}
{"text": "This finding suggests that the inhibition of P - gp by ketoconazole , along with its effect on CYP3A4 , needs to be considered when designing a DDI study of ketoconazole with a victim drug that is a dual substrate .", "entity": [{"entity": "ketoconazole", "entity_type": "Chemical", "pos": [55, 67]}, {"entity": "ketoconazole", "entity_type": "Chemical", "pos": [157, 169]}], "task": "NER"}
{"text": "Construction of robust enzyme nanocapsules for effective organophosphate decontamination , detoxification , and protection .", "entity": [{"entity": "organophosphate", "entity_type": "Chemical", "pos": [57, 72]}], "task": "NER"}
{"text": "Nanocapsules of organophosphorous hydrolase with enhanced enzyme activity and stability are prepared via in situ polymerization , providing a novel class of nanoparticles for the decontamination and detoxification of organophosphates such as chemical warfare agents and pesticides .", "entity": [{"entity": "organophosphorous", "entity_type": "Chemical", "pos": [16, 33]}, {"entity": "organophosphates", "entity_type": "Chemical", "pos": [217, 233]}], "task": "NER"}
{"text": "Using the nanocapsules as building blocks , bioactive nanocomposites are also fabricated , enabling their use for organophosphate protection .", "entity": [{"entity": "organophosphate", "entity_type": "Chemical", "pos": [114, 129]}], "task": "NER"}
{"text": "Bioactive formulations with sugar - derived surfactants : a new approach for photoprotection and controlled release of promethazine .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [28, 33]}, {"entity": "promethazine", "entity_type": "Chemical", "pos": [119, 131]}], "task": "NER"}
{"text": "Skin deep : A bioactive formulation for dermal delivery of antihistamines is obtained by using the original properties of catanionic associations towards self - assembly in water .", "entity": [], "task": "NER"}
{"text": "The drug , which participates in its own transport , is preserved from photodegradation when solubilised in the bioactive formulation .", "entity": [], "task": "NER"}
{"text": "The drug release through the skin is also delayed .", "entity": [], "task": "NER"}
{"text": "A simple method for fabricating patterned curvilinear microstructures in poly ( dimethylsiloxane ) by selective wetting .", "entity": [{"entity": "poly ( dimethylsiloxane )", "entity_type": "Chemical", "pos": [73, 98]}], "task": "NER"}
{"text": "The fabrication of patterned microstructures in poly ( dimethylsiloxane ) ( PDMS ) is a prerequisite for soft lithography .", "entity": [{"entity": "poly ( dimethylsiloxane )", "entity_type": "Chemical", "pos": [48, 73]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "Herein , curvilinear surface relief microstructures in PDMS are fabricated through a simple three - stage approach combining microcontact printing ( mu CP ) , selective surface wetting / dewetting and replica molding ( REM ) .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [55, 59]}], "task": "NER"}
{"text": "First , using an original PDMS stamp ( first - generation stamp ) with linear relief features , a chemical pattern on gold substrate is generated by mu CP using hexadecanethiol ( HDT ) as an ink .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "hexadecanethiol", "entity_type": "Chemical", "pos": [161, 176]}, {"entity": "HDT", "entity_type": "Chemical", "pos": [179, 182]}], "task": "NER"}
{"text": "Then , by a dip - coating process , an ordered polyethylene glycol ( PEG ) polymer - dot array forms on the HDT - patterned gold substrate .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [47, 66]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "HDT", "entity_type": "Chemical", "pos": [108, 111]}], "task": "NER"}
{"text": "Finally , based on a REM process , the PEG - dot array on gold substrate is used to fabricate a second - generation PDMS stamp with microcavity array , and the second - generation PDMS stamp is used to generate third - generation PDMS stamp with microbump array .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [116, 120]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [180, 184]}, {"entity": "PDMS", "entity_type": "Chemical", "pos": [230, 234]}], "task": "NER"}
{"text": "These fabricated new - generation stamps are utilized in mu CP and in micromolding in capillaries ( MIMIC ) , allowing the generation of surface micropatterns which cannot be obtained using the original PDMS stamp .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [203, 207]}], "task": "NER"}
{"text": "The method will be useful in producing new - generation PDMS stamps , especially for those who want to use soft lithography in their studies but have no access to the microfabrication facilities .", "entity": [{"entity": "PDMS", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "The discovery of novel human androgen receptor antagonist chemotypes using a combined pharmacophore screening procedure .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Unraveling the mechanisms involved in castration - and therapy - resistant prostate cancer has led to a renewed interest in androgen receptor ( AR ) - targeted therapeutics .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "Anti - androgens that block the activity of the AR therefore remain a valid therapeutic option .", "entity": [{"entity": "androgens", "entity_type": "Chemical", "pos": [7, 16]}], "task": "NER"}
{"text": "However , they must be more effective than , or display a distinct mechanism of action or binding mode from those of bicalutamide and hydroxyflutamide , which are currently in clinical use .", "entity": [{"entity": "bicalutamide", "entity_type": "Chemical", "pos": [117, 129]}, {"entity": "hydroxyflutamide", "entity_type": "Chemical", "pos": [134, 150]}], "task": "NER"}
{"text": "For that reason , the second - generation anti - androgen MDV3100 was developed .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [49, 57]}, {"entity": "MDV3100", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "MDV3100 , however , shares its 4 - cyano - 3 - ( trifluoromethyl ) phenyl group with bicalutamide and hydroxyflutamide required for binding to the AR .", "entity": [{"entity": "MDV3100", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "4 - cyano - 3 - ( trifluoromethyl ) phenyl", "entity_type": "Chemical", "pos": [31, 73]}, {"entity": "bicalutamide", "entity_type": "Chemical", "pos": [85, 97]}, {"entity": "hydroxyflutamide", "entity_type": "Chemical", "pos": [102, 118]}], "task": "NER"}
{"text": "In this work , we used a combined strategy to find new antagonist structures distinct from the 4 - cyano - 3 - ( trifluoromethyl ) phenyl group to avoid cross - resistance for these compounds and to find structures without agonist activity on mutant ARs ( AR W741C and AR T877A ) .", "entity": [{"entity": "4 - cyano - 3 - ( trifluoromethyl ) phenyl", "entity_type": "Chemical", "pos": [95, 137]}], "task": "NER"}
{"text": "We found two novel chemotypes with AR - antagonistic activity ( IC ( 50 ) : 3 - 6 mu M ) by virtual screening and confirmed their biological activity in an androgen - responsive reporter assay .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [156, 164]}], "task": "NER"}
{"text": "The design of our computational approach was validated by the observation of strongly decreased or absence of agonistic activity on the two mutant ARs .", "entity": [], "task": "NER"}
{"text": "Further structural derivatization to optimize the potency of these compounds can render these chemotypes into very promising , alternative AR antagonists for prostate cancer therapy .", "entity": [], "task": "NER"}
{"text": "The Overexpression of Hypomethylated miR - 663 Induces Chemotherapy Resistance in Human Breast Cancer Cells by Targeting Heparin Sulfate Proteoglycan 2 ( HSPG2 ) .", "entity": [{"entity": "Sulfate", "entity_type": "Chemical", "pos": [129, 136]}], "task": "NER"}
{"text": "MicroRNAs are involved in regulating the biology of cancer cells , but their involvement in chemoresistance is not fully understood .", "entity": [], "task": "NER"}
{"text": "We found that miR - 663 was up - regulated in our induced multidrug - resistant MDA - MB - 231 / ADM cell line and that this up - regulation was closely related to chemosensitivity .", "entity": [], "task": "NER"}
{"text": "In the present study , we aimed to clarify the role of miR - 663 in regulating the chemoresistance of breast cancer .", "entity": [], "task": "NER"}
{"text": "MicroRNA microarray and quantitative RT - PCR assays were used to identify differentially expressed microRNAs .", "entity": [], "task": "NER"}
{"text": "Cell apoptosis was evaluated by annexin V / propidium iodide staining , TUNEL , and reactive oxygen species generation analysis .", "entity": [{"entity": "propidium iodide", "entity_type": "Chemical", "pos": [44, 60]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [93, 99]}], "task": "NER"}
{"text": "The expression of miR - 663 and HSPG2 in breast cancer tissues was detected by in situ hybridization and immunohistochemistry .", "entity": [], "task": "NER"}
{"text": "The potential targets of miR - 663 were defined by a luciferase reporter assay .", "entity": [], "task": "NER"}
{"text": "Bisulfite sequencing PCR was used to analyze the methylation status .", "entity": [{"entity": "Bisulfite", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "We found that miR - 663 was significantly elevated in MDA - MB - 231 / ADM cells , and the down - regulation of miR - 663 sensitized MDA - MB - 231 / ADM cells to both cyclophosphamide and docetaxel .", "entity": [{"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [168, 184]}, {"entity": "docetaxel", "entity_type": "Chemical", "pos": [189, 198]}], "task": "NER"}
{"text": "The overexpression of miR - 663 in breast tumor tissues was associated with chemoresistance ; in MDA - MB - 231 cells , this chemoresistance was accompanied by the down - regulation of HSPG2 , which was identified as a target of miR - 663 .", "entity": [], "task": "NER"}
{"text": "MDA - MB - 231 / ADM contained fewer methylated CpG sites than its parental cell line , and miR - 663 expression in MDA - MB - 231 cells was reactivated by 5 - aza - 29 - deoxycytidine treatment , indicating that DNA methylation may play a functional role in the expression of miR - 663 .", "entity": [{"entity": "CpG", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "5 - aza - 29 - deoxycytidine", "entity_type": "Chemical", "pos": [156, 184]}], "task": "NER"}
{"text": "Our findings suggest that the overexpression of hypomethylated miR - 663 induced chemoresistance in breast cancer cells by down - regulating HSPG2 , thus providing a potential target for the development of an microRNA - based approach for breast cancer therapy .", "entity": [], "task": "NER"}
{"text": "A concise synthesis of pyrazole analogues of combretastatin A1 as potent anti - tubulin agents .", "entity": [{"entity": "pyrazole", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "combretastatin A1", "entity_type": "Chemical", "pos": [45, 62]}], "task": "NER"}
{"text": "Combretastatin A1 ( CA1 ) binds to the beta - subunit at the colchicine binding site of tubulin and inhibits polymerization .", "entity": [{"entity": "Combretastatin A1", "entity_type": "Chemical", "pos": [0, 17]}, {"entity": "CA1", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "colchicine", "entity_type": "Chemical", "pos": [61, 71]}], "task": "NER"}
{"text": "As such , it is both an antitumor agent and a vascular disrupting agent .", "entity": [], "task": "NER"}
{"text": "It has been shown to be at least tenfold more potent than combretastatin A4 ( CA4 ) in terms of vascular shutdown , which correlates with its metabolism to reactive ortho - quinone species that are assumed to be directly cytotoxic in tumor cells .", "entity": [{"entity": "combretastatin A4", "entity_type": "Chemical", "pos": [58, 75]}, {"entity": "CA4", "entity_type": "Chemical", "pos": [78, 81]}, {"entity": "ortho - quinone", "entity_type": "Chemical", "pos": [165, 180]}], "task": "NER"}
{"text": "A series of 3 , 4 - diarylpyrazoles were concisely synthesized , one of which , 3 - methoxy - 6 - [ 4 - ( 3 , 4 , 5 - trimethoxyphenyl ) - 1H - pyrazol - 3 - yl ] benzene - 1 , 2 - diol ( 27 ) , proved to be a cytotoxic anti - tubulin agent with low nanomolar potency .", "entity": [{"entity": "3 , 4 - diarylpyrazoles", "entity_type": "Chemical", "pos": [12, 35]}, {"entity": "3 - methoxy - 6 - [ 4 - ( 3 , 4 , 5 - trimethoxyphenyl ) - 1H - pyrazol - 3 - yl ] benzene - 1 , 2 - diol", "entity_type": "Chemical", "pos": [80, 185]}], "task": "NER"}
{"text": "We also report that combretastatins , including CA1 , CA4 , and 27 , are effective against mesothelioma cell lines and therefore have significant clinical promise .", "entity": [{"entity": "combretastatins", "entity_type": "Chemical", "pos": [20, 35]}, {"entity": "CA1", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "CA4", "entity_type": "Chemical", "pos": [54, 57]}], "task": "NER"}
{"text": "Metabolism experiments demonstrate that 27 retains the ability to form ortho - quinone species , while the pyrazole ring shows high metabolic stability , suggesting that this compound might result in better pharmacokinetic profiles than CA1 , with similar pharmacodynamic properties and clinical potential .", "entity": [{"entity": "ortho - quinone", "entity_type": "Chemical", "pos": [71, 86]}, {"entity": "pyrazole", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "CA1", "entity_type": "Chemical", "pos": [237, 240]}], "task": "NER"}
{"text": "Understanding quantitative structure - property relationships uncertainty in environmental fate modeling .", "entity": [], "task": "NER"}
{"text": "In cases in which experimental data on chemical - specific input parameters are lacking , chemical regulations allow the use of alternatives to testing , such as in silico predictions based on quantitative structure - property relationships ( QSPRs ) .", "entity": [], "task": "NER"}
{"text": "Such predictions are often given as point estimates ; however , little is known about the extent to which uncertainties associated with QSPR predictions contribute to uncertainty in fate assessments .", "entity": [], "task": "NER"}
{"text": "In the present study , QSPR - induced uncertainty in overall persistence ( POV ) and long - range transport potential ( LRTP ) was studied by integrating QSPRs into probabilistic assessments of five polybrominated diphenyl ethers ( PBDEs ) , using the multimedia fate model Simplebox .", "entity": [{"entity": "polybrominated diphenyl ethers", "entity_type": "Chemical", "pos": [199, 229]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [232, 237]}], "task": "NER"}
{"text": "The uncertainty analysis considered QSPR predictions of the fate input parameters ' melting point , water solubility , vapor pressure , organic carbon - water partition coefficient , hydroxyl radical degradation , biodegradation , and photolytic degradation .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [144, 150]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [183, 191]}], "task": "NER"}
{"text": "Uncertainty in POV and LRTP was dominated by the uncertainty in direct photolysis and the biodegradation half - life in water .", "entity": [], "task": "NER"}
{"text": "However , the QSPRs developed specifically for PBDEs had a relatively low contribution to uncertainty .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [47, 52]}], "task": "NER"}
{"text": "These findings suggest that the reliability of the ranking of PBDEs on the basis of POV and LRTP can be substantially improved by developing better QSPRs to estimate degradation properties .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [62, 67]}], "task": "NER"}
{"text": "The present study demonstrates the use of uncertainty and sensitivity analyses in nontesting strategies and highlights the need for guidance when compounds fall outside the applicability domain of a QSPR .", "entity": [], "task": "NER"}
{"text": "2013 ; 32 : 1069 - 1076 .", "entity": [], "task": "NER"}
{"text": "Balance of coordination and hydrophobic interaction in the formation of bilayers in metal - coordinated surfactant mixtures .", "entity": [], "task": "NER"}
{"text": "Metal - ligand coordination and hydrophobic interaction are two significant driving forces in the aggregation of mixtures of M ( n + ) surfactants and alkyldimethylamine oxide ( CnDMAO ) in aqueous solutions .", "entity": [{"entity": "alkyldimethylamine oxide", "entity_type": "Chemical", "pos": [151, 175]}, {"entity": "CnDMAO", "entity_type": "Chemical", "pos": [178, 184]}], "task": "NER"}
{"text": "The coordinated systems exhibit rich aggregation behavior .", "entity": [], "task": "NER"}
{"text": "This study investigated the effect of M ( n + ) ions ( Zn ( 2 + ) , Ca ( 2 + ) , Ba ( 2 + ) , Al ( 3 + ) , Fe ( 3 + ) , La ( 3 + ) , Eu ( 3 + ) , and Tb ( 3 + ) ) and hydrophobic chains ( hydrocarbon and fluorocarbon ) on the formation of metal - coordinated bilayers .", "entity": [{"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [68, 78]}, {"entity": "Ba ( 2 + )", "entity_type": "Chemical", "pos": [81, 91]}, {"entity": "Al ( 3 + )", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "Fe ( 3 + )", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "La ( 3 + )", "entity_type": "Chemical", "pos": [120, 130]}, {"entity": "Eu ( 3 + )", "entity_type": "Chemical", "pos": [133, 143]}, {"entity": "Tb ( 3 + )", "entity_type": "Chemical", "pos": [150, 160]}, {"entity": "hydrocarbon", "entity_type": "Chemical", "pos": [188, 199]}, {"entity": "fluorocarbon", "entity_type": "Chemical", "pos": [204, 216]}], "task": "NER"}
{"text": "We found that fluorocarbon chains and branched hydrocarbon chains are preferable to the corresponding linear hydrocarbon chains for the formation of an L alpha phase .", "entity": [{"entity": "fluorocarbon", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "hydrocarbon", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "hydrocarbon", "entity_type": "Chemical", "pos": [109, 120]}], "task": "NER"}
{"text": "Moreover , L alpha phases formed by fluorocarbon chains exhibited higher viscoelasticity than ones formed by the hydrocarbons , and the bilayers formed by branched chains were rather flexible , revealing obvious undulation .", "entity": [{"entity": "fluorocarbon", "entity_type": "Chemical", "pos": [36, 48]}, {"entity": "hydrocarbons", "entity_type": "Chemical", "pos": [113, 125]}], "task": "NER"}
{"text": "The construction of bilayers was also strongly affected by metal ions due to their variable coordination ability with CnDMAO .", "entity": [{"entity": "CnDMAO", "entity_type": "Chemical", "pos": [118, 124]}], "task": "NER"}
{"text": "Our results contribute to the understanding of the formation of metal - coordinated bilayers , which is driven by the interplay of noncovalent forces .", "entity": [], "task": "NER"}
{"text": "A natural topological insulator .", "entity": [], "task": "NER"}
{"text": "The earth ' s crust and outer space are rich sources of technologically relevant materials which have found application in a wide range of fields .", "entity": [], "task": "NER"}
{"text": "Well - established examples are diamond , one of the hardest known materials , or graphite as a suitable precursor of graphene .", "entity": [{"entity": "diamond", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "graphite", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [118, 126]}], "task": "NER"}
{"text": "The ongoing drive to discover novel materials useful for ( opto ) electronic applications has recently drawn strong attention to topological insulators .", "entity": [], "task": "NER"}
{"text": "Here , we report that Kawazulite , a mineral with the approximate composition Bi2 ( Te , Se ) 2 ( Se , S ) , represents a naturally occurring topological insulator whose electronic properties compete well with those of its synthetic counterparts .", "entity": [{"entity": "Kawazulite", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "Bi2 ( Te , Se ) 2 ( Se , S )", "entity_type": "Chemical", "pos": [78, 106]}], "task": "NER"}
{"text": "Kawazulite flakes with a thickness of a few tens of nanometers were prepared by mechanical exfoliation .", "entity": [], "task": "NER"}
{"text": "They exhibit a low intrinsic bulk doping level and correspondingly a sizable mobility of surface state carriers of more than 1000 cm ( 2 ) / ( V s ) at low temperature .", "entity": [], "task": "NER"}
{"text": "Based on these findings , further minerals which due to their minimized defect densities display even better electronic characteristics may be identified in the future .", "entity": [], "task": "NER"}
{"text": "Robust ordered cubic mesostructured polymer / silica composite films grown at the air / water interface .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [46, 52]}], "task": "NER"}
{"text": "Polymer / silica composite films , stable to calcination , were produced using catanionic surfactant mixtures ( hexadecyltrimethylammonium bromide ( CTAB ) and sodium dodecyl sulfate ( SDS ) ) and polymers ( polyethylenimine ( PEI ) or polyacrylamide ( PAAm ) ) at the air / water interface .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "hexadecyltrimethylammonium bromide", "entity_type": "Chemical", "pos": [112, 146]}, {"entity": "CTAB", "entity_type": "Chemical", "pos": [149, 153]}, {"entity": "sodium dodecyl sulfate", "entity_type": "Chemical", "pos": [160, 182]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [185, 188]}, {"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [208, 224]}, {"entity": "PEI", "entity_type": "Chemical", "pos": [227, 230]}, {"entity": "polyacrylamide", "entity_type": "Chemical", "pos": [236, 250]}, {"entity": "PAAm", "entity_type": "Chemical", "pos": [253, 257]}], "task": "NER"}
{"text": "Film formation processes were probed by time - resolved neutron reflectivity measurements .", "entity": [], "task": "NER"}
{"text": "Grazing incidence X - ray diffraction ( GID ) measurements indicate that the mesophase geometry of the interfacial films could be controlled to give lamellar , 2D hexagonal , and several cubic phases ( Pn3 m , Fm3 m , and Im3 m ) by varying the polyelectrolyte molecular weight , polyelectrolyte chemical nature , or the cationic : anionic surfactant molar ratio .", "entity": [], "task": "NER"}
{"text": "On the basis of GID results , a phase diagram for the catanionic surfactant / polyelectrolyte / TMOS film system was drawn .", "entity": [{"entity": "TMOS", "entity_type": "Chemical", "pos": [96, 100]}], "task": "NER"}
{"text": "These films can be easily removed from the interface and mesoporous silica films which retain the film geometry can be obtained after calcination ; moreover , this film preparation method provides a simple way to impart polymer functionality into the mesostructured silica wall , which means these films have potential applications in a variety of fields such as catalysis , molecular separation , and drug delivery .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [68, 74]}, {"entity": "silica", "entity_type": "Chemical", "pos": [266, 272]}], "task": "NER"}
{"text": "The circadian clock circuitry and the AHR signaling pathway in physiology and pathology .", "entity": [], "task": "NER"}
{"text": "Life forms populating the Earth must face environmental challenges to assure individual and species survival .", "entity": [], "task": "NER"}
{"text": "The strategies predisposed to maintain organismal homeostasis and grant selective advantage rely on anticipatory phenomena facing periodic modifications , and compensatory phenomena facing unpredictable changes .", "entity": [], "task": "NER"}
{"text": "Biological processes bringing about these responses are respectively driven by the circadian timing system , a complex of biological oscillators entrained to the environmental light / dark cycle , and by regulatory and metabolic networks that precisely direct the body ' s adjustments to variations of external conditions and internal milieu .", "entity": [], "task": "NER"}
{"text": "A critical role in organismal homeostatic functions is played by the aryl hydrocarbon receptor ( AHR ) complex , which senses environmental and endogenous compounds , influences metabolic responses controlling phase I / II gene expression , and modulates vital phenomena such as development , inflammation and adaptive immunity .", "entity": [{"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [69, 85]}], "task": "NER"}
{"text": "A physiological cross - talk between circadian and AHR signaling pathways has been evidenced .", "entity": [], "task": "NER"}
{"text": "The alteration of AHR signaling pathway deriving from genetic damage with polymorphisms or mutations , or produced by exogenous or endogenous AHR activation , and chronodisruption caused by mismatch between the body ' s internal clock and geophysical time / social schedules , are capable of triggering pathological mechanisms involved in metabolic , immune - related and neoplastic diseases .", "entity": [], "task": "NER"}
{"text": "On the other hand , the molecular components of the circadian clock circuitry and AHR signaling pathway may represent useful tools for preventive interventions and valuable targets of therapeutic approaches .", "entity": [], "task": "NER"}
{"text": "Deficient fear recognition in regular cocaine users is not attributable to elevated impulsivity or conduct disorder prior to cocaine use .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "We previously reported that regular recreational intranasal cocaine users exhibit impaired recognition of facial expressions of fear compared to occasional cocaine users and cocaine - na i ve controls .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [156, 163]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [174, 181]}], "task": "NER"}
{"text": "The aim of the present study was to re - investigate this phenomenon after controlling for impulsivity , conduct disorder ( CD ) and anti - social personality disorder ( ASPD ) .", "entity": [], "task": "NER"}
{"text": "We employed a cross - sectional design to compare 31 cocaine - na i ve participants , 35 occasional cocaine users and 20 regular recreational cocaine users .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [53, 60]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [100, 107]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [142, 149]}], "task": "NER"}
{"text": "An emotional facial expression ( EFE ) task which comprised a male and a female face expressing six basic emotions morphed to differing degrees of emotional intensity was administered together with questionnaires to assess : CD , ASPD and impulsiveness .", "entity": [], "task": "NER"}
{"text": "ASPD was not a significant covariate for EFE performance but impulsiveness and CD were significant covariates .", "entity": [], "task": "NER"}
{"text": "After treating impulsiveness and CD as covariates we again observed a group difference in fear recognition ability attributable to the particularly impaired performance of regular cocaine users .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [180, 187]}], "task": "NER"}
{"text": "This suggests that , although elevated impulsiveness and CD before the age of 15 years , may predispose a relative inability to recognize facial expressions of fear in adulthood , subsequent regular recreational use of cocaine represents an additional factor that is specifically associated with a selective deficit in fear recognition .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [219, 226]}], "task": "NER"}
{"text": "Painting by numbers : increasing the parts list for chromatin domains .", "entity": [], "task": "NER"}
{"text": "In this issue of Molecular Cell , van Bemmel and colleagues ( 2013 ) report the genome - wide mapping of 42 novel chromatin factors , systematically identifying new components of the various chromatin domains present in fly cells .", "entity": [], "task": "NER"}
{"text": "Isolation , identification and antimicrobial activity of propolis - associated fungi .", "entity": [], "task": "NER"}
{"text": "Propolis is a natural product widely known for its medicinal properties .", "entity": [], "task": "NER"}
{"text": "In this work , fungi present on propolis samples were isolated , identified and tested for the production of antimicrobial metabolites .", "entity": [], "task": "NER"}
{"text": "Twenty - two fungal isolates were obtained , some of which were identified as Alternaria alternata , Aspergillus flavus , Bipolaris hawaiiensis , Fusarium merismoides , Lasiodiplodia theobromae , Penicillium citrinum , Penicillium crustosum , Penicillium janthinellum , Penicillium purpurogenum , Pestalotiopsis palustris , Tetracoccosporium paxianum and Trichoderma koningii .", "entity": [], "task": "NER"}
{"text": "These fungi were grown in liquid media to obtain crude extracts that were evaluated for their antibiotic activity against pathogenic bacteria , yeast and Cladosporium cladosporioides and A . flavus .", "entity": [], "task": "NER"}
{"text": "The most active extract was obtained from L . theobromae ( minimum inhibitory concentration = 64 mu g / mL against Listeria monocitogenes ) .", "entity": [], "task": "NER"}
{"text": "Some extracts showed to be more active than the positive control in the inhibition of Staphylococcus aureus and L . monocitogenes .", "entity": [], "task": "NER"}
{"text": "Therefore , propolis is a promising source of fungi , which produces active agents against relevant food poisoning bacteria and crop - associated fungi .", "entity": [], "task": "NER"}
{"text": "Long - term potentiation : Peeling the onion .", "entity": [], "task": "NER"}
{"text": "Since the discovery of long - term potentiation ( LTP ) , thousands of papers have been published on this phenomenon .", "entity": [], "task": "NER"}
{"text": "With this massive amount of information , it is often difficult , especially for someone not directly involved in the field , not to be overwhelmed .", "entity": [], "task": "NER"}
{"text": "The goal of this review is to peel away as many layers as possible , and probe the core properties of LTP .", "entity": [], "task": "NER"}
{"text": "We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential , but rather modulate , often in indirect ways , the threshold and / or magnitude of LTP .", "entity": [], "task": "NER"}
{"text": "What is required is NMDA receptor activation followed by CaMKII activation .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [20, 24]}], "task": "NER"}
{"text": "The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse .", "entity": [{"entity": "AMPA", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "This recruitment is independent of AMPA receptor subunit type , but absolutely requires an adequate pool of surface receptors .", "entity": [{"entity": "AMPA", "entity_type": "Chemical", "pos": [35, 39]}], "task": "NER"}
{"text": "An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment .", "entity": [], "task": "NER"}
{"text": "Disposition and Metabolism of GSK2251052 in Humans : A Novel Boron - Containing Antibiotic .", "entity": [{"entity": "GSK2251052", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "Boron", "entity_type": "Chemical", "pos": [61, 66]}], "task": "NER"}
{"text": "( S ) - 3 - ( Aminomethyl ) - 7 - ( 3 - hydroxypropoxy ) - 1 - hydroxy - 1 , 3 - dihydro - 2 , 1 - benzoxaborole ( GSK2251052 ) is a novel boron - containing antibiotic that inhibits bacterial leucyl tRNA synthetase , and that has been in development for the treatment of serious Gram - negative infections .", "entity": [{"entity": "( S ) - 3 - ( Aminomethyl ) - 7 - ( 3 - hydroxypropoxy ) - 1 - hydroxy - 1 , 3 - dihydro - 2 , 1 - benzoxaborole", "entity_type": "Chemical", "pos": [0, 112]}, {"entity": "GSK2251052", "entity_type": "Chemical", "pos": [115, 125]}, {"entity": "boron", "entity_type": "Chemical", "pos": [139, 144]}, {"entity": "leucyl", "entity_type": "Chemical", "pos": [193, 199]}], "task": "NER"}
{"text": "In this study , six healthy adult male subjects received a single i . v . dose of [ ( 14 ) C ] GSK2251052 , 1500 mg infused over 1 hour .", "entity": [{"entity": "[ ( 14 ) C ] GSK2251052", "entity_type": "Chemical", "pos": [82, 105]}], "task": "NER"}
{"text": "Blood , urine , and feces were collected over an extended period of 14 days , and accelerator mass spectrometry was used to quantify low levels of radioactivity in plasma at later time points to supplement the less - sensitive liquid scintillation counting technique .", "entity": [], "task": "NER"}
{"text": "An excellent mass balance recovery was achieved representing a mean total of 98 . 2 % of the dose , including 90 . 5 % recovered in the urine .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic analysis demonstrated that radioactivity was moderately associated with the blood cellular components , and together with GSK2251052 , both were highly distributed into tissues .", "entity": [{"entity": "GSK2251052", "entity_type": "Chemical", "pos": [138, 148]}], "task": "NER"}
{"text": "The parent compound had a much shorter half - life than total radioactivity in plasma , approximately 11 . 6 hours compared with 96 hours .", "entity": [], "task": "NER"}
{"text": "GSK2251052 and its major metabolite M3 , which resulted from oxidation of the propanol side chain to the corresponding carboxylic acid , comprised the majority of the plasma radioactivity , 37 and 53 % of the area under the plasma versus time concentration curve from time zero to infinity , respectively .", "entity": [{"entity": "GSK2251052", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "propanol", "entity_type": "Chemical", "pos": [78, 86]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [119, 134]}], "task": "NER"}
{"text": "Additionally , M3 was eliminated renally , and was demonstrated to be responsible for the long plasma radioactivity elimination half - life .", "entity": [], "task": "NER"}
{"text": "A combination of in vitro metabolism experiments and a pharmacokinetic study in monkeys with the inhibitor 4 - methylpyrazole provided strong evidence that alcohol dehydrogenase , potentially in association with aldehyde dehydrogenase , is the primary enzyme involved in the formation of the M3 metabolite .", "entity": [{"entity": "4 - methylpyrazole", "entity_type": "Chemical", "pos": [107, 125]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [156, 163]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [212, 220]}], "task": "NER"}
{"text": "Strain - dependent dysregulation of one - carbon metabolism in male mice is associated with choline - and folate - deficient diet - induced liver injury .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [42, 48]}, {"entity": "choline", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "folate", "entity_type": "Chemical", "pos": [106, 112]}], "task": "NER"}
{"text": "Dysregulation of one - carbon metabolism - related metabolic processes is a major contributor to the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [23, 29]}], "task": "NER"}
{"text": "It is well established that genetic and gender - specific variations in one - carbon metabolism contribute to the vulnerability to NAFLD in humans .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [78, 84]}], "task": "NER"}
{"text": "To examine the role of one - carbon metabolism dysregulation in the pathogenesis and individual susceptibility to NAFLD , we used a \" population - based \" mouse model where male mice from 7 inbred were fed a choline - and folate - deficient ( CFD ) diet for 12 wk .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [29, 35]}, {"entity": "choline", "entity_type": "Chemical", "pos": [208, 215]}, {"entity": "folate", "entity_type": "Chemical", "pos": [222, 228]}], "task": "NER"}
{"text": "Strain - dependent down - regulation of several key one - carbon metabolism genes , including methionine adenosyltransferase 1 alpha ( Mat1a ) , cystathionine - beta - synthase ( Cbs ) , methylenetetrahydrofolate reductase ( Mthfr ) , adenosyl - homocysteinase ( Ahcy ) , and methylenetetrahydrofolate dehydrogenase 1 ( Mthfd1 ) , was observed .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [58, 64]}, {"entity": "methionine", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "cystathionine", "entity_type": "Chemical", "pos": [145, 158]}, {"entity": "methylenetetrahydrofolate", "entity_type": "Chemical", "pos": [187, 212]}, {"entity": "adenosyl", "entity_type": "Chemical", "pos": [235, 243]}, {"entity": "methylenetetrahydrofolate", "entity_type": "Chemical", "pos": [276, 301]}], "task": "NER"}
{"text": "These changes were strongly associated with interstrain variability in liver injury ( steatosis , necrosis , inflammation , and activation of fibrogenesis ) and hyperhomocysteinemia .", "entity": [], "task": "NER"}
{"text": "Mechanistically , the decreased expression of Mat1a , Ahcy , and Mthfd1 was linked to a reduced level and promoter binding of transcription factor CCAAT / enhancer binding protein beta ( CEBP beta ) , which directly regulates their transcription .", "entity": [], "task": "NER"}
{"text": "The strain specificity of diet - induced dysregulation of one - carbon metabolism suggests that interstrain variation in the regulation of one - carbon metabolism may contribute to the differential vulnerability to NFLD and that correcting the imbalance may be considered as preventive and treatment strategies for NAFLD . - Pogribny , I .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [64, 70]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [145, 151]}], "task": "NER"}
{"text": "P . , Kutanzi , K . , Melnyk , S . , de Conti , A . , Tryndyak , V . , Montgomery , B . , Pogribna , M . , Muskhelishvili , L . , Latendresse , J .", "entity": [], "task": "NER"}
{"text": "R . , James , S .", "entity": [], "task": "NER"}
{"text": "J . , Beland , F .", "entity": [], "task": "NER"}
{"text": "A . , Rusyn , I .", "entity": [], "task": "NER"}
{"text": "Post - synthesis , characterization and catalytic properties of fluorine - planted MWW - type titanosilicate .", "entity": [{"entity": "fluorine", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "titanosilicate", "entity_type": "Chemical", "pos": [94, 108]}], "task": "NER"}
{"text": "F - Ti - MWW was post - synthesized by implanting fluorine species into a Ti - MWW framework through an acid treatment process in the presence of ammonium fluoride .", "entity": [{"entity": "F - Ti", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [74, 76]}, {"entity": "ammonium fluoride", "entity_type": "Chemical", "pos": [146, 163]}], "task": "NER"}
{"text": "The effects of NH4F addition amount , acid treatment temperature and precursor Ti content were investigated on the incorporation of F species , the zeolite structure and the coordination sites of Ti .", "entity": [{"entity": "NH4F", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [79, 81]}, {"entity": "F", "entity_type": "Chemical", "pos": [132, 133]}, {"entity": "zeolite", "entity_type": "Chemical", "pos": [148, 155]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [196, 198]}], "task": "NER"}
{"text": "Fluorine - implanting improved the surface hydrophobicity of the zeolite and altered the electropositivity nearby the tetrahedral Ti sites through forming the SiO3 / 2F and SiO4 / 2F ( - ) units .", "entity": [{"entity": "Fluorine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "zeolite", "entity_type": "Chemical", "pos": [65, 72]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [130, 132]}, {"entity": "SiO3", "entity_type": "Chemical", "pos": [159, 163]}, {"entity": "2F", "entity_type": "Chemical", "pos": [166, 168]}, {"entity": "SiO4", "entity_type": "Chemical", "pos": [173, 177]}, {"entity": "2F ( - )", "entity_type": "Chemical", "pos": [180, 188]}], "task": "NER"}
{"text": "The negative effect of SiO4 / 2F ( - ) units in F - Ti - MWW was eliminated selectively by convenient anion - exchange with various alkali chlorides .", "entity": [{"entity": "SiO4", "entity_type": "Chemical", "pos": [23, 27]}, {"entity": "2F ( - )", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "F - Ti", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "alkali chlorides", "entity_type": "Chemical", "pos": [132, 148]}], "task": "NER"}
{"text": "F - Ti - MWW containing the SiO3 / 2F units possessed better catalytic activity and reusability , and a longer catalyst lifetime than conventional Ti - MWW .", "entity": [{"entity": "F - Ti", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "SiO3", "entity_type": "Chemical", "pos": [28, 32]}, {"entity": "2F", "entity_type": "Chemical", "pos": [35, 37]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [147, 149]}], "task": "NER"}
{"text": "Mechanism of morphology transformation during annealing of nanostructured gold films on glass .", "entity": [], "task": "NER"}
{"text": "Nanostructured , just - percolated gold films were prepared by evaporation on bare glass .", "entity": [], "task": "NER"}
{"text": "Annealing of the films at temperatures close to or higher than the softening temperature of the glass substrate induces morphological transformation to discrete Au islands and gradual embedding of the formed islands in the glass .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [161, 163]}], "task": "NER"}
{"text": "The mechanism and kinetics of these processes are studied here using a combination of in situ high - temperature optical spectroscopy ; ex situ characterization of the island shape by high - resolution scanning electron microscopy ( HRSEM ) , atomic force microcopy ( AFM ) and cross - sectional transmission electron microscopy ( TEM ) ; and numerical simulations of transmission spectra using the Multiple Multipole Program ( MMP ) approach .", "entity": [], "task": "NER"}
{"text": "It is shown that the morphological transformation of just - percolated , 10 nm ( nominal thickness ) Au films evaporated on glass and annealed at 600 degrees C , i . e . , in the vicinity of the substrate glass transition temperature ( Tg = 557 degrees C ) , proceeds via three processes exhibiting different time scales : ( i ) fast recrystallization and dewetting , leading to formation of single - crystalline islands ( minutes ) ; the initial spectrum characteristic of a continuous Au film is transformed to that of an island film , displaying a surface plasmon ( SP ) absorption band .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [101, 103]}, {"entity": "Au", "entity_type": "Chemical", "pos": [487, 489]}], "task": "NER"}
{"text": "( ii ) Reshaping and faceting of the single - crystalline islands accompanied by formation of circumferential glass rims around them ( first few hours ) ; the overall optical response shows a blue shift of the SP band .", "entity": [], "task": "NER"}
{"text": "( iii ) Gradual island embedding in the glass substrate ( tens of hours ) , seen as a characteristic red shift of the SP band .", "entity": [], "task": "NER"}
{"text": "The influence of the annealing atmosphere ( air , vacuum ) on the embedding process is found to be minor .", "entity": [], "task": "NER"}
{"text": "Numerical modeling of the extinction cross - section corresponding to the morphological transformations during island recrystallization and embedding is in qualitative agreement with the experimental data .", "entity": [], "task": "NER"}
{"text": "Quality assessment and discrimination of the roots of Cynanchum auriculatum and Cynanchum wilfordii by HPLC - UV analysis .", "entity": [], "task": "NER"}
{"text": "Cynanchum auriculatum and Cynanchum wilfordii are widely used as folk medicine in Eastern Asia .", "entity": [], "task": "NER"}
{"text": "However , the indeterminacy in the authentic original plant material has resulted in the same appellative name being given to the two plants , and they are commonly misused .", "entity": [], "task": "NER"}
{"text": "Therefore , it is necessary to establish an analytical method for discrimination as well as quality control of the two species .", "entity": [], "task": "NER"}
{"text": "This study was to develop HPLC - UV methods for quality assessment of C . auriculatum and C . wilfordii and discrimination between the two species .", "entity": [], "task": "NER"}
{"text": "Two HPLC methods to analyze eight marker compounds were established and validated .", "entity": [], "task": "NER"}
{"text": "The first method analyzed seven marker compounds simultaneously on a reversed - phase column , while the second method analyzed a single marker compound , conduritol F , which exists only in C . wilfordii , on a Si - column .", "entity": [{"entity": "conduritol F", "entity_type": "Chemical", "pos": [155, 167]}, {"entity": "Si", "entity_type": "Chemical", "pos": [212, 214]}], "task": "NER"}
{"text": "Thirty - nine batches of C . auriculatum and nineteen batches of C . wilfordii that were collected from different geographical regions of South Korea were analyzed by these methods .", "entity": [], "task": "NER"}
{"text": "The constructed data matrix was subjected to principal components analysis and hierarchical cluster analysis in order to classify the samples .", "entity": [], "task": "NER"}
{"text": "The established methods offer a potential strategy for authentication and differentiation of the two species .", "entity": [], "task": "NER"}
{"text": "Promising new molecular targeted therapies in head and neck cancer .", "entity": [], "task": "NER"}
{"text": "Despite advances in multimodality therapies for the treatment of squamous cell carcinoma of the head and neck ( SCCHN ) , survival rates , functional outcomes and toxicities of therapy remain poor .", "entity": [], "task": "NER"}
{"text": "The recognition of the prognostic value of human papillomavirus ( HPV ) status , and the advent of biologically targeted therapies with potential for decreased toxicities and increased selectivity , represent significant developments in our understanding of SCCHN .", "entity": [], "task": "NER"}
{"text": "Targeted agents currently approved or under investigation for SCCHN include epidermal growth factor receptor ( EGFR ) monoclonal antibodies ( cetuximab , panitumumab , zalutumumab , nimotuzumab ) , EGFR tyrosine kinase inhibitors ( gefitinib , erlotinib , lapatinib , afatanib , dacomitinib ) , vascular endothelial growth factor receptor ( VEGFR ) inhibitors ( bevacizumab , sorafenib , sunitinib , vandetanib ) and various inhibitors of other pathways and targets , including phosphatidylinositol 3 ' kinase ( PI3K ) / AKT / mammalian target of rapamycin ( mTOR ) , MET and insulin - like growth factor receptor ( IGF - 1R ) .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [203, 211]}, {"entity": "gefitinib", "entity_type": "Chemical", "pos": [232, 241]}, {"entity": "erlotinib", "entity_type": "Chemical", "pos": [244, 253]}, {"entity": "lapatinib", "entity_type": "Chemical", "pos": [256, 265]}, {"entity": "afatanib", "entity_type": "Chemical", "pos": [268, 276]}, {"entity": "dacomitinib", "entity_type": "Chemical", "pos": [279, 290]}, {"entity": "sorafenib", "entity_type": "Chemical", "pos": [376, 385]}, {"entity": "sunitinib", "entity_type": "Chemical", "pos": [388, 397]}, {"entity": "vandetanib", "entity_type": "Chemical", "pos": [400, 410]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [478, 498]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [547, 556]}], "task": "NER"}
{"text": "On - going clinical trials are evaluating these emerging agents and their combinations in the treatment of SCCHN .", "entity": [], "task": "NER"}
{"text": "Fluorescent probes for G - quadruplex structures .", "entity": [], "task": "NER"}
{"text": "Mounting evidence supports the presence of biologically relevant G - quadruplexes in single - cell organisms , but the existence of endogenous G - quadruplex structures in mammalian cells remains highly controversial .", "entity": [], "task": "NER"}
{"text": "This is due , in part , to the common misconception that DNA and RNA molecules are passive information carriers with relatively little structural or functional complexity .", "entity": [], "task": "NER"}
{"text": "For those working in the field , however , the lack of available tools for characterizing DNA structures in vivo remains a major limitation to addressing fundamental questions about structure - function relationships of nucleic acids .", "entity": [], "task": "NER"}
{"text": "In this review , we present progress towards the direct detection of G - quadruplex structures by using small molecules and modified oligonucleotides as fluorescent probes .", "entity": [], "task": "NER"}
{"text": "While most development has focused on cell - permeable probes that selectively bind to G - quadruplex structures with high affinity , these same probes can induce G - quadruplex folding , thereby making the native conformation of the DNA or RNA molecule ( i . e . , in the absence of probe ) uncertain .", "entity": [], "task": "NER"}
{"text": "For this reason , modified oligonucleotides and fluorescent base analogues that serve as \" internal \" fluorescent probes are presented as an orthogonal means for detecting conformational changes , without necessarily perturbing the equilibria between G - quadruplex , single - stranded , and duplex DNA .", "entity": [], "task": "NER"}
{"text": "The major challenges and motivation for the development of fluorescent probes for G - quadruplex structures are presented , along with a summary of the key photophysical , biophysical , and biological properties of reported examples .", "entity": [], "task": "NER"}
{"text": "The C - terminal extended serine residue is absolutely required in nosiheptide maturation .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}, {"entity": "serine", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "nosiheptide", "entity_type": "Chemical", "pos": [67, 78]}], "task": "NER"}
{"text": "Serine qua non : Substitution of the extended Ser13 in the core peptide of nosiheptide by analogous amino acids prevented enamide dealkylation of the terminal residue for nosiheptide maturation .", "entity": [{"entity": "Serine", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "Ser13", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "nosiheptide", "entity_type": "Chemical", "pos": [75, 86]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [100, 111]}, {"entity": "enamide", "entity_type": "Chemical", "pos": [122, 129]}, {"entity": "nosiheptide", "entity_type": "Chemical", "pos": [171, 182]}], "task": "NER"}
{"text": "Carnosine inhibits A beta ( 42 ) aggregation by perturbing the H - bond network in and around the central hydrophobic cluster .", "entity": [{"entity": "Carnosine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "H", "entity_type": "Chemical", "pos": [63, 64]}], "task": "NER"}
{"text": "Aggregation of the amyloid - beta peptide ( A beta ) into fibrillar structures is a hallmark of Alzheimer ' s disease .", "entity": [], "task": "NER"}
{"text": "Thus , preventing self - assembly of the A beta peptide is an attractive therapeutic strategy .", "entity": [], "task": "NER"}
{"text": "Here , we used experimental techniques and atomistic simulations to investigate the influence of carnosine , a dipeptide naturally occurring in the brain , on A beta aggregation .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [97, 106]}, {"entity": "dipeptide", "entity_type": "Chemical", "pos": [111, 120]}], "task": "NER"}
{"text": "Scanning force microscopy , circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of A beta 42 but nonetheless inhibits amyloid growth .", "entity": [{"entity": "thioflavin T", "entity_type": "Chemical", "pos": [51, 63]}, {"entity": "carnosine", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "Molecular dynamics ( MD ) simulations indicated that carnosine interacts transiently with monomeric A beta 42 by salt bridges with charged side chains , and van der Waals contacts with residues in and around the central hydrophobic cluster ( ( 17 ) LVFFA ( 21 ) ) .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [53, 62]}], "task": "NER"}
{"text": "NMR experiments on the nonaggregative fragment A beta 12 - 28 did not evidence specific intermolecular interactions between the peptide and carnosine , in agreement with MD simulations .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [140, 149]}], "task": "NER"}
{"text": "However , a close inspection of the spectra revealed that carnosine interferes with the local propensity of the peptide to form backbone hydrogen bonds close to the central hydrophobic cluster ( residues E22 , S26 and N27 ) .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [137, 145]}], "task": "NER"}
{"text": "Finally , MD simulations of aggregation - prone A beta heptapeptide segments show that carnosine reduces the propensity to form intermolecular backbone hydrogen bonds in the region 18 - 24 .", "entity": [{"entity": "heptapeptide", "entity_type": "Chemical", "pos": [55, 67]}, {"entity": "carnosine", "entity_type": "Chemical", "pos": [87, 96]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "Taken together , the experimental and simulation results ( cumulative MD sampling of 0 . 2 ms ) suggest that , despite the inability of carnosine to form stable contacts with A beta , it might block the pathway toward toxic aggregates by perturbing the hydrogen bond network near residues with key roles in fibrillogenesis .", "entity": [{"entity": "carnosine", "entity_type": "Chemical", "pos": [136, 145]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [253, 261]}], "task": "NER"}
{"text": "Highly Ordered Hollow Oxide Nanostructures : The Kirkendall Effect at the Nanoscale .", "entity": [{"entity": "Oxide", "entity_type": "Chemical", "pos": [22, 27]}], "task": "NER"}
{"text": "Highly ordered ultra - long oxide nanotubes are fabricated by a simple two - step strategy involving the growth of copper nanowires on nanopatterned template substrates by magnetron sputtering , followed by thermal annealing in air .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [28, 33]}, {"entity": "copper", "entity_type": "Chemical", "pos": [115, 121]}], "task": "NER"}
{"text": "The formation of such tubular nanostructures is explained according to the nanoscale Kirkendall effect .", "entity": [], "task": "NER"}
{"text": "The concept of this new fabrication route is also extendable to create periodic zero - dimensional hollow nanostructures .", "entity": [], "task": "NER"}
{"text": "Solvatochromic Effect on the Photoluminescence of MoS2 Monolayers .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "The effect of surrounding solvents on the photoluminescence ( PL ) of MoS2 monolayers on Si / SiO2 substrates is studied .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [70, 74]}, {"entity": "Si", "entity_type": "Chemical", "pos": [89, 91]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "A redshift ( up to - 60 meV ) is observed for MoS2 monolayers with nonhalogenated solvent surroundings .", "entity": [{"entity": "MoS2", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "A blueshift ( up to 60 meV ) and intensity increase ( 2 - 50 times ) are observed for monolayers with halogenated solvent surroundings .", "entity": [], "task": "NER"}
{"text": "Regio - and Stereocontrolled Synthesis of Oligostilbenoids : Theoretical Highlights at the Supramolecular Level .", "entity": [], "task": "NER"}
{"text": "Oligostilbenoids ( e . g . , ampelopsin F , viniferin , pallidol ) result from homogeneous or heterogeneous coupling of monomeric stilbenoid units , leading to various chemical structures .", "entity": [{"entity": "ampelopsin F", "entity_type": "Chemical", "pos": [29, 41]}, {"entity": "viniferin", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "pallidol", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "stilbenoid", "entity_type": "Chemical", "pos": [130, 140]}], "task": "NER"}
{"text": "Oligostilbenoid synthesis is regio - and stereocontrolled .", "entity": [], "task": "NER"}
{"text": "To tackle this regio - and stereocontrol , a supramolecular chemistry approach is required that can be achieved by quantum chemistry .", "entity": [], "task": "NER"}
{"text": "The stability of noncovalent pi - stacks , formed between two stilbenoid units prior to oxidation , is accurately evaluated with density functional theory ( DFT ) including dispersive effects ( within the DFT - D formalism ) .", "entity": [{"entity": "stilbenoid", "entity_type": "Chemical", "pos": [62, 72]}], "task": "NER"}
{"text": "These noncovalent arrangements drive the regiocontrol .", "entity": [], "task": "NER"}
{"text": "The rest of the chemical pathway is a succession of dearomatization and rearomatization stages .", "entity": [], "task": "NER"}
{"text": "The thermodynamics and kinetics of the processes are calculated with classical hybrid functionals .", "entity": [], "task": "NER"}
{"text": "This study allows discrimination between the two main possible chemical pathways , namely , radical - neutral and radical - radical reactions .", "entity": [], "task": "NER"}
{"text": "The former appears more likely , thermodynamics and kinetics being in perfect agreement with the experimental 1 : 2 ratio obtained for ampelopsin F : pallidol analogues , respectively .", "entity": [{"entity": "ampelopsin F", "entity_type": "Chemical", "pos": [135, 147]}, {"entity": "pallidol", "entity_type": "Chemical", "pos": [150, 158]}], "task": "NER"}
{"text": "Molecular interactions between lecithin and bile salts / acids in oils and their effects on reverse micellization .", "entity": [{"entity": "bile salts / acids", "entity_type": "Chemical", "pos": [44, 62]}], "task": "NER"}
{"text": "It has been known that the addition of bile salts to lecithin organosols induces the formation of reverse wormlike micelles and that the worms are similar to long polymer chains that entangle each other to form viscoelastic solutions .", "entity": [{"entity": "bile salts", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "In this study , we further investigated the effects of different bile salts and bile acids on the growth of lecithin reverse worms in cyclohexane and n - decane .", "entity": [{"entity": "bile salts", "entity_type": "Chemical", "pos": [65, 75]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "cyclohexane", "entity_type": "Chemical", "pos": [134, 145]}, {"entity": "n - decane", "entity_type": "Chemical", "pos": [150, 160]}], "task": "NER"}
{"text": "We utilized rheological and small - angle scattering techniques to analyze the properties and structures of the reverse micelles .", "entity": [], "task": "NER"}
{"text": "All of the bile salts can transform the originally spherical lecithin reverse micelles into wormlike micelles and their rheological behaviors can be described by the single - relaxation - time Maxwell model .", "entity": [{"entity": "bile salts", "entity_type": "Chemical", "pos": [11, 21]}], "task": "NER"}
{"text": "However , their efficiencies to induce the worms are different .", "entity": [], "task": "NER"}
{"text": "In contrast , before phase separation , bile acids can induce only short cylindrical micelles that are not long enough to impart viscoelasticity .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [40, 50]}], "task": "NER"}
{"text": "We used Fourier transform infrared spectroscopy to investigate the interactions between lecithin and bile salts / acids and found that different bile salts / acids employ different functional groups to form hydrogen bonds with lecithin .", "entity": [{"entity": "bile salts / acids", "entity_type": "Chemical", "pos": [101, 119]}, {"entity": "bile salts / acids", "entity_type": "Chemical", "pos": [145, 163]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [207, 215]}], "task": "NER"}
{"text": "Such effects determine the relative positions of the bile salts / acids in the headgroups of lecithin , thus resulting in varying efficiencies to alter the effective critical packing parameter for the formation of wormlike micelles .", "entity": [{"entity": "bile salts / acids", "entity_type": "Chemical", "pos": [53, 71]}], "task": "NER"}
{"text": "This work highlights the importance of intermolecular interactions in molecular self - assembly .", "entity": [], "task": "NER"}
{"text": "Marine drugs best paper award 2013 .", "entity": [], "task": "NER"}
{"text": "To recognize the most outstanding papers in the area of research , development and production of drugs from the sea , including marine natural product chemistry , that have been published in Marine Drugs , we would like to start an annual \" Best Paper Award \" .", "entity": [], "task": "NER"}
{"text": "Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X - linked ciliopathy gene .", "entity": [], "task": "NER"}
{"text": "X - linked retinitis pigmentosa ( XLRP ) is the least common genetic type of retinitis pigmentosa ; however , it has extremely devastating consequences to patients ' activities of daily living .", "entity": [], "task": "NER"}
{"text": "RPGR and RP2 genes expressed in the photoreceptor sensory cilia are predominantly implicated in XLRP ; however , the interpretation of genetic mutations and their correlation with clinical phenotypes remain unknown , and the role of these genes in photoreceptor cilia function is not completely elucidated .", "entity": [], "task": "NER"}
{"text": "Therefore , we evaluated structural characteristics in five female obligate carriers of XLRP by using state - of - the - art non - invasive imaging methods , including adaptive optics ( AO ) scanning laser ophthalmoscopy ( SLO ) .", "entity": [], "task": "NER"}
{"text": "In all five carriers examined , qualitative and quantitative analyses by AO SLO imaging revealed a mosaic pattern of cone disruption , even in the absence of visual symptoms , normal visual acuity and normal macular thickness , on optical coherence tomography and mildly subnormal full - field cone electroretinographic findings .", "entity": [], "task": "NER"}
{"text": "As the technique is sensitive to the level of a single cone , the ability to visualize the cone cells in vivo should be especially useful in other retinal diseases .", "entity": [], "task": "NER"}
{"text": "In addition , further investigation of XLRP carriers may yield insight into how cone structures change over time and ultimately enable understanding of the role of RPGR and RP2 in cone cell survival . European Journal of Human Genetics advance online publication , 27 February 2013 ; doi : 10 . 1038 / ejhg . 2013 . 21 .", "entity": [], "task": "NER"}
{"text": "Control of 10 nm scale cylinder orientation in self - organized sugar - based block copolymer thin films .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [64, 69]}], "task": "NER"}
{"text": "The present paper describes the orientational control of 10 nm scale cylinders in sugar - based block copolymer thin films by simply varying the composition of the annealing co - solvent .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [82, 87]}], "task": "NER"}
{"text": "The affinity of the block copolymer to the solvent vapor could be systematically adjusted in this way .", "entity": [], "task": "NER"}
{"text": "Multiphase chemistry of atmospheric amines .", "entity": [{"entity": "amines", "entity_type": "Chemical", "pos": [36, 42]}], "task": "NER"}
{"text": "Heterogeneous reactions of amines have been recently shown to play an important role in the formation and transformation of atmospheric aerosols .", "entity": [{"entity": "amines", "entity_type": "Chemical", "pos": [27, 33]}], "task": "NER"}
{"text": "This perspective summarizes the latest laboratory progress in the multiphase chemistry of amines .", "entity": [{"entity": "amines", "entity_type": "Chemical", "pos": [90, 96]}], "task": "NER"}
{"text": "Particular emphasis is given to the contributions of amines to new particle formation , growth of submicron particles , and alteration in the physiochemical properties of pre - existing particles , including hygroscopicity , thermostability , density , phase , and optical properties , from exposure to gaseous amines .", "entity": [{"entity": "amines", "entity_type": "Chemical", "pos": [53, 59]}, {"entity": "amines", "entity_type": "Chemical", "pos": [311, 317]}], "task": "NER"}
{"text": "The atmospheric implications of the multiphase reactions of amines , including the potential impact on direct and indirect climate forcing of aerosols , and future research directions are discussed .", "entity": [{"entity": "amines", "entity_type": "Chemical", "pos": [60, 66]}], "task": "NER"}
{"text": "When direct health - care professional communications have an impact on inappropriate and unsafe use of medicines .", "entity": [], "task": "NER"}
{"text": "Serious safety issues relating to drugs are communicated to health - care professionals via Direct Health - Care Professional Communications ( DHPCs ) .", "entity": [], "task": "NER"}
{"text": "We explored which characteristics determined the impact of DHPCs issued in the Netherlands for ambulatory - care drugs ( 2001 - 2008 ) .", "entity": [], "task": "NER"}
{"text": "With multiple linear regression , we examined the impact on the relative change in new drug use post - DHPC of the following : time to DHPC , trend in use , degree of innovation , specialist drug , first / repeated DHPC , DHPC template , and type of safety issue .", "entity": [], "task": "NER"}
{"text": "DHPCs have less impact on use of specialist drugs than nonspecialist drugs ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "The DHPCs ' impact increased after availability of a template emphasizing the main problem ( P < 0 . 05 ) , and for safety issues with a risk of death and / or disability ( both P < 0 . 05 ) ( adjusted R (2) = 0 . 392 ) .", "entity": [], "task": "NER"}
{"text": "Risk communication can be effective , specifically in case of well - structured information , and very serious safety issues .", "entity": [], "task": "NER"}
{"text": "Effectiveness may improve by tailoring DHPCs and adding other communication channels , for example for drugs that are increasingly being used .", "entity": [], "task": "NER"}
{"text": "Estimation of renal cell carcinoma treatment effects from disease progression modeling .", "entity": [], "task": "NER"}
{"text": "To improve future drug development efficiency in renal cell carcinoma ( RCC ) , a disease - progression model was developed with longitudinal tumor size data from a phase III trial of sorafenib in RCC .", "entity": [{"entity": "sorafenib", "entity_type": "Chemical", "pos": [184, 193]}], "task": "NER"}
{"text": "The best - fit model was externally evaluated on 145 placebo - treated patients in a phase III trial of pazopanib ; the model incorporated baseline tumor size , a linear disease - progression component , and an exponential drug effect ( DE ) parameter .", "entity": [{"entity": "pazopanib", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "With the model - estimated effect of sorafenib on RCC growth , we calculated the power of randomized phase II trials between sorafenib and hypothetical comparators over a range of effects .", "entity": [{"entity": "sorafenib", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "sorafenib", "entity_type": "Chemical", "pos": [125, 134]}], "task": "NER"}
{"text": "A hypothetical comparator with 80 % greater DE than sorafenib would have 82 % power ( one - sided alpha = 0 . 1 ) with 50 patients per arm .", "entity": [{"entity": "sorafenib", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "Model - based quantitation of treatment effect with computed tomography ( CT ) imaging offers a scaffold on which to develop new , more efficient , phase II trial end points and analytic strategies for RCC .", "entity": [], "task": "NER"}
{"text": "Effect of miR - 21 on Renal Fibrosis by Regulating MMP - 9 and TIMP1 in kk - ay Diabetic Nephropathy Mice .", "entity": [], "task": "NER"}
{"text": "MicroRNAs ( miRs ) play important roles in initiation and progression of many pathologic processes .", "entity": [], "task": "NER"}
{"text": "However , the roles of miRs in diabetic nephropathy remain unclear .", "entity": [], "task": "NER"}
{"text": "This study was to determine whether miR - 21 was involved in diabetic nephropathy and to explore the relationship between miR - 21 and MMP9 / TIMP1 expression in diabetic nephropathy .", "entity": [], "task": "NER"}
{"text": "In situ hybridization studies showed that miR - 21 was primarily localized and distributed in cortical glomerular and renal tubular cells in diabetic kk - ay kidney .", "entity": [], "task": "NER"}
{"text": "Real - time quantitative RT - PCR demonstrated that the expression of miR - 21 was significantly increased in kk - ay mice , compared with control C57BL mice .", "entity": [], "task": "NER"}
{"text": "Interestingly , miR - 21 expression positively correlated with urine albumin creatine ratio ( ACR ) , TIMP1 , collagen IV ( ColIV ) , and fibronectin ( FN ) ; while negatively correlated with creatine clearance ratio ( Ccr ) and MMP - 9 protein .", "entity": [{"entity": "creatine", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "creatine", "entity_type": "Chemical", "pos": [192, 200]}], "task": "NER"}
{"text": "Importantly , antagomir - 21 not only ameliorated Ccr and ACR but also decreased TIMP1 , ColIV , and FN proteins .", "entity": [], "task": "NER"}
{"text": "In conclusion , our data demonstrate that miR - 21 contributes to renal fibrosis by mediating MMP9 / TIMP1 and that inhibition of miR - 21 may be a novel target for diabetic nephropathy .", "entity": [], "task": "NER"}
{"text": "Probing the Metabotropic Glutamate Receptor 5 ( mGlu5 ) Positive Allosteric Modulator ( PAM ) Binding Pocket : Discovery of Point Mutations That Engender a \" Molecular Switch \" in PAM Pharmacology .", "entity": [{"entity": "Glutamate", "entity_type": "Chemical", "pos": [25, 34]}], "task": "NER"}
{"text": "Positive allosteric modulation of metabotropic glutamate receptor subtype 5 ( mGlu5 ) is a promising novel approach for the treatment of schizophrenia and cognitive disorders .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "Allosteric binding sites are topographically distinct from the endogenous ligand ( orthosteric ) binding site , allowing for co - occupation of a single receptor with the endogenous ligand and an allosteric modulator .", "entity": [], "task": "NER"}
{"text": "Negative allosteric modulators ( NAMs ) inhibit and positive allosteric modulators ( PAMs ) enhance the affinity and / or efficacy of the orthosteric agonist .", "entity": [], "task": "NER"}
{"text": "The molecular determinants that govern mGlu5 modulator affinity versus cooperativity are not well understood .", "entity": [], "task": "NER"}
{"text": "Focusing on the modulators based on the acetylene scaffold , we sought to determine the molecular interactions that contribute to PAM versus NAM pharmacology .", "entity": [{"entity": "acetylene", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "Generation of a comparative model of the transmembrane - spanning region of mGlu5 served as a tool to predict and interpret the impact of mutations in this region .", "entity": [], "task": "NER"}
{"text": "Application of an operational model of allosterism allowed for determination of PAM and NAM affinity estimates at receptor constructs that possessed no detectable radioligand binding as well as delineation of effects on affinity versus cooperativity .", "entity": [], "task": "NER"}
{"text": "Novel mutations within the transmembrane domain ( TM ) regions were identified that had differential effects on acetylene PAMs versus 2 - methyl - 6 - ( phenylethynyl ) - pyridine , a prototypical NAM .", "entity": [{"entity": "acetylene", "entity_type": "Chemical", "pos": [112, 121]}, {"entity": "2 - methyl - 6 - ( phenylethynyl ) - pyridine", "entity_type": "Chemical", "pos": [134, 179]}], "task": "NER"}
{"text": "Three conserved amino acids ( Y658 , T780 , and S808 ) and two nonconserved residues ( P654 and A809 ) were identified as key determinants of PAM activity .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [16, 27]}], "task": "NER"}
{"text": "Interestingly , we identified two point mutations in TMs 6 and 7 that , when mutated , engender a mode switch in the pharmacology of certain PAMs .", "entity": [], "task": "NER"}
{"text": "Coactivators enable glucocorticoid receptor recruitment to fine - tune estrogen receptor transcriptional responses .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [71, 79]}], "task": "NER"}
{"text": "Nuclear receptors ( NRs ) are central regulators of pathophysiological processes ; however , how their responses intertwine is still not fully understood .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine whether and how steroid NRs can influence each other ' s activity under co - agonist treatment .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "We used a unique system consisting of a multicopy integration of an estrogen receptor responsive unit that allows direct visualization and quantification of estrogen receptor alpha ( ER alpha ) DNA binding , co - regulator recruitment and transcriptional readout .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "We find that ER alpha DNA loading is required for other type I nuclear receptors to be co - recruited after dual agonist treatment .", "entity": [], "task": "NER"}
{"text": "We focused on ER alpha / glucocorticoid receptor interplay and demonstrated that it requires steroid receptor coactivators ( SRC - 2 , SRC - 3 ) and the mediator component MED14 .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [93, 100]}], "task": "NER"}
{"text": "We then validated this cooperative interplay on endogenous target genes in breast cancer cells .", "entity": [], "task": "NER"}
{"text": "Taken together , this work highlights another layer of mechanistic complexity through which NRs cross - talk with each other on chromatin under multiple hormonal stimuli .", "entity": [], "task": "NER"}
{"text": "Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [81, 89]}], "task": "NER"}
{"text": "Personalizing intravenous ( IV ) busulfan doses in children using therapeutic drug monitoring ( TDM ) is an integral component of hematopoietic cell transplant .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "The authors sought to characterize initial dosing and TDM of IV busulfan , along with factors associated with busulfan clearance , in 729 children who underwent busulfan TDM from December 2005 to December 2008 .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "busulfan", "entity_type": "Chemical", "pos": [110, 118]}, {"entity": "busulfan", "entity_type": "Chemical", "pos": [161, 169]}], "task": "NER"}
{"text": "The initial IV busulfan dose in children weighing <= 12 kg ranged 4 . 8 - fold , with only 19 % prescribed the package insert dose of 1 . 1 mg / kg .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "In those children weighing > 12 kg , the initial dose ranged 5 . 4 - fold , and 79 % were prescribed the package insert dose .", "entity": [], "task": "NER"}
{"text": "The initial busulfan dose achieved the target exposure in only 24 . 3 % of children .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [12, 20]}], "task": "NER"}
{"text": "A wide range of busulfan exposures were targeted for children with the same disease ( eg , 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia ) .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "busulfan", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained .", "entity": [], "task": "NER"}
{"text": "Busulfan clearance varied by age and dosing frequency but not by underlying disease .", "entity": [{"entity": "Busulfan", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The authors - group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM ( eg , limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation ) may affect clinical outcomes in children .", "entity": [{"entity": "busulfan", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "Comparing the pharmacokinetics of doxylamine / pyridoxine delayed - release combination in nonpregnant women of reproductive age and women in the first trimester of pregnancy .", "entity": [{"entity": "doxylamine", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "pyridoxine", "entity_type": "Chemical", "pos": [47, 57]}], "task": "NER"}
{"text": "Although Diclectin ( doxylamine / pyridoxine delayed - released combination ) is widely used in Canada , its pharmacokinetics ( PK ) during pregnancy has never been described .", "entity": [{"entity": "Diclectin", "entity_type": "Chemical", "pos": [9, 18]}, {"entity": "doxylamine", "entity_type": "Chemical", "pos": [21, 31]}, {"entity": "pyridoxine", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "The objective of this study was to compare the PK of doxylamine / pyridoxine delayed - released combination in pregnant versus nonpregnant women .", "entity": [{"entity": "doxylamine", "entity_type": "Chemical", "pos": [53, 63]}, {"entity": "pyridoxine", "entity_type": "Chemical", "pos": [66, 76]}], "task": "NER"}
{"text": "The apparent clearances ( CL ) of doxylamine and pyridoxal 5 ' - phosphate ( PLP ; the active metabolite of vitamin B ( 6 ) ) during the first - trimester pregnancy in women who participated in a Diclectin randomized trial were compared with those of healthy , adult , nonpregnant women who participated in a voluntary PK trial .", "entity": [{"entity": "doxylamine", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "pyridoxal 5 ' - phosphate", "entity_type": "Chemical", "pos": [49, 74]}, {"entity": "PLP", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "vitamin B ( 6 )", "entity_type": "Chemical", "pos": [108, 123]}, {"entity": "Diclectin", "entity_type": "Chemical", "pos": [196, 205]}], "task": "NER"}
{"text": "Eighteen nonpregnant women were compared with 50 pregnant women who were treated with Diclectin .", "entity": [{"entity": "Diclectin", "entity_type": "Chemical", "pos": [86, 95]}], "task": "NER"}
{"text": "There was no difference in the apparent CL of doxylamine in women in their first trimester of pregnancy when compared with nonpregnant women on day 4 ( median = 196 . 7 vs 249 . 5 mL / h / kg , respectively , P = . 065 ) , day 8 ( median = 248 . 4 vs 249 . 5 mL / h / kg , respectively , P = . 82 ) , and day 15 ( median = 200 . 9 vs 249 . 5 mL / h / kg , respectively , P = . 55 ) .", "entity": [{"entity": "doxylamine", "entity_type": "Chemical", "pos": [46, 56]}], "task": "NER"}
{"text": "No difference was found in the apparent CL of PLP on day 15 ( median = 342 . 3 vs 314 . 7 mL / h / kg , respectively , P = . 92 ) .", "entity": [], "task": "NER"}
{"text": "There was no pregnancy - induced effect in the apparent CL of either doxylamine or PLP in women during the first trimester of pregnancy despite the existence of morning sickness .", "entity": [{"entity": "doxylamine", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "PLP", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "Light energy collection in a porphyrin - imide - corrole ensemble .", "entity": [{"entity": "porphyrin - imide - corrole", "entity_type": "Chemical", "pos": [29, 56]}], "task": "NER"}
{"text": "An assembly consisting of three units , that is , a meso - substituted corrole ( ) , 1 , 8 naphthaleneimide ( ) , and a Zn porphyrin ( ) , has been synthesized .", "entity": [{"entity": "meso - substituted corrole", "entity_type": "Chemical", "pos": [52, 78]}, {"entity": "1 , 8 naphthaleneimide", "entity_type": "Chemical", "pos": [85, 107]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [120, 122]}, {"entity": "porphyrin", "entity_type": "Chemical", "pos": [123, 132]}], "task": "NER"}
{"text": "NIE is connected to C3 through a 1 , 3 - phenylene bridge and to the ZnP unit through a direct C <F8FF> C bond .", "entity": [{"entity": "NIE", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "1 , 3 - phenylene", "entity_type": "Chemical", "pos": [33, 50]}, {"entity": "ZnP", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "C <F8FF> C", "entity_type": "Chemical", "pos": [95, 105]}], "task": "NER"}
{"text": "The convergent synthetic strategy includes the preparation of a trans - A2 B - corrole possessing the imide unit , followed by Sonogashira coupling with a meso - substituted A3 B - porphyrin .", "entity": [{"entity": "trans - A2 B - corrole", "entity_type": "Chemical", "pos": [64, 86]}, {"entity": "imide", "entity_type": "Chemical", "pos": [102, 107]}, {"entity": "meso - substituted A3 B - porphyrin", "entity_type": "Chemical", "pos": [155, 190]}], "task": "NER"}
{"text": "The photophysical processes in the resulting triad are examined and compared with those of the corresponding dyad and the constituent reference models , , and .", "entity": [], "task": "NER"}
{"text": "Excitation of the NIE unit in leads to a fast energy transfer of 98 % efficiency to C3 with a rate ken = 7 . 5 x 10 ( 10 ) s ( - 1 ) , whereas excitation of the corrole unit leads to a reactivity of the excited state identical to that of the model , with a deactivation rate to the ground state k = 2 . 5 x 10 ( 8 ) s ( - 1 ) .", "entity": [{"entity": "NIE", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "corrole", "entity_type": "Chemical", "pos": [161, 168]}], "task": "NER"}
{"text": "Energy transfer to C3 and to ZnP moieties follows excitation of NIE in the triad .", "entity": [{"entity": "ZnP", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "NIE", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "The rates are ken = 7 . 5 x 10 ( 10 ) s ( - 1 ) and ken = 2 . 5 x 10 ( 10 ) s ( - 1 ) for the sensitization of the C3 and ZnP unit , respectively .", "entity": [{"entity": "ZnP", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "The light energy transferred from NIE to Zn porphyrin unit is ultimately funneled to the corrole component , which is the final recipient of the excitation energy absorbed by the different components of the array .", "entity": [{"entity": "NIE", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "porphyrin", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "corrole", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "The latter process occurs with a rate ken = 3 . 4 x 10 ( 9 ) s ( - 1 ) and 89 % efficiency .", "entity": [], "task": "NER"}
{"text": "Energy transfer processes take place in all cases by a F o rster ( dipole - dipole ) mechanism .", "entity": [], "task": "NER"}
{"text": "The theory predicts quite satisfactorily the rate for the ZnP / C3 couple , where components are separated by about 23 A , but results in calculated rates that are one to two orders of magnitude higher for the couples NIE / ZnP ( D / A ) and NIE / C3 , which are separated by distances of about 14 and 10 A , respectively .", "entity": [{"entity": "ZnP", "entity_type": "Chemical", "pos": [58, 61]}, {"entity": "NIE", "entity_type": "Chemical", "pos": [218, 221]}, {"entity": "ZnP", "entity_type": "Chemical", "pos": [224, 227]}, {"entity": "NIE", "entity_type": "Chemical", "pos": [242, 245]}], "task": "NER"}
{"text": "Protective effect of butylated hydroxytoluene on ferric nitrilotriacetate induced hepatotoxicity and oxidative stress in mice .", "entity": [{"entity": "butylated hydroxytoluene", "entity_type": "Chemical", "pos": [21, 45]}, {"entity": "ferric nitrilotriacetate", "entity_type": "Chemical", "pos": [49, 73]}], "task": "NER"}
{"text": "The present study was undertaken to evaluate the possible ameliorating effect of butylated hydroxyl toluene ( BHT ) , associated with ferric nitrilotriacetate ( Fe - NTA ) - induced oxidative stress and liver injury in mice .", "entity": [{"entity": "butylated hydroxyl toluene", "entity_type": "Chemical", "pos": [81, 107]}, {"entity": "BHT", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "ferric nitrilotriacetate", "entity_type": "Chemical", "pos": [134, 158]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [161, 169]}], "task": "NER"}
{"text": "The treatment of mice with Fe - NTA alone enhances ornithine decarboxylase activity to 4 . 6 folds , protein carbonyl formation increased up to 2 . 9 folds and DNA synthesis expressed in terms of [ ( 3 ) H ] thymidine incorporation increased to 3 . 2 folds , and antioxidants and antioxidant enzymes decreased to 1 . 8 - 2 . 5 folds , compared with the corresponding saline - treated controls .", "entity": [{"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "ornithine", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [109, 117]}, {"entity": "[ ( 3 ) H ] thymidine", "entity_type": "Chemical", "pos": [196, 217]}], "task": "NER"}
{"text": "These changes were reversed significantly ( p < 0 . 001 ) in animals receiving a pretreatment of BHT .", "entity": [{"entity": "BHT", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "Our data show that BHT can reciprocate the toxic effects of Fe - NTA and can serve as a potent chemopreventive agent .", "entity": [{"entity": "BHT", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "Fe - NTA", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "Cytotoxicity and uptake of archaeosomes prepared from Aeropyrum pernix lipids .", "entity": [], "task": "NER"}
{"text": "Archaeon Aeropyrum pernix K1 is an obligate aerobic hyperthermophilic organism with C ( 25 , 25 ) - archeol membrane lipids with head groups containing inositol .", "entity": [{"entity": "inositol", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "Interactions of archaeosomes , liposomes prepared from lipids of A . pernix , with mammalian cells in vitro were studied .", "entity": [], "task": "NER"}
{"text": "In vitro cytotoxicity was tested on five different cell lines : rodent mouse melanoma cells ( B16 - F1 ) and Chinese hamster ovary ( CHO ) cells , and three human cell lines - epithelial colorectal adenocarcinoma cells ( CACO - 2 ) , liver hepatocellular carcinoma cell line ( Hep G2 ) and endothelial umbilical vein cell line ( EA . hy926 ) .", "entity": [], "task": "NER"}
{"text": "Archaeosomes were nontoxic to human Hep G2 , CACO - 2 and mildly toxic to rodent CHO and B16 - F1 cells but showed strong cytotoxic effect on EA . hy926 cells .", "entity": [], "task": "NER"}
{"text": "Confocal microscopy revealed that archaeosomes are taken up by endocytosis .", "entity": [], "task": "NER"}
{"text": "The uptake of archaeosomes and the release of loaded calcein are more prominent in EA . hy926 cells , which is in line with high toxicity toward these cells .", "entity": [{"entity": "calcein", "entity_type": "Chemical", "pos": [53, 60]}], "task": "NER"}
{"text": "The mechanisms of uptake , release and action in these cells as well as in vivo functioning have to be further studied for possible targeted drug delivery .", "entity": [], "task": "NER"}
{"text": "A 90 - day subchronic toxicity study of neem oil , a Azadirachta indica oil , in mice .", "entity": [], "task": "NER"}
{"text": "To determine the no - observed - adverse - effect level ( NOAEL ) of exposure and target organs of neem oil for establishing safety criteria for human exposure , the subchronic toxicity study with neem oil in mice was evaluated .", "entity": [], "task": "NER"}
{"text": "The mice ( 10 per sex for each dose ) was orally administered with neem oil with the doses of 0 ( to serve as a control ) , 177 , 533 and 1600 mg / kg / day for 90 days .", "entity": [], "task": "NER"}
{"text": "After the treatment period , observation of reversibility or persistence of any toxic effects , mice were continuously fed without treatment for the following 30 days .", "entity": [], "task": "NER"}
{"text": "During the two test periods , the serum biochemistry , organ weight and histopathology were examined .", "entity": [], "task": "NER"}
{"text": "The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group .", "entity": [], "task": "NER"}
{"text": "At the 90th day , the histopathological examinations showed that the 1600 mg / kg / day dose of neem oil had varying degrees of damage on each organ except heart , uterus and ovarian .", "entity": [], "task": "NER"}
{"text": "After 30 - day recovery , the degree of lesions to the tissues was lessened or even restored .", "entity": [], "task": "NER"}
{"text": "The NOAEL of neem oil was 177 mg / kg / day for mice and the target organs of neem oil were determined to be testicle , liver and kidneys .", "entity": [], "task": "NER"}
{"text": "Simultaneous high - performance liquid chromatographic determination of a rhein - diclofenac prodrug and its active compounds .", "entity": [{"entity": "rhein", "entity_type": "Chemical", "pos": [74, 79]}, {"entity": "diclofenac", "entity_type": "Chemical", "pos": [82, 92]}], "task": "NER"}
{"text": "In order to study the hydrolytic characterization of an anti - inflammatory prodrug ( RD - 1 ) in vitro , a simple , specific , precise and accurate method for the simultaneous determination of prodrug and its two hydrolytic active compounds was development using reverse phase high - performance liquid chromatography ( RP - HPLC ) .", "entity": [], "task": "NER"}
{"text": "The chromatographic separation was performed on an ODS - 2 C18 column ( 250 mm x 4 . 6 mm , 5 . 0 microm particle size ) with a simple elution programme .", "entity": [], "task": "NER"}
{"text": "The mobile phase was methanol - 0 . 1 % phosphoric acid solution ( adjusted pH to 2 . 3 ) ( 80 : 20 , v / v ) ; wavelength of 257nm and mobile phase flow rate of 1 . 0 mL / min was utilized for the quantitative analysis .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "phosphoric acid", "entity_type": "Chemical", "pos": [40, 55]}], "task": "NER"}
{"text": "Excellent linear behaviors over the investigated concentration ranges were observed with the values of R2 higher than 0 . 999 for all the analytes .", "entity": [], "task": "NER"}
{"text": "The validated method was successfully applied to the simultaneous determination of prodrug and its active components .", "entity": [], "task": "NER"}
{"text": "Rapid identification of sibutramine in dietary supplements using a stepwise approach .", "entity": [{"entity": "sibutramine", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "Adulteration of botanical food supplements with undeclared synthetic drugs is a common problem .", "entity": [], "task": "NER"}
{"text": "One of the most affected product groups are the slimming agents .", "entity": [], "task": "NER"}
{"text": "There are no analytical protocols for the detection of synthetic adulterants from these products .", "entity": [], "task": "NER"}
{"text": "The present study aimed at the development of a multistep analytical method for the quick and reliable determination of sibutramine , one of the most common adulterants among botanical food supplements .", "entity": [{"entity": "sibutramine", "entity_type": "Chemical", "pos": [120, 131]}], "task": "NER"}
{"text": "The extract of a sibutramine - containing slimming formula was analysed by colour tests , TLC , HPLC - DAD , MS and NMR .", "entity": [{"entity": "sibutramine", "entity_type": "Chemical", "pos": [17, 28]}], "task": "NER"}
{"text": "The multistep method proposed by the authors allows the quick identification of sibutramine in counterfeit samples in laboratories with different instrumentation .", "entity": [{"entity": "sibutramine", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "Development and validation of a simple LC method for the determination of phenacetin , coumarin , tolbutamide , chlorzoxazone , testosterone and their metabolites as markers of cytochromes 1A2 , 2A6 , 2C11 , 2E1 and 3A2 in rat microsomal medium .", "entity": [{"entity": "phenacetin", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "coumarin", "entity_type": "Chemical", "pos": [87, 95]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [98, 109]}, {"entity": "chlorzoxazone", "entity_type": "Chemical", "pos": [112, 125]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [128, 140]}], "task": "NER"}
{"text": "Cytochrome P450 enzymes are responsible for the oxidative metabolism of most pharmaceutical compounds .", "entity": [], "task": "NER"}
{"text": "A \" cocktail \" approach which employs simultaneous administration of a mixture of substrates of CYP enzymes was often used to assess the metabolic activity of multiple P450 forms in one experiment .", "entity": [], "task": "NER"}
{"text": "Phenacetin , coumarin , tolbutamide , chlorzoxazone and testosterone are commonly used as probe substrates to evaluate cytochrome P450 function .", "entity": [{"entity": "Phenacetin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "coumarin", "entity_type": "Chemical", "pos": [13, 21]}, {"entity": "tolbutamide", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "chlorzoxazone", "entity_type": "Chemical", "pos": [38, 51]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [56, 68]}], "task": "NER"}
{"text": "An analytical strategy to simultaneously extract and analyze the five probe substrates and their major metabolites by HPLC - DAD was developed .", "entity": [], "task": "NER"}
{"text": "The incubation was done with all the substrates in one step .", "entity": [], "task": "NER"}
{"text": "The ten analytes were extracted simultaneously by solid - phase extraction ( SPE ) from rat liver microsomes .", "entity": [], "task": "NER"}
{"text": "A C18 analytical column and mobile phase composed of acetonitrile and 0 . 02 % aqueous phosphoric acid were used for the chromatographic separation with DAD detection .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [53, 65]}, {"entity": "phosphoric acid", "entity_type": "Chemical", "pos": [87, 102]}], "task": "NER"}
{"text": "Limits of quantification varied between 0 . 02378 and 0 . 2361 microg / mL which contributed to quantify all these drugs and metabolites with UV detection .", "entity": [], "task": "NER"}
{"text": "The method is applicable for the modeling and description of pharmacological interactions on rat cytochromes P450 or can be used for in vitro evaluation of cytochromes 1A2 , 2A6 , 2C11 , 2E1 and 3A2 .", "entity": [], "task": "NER"}
{"text": "Synergistic antitumor activity from two - stage delivery of targeted toxins and endosome - disrupting nanoparticles .", "entity": [], "task": "NER"}
{"text": "Plant - derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells .", "entity": [], "task": "NER"}
{"text": "We tested a concept for two - stage delivery , whereby tumor cells precoated with an antibody - targeted gelonin toxin were killed by exposure to endosome - disrupting polymer nanoparticles .", "entity": [], "task": "NER"}
{"text": "Co - internalization of particles and tumor cell - bound gelonin led to cytosolic delivery and > 50 - fold enhancement of toxin efficacy .", "entity": [], "task": "NER"}
{"text": "This approach allows the extreme potency of gelonin to be focused on tumors with significantly reduced potential for off - target toxicity .", "entity": [], "task": "NER"}
{"text": "Temperature dependence of transport properties of spiro - MeOTAD as a hole transport material in solid - state dye - sensitized solar cells .", "entity": [{"entity": "spiro - MeOTAD", "entity_type": "Chemical", "pos": [50, 64]}], "task": "NER"}
{"text": "The internal transport and recombination parameters of solid - state dye - sensitized solar cells ( ssDSCs ) using the amorphous organic semiconductor 2 , 2 ' , 7 , 7 ' - tetrakis ( N , N - di - p - methoxyphenylamine ) - 9 , 9 ' - spirobifluorene ( spiro - MeOTAD ) as a hole transport material ( HTM ) are investigated using electrical impedance spectroscopy .", "entity": [{"entity": "2 , 2 ' , 7 , 7 ' - tetrakis ( N , N - di - p - methoxyphenylamine ) - 9 , 9 ' - spirobifluorene", "entity_type": "Chemical", "pos": [151, 247]}, {"entity": "spiro - MeOTAD", "entity_type": "Chemical", "pos": [250, 264]}], "task": "NER"}
{"text": "Devices were fabricated using flat and nanostructured TiO2 and compared to systems using nanostructured ZrO2 to differentiate between the transport processes within the different components of the ssDSC .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "ZrO2", "entity_type": "Chemical", "pos": [104, 108]}], "task": "NER"}
{"text": "The effect of chemically p - doping the HTM on its transport was investigated , and its temperature dependence was examined and analyzed using the Arrhenius equation .", "entity": [], "task": "NER"}
{"text": "Using this approach the activation energy of the hole hopping transport within the undoped spiro - MeOTAD film was determined to be 0 . 34 +/- 0 . 02 and 0 . 40 +/- 0 . 02 eV for the mesoporous TiO2 and ZrO2 systems , respectively .", "entity": [{"entity": "spiro - MeOTAD", "entity_type": "Chemical", "pos": [91, 105]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [194, 198]}, {"entity": "ZrO2", "entity_type": "Chemical", "pos": [203, 207]}], "task": "NER"}
{"text": "In vivo genotoxicity and oxidative stress evaluation of an ethanolic extract from piqui a ( Caryocar villosum ) pulp .", "entity": [], "task": "NER"}
{"text": "In this study , the ethanolic extract obtained from piqui a pulp was assessed for genotoxicity and oxidative stress by employing the micronucleus test in bone marrow and peripheral blood cells in addition to comet , thiobarbituric - acid - reactive substances ( TBARS ) , and reduced glutathione assays in the liver , kidney , and heart .", "entity": [{"entity": "thiobarbituric - acid", "entity_type": "Chemical", "pos": [216, 237]}, {"entity": "reduced glutathione", "entity_type": "Chemical", "pos": [276, 295]}], "task": "NER"}
{"text": "Additionally , phytochemical analyses were performed to identify and quantify the chemical constituents of the piqui a extract .", "entity": [], "task": "NER"}
{"text": "Wistar rats were treated by gavage with an ethanolic extract from piqui a pulp ( 75 mg / kg body weight ) for 14 days , and 24 h prior to euthanasia , they received an injection of saline or doxorubicin ( 15 mg / kg body weight , intraperoneally ) .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [191, 202]}], "task": "NER"}
{"text": "The results demonstrated that piqui a extract at the tested dose was genotoxic but not mutagenic , and it increased the TBARS levels in the heart .", "entity": [], "task": "NER"}
{"text": "Further studies are required to fully elucidate how the properties of ethanolic extract of piqui a pulp can affect human health .", "entity": [], "task": "NER"}
{"text": "Kimchi , a fermented vegetable , improves serum lipid profiles in healthy young adults : randomized clinical trial .", "entity": [], "task": "NER"}
{"text": "Abstract Vegetable - based diets have generally focused on their health benefits including negative associations with the serum cholesterol concentrations .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [128, 139]}], "task": "NER"}
{"text": "The aim of this study was to investigate whether serum lipid concentrations are influenced by the amount of kimchi intake .", "entity": [], "task": "NER"}
{"text": "For the study , 100 volunteers were assigned to 2 dietary groups , low ( 15 g / day , n = 50 ) and high ( 210 g / day , n = 50 ) kimchi intake , and were housed together in a dormitory for 7 days .", "entity": [], "task": "NER"}
{"text": "Identical meals except with different amount of kimchi were provided and subjects were instructed to maintain their normal physical activity .", "entity": [], "task": "NER"}
{"text": "Concentrations of fasting blood glucose ( FBG ) , total glucose , total cholesterol and low density lipoprotein ( LDL ) - C significantly decreased in both groups after 7 days of kimchi intake , but the effects were dose dependent .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "Lipid lowering effects of kimchi were more profound in the subjects with total cholesterol and LDL - C level over 190 and 130 mg / dL , respectively , in both groups .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [79, 90]}], "task": "NER"}
{"text": "FBG was significantly decreased in the high kimchi intake as compared to the low intake group ( P = . 003 ) .", "entity": [], "task": "NER"}
{"text": "In conclusion , greater consumption of kimchi improved FBG and serum total cholesterol in young healthy adults .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "Chronic food administration of Salvia sclarea oil reduces animals ' anxious and dominant behavior .", "entity": [], "task": "NER"}
{"text": "Recent studies indicate that an oil extract from Salvia sclarea may provide clinical benefits in various pathological conditions .", "entity": [], "task": "NER"}
{"text": "In comparison to extracts from other Salvia species , S . sclarea oil contains twice as much omega - 3 fatty acids , which are involved in eicosanoid synthesis pathways , and has been found to contain significant levels of the psychoactive monoterpane linalool .", "entity": [{"entity": "omega - 3 fatty acids", "entity_type": "Chemical", "pos": [93, 114]}, {"entity": "eicosanoid", "entity_type": "Chemical", "pos": [139, 149]}, {"entity": "linalool", "entity_type": "Chemical", "pos": [252, 260]}], "task": "NER"}
{"text": "In the present study , we examined the mood stabilizing and anxiolytic - like effects of chronic food administration of S . sclarea oil extract on behavioral and physiological parameters of mice with prominent dominant and submissive features in behavioral assays used to test mood stabilizing and antidepressant drugs .", "entity": [], "task": "NER"}
{"text": "Experimental animals received oil supplemented food from the age of 4 weeks or from conception via their pregnant dams .", "entity": [], "task": "NER"}
{"text": "Each age group received either S . sclarea oil - or sunflower oil - enriched feed .", "entity": [], "task": "NER"}
{"text": "Dominant animals , whose pregnant mothers received S . sclarea oil - enriched feed from the date of conception , showed a significant reduction of dominant and anxiety - like behavior , in comparison to their sunflower oil - treated counterparts .", "entity": [], "task": "NER"}
{"text": "S . sclarea oil - treated submissive animals exhibited a similar tendency , and showed a significant reduction in blood corticosterone levels .", "entity": [{"entity": "corticosterone", "entity_type": "Chemical", "pos": [120, 134]}], "task": "NER"}
{"text": "These findings enforce the hypothesis that S . sclarea oil possesses anxiolytic properties .", "entity": [], "task": "NER"}
{"text": "Development of an in vitro dendritic cell - based test for skin sensitizer identification .", "entity": [], "task": "NER"}
{"text": "The sensitizing potential of chemicals is currently assessed using animal models .", "entity": [], "task": "NER"}
{"text": "However , ethical and economic concerns and the recent European legislative framework triggered intensive research efforts in the development and validation of alternative methods .", "entity": [], "task": "NER"}
{"text": "Therefore , the aim of this study was to develop an in vitro predictive test based on the analysis and integration of gene expression and intracellular signaling profiles of chemical - exposed skin - derived dendritic cells .", "entity": [], "task": "NER"}
{"text": "Cells were treated with four known sensitizers and two nonsensitizers , and the effects on the expression of 20 candidate genes and the activation of MAPK , PI3K / Akt , and NF - kappa B signaling pathways were analyzed by real - time reverse transcription polymerase chain reaction and Western blotting , respectively .", "entity": [], "task": "NER"}
{"text": "Genes Trxr1 , Hmox1 , Nqo1 , and Cxcl10 and the p38 MAPK and JNK signaling pathways were identified as good predictor variables and used to construct a dichotomous classifier .", "entity": [], "task": "NER"}
{"text": "For validation of the model , 12 new chemicals were then analyzed in a blind assay , and from these , 11 were correctly classified .", "entity": [], "task": "NER"}
{"text": "Considering the total of 18 compounds tested here , 17 were correctly classified , representing a concordance of 94 % , with a sensitivity of 92 % ( 12 of 13 sensitizers identified ) and a specificity of 100 % ( 5 of 5 nonsensitizers identified ) .", "entity": [], "task": "NER"}
{"text": "Additionally , we tested the ability of our model to discriminate sensitizers from nonallergenic but immunogenic compounds such as lipopolysaccharide ( LPS ) .", "entity": [], "task": "NER"}
{"text": "LPS was correctly classified as a nonsensitizer .", "entity": [], "task": "NER"}
{"text": "Overall , our results indicate that the analysis of proposed gene and signaling pathway signatures in a mouse fetal skin - derived dendritic cell line represents a valuable model to be integrated in a future in vitro test platform .", "entity": [], "task": "NER"}
{"text": "Single - molecule spectroscopy on RC - LH1 complexes of Rhodopseudomonas acidophila strain 10050 .", "entity": [], "task": "NER"}
{"text": "We have revisited the RC - LH1 complex from Rhodopseudomonas ( Rps . ) acidophila for single - molecule spectroscopy .", "entity": [], "task": "NER"}
{"text": "For the current study the pigment - protein complexes were stabilized in the detergent buffer solution using a relatively mild detergent ( dodecyl - beta - D - maltoside ( DDM ) instead of lauryldimethylamine N - oxide ( LDAO ) ) .", "entity": [{"entity": "dodecyl - beta - D - maltoside", "entity_type": "Chemical", "pos": [139, 169]}, {"entity": "DDM", "entity_type": "Chemical", "pos": [172, 175]}, {"entity": "lauryldimethylamine N - oxide", "entity_type": "Chemical", "pos": [189, 218]}, {"entity": "LDAO", "entity_type": "Chemical", "pos": [221, 225]}], "task": "NER"}
{"text": "This leads to a significant reduction of the fraction of broken / dissociated RC - LH1 complexes with respect to previous studies and has allowed us to investigate a sufficiently large sample of individual RC - LH1 complexes .", "entity": [], "task": "NER"}
{"text": "For most of the complexes the fluorescence - excitation spectra exhibit a narrow spectral feature at the red end of the spectrum .", "entity": [], "task": "NER"}
{"text": "Analysis of the statistics of the spectral properties yields a close resemblance with the results obtained on RC - LH1 complexes from Rps . palustris for which a low - resolution X - ray structure is available .", "entity": [], "task": "NER"}
{"text": "Based on this comparison we come to the conclusion that for both species the RC - LH1 complex can be described by the same structural model , that is , an overall elliptical assembly of pigments that features a gap .", "entity": [], "task": "NER"}
{"text": "Examination of the Mode of Action of the Almiramide Family of Natural Products against the Kinetoplastid Parasite Trypanosoma brucei .", "entity": [{"entity": "Almiramide", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "Almiramide C is a marine natural product with low micromolar activity against Leishmania donovani , the causative agent of leishmaniasis .", "entity": [{"entity": "Almiramide C", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "We have now shown that almiramide C is also active against the related parasite Trypanosoma brucei , the causative agent of human African trypanosomiasis .", "entity": [{"entity": "almiramide C", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "A series of activity - based probes have been synthesized to explore both the molecular target of this compound series in T . brucei lysates and site localization through epifluorescence microscopy .", "entity": [], "task": "NER"}
{"text": "These target identification studies indicate that the almiramides likely perturb glycosomal function through disruption of membrane assembly machinery .", "entity": [{"entity": "almiramides", "entity_type": "Chemical", "pos": [54, 65]}], "task": "NER"}
{"text": "Glycosomes , which are organelles specific to kinetoplastid parasites , house the first seven steps of glycolysis and have been shown to be essential for parasite survival in the bloodstream stage .", "entity": [], "task": "NER"}
{"text": "There are currently no reported small - molecule disruptors of glycosome function , making the almiramides unique molecular probes for this understudied parasite - specific organelle .", "entity": [{"entity": "almiramides", "entity_type": "Chemical", "pos": [95, 106]}], "task": "NER"}
{"text": "Additionally , examination of toxicity in an in vivo zebrafish model has shown that these compounds have little effect on organism development , even at high concentrations , and has uncovered a potential side effect through localization of fluorescent derivatives to zebrafish neuromast cells .", "entity": [], "task": "NER"}
{"text": "Combined , these results further our understanding of the potential value of this lead series as development candidates against T . brucei .", "entity": [], "task": "NER"}
{"text": "Achievement of pregnancies in women with primary ovarian insufficiency using close monitoring of follicle development : case reports .", "entity": [], "task": "NER"}
{"text": "Women with primary ovarian insufficiency ( POI ) / premature ovarian failure exhibit hypergonadotropic hypogonadism due to follicle dysfunction and depletion before the age of 40 years .", "entity": [], "task": "NER"}
{"text": "Because ovulation is extremely rare and thought to be unpredictable in women with POI and because no ovulation induction regimens have been shown to be efficacious , oocyte donation is the only evidence - based treatment for women with POI with desired fertility .", "entity": [], "task": "NER"}
{"text": "Oocyte donation is , however , extremely limited in several countries including Japan .", "entity": [], "task": "NER"}
{"text": "Here , we report four women with POI who achieved pregnancies resulting from timed intercourse or intrauterine insemination in combination with cyclic estrogen / progesterone therapy and close monitoring of follicle development .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [151, 159]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [162, 174]}], "task": "NER"}
{"text": "These four patients were diagnosed with POI at the mean age of 27 . 5 +/- 8 . 5 ( mean +/- SD ; range , 19 - 35 ) , subjected to follicle monitoring at the mean age of 29 . 8 +/- 5 . 7 ( 23 - 35 ) , and conceived at the mean age of 34 . 5 +/- 3 . 9 ( 29 - 38 ) .", "entity": [], "task": "NER"}
{"text": "The interval between the initiation of follicle monitoring and pregnancy was 4 . 8 +/- 2 . 8 ( 2 - 8 ) years .", "entity": [], "task": "NER"}
{"text": "In one of the patients , her most recent ovulation occurred after a three - year interval .", "entity": [], "task": "NER"}
{"text": "All four patients had uncomplicated pregnancies with term deliveries .", "entity": [], "task": "NER"}
{"text": "In the event that oocyte donation and adoption are not available and / or various treatments with intensive ovulation induction have been unsuccessful , close and continuous monitoring of follicle growth to identify very rare ovulatory events might be considered for patients with POI and desired fertility .", "entity": [], "task": "NER"}
{"text": "Artificial leaf structures as a UV detector formed by the self - assembly of ZnO nanoparticles .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [77, 80]}], "task": "NER"}
{"text": "Artificial leaf structures have been fabricated by the self - assembly of ZnO nanoparticles .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [74, 77]}], "task": "NER"}
{"text": "A hydrothermal method was used to synthesize the nanoparticles .", "entity": [], "task": "NER"}
{"text": "The self - assembly patterns showed asymmetric dendritic morphologies , larger surface - to - volume ratios , a broad absorption band and high resistance .", "entity": [], "task": "NER"}
{"text": "A non - equilibrium two - stage - formation process included diffusion limited aggregation , and the phase - field model was introduced to explain the formation mechanism of the pattern .", "entity": [], "task": "NER"}
{"text": "A high - performance ultraviolet detector was fabricated on the artificial leaf structures , which showed that the current under the irradiation of a UV lamp ( 1 . 21 mW cm ( - 2 ) ) was about 10 ( 4 ) times greater than in the dark .", "entity": [], "task": "NER"}
{"text": "The various and functional properties of the pattern show us the vast prospects of potential applications for light harvesting systems and other optical - electric devices .", "entity": [], "task": "NER"}
{"text": "Synthesis of pyrido [ 2 , 3 - d ] [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] pyrimidin - 5 - ones as potential antimicrobial agents .", "entity": [{"entity": "pyrido [ 2 , 3 - d ] [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] pyrimidin - 5 - ones", "entity_type": "Chemical", "pos": [13, 91]}], "task": "NER"}
{"text": "Synthesis of new derivatives of pyrido [ 2 , 3 - d ] [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] pyrimidin - 5 - one via reaction of 7 - ( 4 - bromophenyl ) - 1 , 2 - dihydro - 5 - ( 4 - fluorophenyl ) - 2 - thioxopyrido [ 2 , 3 - d ] pyrimidin - 4 ( 3H ) - one with hydrazonoyl chlorides or reaction of 2 - hydrazino - pyrido [ 2 , 3 - d ] pyrimidin - 4 ( 3H ) - one with different aldehydes followed by cyclization of the products .", "entity": [{"entity": "pyrido [ 2 , 3 - d ] [ 1 , 2 , 4 ] triazolo [ 4 , 3 - a ] pyrimidin - 5 - one", "entity_type": "Chemical", "pos": [32, 109]}, {"entity": "7 - ( 4 - bromophenyl ) - 1 , 2 - dihydro - 5 - ( 4 - fluorophenyl ) - 2 - thioxopyrido [ 2 , 3 - d ] pyrimidin - 4 ( 3H ) - one", "entity_type": "Chemical", "pos": [126, 254]}, {"entity": "hydrazonoyl chlorides", "entity_type": "Chemical", "pos": [260, 281]}, {"entity": "2 - hydrazino - pyrido [ 2 , 3 - d ] pyrimidin - 4 ( 3H ) - one", "entity_type": "Chemical", "pos": [297, 360]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [376, 385]}], "task": "NER"}
{"text": "All the newly synthesized compounds were evaluated for their antimicrobial activities and also their minimum inhibitory concentration against most of test organisms was performed .", "entity": [], "task": "NER"}
{"text": "Amongst the tested compounds displayed excellent activity against all the tested microorganisms except SR and PA .", "entity": [], "task": "NER"}
{"text": "Glutathione dimerization - based plasmonic nanoswitch for biodetection of reactive oxygen and nitrogen species .", "entity": [{"entity": "Glutathione", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [83, 89]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "Reactive oxygen and nitrogen species ( ROS and RNS ) are continuously produced in the cellular systems and are controlled by several antioxidant mechanisms .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [9, 15]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "Here , we developed a straightforward , sensitive , and quantitative assay for the colorimetric and spectroscopic detection of various ROS and RNS such as H2O2 , . OH , ( - ) OCl , NO . , and O2 ( - ) using glutathione - modified gold nanoparticles ( GSH - AuNPs ) .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [155, 159]}, {"entity": ". OH", "entity_type": "Chemical", "pos": [162, 166]}, {"entity": "( - ) OCl", "entity_type": "Chemical", "pos": [169, 178]}, {"entity": "NO .", "entity_type": "Chemical", "pos": [181, 185]}, {"entity": "O2 ( - )", "entity_type": "Chemical", "pos": [192, 200]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [207, 218]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [251, 254]}], "task": "NER"}
{"text": "A basic principle here is that the GSHs on the AuNP surface can be readily detached via the formation of glutathione disulfides upon the addition of ROS and RNS , and destabilized particles can aggregate to generate the plasmonic couplings between plasmonic AuNPs that trigger the red shift in UV - vis spectrum and solution color change .", "entity": [{"entity": "GSHs", "entity_type": "Chemical", "pos": [35, 39]}, {"entity": "glutathione disulfides", "entity_type": "Chemical", "pos": [105, 127]}], "task": "NER"}
{"text": "For nonradical species such as H2O2 , this process can be more efficiently achieved by converting them into radical species via the Fenton reaction .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "Using this strategy , we were able to rapidly and quantitatively distinguish among cancerous and normal cells based on ROS and RNS production .", "entity": [], "task": "NER"}
{"text": "Twisting bilayer graphene superlattices .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "Bilayer graphene is an intriguing material in that its electronic structure can be altered by changing the stacking order or the relative twist angle , yielding a new class of low - dimensional carbon system .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [8, 16]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [194, 200]}], "task": "NER"}
{"text": "Twisted bilayer graphene can be obtained by ( i ) thermal decomposition of SiC ; ( ii ) chemical vapor deposition ( CVD ) on metal catalysts ; ( iii ) folding graphene ; or ( iv ) stacking graphene layers one atop the other , the latter of which suffers from interlayer contamination .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "SiC", "entity_type": "Chemical", "pos": [75, 78]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [159, 167]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [189, 197]}], "task": "NER"}
{"text": "Existing synthesis protocols , however , usually result in graphene with polycrystalline structures .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "The present study investigates bilayer graphene grown by ambient pressure CVD on polycrystalline Cu .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [39, 47]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [97, 99]}], "task": "NER"}
{"text": "Controlling the nucleation in early stage growth allows the constituent layers to form single hexagonal crystals .", "entity": [], "task": "NER"}
{"text": "New Raman active modes are shown to result from the twist , with the angle determined by transmission electron microscopy .", "entity": [], "task": "NER"}
{"text": "The successful growth of single - crystal bilayer graphene provides an attractive jumping - off point for systematic studies of interlayer coupling in misoriented few - layer graphene systems with well - defined geometry .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [175, 183]}], "task": "NER"}
{"text": "Acyclic nucleoside phosphonates containing a second phosphonate group are potent inhibitors of 6 - oxopurine phosphoribosyltransferases and have antimalarial activity .", "entity": [{"entity": "Acyclic nucleoside phosphonates", "entity_type": "Chemical", "pos": [0, 31]}, {"entity": "phosphonate", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "6 - oxopurine", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "Acyclic nucleoside phosphonates ( ANPs ) that contain a 6 - oxopurine base are good inhibitors of the Plasmodium falciparum ( Pf ) and Plasmodium vivax ( Pv ) 6 - oxopurine phosphoribosyltransferases ( PRTs ) .", "entity": [{"entity": "Acyclic nucleoside phosphonates", "entity_type": "Chemical", "pos": [0, 31]}, {"entity": "ANPs", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "6 - oxopurine", "entity_type": "Chemical", "pos": [56, 69]}, {"entity": "6 - oxopurine", "entity_type": "Chemical", "pos": [159, 172]}], "task": "NER"}
{"text": "Chemical modifications based on the crystal structure of 2 - ( phosphonoethoxy ) ethylguanine ( PEEG ) in complex with human HGPRT have led to the design of new ANPs .", "entity": [{"entity": "2 - ( phosphonoethoxy ) ethylguanine", "entity_type": "Chemical", "pos": [57, 93]}, {"entity": "PEEG", "entity_type": "Chemical", "pos": [96, 100]}, {"entity": "ANPs", "entity_type": "Chemical", "pos": [161, 165]}], "task": "NER"}
{"text": "These novel compounds contain a second phosphonate group attached to the ANP scaffold .", "entity": [{"entity": "phosphonate", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "ANP", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "{ [ ( 2 - [ ( Guanine - 9H - yl ) methyl ] propane - 1 , 3 - diyl ) bis ( oxy ) ] bis ( methylene ) } diphosphonic acid ( compound 17 ) exhibited a Ki value of 30 nM for human HGPRT and 70 nM for Pf HGXPRT .", "entity": [{"entity": "{ [ ( 2 - [ ( Guanine - 9H - yl ) methyl ] propane - 1 , 3 - diyl ) bis ( oxy ) ] bis ( methylene ) } diphosphonic acid", "entity_type": "Chemical", "pos": [0, 119]}], "task": "NER"}
{"text": "The crystal structure of this compound in complex with human HGPRT shows that it fills or partially fills three critical locations in the active site : the binding sites of the purine base , the 5 ' - phosphate group , and pyrophosphate .", "entity": [{"entity": "purine", "entity_type": "Chemical", "pos": [177, 183]}, {"entity": "5 ' - phosphate", "entity_type": "Chemical", "pos": [195, 210]}, {"entity": "pyrophosphate", "entity_type": "Chemical", "pos": [223, 236]}], "task": "NER"}
{"text": "This is the first HG ( X ) PRT inhibitor that has been able to achieve this result .", "entity": [], "task": "NER"}
{"text": "Prodrugs have been synthesized resulting in IC50 values as low as 3 . 8 mu M for Pf grown in cell culture , up to 25 - fold lower compared to the parent compounds .", "entity": [], "task": "NER"}
{"text": "Synthesis of novel estrogen receptor antagonists using metal - catalyzed coupling reactions and characterization of their biological activity .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [19, 27]}], "task": "NER"}
{"text": "Estrogen receptor ( ER ) antagonists are valuable in the treatment of ER - positive human breast cancer .", "entity": [{"entity": "Estrogen", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "In this study , we designed and synthesized nine new derivatives of 17 beta - estradiol ( E2 ) with a bulky side chain attached to its C - 7 alpha position , and determined their ER antagonistic activity using in vitro bioassays .", "entity": [{"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [68, 87]}], "task": "NER"}
{"text": "Four of the derivatives showed a strong inhibition of ER alpha transactivation activity in a luciferase reporter assay and blocked ER alpha interactions with coactivators .", "entity": [], "task": "NER"}
{"text": "Similarly , these derivatives also strongly inhibited the growth of the ER alpha - positive human breast cancer cells .", "entity": [], "task": "NER"}
{"text": "Computational docking analysis was conducted to model the interaction of these antagonists with the human ER alpha and showed that they could tightly bind to the ER alpha in a manner similar to that of ICI - 182 , 780 , a pure ER antagonist .", "entity": [{"entity": "ICI - 182 , 780", "entity_type": "Chemical", "pos": [202, 217]}], "task": "NER"}
{"text": "These results provide an example that attachment of a bulky side chain to the C - 7 alpha position of E2 can produce ER antagonists with ER affinity comparable to that of ICI - 182 , 780 .", "entity": [{"entity": "ICI - 182 , 780", "entity_type": "Chemical", "pos": [171, 186]}], "task": "NER"}
{"text": "Device physics and operation of lateral bulk heterojunction devices .", "entity": [], "task": "NER"}
{"text": "Measurements of lateral bulk heterojunction ( BHJ ) devices have recently been reported as a means to characterize charge transport and recombination properties within organic photovoltaic ( OPV ) materials .", "entity": [], "task": "NER"}
{"text": "These structures allow for the direct measurement of the lateral extents of the space charge regions , potential and electric field profiles , current versus voltage characteristics , and other physical and chemical properties .", "entity": [], "task": "NER"}
{"text": "This article describes numerical simulations that show three different transport regimes present within lateral BHJ devices and two different experimental methods , which verify those findings .", "entity": [], "task": "NER"}
{"text": "These measurement techniques utilize typical confocal microscopy tools as well as steady - state current versus voltage measurements on high aspect ratio nanofabricated structures in order to probe the material properties between the electrodes .", "entity": [], "task": "NER"}
{"text": "Experimental results show that the lateral extents of space charge regions within these devices are approximately 1 - 5 mu m , which are related to the drift lengths of the charge carriers , and that the mechanism of bimolecular recombination is shown to be a bulk material property .", "entity": [], "task": "NER"}
{"text": "The results within this article describe a series of methods to evaluate charge transport and recombination along the in - plane direction in BHJ films and provide complementary insights to those obtained from vertical - device - based measurements .", "entity": [], "task": "NER"}
{"text": "Practical approach for measuring heat capacity of pharmaceutical crystals / glasses by modulated - temperature differential scanning calorimetry .", "entity": [], "task": "NER"}
{"text": "A practical protocol to obtain accurate heat capacity values of pharmaceutical compounds using modulated - temperature differential scanning calorimetry was established .", "entity": [], "task": "NER"}
{"text": "Three pharmaceutical compounds , acetaminophen , indomethacin , and tri - O - methyl - beta - cyclodextrin were used as model compounds .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [33, 46]}, {"entity": "indomethacin", "entity_type": "Chemical", "pos": [49, 61]}, {"entity": "tri - O - methyl - beta - cyclodextrin", "entity_type": "Chemical", "pos": [68, 106]}], "task": "NER"}
{"text": "Powder samples did not produce reproducible results , presumably due to inclusion of gas in gap of powders that influenced the measured heat capacity and thermal homogeneity in the sample .", "entity": [], "task": "NER"}
{"text": "Thus , the amorphous characteristics were evaluated using quench - cooled samples .", "entity": [], "task": "NER"}
{"text": "Crystalline samples were obtained by partially melting the sample to allow recrystallization using the residual crystal as a template .", "entity": [], "task": "NER"}
{"text": "Optimum sample mass was about 10 mg .", "entity": [], "task": "NER"}
{"text": "Use of too small sample size resulted in poor reproducibility due to localization of the sample in the pan , while too large size resulted in low heat capacity values probably because of heterogeneity of the sample temperature .", "entity": [], "task": "NER"}
{"text": "The optimum modulation period was in the range of 60 s and 90 s , to which the ramp rates of 2 degrees C / min and 1 degrees C / min , respectively , were applied .", "entity": [], "task": "NER"}
{"text": "The ramp amplitude was less significant in the evaluation .", "entity": [], "task": "NER"}
{"text": "This information should help in comprehending basic characteristics of pharmaceutical compounds .", "entity": [], "task": "NER"}
{"text": "Particle condition change in emulsion admixture evaluated by in situ flow particle imaging analysis .", "entity": [], "task": "NER"}
{"text": "We evaluated the particle state change in emulsion admixtures using in situ flow particle imaging analysis ( FPIA ) .", "entity": [], "task": "NER"}
{"text": "Ropion (R) intravenous ( flurbiprofen axetil : Ropion (R) ) served as the model emulsion formulation .", "entity": [{"entity": "Ropion", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "flurbiprofen axetil", "entity_type": "Chemical", "pos": [25, 44]}, {"entity": "Ropion", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "A binary mixture of Ropion (R) and normal saline ( NS ) , and a ternary admixture of Ropion (R) , NS , and Gaster (R) injection ( famotidine : Gaster (R) ) or Primperan (R) injection ( metoclopramide hydrochloride : Primperan (R) ) were prepared and the change in emulsion particle state was analyzed using FPIA under in situ condition .", "entity": [{"entity": "Ropion", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "Ropion", "entity_type": "Chemical", "pos": [85, 91]}, {"entity": "Gaster", "entity_type": "Chemical", "pos": [107, 113]}, {"entity": "famotidine", "entity_type": "Chemical", "pos": [130, 140]}, {"entity": "Gaster", "entity_type": "Chemical", "pos": [143, 149]}, {"entity": "Primperan", "entity_type": "Chemical", "pos": [159, 168]}, {"entity": "metoclopramide hydrochloride", "entity_type": "Chemical", "pos": [185, 213]}, {"entity": "Primperan", "entity_type": "Chemical", "pos": [216, 225]}], "task": "NER"}
{"text": "The effect of storage on pH change and the chemical stability of flurbiprofen axetil were also investigated .", "entity": [{"entity": "flurbiprofen axetil", "entity_type": "Chemical", "pos": [65, 84]}], "task": "NER"}
{"text": "In Ropion (R) , various particle images ( mean diameter : 2 . 4 micro m ) were obtained .", "entity": [{"entity": "Ropion", "entity_type": "Chemical", "pos": [3, 9]}], "task": "NER"}
{"text": "From our analysis of changes in scattergrams and particle images , changing behaviors of emulsion particles as a function of storage time depended on the systems of admixture samples .", "entity": [], "task": "NER"}
{"text": "In Ropion (R) / NS and Ropion (R) / Gaster (R) / NS systems , mean particle size and particle number increased with lengthening storage time ; however , these values were dramatically increased beyond 6 h in the Ropion (R) / Primperan (R) / NS system , corresponding to a decrease in measured pH .", "entity": [{"entity": "Ropion", "entity_type": "Chemical", "pos": [3, 9]}, {"entity": "Ropion", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "Gaster", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "Ropion", "entity_type": "Chemical", "pos": [212, 218]}, {"entity": "Primperan", "entity_type": "Chemical", "pos": [225, 234]}], "task": "NER"}
{"text": "The decomposition of flurbiprofen axetil due to incompatibility was not observed in all systems .", "entity": [{"entity": "flurbiprofen axetil", "entity_type": "Chemical", "pos": [21, 40]}], "task": "NER"}
{"text": "Detailed information on the change in emulsion particle state was obtained using FPIA , indicating that this method is useful to evaluate state changes in emulsion admixtures under in situ condition .", "entity": [], "task": "NER"}
{"text": "Ca2 + - dependent protein kinase11 and 24 modulate the activity of the inward rectifying K + channels in Arabidopsis pollen tubes .", "entity": [{"entity": "Ca2 +", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "K +", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Potassium ( K ( + ) ) influx into pollen tubes via K ( + ) transporters is essential for pollen tube growth ; however , the mechanism by which K ( + ) transporters are regulated in pollen tubes remains unknown .", "entity": [{"entity": "Potassium", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [51, 58]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [143, 150]}], "task": "NER"}
{"text": "Here , we report that Arabidopsis thaliana Ca ( 2 + ) - dependent protein kinase11 ( CPK11 ) and CPK24 are involved in Ca ( 2 + ) - dependent regulation of the inward K ( + ) ( K ( + ) in ) channels in pollen tubes .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [43, 53]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [119, 129]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [167, 174]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [177, 184]}], "task": "NER"}
{"text": "Using patch - clamp analysis , we demonstrated that K ( + ) in currents of pollen tube protoplasts were inhibited by elevated [ Ca ( 2 + ) ] cyt .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [128, 138]}], "task": "NER"}
{"text": "However , disruption of CPK11 or CPK24 completely impaired the Ca ( 2 + ) - dependent inhibition of K ( + ) in currents and enhanced pollen tube growth .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "Moreover , the cpk11 cpk24 double mutant exhibited similar phenotypes as the corresponding single mutants , suggesting that these two CDPKs function in the same signaling pathway .", "entity": [], "task": "NER"}
{"text": "Bimolecular fluorescence complementation and coimmunoprecipitation experiments showed that CPK11 could interact with CPK24 in vivo .", "entity": [], "task": "NER"}
{"text": "Furthermore , CPK11 phosphorylated the N terminus of CPK24 in vitro , suggesting that these two CDPKs work together as part of a kinase cascade .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [39, 40]}], "task": "NER"}
{"text": "Electrophysiological assays demonstrated that the Shaker pollen K ( + ) in channel is the main contributor to pollen tube K ( + ) in currents and acts as the downstream target of the CPK11 - CPK24 pathway .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [64, 71]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [122, 129]}], "task": "NER"}
{"text": "We conclude that CPK11 and CPK24 together mediate the Ca ( 2 + ) - dependent inhibition of K ( + ) in channels and participate in the regulation of pollen tube growth in Arabidopsis .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [54, 64]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [91, 98]}], "task": "NER"}
{"text": "Overdosage of Hand2 causes limb and heart defects in the human chromosomal disorder partial trisomy distal 4q .", "entity": [], "task": "NER"}
{"text": "Partial trisomy distal 4q ( denoted 4q + ) is a human chromosomal disorder caused by duplication of the distal end of the long arm of chromosome 4 ( Chr4 ) .", "entity": [], "task": "NER"}
{"text": "This disorder manifests typical phenotypes , including craniofacial , renal , heart and thumb developmental defects .", "entity": [], "task": "NER"}
{"text": "Although these clinical features are likely caused by a dosage imbalance in the gene network involving the trisomic region , the causative gene or genes and the molecular bases are largely unknown .", "entity": [], "task": "NER"}
{"text": "Here , we report mouse Recombination - induced mutation 4 ( Rim4 ) as a model animal of 4q + .", "entity": [], "task": "NER"}
{"text": "The Rim4 genome contains an insertion of a 6 . 5 Mb fragment from mouse chromosome 8 into chromosome 6 .", "entity": [], "task": "NER"}
{"text": "This insertion fragment contains 17 genes , including Hand2 , that encode the basic helix - loop - helix transcription factor and is syntenic to the distal end of human Chr4 , 4q32 . 3 to 4q34 . 1 , which is responsible for 4q + .", "entity": [], "task": "NER"}
{"text": "A comparison of phenotypes between patients with Rim4 and 4q + revealed that Rim4 shows direct parallels with many phenotypes of 4q + such as craniofacial , heart , cervical vertebra and limb deformities .", "entity": [], "task": "NER"}
{"text": "Rebalancing the gene dosage by a genetic cross with Hand2 knockout mice ameliorated symptoms of the heart and limb deformities of Rim4 .", "entity": [], "task": "NER"}
{"text": "Conversely , an increase in copy number of Hand2 in wild - type mice recaptures the heart and limb deformities of Rim4 .", "entity": [], "task": "NER"}
{"text": "Our results collectively demonstrate that overdosage of Hand2 is a major cause for at least the limb and heart phenotypes of 4q + and that mouse Rim4 provides a unique animal model for understanding the molecular bases underlying the complex phenotypes of 4q + .", "entity": [], "task": "NER"}
{"text": "Ultrasensitive non - resonant detection of ultrasound with plasmonic metamaterials .", "entity": [], "task": "NER"}
{"text": "Optical sensors for ultrasound detection provide high sensitivity and bandwidth , essential for photoacoustic imaging in clinical diagnostics and biomedical research .", "entity": [], "task": "NER"}
{"text": "Implementing plasmonic metamaterials in a non - resonant regime facilitates sub - nanosecond , highly sensitive detectors while eliminating cumbersome optical alignment necessary for resonant sensors .", "entity": [], "task": "NER"}
{"text": "Luminescent conjugated oligothiophenes for sensitive fluorescent assignment of protein inclusion bodies .", "entity": [{"entity": "oligothiophenes", "entity_type": "Chemical", "pos": [23, 38]}], "task": "NER"}
{"text": "Small hydrophobic ligands identifying intracellular protein deposits are of great interest , as protein inclusion bodies are the pathological hallmark of several degenerative diseases .", "entity": [], "task": "NER"}
{"text": "Here we report that fluorescent amyloid ligands , termed luminescent conjugated oligothiophenes ( LCOs ) , rapidly and with high sensitivity detect protein inclusion bodies in skeletal muscle tissue from patients with sporadic inclusion body myositis ( s - IBM ) .", "entity": [{"entity": "oligothiophenes", "entity_type": "Chemical", "pos": [80, 95]}], "task": "NER"}
{"text": "LCOs having a conjugated backbone of at least five thiophene units emitted strong fluorescence upon binding , and showed co - localization with proteins reported to accumulate in s - IBM protein inclusion bodies .", "entity": [{"entity": "thiophene", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "Compared with conventional amyloid ligands , LCOs identified a larger fraction of immunopositive inclusion bodies .", "entity": [], "task": "NER"}
{"text": "When the conjugated thiophene backbone was extended with terminal carboxyl groups , the LCO revealed striking spectral differences between distinct protein inclusion bodies .", "entity": [{"entity": "thiophene", "entity_type": "Chemical", "pos": [20, 29]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "We conclude that 1 ) LCOs are sensitive , rapid and powerful tools for identifying protein inclusion bodies and 2 ) LCOs identify a wider range of protein inclusion bodies than conventional amyloid ligands .", "entity": [], "task": "NER"}
{"text": "Comparative Binding Energy ( COMBINE ) Analysis for Understanding the Binding Determinants of Type II Dehydroquinase Inhibitors .", "entity": [], "task": "NER"}
{"text": "Herein we report comparative binding energy ( COMBINE ) analyses to derive quantitative structure - activity relationship ( QSAR ) models that help rationalize the determinants of binding affinity for inhibitors of type II dehydroquinase ( DHQ2 ) , the third enzyme of the shikimic acid pathway .", "entity": [{"entity": "shikimic acid", "entity_type": "Chemical", "pos": [273, 286]}], "task": "NER"}
{"text": "Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2 , which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells .", "entity": [], "task": "NER"}
{"text": "These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor design .", "entity": [], "task": "NER"}
{"text": "Over - the - Counter Access to Emergency Contraception without Age Restriction : An Opinion of the Women ' s Health Practice and Research Network of the American College of Clinical Pharmacy .", "entity": [], "task": "NER"}
{"text": "Family planning remains a high priority area for the United States , with goals to increase the proportion of pregnancies that are intended , reduce pregnancy rates among adolescents , and increase contraceptive use prioritized in the Healthy People 2020 objectives .", "entity": [], "task": "NER"}
{"text": "Contraception intended for use after unprotected intercourse , known as emergency contraception , remains underutilized .", "entity": [], "task": "NER"}
{"text": "Levonorgestrel is one method of oral emergency contraception , which prevents fertilization and does not disrupt an already established pregnancy ; thus , timing of administration is critical .", "entity": [{"entity": "Levonorgestrel", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Despite data demonstrating safety and efficacy , evidence - based decision making has been overshadowed by politically charged actions involving levonorgestrel emergency contraception for over a decade .", "entity": [{"entity": "levonorgestrel", "entity_type": "Chemical", "pos": [145, 159]}], "task": "NER"}
{"text": "The Women ' s Health Practice and Research Network of the American College of Clinical Pharmacy supports expanded access to levonorgestrel emergency contraception and removal of barriers such as age restrictions on the nonprescription drug product .", "entity": [{"entity": "levonorgestrel", "entity_type": "Chemical", "pos": [124, 138]}], "task": "NER"}
{"text": "Pharmacists remain a key provider of emergency contraceptive services and can help ensure timely access .", "entity": [], "task": "NER"}
{"text": "In states where direct pharmacy access to emergency contraception is available , pharmacists are encouraged to participate .", "entity": [], "task": "NER"}
{"text": "Education , research , and advocacy are other important responsibilities for pharmacists in this arena .", "entity": [], "task": "NER"}
{"text": "Selective functionalization of the internal and the external surfaces of mesoporous silicon by liquid masking .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "A general approach for selective , differential functionalization of the interior and exterior surfaces of mesoporous Si is reported .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [118, 120]}], "task": "NER"}
{"text": "The method employs two immiscible liquids , one inert and the other chemically reactive with the porous Si nanostructure .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [104, 106]}], "task": "NER"}
{"text": "First , a porous Si sample is prepared by electrochemical etch and then it is mildly oxidized , which places a thin layer of silicon oxide at the surface .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [17, 19]}, {"entity": "silicon oxide", "entity_type": "Chemical", "pos": [125, 138]}], "task": "NER"}
{"text": "The inner pore walls of the partially oxidized porous Si film are then infiltrated with an inert liquid ( octane ) .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "octane", "entity_type": "Chemical", "pos": [106, 112]}], "task": "NER"}
{"text": "The sample is then immersed in aqueous solution containing hydrogen fluoride ( HF ) , which serves as the reactive liquid .", "entity": [{"entity": "hydrogen fluoride", "entity_type": "Chemical", "pos": [59, 76]}, {"entity": "HF", "entity_type": "Chemical", "pos": [79, 81]}], "task": "NER"}
{"text": "The hydrophobic phase is retained in the interior of the porous nanostructure , and HF ( aq ) attacks only the exposed surfaces of the oxidized porous Si sample , generating a hydrophobic , hydrogen - terminated ( Si - H ) outer layer .", "entity": [{"entity": "HF", "entity_type": "Chemical", "pos": [84, 86]}, {"entity": "Si", "entity_type": "Chemical", "pos": [151, 153]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [190, 198]}, {"entity": "Si - H", "entity_type": "Chemical", "pos": [214, 220]}], "task": "NER"}
{"text": "The reaction is self - limiting due to the immiscibility of octane and water , and the extent of penetration of the Si - H surface into the porous layer is dependent on the time of exposure to HF ( aq ) .", "entity": [{"entity": "octane", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "Si - H", "entity_type": "Chemical", "pos": [116, 122]}, {"entity": "HF", "entity_type": "Chemical", "pos": [193, 195]}], "task": "NER"}
{"text": "The Si - H surface can then be modified by thermal hydrosilylation ( 1 - dodecene or 10 - bromo - 1 - decene ) in a subsequent step , resulting in a bifunctional porous Si film containing hydrophobic pore entrances to hydrophilic inner pores .", "entity": [{"entity": "Si - H", "entity_type": "Chemical", "pos": [4, 10]}, {"entity": "1 - dodecene", "entity_type": "Chemical", "pos": [69, 81]}, {"entity": "10 - bromo - 1 - decene", "entity_type": "Chemical", "pos": [85, 108]}, {"entity": "Si", "entity_type": "Chemical", "pos": [169, 171]}], "task": "NER"}
{"text": "The hydrophobic dodecyl species at the mouths of the pores is found to form a barrier for molecular transport ; it decreases the rate of leaching ( into water ) of a rhodamine test molecule that is preloaded into the sample by > 8 fold .", "entity": [{"entity": "dodecyl", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "rhodamine", "entity_type": "Chemical", "pos": [166, 175]}], "task": "NER"}
{"text": "What Can We Learn about Dispersion from the Conformer Surface of n - Pentane ?", "entity": [{"entity": "n - Pentane", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "In earlier work [ Gruzman , D . ; Karton , A . ; Martin , J . M . L . J . Phys . Chem . A 2009 , 113 , 11974 ] , we showed that conformer energies in alkanes ( and other systems ) are highly dispersion - driven and that uncorrected DFT functionals fail badly at reproducing them , while simple empirical dispersion corrections tend to overcorrect .", "entity": [{"entity": "alkanes", "entity_type": "Chemical", "pos": [150, 157]}], "task": "NER"}
{"text": "To gain greater insight into the nature of the phenomenon , we have mapped the torsional surface of n - pentane to 10 - degree resolution at the CCSD ( T ) - F12 level near the basis set limit .", "entity": [{"entity": "n - pentane", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "The data obtained have been decomposed by order of perturbation theory , excitation level , and same - spin vs opposite - spin character .", "entity": [], "task": "NER"}
{"text": "A large number of approximate electronic structure methods have been considered , as well as several empirical dispersion corrections .", "entity": [], "task": "NER"}
{"text": "Our chief conclusions are as follows : ( a ) the effect of dispersion is dominated by same - spin correlation ( or triplet - pair correlation , from a different perspective ) ; ( b ) singlet - pair correlation is important for the surface , but qualitatively very dissimilar to the dispersion component ; ( c ) single and double excitations beyond third order are essentially unimportant for this surface ; ( d ) connected triple excitations do play a role but are statistically very similar to the MP2 singlet - pair correlation ; ( e ) the form of the damping function is crucial for good performance of empirical dispersion corrections ; ( f ) at least in the lower - energy regions , SCS - MP2 and especially MP2 . 5 perform very well ; ( g ) novel spin - component scaled double hybrid functionals such as DSD - PBEP86 - D2 acquit themselves very well for this problem .", "entity": [], "task": "NER"}
{"text": "Adhesion of Mussel Foot Protein - 3 to TiO2 Surfaces : the Effect of pH .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "The underwater adhesion of marine mussels relies on mussel foot proteins ( mfps ) rich in the catecholic amino acid 3 , 4 - dihydroxyphenylalanine ( Dopa ) .", "entity": [{"entity": "3 , 4 - dihydroxyphenylalanine", "entity_type": "Chemical", "pos": [116, 146]}, {"entity": "Dopa", "entity_type": "Chemical", "pos": [149, 153]}], "task": "NER"}
{"text": "As a side chain , Dopa is capable of strong bidentate interactions with a variety of surfaces , including many minerals and metal oxides .", "entity": [{"entity": "Dopa", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "metal oxides", "entity_type": "Chemical", "pos": [124, 136]}], "task": "NER"}
{"text": "Titanium is among the most widely used medical implant material and quickly forms a TiO2 passivation layer under physiological conditions .", "entity": [{"entity": "Titanium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [84, 88]}], "task": "NER"}
{"text": "Understanding the binding mechanism of Dopa to TiO2 surfaces is therefore of considerable theoretical and practical interest .", "entity": [{"entity": "Dopa", "entity_type": "Chemical", "pos": [39, 43]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [47, 51]}], "task": "NER"}
{"text": "Using a surface forces apparatus , we explored the force - distance profiles and adhesion energies of mussel foot protein 3 ( mfp - 3 ) to TiO2 surfaces at three different pHs ( pH 3 , 5 . 5 and 7 . 5 ) .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "At pH 3 , mfp - 3 showed the strongest adhesion force on TiO2 , with an adhesion energy of ~ - 7 . 0 mJ / m ( 2 ) .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "Increasing the pH gives rise to two opposing effects : ( 1 ) increased oxidation of Dopa , thus , decreasing availability for the Dopa - mediated adhesion , and ( 2 ) increased bidentate Dopa - Ti coordination , leading to the further stabilization of the Dopa group and , thus , an increase in adhesion force .", "entity": [{"entity": "Dopa", "entity_type": "Chemical", "pos": [84, 88]}, {"entity": "Dopa", "entity_type": "Chemical", "pos": [130, 134]}, {"entity": "Dopa", "entity_type": "Chemical", "pos": [187, 191]}, {"entity": "Ti", "entity_type": "Chemical", "pos": [194, 196]}, {"entity": "Dopa", "entity_type": "Chemical", "pos": [256, 260]}], "task": "NER"}
{"text": "Both effects were reflected in the resonance - enhanced Raman spectra obtained at the three deposition pHs .", "entity": [], "task": "NER"}
{"text": "The two competing effects give rise to a higher adhesion force of mfp - 3 on the TiO2 surface at pH 7 . 5 than at pH 5 . 5 .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "Our results suggest that Dopa - containing proteins and synthetic polymers have great potential as coating materials for medical implant materials , particularly if redox activity can be controlled .", "entity": [{"entity": "Dopa", "entity_type": "Chemical", "pos": [25, 29]}], "task": "NER"}
{"text": "Synthetic Approaches to RBC Mimicry and Oxygen Carrier Systems .", "entity": [{"entity": "Oxygen", "entity_type": "Chemical", "pos": [40, 46]}], "task": "NER"}
{"text": "Whole blood or red blood cell ( RBC ) transfusions are highly significant , clinically , for blood replacement therapies in traumatic injuries , presurgical conditions , and anemias .", "entity": [], "task": "NER"}
{"text": "However , natural RBC - based products suffer from limited shelf life due to pathological contamination and also present risks of refractoriness , graft - versus - host disease , immunosuppression , and acute lung injury .", "entity": [], "task": "NER"}
{"text": "These issues can be only partially resolved by pathogen reduction technologies , serological blood testing , leukoreduction , and specialized storage ; hence , they severely affect the efficacy and safety of the blood products .", "entity": [], "task": "NER"}
{"text": "Consequently , there is a significant interest in synthetic RBC analogues that can mimic its oxygen - transport properties while allowing convenient manufacture , reproducibility , long shelf life , and reduced biological risks .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [93, 99]}], "task": "NER"}
{"text": "To this end , the current Review provides a comprehensive description and discussion of the various research approaches and current state - of - the - art in synthetically mimicking RBC ' s oxygen - carrying biochemical properties , as well as the biophysical parameters ( shape , size and mechanical modulus ) that influence RBCs ' hemodynamic transport properties in blood flow .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [190, 196]}], "task": "NER"}
{"text": "Diabetes , perioperative ischaemia and volatile anaesthetics : consequences of derangements in myocardial substrate metabolism .", "entity": [], "task": "NER"}
{"text": "Volatile anaesthetics exert protective effects on the heart against perioperative ischaemic injury .", "entity": [], "task": "NER"}
{"text": "However , there is growing evidence that these cardioprotective properties are reduced in case of type 2 diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "A strong predictor of postoperative cardiac function is myocardial substrate metabolism .", "entity": [], "task": "NER"}
{"text": "In the type 2 diabetic heart , substrate metabolism is shifted from glucose utilisation to fatty acid oxidation , resulting in metabolic inflexibility and cardiac dysfunction .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [68, 75]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [91, 101]}], "task": "NER"}
{"text": "The ischaemic heart also loses its metabolic flexibility and can switch to glucose or fatty acid oxidation as its preferential state , which may deteriorate cardiac function even further in case of type 2 diabetes mellitus . Recent experimental studies suggest that the cardioprotective properties of volatile anaesthetics partly rely on changing myocardial substrate metabolism .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [75, 82]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [86, 96]}], "task": "NER"}
{"text": "Interventions that target at restoration of metabolic derangements , like lifestyle and pharmacological interventions , may therefore be an interesting candidate to reduce perioperative complications .", "entity": [], "task": "NER"}
{"text": "This review will focus on the current knowledge regarding myocardial substrate metabolism during volatile anaesthesia in the obese and type 2 diabetic heart during perioperative ischaemia .", "entity": [], "task": "NER"}
{"text": "Repurposing CRISPR as an RNA - guided platform for sequence - specific control of gene expression .", "entity": [], "task": "NER"}
{"text": "Targeted gene regulation on a genome - wide scale is a powerful strategy for interrogating , perturbing , and engineering cellular systems .", "entity": [], "task": "NER"}
{"text": "Here , we develop a method for controlling gene expression based on Cas9 , an RNA - guided DNA endonuclease from a type II CRISPR system .", "entity": [], "task": "NER"}
{"text": "We show that a catalytically dead Cas9 lacking endonuclease activity , when coexpressed with a guide RNA , generates a DNA recognition complex that can specifically interfere with transcriptional elongation , RNA polymerase binding , or transcription factor binding .", "entity": [], "task": "NER"}
{"text": "This system , which we call CRISPR interference ( CRISPRi ) , can efficiently repress expression of targeted genes in Escherichia coli , with no detectable off - target effects .", "entity": [], "task": "NER"}
{"text": "CRISPRi can be used to repress multiple target genes simultaneously , and its effects are reversible .", "entity": [], "task": "NER"}
{"text": "We also show evidence that the system can be adapted for gene repression in mammalian cells .", "entity": [], "task": "NER"}
{"text": "This RNA - guided DNA recognition platform provides a simple approach for selectively perturbing gene expression on a genome - wide scale .", "entity": [], "task": "NER"}
{"text": "Novel effects of ectoine , a bacteria - derived natural tetrahydropyrimidine , in experimental colitis .", "entity": [{"entity": "ectoine", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "tetrahydropyrimidine", "entity_type": "Chemical", "pos": [56, 76]}], "task": "NER"}
{"text": "Evidence suggests an important role of intestinal barrier dysfunction in the etiology of inflammatory bowel disease ( IBD ) .", "entity": [], "task": "NER"}
{"text": "Therefore stabilizing mucosal barrier function constitutes a new therapeutic approach in its management .", "entity": [], "task": "NER"}
{"text": "Ectoine is a compatible solute produced by aerobic chemoheterotrophic and halophilic / halotolerant bacteria , where it acts as osmoprotectant and effective biomembrane stabilizer , protecting the producing cells from extreme environmental stress .", "entity": [{"entity": "Ectoine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Since this natural compound was also shown to prevent inflammatory responses associated with IBD , its potential usefulness was studied in a model of colitis .", "entity": [], "task": "NER"}
{"text": "Groups of rats were treated orally with different doses of ectoine ( 30 - 300mg / kg ) or sulfasalazine ( reference drug ) daily for 11 days .", "entity": [{"entity": "ectoine", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "sulfasalazine", "entity_type": "Chemical", "pos": [90, 103]}], "task": "NER"}
{"text": "On day 8 colitis was induced by intracolonic instillation of 2 , 4 , 6 - trinitrobenzenesulfonic acid , when overt signs of lesions develop within the next 3 days .", "entity": [{"entity": "2 , 4 , 6 - trinitrobenzenesulfonic acid", "entity_type": "Chemical", "pos": [61, 101]}], "task": "NER"}
{"text": "On day 12 , blood was withdrawn from the retro - orbital plexus of the rats and the animals were sacrificed .", "entity": [], "task": "NER"}
{"text": "The colon was excised and examined macroscopically and microscopically .", "entity": [], "task": "NER"}
{"text": "Relevant parameters of oxidative stress and inflammation were measured in serum and colon homogenates .", "entity": [], "task": "NER"}
{"text": "Induction of colitis led to marked weight loss , significant histopathological changes of the colon , and variable changes in levels of myeloperoxidase , reduced glutathione , malondialdehyde , and all inflammatory markers tested .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [162, 173]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [176, 191]}], "task": "NER"}
{"text": "Treatment with ectoine ameliorated the inflammatory changes in TNBS - induced colitis .", "entity": [{"entity": "ectoine", "entity_type": "Chemical", "pos": [15, 22]}], "task": "NER"}
{"text": "This effect was associated with reduction in the levels of TNF - alpha , IL - 1 beta , ICAM - 1 , PGE2 and LTB4 .", "entity": [], "task": "NER"}
{"text": "The findings suggest that intestinal barrier stabilizers from natural sources could offer new therapeutic measures for the management of IBD .", "entity": [], "task": "NER"}
{"text": "Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer ( Verbenaceae ) .", "entity": [], "task": "NER"}
{"text": "Medicinal plants are one of the most important sources of drugs used in the pharmaceutical industry .", "entity": [], "task": "NER"}
{"text": "Among traditional medicinal plants , Lippia gracilis Schauer ( Verbenaceae ) had been used for several medicinal purposes in Brazilian northeastern .", "entity": [], "task": "NER"}
{"text": "In this study , leaf essential oil ( EO ) of L . gracilis was prepared using hydrodistillation .", "entity": [], "task": "NER"}
{"text": "Followed by GC - MS analysis , its composition was characterized by the presence of thymol ( 55 . 50 % ) , as major constituent .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [84, 90]}], "task": "NER"}
{"text": "The effects of EO on cell proliferation and apoptosis induction were investigated in HepG2 cells .", "entity": [], "task": "NER"}
{"text": "Furthermore , mice bearing Sarcoma 180 tumor cells were used to confirm its in vivo effectiveness .", "entity": [], "task": "NER"}
{"text": "EO and its constituents ( thymol , p - cymene , gamma - terpinene and myrcene ) displayed cytotoxicity to different tumor cell lines .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "p - cymene", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "gamma - terpinene", "entity_type": "Chemical", "pos": [48, 65]}, {"entity": "myrcene", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "EO treatment caused G1 arrest in HepG2 cells accompanied by the induction of DNA fragmentation without affecting cell membrane integrity .", "entity": [], "task": "NER"}
{"text": "Cell morphology consistent with apoptosis and a remarkable activation of caspase - 3 were also observed , suggesting induction of caspase - dependent apoptotic cell death .", "entity": [], "task": "NER"}
{"text": "In vivo antitumor study showed tumor growth inhibition rates of 38 . 5 - 41 . 9 % .", "entity": [], "task": "NER"}
{"text": "In conclusion , the tested essential oil of L . gracilis leaves , which has thymol as its major constituent , possesses significant in vitro and in vivo antitumor activity .", "entity": [{"entity": "thymol", "entity_type": "Chemical", "pos": [76, 82]}], "task": "NER"}
{"text": "These data suggest that leaf essential oil of L . gracilis is a potential medicinal resource .", "entity": [], "task": "NER"}
{"text": "A mitochondrial ribosomal and RNA decay pathway blocks cell proliferation .", "entity": [], "task": "NER"}
{"text": "Proliferating cells require coordinated gene expression between the nucleus and mitochondria in order to divide , ensuring sufficient organelle number in daughter cells [ 1 ] .", "entity": [], "task": "NER"}
{"text": "However , the machinery and mechanisms whereby proliferating cells monitor mitochondria and coordinate organelle biosynthesis remain poorly understood .", "entity": [], "task": "NER"}
{"text": "Antibiotics inhibiting mitochondrial translation have emerged as therapeutics for human cancers because they block cell proliferation [ 2 , 3 ] .", "entity": [], "task": "NER"}
{"text": "These proliferative defects were attributable to modest decreases in mitochondrial respiration [ 3 , 4 ] , even though tumors are mainly glycolytic [ 5 ] and mitochondrial respiratory chain function appears to play a minor role in cell proliferation in vivo [ 6 ] .", "entity": [], "task": "NER"}
{"text": "Here we challenge this interpretation by demonstrating that one class of antiproliferative antibiotic induces stalled mitochondrial ribosomes , which triggers a mitochondrial ribosome and RNA decay pathway .", "entity": [], "task": "NER"}
{"text": "Rescue of the stalled mitochondrial ribosomes initiates a retrograde signaling response to block cell proliferation and occurs prior to any loss of mitochondrial respiration .", "entity": [], "task": "NER"}
{"text": "The loss of respiratory chain function is simply a downstream effect of impaired mitochondrial translation and not the antiproliferative signal .", "entity": [], "task": "NER"}
{"text": "This mitochondrial ribosome quality - control pathway is actively monitored in cells and constitutes an important organelle checkpoint for cell division .", "entity": [], "task": "NER"}
{"text": "High rates of pregnancy loss by subordinates leads to high reproductive skew in wild golden lion tamarins ( Leontopithecus rosalia ) .", "entity": [], "task": "NER"}
{"text": "Across taxa , cooperative breeding has been associated with high reproductive skew .", "entity": [], "task": "NER"}
{"text": "Cooperatively breeding golden lion tamarins ( Leontopithecus rosalia ) were long thought to have a monogynous mating system in which reproduction was limited to a single dominant female .", "entity": [], "task": "NER"}
{"text": "Subordinates with few reproductive opportunities delayed dispersal and remained in the natal group to provide alloparental care to siblings , thus allowing dominant reproductive females to meet the energetic needs associated with high rates of reproduction and successful infant rearing .", "entity": [], "task": "NER"}
{"text": "The goal of this study was to re - assess monogyny in wild golden lion tamarin groups based upon pregnancy diagnoses that used non - invasive enzyme immunoassay for progesterone and cortisol , combined with weekly data on individual weight gain , bi - annual physical examinations noting pregnancy and lactation status and daily behavioral observations .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [165, 177]}, {"entity": "cortisol", "entity_type": "Chemical", "pos": [182, 190]}], "task": "NER"}
{"text": "We established quantitative and qualitative criteria to detect and determine the timing of pregnancies that did not result in the birth of infants .", "entity": [], "task": "NER"}
{"text": "Pregnancy polygyny occurred in 83 % of golden lion tamarin groups studied .", "entity": [], "task": "NER"}
{"text": "The loss of 64 % of subordinate pregnancies compared to only 15 % by dominant females limited reproductive success mainly to dominant females , thus maintaining high reproductive skew in female golden lion tamarins .", "entity": [], "task": "NER"}
{"text": "Pregnancy loss by subordinate adults did not appear to result from dominant interference in subordinate hormonal mechanisms , but more likely resulted from subordinate abandonment of newborn infants to mitigate dominant aggression .", "entity": [], "task": "NER"}
{"text": "Synthesis of novel 2 - amino - 4 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 6 - aryl - 4H - pyran - 3 - carbonitrile derivatives as antimicrobial and antioxidant agents .", "entity": [{"entity": "2 - amino - 4 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 6 - aryl - 4H - pyran - 3 - carbonitrile", "entity_type": "Chemical", "pos": [19, 136]}], "task": "NER"}
{"text": "As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems , we have synthesized new compounds viz . , 2 - amino - 4 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 6 - aryl - 4H - pyran - 3 - carbonitriles ( 2a - i ) , 4 , 5 - diamino - 6 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 8 - aryl - 2 - oxo - 2 , 6 - dihydrodipyrano [ 2 , 3 - b : 3 , 2 - e ] pyridine - 3 - carbonitriles ( 3a - i ) , 4 - amino - 5 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 - yl ) - 7 - aryl - 1H - pyrano [ 2 , 3 - d ] pyrimidin - 2 ( 5H ) - ones ( 4a - i ) , 4 - amino - 5 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 7 - aryl - 1H - pyrano [ 2 , 3 - d ] pyrimidin - 2 ( 5H ) - thiones ( 5a - i ) , 4 - ( 5 ' - subtituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 6 - aryl - 1 , 4 - dihydropyrano [ 2 , 3 - c ] pyrazol - 3 - amines ( 6a - i ) and 5 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 7 - aryl - 3H - pyrano [ 2 , 3 - d ] pyrimidin - 4 ( 5H ) - ones ( 7a - i ) .", "entity": [{"entity": "indole", "entity_type": "Chemical", "pos": [80, 86]}, {"entity": "2 - amino - 4 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 6 - aryl - 4H - pyran - 3 - carbonitriles", "entity_type": "Chemical", "pos": [180, 298]}, {"entity": "4 , 5 - diamino - 6 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 8 - aryl - 2 - oxo - 2 , 6 - dihydrodipyrano [ 2 , 3 - b : 3 , 2 - e ] pyridine - 3 - carbonitriles", "entity_type": "Chemical", "pos": [312, 494]}, {"entity": "4 - amino - 5 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 - yl ) - 7 - aryl - 1H - pyrano [ 2 , 3 - d ] pyrimidin - 2 ( 5H ) - ones", "entity_type": "Chemical", "pos": [508, 647]}, {"entity": "4 - amino - 5 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 7 - aryl - 1H - pyrano [ 2 , 3 - d ] pyrimidin - 2 ( 5H ) - thiones", "entity_type": "Chemical", "pos": [661, 805]}, {"entity": "4 - ( 5 ' - subtituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 6 - aryl - 1 , 4 - dihydropyrano [ 2 , 3 - c ] pyrazol - 3 - amines", "entity_type": "Chemical", "pos": [819, 950]}, {"entity": "5 - ( 5 ' - substituted 2 ' - phenyl - 1H - indol - 3 ' - yl ) - 7 - aryl - 3H - pyrano [ 2 , 3 - d ] pyrimidin - 4 ( 5H ) - ones", "entity_type": "Chemical", "pos": [966, 1095]}], "task": "NER"}
{"text": "Antibacterial activity results revealed that , compound 6a showed promising activity versus Escherichia coli , Staphylococcus aureus and Klebsiella pneumoniae .", "entity": [], "task": "NER"}
{"text": "Compound 6d exhibited good activity against S . aureus , K . pneumoniae and Pseudomonas aeruginosa .", "entity": [], "task": "NER"}
{"text": "Antifungal activity results indicated that , compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus .", "entity": [], "task": "NER"}
{"text": "In case of antioxidant activity , compound 4a showed promising radical scavenging activity , ferric ions ( Fe ( 3 + ) ) reducing antioxidant power ( FRAP ) and metal chelating activity .", "entity": [{"entity": "ferric", "entity_type": "Chemical", "pos": [93, 99]}, {"entity": "Fe ( 3 + )", "entity_type": "Chemical", "pos": [107, 117]}], "task": "NER"}
{"text": "Antiproliferative effect of two novel COX - 2 inhibitors on human keratinocytes .", "entity": [], "task": "NER"}
{"text": "Selective COX - 2 inhibitors ( COXib ) belonging to the class of diaryl heterocycles ( e . g . , celecoxib , rofecoxib , etc . ) , are devoid of the undesirable effects due to their capacity to inhibit selectively inducible ( COX - 2 ) , responsible for inflammatory effects but not constitutive cyclooxygenase - 1 ( COX - 1 ) ( COX ) ; responsible for cytoprotective effects on gastric mucosa .", "entity": [{"entity": "diaryl heterocycles", "entity_type": "Chemical", "pos": [65, 84]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [97, 106]}, {"entity": "rofecoxib", "entity_type": "Chemical", "pos": [109, 118]}], "task": "NER"}
{"text": "In addition , several reports have identified an increased risk of cardiovascular events associated with the use of COXib .", "entity": [], "task": "NER"}
{"text": "We have developed a new series of anti - inflammatory agents ( 1 , 5 - diarylpyrrole - 3 - alkoxyethyl esters and ethers ) .", "entity": [{"entity": "1 , 5 - diarylpyrrole - 3 - alkoxyethyl esters and ethers", "entity_type": "Chemical", "pos": [63, 120]}], "task": "NER"}
{"text": "To evaluate the effect of two 1 , 5 - diarylpyrrole - 3 - alkoxyethyl ethers , VA441 and VA428 ( up to 100 mu M ) , respectively , in comparison with two well known COXib , celecoxib and rofecoxib , on HaCaT cell ( keratinocytes ) proliferation and toxicity .", "entity": [{"entity": "1 , 5 - diarylpyrrole - 3 - alkoxyethyl ethers", "entity_type": "Chemical", "pos": [30, 76]}, {"entity": "VA441", "entity_type": "Chemical", "pos": [79, 84]}, {"entity": "VA428", "entity_type": "Chemical", "pos": [89, 94]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [173, 182]}, {"entity": "rofecoxib", "entity_type": "Chemical", "pos": [187, 196]}], "task": "NER"}
{"text": "Crucial molecules in cell cycle progression , i . e . NF kappa B and ERK as targets / mediators and cyclin D1 and p21 Cip1 / Kip as final effectors were evaluated by Western blot , immunohystochemistry and q - PCR analysis .", "entity": [], "task": "NER"}
{"text": "Both compounds , VA441 and VA428 , showed a strong inhibition of cell proliferation , and did not exhibit cytotoxicity .", "entity": [{"entity": "VA441", "entity_type": "Chemical", "pos": [17, 22]}, {"entity": "VA428", "entity_type": "Chemical", "pos": [27, 32]}], "task": "NER"}
{"text": "The anti - proliferative effect was accompanied by a strong activation of ERK and induction of the cell cycle inhibitor p21 .", "entity": [], "task": "NER"}
{"text": "In addition , there was a clear inhibition of the transcription factor NF - kappa B and downregulation of cyclin D1 , with enforced inhibition of the HaCaT cell cycle progression .", "entity": [], "task": "NER"}
{"text": "These data suggest that compounds VA441 and VA428 , along with their role in inhibiting COX - 2 and inflammation , could have a possible therapeutic ( topical and systemic ) use against skin proliferative disorders , such as psoriasis .", "entity": [{"entity": "VA441", "entity_type": "Chemical", "pos": [34, 39]}, {"entity": "VA428", "entity_type": "Chemical", "pos": [44, 49]}], "task": "NER"}
{"text": "Role of oxidative stress in chemical allergens induced skin cells activation .", "entity": [], "task": "NER"}
{"text": "Allergic contact dermatitis ( ACD ) is an important occupational and environmental disease caused by topical exposure to chemical allergens .", "entity": [], "task": "NER"}
{"text": "It describes the adverse effects that may results when exposure to a chemical elicits a T cell - mediated inflammatory skin disease .", "entity": [], "task": "NER"}
{"text": "The ability of contact sensitizers to induce the oxidative stress pathway in keratinocytes and dendritic cells has been confirmed by several authors .", "entity": [], "task": "NER"}
{"text": "Reactive oxygen species ( ROS ) can serve as essential second messengers mediating cellular responses resulting in immune cells activation .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [9, 15]}], "task": "NER"}
{"text": "Oxidative stress may be the starter point , as it leads to the activation of transcription factors and signaling pathways , including NF - kB and p38 MAPK , which leads to the release of cytokines and chemokines .", "entity": [], "task": "NER"}
{"text": "ROS are also involved in the activation of the NLRP3 / NALP3 inflammasome , which is required to direct the proteolytic maturation of inflammatory cytokines such as IL - 1 beta and IL - 18 , which are all integral to the process of dendritic cells mobilization , migration and functional maturation .", "entity": [], "task": "NER"}
{"text": "Moreover , emerging evidence correlates ROS to changes in the constitution of the extracellular microenvironment found to facilitate ACD .", "entity": [], "task": "NER"}
{"text": "The purpose of this review is to provide both conceptual and technical frameworks on the role of oxidative stress in chemical allergy .", "entity": [], "task": "NER"}
{"text": "Relative expression of cholesterol transport - related proteins and inflammation markers through the induction of 7 - ketosterol - mediated stress in Caco - 2 cells .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "7 - ketosterol", "entity_type": "Chemical", "pos": [114, 128]}], "task": "NER"}
{"text": "Human diets contain sterol oxidation products that can induce cytotoxic effects , mainly caused by cholesterol oxides .", "entity": [{"entity": "sterol", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "cholesterol oxides", "entity_type": "Chemical", "pos": [99, 117]}], "task": "NER"}
{"text": "However , phytosterol oxides effects have been less extensively investigated .", "entity": [{"entity": "phytosterol oxides", "entity_type": "Chemical", "pos": [10, 28]}], "task": "NER"}
{"text": "This study evaluates the production of inflammatory biomarkers ( IL - 1 beta , IL - 8 , IL - 10 , TNF alpha ) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism ( NPC1L1 , ABCG5 / 8 , HMGCoA , ACAT ) produced by 7 - ketosterols ( stigmasterol / cholesterol ) in Caco - 2 cells .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [183, 194]}, {"entity": "HMGCoA", "entity_type": "Chemical", "pos": [244, 250]}, {"entity": "7 - ketosterols", "entity_type": "Chemical", "pos": [272, 287]}, {"entity": "stigmasterol", "entity_type": "Chemical", "pos": [290, 302]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [305, 316]}], "task": "NER"}
{"text": "These effects were linked to intracellular signaling pathways by using several inhibitors .", "entity": [], "task": "NER"}
{"text": "Results showed 7 - ketostigmasterol to have a greater proinflammatory potential than 7 - ketocholesterol .", "entity": [{"entity": "7 - ketostigmasterol", "entity_type": "Chemical", "pos": [15, 35]}, {"entity": "7 - ketocholesterol", "entity_type": "Chemical", "pos": [85, 104]}], "task": "NER"}
{"text": "In non - pre - treated cells , only efflux transporters were down - regulated by 7 - ketosterols , showing a greater influence upon ABCG5 expression .", "entity": [{"entity": "7 - ketosterols", "entity_type": "Chemical", "pos": [81, 96]}], "task": "NER"}
{"text": "Cell - pre - incubation with bradykinin induced changes in ABCG expression levels after 7 - ketostigmasterol - incubation ; however , the energetic metabolism inhibition reduced NPC1L1 expression only in 7 - ketocholesterol - incubated cells .", "entity": [{"entity": "bradykinin", "entity_type": "Chemical", "pos": [29, 39]}, {"entity": "7 - ketostigmasterol", "entity_type": "Chemical", "pos": [88, 108]}, {"entity": "7 - ketocholesterol", "entity_type": "Chemical", "pos": [204, 223]}], "task": "NER"}
{"text": "In non - pre - treated cells , HMG - CoA was up - regulated by both 7 - ketosterols .", "entity": [{"entity": "HMG - CoA", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "7 - ketosterols", "entity_type": "Chemical", "pos": [68, 83]}], "task": "NER"}
{"text": "However , exposure to inhibitors down - regulated the expression levels , mainly in 7 - ketocholesterol - incubated cells .", "entity": [{"entity": "7 - ketocholesterol", "entity_type": "Chemical", "pos": [84, 103]}], "task": "NER"}
{"text": "While ACAT expression values in non - pre - treated cells were unchanged , exposure to inhibitors caused down - regulation of mRNA levels .", "entity": [], "task": "NER"}
{"text": "These results suggest that internalization and excretion of 7 - ketostigmasterol is probably influenced by [ Ca ] i , which also could mediate HMGCoA activity in POPs metabolism .", "entity": [{"entity": "7 - ketostigmasterol", "entity_type": "Chemical", "pos": [60, 80]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [109, 111]}, {"entity": "HMGCoA", "entity_type": "Chemical", "pos": [143, 149]}], "task": "NER"}
{"text": "However , energetic metabolism and reducing equivalents exert different influences upon the 7 - ketosterol internalization .", "entity": [{"entity": "7 - ketosterol", "entity_type": "Chemical", "pos": [92, 106]}], "task": "NER"}
{"text": "Neuroprotective effects of neolignans isolated from Magnoliae Cortex against glutamate - induced apoptotic stimuli in HT22 cells .", "entity": [{"entity": "neolignans", "entity_type": "Chemical", "pos": [27, 37]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [77, 86]}], "task": "NER"}
{"text": "In the course of screening for neuroprotective natural products , Magnoliae Cortex showed potent inhibition of hippocampal neuronal HT22 cell death .", "entity": [], "task": "NER"}
{"text": "Obovatol , honokiol , and magnolol were isolated from the ethanolic extract of Magnoliae Cortex .", "entity": [{"entity": "Obovatol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "honokiol", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "magnolol", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "Isolated compounds obovatol , honokiol , and magnolol were protective against 5mM glutamate - induced cell death .", "entity": [{"entity": "obovatol", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "honokiol", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "magnolol", "entity_type": "Chemical", "pos": [45, 53]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "When cells were stressed using glutamate , cell viability decreased to 16 . 98 +/- 4 . 58 % over the control ( 100 . 00 +/- 10 . 15 % ) .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "In contrast , 10 mu M obovatol , 10 mu M honokiol , and 50 mu M magnolol increased cell viability to 91 . 80 +/- 1 . 70 % , 93 . 59 +/- 1 . 93 % , and 85 . 36 +/- 7 . 40 % , respectively .", "entity": [{"entity": "obovatol", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "honokiol", "entity_type": "Chemical", "pos": [41, 49]}, {"entity": "magnolol", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "The neuroprotective effects of obovatol and honokiol were attributable to the inhibition of intracellular reactive oxygen species production , followed by protection of the mitochondrial membrane potential ( Delta Psi m ) , recovery of Bcl - 2 and Bid levels , inhibition of apoptosis - inducing factor expression , and phosphorylation of mitogen - activated protein kinases such as p38 kinases , extracellular signal - regulated kinases , and c - Jun N - terminal kinases .", "entity": [{"entity": "obovatol", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "honokiol", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [115, 121]}, {"entity": "N", "entity_type": "Chemical", "pos": [452, 453]}], "task": "NER"}
{"text": "On the contrary , magnolol did not show any significant effect on the Delta Psi m and apoptotic factors .", "entity": [{"entity": "magnolol", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "Among three compounds , obovatol most strongly scavenged 2 , 2 - diphenyl - 1 - picrylhydrazyl radicals and inhibited the elevation of intracellular reactive oxygen species levels in glutamate - stressed HT22 cells .", "entity": [{"entity": "obovatol", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "2 , 2 - diphenyl - 1 - picrylhydrazyl", "entity_type": "Chemical", "pos": [57, 94]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [158, 164]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [183, 192]}], "task": "NER"}
{"text": "These data suggest that obovatol and honokiol may have clinical applications for preventing neurodegenerative disorders .", "entity": [{"entity": "obovatol", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "honokiol", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP - 9 through Akt pathway in MDA - MB - 231 breast cancer cells .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [43, 47]}], "task": "NER"}
{"text": "Invasion , either directly or via metastasis formation , is the main cause of death in cancer patients , development of efficient anti - invasive agents is an important research challenge .", "entity": [], "task": "NER"}
{"text": "In order to obtain more potent inhibitors , a series of brartemicin analogs were synthesized and evaluated for their inhibitory activity against invasion .", "entity": [{"entity": "brartemicin", "entity_type": "Chemical", "pos": [56, 67]}], "task": "NER"}
{"text": "Among the synthetic analogs tested , DMBT , 6 , 6 ' - bis ( 2 , 3 - dimethoxybenzoyl ) - a , a - d - trehalose , was found to be the most potent anti - invasive agent .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [37, 41]}, {"entity": "6 , 6 ' - bis ( 2 , 3 - dimethoxybenzoyl ) - a , a - d - trehalose", "entity_type": "Chemical", "pos": [44, 110]}], "task": "NER"}
{"text": "But the effects of DMBT on breast cancer cells were not known .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [19, 23]}], "task": "NER"}
{"text": "In this study , the effects of DMBT on invasion and metastasis in MDA - MB - 231 cells were investigated .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "MTT assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "DMBT", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "DMBT could inhibit invasion , migration and tube formation of HUVECs .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Gelatin zymography showed that DMBT inhibited secretion and activity of MMP - 9 .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF , p - VEGFR - 2 , p - EGFR , and p - Akt .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [35, 39]}], "task": "NER"}
{"text": "These results suggested that DMBT could inhibit invasion and angiogenesis by downregulation of VEGFand MMP - 9 , resulting from the inhibition of Akt pathway .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "DMBT might be a promising lead molecule for the anti - metastasis and serve as a therapeutic agent to inhibit breast cancer cell invasion and metastasis .", "entity": [{"entity": "DMBT", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Curcumin loaded solid lipid nanoparticles : An efficient formulation approach for cerebral ischemic reperfusion injury in rats .", "entity": [{"entity": "Curcumin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "SCOPE : To evaluate curcumin loaded solid lipid nanoparticles ( C - SLNs ) in the experimental paradigm of cerebral ischemia ( BCCAO model ) in rats .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "METHODS AND RESULTS : Oral administration of free curcumin and C - SLNs ( 25 and 50mg / kg ) was started 5days prior and continued for 3days after BCCAO .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Alleviation in behavioral , oxidative and nitrosative stress , acetylcholinesterase , mitochondrial enzyme complexes , and physiological parameters were assessed .", "entity": [], "task": "NER"}
{"text": "Confirmation of effective brain delivery of C - SLNs ( p . o ) was done using biodistribution studies in mice and confocal microscopy of rat brain section .", "entity": [], "task": "NER"}
{"text": "There was an improvement of 90 % in cognition and 52 % inhibition of acetylcholinesterase versus cerebral ischemic group ( I / R ) .", "entity": [], "task": "NER"}
{"text": "Neurological scoring improved by 79 % .", "entity": [], "task": "NER"}
{"text": "Levels of superoxide dismutase , catalase , glutathione , and mitochondrial complex enzyme activities were significantly increased , while lipid peroxidation , nitrite , and acetylcholinesterase levels decreased ( p < 0 . 05 ) after C - SLNs administration .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [44, 55]}, {"entity": "nitrite", "entity_type": "Chemical", "pos": [160, 167]}], "task": "NER"}
{"text": "It is noteworthy to report the restoration of SOD , GSH , catalase , and mitochondrial complex enzyme levels equivalent to sham control values .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "Gamma - scintigraphic studies show 16 . 4 and 30 times improvement in brain bioavailability ( AUC ) upon oral and i . v administration of C - SLNs versus solubilized curcumin ( C - S ) .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [166, 174]}], "task": "NER"}
{"text": "CONCLUSIONS : Study indicates protective role of curcumin against cerebral ischemic insult ; provided it is packaged suitably for improved brain delivery .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Steroids excreted in urine by neonates with 21 - hydroxylase deficiency .", "entity": [{"entity": "Steroids", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Characterization , using GC - MS and GC - MS / MS , of 11oxo - pregnanes and 11oxo - pregnenes .", "entity": [{"entity": "11oxo - pregnanes", "entity_type": "Chemical", "pos": [55, 72]}, {"entity": "11oxo - pregnenes", "entity_type": "Chemical", "pos": [77, 94]}], "task": "NER"}
{"text": "In 21 - hydroxylase deficiency , urinary metabolites of 21 - deoxycortisol , mainly derived from its 11oxo form 21 - deoxycortisone , are indicators of intra - adrenal overproduction of 17 - hydroxyprogesterone .", "entity": [{"entity": "21 - deoxycortisol", "entity_type": "Chemical", "pos": [56, 74]}, {"entity": "11oxo", "entity_type": "Chemical", "pos": [101, 106]}, {"entity": "21 - deoxycortisone", "entity_type": "Chemical", "pos": [112, 131]}, {"entity": "17 - hydroxyprogesterone", "entity_type": "Chemical", "pos": [186, 210]}], "task": "NER"}
{"text": "In affected neonates these metabolites are numerous and most have not been previously described .", "entity": [], "task": "NER"}
{"text": "This work forms the concluding part of a comprehensive study of urinary steroids , aiming to enhance the diagnosis of this disorder and to further elucidate steroid metabolism in neonates .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [72, 80]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [157, 164]}], "task": "NER"}
{"text": "Cortisol metabolites found in untreated patients , similarly almost exclusively present in their 11oxo form in neonates , have been included for completeness .", "entity": [{"entity": "Cortisol", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "11oxo", "entity_type": "Chemical", "pos": [97, 102]}], "task": "NER"}
{"text": "Steroids were analyzed , after extraction and enzymatic conjugate hydrolysis , as methyloxime - trimethylsilyl ether derivatives on gas - chromatographs coupled to quadrupole and ion - trap mass - spectrometers .", "entity": [{"entity": "Steroids", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "methyloxime - trimethylsilyl ether", "entity_type": "Chemical", "pos": [82, 116]}], "task": "NER"}
{"text": "GC - MS and GC - MS / MS spectra were used together to determine the structure of hitherto undescribed 11oxo - pregnane ( enes ) .", "entity": [{"entity": "11oxo - pregnane ( enes )", "entity_type": "Chemical", "pos": [103, 128]}], "task": "NER"}
{"text": "Few GC - MS features were associated with the presence of the non - derivatizeable 11oxo group in pregnane ( ene ) s .", "entity": [{"entity": "11oxo", "entity_type": "Chemical", "pos": [83, 88]}, {"entity": "pregnane ( ene ) s", "entity_type": "Chemical", "pos": [98, 116]}], "task": "NER"}
{"text": "GC - MS / MS contributed only to the characterization of structures outside the C - ring , as described in the preceding parts of this study .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [1, 2]}], "task": "NER"}
{"text": "Parallels were found between the metabolism of 21 - deoxycortisone and cortisone .", "entity": [{"entity": "21 - deoxycortisone", "entity_type": "Chemical", "pos": [47, 66]}, {"entity": "cortisone", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "The major metabolic pathway was that of classical 3 alpha , 5 beta - reduction with a prominent further hydroxylation , predominantly at C6 .", "entity": [], "task": "NER"}
{"text": "Oxidation of the 6 - hydroxyl was also common .", "entity": [{"entity": "6 - hydroxyl", "entity_type": "Chemical", "pos": [17, 29]}], "task": "NER"}
{"text": "We conclude that further oxygenated metabolites of 21 - deoxycortisone have potential as more reliable markers of 21 - hydroxylase deficiency in the early neonatal period , because their levels are higher during that period of life than for the classical marker 11oxo - pregnanetriol .", "entity": [{"entity": "21 - deoxycortisone", "entity_type": "Chemical", "pos": [51, 70]}, {"entity": "11oxo - pregnanetriol", "entity_type": "Chemical", "pos": [262, 283]}], "task": "NER"}
{"text": "In vivo assessment of specific cytotoxic T lymphocyte killing .", "entity": [], "task": "NER"}
{"text": "The direct killing of target cells by cytotoxic T lymphocytes ( CTLs ) plays a fundamental role in protective immunity to viral , bacterial , protozoan and fungi infections , as well as to tumor cells .", "entity": [], "task": "NER"}
{"text": "In vivo cytotoxic assays take into account the interaction of target and effector cells in the context of the proper microenvironment making the analysis biologically more relevant than in vitro cytotoxic assays .", "entity": [], "task": "NER"}
{"text": "Thus , the development , improvement and validation of in vivo methods are necessary in view of the importance of the results they may provide .", "entity": [], "task": "NER"}
{"text": "We describe and discuss in this manuscript a method to evaluate in vivo specific cytotoxic T lymphocyte killing .", "entity": [], "task": "NER"}
{"text": "We used as model system mice immunized with human recombinant replication - deficient adenovirus 5 ( HAd5 ) containing different transgenes as the trigger of a CTL - mediated immune response .", "entity": [], "task": "NER"}
{"text": "To these mice , we adoptively transferred syngeneic cells labeled with different vital fluorescent dyes .", "entity": [], "task": "NER"}
{"text": "Donor cells were pulsed ( target ) or not ( control non - target ) with distinct CD8 T - cell epitopes , mixed in a 1 : 1 ratio and injected i . v . into immunized or non - immunized recipient mice .", "entity": [], "task": "NER"}
{"text": "After 18 - 24h , spleen cells are collected and analysed by flow cytometry .", "entity": [], "task": "NER"}
{"text": "A deviation from the 1 : 1 ratio of control and target cell populations indicates antigen specific lysis of target cells .", "entity": [], "task": "NER"}
{"text": "Protein nitration promotes inducible nitric oxide synthase transcription mediated by NF - kappa B in high glucose - stimulated human lens epithelial cells .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "Although an important event in hyperglycaemia - induced oxidative stress is the nuclear factor - kappa b ( NF - kappa B ) - activated inducible nitric oxide synthase ( iNOS ) expression , the underlying mechanism is not fully characterized .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [144, 156]}], "task": "NER"}
{"text": "Peroxynitrite , formed from NO and superoxide , can induce multiple proteins nitration , even including NF - kappa B and iNOS , to alter their functions .", "entity": [{"entity": "Peroxynitrite", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "NO", "entity_type": "Chemical", "pos": [28, 30]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [35, 45]}], "task": "NER"}
{"text": "In this study , we found high glucose caused conspicuous nitration of nuclear NF - kappa B p65 and its co - activator p300 in human lens epithelial cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "The nitration of NF - kappa B and p300 promoted their co - localization and binding to ensure the activation of the iNOS gene transcription .", "entity": [], "task": "NER"}
{"text": "Moreover , nearly all predicted NF - kappa B binding sites in the human iNOS gene promoter were responsive to high glucose stimulation , might for a synergistic role .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [115, 122]}], "task": "NER"}
{"text": "While , only the NF - kappa B binding site - 5212 showed significant alterations by high glucose and peroxynitrite stimulations , indicating it a more important role in the protein nitration promoted iNOS gene transcription .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "peroxynitrite", "entity_type": "Chemical", "pos": [101, 114]}], "task": "NER"}
{"text": "Our results demonstrated that protein nitration can promote the NF - kappa B - activated iNOS gene transcription in human lens epithelial cells by high glucose stimulation .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [152, 159]}], "task": "NER"}
{"text": "Effect of serum on diesel exhaust particles ( DEP ) - induced apoptosis of airway epithelial cells in vitro .", "entity": [], "task": "NER"}
{"text": "Patients with chronic airway diseases may be more susceptible to adverse effects of air pollutants including diesel exhaust particles ( DEP ) .", "entity": [], "task": "NER"}
{"text": "We investigated effects of foetal calf serum ( FCS ) on DEP - induced changes in airway epithelial cell apoptosis and inflammation .", "entity": [], "task": "NER"}
{"text": "DEP ( 50 - 200 mu g / ml ) increased A549 cell viability in the absence of FCS .", "entity": [], "task": "NER"}
{"text": "In the presence of 3 . 3 % FCS , DEP ( 50 - 400 mu g / ml ) decreased A549 cell viability .", "entity": [], "task": "NER"}
{"text": "N - acetylcysteine ( NAC , 33 mM ) and the c - jun N - terminal kinase ( JNK ) inhibitor ( SP600125 , 33 mu M ) further decreased the viability in the presence of DEP ( 200 mu g / ml ) and 3 . 3 % FCS .", "entity": [{"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [21, 24]}, {"entity": "N", "entity_type": "Chemical", "pos": [51, 52]}, {"entity": "SP600125", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "Under serum - free ( SF ) condition , DEP ( 50 mu g / ml ) reduced apoptotic cells ; however , when 3 . 3 % FCS added to the culture medium , this effect was abolished .", "entity": [], "task": "NER"}
{"text": "DEP ( 200 mu g / ml ) induced mRNA expression of p21 ( CIP1 / WAF1 ) both in absence or presence of 3 . 3 % FCS and enhanced JNK2 mRNA expression only in the presence of 3 . 3 % FCS .", "entity": [], "task": "NER"}
{"text": "Under SF condition , DEP ( 50 mu g / ml ) induced mRNA expression for p27 and p53 , whereas cyclin E mRNA expression was inhibited by DEP ( 50 and 200 mu g / ml ) .", "entity": [], "task": "NER"}
{"text": "Furthermore , DEP ( 200 mu g / ml ) decreased the release of interleukin ( IL ) - 8 in the absence of FCS .", "entity": [], "task": "NER"}
{"text": "In conclusion , FCS modulates effects of DEP on cell death , cell cycle and apoptosis regulating proteins , and IL - 8 release by activating oxidant stress pathways , JNK and NF - kappa B .", "entity": [], "task": "NER"}
{"text": "Extravasation of serum , as occurs in the inflamed airways of patients with chronic airway diseases such as asthma and COPD , may render airway epithelial cells more susceptible to the deleterious effects of DEP .", "entity": [], "task": "NER"}
{"text": "Neuropeptide S enhances memory and mitigates memory impairment induced by MK801 , scopolamine or A beta 1 - 42 in mice novel object and object location recognition tasks .", "entity": [{"entity": "MK801", "entity_type": "Chemical", "pos": [74, 79]}, {"entity": "scopolamine", "entity_type": "Chemical", "pos": [82, 93]}], "task": "NER"}
{"text": "Neuropeptide S ( NPS ) , the endogenous ligand of NPSR , has been shown to promote arousal and anxiolytic - like effects .", "entity": [], "task": "NER"}
{"text": "According to the predominant distribution of NPSR in brain tissues associated with learning and memory , NPS has been reported to modulate cognitive function in rodents .", "entity": [], "task": "NER"}
{"text": "Here , we investigated the role of NPS in memory formation , and determined whether NPS could mitigate memory impairment induced by selective N - methyl - d - aspartate receptor antagonist MK801 , muscarinic cholinergic receptor antagonist scopolamine or A beta 1 - 42 in mice , using novel object and object location recognition tasks .", "entity": [{"entity": "N - methyl - d - aspartate", "entity_type": "Chemical", "pos": [142, 168]}, {"entity": "MK801", "entity_type": "Chemical", "pos": [189, 194]}, {"entity": "scopolamine", "entity_type": "Chemical", "pos": [240, 251]}], "task": "NER"}
{"text": "Intracerebroventricular ( i . c . v . ) injection of 1 nmol NPS 5 min after training not only facilitated object recognition memory formation , but also prolonged memory retention in both tasks .", "entity": [], "task": "NER"}
{"text": "The improvement of object recognition memory induced by NPS could be blocked by the selective NPSR antagonist SHA 68 , indicating pharmacological specificity .", "entity": [{"entity": "SHA 68", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "Then , we found that i . c . v . injection of NPS reversed memory disruption induced by MK801 , scopolamine or A beta 1 - 42 in both tasks .", "entity": [{"entity": "MK801", "entity_type": "Chemical", "pos": [88, 93]}, {"entity": "scopolamine", "entity_type": "Chemical", "pos": [96, 107]}], "task": "NER"}
{"text": "In summary , our results indicate that NPS facilitates memory formation and prolongs the retention of memory through activation of the NPSR , and mitigates amnesia induced by blockage of glutamatergic or cholinergic system or by A beta 1 - 42 , suggesting that NPS / NPSR system may be a new target for enhancing memory and treating amnesia .", "entity": [], "task": "NER"}
{"text": "Antivenom for snakebite envenoming in Sri Lanka : The need for geographically specific antivenom and improved efficacy .", "entity": [], "task": "NER"}
{"text": "Sri Lanka is a tropical developing island nation that endures significant economic and medical burden as a result of snakebite envenomation , having not only a high prevalence of envenomations , but also one of the highest incidence rates ( 200 snakebites / 100 , 000 people / year ) of venomous snakebite in the world ( Kasturiratne et al . , 2005 ) .", "entity": [], "task": "NER"}
{"text": "Ironically , the very snakes responsible for this human morbidity and mortality are a valuable a biomedical and ecological national resource , despite the medical and economic consequences of envenomation .", "entity": [], "task": "NER"}
{"text": "Currently , no snake antivenom is produced using venoms from native Sri Lankan snakes as immunogens , and there is a true need for an efficacious Sri Lanka , poly - specific snake antivenom .", "entity": [], "task": "NER"}
{"text": "An approach to fulfilling this need via combining the scientific , technological and economical resources from Costa Rica and the United States with the knowledge and talent of Sri Lankan official governmental agencies , legal counsels , environmental , medical and veterinary academic institutions , and religious and cultural leaders has been initiated , coordinated and funded by Animal Venom Research International ( AVRI ) , a nonprofit charity .", "entity": [], "task": "NER"}
{"text": "This bridging of nations and the cooperative pooling of their resources represents a potential avenue for antivenom development in a developing country that suffers the consequences of few specific resources for the medical management of venomous snakebite .", "entity": [], "task": "NER"}
{"text": "The desired final outcome of such an endeavor for Sri Lanka is , most importantly , improved medical outcomes for snakebite patients , with enhanced and expanded science and technology relating to snake venoms and antivenoms , and the collateral benefits of reduced economic cost for the country .", "entity": [], "task": "NER"}
{"text": "In chemico evaluation of prohapten skin sensitizers : behavior of 2 - methoxy - 4 - ( (1) (3) C ) methylphenol in the peroxidase peptide reactivity assay ( PPRA ) as an alternative to animal testing .", "entity": [{"entity": "2 - methoxy - 4 - ( (1) (3) C ) methylphenol", "entity_type": "Chemical", "pos": [66, 110]}], "task": "NER"}
{"text": "In chemico methods , based on the assessment of a hapten ' s reactivity toward peptides , have been proposed as alternative methods for the assessment of the skin sensitizing potential of chemicals .", "entity": [], "task": "NER"}
{"text": "However , even with these approaches showing promise , a major drawback is the activation of prohaptens , i . e . molecules needing a metabolic activation to become reactive and therefore sensitizing .", "entity": [], "task": "NER"}
{"text": "Recently , it has been proposed to couple an enzymatic activation step based on horseradish peroxidase ( HRP ) / hydrogen peroxide to such peptide reactivity assays .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [113, 130]}], "task": "NER"}
{"text": "To evaluate this approach , the behavior of 2 - methoxy - 4 - methylphenol ( 2M4MP ) , reported as a moderate sensitizer according to the Local Lymph Node Assay ( LLNA ) , has been investigated in this assay .", "entity": [{"entity": "2 - methoxy - 4 - methylphenol", "entity_type": "Chemical", "pos": [44, 74]}, {"entity": "2M4MP", "entity_type": "Chemical", "pos": [77, 82]}], "task": "NER"}
{"text": "To follow the reaction with the peptides and characterize more easily intermediates and adducts , the molecule was first ( 13 ) C isotopically substituted at the most probable reactive position .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [121, 129]}], "task": "NER"}
{"text": "When 2M4MP was incubated with HRP / H2O2 in a mixture PBS ( pH 7 . 4 , 0 . 1M ) / acetonitrile 2 : 1 , two main products were formed deriving from the formation of a quinone methide 2M4MQ subsequently trapped by either H2O2 or H2O to form a benzylic hydroperoxide or alcohol , respectively .", "entity": [{"entity": "2M4MP", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [82, 94]}, {"entity": "2M4MQ", "entity_type": "Chemical", "pos": [182, 187]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [219, 223]}, {"entity": "H2O", "entity_type": "Chemical", "pos": [227, 230]}, {"entity": "benzylic hydroperoxide", "entity_type": "Chemical", "pos": [241, 263]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [267, 274]}], "task": "NER"}
{"text": "When nucleophiles such as GSH or a peptide containing a cysteine residue ( Pep - Cys ) were present in the reaction medium , the quinone methide 2M4MQ was trapped by the more nucleophilic thiol function to form thio - adducts .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "2M4MQ", "entity_type": "Chemical", "pos": [145, 150]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [188, 193]}, {"entity": "thio", "entity_type": "Chemical", "pos": [211, 215]}], "task": "NER"}
{"text": "No modifications of 2M4MP were observed when the same reactions were carried out without HRP confirming that the activation of the molecule was enzyme related .", "entity": [{"entity": "2M4MP", "entity_type": "Chemical", "pos": [20, 25]}], "task": "NER"}
{"text": "Amino nucleophiles were shown to be far less reactive towards the quinone methide 2M4MQ with only tiny formation of adducts with lysine or arginine side chains .", "entity": [{"entity": "Amino", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "2M4MQ", "entity_type": "Chemical", "pos": [82, 87]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [129, 135]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "In addition we demonstrated that the same enzymatic activation could also take place in a microemulsion based on sodium dodecyl sulfate / tert - butanol / chloroform / buffer .", "entity": [{"entity": "sodium dodecyl sulfate", "entity_type": "Chemical", "pos": [113, 135]}, {"entity": "tert - butanol", "entity_type": "Chemical", "pos": [138, 152]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [155, 165]}], "task": "NER"}
{"text": "Which metabolites circulate ?", "entity": [], "task": "NER"}
{"text": "Characterization of the circulating metabolites for a new chemical entity in humans is essential for safety assessment , an understanding of their contributions to pharmacologic activities , and their potential involvement in drug - drug interactions .", "entity": [], "task": "NER"}
{"text": "This review examines the abundance of metabolites relative to the total parent drug [ metabolite - to - parent ( M / P ) ratio ] from 125 drugs in relation to their structural and physicochemical characteristics , lipoidal permeability , protein binding , and fractional formation from parent ( fm ) .", "entity": [], "task": "NER"}
{"text": "Our analysis suggests that fm is the major determinant of total drug M / P ratio for amine , alcohol , N - and S - oxide , and carboxylic acid metabolites .", "entity": [{"entity": "amine", "entity_type": "Chemical", "pos": [85, 90]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [93, 100]}, {"entity": "N - and S - oxide", "entity_type": "Chemical", "pos": [103, 120]}, {"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [127, 142]}], "task": "NER"}
{"text": "Passage from the hepatocyte to systemic circulation does not appear to be limiting owing to the vast majority of metabolites formed being relatively lipid permeable .", "entity": [], "task": "NER"}
{"text": "In some cases , active transport plays an important role in this process ( e . g . , carboxylic acid metabolites ) .", "entity": [{"entity": "carboxylic acid", "entity_type": "Chemical", "pos": [85, 100]}], "task": "NER"}
{"text": "Differences in total parent drug clearance and metabolite clearance are attenuated by the reduction in lipophilicity introduced by the metabolic step and resultant compensatory changes in unbound clearance and protein binding .", "entity": [], "task": "NER"}
{"text": "A small subclass of these drugs ( e . g . , terfenadine ) is unintentional prodrugs with very high parent drug clearance , resulting in very high M / P ratios .", "entity": [{"entity": "terfenadine", "entity_type": "Chemical", "pos": [44, 55]}], "task": "NER"}
{"text": "In contrast , arenol metabolites show a more complex relationship with fm due largely to the new metabolic routes ( conjugation ) available to the metabolite compared with the parent drug molecule .", "entity": [{"entity": "arenol", "entity_type": "Chemical", "pos": [14, 20]}], "task": "NER"}
{"text": "For these metabolites , a more thorough understanding of the elimination clearance of the metabolite is critical to discern the likelihood of whether the phenol will constitute a major circulating metabolite .", "entity": [{"entity": "phenol", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "Alternariol induces abnormal nuclear morphology and cell cycle arrest in murine RAW 264 . 7 macrophages .", "entity": [{"entity": "Alternariol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The mycotoxin alternariol ( AOH ) , a frequent contaminant in fruit and cereal products , is known to induce DNA damage with subsequent cell cycle arrest .", "entity": [{"entity": "alternariol", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "AOH", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "Here we elucidated the effects of AOH on stages of cell cycle progression using the RAW 264 . 7 macrophage model .", "entity": [{"entity": "AOH", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "AOH resulted in an accumulation of cells in the G2 / M - phase ( 4N ) .", "entity": [{"entity": "AOH", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Most cells exhibited a large G2 nucleus whereas numbers of true mitotic cells were reduced relative to control .", "entity": [], "task": "NER"}
{"text": "Both cyclin B1 and p - cdc2 levels increased , while cyclin B1 remained in the cytoplasm ; suggesting arrest in the G2 / M transition point .", "entity": [], "task": "NER"}
{"text": "Remarkably , after exposure to AOH for 24h , most of the cells exhibited abnormally shaped nuclei , as evidenced by partly divided nuclei , nuclear blebs , polyploidy and micronuclei ( MN ) .", "entity": [{"entity": "AOH", "entity_type": "Chemical", "pos": [31, 34]}], "task": "NER"}
{"text": "AOH treatment also induced abnormal Aurora B bridges , suggesting that cytokinesis was interfered within cells undergoing karyokinesis .", "entity": [{"entity": "AOH", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "A minor part of the resultant G1 tetraploid ( 4N ) cells re - entered the S - phase and progressed to 8N cells .", "entity": [], "task": "NER"}
{"text": "pH - sensitive nanocargo based on smart polymer functionalized graphene oxide for site - specific drug delivery .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [63, 77]}], "task": "NER"}
{"text": "Graphene oxide ( GO ) was functionalized covalently with pH - sensitive poly ( 2 - ( diethylamino ) ethyl methacrylate ) ( PDEA ) by surface - initiated in situ atom transfer radical polymerization .", "entity": [{"entity": "Graphene oxide", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "poly ( 2 - ( diethylamino ) ethyl methacrylate )", "entity_type": "Chemical", "pos": [72, 120]}, {"entity": "PDEA", "entity_type": "Chemical", "pos": [123, 127]}], "task": "NER"}
{"text": "The structure of the PDEA - grafted GO ( GO - PDEA ) were examined by Fourier - transform infrared spectroscopy , proton nuclear magnetic resonance spectroscopy , X - ray photoelectron spectroscopy , thermogravimetric analysis and atomic force microscopy .", "entity": [{"entity": "PDEA - grafted GO", "entity_type": "Chemical", "pos": [21, 38]}, {"entity": "GO - PDEA", "entity_type": "Chemical", "pos": [41, 50]}], "task": "NER"}
{"text": "The grafted PDEA endowed the GO sheets with good solubility and stability in physiological solutions .", "entity": [{"entity": "PDEA", "entity_type": "Chemical", "pos": [12, 16]}], "task": "NER"}
{"text": "Simple physisorption by pi - pi stacking and hydrophobic interactions on GO - PDEA can be used to load camptothecin ( CPT ) , a widely used water - insoluble cancer drug .", "entity": [{"entity": "GO - PDEA", "entity_type": "Chemical", "pos": [73, 82]}, {"entity": "camptothecin", "entity_type": "Chemical", "pos": [103, 115]}, {"entity": "CPT", "entity_type": "Chemical", "pos": [118, 121]}], "task": "NER"}
{"text": "The loaded CPT was released only at the lower ( acidic ) pH normally found in a tumor environment but not in basic and neutral pH .", "entity": [{"entity": "CPT", "entity_type": "Chemical", "pos": [11, 14]}], "task": "NER"}
{"text": "GO - PDEA did not show practical toxicity to N2a cancer cells but the GO - PDEA - CPT complex exhibited high potency in killing N2a cancer cells in vitro .", "entity": [{"entity": "GO - PDEA", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "GO - PDEA - CPT", "entity_type": "Chemical", "pos": [70, 85]}], "task": "NER"}
{"text": "These results suggest that the GO - PDEA nanocargo carrier might be a promising material for site - specific anticancer drug delivery and controlled release .", "entity": [{"entity": "GO - PDEA", "entity_type": "Chemical", "pos": [31, 40]}], "task": "NER"}
{"text": "Revised conformational assignments and conformational evolution of tyrosine by laser desorption supersonic jet laser spectroscopy .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "The number of conformers and their structures of tyrosine are reassigned on the basis of resonance enhanced multiphoton ionization ( REMPI ) , ultraviolet - ultraviolet hole burning ( UV - UV HB ) , infrared ( IR ) dip spectra , and quantum chemical calculations .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "From comparison between REMPI and UV - UV HB spectra , it was found that 12 conformers coexist in the supersonic jet .", "entity": [], "task": "NER"}
{"text": "The structures of these conformers are determined by the IR spectra and theoretical calculations .", "entity": [], "task": "NER"}
{"text": "The number of conformers is more than that reported in the previous reports ( 8 conformers ) , and is rationalized by the systematic formation of conformers from simpler molecules without substituents , just like evolution .", "entity": [], "task": "NER"}
{"text": "The importance of dipole - dipole interaction between an amino - acid chain and hydroxyl group at the benzene ring was also discussed .", "entity": [{"entity": "amino - acid", "entity_type": "Chemical", "pos": [57, 69]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [80, 88]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "Mutant B - RAF - Mcl - 1 survival signaling depends on the STAT3 transcription factor .", "entity": [], "task": "NER"}
{"text": "Approximately 50 % of melanomas depend on mutant B - RAF for proliferation , metastasis and survival .", "entity": [], "task": "NER"}
{"text": "The inhibition of oncogenic B - RAF with highly targeted compounds has produced remarkable albeit short - lived clinical responses in B - RAF mutant melanoma patients .", "entity": [], "task": "NER"}
{"text": "Reactivation of signaling downstream of B - RAF is frequently associated with acquired resistance to B - RAF inhibitors , and the identification of B - RAF targets may provide new strategies for managing melanoma .", "entity": [], "task": "NER"}
{"text": "Oncogenic B - RAF ( V600E ) is known to promote the stabilizing phosphorylation of the anti - apoptotic protein Mcl - 1 , implicated in melanoma survival and chemoresistance .", "entity": [], "task": "NER"}
{"text": "We now show that B - RAF ( V600E ) signaling also induces the transcription of Mcl - 1 in melanocytes and melanoma .", "entity": [], "task": "NER"}
{"text": "We demonstrate that activation of STAT3 serine - 727 and tyrosine - 705 phosphorylations is promoted by B - RAF ( V600E ) activity and that the Mcl - 1 promoter is dependent on a STAT consensus - site for B - RAF - mediated activation .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [40, 46]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [57, 65]}], "task": "NER"}
{"text": "Consequently , suppression of STAT3 activity disrupted B - RAF ( V600E ) - mediated induction of Mcl - 1 and reduced melanoma cell survival .", "entity": [], "task": "NER"}
{"text": "We propose that STAT3 has a central role in the survival and contributes to chemoresistance of B - RAF ( V600E ) melanoma . Oncogene advance online publication , 4 March 2013 ; doi : 10 . 1038 / onc . 2013 . 45 .", "entity": [], "task": "NER"}
{"text": "Active silver nanoparticles for wound healing .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [7, 13]}], "task": "NER"}
{"text": "In this preliminary study , the silver nanoparticle ( Ag NP ) - based dressing , Acticoat (TM) Flex 3 , has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [32, 38]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "The in vitro results show that Ag NPs greatly reduce mitochondrial activity , while cellular staining techniques show that nuclear integrity is maintained , with no signs of cell death .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [31, 33]}], "task": "NER"}
{"text": "For the first time , transmission electron microscopy ( TEM ) and inductively coupled plasma mass spectrometry ( ICP - MS ) analyses were carried out on skin biopsies taken from a single patient during treatment .", "entity": [], "task": "NER"}
{"text": "The results show that Ag NPs are released as aggregates and are localized in the cytoplasm of fibroblasts .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [22, 24]}], "task": "NER"}
{"text": "No signs of cell death were observed , and the nanoparticles had different distributions within the cells of the upper and lower dermis .", "entity": [], "task": "NER"}
{"text": "Depth profiles of the Ag concentrations were determined along the skin biopsies .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [22, 24]}], "task": "NER"}
{"text": "In the healed sample , most of the silver remained in the surface layers , whereas in the unhealed sample , the silver penetrated more deeply .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [35, 41]}, {"entity": "silver", "entity_type": "Chemical", "pos": [112, 118]}], "task": "NER"}
{"text": "The Ag concentrations in the cell cultures were also determined .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [4, 6]}], "task": "NER"}
{"text": "Clinical observations and experimental data collected here are consistent with previously published articles and support the safety of Ag NP - based dressing in wound treatment .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [135, 137]}], "task": "NER"}
{"text": "Assessment of the abuse liability of ABT - 288 , a novel histamine H3 receptor antagonist .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "RATIONALE : Histamine H3 receptor antagonists , such as ABT - 288 , have been shown to possess cognitive - enhancing and wakefulness - promoting effects .", "entity": [{"entity": "Histamine", "entity_type": "Chemical", "pos": [12, 21]}, {"entity": "ABT - 288", "entity_type": "Chemical", "pos": [56, 65]}], "task": "NER"}
{"text": "On the surface , this might suggest that H3 antagonists possess psychomotor stimulant - like effects and , as such , may have the potential for abuse .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The aim of the present study was to further characterize whether ABT - 288 possesses stimulant - like properties and whether its pharmacology gives rise to abuse liability .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [78, 87]}], "task": "NER"}
{"text": "METHODS : The locomotor - stimulant effects of ABT - 288 were measured in mice and rats , and potential development of sensitization was addressed .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "Drug discrimination was used to assess amphetamine - like stimulus properties , and drug self - administration was used to evaluate reinforcing effects of ABT - 288 .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "ABT - 288", "entity_type": "Chemical", "pos": [155, 164]}], "task": "NER"}
{"text": "The potential development of physical dependence was also studied .", "entity": [], "task": "NER"}
{"text": "RESULTS : ABT - 288 lacked locomotor - stimulant effects in both rats and mice .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [10, 19]}], "task": "NER"}
{"text": "Repeated administration of ABT - 288 did not result in cross - sensitization to the stimulant effects of d - amphetamine in mice , suggesting that there is little overlap in circuitries upon which the two drugs interact for motor activity .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "d - amphetamine", "entity_type": "Chemical", "pos": [105, 120]}], "task": "NER"}
{"text": "ABT - 288 did not produce amphetamine - like discriminative stimulus effects in drug discrimination studies nor was it self - administered by rats trained to self - administer cocaine .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [26, 37]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [176, 183]}], "task": "NER"}
{"text": "There were no signs of physical dependence upon termination of repeated administration of ABT - 288 for 30 days .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [90, 99]}], "task": "NER"}
{"text": "CONCLUSIONS : The sum of these preclinical data , the first of their kind applied to H3 antagonists , indicates that ABT - 288 is unlikely to possess a high potential for abuse in the human population and suggests that H3 antagonists , as a class , are similar in this regard .", "entity": [{"entity": "ABT - 288", "entity_type": "Chemical", "pos": [117, 126]}], "task": "NER"}
{"text": "Optimized templates for bottom - up growth of high - performance integrated biomolecular detectors .", "entity": [], "task": "NER"}
{"text": "Electrochemical deposition of metals represents an important approach in the bottom - up fabrication of nanostructures and microstructures .", "entity": [], "task": "NER"}
{"text": "We have used this approach to generate high - performance chip - based biosensors using silicon as a platform for the generation of sensor arrays .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [88, 95]}], "task": "NER"}
{"text": "Here , we explore the applicability of different materials to support the electrodeposition and identify the parameters that are essential for robust sensor growth .", "entity": [], "task": "NER"}
{"text": "We show that inexpensive materials can be used as templates for electrodeposition , and demonstrate that these low - cost sensors exhibit clinically - relevant levels of sensitivity and specificity .", "entity": [], "task": "NER"}
{"text": "In particular , we prove herein that the glass - based sensors successfully detect E . coli in urine , when present at the 100 cfu mu L ( - 1 ) levels found typically in samples of patients with urinary tract infections .", "entity": [], "task": "NER"}
{"text": "Current self - complianced and self - rectifying resistive switching in Ag - electroded single Na - doped ZnO nanowires .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [72, 74]}, {"entity": "Na", "entity_type": "Chemical", "pos": [95, 97]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "We demonstrate current self - complianced and self - rectifying bipolar resistive switching in an Ag - electroded Na - doped ZnO nanowire device .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "Na", "entity_type": "Chemical", "pos": [114, 116]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [125, 128]}], "task": "NER"}
{"text": "The resistive switching is controlled by the formation and rupture of an Ag nanoisland chain on the surface along the Na - doped ZnO nanowire .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [73, 75]}, {"entity": "Na", "entity_type": "Chemical", "pos": [118, 120]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "Na - doping plays important roles in both the self - compliance and self - rectifying properties .", "entity": [{"entity": "Na", "entity_type": "Chemical", "pos": [0, 2]}], "task": "NER"}
{"text": "Mesenchymal stem cells secretome : a new paradigm for central nervous system regeneration ?", "entity": [], "task": "NER"}
{"text": "The low regeneration potential of the central nervous system ( CNS ) represents a challenge for the development of new therapeutic strategies .", "entity": [], "task": "NER"}
{"text": "Mesenchymal stem cells ( MSCs ) have been proposed as a possible therapeutic tool for CNS disorders .", "entity": [], "task": "NER"}
{"text": "In addition to their differentiation potential , it is well accepted nowadays that their beneficial actions can also be mediated by their secretome .", "entity": [], "task": "NER"}
{"text": "Indeed , it was already demonstrated , both in vitro and in vivo , that MSCs are able to secrete a broad range of neuroregulatory factors that promote an increase in neurogenesis , inhibition of apoptosis and glial scar formation , immunomodulation , angiogenesis , neuronal and glial cell survival , as well as relevant neuroprotective actions on different pathophysiological contexts .", "entity": [], "task": "NER"}
{"text": "Considering their protective action in lesioned sites , MSCs ' secretome might also improve the integration of local progenitor cells in neuroregeneration processes , opening a door for their future use as therapeutical strategies in human clinical trials .", "entity": [], "task": "NER"}
{"text": "Thus , in this review we analyze the current understanding of MSCs secretome as a new paradigm for the treatment of CNS neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "The hazardous effects of the three natural food dyes on developmental stages and longevity of Drosophila melanogaster .", "entity": [], "task": "NER"}
{"text": "Nowadays , food dyes obtained from herbal , animal , microbial and mineral sources are widely used as food additives .", "entity": [], "task": "NER"}
{"text": "In this study , the toxic effects of three different natural food dyes ( carmine , turmeric and annatto ) on 72 +/- 4 h larvae of Oregon - R wild type of Drosophila melanogaster were investigated .", "entity": [{"entity": "carmine", "entity_type": "Chemical", "pos": [73, 80]}], "task": "NER"}
{"text": "For this purpose , four different application doses ( 50 , 75 , 100 , 125 mg mL ( - 1 ) ) were chosen by means of preliminary studies .", "entity": [], "task": "NER"}
{"text": "It was determined that larval mortality increased with increasing concentration in the application groups and the toxicity order was carmine > turmeric > annatto .", "entity": [{"entity": "carmine", "entity_type": "Chemical", "pos": [133, 140]}], "task": "NER"}
{"text": "It was observed that the survival rate was highest in the control with 98 % and lowest in 125 mg mL ( - 1 ) carmine with 16 % .", "entity": [{"entity": "carmine", "entity_type": "Chemical", "pos": [108, 115]}], "task": "NER"}
{"text": "In addition , the average lifespan of the adult individuals obtained from third instar larvae was also studied .", "entity": [], "task": "NER"}
{"text": "While the average lifespan was 40 . 88 +/- 1 . 44 days in the control group , these values were 10 . 81 +/- 0 . 55 - 23 . 90 +/- 1 . 27 days in the carmine group , 15 . 00 +/- 0 . 80 - 22 . 42 +/- 1 . 43 days in the turmeric group and 10 . 33 +/- 1 . 03 - 35 . 68 +/- 1 . 54 days in the annatto group , respectively .", "entity": [{"entity": "carmine", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "According to the obtained results , when both the developmental period from larvae into adults and the lifespan of the developing adults were compared with the control group , the food dyes were found to be toxic and the toxicity order of carmine > turmeric > annatto was identified .", "entity": [{"entity": "carmine", "entity_type": "Chemical", "pos": [239, 246]}], "task": "NER"}
{"text": "Which density functional is close to CCSD accuracy to describe geometry and interaction energy of small non - covalent dimers ?", "entity": [], "task": "NER"}
{"text": "A benchmark study using gaussian09 .", "entity": [], "task": "NER"}
{"text": "A benchmark study on all possible density functional theory ( DFT ) methods in Gaussian09 is done to locate functionals that agree well with CCSD / aug - cc - pVTZ geometry and Ave - CCSD ( T ) / ( Q - T ) interaction energy ( Eint ) for small non - covalently interacting molecular dimers in \" dispersion - dominated \" ( class 1 ) , \" dipole - induced dipole \" ( class 2 ) , and \" dipole - dipole \" ( class 3 ) classes .", "entity": [], "task": "NER"}
{"text": "A DFT method is recommended acceptable if the geometry showed close agreement to CCSD result ( RMSD < 0 . 045 ) and Eint was within 80 - 120 % accuracy .", "entity": [], "task": "NER"}
{"text": "Among 382 tested functionals , 1 - 46 % gave good geometry , 13 - 44 % gave good Eint , while 1 - 33 % satisfied geometry and energy criteria .", "entity": [], "task": "NER"}
{"text": "Further screening to locate the best performing functionals for all the three classes was made by counting the acceptable values of energy and geometry given by each functionals .", "entity": [], "task": "NER"}
{"text": "The meta - generalized gradient approximation ( GGA ) functional M06L was the best performer with total 14 hits ; seven acceptable energies and seven acceptable geometries .", "entity": [], "task": "NER"}
{"text": "This was the only functional \" recommended \" for at least two dimers in each class .", "entity": [], "task": "NER"}
{"text": "The functionals M05 , B2PLYPD , B971 , mPW2PLYPD , PBEB95 , and CAM - B3LYP gave 11 hits while PBEhB95 , PW91B95 , Wb97x , BRxVP86 , BRxP86 , HSE2PBE , HSEh1PBE , PBE1PBE , PBEh1PBE , and PW91TPSS gave 10 hits .", "entity": [], "task": "NER"}
{"text": "Among these , M05 , B971 , mPW2PLYPD , Wb97x , and PW91TPSS were among the \" recommended \" list of at least one dimer from each class .", "entity": [], "task": "NER"}
{"text": "Long - range correction ( LC ) of Hirao and coworkers to exchange - correlation functionals showed massive improvement in geometry and Eint .", "entity": [], "task": "NER"}
{"text": "The best performing LC - functionals were LC - G96KCIS and LC - PKZBPKZB .", "entity": [], "task": "NER"}
{"text": "Our results predict that M06L is the most trustworthy DFT method in Gaussian09 to study small non - covalently interacting systems .", "entity": [], "task": "NER"}
{"text": "Unusual amino acids and monofluoroacetate from Dichapetalum michelsonii ( Umutambasha ) , a toxic plant from Rwanda .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [8, 19]}, {"entity": "monofluoroacetate", "entity_type": "Chemical", "pos": [24, 41]}], "task": "NER"}
{"text": "In the course of our investigations on Umutambasha in order to identify its convulsant principles , small quantities of monofluoroacetate were observed in stem bark , leaves , and fruits of this plant newly identified as Dichapetalum michelsonii Hauman .", "entity": [{"entity": "monofluoroacetate", "entity_type": "Chemical", "pos": [120, 137]}], "task": "NER"}
{"text": "Conclusive evidence for a monofluoroacetate presence came from its isolation from the freeze - dried extract of stem bark .", "entity": [{"entity": "monofluoroacetate", "entity_type": "Chemical", "pos": [26, 43]}], "task": "NER"}
{"text": "Three free unusual amino acids , named N - methyl - alpha - alanine , N - methyl - beta - alanine , and 2 , 7 - diaminooctan - 1 , 8 - dioic acid , described for the first time in a plant , and known trigonelline were also isolated from the stem bark of D . michelsonii .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "N - methyl - alpha - alanine", "entity_type": "Chemical", "pos": [39, 67]}, {"entity": "N - methyl - beta - alanine", "entity_type": "Chemical", "pos": [70, 97]}, {"entity": "2 , 7 - diaminooctan - 1 , 8 - dioic acid", "entity_type": "Chemical", "pos": [104, 145]}, {"entity": "trigonelline", "entity_type": "Chemical", "pos": [200, 212]}], "task": "NER"}
{"text": "Structure elucidations were mainly achieved by spectroscopic methods ( 1H - NMR , 2D - NMR , MS ) and by comparison with authentic references .", "entity": [{"entity": "1H", "entity_type": "Chemical", "pos": [71, 73]}], "task": "NER"}
{"text": "These unusual amino acids were detected by a fast , reliable TLC analysis in all our batches of Umutambasha , suggesting that they could be used for identification purposes in case of human or livestock intoxications .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Finally , EEG recordings and behavioural observations performed in mice suggested that the convulsive patterns produced by Umutambasha are the consequence of monofluoroacetate presence in D . michelsonii .", "entity": [{"entity": "monofluoroacetate", "entity_type": "Chemical", "pos": [158, 175]}], "task": "NER"}
{"text": "Robust Synthesis of Gold Cubic Nanoframes through a Combination of Galvanic Replacement , Gold Deposition , and Silver Dealloying .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [112, 118]}], "task": "NER"}
{"text": "A facile , robust approach to the synthesis of Au cubic nanoframes is described .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [47, 49]}], "task": "NER"}
{"text": "The synthesis involves three major steps : 1 ) preparation of Au - Ag alloyed nanocages using a galvanic replacement reaction between Ag nanocubes and HAuCl4 ; 2 ) deposition of thin layers of pure Au onto the surfaces of the nanocages by reducing HAuCl4 with ascorbic acid , and ; 3 ) formation of Au cubic nanoframes through a dealloying process with HAuCl4 .", "entity": [{"entity": "Au - Ag", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [134, 136]}, {"entity": "HAuCl4", "entity_type": "Chemical", "pos": [151, 157]}, {"entity": "Au", "entity_type": "Chemical", "pos": [198, 200]}, {"entity": "HAuCl4", "entity_type": "Chemical", "pos": [248, 254]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [260, 273]}, {"entity": "Au", "entity_type": "Chemical", "pos": [299, 301]}, {"entity": "HAuCl4", "entity_type": "Chemical", "pos": [353, 359]}], "task": "NER"}
{"text": "The key to the formation of Au cubic nanoframes is to coat the surfaces of the Au - Ag nanocages with sufficiently thick layers of Au before they are dealloyed .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [28, 30]}, {"entity": "Au - Ag", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "Au", "entity_type": "Chemical", "pos": [131, 133]}], "task": "NER"}
{"text": "The Au layer could prevent the skeleton of a nanocage from being fragmented during the dealloying step .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [4, 6]}], "task": "NER"}
{"text": "The as - prepared Au cubic nanoframes exhibit tunable localized surface plasmon resonance peaks in the near - infrared region , but with much lower Ag content as compared with the initial Au - Ag nanocages .", "entity": [{"entity": "Au", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [148, 150]}, {"entity": "Au - Ag", "entity_type": "Chemical", "pos": [188, 195]}], "task": "NER"}
{"text": "Prenatal bisphenol a exposure alters sex - specific estrogen receptor expression in the neonatal rat hypothalamus and amygdala .", "entity": [{"entity": "bisphenol a", "entity_type": "Chemical", "pos": [9, 20]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Bisphenol A ( BPA ) exposure is ubiquitous , and in laboratory animals , early - life BPA exposure has been shown to alter sex - specific neural organization , neuroendocrine physiology , and behavior .", "entity": [{"entity": "Bisphenol A", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "The specific mechanisms underlying these brain - related outcomes , however , remain largely unknown , constraining the capacity to ascertain the potential human relevance of neural effects observed in animal models .", "entity": [], "task": "NER"}
{"text": "In the perinatal rat brain , estrogen is masculinizing , suggesting that BPA - induced perturbation of estrogen receptor ( ESR ) expression may underpin later in - life neuroendocrine effects .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [73, 76]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "We hypothesized that prenatal BPA exposure alters sex - specific ESR1 ( ER alpha ) and ESR2 ( ER beta ) expression in postnatal limbic nuclei .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "Sprague Dawley rats were mated and gavaged on gestational days ( GDs ) 6 - 21 with vehicle , 2 . 5 or 25 mu g / kg bw / day BPA , or 5 or 10 mu g / kg bw / day ethinyl estradiol .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "ethinyl estradiol", "entity_type": "Chemical", "pos": [160, 177]}], "task": "NER"}
{"text": "An additional group was restrained but not gavaged ( na i ve control ) .", "entity": [], "task": "NER"}
{"text": "Offspring were sacrificed the day after birth to quantify ESR gene expression throughout the hypothalamus and amygdala by in situ hybridization .", "entity": [], "task": "NER"}
{"text": "Relative to the vehicle group , significant effects of BPA were observed on ESR1 and ESR2 expression throughout the mediobasal hypothalamus and amygdala in both sexes .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "Significant differences in ESR expression were also observed in the mediobasal hypothalamus and amygdala of the na i ve control group compared with the vehicle group , highlighting the potential for gavage to influence gene expression in the developing brain .", "entity": [], "task": "NER"}
{"text": "These results indicate that ESR expression in the neonatal brain of both sexes can be altered by low - dose prenatal BPA exposure .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [117, 120]}], "task": "NER"}
{"text": "Ultrasensitive optical shape characterization of gold nanoantennas using second harmonic generation .", "entity": [], "task": "NER"}
{"text": "Second harmonic generation from plasmonic nanoantennas is investigated numerically using a surface integral formulation for the calculation of both the fundamental and the second harmonic electric field .", "entity": [], "task": "NER"}
{"text": "The comparison between a realistic and an idealized gold nanoantenna shows that second harmonic generation is extremely sensitive to asymmetry in the nanostructure shape even in cases where the linear response is barely modified .", "entity": [], "task": "NER"}
{"text": "Interestingly , minute geometry asymmetry and surface roughness are clearly revealed by far - field analysis , demonstrating that second harmonic generation is a promising tool for the sensitive optical characterization of plasmonic nanostructures .", "entity": [], "task": "NER"}
{"text": "Furthermore , defects located where the linear field is strong ( e . g . , in the antenna gap ) do not necessarily have the strongest impact on the second harmonic signal .", "entity": [], "task": "NER"}
{"text": "Cellulose - ethylenediaminetetraacetic Acid conjugates protect Mammalian cells from bacterial cells .", "entity": [{"entity": "ethylenediaminetetraacetic Acid", "entity_type": "Chemical", "pos": [12, 43]}], "task": "NER"}
{"text": "Cellulose - ethylenediaminetetraacetic acid ( EDTA ) conjugates were synthesized by the esterification of cellulose with ethylenediaminetetraacetic dianhydride ( EDTAD ) .", "entity": [{"entity": "ethylenediaminetetraacetic acid", "entity_type": "Chemical", "pos": [12, 43]}, {"entity": "EDTA", "entity_type": "Chemical", "pos": [46, 50]}, {"entity": "ethylenediaminetetraacetic dianhydride", "entity_type": "Chemical", "pos": [121, 159]}, {"entity": "EDTAD", "entity_type": "Chemical", "pos": [162, 167]}], "task": "NER"}
{"text": "The new materials provided potent antimicrobial activities against Staphylococcus aureus ( S . aureus , Gram - positive bacteria ) and Pseudomonas aeruginosa ( P . aeruginosa , Gram - negative bacteria ) , and inhibited the formation of bacterial biofilms .", "entity": [], "task": "NER"}
{"text": "The biocompatibility of the new cellulose - EDTA conjugates was evaluated with mouse skin fibroblasts for up to 14 days .", "entity": [{"entity": "EDTA", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "SEM observation and DNA content analysis suggested that the new materials sustained the viability of fibroblast cells .", "entity": [], "task": "NER"}
{"text": "Moreover , in mouse skin fibroblast - bacteria co - culture systems , the new cellulose - EDTA conjugates prevented bacterial biofilm formation and protected the mammalian cells from the bacterial cells for at least one day .", "entity": [{"entity": "EDTA", "entity_type": "Chemical", "pos": [90, 94]}], "task": "NER"}
{"text": "High quality CdHgTe nanocrystals with strong near - infrared emission : relationship between composition and cytotoxic effects .", "entity": [{"entity": "CdHgTe", "entity_type": "Chemical", "pos": [13, 19]}], "task": "NER"}
{"text": "High quality CdHgTe quasi core / shell nanocrystals ( NCs ) were prepared via the one - step method .", "entity": [{"entity": "CdHgTe", "entity_type": "Chemical", "pos": [13, 19]}], "task": "NER"}
{"text": "The relationship between the composition , structure , and property was systematically investigated by the combination of X - ray photoelectron spectroscopy ( XPS ) , inductively coupled plasma atomic emission ( ICP ) , and the photoluminescence ( PL ) measurements .", "entity": [], "task": "NER"}
{"text": "The quantum yield ( QY ) was ~ 50 % when the feed ratio of Cd ( 2 + ) to Hg ( 2 + ) was equal to 1 .", "entity": [{"entity": "Cd ( 2 + )", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [73, 83]}], "task": "NER"}
{"text": "The PL property was further polished , and the QY was improved to ~ 80 % through the variance of the prepared conditions such as the ratio of ligand to metal ion and HTe ( - ) to metal ion , pH value , and temperature .", "entity": [{"entity": "HTe ( - )", "entity_type": "Chemical", "pos": [166, 175]}], "task": "NER"}
{"text": "In addition , the cytotoxic effects of CdHgTe NCs were systematically studied .", "entity": [{"entity": "CdHgTe", "entity_type": "Chemical", "pos": [39, 45]}], "task": "NER"}
{"text": "The results showed that , for Cd0 . 21Hg0 . 79Te NCs , its quasi core / shell structure was very stable and little cadmium ions were released .", "entity": [{"entity": "Cd0 . 21Hg0 . 79Te", "entity_type": "Chemical", "pos": [30, 48]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [115, 122]}], "task": "NER"}
{"text": "As a result , such NCs showed little cytotoxicity and would find applications in tissue imaging or detection .", "entity": [], "task": "NER"}
{"text": "Isolation of thermally stable cellulose nanocrystals by phosphoric Acid hydrolysis .", "entity": [{"entity": "phosphoric Acid", "entity_type": "Chemical", "pos": [56, 71]}], "task": "NER"}
{"text": "On account of their intriguing mechanical properties , low cost , and renewable nature , high - aspect - ratio cellulose nanocrystals ( CNCs ) are an attractive component for many nanomaterials .", "entity": [], "task": "NER"}
{"text": "Due to hydrogen bonding between their surface hydroxyl groups , unmodified CNCs ( H - CNCs ) aggregate easily and are often difficult to disperse .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [7, 15]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [46, 54]}], "task": "NER"}
{"text": "It is shown here that on account of ionic repulsion between charged surface groups , slightly phosphorylated CNCs ( P - CNCs , average dimensions 31 +/- 14 x 316 +/- 127 nm , surface charge density = 10 . 8 +/- 2 . 7 mmol / kg cellulose ) , prepared by controlled hydrolysis of cotton with phosphoric acid , are readily dispersible and form stable dispersions in polar solvents such as water , dimethyl sulfoxide , and dimethylformamide .", "entity": [{"entity": "phosphoric acid", "entity_type": "Chemical", "pos": [290, 305]}, {"entity": "dimethyl sulfoxide", "entity_type": "Chemical", "pos": [394, 412]}, {"entity": "dimethylformamide", "entity_type": "Chemical", "pos": [419, 436]}], "task": "NER"}
{"text": "Thermogravimetric analyses reveal that these P - CNCs exhibit a much higher thermal stability than partially sulfated CNCs ( S - CNCs ) , which are frequently employed , but suffer from limited thermal stability .", "entity": [], "task": "NER"}
{"text": "Nanocomposites of an ethylene oxide - epichlorohydrin copolymer and H - CNCs , S - CNCs , and P - CNCs were prepared , and their mechanical properties were studied by dynamic mechanical thermal analysis .", "entity": [{"entity": "ethylene oxide", "entity_type": "Chemical", "pos": [21, 35]}, {"entity": "epichlorohydrin", "entity_type": "Chemical", "pos": [38, 53]}], "task": "NER"}
{"text": "The results show that P - CNCs offer a reinforcing capability that is comparable to that of H - CNCs or S - CNCs .", "entity": [], "task": "NER"}
{"text": "Electronic transitions of protonated and deprotonated amino acids in aqueous solution in the region 145 - 300 nm studied by attenuated total reflection far - ultraviolet spectroscopy .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [54, 65]}], "task": "NER"}
{"text": "The electronic transitions of 20 naturally occurring amino acids in aqueous solution were studied with attenuated total reflection far - ultraviolet ( ATR - FUV ) spectroscopy in the region from 145 to 300 nm .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [53, 64]}], "task": "NER"}
{"text": "From the measured ATR spectra of sample solutions , the FUV absorption spectra attributed to the amino acids were separated from the intense solvent absorption by using a modified Kramers - Kronig transformation method .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [97, 108]}], "task": "NER"}
{"text": "The FUV absorption spectra of the amino acids reflect the protonation states of the backbone and side - chain structures .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [34, 45]}], "task": "NER"}
{"text": "The contributions of the side chains to the spectra were also examined from the difference spectra subtracting the corresponding Gly spectrum from each spectrum .", "entity": [{"entity": "Gly", "entity_type": "Chemical", "pos": [129, 132]}], "task": "NER"}
{"text": "The observed spectra were compared mostly with the electronic transition studies of the molecular fragments of the amino acids in gas phase .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [115, 126]}], "task": "NER"}
{"text": "The FUV spectra of the amino acids exhibited the intra - and intermolecular electronic interactions of the solute - solute as well as the solute - solvent , and those are essential factors to elucidate UV photochemical processes of the amino acids in aqueous solution .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [23, 34]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [236, 247]}], "task": "NER"}
{"text": "Perspectives offered by single - domain antibodies in clinical diagnostic of pediatric tumors .", "entity": [], "task": "NER"}
{"text": "The results accrued in the last few years have clearly showed that recombinant antibodies , and specifically single - domain antibodies , represent valid alternatives to conventional IgGs for in vivo imaging .", "entity": [], "task": "NER"}
{"text": "It does not simply mean that antibody fragments can substitute full - length antibodies , but that they are substantially more suitable for some applications and can perform other functions for which no real alternative is available .", "entity": [], "task": "NER"}
{"text": "Brain imaging with multi - functional probes is an evident example , but the promising results obtained with micro - PET and - SPECT in murine models could lead in short time to a revolutionary change in clinical diagnostics .", "entity": [], "task": "NER"}
{"text": "Brilliant applications of single - domain antibody - dependent imaging have enabled us to understand how the tracer mass and avidity can be engineered to modulate pharmacokinetic features such as clearance , tumor penetration , and binding affinity with the aim of optimizing specific responses .", "entity": [], "task": "NER"}
{"text": "The potential of these reagents and the increasing interest for them is evidenced by the exponential growth of publications and the multiplication of the proposed applications in which they are used .", "entity": [], "task": "NER"}
{"text": "This review wishes to provide an update of this fast moving subject and to indicate what may be the next foreseeable technical progress .", "entity": [], "task": "NER"}
{"text": "Artificial neural network analysis of data from multiple in vitro assays for prediction of skin sensitization potency of chemicals .", "entity": [], "task": "NER"}
{"text": "In order to develop in vitro risk assessment systems for skin sensitization , it is important to predict a threshold from the murine local lymph node assay ( LLNA ) .", "entity": [], "task": "NER"}
{"text": "We first confirmed that the combination of the human Cell Line Activation Test ( h - CLAT ) and the SH test improved the accuracy and sensitivity of prediction of LLNA data compared with each individual test .", "entity": [], "task": "NER"}
{"text": "Next , we assessed the mutual correlations among maximum amount of change of cell - surface thiols ( MAC value ) in the SH test , CV75 value ( concentration giving 75 % cell viability ) in a cytotoxicity assay , EC150 and EC200 values ( thresholds concentrations of CD86 and CD54 expression , respectively ) in h - CLAT and published LLNA thresholds of 64 chemicals .", "entity": [{"entity": "thiols", "entity_type": "Chemical", "pos": [92, 98]}], "task": "NER"}
{"text": "Based on the results , we selected MAC value and the minimum of CV75 , EC150 ( CD86 ) and EC200 ( CD54 ) as descriptors for the input layer of an artificial neural network ( ANN ) system .", "entity": [], "task": "NER"}
{"text": "The ANN - predicted values were well correlated with reported LLNA thresholds .", "entity": [], "task": "NER"}
{"text": "We also found a correlation between the SH test and the peptide - binding assay used to evaluate hapten - protein complex formation .", "entity": [], "task": "NER"}
{"text": "Thus , this model , which we designate as the \" iSENS ver .", "entity": [], "task": "NER"}
{"text": "1 \" , may be useful for risk assessment of skin sensitization potential of chemicals from in vitro test data .", "entity": [], "task": "NER"}
{"text": "Considering the impact drug - like properties have on the chance of success .", "entity": [], "task": "NER"}
{"text": "Many definitions of ' drug - like ' compound properties have been published ; based on the analysis of simple molecular properties of successful drugs .", "entity": [], "task": "NER"}
{"text": "These are typically presented as rules that define acceptable boundaries for these properties .", "entity": [], "task": "NER"}
{"text": "When a compound does not ' fit ' within these boundaries then its properties differ from those of the majority of drugs , which could indicate a higher risk of poor pharmacokinetics or safety outcomes in vivo .", "entity": [], "task": "NER"}
{"text": "Here , we review the strengths and weaknesses of these rules and note , in particular , that the overly rigid application of strict cut - off points can introduce artificial distinctions between similar compounds , running the risk of missing valuable opportunities .", "entity": [], "task": "NER"}
{"text": "Alternatively , compounds can be ranked according to their similarity to marketed drugs using a continuous measure of drug - likeness .", "entity": [], "task": "NER"}
{"text": "However , being similar to known drugs does not necessarily mean that a compound is more likely to become a drug and we demonstrate how a new approach , employing Bayesian methods , can be used to compare a set of successful drugs with a set of non - drug compounds to identify those properties that give the greatest distinction between the two sets , and hence the greatest increase in the likelihood of a compound becoming a successful drug .", "entity": [], "task": "NER"}
{"text": "This analysis further illustrates that guidelines for drug - likeness might not be generally applicable across all compound and target classes or therapeutic indications .", "entity": [], "task": "NER"}
{"text": "Therefore , it might be more appropriate to consider specific guidelines for drug - likeness that are project specific .", "entity": [], "task": "NER"}
{"text": "Synthesis of a paraffin phase change material microencapsulated in a siloxane polymer .", "entity": [{"entity": "paraffin", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "siloxane", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "The coemulsification method suitable for the formulation of microcapsules of n - eicosane coated with a polysiloxane is developed .", "entity": [{"entity": "n - eicosane", "entity_type": "Chemical", "pos": [77, 89]}, {"entity": "polysiloxane", "entity_type": "Chemical", "pos": [104, 116]}], "task": "NER"}
{"text": "This method allows to synthesize core - shell microcapsules of paraffin which have the shape of spheres or distorted spheres and are designed for the use as phase change materials .", "entity": [{"entity": "paraffin", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "The microcapsules are formed in aqueous phase by the precipitation of n - eicosane together with modified polyhydromethylsiloxane from a common solvent which is miscible with aqueous media .", "entity": [{"entity": "n - eicosane", "entity_type": "Chemical", "pos": [70, 82]}, {"entity": "polyhydromethylsiloxane", "entity_type": "Chemical", "pos": [106, 129]}], "task": "NER"}
{"text": "The polysiloxane is modified by the attachment of silylvinyl and alkoxy functions before coemulsification with the paraffin .", "entity": [{"entity": "polysiloxane", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "silylvinyl", "entity_type": "Chemical", "pos": [50, 60]}, {"entity": "alkoxy", "entity_type": "Chemical", "pos": [65, 71]}, {"entity": "paraffin", "entity_type": "Chemical", "pos": [115, 123]}], "task": "NER"}
{"text": "It also contains the Pt ( 0 ) Karstedt catalyst .", "entity": [{"entity": "Pt ( 0 ) Karstedt catalyst", "entity_type": "Chemical", "pos": [21, 47]}], "task": "NER"}
{"text": "The microcapsules formed by coemulsification are stabilized by the in situ cross - linking of the polysiloxane shell .", "entity": [{"entity": "polysiloxane", "entity_type": "Chemical", "pos": [98, 110]}], "task": "NER"}
{"text": "The shell is additionally modified by the in situ generation of silanol groups which provide colloidal stabilization of microspheres in aqueous phase .", "entity": [{"entity": "silanol", "entity_type": "Chemical", "pos": [64, 71]}], "task": "NER"}
{"text": "Microcapsules were studied by DSC , SEM , optical polarized microscope , and by thermooptical analysis ( TOA ) .", "entity": [], "task": "NER"}
{"text": "Differential surface properties of commercial crystalline telmisartan samples .", "entity": [{"entity": "telmisartan", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "The aim of the present study was to investigate differences in surface chemistry of commercially available telmisartan ( TMS ) samples in Indian market and to correlate them to the surface molecular environment .", "entity": [{"entity": "telmisartan", "entity_type": "Chemical", "pos": [107, 118]}, {"entity": "TMS", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "Comprehensive characterization of material properties of four TMS samples from different sources showed that all samples exhibited same polymorphic form , but different particle shape , particle size distribution , surface energetics and surface chemistry .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [62, 65]}], "task": "NER"}
{"text": "Wettability and surface free energy were determined using sessile drop contact angle technique .", "entity": [], "task": "NER"}
{"text": "TMS samples exhibited significant variations in their wetting behavior .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The role of crystal shape , particle size distribution , surface energetics and surface chemistry in controlling TMS powder wettability was collectively explored by contact angle experiments .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [113, 116]}], "task": "NER"}
{"text": "Evaluation of work of adhesion ( Wa ) , immersion ( Wi ) and spreading ( Ws ) indicated that samples had differential wetting behavior .", "entity": [], "task": "NER"}
{"text": "The surface chemistry was elucidated by X - ray photoelectron spectroscopy ( XPS ) .", "entity": [], "task": "NER"}
{"text": "The surface polarity index was determined by XPS and expressed as ( oxygen + nitrogen ) - to - ( carbon ) atomic concentration ratio .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [68, 74]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [97, 103]}], "task": "NER"}
{"text": "It was found to be different for all four TMS samples .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [42, 45]}], "task": "NER"}
{"text": "Crystal morphology of TMS polymorph A was predicted using Bravais - Friedel Donnay - Harker ( BFDH ) method .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [22, 25]}], "task": "NER"}
{"text": "Molecular lipophilic surface potential ( MLSP ) data for TMS showed the varied surface lipophilic environment throughout the molecule .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [57, 60]}], "task": "NER"}
{"text": "Hence it can be concluded that the differential abundance of surface elements play an important role in controlling the biopharmaceutical performance of TMS powder samples .", "entity": [{"entity": "TMS", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "Analytical chemistry , toxicology , epidemiology and health impact assessment of melamine in infant formula : Recent progress and developments .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [81, 89]}], "task": "NER"}
{"text": "This review summarizes the most recent scientific literature and regulations regarding analytical chemistry , toxicology , epidemiology , exposure , and risk assessment of melamine in infant formula .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [172, 180]}], "task": "NER"}
{"text": "For analyses , enzyme - linked immunosorbent assay , high - performance liquid chromatography , capillary electrophoresis , gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry have commonly been used .", "entity": [], "task": "NER"}
{"text": "Organization of proficiency test programs provided good evidence to facilitate granting laboratories accreditation and to ascertain the measurement reliability of melamine methods .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [163, 171]}], "task": "NER"}
{"text": "Metabolic studies demonstrated that melamine is predominantly restricted to blood or extracellular fluid and is not extensively distributed to organs and tissues .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Studies of human renal histopathology and clinical diagnoses indicated that melamine - related obstructive nephropathy derives from melamine precipitation in the lower urinary tract , with stones that are thought to be melamine - uric acid complexes .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "melamine", "entity_type": "Chemical", "pos": [132, 140]}, {"entity": "melamine", "entity_type": "Chemical", "pos": [219, 227]}, {"entity": "uric acid", "entity_type": "Chemical", "pos": [230, 239]}], "task": "NER"}
{"text": "Epidemiologic studies showed that the occurrence of melamine - related urolithiasis is related to both the concentration of melamine in ingested milk products and the duration of ingestion .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "melamine", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "Long - term follow - up cohort studies should be continued to further investigate the epidemic and chronic hazard of melamine - induced nephrotoxicity .", "entity": [{"entity": "melamine", "entity_type": "Chemical", "pos": [117, 125]}], "task": "NER"}
{"text": "The World Health Organization set a tolerable daily intake of 0 . 2mg / kgbw / day to be applied to \" the whole population including infants \" .", "entity": [], "task": "NER"}
{"text": "Other authorities and research institutes have set / proposed lower values .", "entity": [], "task": "NER"}
{"text": "Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine : Correlations with amphetamine - induced neurotoxicity .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [111, 122]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [143, 154]}], "task": "NER"}
{"text": "The neurotrophic factors pleiotrophin ( PTN ) and midkine ( MK ) have been shown to modulate amphetamine - induced neurotoxicity .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "Accordingly , PTN - / - and MK - / - mice show an increased vulnerability to amphetamine - induced neurotoxic effects .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [77, 88]}], "task": "NER"}
{"text": "In an effort to uncover new pharmacological targets to prevent amphetamine neurotoxic effects , we have now used a proteomic approach to study protein phosphorylation , in which we combined phosphoprotein enrichment , by immobilized metal affinity chromatography ( IMAC ) , with two - dimensional gel electrophoresis and mass spectrometry , in order to identify the phosphoproteins regulated in the striatum of PTN - / - , MK - / - and wild type ( WT ) mice treated with amphetamine .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [63, 74]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [471, 482]}], "task": "NER"}
{"text": "We identified 13 differentially expressed phosphoproteins that are judged to be relevant in the neuroprotective roles of PTN and MK against amphetamine - induced neurotoxicity .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [140, 151]}], "task": "NER"}
{"text": "It is very interesting to note that 4 of these phosphoproteins , annexin A7 ( ANXA7 ) , COP9 signalosome subunit 5 ( COPS5 ) , aldehyde dehydrogenase family 1 member A1 ( ALDH1A1 ) and creatine kinase U - type ( CKMT1 ) , are known to be involved in Parkinson ' s disease , a result of significant importance since PTN and MK have been also demonstrated to limit Parkinson ' s disease ( PD ) progress and have been suggested to be among the important genetic factors possibly preventing the development of PD in methamphetamine abusers .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [127, 135]}, {"entity": "creatine", "entity_type": "Chemical", "pos": [185, 193]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [512, 527]}], "task": "NER"}
{"text": "The data identify phosphoproteins differentially regulated by amphetamine treatment and / or the presence of endogenous PTN / MK which may be relevant mediators of PTN / MK neuroprotective effects against amphetamine - induced neurotoxicity .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [62, 73]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [205, 216]}], "task": "NER"}
{"text": "The data support further studies to validate the phosphoproteins here identified as possible new pharmacological targets to prevent amphetamine neurotoxic effects .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "The catechol - O - methyltransferase ( COMT ) Val158Met polymorphism may be a risk factor for nicotine addiction .", "entity": [{"entity": "catechol", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "O", "entity_type": "Chemical", "pos": [15, 16]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "This study examined the influence of the COMT Val158Met polymorphism on subjective , physiological and cognitive effects of intravenous ( IV ) nicotine use in African Americans ( AAs ; n = 56 ) and European Americans ( EAs ; n = 68 ) smokers .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [143, 151]}], "task": "NER"}
{"text": "Overnight abstinent smokers received saline followed by 0 . 5 and 1 . 0 mg per 70 kg doses of nicotine , administered 30 min apart .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "Smokers with valine ( Val ) / Val genotype , compared with methionine ( Met ) carriers , had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking .", "entity": [{"entity": "valine", "entity_type": "Chemical", "pos": [13, 19]}, {"entity": "Val", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "Val", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "methionine", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "Met", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [137, 145]}], "task": "NER"}
{"text": "Women with Val / Val genotype reported greater difficulty concentrating and irritability than men with Val / Val or Met carrier genotypes .", "entity": [{"entity": "Val", "entity_type": "Chemical", "pos": [11, 14]}, {"entity": "Val", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "Val", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "Val", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "Met", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "The Val / Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure .", "entity": [{"entity": "Val", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "Val", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val / Val genotype smokers . The Pharmacogenomics Journal advance online publication , 5 March 2013 ; doi : 10 . 1038 / tpj . 2013 . 1 .", "entity": [{"entity": "Val", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "Val", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "Exclusive skeletal muscle correction does not modulate dystrophic heart disease in the aged mdx model of Duchenne cardiomyopathy .", "entity": [], "task": "NER"}
{"text": "Duchenne muscular dystrophy ( DMD ) is characterized by severe degeneration and necrosis of both skeletal and cardiac muscle .", "entity": [], "task": "NER"}
{"text": "While many experimental therapies have shown great promise in treating skeletal muscle disease , an effective therapy for Duchenne cardiomyopathy remains a challenge in large animal models and human patients .", "entity": [], "task": "NER"}
{"text": "The current views on cardiac consequences of skeletal muscle - centered therapy are controversial .", "entity": [], "task": "NER"}
{"text": "Studies performed in young adult mdx mice ( a mild DMD mouse model ) have yielded opposing results .", "entity": [], "task": "NER"}
{"text": "Since mdx mice do not develop dystrophic cardiomyopathy until >= 21 months of age , we reasoned that old mdx mice may represent a better model to assess the impact of skeletal muscle rescue on dystrophic heart disease .", "entity": [], "task": "NER"}
{"text": "Here , we aged skeletal muscle - specific micro - dystrophin transgenic mdx mice to 23 months and examined the cardiac phenotype .", "entity": [], "task": "NER"}
{"text": "As expected , transgenic mdx mice had minimal skeletal muscle disease and they also outperformed original mdx mice on treadmill running .", "entity": [], "task": "NER"}
{"text": "On cardiac examination , the dystrophin - null heart of transgenic mdx mice displayed severe cardiomyopathy matching that of non - transgenic mdx mice .", "entity": [], "task": "NER"}
{"text": "Specifically , both the strains showed similar heart fibrosis and cardiac function deterioration in systole and diastole .", "entity": [], "task": "NER"}
{"text": "Cardiac output and ejection fraction were also equally compromised .", "entity": [], "task": "NER"}
{"text": "Our results suggest that skeletal muscle rescue neither aggravates nor alleviates cardiomyopathy in aged mdx mice .", "entity": [], "task": "NER"}
{"text": "These findings underscore the importance of treating both skeletal and cardiac muscles in DMD therapy .", "entity": [], "task": "NER"}
{"text": "Transfection of Mammalian Cells Using Block Copolypeptide Vesicles .", "entity": [], "task": "NER"}
{"text": "An arginine - leucine block copolypeptide ( R60 L20 ) is synthesized , which is capable of forming vesicles with controllable sizes , able to transport hydrophilic cargo across the cell membrane , and exhibit relatively low cytotoxicity .", "entity": [{"entity": "arginine", "entity_type": "Chemical", "pos": [3, 11]}, {"entity": "leucine", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "The R60 L20 vesicles also possess the ability to deliver DNA into mammalian cells for transfection .", "entity": [], "task": "NER"}
{"text": "Although the transfection efficiency is lower than that of the commercially available transfection agent Lipofectamine 2000 , the R60 L20 vesicles are able to achieve transfection with significantly lower cytotoxicity and immunogenicity .", "entity": [{"entity": "Lipofectamine 2000", "entity_type": "Chemical", "pos": [105, 123]}], "task": "NER"}
{"text": "This behavior is potentially due to its stronger interaction with DNA which subsequently provides better protection against anionic heparin .", "entity": [], "task": "NER"}
{"text": "Buffer - Stable Chitosan - Polyglutamic Acid Hybrid Nanoparticles for Biomedical Applications .", "entity": [{"entity": "Polyglutamic Acid", "entity_type": "Chemical", "pos": [27, 44]}], "task": "NER"}
{"text": "In spite of their attractive features , widespread biomedical applications of CS nanoparticles are yet to be realized due to their poor stability in physiological conditions , such as in buffer system at pH 7 . 4 .", "entity": [], "task": "NER"}
{"text": "Buffer - stable chitosan - based hybrid NPs ( HNPs ) are reported and characterized .", "entity": [], "task": "NER"}
{"text": "Buffer stability is achieved by introducing polyglutamic acid to chitosan .", "entity": [{"entity": "polyglutamic acid", "entity_type": "Chemical", "pos": [44, 61]}], "task": "NER"}
{"text": "The effect of PGA to CS molar ratio and crosslinking on HNP integrity , buffer stability , and biodegradability are studied .", "entity": [{"entity": "PGA", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "Preliminary in vitro studies are carried out to evaluate targeted uptake efficiency of folate conjugated HNPs .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [87, 93]}], "task": "NER"}
{"text": "Successful demonstration of buffer stability and cancer cell targeting by HNPs achieves important milestones for chitosan - based nanoparticle technology .", "entity": [], "task": "NER"}
{"text": "Ni ( II ) - NTA Modified Poly ( ethylene imine ) Glycopolymers : Physicochemical Properties and First In Vitro Study of Polyplexes Formed with HIV - Derived Peptides .", "entity": [{"entity": "Ni ( II ) - NTA", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "Poly ( ethylene imine )", "entity_type": "Chemical", "pos": [25, 48]}], "task": "NER"}
{"text": "Alternative delivery entities are desirable in immunotherapies in which polyplexes are widely formed by electrostatic interactions to induce cellular uptake processes for bioactive molecules .", "entity": [], "task": "NER"}
{"text": "In our study , biocompatible Ni ( II ) - nitrilo ( triacetic acid ) - modified poly ( ethylene imine ) - maltose ( Ni - NTA - DG ) is realized and evaluated as complexation agent against His - tagged peptides using fluorescence polarization and dynamic light scattering .", "entity": [{"entity": "Ni ( II ) - nitrilo ( triacetic acid )", "entity_type": "Chemical", "pos": [29, 67]}, {"entity": "poly ( ethylene imine ) - maltose", "entity_type": "Chemical", "pos": [79, 112]}, {"entity": "Ni - NTA - DG", "entity_type": "Chemical", "pos": [115, 128]}, {"entity": "His", "entity_type": "Chemical", "pos": [187, 190]}], "task": "NER"}
{"text": "The polyplexes are stable until a pH of 6 . 5 - 6 . 0 , and also up to 50 mM of imidazole .", "entity": [{"entity": "imidazole", "entity_type": "Chemical", "pos": [80, 89]}], "task": "NER"}
{"text": "A first uptake approach shows that polyplexes lead to an increase in peptide uptake in monocyte - derived immature dendritic cells .", "entity": [], "task": "NER"}
{"text": "In summary , Ni - NTA - DG represents a promising ( delivery ) platform for forthcoming in vitro applications .", "entity": [{"entity": "Ni - NTA - DG", "entity_type": "Chemical", "pos": [13, 26]}], "task": "NER"}
{"text": "Supramolecular cl . . . h and o . . . h interactions in self - assembled 1 , 5 - dichloroanthraquinone layers on au ( 111 ) .", "entity": [{"entity": "cl", "entity_type": "Chemical", "pos": [15, 17]}, {"entity": "h", "entity_type": "Chemical", "pos": [24, 25]}, {"entity": "o", "entity_type": "Chemical", "pos": [30, 31]}, {"entity": "h", "entity_type": "Chemical", "pos": [38, 39]}, {"entity": "1 , 5 - dichloroanthraquinone", "entity_type": "Chemical", "pos": [73, 102]}, {"entity": "au ( 111 )", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "The role of halogen bonds in self - assembled networks for systems with Br and I ligands has recently been studied with scanning tunneling microscopy ( STM ) , which provides physical insight at the atomic scale .", "entity": [{"entity": "halogen", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "Br", "entity_type": "Chemical", "pos": [72, 74]}, {"entity": "I", "entity_type": "Chemical", "pos": [79, 80]}], "task": "NER"}
{"text": "Here , we study the supramolecular interactions of 1 , 5 - dichloroanthraquinone molecules on Au ( 111 ) , including Cl ligands , by using STM .", "entity": [{"entity": "1 , 5 - dichloroanthraquinone", "entity_type": "Chemical", "pos": [51, 80]}, {"entity": "Au ( 111 )", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [117, 119]}], "task": "NER"}
{"text": "Two different molecular structures of chevron and square networks are observed , and their molecular models are proposed .", "entity": [], "task": "NER"}
{"text": "Both molecular structures are stabilized by intermolecular Cl . . . H and O . . . H hydrogen bonds with marginal contributions from Cl - related halogen bonds , as revealed by density functional theory calculations .", "entity": [{"entity": "Cl", "entity_type": "Chemical", "pos": [59, 61]}, {"entity": "H", "entity_type": "Chemical", "pos": [68, 69]}, {"entity": "O", "entity_type": "Chemical", "pos": [74, 75]}, {"entity": "H", "entity_type": "Chemical", "pos": [82, 83]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [132, 134]}, {"entity": "halogen", "entity_type": "Chemical", "pos": [145, 152]}], "task": "NER"}
{"text": "Our study shows that , in contrast to Br - and I - related halogen bonds , Cl - related halogen bonds weakly contribute to the molecular structure due to a modest positive potential ( sigma hole ) of the Cl ligands .", "entity": [{"entity": "Br", "entity_type": "Chemical", "pos": [38, 40]}, {"entity": "I", "entity_type": "Chemical", "pos": [47, 48]}, {"entity": "halogen", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [75, 77]}, {"entity": "halogen", "entity_type": "Chemical", "pos": [88, 95]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [204, 206]}], "task": "NER"}
{"text": "Dissecting the relative contribution of OATP1B1 - mediated uptake of xenobiotics into human hepatocytes using siRNA .", "entity": [], "task": "NER"}
{"text": "Organic anion transporting polypeptide 1B1 plays a pivotal role in the disposition of many anionic drugs .", "entity": [], "task": "NER"}
{"text": "Significant overlap in substrate specificity between individual OATP isoforms has hampered the identification of the relative importance of individual isoforms for hepatic uptake of xenobiotics .", "entity": [], "task": "NER"}
{"text": "The present study focused on the use of siRNA technology to decrease OATP1B1 selectively in human hepatocytes .", "entity": [], "task": "NER"}
{"text": "Following delivery of siRNA by the novel lipid , AtuFECT01 , mRNA expression of OATP1B1 was reduced by 94 % - 98 % with no significant toxicity .", "entity": [], "task": "NER"}
{"text": "Off - target effects were also shown to be minimal as evidenced by the expression of common drug metabolizing enzymes , transporters , nuclear receptors and associated co - regulators .", "entity": [], "task": "NER"}
{"text": "Uptake of estrone - 3 - sulfate ( 5 nM ) by OATP1B1 was reduced by 82 % - 95 % .", "entity": [{"entity": "estrone - 3 - sulfate", "entity_type": "Chemical", "pos": [10, 31]}], "task": "NER"}
{"text": "This methodology was subsequently used to assess the relative contribution of OATP1B1 uptake in human hepatocytes for olmesartan ( 42 % - 62 % ) , valsartan ( 28 % - 81 % ) , rosuvastatin ( 64 % - 72 % ) , pitavastatin ( 84 % - 98 % ) and lopinavir ( 64 % - 89 % ) .", "entity": [{"entity": "olmesartan", "entity_type": "Chemical", "pos": [118, 128]}, {"entity": "valsartan", "entity_type": "Chemical", "pos": [147, 156]}, {"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [175, 187]}, {"entity": "pitavastatin", "entity_type": "Chemical", "pos": [206, 218]}, {"entity": "lopinavir", "entity_type": "Chemical", "pos": [239, 248]}], "task": "NER"}
{"text": "These data are consistent with previous values obtained using a relative activity factor approach .", "entity": [], "task": "NER"}
{"text": "The siRNA approach provides a robust and reproducible method for assessing the relative contribution of OATP1B1 to hepatic uptake of new chemical entities .", "entity": [], "task": "NER"}
{"text": "The technique also has potential utility in facilitating detailed characterization of drug - drug interactions involving hepatic drug transporters .", "entity": [], "task": "NER"}
{"text": "Synthesis of mixed ceramic Mg ( x ) Zn ( 1 - x ) O nanofibers via Mg2 + doping using sol - gel electrospinning .", "entity": [{"entity": "Mg ( x ) Zn ( 1 - x ) O", "entity_type": "Chemical", "pos": [27, 50]}, {"entity": "Mg2 +", "entity_type": "Chemical", "pos": [66, 71]}], "task": "NER"}
{"text": "We report on the synthesis of tuned energy band gap Mg ( x ) Zn ( 1 - x ) O nanofibers ( NFs ) with different Mg ( 2 + ) content via the sol - gel electrospinning ( ES ) technique wherein the addition of the doping material affects not only the morphologies of as - spun ZnAc / PVA and MgAc / ZnAc / PVA nanofibers but also the crystal microstructure and optical properties of calcined ZnO and Mg ( x ) Zn ( 1 - x ) O nanofibers .", "entity": [{"entity": "Mg ( x ) Zn ( 1 - x ) O", "entity_type": "Chemical", "pos": [52, 75]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [110, 120]}, {"entity": "ZnAc", "entity_type": "Chemical", "pos": [271, 275]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [278, 281]}, {"entity": "MgAc", "entity_type": "Chemical", "pos": [286, 290]}, {"entity": "ZnAc", "entity_type": "Chemical", "pos": [293, 297]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [300, 303]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [386, 389]}, {"entity": "Mg ( x ) Zn ( 1 - x ) O", "entity_type": "Chemical", "pos": [394, 417]}], "task": "NER"}
{"text": "Following an appropriate aqueous solution preparation of magnesium acetate ( MgAc ) and zinc acetate ( ZnAc ) with poly ( vinyl alcohol ) ( PVA ) , electrospinning is performed and then as - spun nanofibers are calcined in an air atmosphere at 600 degrees C for 3 h .", "entity": [{"entity": "magnesium acetate", "entity_type": "Chemical", "pos": [57, 74]}, {"entity": "MgAc", "entity_type": "Chemical", "pos": [77, 81]}, {"entity": "zinc acetate", "entity_type": "Chemical", "pos": [88, 100]}, {"entity": "ZnAc", "entity_type": "Chemical", "pos": [103, 107]}, {"entity": "poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [115, 137]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [140, 143]}], "task": "NER"}
{"text": "As - spun and calcined nanofiber diameters and morphologies are evaluated with scanning ( SEM ) and transmission ( TEM ) electron microscopies , whereas crystalline microstructural interpretations of ZnO and Mg ( x ) Zn ( 1 - x ) O are conducted with wide - angle X - ray diffraction spectra ( XRD ) .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [200, 203]}, {"entity": "Mg ( x ) Zn ( 1 - x ) O", "entity_type": "Chemical", "pos": [208, 231]}], "task": "NER"}
{"text": "Surface chemical composition and elemental evaluation of calcined nanofibers are examined with X - ray photoelectron spectroscopy ( XPS ) , and optical properties and crystal defect analyses of the calcined nanofibers are conducted with photoluminescence spectra ( PL ) .", "entity": [], "task": "NER"}
{"text": "We observe a sharp reduction in fiber diameter upon calcination as a result of the removal of organic species from the fibers and conversion of ceramic precursors into ceramic nanofibers , and the appearance of a range of fiber morphologies from \" bead in a string \" to \" sesame seed \" coverage depending on fiber composition .", "entity": [], "task": "NER"}
{"text": "Because Zn ( 2 + ) and Mg ( 2 + ) have similar ionicity and atomic radii , some Zn ( 2 + ) atoms are replaced by Mg ( 2 + ) atoms in the crystals , leading to a change in the properties of crystal lattices .", "entity": [{"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [8, 18]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [113, 123]}], "task": "NER"}
{"text": "The band gap energy of the calcined fibers increases significantly with addition of Mg ( 2 + ) along with an increase in the ultraviolet ( UV ) photoluminescence emission of the fibers .", "entity": [{"entity": "Mg ( 2 + )", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "Fengycin C Produced by Bacillus subtilis EA - CB0015 .", "entity": [{"entity": "Fengycin C", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Bacillus subtilis EA - CB0015 was isolated from the phyllosphere of a banana plant and tested for its potential to produce bioactive compounds against Mycosphaerella fijiensis .", "entity": [], "task": "NER"}
{"text": "Using a dual plate culture technique the cell - free supernatant of B . subtilis EA - CB0015 produced inhibition values of 89 +/- 1 % .", "entity": [], "task": "NER"}
{"text": "The active compounds were purified by solid - phase extraction and HPLC , and their primary structures determined using mass spectrometry and amino acid analysis .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [142, 152]}], "task": "NER"}
{"text": "A new fengycin isoform , fengycin C , with the amino acid sequence Glu - Orn - Tyr - Thr - Glu - Val - Pro - Gln - Thr - Ile was isolated .", "entity": [{"entity": "fengycin", "entity_type": "Chemical", "pos": [6, 14]}, {"entity": "fengycin C", "entity_type": "Chemical", "pos": [25, 35]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "Glu - Orn - Tyr - Thr - Glu - Val - Pro - Gln - Thr - Ile", "entity_type": "Chemical", "pos": [67, 124]}], "task": "NER"}
{"text": "The peptidic moiety differs from fengycin B at position 9 and from fengycin A at positions 6 and 9 .", "entity": [{"entity": "fengycin B", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "fengycin A", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "The beta - hydroxy fatty acyl chain is connected to the N - terminal of the decapeptide and can be saturated or unsaturated , ranging from 14 to 18 carbons .", "entity": [{"entity": "beta - hydroxy fatty acyl", "entity_type": "Chemical", "pos": [4, 29]}, {"entity": "N", "entity_type": "Chemical", "pos": [56, 57]}, {"entity": "decapeptide", "entity_type": "Chemical", "pos": [76, 87]}, {"entity": "carbons", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "The C - terminal residue of the peptidic moiety is linked to the tyrosine residue at position 3 , forming the branching point of the acyl peptide and the eight - membered cyclic lactone .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [65, 73]}, {"entity": "acyl", "entity_type": "Chemical", "pos": [133, 137]}, {"entity": "cyclic lactone", "entity_type": "Chemical", "pos": [171, 185]}], "task": "NER"}
{"text": "Controlling spontaneous emission with plasmonic optical patch antennas .", "entity": [], "task": "NER"}
{"text": "We experimentally demonstrate the control of the spontaneous emission rate and the radiation pattern of colloidal quantum dots deterministically positioned in a plasmonic patch antenna .", "entity": [], "task": "NER"}
{"text": "The antenna consists of a thin gold microdisk separated from a planar gold layer by a few tens of nanometers thick dielectric layer .", "entity": [], "task": "NER"}
{"text": "The emitters are shown to radiate through the entire patch antenna in a highly directional and vertical radiation pattern .", "entity": [], "task": "NER"}
{"text": "Strong acceleration of spontaneous emission is observed , depending on the antenna geometry .", "entity": [], "task": "NER"}
{"text": "Considering the double dipole structure of the emitters , this corresponds to a Purcell factor up to 80 for dipoles perpendicular to the disk .", "entity": [], "task": "NER"}
{"text": "Redox regulation of protein kinases .", "entity": [], "task": "NER"}
{"text": "Reactive oxygen species ( ROS ) have been long regarded as by - products of a cascade of reactions stemming from cellular oxygen metabolism , which , if they accumulate to toxic levels , can have detrimental effects on cellular biomolecules .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [9, 15]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [122, 128]}], "task": "NER"}
{"text": "However , more recently , the recognition of ROS as mediators of cellular communications has led to their classification as signalling mediators in their own right .", "entity": [], "task": "NER"}
{"text": "The prototypic redox - regulated targets downstream of ROS are the protein tyrosine phosphatases , and the wealth of research that has focused on this area has come to shape our understanding of how redox - signalling contributes to and facilitates protein tyrosine phosphorylation signalling cascades .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [75, 83]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [257, 265]}], "task": "NER"}
{"text": "However , it is becoming increasingly apparent that there is more to this system than simply the negative regulation of protein tyrosine phosphatases .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "Identification of redox - sensitive kinases such as Src led to the slow emergence of a role for redox regulation of tyrosine kinases .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "A flow of evidence , which has increased exponentially in recent times as a result of the development of new methods for the detection of oxidative modifications , demonstrates that , by concurrent oxidative activation of tyrosine kinases , ROS fine tune the duration and amplification of the phosphorylation signal .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [222, 230]}], "task": "NER"}
{"text": "A more thorough understanding of the complex regulatory mechanism of redox - modification will allow targeting of both the production of ROS and their downstream effectors for therapeutic purposes .", "entity": [], "task": "NER"}
{"text": "The present review assesses the most relevant recent literature that demonstrates a role for kinase regulation by oxidation , highlights the most significant findings and proposes future directions for this crucial area of redox biology .", "entity": [], "task": "NER"}
{"text": "Antitubercular diterpenoids from Vitex trifolia .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [15, 27]}], "task": "NER"}
{"text": "A new halimane diterpenoid , 13 - hydroxy - 5 ( 10 ) , 14 - halimadien - 6 - one ( 1 ) and two new labdane diterpenoids , 6 alpha , 7 alpha - diacetoxy - 13 - hydroxy - 8 ( 9 ) , 14 - labdadien ( 2 ) and 9 - hydroxy - 13 ( 14 ) - labden - 15 , 16 - olide ( 3 ) , were isolated for the first time , along with fifteen known compounds , from the hexane soluble fraction of methanolic extract of Vitex trifolia leaves .", "entity": [{"entity": "halimane diterpenoid", "entity_type": "Chemical", "pos": [6, 26]}, {"entity": "13 - hydroxy - 5 ( 10 ) , 14 - halimadien - 6 - one", "entity_type": "Chemical", "pos": [29, 80]}, {"entity": "labdane diterpenoids", "entity_type": "Chemical", "pos": [99, 119]}, {"entity": "6 alpha , 7 alpha - diacetoxy - 13 - hydroxy - 8 ( 9 ) , 14 - labdadien", "entity_type": "Chemical", "pos": [122, 193]}, {"entity": "9 - hydroxy - 13 ( 14 ) - labden - 15 , 16 - olide", "entity_type": "Chemical", "pos": [204, 254]}, {"entity": "hexane", "entity_type": "Chemical", "pos": [344, 350]}], "task": "NER"}
{"text": "The structures of these new diterpenoids were elucidated by spectral analysis .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "Their relative configurations were established using analysis of NOESY correlations and coupling constants observed in ( 1 ) H NMR .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [119, 126]}], "task": "NER"}
{"text": "Compounds 2 , 3 and another known diterpenoid , isoambreinolide ( 4 ) were evaluated for antitubercular activity .", "entity": [{"entity": "diterpenoid", "entity_type": "Chemical", "pos": [34, 45]}, {"entity": "isoambreinolide", "entity_type": "Chemical", "pos": [48, 63]}], "task": "NER"}
{"text": "3 and 4 exhibited antitubercular activity ( MIC = 100 and 25 mu g / ml ) against Mycobacterium tuberculosis H37Rv in BACTEC - 460 assay .", "entity": [], "task": "NER"}
{"text": "Aldehyde oxidase importance in vivo in xenobiotic metabolism : imidacloprid nitroreduction in mice .", "entity": [{"entity": "Aldehyde", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "imidacloprid", "entity_type": "Chemical", "pos": [63, 75]}], "task": "NER"}
{"text": "Aldehyde oxidase ( AOX ) metabolizes many xenobiotics in vitro , but its importance in vivo is usually unknown relative to cytochrome P450s ( CYPs ) and other detoxification systems .", "entity": [{"entity": "Aldehyde", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Currently , the most important insecticides are neonicotinoids , which are metabolized in vitro by AOX on reduction of the nitroimino group and by CYPs via oxidation reactions .", "entity": [{"entity": "neonicotinoids", "entity_type": "Chemical", "pos": [48, 62]}, {"entity": "nitroimino", "entity_type": "Chemical", "pos": [123, 133]}], "task": "NER"}
{"text": "The goal of this study was to establish the relative importance of AOX and CYPs in vivo using the mouse model .", "entity": [], "task": "NER"}
{"text": "The procedure was to reduce liver AOX activity by providing tungsten or hydralazine in the drinking water or to use the AOX - deficient DBA / 2 mouse strain .", "entity": [{"entity": "tungsten", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "hydralazine", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "None of these approaches reduced CYP activity measured in vitro with an isozyme nonspecific substrate .", "entity": [], "task": "NER"}
{"text": "Liver AOX activity was reduced by 45 % with tungsten and 61 % with hydralazine and 81 % in AOX - deficient mice relative to controls .", "entity": [{"entity": "tungsten", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "hydralazine", "entity_type": "Chemical", "pos": [67, 78]}], "task": "NER"}
{"text": "When mice were treated ip with the major neonicotinoid imidacloprid ( IMI ) , metabolism by CYP oxidation reactions was not appreciably affected , whereas the AOX - generated nitrosoguanidine metabolite was decreased by 30 % with tungsten and 56 % with hydralazine and 86 % in the AOX - deficient mice .", "entity": [{"entity": "imidacloprid", "entity_type": "Chemical", "pos": [55, 67]}, {"entity": "IMI", "entity_type": "Chemical", "pos": [70, 73]}, {"entity": "nitrosoguanidine", "entity_type": "Chemical", "pos": [175, 191]}, {"entity": "tungsten", "entity_type": "Chemical", "pos": [230, 238]}, {"entity": "hydralazine", "entity_type": "Chemical", "pos": [253, 264]}], "task": "NER"}
{"text": "The other IMI nitroreduction metabolite , desnitro - IMI , was decreased by 55 % , 65 % , and 81 % with tungsten , hydralazine , and in the AOX - deficient mice , respectively .", "entity": [{"entity": "IMI", "entity_type": "Chemical", "pos": [10, 13]}, {"entity": "IMI", "entity_type": "Chemical", "pos": [53, 56]}, {"entity": "tungsten", "entity_type": "Chemical", "pos": [104, 112]}, {"entity": "hydralazine", "entity_type": "Chemical", "pos": [115, 126]}], "task": "NER"}
{"text": "Thus , decreasing liver AOX activity by three quite different procedures gave a corresponding decrease for in vivo reductive metabolites in the liver of IMI - treated mice .", "entity": [{"entity": "IMI", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "Possible AOX involvement in IMI metabolism in insects was evaluated using AOX - expressing and AOX - deficient Drosophila , but no differences were found in IMI nitroreduction or sensitivity between the two strains .", "entity": [{"entity": "IMI", "entity_type": "Chemical", "pos": [28, 31]}, {"entity": "IMI", "entity_type": "Chemical", "pos": [157, 160]}], "task": "NER"}
{"text": "This is the first study to establish the in vivo relevance of AOX in neonicotinoid metabolism in mammals and one of the first for xenobiotics in general .", "entity": [{"entity": "neonicotinoid", "entity_type": "Chemical", "pos": [69, 82]}], "task": "NER"}
{"text": "Modulation of membrane phospholipids , the cytosolic calcium influx and cell proliferation following treatment of B16 - F10 cells with recombinant phospholipase - D from Loxosceles intermedia ( brown spider ) venom .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [53, 60]}], "task": "NER"}
{"text": "The mechanism through which brown spiders ( Loxosceles genus ) cause dermonecrosis , dysregulated inflammatory responses , hemolysis and platelet aggregation , which are effects reported following spider bites , is currently attributed to the presence of phospholipase - D in the venom .", "entity": [], "task": "NER"}
{"text": "In the present investigation , through two - dimensional immunoblotting , we observed immunological cross - reactivity for at least 25 spots in crude Loxosceles intermedia venom , indicating high expression levels for different isoforms of phospholipase - D .", "entity": [], "task": "NER"}
{"text": "Using a recombinant phospholipase - D from the venom gland of L . intermedia ( LiRecDT1 ) in phospholipid - degrading kinetic experiments , we determined that this phospholipase - D mainly hydrolyzes synthetic sphingomyelin in a time - dependent manner , generating ceramide 1 - phosphate plus choline , as well as lysophosphatidylcholine , generating lysophosphatidic acid plus choline , but exhibits little activity against phosphatidylcholine .", "entity": [{"entity": "sphingomyelin", "entity_type": "Chemical", "pos": [210, 223]}, {"entity": "ceramide 1 - phosphate", "entity_type": "Chemical", "pos": [266, 288]}, {"entity": "choline", "entity_type": "Chemical", "pos": [294, 301]}, {"entity": "lysophosphatidylcholine", "entity_type": "Chemical", "pos": [315, 338]}, {"entity": "lysophosphatidic acid", "entity_type": "Chemical", "pos": [352, 373]}, {"entity": "choline", "entity_type": "Chemical", "pos": [379, 386]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [426, 445]}], "task": "NER"}
{"text": "Through immunofluorescence assays with antibodies against LiRecDT1 and using a recombinant GFP - LiRecDT1 fusion protein , we observed direct binding of LiRecDT1 to the membrane of B16 - F10 cells .", "entity": [], "task": "NER"}
{"text": "We determined that LiRecDT1 hydrolyzes phospholipids in detergent extracts and from ghosts of B16 - F10 cells , generating choline , indicating that the enzyme can access and modulate and has activity against membrane phospholipids .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "Additionally , using Fluo - 4 , a calcium - sensitive fluorophore , it was shown that treatment of cells with phospholipase - D induced an increase in the calcium concentration in the cytoplasm , but without altering viability or causing damage to cells .", "entity": [{"entity": "Fluo - 4", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [155, 162]}], "task": "NER"}
{"text": "Finally , based on the known endogenous activity of phospholipase - D as an inducer of cell proliferation and the fact that LiRecDT1 binds to the cell surface , hydrolyzing phospholipids to generate bioactive lipids , we employed LiRecDT1 as an exogenous source of phospholipase - D in B16 - F10 cells .", "entity": [], "task": "NER"}
{"text": "Treatment of the cells was effective in increasing their proliferation in a time - and concentration - dependent manner , especially in the presence of synthetic sphingomyelin in the medium .", "entity": [{"entity": "sphingomyelin", "entity_type": "Chemical", "pos": [162, 175]}], "task": "NER"}
{"text": "The results described herein indicate the ability of brown spider phospholipase - D to induce the generation of bioactive phospholipids , calcium influx into the cytoplasm and cell proliferation , suggesting that this molecule can be used as a bioactive tool for experimental protocols in cell biology .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "Identification of functionally relevant lysine residues that modulate human farnesoid x receptor activation .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [40, 46]}], "task": "NER"}
{"text": "Base amino acid lysine residues play an important role in regulation of nuclear receptors [ e . g . , farnesyl X receptor ( FXR ) ] , leading to enhanced or suppressed biologic activity .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [5, 15]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [16, 22]}, {"entity": "farnesyl", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "To understand the molecular mechanisms and the subsequent effects in modulating FXR functions in diverse biologic processes , we individually replaced eight highly conserved lysine residues of human FXR ( hFXR ) with arginine .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [174, 180]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [217, 225]}], "task": "NER"}
{"text": "The effects of each mutated FXR on target gene activation , subcellular localization , protein - protein association , and protein - DNA interaction were investigated .", "entity": [], "task": "NER"}
{"text": "Results demonstrated that K122R , K210R , K339R , and K460R mutants of hFXR significantly impaired target gene [ organic solute transporter alpha / beta and bile salt export pump ( BSEP ) ] promoter reporter activity in a ligand - dependent fashion .", "entity": [{"entity": "bile salt", "entity_type": "Chemical", "pos": [157, 166]}], "task": "NER"}
{"text": "None of the four mutants affected the nuclear localization of FXR .", "entity": [], "task": "NER"}
{"text": "Protein interaction studies show that K210R slightly but significantly decreased FXR / retinoid X receptor ( RXR ) binding affinity but enhanced the interaction of FXR with lysine methyltransferase Set7 / 9 by ~ 21 % .", "entity": [{"entity": "retinoid", "entity_type": "Chemical", "pos": [87, 95]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [173, 179]}], "task": "NER"}
{"text": "K460R decreased the FXR interaction with Set7 / 9 by ~ 45 % but had no significant effects on interaction with RXR .", "entity": [], "task": "NER"}
{"text": "Electrophoretic mobility shift assays demonstrated that hFXR - K210R and - K339R reduced the protein - DNA ( IR1 element at hBSEP promoter ) binding affinity by ~ 80 and ~ 90 % , respectively .", "entity": [], "task": "NER"}
{"text": "Computational - based protein modeling studies were consistent with these results and provided further insights into the potential underlying mechanisms responsible for these results .", "entity": [], "task": "NER"}
{"text": "In conclusion , four highly conserved lysine residues of hFXR , K122 , K210 , K339 , and K460 , have been identified that play a critical role in FXR target gene regulation and molecular interaction ( protein - protein and protein - DNA ) .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [38, 44]}], "task": "NER"}
{"text": "NMR - based metabonomic in hippocampus , nucleus accumbens and prefrontal cortex of methamphetamine - sensitized rats .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [84, 99]}], "task": "NER"}
{"text": "( 1 ) H NMR spectroscopy was applied to investigate the changes of cerebral metabolites in brain hippocampus , nucleus accumbens ( NAC ) and prefrontal cortex ( PFC ) of the rats subjected to subcutaneous twice - daily injections of 2 . 5mg / kg methamphetamine ( MAP ) for 7 days .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [246, 261]}, {"entity": "MAP", "entity_type": "Chemical", "pos": [264, 267]}], "task": "NER"}
{"text": "The results indicated that MAP exposure induced significant behavioral sensitization and altered cerebral metabolites in rats .", "entity": [{"entity": "MAP", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "The neurotransmitters glutamate , glutamine and GABA significantly decreased in hippocampus , NAC and PFC .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "Specifically , increased succinic acid semialdehyde , a metabolism product of GABA , was observed in hippocampus .", "entity": [{"entity": "succinic acid semialdehyde", "entity_type": "Chemical", "pos": [25, 51]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [78, 82]}], "task": "NER"}
{"text": "Additionally , decreased serotonin was observed in both NAC and PFC , whereas decreased dopamine was only observed in NAC after repeated MAP treatment .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [25, 34]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [88, 96]}, {"entity": "MAP", "entity_type": "Chemical", "pos": [137, 140]}], "task": "NER"}
{"text": "Glutathione obviously decreased in above brain regions , whereas acetylcysteine declined in hippocampus and NAC , and taurine declined in NAC and PFC .", "entity": [{"entity": "Glutathione", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "acetylcysteine", "entity_type": "Chemical", "pos": [65, 79]}, {"entity": "taurine", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "Homocysteic acid was elevated in hippocampus and NAC by repeated MAP administration .", "entity": [{"entity": "Homocysteic acid", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "MAP", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "Membrane ingredients like phosphocholine elevated in response to MAP administration in NAC and PFC .", "entity": [{"entity": "phosphocholine", "entity_type": "Chemical", "pos": [26, 40]}, {"entity": "MAP", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "N - Acetyl - aspartate , a marker of neuronal viability , decreased in the three regions ; however , myo - inositol , a glial cell marker , increased in hippocampus and PFC .", "entity": [{"entity": "N - Acetyl - aspartate", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "myo - inositol", "entity_type": "Chemical", "pos": [101, 115]}], "task": "NER"}
{"text": "Tricarboxylic acid cycle intermediate products , such as alpha - ketoglutarate , succinate , citrate and the methionine significantly decreased in above three brain regions after MAP administration ; however , ADP decreased in hippocampus .", "entity": [{"entity": "Tricarboxylic acid", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "alpha - ketoglutarate", "entity_type": "Chemical", "pos": [57, 78]}, {"entity": "succinate", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [93, 100]}, {"entity": "methionine", "entity_type": "Chemical", "pos": [109, 119]}, {"entity": "MAP", "entity_type": "Chemical", "pos": [179, 182]}, {"entity": "ADP", "entity_type": "Chemical", "pos": [210, 213]}], "task": "NER"}
{"text": "These results indicate that repeated MAP treatment causes neurotransmitters disturbance , imbalance between oxidative stress and antioxidants , and gliosis in hippocampus , NAC and PFC .", "entity": [{"entity": "MAP", "entity_type": "Chemical", "pos": [37, 40]}], "task": "NER"}
{"text": "Profound metabolic changes detected across brain regions provide the first evidence of metabonomic changes in MAP - induced sensitized rats .", "entity": [{"entity": "MAP", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "Alcohol cirrhosis alters nuclear receptor and drug transporter expression in human liver .", "entity": [{"entity": "Alcohol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Unsafe use of alcohol results in approximately 2 . 5 million deaths worldwide , with cirrhosis contributing to 16 . 6 % of reported deaths .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "Serum insulin levels are often elevated in alcoholism and may result in diabetes , which is why alcoholic liver disease and diabetes often are present together .", "entity": [], "task": "NER"}
{"text": "Because there is a sizable population with these diseases alone or in combination , the purpose of this study was to determine whether transporter expression in human liver is affected by alcoholic cirrhosis , diabetes , and alcoholic cirrhosis coexisting with diabetes .", "entity": [], "task": "NER"}
{"text": "Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals and can be determinants of drug - induced liver injury .", "entity": [], "task": "NER"}
{"text": "Drug transporter expression and transcription factor - relative mRNA and protein expression in normal , diabetic , cirrhotic , and cirrhosis with diabetes human livers were quantified .", "entity": [], "task": "NER"}
{"text": "Cirrhosis significantly increased ABCC4 , 5 , ABCG2 , and solute carrier organic anion ( SLCO ) 2B1 mRNA expression and decreased SLCO1B3 mRNA expression in the liver .", "entity": [], "task": "NER"}
{"text": "ABCC1 , 3 - 5 , and ABCG2 protein expression was also upregulated by alcoholic cirrhosis .", "entity": [], "task": "NER"}
{"text": "ABCC3 - 5 and ABCG2 protein expression was also upregulated in diabetic cirrhosis .", "entity": [], "task": "NER"}
{"text": "Cirrhosis increased nuclear factor E2 - related factor 2 mRNA expression , whereas it decreased pregnane - X - receptor and farnesoid - X - receptor mRNA expression in comparison with normal livers .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "Hierarchical cluster analysis indicated that expressions of ABCC2 , 3 , and 6 ; SLCO1B1 and 1B3 ; and ABCC4 and 5 were more closely related in the livers from this cohort .", "entity": [], "task": "NER"}
{"text": "Overall , alcoholic cirrhosis altered transporter expression in human liver .", "entity": [], "task": "NER"}
{"text": "Octahedral Co3O4 particles threaded by carbon nanotube arrays as integrated structure anodes for lithium ion batteries .", "entity": [{"entity": "Co3O4", "entity_type": "Chemical", "pos": [11, 16]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [39, 45]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [97, 104]}], "task": "NER"}
{"text": "Octahedral Co3O4 particles threaded by ultra - long multi - walled carbon nanotube ( MWCNT ) arrays were prepared by a hydrothermal process and subsequent calcination .", "entity": [{"entity": "Co3O4", "entity_type": "Chemical", "pos": [11, 16]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [67, 73]}], "task": "NER"}
{"text": "The Co3O4 octahedron with the ( 111 ) facets attaches to MWCNTs uniformly and closely .", "entity": [{"entity": "Co3O4", "entity_type": "Chemical", "pos": [4, 9]}], "task": "NER"}
{"text": "The composite can be used as an integrated anode for lithium ion batteries ( LIBs ) without any other additives ( such as conductive additives and polymer binder ) , which exhibits a high reversible capacity of 725 mA h g ( - 1 ) at a current density of 100 mA g ( - 1 ) , and excellent cyclic stability without capacity degradation over 100 cycles at a current density of 500 mA g ( - 1 ) .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [53, 60]}], "task": "NER"}
{"text": "The high performance can be attributed to the unique structure : ( i ) the ultra - long MWCNT array facilitates fast electron transfer ; ( ii ) the tight adhesion between Co3O4 and MWCNTs prevents particle drifting and agglomeration ; ( iii ) the free space between MWCNTs promotes fast ion transport and alleviates the large volume variation during discharge - charge process .", "entity": [{"entity": "Co3O4", "entity_type": "Chemical", "pos": [171, 176]}], "task": "NER"}
{"text": "This work demonstrates the great potential of MWCNT arrays as substrate and provides insights for the design and direct use of MWCNT array - based materials in LIBs , which will be helpful for future development of high - performance electrode materials .", "entity": [], "task": "NER"}
{"text": "Clinical proof - of - concept study with MSDC - 0160 , a prototype mTOT - modulating insulin sensitizer .", "entity": [{"entity": "MSDC - 0160", "entity_type": "Chemical", "pos": [41, 52]}], "task": "NER"}
{"text": "It may be possible to achieve insulin sensitivity through the recently identified mitochondrial target of thiazolidinediones ( mTOT ) , thereby avoiding peroxisome proliferator - activated receptor - gamma ( PPAR - gamma ) - dependent side effects .", "entity": [{"entity": "thiazolidinediones", "entity_type": "Chemical", "pos": [106, 124]}], "task": "NER"}
{"text": "In this phase IIb clinical trial , 258 patients with type 2 diabetes completed a 12 - week protocol with 50 , 100 , or 150 mg of MSDC - 0160 ( an mTOT modulator ) , 45 mg pioglitazone HCl ( a PPAR - gamma agonist ) , or a placebo .", "entity": [{"entity": "MSDC - 0160", "entity_type": "Chemical", "pos": [129, 140]}, {"entity": "pioglitazone HCl", "entity_type": "Chemical", "pos": [171, 187]}], "task": "NER"}
{"text": "The two active treatments lowered fasting glucose levels to the same extent .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [42, 49]}], "task": "NER"}
{"text": "The decreases in glycated hemoglobin ( HbA1c ) observed with the two higher doses of MSDC - 0160 were not different from those associated with pioglitazone .", "entity": [{"entity": "MSDC - 0160", "entity_type": "Chemical", "pos": [85, 96]}, {"entity": "pioglitazone", "entity_type": "Chemical", "pos": [143, 155]}], "task": "NER"}
{"text": "By contrast , fluid retention as evidenced by reduction in hematocrit , red blood cells , and total hemoglobin was 50 % less in the MSDC - 0160 - treated groups .", "entity": [{"entity": "MSDC - 0160", "entity_type": "Chemical", "pos": [132, 143]}], "task": "NER"}
{"text": "There was also a smaller increase in high - molecular - weight ( HMW ) adiponectin with MSDC - 0160 than with pioglitazone ( P < 0 . 0001 ) , suggesting that MSDC - 0160 produces less expansion of white adipose tissue .", "entity": [{"entity": "MSDC - 0160", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "pioglitazone", "entity_type": "Chemical", "pos": [110, 122]}, {"entity": "MSDC - 0160", "entity_type": "Chemical", "pos": [158, 169]}], "task": "NER"}
{"text": "Thus , mTOT modulators may have glucose - lowering effects similar to those of pioglitazone but without the adverse effects associated with PPAR - gamma agonists .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "pioglitazone", "entity_type": "Chemical", "pos": [79, 91]}], "task": "NER"}
{"text": "Novel insights into the biology of interleukin - 32 .", "entity": [], "task": "NER"}
{"text": "Interleukin ( IL ) - 32 is known as a proinflammatory cytokine that is likely involved in several diseases , including infections , chronic inflammation , and cancer .", "entity": [], "task": "NER"}
{"text": "Since the first report in 2005 , IL - 32 has been the subject of numerous studies to unravel the biological function of this molecule .", "entity": [], "task": "NER"}
{"text": "For example , silencing of endogenous IL - 32 in primary or cell lines of human origin consistently suppressed responses to Toll - like receptors .", "entity": [], "task": "NER"}
{"text": "The protein folding structure of the six isoforms of IL - 32 does not resemble that of any classical cytokine and as of this writing , a specific IL - 32 receptor has not been identified .", "entity": [], "task": "NER"}
{"text": "Instead , we propose a mechanism by which exposure to extracellular IL - 32 or overexpression of the molecule results in binding to intracellular partners that influences functions such as gene expression , cell death , or survival .", "entity": [], "task": "NER"}
{"text": "As such , this review offers insights into the role of IL - 32 in several diseases , host defense , inflammation , immune function , and cancer .", "entity": [], "task": "NER"}
{"text": "Finally , possibilities to target IL - 32 in several diseases are proposed .", "entity": [], "task": "NER"}
{"text": "A method for non - invasive full - field imaging and quantification of chemical species .", "entity": [], "task": "NER"}
{"text": "We present a novel method for full - field scalar visualization and quantification of species concentration fields .", "entity": [], "task": "NER"}
{"text": "We term this method species - altered fluorescence imaging ( SAFI ) .", "entity": [], "task": "NER"}
{"text": "The method employs electrically neutral fluorescent dyes whose quantum yields are selectively quenched or enhanced by species of interest .", "entity": [], "task": "NER"}
{"text": "SAFI enables simultaneous imaging of material interfaces and provides non - invasive , scalar - field quantitation of two - dimensional species concentration fields .", "entity": [], "task": "NER"}
{"text": "We describe criteria for choosing SAFI dyes and tabulate 35 promising SAFI dyes and their relevant properties .", "entity": [], "task": "NER"}
{"text": "Next , we describe species concentration quantification with SAFI via Stern - Volmer quenching and discuss the sensitivity and resolution of our method .", "entity": [], "task": "NER"}
{"text": "We demonstrate this method with two dyes , 6 - methoxy - N - ( 3 - sulfopropyl ) quinolinium ( SPQ ) and 10 - ( 3 - sulfopropyl ) acridinium betaine ( SAB ) .", "entity": [{"entity": "6 - methoxy - N - ( 3 - sulfopropyl ) quinolinium", "entity_type": "Chemical", "pos": [43, 92]}, {"entity": "SPQ", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "10 - ( 3 - sulfopropyl ) acridinium betaine", "entity_type": "Chemical", "pos": [105, 148]}, {"entity": "SAB", "entity_type": "Chemical", "pos": [151, 154]}], "task": "NER"}
{"text": "We demonstrate our method in full - field visualization of several challenging electrokinetic flows : isotachophoresis ( ITP ) in both cationic and anionic modes , and in a convective electrokinetic instability ( EKI ) flow .", "entity": [], "task": "NER"}
{"text": "Through these experiments we collectively quantify ion concentration shock velocities , simultaneously measure concentrations of five species , and quantify the development of an unsteady , chaotic , 2D flow .", "entity": [], "task": "NER"}
{"text": "Gram - scale synthesis of graphene sheets by a catalytic arc - discharge method .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "Flake graphite is used as carbon source and ZnO or ZnS as catalyst in the synthesis of high - quality graphene sheets .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [6, 14]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [44, 47]}, {"entity": "ZnS", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "A catalytic growth mechanism for cathode - part graphene synthesis in the arc - discharge apparatus and an exfoliation mechanism for wall - part graphene synthesis are introduced .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [145, 153]}], "task": "NER"}
{"text": "N - doped cathode - part graphene and undoped wall - part graphene are formed simultaneously .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [0, 1]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [58, 66]}], "task": "NER"}
{"text": "Peptides as the next generation of anti - infectives .", "entity": [], "task": "NER"}
{"text": "Synthesis and large - scale manufacturing technologies are now available for the commercial production of even the most complex peptide anti - infectives .", "entity": [], "task": "NER"}
{"text": "Married with the potential of this class of molecule as the next generation of effective , resistance - free and safe antimicrobials , and a much better understanding of their biology , pharmacology and pharmacodynamics , the first regulatory approvals and introduction into clinical practice of these promising drug candidates will likely be soon .", "entity": [], "task": "NER"}
{"text": "This is a key juncture in the history / life cycle of peptide anti - infectives and , perhaps , their commercial and therapeutic potential is about to be realized .", "entity": [], "task": "NER"}
{"text": "This review highlights the promise of these agents as the next generation of therapeutics and summarizes the challenges faced in , and lessons learned from , the past .", "entity": [], "task": "NER"}
{"text": "Simultaneously strong and tough ultrafine continuous nanofibers .", "entity": [], "task": "NER"}
{"text": "Strength of structural materials and fibers is usually increased at the expense of strain at failure and toughness .", "entity": [], "task": "NER"}
{"text": "Recent experimental studies have demonstrated improvements in modulus and strength of electrospun polymer nanofibers with reduction of their diameter .", "entity": [], "task": "NER"}
{"text": "Nanofiber toughness has not been analyzed ; however , from the classical materials property trade - off , one can expect it to decrease .", "entity": [], "task": "NER"}
{"text": "Here , on the basis of a comprehensive analysis of long ( 5 - 10 mm ) individual polyacrylonitrile nanofibers , we show that nanofiber toughness also dramatically improves .", "entity": [{"entity": "polyacrylonitrile", "entity_type": "Chemical", "pos": [81, 98]}], "task": "NER"}
{"text": "Reduction of fiber diameter from 2 . 8 mu m to ~ 100 nm resulted in simultaneous increases in elastic modulus from 0 . 36 to 48 GPa , true strength from 15 to 1750 MPa , and toughness from 0 . 25 to 605 MPa with the largest increases recorded for the ultrafine nanofibers smaller than 250 nm .", "entity": [], "task": "NER"}
{"text": "The observed size effects showed no sign of saturation .", "entity": [], "task": "NER"}
{"text": "Structural investigations and comparisons with mechanical behavior of annealed nanofibers allowed us to attribute ultrahigh ductility ( average failure strain stayed over 50 % ) and toughness to low nanofiber crystallinity resulting from rapid solidification of ultrafine electrospun jets .", "entity": [], "task": "NER"}
{"text": "Demonstrated superior mechanical performance coupled with the unique macro - nano nature of continuous nanofibers makes them readily available for macroscopic materials and composites that can be used in safety - critical applications .", "entity": [], "task": "NER"}
{"text": "The proposed mechanism of simultaneously high strength , modulus , and toughness challenges the prevailing 50 year old paradigm of high - performance polymer fiber development calling for high polymer crystallinity and may have broad implications in fiber science and technology .", "entity": [], "task": "NER"}
{"text": "Diameter - Dependent Photocurrent in InAsSb Nanowire Infrared Photodetectors .", "entity": [{"entity": "InAsSb", "entity_type": "Chemical", "pos": [37, 43]}], "task": "NER"}
{"text": "Photoconductors using vertical arrays of InAs / InAs1 - xSbx nanowires with varying Sb composition x have been fabricated and characterized .", "entity": [{"entity": "InAs", "entity_type": "Chemical", "pos": [41, 45]}, {"entity": "InAs1 - xSbx", "entity_type": "Chemical", "pos": [48, 60]}, {"entity": "Sb", "entity_type": "Chemical", "pos": [84, 86]}], "task": "NER"}
{"text": "The spectrally resolved photocurrents are strongly diameter dependent with peaks , which are red - shifted with diameter , appearing for thicker wires .", "entity": [], "task": "NER"}
{"text": "Results from numerical simulations are in good agreement with the experimental data and reveal that the peaks are due to resonant modes that enhance the coupling of light into the wires .", "entity": [], "task": "NER"}
{"text": "Through proper selection of wire diameter , the absorptance can be increased by more than 1 order of magnitude at a specific wavelength compared to a thin planar film with the same amount of material .", "entity": [], "task": "NER"}
{"text": "A maximum 20 % cutoff wavelength of 5 . 7 mu m is obtained at 5 K for a wire diameter of 717 nm at a Sb content of x = 0 . 62 , but simulations predict that detection at longer wavelengths can be achieved by increasing the diameter .", "entity": [{"entity": "Sb", "entity_type": "Chemical", "pos": [101, 103]}], "task": "NER"}
{"text": "Furthermore , photodetection in InAsSb nanowire arrays integrated on Si substrates is also demonstrated .", "entity": [{"entity": "InAsSb", "entity_type": "Chemical", "pos": [32, 38]}, {"entity": "Si", "entity_type": "Chemical", "pos": [69, 71]}], "task": "NER"}
{"text": "Slip length measurement of confined air flow on three smooth surfaces .", "entity": [], "task": "NER"}
{"text": "An experimental measurement of the slip length of air flow close to three different solid surfaces is presented .", "entity": [], "task": "NER"}
{"text": "The substrate was driven by a nanopositioner moving toward an oscillating glass sphere glued to an atomic force microscopy ( AFM ) cantilever .", "entity": [], "task": "NER"}
{"text": "A large separation distance was used to get more effective data .", "entity": [], "task": "NER"}
{"text": "The slip length value was obtained by analyzing the amplitude and phase data of the cantilever .", "entity": [], "task": "NER"}
{"text": "The measurements show that the slip length does not depend on the oscillation amplitude of the cantilever .", "entity": [], "task": "NER"}
{"text": "Because of the small difference among the slip lengths of the three surfaces , a simplified analysis method was used .", "entity": [], "task": "NER"}
{"text": "The results show that on glass , graphite , and mica surfaces the slip lengths are 98 , 234 , and 110 nm , respectively .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "mica", "entity_type": "Chemical", "pos": [48, 52]}], "task": "NER"}
{"text": "Templating Sub - 10 nm Atomic Layer Deposited Oxide Nanostructures on Graphene via One - Dimensional Organic Self - Assembled Monolayers .", "entity": [{"entity": "Oxide", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "Graphene", "entity_type": "Chemical", "pos": [70, 78]}], "task": "NER"}
{"text": "Molecular - scale control over the integration of disparate materials on graphene is a critical step in the development of graphene - based electronics and sensors .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [73, 81]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [123, 131]}], "task": "NER"}
{"text": "Here , we report that self - assembled monolayers of 10 , 12 - pentacosadiynoic acid ( PCDA ) on epitaxial graphene can be used to template the reaction and directed growth of atomic layer deposited ( ALD ) oxide nanostructures with sub - 10 nm lateral resolution .", "entity": [{"entity": "10 , 12 - pentacosadiynoic acid", "entity_type": "Chemical", "pos": [53, 84]}, {"entity": "PCDA", "entity_type": "Chemical", "pos": [87, 91]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [207, 212]}], "task": "NER"}
{"text": "PCDA spontaneously assembles into well - ordered domains consisting of one - dimensional molecular chains that coat the entire graphene surface in a manner consistent with the symmetry of the underlying graphene lattice .", "entity": [{"entity": "PCDA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [127, 135]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [203, 211]}], "task": "NER"}
{"text": "Subsequently , zinc oxide and alumina ALD precursors are shown to preferentially react with the functional moieties of PCDA , resulting in templated oxide nanostructures .", "entity": [{"entity": "zinc oxide", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "alumina", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "PCDA", "entity_type": "Chemical", "pos": [119, 123]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [149, 154]}], "task": "NER"}
{"text": "The retention of the original one - dimensional molecular ordering following ALD is dependent on the chemical reaction pathway and the stability of the monolayer , which can be enhanced via ultraviolet - induced molecular cross - linking .", "entity": [], "task": "NER"}
{"text": "Oversampling to Overcome Overfitting : Exploring the Relationship between Data Set Composition , Molecular Descriptors , and Predictive Modeling Methods .", "entity": [], "task": "NER"}
{"text": "The traditional biological assay is very time - consuming , and thus the ability to quickly screen large numbers of compounds against a specific biological target is appealing .", "entity": [], "task": "NER"}
{"text": "To speed up the biological evaluation of compounds , high - throughput screening is widely used in the fields of biomedical , biological information , and drug discovery .", "entity": [], "task": "NER"}
{"text": "The research presented in this study focuses on the use of support vector machines , a machine learning method , various classes of molecular descriptors , and different sampling techniques to overcome overfitting to classify compounds for cytotoxicity with respect to the Jurkat cell line .", "entity": [], "task": "NER"}
{"text": "The cell cytotoxicity data set is imbalanced ( a few active compounds and very many inactive compounds ) , and the ability of the predictive modeling methods is adversely affected in these situations .", "entity": [], "task": "NER"}
{"text": "Commonly imbalanced data sets are overfit with respect to the dominant classified end point ; in this study the models routinely overfit toward inactive ( noncytotoxic ) compounds when the imbalance was substantial .", "entity": [], "task": "NER"}
{"text": "Support vector machine ( SVM ) models were used to probe the proficiency of different classes of molecular descriptors and oversampling ratios .", "entity": [], "task": "NER"}
{"text": "The SVM models were constructed from 4D - FPs , MOE ( 1D , 2D , and 21 / 2D ) , noNP + MOE , and CATS2D trial descriptors pools and compared to the predictive abilities of CATS2D - based random forest models .", "entity": [], "task": "NER"}
{"text": "Compared to previous results in the literature , the SVM models built from oversampled data sets exhibited better predictive abilities for the training and external test sets .", "entity": [], "task": "NER"}
{"text": "Isolation of Ciliatamide D from a Marine Sponge Stelletta sp . and a Reinvestigation of the Configuration of Ciliatamide A .", "entity": [{"entity": "Ciliatamide D", "entity_type": "Chemical", "pos": [13, 26]}, {"entity": "Ciliatamide A", "entity_type": "Chemical", "pos": [109, 122]}], "task": "NER"}
{"text": "A new lipopeptide , ciliatamide D ( 1 ) , was isolated from a marine sponge Stelletta sp . , collected at Oshimashinsone , together with the known compound ciliatamide A ( 2 ) .", "entity": [{"entity": "ciliatamide D", "entity_type": "Chemical", "pos": [20, 33]}, {"entity": "ciliatamide A", "entity_type": "Chemical", "pos": [156, 169]}], "task": "NER"}
{"text": "Ciliatamide D ( 1 ) is a congener of 2 , in which N - Me - Phe is replaced by N - Me - Met ( O ) .", "entity": [{"entity": "Ciliatamide D", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "N - Me - Phe", "entity_type": "Chemical", "pos": [50, 62]}, {"entity": "N - Me - Met ( O )", "entity_type": "Chemical", "pos": [78, 96]}], "task": "NER"}
{"text": "Marfey ' s analysis of the acid hydrolysate of 1 demonstrated that the two constituent amino acids were both in the l - form .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "This result prompted us to carefully investigate the configuration of 2 , resulting in the assignment of the l - form for both residues .", "entity": [], "task": "NER"}
{"text": "Chemical ligation of oligodeoxynucleotides by X - irradiation and its application to regulation of G - quadruplex formation .", "entity": [], "task": "NER"}
{"text": "We demonstrated radiolytic ligation of oligodeoxynucleotides ( ODNs ) possessing disulfide bond and its application to regulation of DNA quadruplex formation .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "G - rich hexamer ODNs had poor ability to form quadruplex , while X - irradiation of the ODNs induced interstrand exchange reaction at disulfide bond to form ligated 12 mer ODNs , leading to the ready formation of quadruplex due to the entropic effect .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "Since complexation of the ligated ODNs with hemin in the presence of K ( + ) showed strong soret band absorption and also catalyzed the H ( 2 ) O ( 2 ) - mediated oxidation of luminol , it appears that the quadruplex formed from ligated ODNs showed a function similar to native DNA quadruplex .", "entity": [{"entity": "hemin", "entity_type": "Chemical", "pos": [44, 49]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [69, 76]}, {"entity": "H ( 2 ) O ( 2 )", "entity_type": "Chemical", "pos": [136, 151]}, {"entity": "luminol", "entity_type": "Chemical", "pos": [176, 183]}], "task": "NER"}
{"text": "Anti - adipogenic diarylheptanoids from Alnus hirsuta f . sibirica on 3T3 - L1 cells .", "entity": [{"entity": "diarylheptanoids", "entity_type": "Chemical", "pos": [18, 34]}], "task": "NER"}
{"text": "A new diarylheptanoid , ( 5S ) - hydroxy - 1 - ( 3 , 4 - dihydroxyphenyl ) - 7 - ( 4 - hydroxyphenyl ) - hepta - 1E - en - 3 - one ( 1 ) , was isolated along with seventeen known diarylheptanoids ( 2 - 18 ) from the methanol extract of Alnus hirsuta f . sibirica leaves using bioactivity - guided fractionation .", "entity": [{"entity": "diarylheptanoid", "entity_type": "Chemical", "pos": [6, 21]}, {"entity": "( 5S ) - hydroxy - 1 - ( 3 , 4 - dihydroxyphenyl ) - 7 - ( 4 - hydroxyphenyl ) - hepta - 1E - en - 3 - one", "entity_type": "Chemical", "pos": [24, 130]}, {"entity": "diarylheptanoids", "entity_type": "Chemical", "pos": [179, 195]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [216, 224]}], "task": "NER"}
{"text": "Among the isolated compounds , compounds 1 and 2 and 4 - 12 reduced lipid accumulation dose - dependently in 3T3 - L1 preadipocytes .", "entity": [], "task": "NER"}
{"text": "Of the compounds active in the present assay system , the most potent compound 7 , platyphyllonol - 5 - O - beta - d - xylopyranoside , significantly suppressed the induction of peroxisome proliferator activated receptor gamma ( PPAR gamma and CCAAT / enhancer binding protein alpha ( C / EBP alpha ) protein expression , and inhibited adipocyte differentiation induced by troglitazone , a PPAR gamma agonist .", "entity": [{"entity": "platyphyllonol - 5 - O - beta - d - xylopyranoside", "entity_type": "Chemical", "pos": [83, 133]}, {"entity": "troglitazone", "entity_type": "Chemical", "pos": [373, 385]}], "task": "NER"}
{"text": "It was demonstrated that compound 7 has anti - adipogenic activity mediated by the regulation of PPAR gamma dependent pathways .", "entity": [], "task": "NER"}
{"text": "Experience - dependent homeostatic synaptic plasticity in neocortex .", "entity": [], "task": "NER"}
{"text": "The organism ' s ability to adapt to the changing sensory environment is due in part to the ability of the nervous system to change with experience .", "entity": [], "task": "NER"}
{"text": "Input and synapse specific Hebbian plasticity , such as long - term potentiation ( LTP ) and long - term depression ( LTD ) , are critical for sculpting the nervous system to wire its circuit in tune with the environment and for storing memories .", "entity": [], "task": "NER"}
{"text": "However , these synaptic plasticity mechanisms are innately unstable and require another mode of plasticity that maintains homeostasis to allow neurons to function within a desired dynamic range .", "entity": [], "task": "NER"}
{"text": "Several modes of homeostatic adaptation are known , some of which work at the synaptic level .", "entity": [], "task": "NER"}
{"text": "This review will focus on the known mechanisms of experience - induced homeostatic synaptic plasticity in the neocortex and their potential function in sensory cortex plasticity .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' Homeostatic Plasticity ' .", "entity": [], "task": "NER"}
{"text": "Gimatecan and other camptothecin derivatives poison Leishmania DNA - topoisomerase IB leading to a strong leishmanicidal effect .", "entity": [{"entity": "Gimatecan", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "camptothecin", "entity_type": "Chemical", "pos": [20, 32]}], "task": "NER"}
{"text": "The aim of this work is the in vitro and ex vivo assessment of the leishmanicidal activity of camptothecin and three analogues used in cancer therapy : topotecan ( Hycantim ( (R) ) ) , gimatecan ( ST1481 ) and the pro - drug irinotecan ( Camptosar ( (R) ) ) as well as its active metabolite SN - 38 against Leishmania infantum .", "entity": [{"entity": "camptothecin", "entity_type": "Chemical", "pos": [94, 106]}, {"entity": "topotecan", "entity_type": "Chemical", "pos": [152, 161]}, {"entity": "Hycantim", "entity_type": "Chemical", "pos": [164, 172]}, {"entity": "gimatecan", "entity_type": "Chemical", "pos": [185, 194]}, {"entity": "ST1481", "entity_type": "Chemical", "pos": [197, 203]}, {"entity": "irinotecan", "entity_type": "Chemical", "pos": [225, 235]}, {"entity": "Camptosar", "entity_type": "Chemical", "pos": [238, 247]}, {"entity": "SN - 38", "entity_type": "Chemical", "pos": [291, 298]}], "task": "NER"}
{"text": "The activity of camptothecin and its derivatives was studied on extracellular L . infantum infrared - emitting promastigotes and on an ex vivo murine model of infected splenocytes with L . infantum fluorescent amastigotes .", "entity": [{"entity": "camptothecin", "entity_type": "Chemical", "pos": [16, 28]}], "task": "NER"}
{"text": "In situ formation of SDS / KCl precipitable DNA - protein complexes in Leishmania promastigotes indicated that these drugs are DNA topoisomerase IB poisons .", "entity": [], "task": "NER"}
{"text": "The inhibitory potency of camptothecin derivatives on recombinant L . infantum topoisomerase IB was assessed in vitro showing that gimatecan is the most active compound preventing the relaxation of supercoiled DNA at submicromolar concentrations .", "entity": [{"entity": "camptothecin", "entity_type": "Chemical", "pos": [26, 38]}, {"entity": "gimatecan", "entity_type": "Chemical", "pos": [131, 140]}], "task": "NER"}
{"text": "Cleavage equilibrium assays in Leishmania topoisomerase IB show that gimatecan changes the equilibrium towards cleavage at much lower concentrations than the other camptothecin derivatives and that this effect persists over time .", "entity": [{"entity": "gimatecan", "entity_type": "Chemical", "pos": [69, 78]}, {"entity": "camptothecin", "entity_type": "Chemical", "pos": [164, 176]}], "task": "NER"}
{"text": "Gimatecan and camptothecin were the most powerful compounds preventing cell growth of free - living L . infantum promastigotes within the same concentration range .", "entity": [{"entity": "Gimatecan", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "camptothecin", "entity_type": "Chemical", "pos": [14, 26]}], "task": "NER"}
{"text": "All these compounds killed L . infantum splenocyte - infecting amastigotes within the nanomolar range .", "entity": [], "task": "NER"}
{"text": "The amastigote form showed higher sensitivity to topoisomerase IB poisons ( with high therapeutic selectivity indexes ) than free - living promastigotes .", "entity": [], "task": "NER"}
{"text": "All the compounds assayed poisoned L . infantum DNA topoisomerase IB leading to a strong leishmanicidal effect .", "entity": [], "task": "NER"}
{"text": "Camptothecin derivatives are suitable for reducing the parasitic burden of ex vivo infected splenocytes .", "entity": [{"entity": "Camptothecin", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "The selectivity index of gimatecan makes it a promising drug against this neglected disease .", "entity": [{"entity": "gimatecan", "entity_type": "Chemical", "pos": [25, 34]}], "task": "NER"}
{"text": "Molecular markers from three organellar genomes unravel complex taxonomic relationships within the coralline algal genus Chiharaea ( Corallinales , Rhodophyta ) .", "entity": [], "task": "NER"}
{"text": "The use of molecular markers in taxonomic studies has become a standard practice in biology .", "entity": [], "task": "NER"}
{"text": "However , consensus on which markers to use at the species level is lacking because evolutionary lineages show differences in divergence rates between organellar genomes .", "entity": [], "task": "NER"}
{"text": "Ideally , researchers use multiple lines of evidence when first describing a species , such as the incorporation of several molecular markers from varied genomes ( mitochondrion , plastid and nucleus ) .", "entity": [], "task": "NER"}
{"text": "This study examined species boundaries in the red algal genus Chiharaea .", "entity": [], "task": "NER"}
{"text": "We used five molecular markers , with at least one marker from each genome , coupled with thorough morphological analyses .", "entity": [], "task": "NER"}
{"text": "We recognized three species in Chiharaea ( C . americana , C . rhododactyla sp . nov . , C . silvae ) and two forms ( C . americana f . americana and C . americana f . bodegensis ( H . W . Johansen ) stat . nov . ) .", "entity": [], "task": "NER"}
{"text": "For C . americana f . americana and C . americana f . bodegensis differentiation based on morphological data was reflected in the plastid - encoded large subunit of RuBisCO ( rbcL ) , but was not concordant with either the mitochondrial cytochrome c oxidase subunit 1 ( COI - 5P ) or nuclear internal transcribed spacer ( ITS ) sequence data .", "entity": [], "task": "NER"}
{"text": "We suggest that this discordance is indicative of ongoing hybridization and introgression between populations of C . americana f . americana and C . americana f . bodegensis .", "entity": [], "task": "NER"}
{"text": "In addition , we used a PCR assay with ITS specific primers to amplify multiple ITS variants for collections assignable to C . americana indicating that there is genetic variability within ITS copies most likely due to introgression , crossing over and / or the retention of ancestral variants .", "entity": [], "task": "NER"}
{"text": "Theoretical realization of robust broadband transparency in ultrathin seamless nanostructures by dual blackbodies for near infrared light .", "entity": [], "task": "NER"}
{"text": "We propose a counter - intuitive mechanism of constructing an ultrathin broadband transparent device with two perfect blackbodies .", "entity": [], "task": "NER"}
{"text": "By introducing hybridization of plasmon modes , resonant modes with different symmetries coexist in this system .", "entity": [], "task": "NER"}
{"text": "A broadband transmission spectrum in the near infrared regime is achieved through controlling their coupling strengths , which is governed by the thickness of high refractive index layer .", "entity": [], "task": "NER"}
{"text": "Meanwhile , the transparency bandwidth is found to be tunable in a large range by varying the geometric dimension .", "entity": [], "task": "NER"}
{"text": "More significantly , from the point view of applications , the proposed method of achieving broadband transparency can perfectly tolerate the misalignment and asymmetry of periodic nanoparticles on the top and bottom , which is empowered by the unique dual of coupling - in and coupling - out processes within the pair of blackbodies .", "entity": [], "task": "NER"}
{"text": "Moreover , roughness has little influence on its transmission performance .", "entity": [], "task": "NER"}
{"text": "According to the coupled mode theory , the distinguished transmittance performance is physically interpreted by the radiative decay rate of the entire system .", "entity": [], "task": "NER"}
{"text": "In addition to the feature of uniquely robust broadband transparency , such a ultrathin seamless nanostructure ( in the presence of a uniform silver layer ) also provides polarization - independent and angle - independent operations .", "entity": [], "task": "NER"}
{"text": "Therefore , it may power up a wide spectrum of exciting applications in thin film protection , touch screen techniques , absorber - emitter transformation , etc .", "entity": [], "task": "NER"}
{"text": "Benzenesulfonamides : a unique class of chemokine receptor type 4 inhibitors .", "entity": [{"entity": "Benzenesulfonamides", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "The interaction of CXCR4 with CXCL12 ( SDF - 1 ) plays a critical role in cancer metastasis by facilitating the homing of tumor cells to metastatic sites .", "entity": [], "task": "NER"}
{"text": "Based on our previously published work on CXCR4 antagonists , we have synthesized a series of aryl sulfonamides that inhibit the CXCR4 / CXCL12 interaction .", "entity": [{"entity": "aryl sulfonamides", "entity_type": "Chemical", "pos": [94, 111]}], "task": "NER"}
{"text": "Analogue bioactivities were assessed with binding affinity and Matrigel invasion assays .", "entity": [], "task": "NER"}
{"text": "Computer modeling was employed to evaluate a selection of the new analogues docked into the CXCR4 X - ray structure and to rationalize discrepancies between the affinity and Matrigel in vitro assays .", "entity": [], "task": "NER"}
{"text": "A lead compound displays nanomolar potency in the binding affinity assay ( IC ( 50 ) = 8 . 0 nM ) and the Matrigel invasion assay ( 100 % blockade of invasion at 10 nM ) .", "entity": [], "task": "NER"}
{"text": "These data demonstrate that benzenesulfonamides are a unique class of CXCR4 inhibitors with high potency .", "entity": [{"entity": "benzenesulfonamides", "entity_type": "Chemical", "pos": [28, 47]}], "task": "NER"}
{"text": "Hydrogen - bond reinforced vanadia nanofiber paper of high stiffness .", "entity": [{"entity": "Hydrogen", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "vanadia", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "Low - temperature , solution - based self - assembly of vanadia nanofibers yields a free - standing , ceramic paper with an outstanding combination of high strength , stiffness , and macroscopic flexibility .", "entity": [{"entity": "vanadia", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "Its excellent mechanical performance results from a brick - and - mortar like architecture , which combines strong covalent bonding within the single - crystalline nanofibers with an intricate hydrogen bonding network between them .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [193, 201]}], "task": "NER"}
{"text": "Hedgehog signaling acts with the temporal cascade to promote neuroblast cell cycle exit .", "entity": [], "task": "NER"}
{"text": "In Drosophila postembryonic neuroblasts , transition in gene expression programs of a cascade of transcription factors ( also known as the temporal series ) acts together with the asymmetric division machinery to generate diverse neurons with distinct identities and regulate the end of neuroblast proliferation .", "entity": [], "task": "NER"}
{"text": "However , the underlying mechanism of how this \" temporal series \" acts during development remains unclear .", "entity": [], "task": "NER"}
{"text": "Here , we show that Hh signaling in the postembryonic brain is temporally regulated ; excess ( earlier onset of ) Hh signaling causes premature neuroblast cell cycle exit and under - proliferation , whereas loss of Hh signaling causes delayed cell cycle exit and excess proliferation .", "entity": [], "task": "NER"}
{"text": "Moreover , the Hh pathway functions downstream of Castor but upstream of Grainyhead , two components of the temporal series , to schedule neuroblast cell cycle exit .", "entity": [], "task": "NER"}
{"text": "Interestingly , hh is likely a target of Castor .", "entity": [], "task": "NER"}
{"text": "Hence , Hh signaling provides a link between the temporal series and the asymmetric division machinery in scheduling the end of neurogenesis .", "entity": [], "task": "NER"}
{"text": "Influence of aqueous media properties on aggregation and solubility of four structurally related meso - porphyrin photosensitizers evaluated by spectrophotometric measurements .", "entity": [{"entity": "meso - porphyrin", "entity_type": "Chemical", "pos": [97, 113]}], "task": "NER"}
{"text": "Porphyrin photosensitizers tend to aggregate in aqueous solutions even in the micromolar concentration range .", "entity": [{"entity": "Porphyrin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "This is a challenge during formulation of e . g . , parenteral preparations for photodynamic cancer therapy , or preparations for local or topical administration in antimicrobial photodynamic therapy .", "entity": [], "task": "NER"}
{"text": "Monomerization is essential to achieve biocompatible drug formulations of high bioavailability and physiological response ( i . e . , photoreactivity ) and low toxicity .", "entity": [], "task": "NER"}
{"text": "The aggregation and solubilization of four structurally related meso - tetraphenyl porphyrin photosensitizers with nonionic ( 4 - hydroxy ) , anionic ( 4 - sulphonate ; 4 - carboxy ) and cationic ( 4 - trimethylanilinium ) substituents were evaluated in various vehicles by use of UV - Vis spectroscopy .", "entity": [{"entity": "meso - tetraphenyl porphyrin", "entity_type": "Chemical", "pos": [64, 92]}, {"entity": "4 - hydroxy", "entity_type": "Chemical", "pos": [126, 137]}, {"entity": "4 - sulphonate", "entity_type": "Chemical", "pos": [152, 166]}, {"entity": "4 - carboxy", "entity_type": "Chemical", "pos": [169, 180]}, {"entity": "4 - trimethylanilinium", "entity_type": "Chemical", "pos": [198, 220]}], "task": "NER"}
{"text": "Substituents , overall charge and charge distribution influenced the pKa - values and interaction of the porphyrins with different solvents , excipients and impurities .", "entity": [{"entity": "porphyrins", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "Modification of medium polarity and solubilization by the nonionic surfactant Tween 80 adjusted the acid - base equilibria and increased the solubility by reduction of porphyrin aggregation .", "entity": [{"entity": "Tween 80", "entity_type": "Chemical", "pos": [78, 86]}, {"entity": "porphyrin", "entity_type": "Chemical", "pos": [168, 177]}], "task": "NER"}
{"text": "The selected porphyrins were sensitive towards ionic strength , temperature and inorganic impurities to various extents .", "entity": [{"entity": "porphyrins", "entity_type": "Chemical", "pos": [13, 23]}], "task": "NER"}
{"text": "The results will be further used during development of parenteral and topical formulations of porphyrin photosensitizers for use in photodynamic therapy of cancer and bacterial infections .", "entity": [{"entity": "porphyrin", "entity_type": "Chemical", "pos": [94, 103]}], "task": "NER"}
{"text": "Folate Conjugation to Polymeric Micelles via Boronic Acid Ester to Deliver Platinum Drugs to Ovarian Cancer Cell Lines .", "entity": [{"entity": "Folate", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "Boronic Acid Ester", "entity_type": "Chemical", "pos": [45, 63]}, {"entity": "Platinum", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "In this study , a novel technique was used for the reversible attachment of folic acid on the surface of polymeric micelles for a tumor - specific drug delivery system .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [76, 86]}], "task": "NER"}
{"text": "The reversible conjugation is based on the interaction between phenylboronic acid ( PBA ) and dopamine to form a borate ester .", "entity": [{"entity": "phenylboronic acid", "entity_type": "Chemical", "pos": [63, 81]}, {"entity": "PBA", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [94, 102]}, {"entity": "borate ester", "entity_type": "Chemical", "pos": [113, 125]}], "task": "NER"}
{"text": "The conjugation is fast and efficient and in vitro experiments via confocal fluorescent microscopy show that the linker is stable in for several hours .", "entity": [], "task": "NER"}
{"text": "Reversible addition - fragmentation chain transfer ( RAFT ) polymerization was used to synthesize two various sized water - soluble block copolymer of oligoethylene glycol methylether methacylate and methyl acrylic acid ( POEGMEMA35 - b - PMAA200 and POEGMEMA26 - b - PMAA90 ) .", "entity": [{"entity": "oligoethylene glycol methylether methacylate", "entity_type": "Chemical", "pos": [151, 195]}, {"entity": "methyl acrylic acid", "entity_type": "Chemical", "pos": [200, 219]}, {"entity": "POEGMEMA35 - b - PMAA200", "entity_type": "Chemical", "pos": [222, 246]}, {"entity": "POEGMEMA26 - b - PMAA90", "entity_type": "Chemical", "pos": [251, 274]}], "task": "NER"}
{"text": "The platinum drug , oxoplatin , was then subsequently attached to the polymer via ester formation leading to platinum loading of 12 wt % as determined by TGA .", "entity": [{"entity": "platinum", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "oxoplatin", "entity_type": "Chemical", "pos": [20, 29]}, {"entity": "platinum", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "The platinum - induced amphiphilic block copolymers that consequently led to the formation of micelles of sizes 150 and 20 nm in an aqueous environment with the longer PMAA block forming larger micelles .", "entity": [{"entity": "platinum", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "PMAA", "entity_type": "Chemical", "pos": [168, 172]}], "task": "NER"}
{"text": "The small micelles were in addition cross - linked using 1 , 8 - diaminooctane to further stabilize their structure .", "entity": [{"entity": "1 , 8 - diaminooctane", "entity_type": "Chemical", "pos": [57, 78]}], "task": "NER"}
{"text": "The targeting ability of folate conjugated polymeric micelles was investigated against two types of tumor cell lines : A549 ( - FR ) and OVCAR - 3 ( + FR ) .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [25, 31]}], "task": "NER"}
{"text": "The cell line growth inhibitory efficacy of material synthesized was evaluated by using SRB method .", "entity": [], "task": "NER"}
{"text": "The results revealed that folate conjugated micelles showed higher activity in FR + OVCAR - 3 cells but not in FR - A549 cells .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [26, 32]}], "task": "NER"}
{"text": "Similar results were obtained for both small and large micelles without the conjugation of folate .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [91, 97]}], "task": "NER"}
{"text": "Comparing large and small micelles it can be observed that larger micelles are more efficient , which has been attributed to the lower stability of the smaller micelles .", "entity": [], "task": "NER"}
{"text": "Micelle stabilization via cross - linking could indeed increase the toxicity of the drug carrier .", "entity": [], "task": "NER"}
{"text": "Synthesis and relaxometric characterization of a MRI Gd - based probe responsive to glutamic acid decarboxylase enzymatic activity .", "entity": [{"entity": "Gd", "entity_type": "Chemical", "pos": [53, 55]}, {"entity": "glutamic acid", "entity_type": "Chemical", "pos": [84, 97]}], "task": "NER"}
{"text": "Novel contrast agent based systems , which selectively visualize specific cells , e . g . , neurons in the brain , would be of substantial importance for the fast developing field of molecular magnetic resonance imaging ( MRI ) .", "entity": [], "task": "NER"}
{"text": "We report here the synthesis and in vitro validation of a Gd ( III ) - based contrast agent designed to act as an MRI responsive probe for imaging the activity of the enzyme glutamic acid decarboxylase ( GAD ) present in neurons .", "entity": [{"entity": "Gd ( III )", "entity_type": "Chemical", "pos": [58, 68]}, {"entity": "glutamic acid", "entity_type": "Chemical", "pos": [174, 187]}], "task": "NER"}
{"text": "Upon the action of the enzyme , the Gd ( III ) complex increases its hydration sphere and takes on a residual positive charge that promotes its binding to endogenous macromolecules .", "entity": [{"entity": "Gd ( III )", "entity_type": "Chemical", "pos": [36, 46]}], "task": "NER"}
{"text": "Both effects contribute in a synergic way to generate a marked relaxation enhancement , which directly reports enzyme activity and will allow activity detection of GAD positive cells in vitro and in vivo selectively .", "entity": [], "task": "NER"}
{"text": "The finely regulating well - defined functional polymeric nanocarriers for anti - tumor immunotherapy .", "entity": [], "task": "NER"}
{"text": "Cancer is the second leading cause of death around the world .", "entity": [], "task": "NER"}
{"text": "Cancer may be induced by viral infection ( EBV , HBV and HPV ) , bacterial infection ( Helicobacter pylori ) , carcinogen , ultraviolet ( UV ) radiation exposure , and genetic mutation .", "entity": [], "task": "NER"}
{"text": "Tumor can be suppressed by traditional surgery , radiotherapy , and / or chemotherapy with devastating side effects and very poor quality of postoperative life .", "entity": [], "task": "NER"}
{"text": "The therapeutic index has been further promoted by the newly developed nanomedicine .", "entity": [], "task": "NER"}
{"text": "However , the disseminated tumor cells can result in micrometastases .", "entity": [], "task": "NER"}
{"text": "So the cancer can just be supresssed but not cured by these ways .", "entity": [], "task": "NER"}
{"text": "Fortunately , the developments of immunology have successfully improved many disciplines with special effort on oncology .", "entity": [], "task": "NER"}
{"text": "Various immune cells including B cells , T - lymphocytes ( TL ) , natural killer ( NK ) cells , dendritic cells ( DCs ) , macrophages , and polymorphonuclear leukocytes are recruited to the tumor .", "entity": [], "task": "NER"}
{"text": "These immune cells can recognize , eliminate , and protect the body from viral , bacterial infections , and the transformed cells ( pre - cancer cell ) extension .", "entity": [], "task": "NER"}
{"text": "The modification of host immune system , and / or the utilization of components of the immune system for cancer treatment are called immunotherapy .", "entity": [], "task": "NER"}
{"text": "The immunotherapy is not only to target and kill tumor cells in aspecific manner , but also to alert the immune system to eradicate the disseminated tumor cells present in the blood circulation and micro - metastases in remote organs .", "entity": [], "task": "NER"}
{"text": "Herein , the development of immunology , cancer immunotherapy , tumor immuno escape was introduced firstly .", "entity": [], "task": "NER"}
{"text": "Then the correlations between host , the tumor and the nano particulates were proposed .", "entity": [], "task": "NER"}
{"text": "And how to improve the cancer immunotherapy by finely nanocarrier ' s engineering ( nanoimmunotherapy ) was systematically illustrated with special focus on the unique pathology of tumor microenviroments and properties of immuno cells .", "entity": [], "task": "NER"}
{"text": "A new sesquiterpene lactone from Salvia plebeia .", "entity": [{"entity": "sesquiterpene lactone", "entity_type": "Chemical", "pos": [6, 27]}], "task": "NER"}
{"text": "A new eudesmanolide , 1 alpha - acetoxy - 8 alpha , 9 beta - dihydroxy - 2 - oxo - eudesman - 3 , 7 ( 11 ) - dien - 8 , 12 - olide ( 2 ) , together with a known eudesmanolide , 1 alpha - acetoxy - 8 alpha - hydroxy - 2 - oxo - eudesman - 3 , 7 ( 11 ) - dien - 8 , 12 - olide ( 1 ) , and a known flavone , 4 ' , 5 , 7 - trihydroxy - 6 - methoxyflavone ( 3 ) , was isolated from the plant of Salvia plebeia .", "entity": [{"entity": "eudesmanolide", "entity_type": "Chemical", "pos": [6, 19]}, {"entity": "1 alpha - acetoxy - 8 alpha , 9 beta - dihydroxy - 2 - oxo - eudesman - 3 , 7 ( 11 ) - dien - 8 , 12 - olide", "entity_type": "Chemical", "pos": [22, 130]}, {"entity": "eudesmanolide", "entity_type": "Chemical", "pos": [161, 174]}, {"entity": "1 alpha - acetoxy - 8 alpha - hydroxy - 2 - oxo - eudesman - 3 , 7 ( 11 ) - dien - 8 , 12 - olide", "entity_type": "Chemical", "pos": [177, 274]}, {"entity": "flavone", "entity_type": "Chemical", "pos": [295, 302]}, {"entity": "4 ' , 5 , 7 - trihydroxy - 6 - methoxyflavone", "entity_type": "Chemical", "pos": [305, 350]}], "task": "NER"}
{"text": "Three compounds were structurally elucidated by spectroscopic and chemical methods .", "entity": [], "task": "NER"}
{"text": "The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition .", "entity": [], "task": "NER"}
{"text": "Since its identification in 1988 and the recognition of its primary role as a potent vasoconstrictor , endothelin has been extensively studied and is now considered as a ubiquitous protein , involved in important aspects of human homeostasis as well as in several pathophysiological pathways , mostly associated with cardiovascular disease .", "entity": [], "task": "NER"}
{"text": "From an evolutionary point of view , endothelin consists a primitive molecule with the rare characteristic of being exactly the same in all mammals , thus permitting scientists to perform experiments in animals and doing predictions for humans .", "entity": [], "task": "NER"}
{"text": "The understanding of its contribution to the genesis , evolution and maintenance of disease through activation of special receptor subtypes has led to the development of both selective and unselective receptor antagonists .", "entity": [], "task": "NER"}
{"text": "Despite the disappointing results of these antagonists in the field of heart failure , almost from the initial animal trials of bosentan , a dual endothelin receptor antagonist , in pulmonary arterial hypertension , it has been demonstrated that the drug leads at least to hemodynamic and clinical improvement of the patients , thus receiving official approval for the management of this rare but eventually lethal disease .", "entity": [{"entity": "bosentan", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "Resistant hypertension is another area where endothelin receptor blockers might potentially play a role , while the pathophysiological role of endothelin in atherosclerotic coronary artery disease is well - established and the relative research goes on .", "entity": [], "task": "NER"}
{"text": "The main goal of this review is to describe the endothelin system and mostly to enlighten its role in pathophysiologic pathways , as well to state the relative research in the various fields of cardiovascular disease and also highlight its prognostic significance wherever there exists one .", "entity": [], "task": "NER"}
{"text": "Asymmetric Dimethylarginine ( ADMA ) : A Promising Biomarker for Cardiovascular Disease ?", "entity": [{"entity": "Asymmetric Dimethylarginine", "entity_type": "Chemical", "pos": [0, 27]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "Asymmetric Dimethylarginine ( ADMA ) is an endogenous inhibitor of nitric oxide ( NO ) production .", "entity": [{"entity": "Asymmetric Dimethylarginine", "entity_type": "Chemical", "pos": [0, 27]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [30, 34]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [67, 79]}, {"entity": "NO", "entity_type": "Chemical", "pos": [82, 84]}], "task": "NER"}
{"text": "ADMA is generated from methylation of arginine residues by protein arginine methyltransferases ( PRMTs ) and subsequent proteolysis , while its elimination is achieved mainly by degradation with dimethylarginine dimethylaminohydrolase ( DDAH ) .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [38, 46]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [67, 75]}, {"entity": "dimethylarginine", "entity_type": "Chemical", "pos": [195, 211]}], "task": "NER"}
{"text": "Oxidative stress , endothelial nitric oxide synthase ( eNOS ) inhibition , eNOS uncoupling , inflammation and shear stress play a pivotal role in ADMA pathophysiology by managing PRMT / DDAH expression and NO synthesis and leading to a common result - endothelial dysfunction .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [31, 43]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [146, 150]}, {"entity": "NO", "entity_type": "Chemical", "pos": [206, 208]}], "task": "NER"}
{"text": "Endothelial dysfunction seems to be the common finding in studies investigating the role of ADMA in cardiovascular disease ( CVD ) .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [92, 96]}], "task": "NER"}
{"text": "High - performance liquid chromatography ( HPLC ) , mass spectrometry ( MS ) and enzyme - linked immunosorbent assay ( ELISA ) are the existing methods for ADMA quantification .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [156, 160]}], "task": "NER"}
{"text": "However , none of them fulfils all the criteria to be characterized as \" gold standard \" .", "entity": [], "task": "NER"}
{"text": "ADMA is significantly associated with risk factors for CVD and almost with every disease of the cardiovascular system ; showing an independent , strong prognostic value for mortality and future cardiovascular events .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "This article aims to review the current knowledge about ADMA biology and metabolism , pathophysiological mechanisms implicating ADMA in CVD , methods for the determination of ADMA and its association with CVD risk factors and established CVDs .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [56, 60]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [128, 132]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [175, 179]}], "task": "NER"}
{"text": "Chitosan - thioglycolic Acid as a versatile antimicrobial agent .", "entity": [{"entity": "thioglycolic Acid", "entity_type": "Chemical", "pos": [11, 28]}], "task": "NER"}
{"text": "As functionalized chitosans hold great potential for the development of effective and broad - spectrum antibiotics , representative chitosan derivatives were tested for antimicrobial activity in neutral media : trimethyl chitosan ( TMC ) , carboxy - methyl chitosan ( CMC ) , and chitosan - thioglycolic acid ( TGA ; medium molecular weight : MMW - TGA ; low molecular weight : LMW - TGA ) .", "entity": [{"entity": "trimethyl", "entity_type": "Chemical", "pos": [211, 220]}, {"entity": "carboxy - methyl", "entity_type": "Chemical", "pos": [240, 256]}, {"entity": "thioglycolic acid", "entity_type": "Chemical", "pos": [291, 308]}, {"entity": "TGA", "entity_type": "Chemical", "pos": [311, 314]}, {"entity": "TGA", "entity_type": "Chemical", "pos": [349, 352]}, {"entity": "TGA", "entity_type": "Chemical", "pos": [384, 387]}], "task": "NER"}
{"text": "Colony forming assays indicated that LMW - TGA displayed superior antimicrobial activity over the other derivatives tested : a 30 min incubation killed 100 % Streptococcus sobrinus ( Gram - positive bacteria ) and reduced colony counts by 99 . 99 % in Neisseria subflava ( Gram - negative bacteria ) and 99 . 97 % in Candida albicans ( fungi ) .", "entity": [{"entity": "TGA", "entity_type": "Chemical", "pos": [43, 46]}], "task": "NER"}
{"text": "To elucidate LMW - TGA effects at the cellular level , microscopic studies were performed .", "entity": [{"entity": "TGA", "entity_type": "Chemical", "pos": [19, 22]}], "task": "NER"}
{"text": "Use of fluorescein isothiocyanate ( FITC ) - labeled chitosan derivates in confocal microscopy showed that LMW - TGA attaches to microbial cell walls , while transmission electron microscopy indicated that this derivative severely affects cell wall integrity and intracellular ultrastructure in all species tested .", "entity": [{"entity": "fluorescein isothiocyanate", "entity_type": "Chemical", "pos": [7, 33]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "TGA", "entity_type": "Chemical", "pos": [113, 116]}], "task": "NER"}
{"text": "We therefore propose LMW - TGA as a promising and effective broad - band antimicrobial compound .", "entity": [{"entity": "TGA", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "New surface - enhanced Raman scattering platforms : composite calcium carbonate microspheres coated with astralen and silver nanoparticles .", "entity": [{"entity": "calcium carbonate", "entity_type": "Chemical", "pos": [62, 79]}, {"entity": "silver", "entity_type": "Chemical", "pos": [118, 124]}], "task": "NER"}
{"text": "Surface - enhanced Raman scattering ( SERS ) microspectroscopy is a very promising label - free , noncontact , and nondestructive method for real - time monitoring of extracellular matrix ( ECM ) development and cell integration in scaffolds for tissue engineering .", "entity": [], "task": "NER"}
{"text": "Here , we prepare a new type of micrometer - sized SERS substrate , core - shell microparticles composed of solid carbonate core coated with silver nanoparticles and polyhedral multishell fullerene - like structure , astralen .", "entity": [{"entity": "carbonate", "entity_type": "Chemical", "pos": [114, 123]}, {"entity": "silver", "entity_type": "Chemical", "pos": [141, 147]}, {"entity": "fullerene", "entity_type": "Chemical", "pos": [188, 197]}], "task": "NER"}
{"text": "Astralen has been assembled with polyallylamine hydrochloride ( PAH ) by the layer - by - layer manner followed by Ag nanoparticle formation by means of a silver mirror reaction , giving the final structure of composite particles CaCO3 ( PAH / astralen ) x / Ag , where x = 1 - 3 .", "entity": [{"entity": "polyallylamine hydrochloride", "entity_type": "Chemical", "pos": [33, 61]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [115, 117]}, {"entity": "silver", "entity_type": "Chemical", "pos": [155, 161]}, {"entity": "CaCO3", "entity_type": "Chemical", "pos": [230, 235]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [238, 241]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [259, 261]}], "task": "NER"}
{"text": "The components of the microparticle carry multiple functionalities : ( i ) an easy identification by Raman imaging ( photostable astralen ) and ( ii ) SERS due to a rough surface of Ag nanoparticles .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [182, 184]}], "task": "NER"}
{"text": "A combination of Ag and astralen nanoparticles provides an enhancement of astralen Raman signal by more than 1 order of magnitude .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [17, 19]}], "task": "NER"}
{"text": "Raman signals of commonly used scaffold components such as polylactide and polyvinyl alcohol as well as ECM component ( hyaluronic acid ) are significantly enhanced .", "entity": [{"entity": "polylactide", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "polyvinyl alcohol", "entity_type": "Chemical", "pos": [75, 92]}], "task": "NER"}
{"text": "Thus , we demonstrate that new mechanically robust and easily detectable ( by astralen signal or optically ) core - shell microspheres based on biocompatible CaCO3 can be used as SERS platform .", "entity": [{"entity": "CaCO3", "entity_type": "Chemical", "pos": [158, 163]}], "task": "NER"}
{"text": "Particle design opens many future perspectives for fabrication of SERS platforms with multiple functions for biomedical applications , for example , for theranostic .", "entity": [], "task": "NER"}
{"text": "Safety assessment of Apoaequorin , a protein preparation : Subchronic toxicity study in rats .", "entity": [], "task": "NER"}
{"text": "Apoaequorin , a calcium - binding protein originally isolated from jellyfish is available commercially as a dietary supplement .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [16, 23]}], "task": "NER"}
{"text": "The objective of the present study was to investigate potential adverse effects , if any , of Apoaequorin , a recombinant protein preparation , in rats following subchronic administration .", "entity": [], "task": "NER"}
{"text": "For this study , Sprague - Dawley ( Hsd : SD (R) ) rats ( 10 / sex / group ) were administered via oral gavage 0 ( control ) , 92 . 6 , 462 . 9 , and 926 . 0mg / kg body weight ( bw ) / day of Apoaequorin preparation , for 90days .", "entity": [], "task": "NER"}
{"text": "The corresponding amount of Apoaequorin protein was 0 , 66 . 7 , 333 . 3 and 666 . 7mg / kg bw / day , respectively .", "entity": [], "task": "NER"}
{"text": "Administration of the Apoaequorin preparation did not result in any mortality .", "entity": [], "task": "NER"}
{"text": "There were no clinical or ophthalmological signs , body weight , body weight gain , food consumption , food efficiency , clinical pathology or histopathological changes attributable to administration of Apoaequorin .", "entity": [], "task": "NER"}
{"text": "Any changes noted were incidental and in agreement with those historically observed in the age and strain of rats used in this study .", "entity": [], "task": "NER"}
{"text": "Based on the results of this study , the No Observed - Adverse - Effect Level ( NOAEL ) for Apoaequorin was determined as 666 . 7mg / kg bw / day , the highest dose tested .", "entity": [], "task": "NER"}
{"text": "Environmental stress , oxytocin receptor gene ( OXTR ) polymorphism , and mental health following collective stress .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "We examined whether the oxytocin receptor gene ( OXTR ) single nucleotide polymorphism ( SNP ) rs53576 genotype buffers the combined impact of negative social environments ( e . g . , interpersonal conflict / constraint ) and economic stress on post - traumatic stress ( PTS ) symptoms and impaired daily functioning following collective stress ( September 11th terrorist attacks ) .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [63, 73]}], "task": "NER"}
{"text": "Saliva was collected by mail and used to genotype 704 respondents .", "entity": [], "task": "NER"}
{"text": "Participants completed Web - based assessments of pre - 9 / 11 mental health , acute stress 9 - 23days after 9 / 11 , the quality of social environments 1year post - 9 / 11 , economic stress 18months post - 9 / 11 , and PTS symptoms and impaired functioning 2 and 3years post - 9 / 11 .", "entity": [], "task": "NER"}
{"text": "Interactions between negative social environments and economic stress were examined separately based on OXTR rs53576 genotype ( GG vs . any A allele ) .", "entity": [], "task": "NER"}
{"text": "For individuals with an A allele , a negative social environment significantly increased PTS symptoms without regard to the level of economic stress experienced .", "entity": [], "task": "NER"}
{"text": "However , for respondents with a GG genotype , negative social environments predicted elevated PTS symptoms only for those also experiencing high economic stress .", "entity": [], "task": "NER"}
{"text": "Gender moderated associations between negative social environments , economic stress , and impaired functioning .", "entity": [], "task": "NER"}
{"text": "The functioning of females was most affected by negative social environments regardless of genotype and economic stress , whereas the functioning of males was differentially susceptible to economic stress depending on OXTR genotype and negative social environments .", "entity": [], "task": "NER"}
{"text": "These findings suggest that it is important to consider the combined impact of gender and ongoing stress in different domains as moderators of genetic vulnerability following collective stress .", "entity": [], "task": "NER"}
{"text": "Oroxylin A reverses P - glycoprotein - mediated multidrug resistance of MCF7 / ADR cells by G2 / M arrest .", "entity": [{"entity": "Oroxylin A", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Oroxylin A is a naturally occurring monoflavonoid isolated from the root of Scutellaria baicalensis Georgi , which has been used in traditional Chinese medicine for its anti - tumor , anti - inflammatory and anti - bacterial properties .", "entity": [{"entity": "Oroxylin A", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "monoflavonoid", "entity_type": "Chemical", "pos": [36, 49]}], "task": "NER"}
{"text": "The purpose of this study is to investigate the reversal effect and the fundamental mechanisms of oroxylin A in MCF7 / ADR cells .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [98, 108]}], "task": "NER"}
{"text": "Data indicated that oroxylin A showed strong reversal potency in MCF7 / ADR cells and the reversal fold ( RF ) reached 4 . 68 .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [20, 30]}], "task": "NER"}
{"text": "After treatment with oroxylin A , MCF7 / ADR cells displayed reduced functional activity and expression of MDR1 at both the protein and mRNA levels .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "Meanwhile , oroxylin A induced cells G2 / M arrest in a concentration - dependent manner by increasing the expression of p - Chk2 ( Thr68 ) .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [12, 22]}], "task": "NER"}
{"text": "Moreover , western blot and EMSA assays were used to reveal the inhibition of NF - kappa B in nucleus and the suppression of NF - kappa B binding activity by oroxylin A .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [158, 168]}], "task": "NER"}
{"text": "NSC 109555 ditosylate - Chk2 inhibitor partly dismissed G2 / M arrest induced by oroxylin A , reversed the increased trend of p - Chk2 and p - P53 ( Ser20 ) , inhibited the decreasing effect of oroxylin A on the expression of P - gp and decreased the reversal fold of 90 mu M oroxylin A from 4 . 68 fold to 1 . 73 fold .", "entity": [{"entity": "NSC 109555 ditosylate", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "oroxylin A", "entity_type": "Chemical", "pos": [81, 91]}, {"entity": "oroxylin A", "entity_type": "Chemical", "pos": [194, 204]}, {"entity": "oroxylin A", "entity_type": "Chemical", "pos": [276, 286]}], "task": "NER"}
{"text": "In conclusion , we suggested that oroxylin A reversed MDR by G2 / M arrest and the underlying mechanism attributed to the suppression of P - gp expression via Chk2 / P53 / NF - kappa B signaling pathway .", "entity": [{"entity": "oroxylin A", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "Neurotrophin 3 genotype and emotional adverse effects of osmotic - release oral system methylphenidate ( OROS - MPH ) in children with attention - deficit / hyperactivity disorder .", "entity": [{"entity": "methylphenidate", "entity_type": "Chemical", "pos": [87, 102]}, {"entity": "MPH", "entity_type": "Chemical", "pos": [112, 115]}], "task": "NER"}
{"text": "Neurotrophin 3 ( NTF3 ) has been studied in relation to the pathophysiology of attention - deficit / hyperactivity disorder ( ADHD ) and mood disorders as well as psychostimulant action .", "entity": [], "task": "NER"}
{"text": "We hypothesized that the risk of an emotional side effect to methylphenidate ( MPH ) treatment may be associated with NTF3 genotypes .", "entity": [{"entity": "methylphenidate", "entity_type": "Chemical", "pos": [61, 76]}, {"entity": "MPH", "entity_type": "Chemical", "pos": [79, 82]}], "task": "NER"}
{"text": "Ninety - six medication - na i ve children with ADHD ( mean age 8 . 70 , standard deviation 1 . 41 years , 79 males ) were genotyped and treated with MPH .", "entity": [{"entity": "MPH", "entity_type": "Chemical", "pos": [150, 153]}], "task": "NER"}
{"text": "At baseline , which was prior to MPH treatment , and after two weeks of medication , investigators asked children and their parents or caregivers about adverse events using a symptom rating scale .", "entity": [{"entity": "MPH", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "ADHD subjects with the A / A genotype at the NTF3 rs6332 polymorphism showed the highest ' Emotionality ' and ' Over - focus / euphoria ' factor scores , followed by those with the G / A genotype and those with the G / G genotype ( p = 0 . 042 and p = 0 . 045 , respectively ) .", "entity": [], "task": "NER"}
{"text": "ADHD subjects with the A / A genotype at the NTF3 rs6332 polymorphism showed the highest ' Proneness to crying ' and ' Nail biting ' item scores , followed by those with the G / A genotype and those with the G / G genotype ( p = 0 . 047 and p = 0 . 017 , respectively ) .", "entity": [], "task": "NER"}
{"text": "These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD .", "entity": [{"entity": "MPH", "entity_type": "Chemical", "pos": [150, 153]}], "task": "NER"}
{"text": "Resveratrol protects against arsenic trioxide - induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress .", "entity": [{"entity": "Resveratrol", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "arsenic trioxide", "entity_type": "Chemical", "pos": [29, 45]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [87, 94]}], "task": "NER"}
{"text": "Arsenic trioxide ( As2O3 ) is an environmental toxicant and a potent antineoplastic agent .", "entity": [{"entity": "Arsenic trioxide", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [19, 24]}], "task": "NER"}
{"text": "Exposure to arsenic causes renal cancer .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [12, 19]}], "task": "NER"}
{"text": "Resveratrol is a well - known polyphenolic compound that is reported to reduce As2O3 - induced cardiotoxicity .", "entity": [{"entity": "Resveratrol", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "polyphenolic", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [79, 84]}], "task": "NER"}
{"text": "The present study aimed to investigate the effect of resveratrol on As2O3 - induced nephrotoxicity and arsenic metabolism .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [53, 64]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [68, 73]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [103, 110]}], "task": "NER"}
{"text": "Chinese Dragon - Li cats were injected with 1 mg / kg As2O3 on alternate days ; resveratrol ( 3 mg / kg ) was administered via the forearm vein 1 h before the As2O3 treatment .", "entity": [{"entity": "As2O3", "entity_type": "Chemical", "pos": [54, 59]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [80, 91]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [159, 164]}], "task": "NER"}
{"text": "On the sixth day , the cats were killed to determine the histological renal damage , renal function , the accumulation of arsenic , and antioxidant activities in the kidney .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [122, 129]}], "task": "NER"}
{"text": "Urine samples were taken for arsenic speciation .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "In the resveratrol + As2O3 - treated group , activities of glutathione peroxidase , catalase , and superoxide dismutase , the ratio of reduced glutathione to oxidized glutathione , the total arsenic concentrations , and the percentage of methylated arsenic in urine were significantly increased .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [7, 18]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [21, 26]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [99, 109]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [143, 154]}, {"entity": "oxidized glutathione", "entity_type": "Chemical", "pos": [158, 178]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [191, 198]}, {"entity": "methylated arsenic", "entity_type": "Chemical", "pos": [238, 256]}], "task": "NER"}
{"text": "The concentrations of renal malondialdehyde , reactive oxygen species , 8 - hydroxydeoxyguanosine , serum creatinine , blood urea nitrogen , and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As2O3 - treated group .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [28, 43]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [55, 61]}, {"entity": "8 - hydroxydeoxyguanosine", "entity_type": "Chemical", "pos": [72, 97]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [106, 116]}, {"entity": "urea", "entity_type": "Chemical", "pos": [125, 129]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [151, 158]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [269, 274]}], "task": "NER"}
{"text": "These results demonstrate that resveratrol could significantly scavenge reactive oxygen species , inhibit As2O3 - induced oxidative damage , and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As2O3 metabolism .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [31, 42]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [81, 87]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [106, 111]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [189, 196]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [230, 235]}], "task": "NER"}
{"text": "These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [31, 42]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [160, 167]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "Global analysis of Drosophila Cys2 - His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants .", "entity": [{"entity": "Cys2", "entity_type": "Chemical", "pos": [30, 34]}, {"entity": "His2", "entity_type": "Chemical", "pos": [37, 41]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [42, 46]}], "task": "NER"}
{"text": "Cys2 - His2 zinc finger proteins ( ZFPs ) are the largest group of transcription factors in higher metazoans .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [12, 16]}], "task": "NER"}
{"text": "A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes .", "entity": [], "task": "NER"}
{"text": "As a first step in this process , we have characterized the DNA - binding specificities of 129 zinc finger sets from Drosophila using a bacterial one - hybrid system .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "This data set contains the DNA - binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date .", "entity": [], "task": "NER"}
{"text": "These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome .", "entity": [], "task": "NER"}
{"text": "Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences , thereby allowing us to define the recognition diversity within this finger set .", "entity": [], "task": "NER"}
{"text": "We find that the characterized fingers can specify 47 of the 64 possible DNA triplets .", "entity": [], "task": "NER"}
{"text": "To confirm the utility of our finger recognition models , we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA - binding specificity .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [154, 158]}], "task": "NER"}
{"text": "These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "Cobicistat : A New Boost for the Treatment of Human Immunodeficiency Virus Infection .", "entity": [{"entity": "Cobicistat", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Ritonavir is commonly used as a pharmacokinetic booster for antiretroviral regimens in the management of human immunodeficiency virus infections .", "entity": [{"entity": "Ritonavir", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Limitations to ritonavir boosting include increased pill burden , adverse effects , and a wide range of clinically significant drug - drug interactions .", "entity": [{"entity": "ritonavir", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "Cobicistat is a new pharmacokinetic booster that is a selective inhibitor of cytochrome P450 3A , the main metabolizing pathway of several antiretrovirals .", "entity": [{"entity": "Cobicistat", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Cobicistat has been studied as a booster for elvitegravir , a second - generation integrase inhibitor , and protease inhibitors .", "entity": [{"entity": "Cobicistat", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "elvitegravir", "entity_type": "Chemical", "pos": [45, 57]}], "task": "NER"}
{"text": "Based on successful clinical trials , a new single - tablet regimen of elvitegravir , cobicistat , emtricitabine , and tenofovir has been approved for the management of treatment - na i ve patients .", "entity": [{"entity": "elvitegravir", "entity_type": "Chemical", "pos": [71, 83]}, {"entity": "cobicistat", "entity_type": "Chemical", "pos": [86, 96]}, {"entity": "emtricitabine", "entity_type": "Chemical", "pos": [99, 112]}, {"entity": "tenofovir", "entity_type": "Chemical", "pos": [119, 128]}], "task": "NER"}
{"text": "Additional studies are underway investigating the safety and efficacy of cobicistat - boosted protease inhibitor regimens for both treatment - na i ve and treatment - experienced patients .", "entity": [{"entity": "cobicistat", "entity_type": "Chemical", "pos": [73, 83]}], "task": "NER"}
{"text": "Cobicistat is well tolerated and may become a preferred booster for antiretroviral regimens , as it can be coformulated with several agents to create simpler regimens .", "entity": [{"entity": "Cobicistat", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Tumor - suppressive Maspin Functions as a Reactive Oxygen Species Scavenger : IMPORTANCE OF CYSTEINE RESIDUES .", "entity": [{"entity": "Oxygen", "entity_type": "Chemical", "pos": [51, 57]}, {"entity": "CYSTEINE", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "Maspin is a member of the serine protease inhibitor ( serpin ) superfamily and displays tumor - suppressing activity by controlling cell migration , proliferation , apoptosis , and adhesion .", "entity": [], "task": "NER"}
{"text": "Here , we provide evidence that maspin acts as a reactive oxygen species ( ROS ) scavenger through oxidation of three structurally exposed cysteine thiols to sulfenic acid .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [58, 64]}, {"entity": "cysteine thiols", "entity_type": "Chemical", "pos": [139, 154]}, {"entity": "sulfenic acid", "entity_type": "Chemical", "pos": [158, 171]}], "task": "NER"}
{"text": "Ablation of these cysteine residues in maspin resulted in a significant increase in total ROS production in mouse mammary TM40D cells .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "Also , cells containing a triple - cysteine mutant of maspin showed elevated ERK1 / 2 activity , a downstream target of ROS , and enhanced proliferation and colony formation .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "These findings establish a novel mechanism by which maspin utilizes its cysteine thiols to inhibit oxidative stress and cell growth .", "entity": [{"entity": "cysteine thiols", "entity_type": "Chemical", "pos": [72, 87]}], "task": "NER"}
{"text": "Biosafety data as confidential business information .", "entity": [], "task": "NER"}
{"text": "Removal of confidentiality claims on biosafety data is necessary to adhere to standard scientific procedures of quality assurance , to increase transparency , to minimize impacts of conflicts of interests , and ultimately to improve public confidence in GMOs .", "entity": [], "task": "NER"}
{"text": "Global iodine nutrition : where do we stand in 2013 ?", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [7, 13]}], "task": "NER"}
{"text": "Background : Dietary iodine intake is required for the production of thyroid hormone .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [69, 84]}], "task": "NER"}
{"text": "Consequences of iodine deficiency include goiter , intellectual impairments , growth retardation , neonatal hypothyroidism , and increased pregnancy loss and infant mortality .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [16, 22]}], "task": "NER"}
{"text": "Summary : In 1990 , the United Nations World Summit for Children established the goal of eliminating iodine deficiency worldwide .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [101, 107]}], "task": "NER"}
{"text": "Considerable progress has since been achieved , largely through programs of universal salt iodization .", "entity": [], "task": "NER"}
{"text": "Approximately 70 % of all households worldwide currently have access to adequately iodized salt .", "entity": [], "task": "NER"}
{"text": "In 2013 , as defined by a national or subnational median urinary iodine concentration of 100 - 299 mu g / L in school - aged children , 111 countries have sufficient iodine intake .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [65, 71]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "Thirty countries remain iodine - deficient ; 9 are moderately deficient , 21 are mildly deficient , and none are currently considered severely iodine - deficient .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [24, 30]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [143, 149]}], "task": "NER"}
{"text": "Ten countries have excessive iodine intake .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [29, 35]}], "task": "NER"}
{"text": "In North America , both the United States and Canada are generally iodine - sufficient , although recent data suggest pregnant U . S . women are mildly iodine - deficient .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [67, 73]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [152, 158]}], "task": "NER"}
{"text": "Emerging issues include discrepancies between urinary iodine status in pregnant women compared to school - aged children in some populations , the problem of re - emerging iodine deficiency in parts of the developed world , the importance of food industry use of iodized salt , regions of iodine excess , and the potential effects of initiatives to lower population sodium consumption on iodine intake .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [54, 60]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [172, 178]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [289, 295]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [366, 372]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [388, 394]}], "task": "NER"}
{"text": "Conclusions : Although substantial progress has been made over the last several decades , iodine deficiency remains a significant health problem worldwide and affects both industrialized and developing nations .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [90, 96]}], "task": "NER"}
{"text": "The ongoing monitoring of population iodine status remains crucially important , and particular attention may need to be paid to monitoring the status of vulnerable populations , such as pregnant women and infants .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [37, 43]}], "task": "NER"}
{"text": "There is also need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [76, 82]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [142, 148]}], "task": "NER"}
{"text": "Finally , it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [89, 95]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [173, 179]}], "task": "NER"}
{"text": "In vivo HIF - mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL - deficient cells to glutamine deprivation .", "entity": [{"entity": "citrate", "entity_type": "Chemical", "pos": [63, 70]}, {"entity": "glutamine", "entity_type": "Chemical", "pos": [118, 127]}], "task": "NER"}
{"text": "Hypoxic and VHL - deficient cells use glutamine to generate citrate and lipids through reductive carboxylation ( RC ) of alpha - ketoglutarate .", "entity": [{"entity": "glutamine", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "alpha - ketoglutarate", "entity_type": "Chemical", "pos": [121, 142]}], "task": "NER"}
{"text": "To gain insights into the role of HIF and the molecular mechanisms underlying RC , we took advantage of a panel of disease - associated VHL mutants and showed that HIF expression is necessary and sufficient for the induction of RC in human renal cell carcinoma ( RCC ) cells .", "entity": [], "task": "NER"}
{"text": "HIF expression drastically reduced intracellular citrate levels .", "entity": [{"entity": "citrate", "entity_type": "Chemical", "pos": [49, 56]}], "task": "NER"}
{"text": "Feeding VHL - deficient RCC cells with acetate or citrate or knocking down PDK - 1 and ACLY restored citrate levels and suppressed RC .", "entity": [{"entity": "acetate", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [50, 57]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "These data suggest that HIF - induced low intracellular citrate levels promote the reductive flux by mass action to maintain lipogenesis .", "entity": [{"entity": "citrate", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "Using [ ( 1 - 13 ) C ] glutamine , we demonstrated in vivo RC activity in VHL - deficient tumors growing as xenografts in mice .", "entity": [{"entity": "[ ( 1 - 13 ) C ] glutamine", "entity_type": "Chemical", "pos": [6, 32]}], "task": "NER"}
{"text": "Lastly , HIF rendered VHL - deficient cells sensitive to glutamine deprivation in vitro , and systemic administration of glutaminase inhibitors suppressed the growth of RCC cells as mice xenografts .", "entity": [{"entity": "glutamine", "entity_type": "Chemical", "pos": [57, 66]}], "task": "NER"}
{"text": "The mitochondrial RNA - binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression .", "entity": [], "task": "NER"}
{"text": "RNA - binding proteins are at the heart of posttranscriptional gene regulation , coordinating the processing , storage , and handling of cellular RNAs .", "entity": [], "task": "NER"}
{"text": "We show here that GRSF1 , previously implicated in the binding and selective translation of influenza mRNAs , is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids .", "entity": [], "task": "NER"}
{"text": "GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA , the ND6 mRNA , and the long noncoding RNAs for cytb and ND5 , each of which contains multiple consensus binding sequences .", "entity": [], "task": "NER"}
{"text": "RNAi - mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability , abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome , and impaired ribosome assembly .", "entity": [], "task": "NER"}
{"text": "This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes .", "entity": [], "task": "NER"}
{"text": "These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression .", "entity": [], "task": "NER"}
{"text": "Adipose subtype - selective recruitment of TLE3 or Prdm16 by PPAR gamma specifies lipid storage versus thermogenic gene programs .", "entity": [], "task": "NER"}
{"text": "Transcriptional effectors of white adipocyte - selective gene expression have not been described .", "entity": [], "task": "NER"}
{"text": "Here we show that TLE3 is a white - selective cofactor that acts reciprocally with the brown - selective cofactor Prdm16 to specify lipid storage and thermogenic gene programs .", "entity": [], "task": "NER"}
{"text": "Occupancy of TLE3 and Prdm16 on certain promoters is mutually exclusive , due to the ability of TLE3 to disrupt the physical interaction between Prdm16 and PPAR gamma .", "entity": [], "task": "NER"}
{"text": "When expressed at elevated levels in brown fat , TLE3 counters Prdm16 , suppressing brown - selective genes and inducing white - selective genes , resulting in impaired fatty acid oxidation and thermogenesis .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [169, 179]}], "task": "NER"}
{"text": "Conversely , mice lacking TLE3 in adipose tissue show enhanced thermogenesis in inguinal white adipose depots and are protected from age - dependent deterioration of brown adipose tissue function .", "entity": [], "task": "NER"}
{"text": "Our results suggest that the establishment of distinct adipocyte phenotypes with different capacities for thermogenesis and lipid storage is accomplished in part through the cell - type - selective recruitment of TLE3 or Prdm16 to key adipocyte target genes .", "entity": [], "task": "NER"}
{"text": "Mechanistic investigation of seeded growth in triblock copolymer stabilized gold nanoparticles .", "entity": [], "task": "NER"}
{"text": "We report the seeded synthesis of gold nanoparticles ( GNPs ) via the reduction of HAuCl4 by ( L31 and F68 ) triblock copolymer ( TBP ) mixtures .", "entity": [{"entity": "HAuCl4", "entity_type": "Chemical", "pos": [83, 89]}], "task": "NER"}
{"text": "In the present study , we focused on [ TBP ] / [ Au ( III ) ] ratios of 1 - 5 ( =~ 1 mM HAuCl4 ) and seed sizes ~ 20 nm .", "entity": [{"entity": "Au ( III )", "entity_type": "Chemical", "pos": [49, 59]}, {"entity": "HAuCl4", "entity_type": "Chemical", "pos": [88, 94]}], "task": "NER"}
{"text": "Under these conditions , the GNP growth rate is dominated by both the TBP and seed concentrations .", "entity": [], "task": "NER"}
{"text": "With seeding , the final GNP size distributions are bimodal .", "entity": [], "task": "NER"}
{"text": "Increasing the seed concentration ( up to ~ 0 . 1 nM ) decreases the mean particle sizes 10 - fold , from ~ 1000 to 100 nm .", "entity": [], "task": "NER"}
{"text": "The particles in the bimodal distribution are formed by the competitive direct growth in solution and the aggregative growth on the seeds .", "entity": [], "task": "NER"}
{"text": "By monitoring kinetics of GNP growth , we propose that ( 1 ) the surface of the GNP seeds embedded in the TBP cavities form catalytic centers for GNP growth and ( 2 ) large GNPs are formed by the aggregation of GNP seeds in an autocatalytic growth process .", "entity": [], "task": "NER"}
{"text": "Systematic study of the basis set superposition error in core - electron correlation effects .", "entity": [], "task": "NER"}
{"text": "In a recent paper , Xu et al .", "entity": [], "task": "NER"}
{"text": "[ J . Phys . Chem . A2012 , 116 , 11668 ] emphasized the importance of core - electron correlation effects to describe the Si2H6BH3 complex and related systems properly .", "entity": [{"entity": "Si2H6BH3", "entity_type": "Chemical", "pos": [123, 131]}], "task": "NER"}
{"text": "Unexpected large energy differences between a frozen core and all electron treatment were observed .", "entity": [], "task": "NER"}
{"text": "In the present study , it will be shown that these energy differences are an artifact of an insufficient choice of basis set and can be attributed to an intramolecular basis set superposition error ( BSSE ) .", "entity": [], "task": "NER"}
{"text": "Although the general problem is known , systematic studies on the effect are scarce .", "entity": [], "task": "NER"}
{"text": "Therefore , the BSSE in related systems is investigated .", "entity": [], "task": "NER"}
{"text": "This study shows that the problem of BSSE for core - electron correlation is quite common if inadequate basis sets are applied and that it amounts to 2 kcal mol ( - 1 ) on average in binding energies for the given test set ( with a maximum of 5 . 8 kcal mol ( - 1 ) ) .", "entity": [], "task": "NER"}
{"text": "Molecular interactions in 1 - butanol + IL solutions by measuring and modeling activity coefficients .", "entity": [{"entity": "1 - butanol", "entity_type": "Chemical", "pos": [26, 37]}], "task": "NER"}
{"text": "Molecular interactions in 1 - butanol + ionic liquid ( IL ) solutions have been investigated by measuring and modeling activity - coefficient data .", "entity": [{"entity": "1 - butanol", "entity_type": "Chemical", "pos": [26, 37]}], "task": "NER"}
{"text": "The activity coefficients in binary solutions containing 1 - butanol and an IL were determined experimentally : the ILs studied were 1 - decyl - 3 - methyl - imidazolium tetracyanoborate ( [ Im10 . 1 ] ( + ) [ tcb ] ( - ) ) , 4 - decyl - 4 - methyl - morpholinium tetracyanoborate ( [ Mo10 . 1 ] ( + ) [ tcb ] ( - ) ) , 1 - decyl - 3 - methyl - imidazolium bis ( trifluoromethylsulfonyl ) imide ( [ Im10 . 1 ] ( + ) [ ntf2 ] ( - ) ) , and 4 - decyl - 4 - methyl - morpholinium bis ( trifluoromethylsulfonyl ) imide ( [ Mo10 . 1 ] ( + ) [ ntf2 ] ( - ) ) .", "entity": [{"entity": "1 - butanol", "entity_type": "Chemical", "pos": [57, 68]}, {"entity": "1 - decyl - 3 - methyl - imidazolium tetracyanoborate", "entity_type": "Chemical", "pos": [133, 186]}, {"entity": "tcb", "entity_type": "Chemical", "pos": [210, 213]}, {"entity": "4 - decyl - 4 - methyl - morpholinium tetracyanoborate", "entity_type": "Chemical", "pos": [226, 280]}, {"entity": "tcb", "entity_type": "Chemical", "pos": [304, 307]}, {"entity": "1 - decyl - 3 - methyl - imidazolium bis ( trifluoromethylsulfonyl ) imide", "entity_type": "Chemical", "pos": [320, 394]}, {"entity": "ntf2", "entity_type": "Chemical", "pos": [418, 422]}, {"entity": "4 - decyl - 4 - methyl - morpholinium bis ( trifluoromethylsulfonyl ) imide", "entity_type": "Chemical", "pos": [439, 514]}, {"entity": "ntf2", "entity_type": "Chemical", "pos": [538, 542]}], "task": "NER"}
{"text": "The methods used to determine the activity coefficients included vapor - pressure osmometry , headspace - gas chromatography , and gas - liquid chromatography .", "entity": [], "task": "NER"}
{"text": "The results from all of these techniques were combined to obtain activity - coefficient data over the entire IL concentration range , and the ion - specific interactions of the ILs investigated were identified with 1 - butanol .", "entity": [{"entity": "1 - butanol", "entity_type": "Chemical", "pos": [215, 226]}], "task": "NER"}
{"text": "The highest ( 1 - butanol ) - IL interactions of the ILs considered in this work were found for [ Im10 . 1 ] ( + ) [ tcb ] ( - ) ; thus , [ Im10 . 1 ] ( + ) [ tcb ] ( - ) showed the highest affinity for 1 - butanol in a binary mixture .", "entity": [{"entity": "1 - butanol", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "1 - butanol", "entity_type": "Chemical", "pos": [203, 214]}], "task": "NER"}
{"text": "The experimental data were modeled with the Perturbed - Chain Statistical Associating Fluid Theory ( PC - SAFT ) .", "entity": [], "task": "NER"}
{"text": "PC - SAFT was able to accurately describe the pure IL and ( 1 - butanol ) - IL data .", "entity": [{"entity": "1 - butanol", "entity_type": "Chemical", "pos": [60, 71]}], "task": "NER"}
{"text": "Moreover , the model was shown to be predictive and extrapolative with respect to concentration and temperature .", "entity": [], "task": "NER"}
{"text": "Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase - 4 ( PDE4 ) .", "entity": [{"entity": "moexipril", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger , cyclic 3 ' 5 ' adenosine monophosphate ( cAMP ) .", "entity": [{"entity": "cyclic nucleotide", "entity_type": "Chemical", "pos": [28, 45]}, {"entity": "cyclic nucleotide", "entity_type": "Chemical", "pos": [151, 168]}, {"entity": "cyclic 3 ' 5 ' adenosine monophosphate", "entity_type": "Chemical", "pos": [188, 226]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [229, 233]}], "task": "NER"}
{"text": "PDE4 inhibitors are known to have anti - inflammatory properties , but their use in the clinic has been hampered by mechanism - associated side effects that limit maximally tolerated doses .", "entity": [], "task": "NER"}
{"text": "In an attempt to initiate the development of better - tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4 - inhibitory activity .", "entity": [], "task": "NER"}
{"text": "With this objective , we utilised a high - throughput computational approach that identified moexipril , a well tolerated and safe angiotensin - converting enzyme ( ACE ) inhibitor , as a PDE4 inhibitor .", "entity": [{"entity": "moexipril", "entity_type": "Chemical", "pos": [93, 102]}, {"entity": "angiotensin", "entity_type": "Chemical", "pos": [131, 142]}], "task": "NER"}
{"text": "Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity .", "entity": [{"entity": "moexipril", "entity_type": "Chemical", "pos": [30, 39]}], "task": "NER"}
{"text": "Employing a FRET - based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP , EPAC1 , we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [126, 130]}, {"entity": "moexipril", "entity_type": "Chemical", "pos": [162, 171]}, {"entity": "forskolin", "entity_type": "Chemical", "pos": [208, 217]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [244, 248]}], "task": "NER"}
{"text": "Finally , we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the small heat shock protein , Hsp20 , by cAMP dependent protein kinase A .", "entity": [{"entity": "moexipril", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [163, 167]}], "task": "NER"}
{"text": "Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window .", "entity": [{"entity": "moexipril", "entity_type": "Chemical", "pos": [22, 31]}], "task": "NER"}
{"text": "Lipid raft modulation by Rp1 reverses multidrug resistance via inactivating MDR - 1 and Src inhibition .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [25, 28]}], "task": "NER"}
{"text": "Multidrug resistance ( MDR ) is a major obstacle to effective cancer therapy .", "entity": [], "task": "NER"}
{"text": "The membrane transporter MDR - 1 ( P - gp , ABCB1 ) , a member of the ATP - binding cassette ( ABC ) transporter family , effluxes anti - cancer drugs from cancer cells .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "Increased activity of MDR - 1 is known to be the main mechanism for multidrug resistance .", "entity": [], "task": "NER"}
{"text": "MDR - 1 is known to be localized in the cholesterol - and sphingolipid - enriched plasma membrane microdomains , known as lipid rafts .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [40, 51]}, {"entity": "sphingolipid", "entity_type": "Chemical", "pos": [58, 70]}], "task": "NER"}
{"text": "Disruption of lipid rafts by cholesterol depletion alters lipid raft functions , indicating that cholesterol is critical for raft function .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [29, 40]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [97, 108]}], "task": "NER"}
{"text": "Because ginsenosides are structurally similar to cholesterol , in this study , we investigated the effect of Rp1 , a novel ginsenoside derivative , on drug resistance using drug - sensitive OVCAR - 8 and drug - resistant NCI / ADR - RES and DXR cells .", "entity": [{"entity": "ginsenosides", "entity_type": "Chemical", "pos": [8, 20]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [49, 60]}, {"entity": "Rp1", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "ginsenoside", "entity_type": "Chemical", "pos": [123, 134]}], "task": "NER"}
{"text": "Rp1 treatment resulted in an accumulation of doxorubicin or rhodamine 123 by decreasing MDR - 1 activity in doxorubicin - resistant cells .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "rhodamine 123", "entity_type": "Chemical", "pos": [60, 73]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [108, 119]}], "task": "NER"}
{"text": "Rp1 synergistically induced cell death with actinomycin D in DXR cells .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "actinomycin D", "entity_type": "Chemical", "pos": [44, 57]}], "task": "NER"}
{"text": "Rp1 appeared to redistribute lipid rafts and MDR - 1 protein .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Moreover , Rp1 reversed resistance to actinomycin D by decreasing MDR - 1 protein levels and Src phosphorylation with modulation of lipid rafts .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [11, 14]}, {"entity": "actinomycin D", "entity_type": "Chemical", "pos": [38, 51]}], "task": "NER"}
{"text": "Addition of cholesterol attenuated Rp1 - induced raft aggregation and MDR - 1 redistribution .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [12, 23]}, {"entity": "Rp1", "entity_type": "Chemical", "pos": [35, 38]}], "task": "NER"}
{"text": "Rp1 and actinomycin D reduced Src activity , and overexpression of active Src decreased the synergistic effect of Rp1 with actinomycin D .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "actinomycin D", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "Rp1", "entity_type": "Chemical", "pos": [114, 117]}, {"entity": "actinomycin D", "entity_type": "Chemical", "pos": [123, 136]}], "task": "NER"}
{"text": "Rp1 - induced drug sensitization was also observed with several anti - cancer drugs , including doxorubicin .", "entity": [{"entity": "Rp1", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [96, 107]}], "task": "NER"}
{"text": "These data suggest that lipid raft - modulating agents can be used to inhibit MDR - 1 activity and thus overcome drug resistance .", "entity": [], "task": "NER"}
{"text": "Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin : Mineralization and its effect on tumor targetability in vivo .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "The in vivo stability and tumor targetability of self - assembled polymeric nanoparticles are crucial for effective drug delivery .", "entity": [], "task": "NER"}
{"text": "In this study , to develop biostable nanoparticles with high tumor targetability , poly ( ethylene glycol ) - conjugated hyaluronic acid nanoparticles ( PEG - HANPs ) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [83, 107]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [153, 156]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [227, 234]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [239, 248]}], "task": "NER"}
{"text": "The resulting nanoparticles ( M - PEG - HANPs ) had a smaller size ( 153 . 7 +/- 4 . 5nm ) than bare PEG - HANPs ( 265 . 1 +/- 9 . 5nm ) , implying that mineralization allows the formation of compact nanoparticles .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Interestingly , when the mineralized nanoparticles were exposed to acidic buffer conditions ( < pH6 . 5 ) , their sizes increased rapidly due to dissolution of the inorganic minerals .", "entity": [], "task": "NER"}
{"text": "Doxorubicin ( DOX ) , chosen as the model anticancer drug , was effectively encapsulated into the bare and mineralized nanoparticles .", "entity": [], "task": "NER"}
{"text": "For bare PEG - HANPs , DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution .", "entity": [], "task": "NER"}
{"text": "On the other hand , DOX release from M - PEG - HANPs was pH - dependent : i . e . DOX was slowly released from nanoparticles under physiological condition ( pH7 . 4 ) , whereas its release rates were much higher at mildly acidic environments ( < pH6 . 5 ) .", "entity": [], "task": "NER"}
{"text": "From in vivo biodistribution study , it was found that M - PEG - HANPs could reach the tumor site more effectively than bare PEG - HANPs .", "entity": [], "task": "NER"}
{"text": "The antitumor efficacy of DOX - loaded nanoparticles was evaluated after systemic administration into the tumor - bearing mice .", "entity": [], "task": "NER"}
{"text": "Of the samples tested , the most effective antitumor efficacy was observed for DOX - loaded M - PEG - HANPs .", "entity": [], "task": "NER"}
{"text": "Overall , these results suggest that M - PEG - HANPs could be a promising carrier for an anticancer drug .", "entity": [], "task": "NER"}
{"text": "The role of DNA methylation and histone acetylation in the regulation of progesterone receptor isoforms expression in human astrocytoma cell lines .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [73, 85]}], "task": "NER"}
{"text": "Many progesterone ( P4 ) effects are mediated by its intracellular receptor ( PR ) , which has two isoforms , PR - A and PR - B , each of them with different function and regulation .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [5, 17]}], "task": "NER"}
{"text": "Differential PR expression in cancer cells has been associated to a PR isoform - specific promoter methylation .", "entity": [], "task": "NER"}
{"text": "In astrocytomas , the most frequent and aggressive brain tumors , PR isoforms expression is directly correlated to the tumor ' s evolution grade .", "entity": [], "task": "NER"}
{"text": "However , there is no evidence of the role of epigenetic regulation of PR expression in astrocytomas .", "entity": [], "task": "NER"}
{"text": "We evaluated the effect of the demethylating agent 5 - aza - 2 ' - deoxycytidine ( 5AzadC ) and the histone deacetylase inhibitor trichostatin A ( TSA ) on PR expression in human astrocytoma cell lines U373 ( grade III ) and D54 ( grade IV ) by RT - PCR and Western blot .", "entity": [{"entity": "5 - aza - 2 ' - deoxycytidine", "entity_type": "Chemical", "pos": [51, 80]}, {"entity": "5AzadC", "entity_type": "Chemical", "pos": [83, 89]}, {"entity": "trichostatin A", "entity_type": "Chemical", "pos": [130, 144]}, {"entity": "TSA", "entity_type": "Chemical", "pos": [147, 150]}], "task": "NER"}
{"text": "Total PR expression increased with 5 mu M 5AzadC treatment , whereas PR - B expression increased with 5 and 10 mu M 5AzadC treatment in U373 cells , but not in D54 cells .", "entity": [{"entity": "5AzadC", "entity_type": "Chemical", "pos": [42, 48]}, {"entity": "5AzadC", "entity_type": "Chemical", "pos": [116, 122]}], "task": "NER"}
{"text": "In U373 cells , PR - A protein content augmented with 10 mu M 5AzadC treatment , while PR - B content increased with 5 and 10 mu M 5AzadC .", "entity": [{"entity": "5AzadC", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "5AzadC", "entity_type": "Chemical", "pos": [131, 137]}], "task": "NER"}
{"text": "PR - B expression was not modified by the TSA concentrations that were used , and the combination with 5AzadC did not change the effects of the latter .", "entity": [{"entity": "TSA", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "5AzadC", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "The study of 5AzadC effects on the number of astrocytoma cells showed that P4 treatment increased the number of U373 cells , whereas 5AzadC and the combined treatment with P4 reduced it .", "entity": [{"entity": "5AzadC", "entity_type": "Chemical", "pos": [13, 19]}, {"entity": "5AzadC", "entity_type": "Chemical", "pos": [133, 139]}], "task": "NER"}
{"text": "Our results suggest that PR - B expression is regulated by methylation and not by histone acetylation in U373 cells , and that DNA demethylation reduced the number of U373 cells .", "entity": [], "task": "NER"}
{"text": "Neutralization of Apis mellifera bee venom activities by suramin .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "In this work we evaluated the ability of suramin , a polysulfonated naphthylurea derivative , to antagonize the cytotoxic and enzymatic effects of the crude venom of Apis mellifera .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [41, 48]}, {"entity": "polysulfonated naphthylurea", "entity_type": "Chemical", "pos": [53, 80]}], "task": "NER"}
{"text": "Suramin was efficient to decrease the lethality in a dose - dependent way .", "entity": [{"entity": "Suramin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "The hemoconcentration caused by lethal dose injection of bee venom was abolished by suramin ( 30 mu g / g ) .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "The edematogenic activity of the venom ( 0 . 3 mu g / g ) was antagonized by suramin ( 10 mu g / g ) in all treatment protocols .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "The changes in the vascular permeability caused by A . mellifera ( 1 mu g / g ) venom were inhibited by suramin ( 30 mu g / g ) in the pre - and posttreatment as well as when the venom was preincubated with suramin .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [104, 111]}, {"entity": "suramin", "entity_type": "Chemical", "pos": [207, 214]}], "task": "NER"}
{"text": "In addition , suramin also inhibited cultured endothelial cell lesion , as well as in vitro myotoxicity , evaluated in mouse extensor digitorumlongus muscle , which was inhibited by suramin ( 10 and 25 mu M ) , decreasing the rate of CK release , showing that suramin protected the sarcolemma against damage induced by components of bee venom ( 2 . 5 mu g / mL ) .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "suramin", "entity_type": "Chemical", "pos": [182, 189]}, {"entity": "suramin", "entity_type": "Chemical", "pos": [260, 267]}], "task": "NER"}
{"text": "Moreover , suramin inhibited the in vivo myotoxicity induced by i . m . injection of A . mellifera venom in mice ( 0 . 5 mu g / g ) .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [11, 18]}], "task": "NER"}
{"text": "The analysis of the area under the plasma CK vs . time curve showed that preincubation , pre - and posttreatment with suramin ( 30 mu g / g ) inhibited bee venom myotoxic activity in mice by about 89 % , 45 % and 40 % , respectively .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "Suramin markedly inhibited the PLA2 activity in a concentration - dependent way ( 1 - 30 mu M ) .", "entity": [{"entity": "Suramin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Being suramin a polyanion molecule , the effects observed may be due to the interaction of its charges with the polycation components present in A . mellifera bee venom .", "entity": [{"entity": "suramin", "entity_type": "Chemical", "pos": [6, 13]}], "task": "NER"}
{"text": "Effects of perinatal exposure to waterborne fluoxetine on memory processing in the cuttlefish Sepia officinalis .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [44, 54]}], "task": "NER"}
{"text": "Recent ecotoxicological studies highlight the increasing presence of pharmaceuticals discharged in the aquatic environment .", "entity": [], "task": "NER"}
{"text": "Amongst them is the antidepressant fluoxetine ( FLX ) , a selective serotonin reuptake inhibitor , primarily indicated for treatment of depression .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "FLX", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "The effect of chronic exposure to FLX on memory processing in 1 - month - old cuttlefish Sepia officinalis was evaluated .", "entity": [{"entity": "FLX", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "Three groups of new - borns were reared in different conditions : one control group ( no FLX ) and two groups exposed to environmental concentrations of FLX ( 1 and 100ng / L ) from 15 days pre - hatching to 1 month post - hatching .", "entity": [{"entity": "FLX", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "FLX", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "Acquisition and retention performances were assessed using the ' prawn - in - the - tube ' procedure .", "entity": [], "task": "NER"}
{"text": "Perinatal exposure to fluoxetine led to significant changes in memory processing of the animals .", "entity": [{"entity": "fluoxetine", "entity_type": "Chemical", "pos": [22, 32]}], "task": "NER"}
{"text": "The lowest observed effect concentration of this antidepressant on learning and retention was 1ng / L which is under the range of environmental contamination .", "entity": [], "task": "NER"}
{"text": "Cuttlefish exposed at low FLX concentration had impaired acquisition capabilities and animals exposed at high FLX concentration displayed a deficit of memory retention compared to the control group that had nonimpaired initial acquisition and retention performances .", "entity": [{"entity": "FLX", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "FLX", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "The results subsequently suggested that FLX - induced changes in cognitive capacities could potentially lead to inappropriate predatory behaviors in the natural environment .", "entity": [{"entity": "FLX", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "The study provides the basis for future studies on how pharmaceutical contaminants disrupt cognition in ecologically and economically relevant marine invertebrates .", "entity": [], "task": "NER"}
{"text": "Synergistic effects between pesticide stress and predator cues : Conflicting results from life history and physiology in the damselfly Enallagma cyathigerum .", "entity": [], "task": "NER"}
{"text": "There is increasing awareness that the negative effects of anthropogenic stressors may be magnified in the presence of natural stressors .", "entity": [], "task": "NER"}
{"text": "Very few of these studies have included physiology , yet including physiological studies may help learning about the mechanistic base of such synergisms at the life history level and identify synergistic interactions not translated in life history traits .", "entity": [], "task": "NER"}
{"text": "We studied in Enallagma cyathigerum damselfly larvae potential synergistic effects between exposure to the pesticide glyphosate and predator cues on a key life history trait , growth rate , its associated behavioural trait , food intake , and three types of physiological traits known to be affected by both stressors in isolation : the stress protein Hsp70 , energy storage and variables related to oxidative stress and damage .", "entity": [{"entity": "glyphosate", "entity_type": "Chemical", "pos": [117, 127]}], "task": "NER"}
{"text": "The pesticide and predator cues reduced growth rate in an additive way .", "entity": [], "task": "NER"}
{"text": "Food intake increased under pesticide exposure and was not affected by the predator cues , indicating physiological mediation of the growth reduction .", "entity": [], "task": "NER"}
{"text": "One potential physiological mechanism was that both stressors additively increased Hsp70 levels , this may also have contributed to the reduced levels of total carbohydrates when exposed to predator cues .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [160, 173]}], "task": "NER"}
{"text": "Chronic exposure to predator cues reduced oxygen consumption , possibly to avoid too high costs of an increased metabolic rate .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [42, 48]}], "task": "NER"}
{"text": "This reduction did not occur in the presence of the pesticide , reflecting the need for energetically expensive defence mechanisms ( such as Hsp70 upregulation ) .", "entity": [], "task": "NER"}
{"text": "When both stressors were combined , there was a reduction of the antioxidant enzyme superoxide dismutase activity ( SOD ) and an associated increase of oxidative damage in lipids .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "While synergistic interactions were not present for growth rate and food intake , they were identified for antioxidant defence and oxidative damage .", "entity": [], "task": "NER"}
{"text": "This novel type of \" hidden \" synergistic interaction may have profound fitness implications , and when ignored will lead to underestimations of the impact of pollutants in natural populations where predators are omnipresent .", "entity": [], "task": "NER"}
{"text": "Can acetylcholinesterase activity be considered as a reliable biomarker for the assessment of cadmium - induced neurotoxicity ?", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [94, 101]}], "task": "NER"}
{"text": "Gon c alves et al .", "entity": [], "task": "NER"}
{"text": "( 2012 ) recently reported the findings of a long - awaited study on the effects of long - term dietary - induced exposure to cadmium ( Cd ) on the acetylcholinesterase ( AChE ) activity of adult rodents ' brain regions .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [126, 133]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [136, 138]}], "task": "NER"}
{"text": "Their study can be regarded as a significant contribution to the field , as there is paucity of information on the AChE activity in brain regions following exposure to Cd .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [168, 170]}], "task": "NER"}
{"text": "However , the Cd - induced modulation of AChE activity is an issue surrounded by controversy .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [14, 16]}], "task": "NER"}
{"text": "We , herein , discuss and summarize the relative in vivo and in vitro experimental data , and set out to answer the straightforward question : can AChE activity be considered as a reliable biomarker for the assessment of Cd - induced neurotoxicity ?", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [221, 223]}], "task": "NER"}
{"text": "At this time , we can not answer in the affirmative because of the variation in techniques used and conclusions reached .", "entity": [], "task": "NER"}
{"text": "We make a plea that authors aiming to explore this potential use of brain AChE activity in the future : ( a ) are aware of the biases that their experimental approach might exert upon this neurochemical parameter , ( b ) avoid the use of anaesthesia as a mode of sacrifice and clarify its timing , ( c ) decide upon the use of previously - studied in vivo experimental schemes ( so that they can provide comparable results ) , and finally , ( d ) identify pharmacological , biochemical and molecular approaches that are appropriate to clarify the implicated mechanism ( s ) through which Cd modifies AChE activity .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [588, 590]}], "task": "NER"}
{"text": "Frank A . Beach Award : Programming of neuroendocrine function by early - life experience : A critical role for the immune system .", "entity": [], "task": "NER"}
{"text": "Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system , and several have a striking etiology in development as well .", "entity": [], "task": "NER"}
{"text": "Our recent evidence using a rodent model of neonatal Escherichiacoli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood , and suggests that the early - life immune history of an individual may be critical to understanding the relative risk of developing later - life mental health disorders in humans .", "entity": [], "task": "NER"}
{"text": "A single neonatal infection programs the function of immune cells within the brain , called microglia , for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits .", "entity": [], "task": "NER"}
{"text": "I describe the important role of the immune system , notably microglia , during brain development , and discuss some of the many ways in which immune activation during early brain development can affect the later - life outcomes of neural function , immune function , and cognition .", "entity": [], "task": "NER"}
{"text": "Changes in Insulin Resistance and HbA1c Are Related to Exercise - Mediated Changes in Body Composition in Older Adults With Type 2 Diabetes : Interim outcomes from the GREAT2DO Trial .", "entity": [], "task": "NER"}
{"text": "OBJECTIVETo investigate changes in body composition after 12 months of high - intensity progressive resistance training ( PRT ) in relation to changes in insulin resistance ( IR ) or glucose homeostasis in older adults with type 2 diabetes . RESEARCH DESIGN AND METHODSOne - hundred three participants were randomized to receive either PRT or sham exercise 3 days per week for 12 months .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [183, 190]}], "task": "NER"}
{"text": "Homeostatic model of assessment 2 ( HOMA2 - IR ) and glycosylated hemoglobin ( HbA1c ) were used as indices of IR and glucose homeostasis .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "Skeletal muscle mass ( SkMM ) and total fat mass were assessed using bioelectrical impedance .", "entity": [], "task": "NER"}
{"text": "Visceral adipose tissue , mid - thigh cross - sectional area , and mid - thigh muscle attenuation were quantified using computed tomography . RESULTSWithin the PRT group , changes in HOMA2 - IR were associated with changes in SkMM ( r = - 0 . 38 ; P = 0 . 04 ) and fat mass ( r = 0 . 42 ; P = 0 . 02 ) .", "entity": [], "task": "NER"}
{"text": "Changes in visceral adipose tissue tended to be related to changes in HOMA2 - IR ( r = 0 . 35 ; P = 0 . 07 ) .", "entity": [], "task": "NER"}
{"text": "Changes in HbA1c were related to changes in mid - thigh muscle attenuation ( r = 0 . 52 ; P = 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "None of these relationships were present in the sham group ( P > 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Using ANCOVA models , participants in the PRT group who had increased SkMM had decreased HOMA2 - IR ( P = 0 . 05 ) and HbA1c ( P = 0 . 09 ) compared with those in the PRT group who lost SkMM .", "entity": [], "task": "NER"}
{"text": "Increases in SkMM in the PRT group decreased HOMA2 - IR ( P = 0 . 07 ) and HbA1c ( P < 0 . 05 ) compared with those who had increased SkMM in the sham group . CONCLUSIONSImprovements in metabolic health in older adults with type 2 diabetes were mediated through improvements in body composition only if they were achieved through high - intensity PRT .", "entity": [], "task": "NER"}
{"text": "Mn @ Si14 + : a singlet fullerene - like endohedrally doped silicon cluster .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Si14 +", "entity_type": "Chemical", "pos": [5, 11]}, {"entity": "fullerene -", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "The electronic structure of Mn @ Si14 ( + ) is determined using DFT and CASPT2 / CASSCF ( 14 , 15 ) computations with large basis sets .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [28, 30]}, {"entity": "Si14 ( + )", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "The endohedrally Mn - doped Si cationic cluster has a D3h fullerene - like structure featuring a closed - shell singlet ground state with a singlet - triplet gap of ~ 1 eV .", "entity": [{"entity": "Mn - doped Si", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "fullerene -", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "A strong stabilizing interaction occurs between the 3d ( Mn ) and the 2D - shell ( Si14 ) orbitals , and a large amount of charge is transferred from the Si14 cage to the Mn dopant .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [57, 59]}, {"entity": "Si14", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "Si14", "entity_type": "Chemical", "pos": [154, 158]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [171, 173]}], "task": "NER"}
{"text": "The 3d ( Mn ) orbitals are filled by encapsulation , and the magnetic moment of Mn is completely quenched .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [9, 11]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [80, 82]}], "task": "NER"}
{"text": "Full occupation of [ 2S , 2P , 2D ] shell orbitals by 18 delocalized electrons confers the doped Mn @ Si14 ( + ) cluster a spherically aromatic character .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [97, 99]}, {"entity": "Si14 ( + )", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "Influence of the novel histamine H3 receptor antagonist ST1283 on voluntary alcohol consumption and ethanol - induced place preference in mice .", "entity": [{"entity": "histamine", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [76, 83]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "RATIONALE : Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol - use disorders in particular through histamine H3 receptors ( H3R ) .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [146, 153]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [192, 201]}], "task": "NER"}
{"text": "OBJECTIVE : In the present study , the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol ( EtOH ) voluntary intake and EtOH - conditioned reward in mice have been investigated .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [119, 126]}, {"entity": "EtOH", "entity_type": "Chemical", "pos": [129, 133]}, {"entity": "EtOH", "entity_type": "Chemical", "pos": [157, 161]}], "task": "NER"}
{"text": "METHODS : Oral EtOH , saccharin , and quinine intake was assessed in a two - bottle choice paradigm using escalating concentrations of alcohol or tastant solutions .", "entity": [{"entity": "EtOH", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "saccharin", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "quinine", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [135, 142]}], "task": "NER"}
{"text": "EtOH - induced place preference ( CPP ) , EtOH - induced locomotor activity , and blood ethanol concentration ( BEC ) were also measured .", "entity": [{"entity": "EtOH", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "EtOH", "entity_type": "Chemical", "pos": [42, 46]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [88, 95]}], "task": "NER"}
{"text": "RESULTS : Following administration of the H3R antagonist ( 2 . 5 , 5 , and 10 mg / kg , i . p . ) , there was a significant dose - dependent decrease in alcohol consumption and preference .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [153, 160]}], "task": "NER"}
{"text": "Importantly , vehicle - and ST1283 ( 5 mg / kg ) - treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes .", "entity": [], "task": "NER"}
{"text": "More interestingly , systemic administration of ST1283 inhibited EtOH - CPP and EtOH - enhanced locomotion .", "entity": [{"entity": "EtOH", "entity_type": "Chemical", "pos": [65, 69]}, {"entity": "EtOH", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "This inhibition was blocked when mice were pretreated with the selective H3R agonist R - ( alpha ) - methyl - histamine ( 10 mg / kg ) .", "entity": [{"entity": "R - ( alpha ) - methyl - histamine", "entity_type": "Chemical", "pos": [85, 119]}], "task": "NER"}
{"text": "Finally , vehicle - and ST1283 - treated mice had similar BECs .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH - CPP by altering its reinforcing effects , suggesting a novel role for histamine signaling in regulation of alcoholism .", "entity": [{"entity": "EtOH", "entity_type": "Chemical", "pos": [65, 69]}, {"entity": "EtOH", "entity_type": "Chemical", "pos": [86, 90]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [163, 172]}], "task": "NER"}
{"text": "Lastly , the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction .", "entity": [{"entity": "EtOH", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Delineating multiple functions of VEGF - A in the adult brain .", "entity": [], "task": "NER"}
{"text": "Vascular endothelial growth factor - A ( abbreviated throughout this review as VEGF ) is mostly known for its angiogenic activity , for its activity as a vascular permeability factor , and for its vascular survival activity [ 1 ] .", "entity": [], "task": "NER"}
{"text": "There is a growing body of evidence , however , that VEGF fulfills additional less ' traditional ' functions in multiple organs , both during development , as well as homeostatic functions in fully developed organs .", "entity": [], "task": "NER"}
{"text": "This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development , functions described elsewhere in this review series .", "entity": [], "task": "NER"}
{"text": "Most functions of VEGF that are essential for proper brain development are , in fact , dispensable in the adult brain as was clearly demonstrated using a conditional brain - specific VEGF loss - of - function ( LOF ) approach .", "entity": [], "task": "NER"}
{"text": "Thus , in contrast to VEGF LOF in the developing brain , a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [ 2 - 4 ] , continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression , hypoxia or apoptosis [ 4 - 7 ] .", "entity": [], "task": "NER"}
{"text": "Yet , VEGF continues to be expressed in the adult brain in a constitutive manner .", "entity": [], "task": "NER"}
{"text": "Moreover , VEGF is expressed in the adult brain in a region - specific manner and in distinctive spatial patterns incompatible with an angiogenic role ( see below ) , strongly suggesting angiogenesis - independent and possibly also perfusion - independent functions .", "entity": [], "task": "NER"}
{"text": "Here we review current knowledge on some of these ' non - traditional ' , often unexpected homeostatic VEGF functions , including those unrelated to its effects on the brain vasculature .", "entity": [], "task": "NER"}
{"text": "These effects could be mediated directly ( on non - vascular cells expressing cognate VEGF receptors ) or indirectly ( via the endothelium ) .", "entity": [], "task": "NER"}
{"text": "Experimental approaches aimed at distinguishing between these possibilities for each particular VEGF function will be described .", "entity": [], "task": "NER"}
{"text": "This review is only concerned with homeostatic functions of VEGF in the normal , non - injured brain .", "entity": [], "task": "NER"}
{"text": "The reader is referred elsewhere in this series for a review on VEGF actions in response to various forms of brain injury and / or brain pathology .", "entity": [], "task": "NER"}
{"text": "Selenium Attenuates Adriamycin - Induced Cardiac Dysfunction via Restoring Expression of ATP - Sensitive Potassium Channels in Rats .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Adriamycin", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "Potassium", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "The possible mechanism of adriamycin ( ADR ) and / or selenium ( Se ) deficiency - induced cardiac dysfunction , and cardioprotective effects of Se against ADR - induced cardiac toxicity were investigated in this study .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [26, 36]}, {"entity": "ADR", "entity_type": "Chemical", "pos": [39, 42]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "Se", "entity_type": "Chemical", "pos": [65, 67]}, {"entity": "Se", "entity_type": "Chemical", "pos": [145, 147]}, {"entity": "ADR", "entity_type": "Chemical", "pos": [156, 159]}], "task": "NER"}
{"text": "Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters .", "entity": [], "task": "NER"}
{"text": "Cardiac glutathione peroxidase ( GPx ) activity was assessed spectrophotometrically .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [8, 19]}], "task": "NER"}
{"text": "Expression of ATP - sensitive potassium channels ( KATP ) subunits - SUR2A and Kir6 . 2 - were examined by real - time PCR and Western blotting .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [30, 39]}], "task": "NER"}
{"text": "The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency ; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co - administration of ADR and Se deficiency .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [111, 114]}, {"entity": "Se", "entity_type": "Chemical", "pos": [118, 120]}, {"entity": "ADR", "entity_type": "Chemical", "pos": [247, 250]}, {"entity": "Se", "entity_type": "Chemical", "pos": [255, 257]}], "task": "NER"}
{"text": "Mechanically , it is novel for us to find down - regulation of KATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency , and more significant inhibition of cardiac KATP gene expression was identified after co - administration of ADR and Se deficiency .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [135, 138]}, {"entity": "Se", "entity_type": "Chemical", "pos": [142, 144]}, {"entity": "ADR", "entity_type": "Chemical", "pos": [266, 269]}, {"entity": "Se", "entity_type": "Chemical", "pos": [274, 276]}], "task": "NER"}
{"text": "Furthermore , cardiac toxicity of ADR was found alleviated by Se supplementation , accompanied by restoring of cardiac GPx activity and cardiac KATP gene expression .", "entity": [{"entity": "ADR", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "Se", "entity_type": "Chemical", "pos": [62, 64]}], "task": "NER"}
{"text": "These results indicate that decreased expression of cardiac KATP is involved in adriamycin and / or Se deficiency - induced cardiac dysfunction ; Se deficiency exacerbates adriamycin - induced cardiac dysfunction by future inhibition of KATP expression ; Se supplementation seems to protect against adriamycin - induced cardiac dysfunction via restoring KATP expression , showing potential clinical application in cancer chemotherapy .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "Se", "entity_type": "Chemical", "pos": [100, 102]}, {"entity": "Se", "entity_type": "Chemical", "pos": [146, 148]}, {"entity": "adriamycin", "entity_type": "Chemical", "pos": [172, 182]}, {"entity": "Se", "entity_type": "Chemical", "pos": [255, 257]}, {"entity": "adriamycin", "entity_type": "Chemical", "pos": [299, 309]}], "task": "NER"}
{"text": "Characteristics and determinants of adult patients with acute poisoning attending the accident and emergency department of a teaching hospital in Qatar .", "entity": [], "task": "NER"}
{"text": "Data about etiologic and demographic characteristics of acute poisoning in adults in Qatar are lacking .", "entity": [], "task": "NER"}
{"text": "This prospective observational study was undertaken to analyze characteristics and possible determinants of acute poisoning in adults in Qatar .", "entity": [], "task": "NER"}
{"text": "During 2010 , 18 , 073 patients attended the emergency department of Hamad General Hospital , a teaching hospital in Qatar .", "entity": [], "task": "NER"}
{"text": "Out of them , 599 ( 3 . 3 % ) patients were diagnosed as \" poisoning case \" with either chemical or pharmaceutical substances .", "entity": [], "task": "NER"}
{"text": "The prevalence rate of poisoning incidence was 35 . 3 / 100 , 000 population .", "entity": [], "task": "NER"}
{"text": "Seven patients died , corresponding with a case - fatality rate of 0 . 39 / 1000 .", "entity": [], "task": "NER"}
{"text": "The majority were male ( 65 % ) and the mean age was 34 years .", "entity": [], "task": "NER"}
{"text": "The poisons involved were mainly chemicals ( 61 . 6 % ) and pharmaceuticals ( 38 . 4 % ) .", "entity": [], "task": "NER"}
{"text": "Female , mainly single , suffered more intentional poisoning compared to male .", "entity": [], "task": "NER"}
{"text": "Of the patients aged 60 years and above ( 7 . 2 % ) , the majority ( 95 . 3 % ) suffered unintentional poisoning with pharmaceuticals ; 56 % with warfarin , 12 % with digoxin and 7 % with insulin .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [146, 154]}, {"entity": "digoxin", "entity_type": "Chemical", "pos": [167, 174]}], "task": "NER"}
{"text": "Multivariate analysis shows that female gender , single status , younger than 35 years of age , being poisoned by pharmaceutical products , and the need for hospitalization are significant determinants for acute intentional poisoning after adjusting all other possible covariates .", "entity": [], "task": "NER"}
{"text": "The findings of this study can be used to establish awareness and prophylactic campaigns in Qatar .", "entity": [], "task": "NER"}
{"text": "Stacking of Short DNA Induces the Gyroid Cubic - to - Inverted Hexagonal Phase Transition in Lipid - DNA Complexes .", "entity": [], "task": "NER"}
{"text": "Lyotropic phases of amphiphiles are a prototypical example of self - assemblies .", "entity": [], "task": "NER"}
{"text": "Their structure is generally determined by amphiphile shape and their phase transitions are primarily governed by composition .", "entity": [], "task": "NER"}
{"text": "In this paper , we demonstrate a new paradigm for membrane shape control where the electrostatic coupling of charged membranes to short DNA ( sDNA ) , with tunable temperature - dependent end - to - end stacking interactions , enables switching between the inverted gyroid cubic structure ( QII ( G ) ) and the inverted hexagonal phase ( HII ( C ) ) .", "entity": [], "task": "NER"}
{"text": "We investigated the structural shape transitions induced in the QII ( G ) phase upon complexation with a series of sDNAs ( 5 , 11 , 24 , and 48 bp ) with three types of end structure ( \" sticky \" adenine ( A ) - thymine ( T ) ( dAdT ) overhangs , no overhang ( blunt ) , and \" nonsticky \" dTdT overhangs ) using synchrotron small - angle X - ray scattering .", "entity": [{"entity": "adenine", "entity_type": "Chemical", "pos": [196, 203]}, {"entity": "thymine", "entity_type": "Chemical", "pos": [212, 219]}], "task": "NER"}
{"text": "Very short 5 bp sDNA with dAdT overhangs and blunt ends induce coexistence of the QII ( G ) and the HII ( C ) phase , with the fraction of QII ( G ) increasing with temperature .", "entity": [], "task": "NER"}
{"text": "Phase coexistence for blunt 5 bp sDNA is observed from 27 degrees C to about 65 degrees C , where the HII ( C ) phase disappears and the temperature dependence of the lattice spacing of the QII ( G ) phase indicates that the sDNA duplexes melt into single strands .", "entity": [], "task": "NER"}
{"text": "The only other sDNA for which melting is observed is 5 bp sDNA with dTdT overhangs , which forms the QII ( G ) phase throughout the studied range of temperature ( 27 degrees C to 85 . 2 degrees C ) .", "entity": [], "task": "NER"}
{"text": "The longer 11 bp sDNA forms coexisting QII ( G ) and HII ( C ) phases ( with the fraction of QII ( G ) again increasing with temperature ) only for \" nonsticky \" dTdT overhangs , while dAdT overhangs and blunt ends exclusively template the HII ( C ) phase .", "entity": [], "task": "NER"}
{"text": "For 24 and 48 bp sDNAs the HII ( C ) phase replaces the QII ( G ) phase at all investigated temperatures , independent of sDNA end structure .", "entity": [], "task": "NER"}
{"text": "Our work demonstrates how the combined effects of sDNA length and end structure ( which determine the temperature - dependent stacking length ) tune the phase behavior of the complexes .", "entity": [], "task": "NER"}
{"text": "These findings are consistent with the hypothesis that sDNAs and sDNA stacks with lengths comparable to or larger than the cubic unit cell length disfavor the highly curved channels present in the QII ( G ) phase , thus driving the QII ( G ) - to - HII ( C ) phase transition .", "entity": [], "task": "NER"}
{"text": "As the temperature is increased , the breaking of stacks due to thermal fluctuations restores increasing percentages of the QII ( G ) phase .", "entity": [], "task": "NER"}
{"text": "Sensing of biologically important cations such as na ( + ) , k ( + ) , ca ( 2 + ) , cu ( 2 + ) , and fe ( 3 + ) using magnetic nanoemulsions .", "entity": [{"entity": "na ( + )", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "k ( + )", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "ca ( 2 + )", "entity_type": "Chemical", "pos": [71, 81]}, {"entity": "cu ( 2 + )", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "fe ( 3 + )", "entity_type": "Chemical", "pos": [101, 111]}], "task": "NER"}
{"text": "We report a simple approach to the ultrasensitive detection of biologically important metal ions using a magnetic nanoemulsion .", "entity": [], "task": "NER"}
{"text": "The nanoemulsion used in our study was an oil - in - water emulsion droplet of average size ~ 190 nm containing ferrimagnetic iron oxide nanoparticles of average size ~ 10 nm .", "entity": [{"entity": "iron oxide", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "In a static magnetic field , the emulsion droplets self - assemble into a nanoarray with distinct interdroplet spacing .", "entity": [], "task": "NER"}
{"text": "In the presence of cations in the solution , the nanofluid array shows a large blue shift in the diffracted Bragg peak and a visually perceivable color change due to changes in the electrical double layer upon the diffusion of cations .", "entity": [], "task": "NER"}
{"text": "The colloidal force - distance measurements in the presence of cations show large variations at the onset of repulsion in the presence of cations .", "entity": [], "task": "NER"}
{"text": "The sensor shows good selectivity to Na ( + ) , K ( + ) , Ca ( 2 + ) , Cu ( 2 + ) , and Fe ( 3 + ) ions and offers a rapid response compared to conventional techniques .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [58, 68]}, {"entity": "Cu ( 2 + )", "entity_type": "Chemical", "pos": [71, 81]}, {"entity": "Fe ( 3 + )", "entity_type": "Chemical", "pos": [88, 98]}], "task": "NER"}
{"text": "This approach can be useful for the recognition of biologically important cations .", "entity": [], "task": "NER"}
{"text": "Steroids Glycosylated with Both d - and l - Arabinoses from the South China Sea Gorgonian Dichotella gemmacea .", "entity": [{"entity": "Steroids", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "d - and l - Arabinoses", "entity_type": "Chemical", "pos": [32, 54]}], "task": "NER"}
{"text": "Three new 19 - hydroxy steroidal glycosides , namely , junceellosides E - G ( 2 - 4 ) , were isolated together with the known analogue junceelloside C ( 1 ) from the South China Sea gorgonian Dichotella gemmacea .", "entity": [{"entity": "19 - hydroxy steroidal glycosides", "entity_type": "Chemical", "pos": [10, 43]}, {"entity": "junceellosides E - G", "entity_type": "Chemical", "pos": [55, 75]}, {"entity": "junceelloside C", "entity_type": "Chemical", "pos": [135, 150]}], "task": "NER"}
{"text": "The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses , chemical methods , and comparison with reported data .", "entity": [], "task": "NER"}
{"text": "These glycosides are found to have sugar moieties of both beta - l - and beta - d - arabinopyranoses by HPLC analysis of their thiocarbamoyl - thiazolidine derivatives and those of authentic d - and l - arabinoses , leading to the structure revision of junceelloside C ( 1 ) .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [35, 40]}, {"entity": "beta - l - and beta - d - arabinopyranoses", "entity_type": "Chemical", "pos": [58, 100]}, {"entity": "thiocarbamoyl - thiazolidine", "entity_type": "Chemical", "pos": [127, 155]}, {"entity": "d - and l - arabinoses", "entity_type": "Chemical", "pos": [191, 213]}, {"entity": "junceelloside C", "entity_type": "Chemical", "pos": [253, 268]}], "task": "NER"}
{"text": "This is the first report of steroidal glycosides from the gorgonian D . gemmacea and the first report of glycosides with beta - l - arabinopyranose from marine sources .", "entity": [{"entity": "beta - l - arabinopyranose", "entity_type": "Chemical", "pos": [121, 147]}], "task": "NER"}
{"text": "In situ forming reduction - sensitive degradable nanogels for facile loading and triggered intracellular release of proteins .", "entity": [], "task": "NER"}
{"text": "In situ forming reduction - sensitive degradable nanogels were designed and developed based on poly ( ethylene glycol ) - b - poly ( 2 - ( hydroxyethyl ) methacrylate - co - acryloyl carbonate ) ( PEG - P ( HEMA - co - AC ) ) block copolymers for efficient loading as well as triggered intracellular release of proteins .", "entity": [{"entity": "poly ( ethylene glycol ) - b - poly ( 2 - ( hydroxyethyl ) methacrylate - co - acryloyl carbonate )", "entity_type": "Chemical", "pos": [95, 194]}, {"entity": "PEG - P ( HEMA - co - AC )", "entity_type": "Chemical", "pos": [197, 223]}], "task": "NER"}
{"text": "PEG - P ( HEMA - co - AC ) copolymers were prepared with controlled Mn of 9 . 1 , 9 . 5 , and 9 . 9 kg / mol and varying numbers of AC units per molecule of 7 , 9 and 11 , respectively ( denoted as copolymer 1 , 2 , and 3 ) by reversible addition - fragmentation chain transfer copolymerization .", "entity": [{"entity": "PEG - P ( HEMA - co - AC )", "entity_type": "Chemical", "pos": [0, 26]}], "task": "NER"}
{"text": "These copolymers were freely soluble in phosphate buffer but formed disulfide - cross - linked nanogels with defined sizes ranging from 72 . 5 to 124 . 1 nm in the presence of cystamine via ring - opening reaction with cyclic carbonate groups .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "disulfide", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "cystamine", "entity_type": "Chemical", "pos": [176, 185]}, {"entity": "cyclic carbonate", "entity_type": "Chemical", "pos": [219, 235]}], "task": "NER"}
{"text": "The sizes of nanogels decreased with increasing AC units as a result of increased cross - linking density .", "entity": [], "task": "NER"}
{"text": "Dynamic light scattering studies showed that these nanogels though stable at physiological conditions were rapidly dissociated in response to 10 mM dithiothreitol ( DTT ) .", "entity": [{"entity": "dithiothreitol", "entity_type": "Chemical", "pos": [148, 162]}, {"entity": "DTT", "entity_type": "Chemical", "pos": [165, 168]}], "task": "NER"}
{"text": "Interestingly , FITC - labeled cytochrome C ( FITC - CC ) could be readily loaded into nanogels with remarkable loading efficiencies ( up to 98 . 2 % ) and loading contents ( up to 48 . 2 wt . % ) .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [16, 20]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "The in vitro release studies showed that release of FITC - CC was minimal under physiological conditions but significantly enhanced under reductive conditions in the presence of 10 mM DTT with about 96 . 8 % of FITC - CC released in 22 h from nanogel 1 .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "DTT", "entity_type": "Chemical", "pos": [184, 187]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [211, 215]}], "task": "NER"}
{"text": "In contrast , protein release from 1 , 4 - butanediamine cross - linked nanogels ( reduction - insensitive control ) remained low under otherwise the same conditions .", "entity": [{"entity": "1 , 4 - butanediamine", "entity_type": "Chemical", "pos": [35, 56]}], "task": "NER"}
{"text": "MTT assays showed that these nanogels were nontoxic to HeLa cells up to a tested concentration of 2 mg / mL .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Confocal microscopy results showed that nanogel 1 delivered and released FITC - CC into the perinuclei region of HeLa cells following 8 h incubation .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "CC - loaded reductively degradable nanogels demonstrated apparently better apoptotic activity than free CC as well as reduction - insensitive controls .", "entity": [], "task": "NER"}
{"text": "These in situ forming , surfactant and oil - free , and reduction - sensitive degradable nanogels are highly promising for targeted protein therapy .", "entity": [], "task": "NER"}
{"text": "Age - Related Macular Degeneration - Associated Silent Polymorphisms in HtrA1 Impair Its Ability To Antagonize Insulin - Like Growth Factor 1 .", "entity": [], "task": "NER"}
{"text": "Synonymous single nucleotide polymorphisms ( SNPs ) within a transcript ' s coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [115, 125]}], "task": "NER"}
{"text": "We report that two common variants of high - temperature requirement A1 ( HTRA1 ) that increase the inherited risk of neovascular age - related macular degeneration ( NvAMD ) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons .", "entity": [{"entity": "Ala34", "entity_type": "Chemical", "pos": [252, 257]}, {"entity": "Gly36", "entity_type": "Chemical", "pos": [262, 267]}], "task": "NER"}
{"text": "The frequent - to - rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1 ' s conformation and function .", "entity": [], "task": "NER"}
{"text": "The protein product generated from the SNP - containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti - HtrA1 antibody .", "entity": [], "task": "NER"}
{"text": "The NvAMD - associated synonymous polymorphisms lie within HtrA1 ' s putative insulin - like growth factor 1 ( IGF - 1 ) binding domain .", "entity": [], "task": "NER"}
{"text": "They reduced HtrA1 ' s abilities to associate with IGF - 1 and to ameliorate IGF - 1 - stimulated signaling events and cellular responses .", "entity": [], "task": "NER"}
{"text": "These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD .", "entity": [], "task": "NER"}
{"text": "Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress .", "entity": [], "task": "NER"}
{"text": "The NAD + - dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells .", "entity": [{"entity": "NAD +", "entity_type": "Chemical", "pos": [4, 9]}], "task": "NER"}
{"text": "In contrast to the well - documented protective actions of Sirt1 , the role of endothelial Sirt2 remains unknown .", "entity": [], "task": "NER"}
{"text": "Using cDNA microarray and PCR validation , we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress .", "entity": [], "task": "NER"}
{"text": "We found that Sirt2 knock down changed expression of 340 genes , which are mainly involved in cellular processes including actin binding , cellular amino acid metabolic process , transmembrane receptor protein serine / threonine kinase signaling , ferrous iron transport , protein transport and localization , cell morphogenesis , and functions associated with endosome membrane and the trans - Golgi network .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [148, 158]}, {"entity": "serine", "entity_type": "Chemical", "pos": [210, 216]}, {"entity": "threonine", "entity_type": "Chemical", "pos": [219, 228]}, {"entity": "ferrous iron", "entity_type": "Chemical", "pos": [248, 260]}], "task": "NER"}
{"text": "These genes and associated functions were largely non - overlapping with those altered by Sirt1 knock down .", "entity": [], "task": "NER"}
{"text": "Moreover , we showed that pharmacological inhibition of Sirt2 attenuated oxidant - induced cell toxicity in endothelial cells .", "entity": [], "task": "NER"}
{"text": "These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress , and may have a primarily distinct role as compared to Sirt1 .", "entity": [], "task": "NER"}
{"text": "Our results may provide a basis for future studies aiming to dissect the specific signaling pathway ( s ) that mediates specific Sirt2 functions in endothelial cells .", "entity": [], "task": "NER"}
{"text": "Genotoxic effects of the water - soluble fraction of heavy oil in the brackish / freshwater amphipod Quadrivisio aff . lutzi ( Gammaridea ) as assessed using the comet assay .", "entity": [], "task": "NER"}
{"text": "Amphipod crustaceans have been widely used as invertebrate models in ecotoxicology due to their importance in the food chain .", "entity": [], "task": "NER"}
{"text": "However , few studies have evaluated the genotoxic effects of pollutants in this model using the comet assay .", "entity": [], "task": "NER"}
{"text": "The main obstacle to using amphipods in the comet assay is the difficulty in obtaining enough blood cells from a single individual .", "entity": [], "task": "NER"}
{"text": "In this study , we evaluated the genotoxic effects of the water - soluble fraction ( WSF ) of heavy oil on the brackish / freshwater amphipod Quadrivisio aff . lutzi , which is common in the coastal lagoons of southeastern Brazil , using hemocytes obtained from single amphipods ( without pooling ) after optimizing hemolymph extraction .", "entity": [], "task": "NER"}
{"text": "The comet assay revealed significantly higher DNA damage levels ( 2 - to 6 - fold higher ) in treated amphipods compared to untreated ones with a sublethal concentration of 17 . 6 % of the WSF within 72 h of treatment .", "entity": [], "task": "NER"}
{"text": "Two independent experiments confirmed an \" up and down \" pattern of DNA damage , measured as the % of DNA contained in the tail of the comets .", "entity": [], "task": "NER"}
{"text": "Elevations in DNA damage levels were observed at the 6 and 48 h time points , while very low levels of DNA damage were observed at the 24 and 72 h time points .", "entity": [], "task": "NER"}
{"text": "Furthermore , the comet assay revealed gender variability in the levels of DNA damage after short - term exposure .", "entity": [], "task": "NER"}
{"text": "Selective poisoning of Ctnnb1 - mutated hepatoma cells in mouse liver tumors by a single application of acetaminophen .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [104, 117]}], "task": "NER"}
{"text": "Mouse liver tumors that harbor activating mutations in Ctnnb1 , encoding beta - catenin , express high levels of various cytochromes P450 ( CYP ) , including CYP2E1 and CYP1A2 .", "entity": [], "task": "NER"}
{"text": "Acetaminophen ( AAP ) is metabolized in hepatocytes by these CYPs to the reactive intermediate N - acetyl - p - benzoquinone - imine , which is toxic to hepatocytes at high doses where depletion of glutathione occurs .", "entity": [{"entity": "Acetaminophen", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "AAP", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "N - acetyl - p - benzoquinone - imine", "entity_type": "Chemical", "pos": [95, 132]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [198, 209]}], "task": "NER"}
{"text": "We have induced liver tumors in mice by treatment with the liver carcinogen N - nitrosodiethylamine followed by chronic treatment with the tumor promoter phenobarbital .", "entity": [{"entity": "N - nitrosodiethylamine", "entity_type": "Chemical", "pos": [76, 99]}, {"entity": "phenobarbital", "entity_type": "Chemical", "pos": [154, 167]}], "task": "NER"}
{"text": "Under this protocol , ~ 80 % of tumors display Ctnnb1 mutations and express high levels of various CYP isoforms .", "entity": [], "task": "NER"}
{"text": "Tumor - bearing animals were given a single intraperitoneal injection of 300 mg / kg body weight AAP , which was well tolerated by the animals .", "entity": [{"entity": "AAP", "entity_type": "Chemical", "pos": [97, 100]}], "task": "NER"}
{"text": "This dose , however , eradicated essentially all larger Ctnnb1 - mutated , CYP - positive liver tumors , killing > 90 % of hepatoma cells : at 2 days after AAP , large necrotic areas filled with cell debris were observed in tumors .", "entity": [{"entity": "AAP", "entity_type": "Chemical", "pos": [156, 159]}], "task": "NER"}
{"text": "These were infiltrated in the following days by immune cells starting from the outer parts of the damaged areas slowly closing the \" wounds \" left from the poisoned tumor cells .", "entity": [], "task": "NER"}
{"text": "During this period , there was increased proliferation of normal hepatocytes , but some residual tumor cells were also proliferating .", "entity": [], "task": "NER"}
{"text": "Our results show that a selective poisoning of Ctnnb1 - mutated liver tumors by administration of AAP is possible in this experimental system .", "entity": [{"entity": "AAP", "entity_type": "Chemical", "pos": [98, 101]}], "task": "NER"}
{"text": "Application of an adapted protocol could be envisaged for neo - adjuvant treatment of human hepatoblastoma which are frequently mutated in CTNNB1 and often show high expression of CYP2E1 .", "entity": [], "task": "NER"}
{"text": "Theoretical study of the thermodynamic and burning properties of oxygen - rich hydrazine derivatives - green and powerful oxidants for energetic materials .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [65, 71]}, {"entity": "hydrazine", "entity_type": "Chemical", "pos": [79, 88]}], "task": "NER"}
{"text": "A series of no - chlorine and oxygen - rich hydrazine derivatives ( hydrazine modified with - NO2 and NO3 ( - ) groups ) was designed and optimized to obtain molecular geometries and electronic structures at density functional theory - B3PW91 / 6 - 311 + + G ( 3df , 3pd ) level .", "entity": [{"entity": "chlorine", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "hydrazine", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "hydrazine", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "NO2", "entity_type": "Chemical", "pos": [94, 97]}, {"entity": "NO3 ( - )", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "Some important properties such as bond dissociation enthalpy , density , natural bond orbitals , thermodynamic parameters , molecular orbital energy and burning rate were then calculated .", "entity": [], "task": "NER"}
{"text": "The simulation results revealed that these compounds exhibit excellent performance , with significant superiority over traditional oxidants found in propellants .", "entity": [], "task": "NER"}
{"text": "Flavonoids and 3 - Arylcoumarin from Pterocarpus soyauxii .", "entity": [{"entity": "Flavonoids", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "3 - Arylcoumarin", "entity_type": "Chemical", "pos": [15, 31]}], "task": "NER"}
{"text": "Phytochemical study on the constituents of the heartwood of Pterocarpus soyauxii led to the isolation of five new isoflavonoids and one new 3 - arylcoumarin , pterosonins A - F ( 1 - 6 ) , together with 17 known analogues , among which 8 , 9 , and 18 were reported as natural products for the first time .", "entity": [{"entity": "isoflavonoids", "entity_type": "Chemical", "pos": [114, 127]}, {"entity": "3 - arylcoumarin", "entity_type": "Chemical", "pos": [140, 156]}, {"entity": "pterosonins A - F", "entity_type": "Chemical", "pos": [159, 176]}], "task": "NER"}
{"text": "Structure elucidation was achieved by way of spectroscopic measurements as well as by comparison with literature data .", "entity": [], "task": "NER"}
{"text": "Only Compound 6 showed potent cytotoxicity against human non - small cell lung cancer ( A549 ) , pancreatic cancer ( Panc - 28 ) , and colon carcinoma ( HCT - 116 ) cells with GI50 values at 7 . 39 , 25 , and 19 . 17 micro M , respectively ; the other isolates showed no cytotoxicity against the above tested cell lines with GI50 values > 50 micro M .", "entity": [], "task": "NER"}
{"text": "Dyslipidemia in type 2 diabetes : prevalence , pathophysiology , and management .", "entity": [], "task": "NER"}
{"text": "Dyslipidemia is one of the key risk factors for cardiovascular disease ( CVD ) in diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "Despite the mounting clinical trial data , the management of dyslipidemia other than lowering the low density lipoprotein cholesterol ( LDL - c ) continues to be controversial .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [122, 133]}], "task": "NER"}
{"text": "The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration , reduced high density lipoprotein cholesterol ( HDL - c ) concentration , and increased concentration of small dense LDL particles .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [69, 81]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [131, 142]}], "task": "NER"}
{"text": "These changes are caused by increased free fatty acid flux secondary to insulin resistance and aggravated by increased inflammatory adipokines .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "The availability of several lipid - lowering drugs and nutritional supplements offers novel and effective options for achieving target lipid levels in people with diabetes .", "entity": [], "task": "NER"}
{"text": "While initiation of drug therapy based on differences in the lipid profile is an option , most practice guidelines recommend statins as first - line therapy .", "entity": [], "task": "NER"}
{"text": "Although the evidence for clinical utility of combination of statins with fibrates or nicotinic acid in reducing cardiovascular events remains inconclusive , the preponderance of evidence suggests that a subgroup who have high triglycerides and low HDL - c levels may benefit from combination therapy of statins and fibrates .", "entity": [{"entity": "fibrates", "entity_type": "Chemical", "pos": [74, 82]}, {"entity": "nicotinic acid", "entity_type": "Chemical", "pos": [86, 100]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [227, 240]}, {"entity": "fibrates", "entity_type": "Chemical", "pos": [316, 324]}], "task": "NER"}
{"text": "The goal of therapy is to achieve at least 30 - 40 % reduction in LDL - c levels .", "entity": [], "task": "NER"}
{"text": "Preferably the LDL - c should be less than 100 mg / dL in low - risk people and less than 70 mg / dL in those at high risk , including people with established CVD .", "entity": [], "task": "NER"}
{"text": "Crystal Structures of a Glycoside Hydrolase Family 20 Lacto - N - biosidase from Bifidobacterium bifidum .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [62, 63]}], "task": "NER"}
{"text": "Human milk oligosaccharides contain a large variety of oligosaccharides , of which lacto - N - biose I ( Gal - beta 1 , 3 - GlcNAc ; LNB ) predominates as a major core structure .", "entity": [{"entity": "lacto - N - biose I", "entity_type": "Chemical", "pos": [83, 102]}, {"entity": "Gal - beta 1 , 3 - GlcNAc", "entity_type": "Chemical", "pos": [105, 130]}, {"entity": "LNB", "entity_type": "Chemical", "pos": [133, 136]}], "task": "NER"}
{"text": "A unique metabolic pathway specific for LNB has recently been identified in the human commensal bifidobacteria .", "entity": [{"entity": "LNB", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "Several strains of infant gut - associated bifidobacteria possess lacto - N - biosidase , a membrane - anchored extracellular enzyme , that liberates LNB from the nonreducing end of human milk oligosaccharides and plays a key role in the metabolic pathway of these compounds .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [74, 75]}, {"entity": "LNB", "entity_type": "Chemical", "pos": [150, 153]}], "task": "NER"}
{"text": "Lacto - N - biosidase belongs to the glycoside hydrolase family 20 , and its reaction proceeds via a substrate - assisted catalytic mechanism .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [8, 9]}], "task": "NER"}
{"text": "Several crystal structures of GH20 beta - N - acetylhexosaminidases , which release monosaccharide GlcNAc from its substrate , have been determined , but to date , a structure of lacto - N - biosidase is unknown .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [42, 43]}, {"entity": "monosaccharide", "entity_type": "Chemical", "pos": [84, 98]}, {"entity": "GlcNAc", "entity_type": "Chemical", "pos": [99, 105]}, {"entity": "N", "entity_type": "Chemical", "pos": [187, 188]}], "task": "NER"}
{"text": "Here , we have determined the first three - dimensional structures of lacto - N - biosidase from Bifidobacterium bifidum JCM1254 in complex with LNB and LNB - thiazoline ( Gal - beta 1 , 3 - GlcNAc - thiazoline ) at 1 . 8 - A resolution .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [78, 79]}, {"entity": "LNB", "entity_type": "Chemical", "pos": [145, 148]}, {"entity": "LNB - thiazoline", "entity_type": "Chemical", "pos": [153, 169]}, {"entity": "Gal - beta 1 , 3 - GlcNAc - thiazoline", "entity_type": "Chemical", "pos": [172, 210]}], "task": "NER"}
{"text": "Lacto - N - biosidase consists of three domains , and the C - terminal domain has a unique beta - trefoil - like fold .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [8, 9]}, {"entity": "C", "entity_type": "Chemical", "pos": [58, 59]}], "task": "NER"}
{"text": "Compared with other beta - N - acetylhexosaminidases , lacto - N - biosidase has a wide substrate - binding pocket with a - 2 subsite specific for beta - 1 , 3 - linked Gal , and the residues responsible for Gal recognition were identified .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [27, 28]}, {"entity": "N", "entity_type": "Chemical", "pos": [63, 64]}, {"entity": "Gal", "entity_type": "Chemical", "pos": [169, 172]}, {"entity": "Gal", "entity_type": "Chemical", "pos": [208, 211]}], "task": "NER"}
{"text": "The bound ligands are recognized by extensive hydrogen bonds at all of their hydroxyls consistent with the enzyme ' s strict substrate specificity for the LNB moiety .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "hydroxyls", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "LNB", "entity_type": "Chemical", "pos": [155, 158]}], "task": "NER"}
{"text": "The GlcNAc sugar ring of LNB is in a distorted conformation near ( 4 ) E , whereas that of LNB - thiazoline is in a ( 4 ) C1 conformation .", "entity": [{"entity": "GlcNAc", "entity_type": "Chemical", "pos": [4, 10]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [11, 16]}, {"entity": "LNB", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "LNB", "entity_type": "Chemical", "pos": [91, 94]}, {"entity": "thiazoline", "entity_type": "Chemical", "pos": [97, 107]}], "task": "NER"}
{"text": "A possible conformational pathway for the lacto - N - biosidase reaction is discussed .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [50, 51]}], "task": "NER"}
{"text": "Degradation and Rearrangement of a Lung Surfactant Lipid at the Air - Water Interface during Exposure to the Pollutant Gas Ozone .", "entity": [{"entity": "Ozone", "entity_type": "Chemical", "pos": [123, 128]}], "task": "NER"}
{"text": "The presence of unsaturated lipids in lung surfactant is important for proper respiratory function .", "entity": [], "task": "NER"}
{"text": "In this work , we have used neutron reflection and surface pressure measurements to study the reaction of the ubiquitous pollutant gas - phase ozone , O3 , with pure and mixed phospholipid monolayers at the air - water interface .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [143, 148]}, {"entity": "O3", "entity_type": "Chemical", "pos": [151, 153]}], "task": "NER"}
{"text": "The results reveal that the reaction of the unsaturated lipid 1 - palmitoyl - 2 - oleoyl - sn - glycero - 3 - phosphocholine , POPC , with ozone leads to the rapid loss of the terminal C9 portion of the oleoyl strand of POPC from the air - water interface .", "entity": [{"entity": "1 - palmitoyl - 2 - oleoyl - sn - glycero - 3 - phosphocholine", "entity_type": "Chemical", "pos": [62, 124]}, {"entity": "POPC", "entity_type": "Chemical", "pos": [127, 131]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [139, 144]}, {"entity": "oleoyl", "entity_type": "Chemical", "pos": [203, 209]}, {"entity": "POPC", "entity_type": "Chemical", "pos": [220, 224]}], "task": "NER"}
{"text": "The loss of the C9 portion from the interface is accompanied by an increase in the surface pressure ( decrease in surface tension ) of the film at the air - water interface .", "entity": [], "task": "NER"}
{"text": "The results suggest that the portion of the oxidized oleoyl strand that is still attached to the lipid headgroup rapidly reverses its orientation and penetrates the air - water interface alongside the original headgroup , thus increasing the surface pressure .", "entity": [{"entity": "oleoyl", "entity_type": "Chemical", "pos": [53, 59]}], "task": "NER"}
{"text": "The reaction of POPC with ozone also leads to a loss of material from the palmitoyl strand , but the loss of palmitoyl material occurs after the loss of the terminal C9 portion from the oleoyl strand of the molecule , suggesting that the palmitoyl material is lost in a secondary reaction step .", "entity": [{"entity": "POPC", "entity_type": "Chemical", "pos": [16, 20]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [26, 31]}, {"entity": "palmitoyl", "entity_type": "Chemical", "pos": [74, 83]}, {"entity": "palmitoyl", "entity_type": "Chemical", "pos": [109, 118]}, {"entity": "oleoyl", "entity_type": "Chemical", "pos": [186, 192]}, {"entity": "palmitoyl", "entity_type": "Chemical", "pos": [238, 247]}], "task": "NER"}
{"text": "Further experiments studying the reaction of mixed monolayers composed of unsaturated lipid POPC and saturated lipid dipalmitoyl - sn - glycero - 3 - phosphocholine , DPPC , revealed that no loss of DPPC from the air - water interface occurs , eliminating the possibility that a reactive species such as an OH radical is formed and is able to attack nearby lipid chains .", "entity": [{"entity": "POPC", "entity_type": "Chemical", "pos": [92, 96]}, {"entity": "dipalmitoyl - sn - glycero - 3 - phosphocholine", "entity_type": "Chemical", "pos": [117, 164]}, {"entity": "DPPC", "entity_type": "Chemical", "pos": [167, 171]}, {"entity": "DPPC", "entity_type": "Chemical", "pos": [199, 203]}, {"entity": "OH", "entity_type": "Chemical", "pos": [307, 309]}], "task": "NER"}
{"text": "The reaction of ozone with the mixed films does cause a significant change in the surface pressure of the air - water interface .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [16, 21]}], "task": "NER"}
{"text": "Thus , the reaction of unsaturated lipids in lung surfactant changes and impairs the physical properties of the film at the air - water interface .", "entity": [], "task": "NER"}
{"text": "MD simulations of the formation of stable clusters in mixtures of alkaline salts and imidazolium - based ionic liquids .", "entity": [{"entity": "alkaline salts", "entity_type": "Chemical", "pos": [66, 80]}, {"entity": "imidazolium", "entity_type": "Chemical", "pos": [85, 96]}], "task": "NER"}
{"text": "Structural and dynamical properties of room - temperature ionic liquids containing the cation 1 - butyl - 3 - methylimidazolium ( [ BMIM ] ( + ) ) and three different anions ( hexafluorophosphate , [ PF6 ] ( - ) , tetrafluoroborate , [ BF4 ] ( - ) , and bis ( trifluoromethylsulfonyl ) imide , [ NTf2 ] ( - ) ) doped with several molar fractions of lithium salts with a common anion at 298 . 15 K and 1 atm were investigated by means of molecular dynamics simulations .", "entity": [{"entity": "1 - butyl - 3 - methylimidazolium", "entity_type": "Chemical", "pos": [94, 127]}, {"entity": "[ BMIM ] ( + )", "entity_type": "Chemical", "pos": [130, 144]}, {"entity": "hexafluorophosphate", "entity_type": "Chemical", "pos": [176, 195]}, {"entity": "[ PF6 ] ( - )", "entity_type": "Chemical", "pos": [198, 211]}, {"entity": "tetrafluoroborate", "entity_type": "Chemical", "pos": [214, 231]}, {"entity": "[ BF4 ] ( - )", "entity_type": "Chemical", "pos": [234, 247]}, {"entity": "bis ( trifluoromethylsulfonyl ) imide", "entity_type": "Chemical", "pos": [254, 291]}, {"entity": "[ NTf2 ] ( - )", "entity_type": "Chemical", "pos": [294, 308]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [349, 356]}], "task": "NER"}
{"text": "The effect of the size of the salt cation was also analyzed by comparing these results with those for mixtures of [ BMIM ] [ PF6 ] with NaPF6 .", "entity": [{"entity": "[ BMIM ] [ PF6 ]", "entity_type": "Chemical", "pos": [114, 130]}, {"entity": "NaPF6", "entity_type": "Chemical", "pos": [136, 141]}], "task": "NER"}
{"text": "Lithium / sodium solvation and ionic mobilities were analyzed via the study of radial distribution functions , coordination numbers , cage autocorrelation functions , mean - square displacements ( including the analysis of both ballistic and diffusive regimes ) , self - diffusion coefficients of all the ionic species , velocity and current autocorrelation functions , and ionic conductivity in all the ionic liquid / salt systems .", "entity": [{"entity": "Lithium", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [10, 16]}], "task": "NER"}
{"text": "We found that lithium and sodium cations are strongly coordinated in two different positions with the anion present in the mixture .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [26, 32]}], "task": "NER"}
{"text": "Moreover , [ Li ] ( + ) and [ Na ] ( + ) cations were found to form bonded - like , long - lived aggregates with the anions in their first solvation shell , which act as very stable kinetic entities within which a marked rattling motion of salt ions takes place .", "entity": [{"entity": "[ Li ] ( + )", "entity_type": "Chemical", "pos": [11, 23]}, {"entity": "[ Na ] ( + )", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "With very long MD simulation runs , this phenomenon is proved to be on the basis of the decrease of self - diffusion coefficients and ionic conductivities previously reported in experimental and computational results .", "entity": [], "task": "NER"}
{"text": "The Emerging Use of Ketamine for Anesthesia and Sedation in Traumatic Brain Injuries .", "entity": [{"entity": "Ketamine", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "BACKGROUND : Traditionally , the use of ketamine for patients with traumatic brain injuries is contraindicated due to the concern of increasing intracranial pressure ( ICP ) .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "These concerns , however , originated from early studies and case reports that were inadequately controlled and designed .", "entity": [], "task": "NER"}
{"text": "Recently , the concern of using ketamine in these patients has been challenged by a number of published studies demonstrating that the use of ketamine was safe in these patients .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [32, 40]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [142, 150]}], "task": "NER"}
{"text": "AIMS : The purpose of this article was to review the current literature in regards to using ketamine in patients with traumatic brain injuries in different clinical settings associated with anesthesia , as well as review the potential mechanisms underlying the neuroprotective effects of ketamine .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [92, 100]}, {"entity": "ketamine", "entity_type": "Chemical", "pos": [288, 296]}], "task": "NER"}
{"text": "RESULTS : Studies examining the use of ketamine for induction , maintenance , and sedation in patients with TBI have had promising results .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "The use of ketamine in a controlled ventilation setting and in combination with other sedative agents has demonstrated no increase in ICP .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "CONCLUSIONS : The role of ketamine as a neuroprotective agent in humans remains inconclusive and adequately powered ; randomized controlled trials performed in patients undergoing surgery for traumatic brain injury are necessary .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "Killed Bacillus subtilis spores expressing streptavidin : a novel carrier of drugs to target cancer cells .", "entity": [], "task": "NER"}
{"text": "Abstract Carriers of drugs in cancer therapy are required to reduce side - effects of the drugs to normal cells .", "entity": [], "task": "NER"}
{"text": "Here we constructed killed recombinant Bacillus subtilis spores ( SA1 ) that expressed streptavidin as a chimeric fusion to the spore coat protein CotB and used the spores as bioparticle carrier .", "entity": [], "task": "NER"}
{"text": "When bound with biotinylated cetuximab these spores could specifically target to the epidermal growth factor receptor on HT 29 colon cancer cells , thereby delivered paclitaxel to the cells with 4 - fold higher efficiency , as indicated by fluorescent intensity of paclitaxel Oregon Green 488 bound to HT29 cells .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [166, 176]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [265, 275]}, {"entity": "Oregon Green 488", "entity_type": "Chemical", "pos": [276, 292]}], "task": "NER"}
{"text": "Based on real - time monitoring of cell index , the IC50 of growth of HT29 cells by paclitaxel - SA1 - cetuximab was estimated to be 2 . 9 nM approximately 5 - fold lower than water - soluble paclitaxel ( 14 . 5 nM ) .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [192, 202]}], "task": "NER"}
{"text": "Instability of DNA content was observed when cells were treated with 16 nM paclitaxel - SA1 - cetuximab , resulting in a 2 - fold enhancement in polyploidy cells .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [75, 85]}], "task": "NER"}
{"text": "Thus , by targeting the release of paclitaxel to HT29 cells , spore - associated cetuximab augmented the inhibitory effect of paclitaxel on cell division and proliferation .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "The SA1 could be used as a \" universal \" drug carrier to target specific biomarkers on cancer cells by conjugating with suitable biotinylated antibodies .", "entity": [], "task": "NER"}
{"text": "9G DNAChip Technology : Self - Assembled Monolayer ( SAM ) of ssDNA for Ultra - Sensitive Detection of Biomarkers .", "entity": [], "task": "NER"}
{"text": "A 9G DNAChip obtained by allowing the formation of a self - assembled monolayer ( SAM ) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers .", "entity": [{"entity": "guanines", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "Using a 9G DNAChip , biomarker in the concentration range of 4 pg / mL to 40 fg / mL can be easily differentiated in the buffer matrix .", "entity": [], "task": "NER"}
{"text": "Moreover , it is the first time that a biomarker with a concentration of 40 fg / mL has been detected in a mixture of proteins without use of any signal amplification technique .", "entity": [], "task": "NER"}
{"text": "Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D - Cdk4 Expression in Non - Small Cell Lung Cancer ( NSCLC ) .", "entity": [{"entity": "Simvastatin", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "Lung cancer is the most common cause of cancer - related death .", "entity": [], "task": "NER"}
{"text": "Nonetheless , a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents .", "entity": [], "task": "NER"}
{"text": "In recent studies , Simvastatin ( SIM ) has demonstrated anti - tumor activity , as well as potent chemopreventive action .", "entity": [{"entity": "Simvastatin", "entity_type": "Chemical", "pos": [20, 31]}, {"entity": "SIM", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "As an inhibitor of 3 - hydroxy - 3 - methylglutaryl - coenzyme A reductase ( HMG - CoA ) , SIM has been shown to stimulate apoptotic cell death .", "entity": [{"entity": "3 - hydroxy - 3 - methylglutaryl - coenzyme A", "entity_type": "Chemical", "pos": [19, 64]}, {"entity": "HMG", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "CoA", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "SIM", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "In this study , an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer ( Non - small cell lung cancer ; NSCLC ) cells ( NCI - H460 ) ; however , induced apoptosis was not observed in NCI - H460 cells .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "SIM", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Protein expression levels of cell cycle regulating proteins Cdk4 , Cyclin D1 , p16 and p27 were markedly altered by SIM .", "entity": [{"entity": "SIM", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "Collectively , our results indicate that SIM inhibits cell proliferation and arrests NCI - H460 cell cycle progression via inhibition of cyclin - dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27 .", "entity": [{"entity": "SIM", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "Our findings suggest that , in addition to the known effects on hypercholesterolemia therapy , SIM may also provide antitumor activity in established NSCLC .", "entity": [{"entity": "SIM", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "Substituted 1 , 6 - diphenylnaphthalenes as FtsZ - targeting antibacterial agents .", "entity": [{"entity": "1 , 6 - diphenylnaphthalenes", "entity_type": "Chemical", "pos": [12, 40]}], "task": "NER"}
{"text": "Agents that disrupt Z - ring formation have the potential , through this unique mechanism , to be effective against several of the newly emerging multidrug - resistant strains of infectious bacteria .", "entity": [], "task": "NER"}
{"text": "Several 1 - phenylbenzo [ c ] phenanthridines exhibit notable antibacterial activity .", "entity": [{"entity": "1 - phenylbenzo [ c ] phenanthridines", "entity_type": "Chemical", "pos": [8, 45]}], "task": "NER"}
{"text": "Based upon their structural similarity to these compounds , a distinct series of substituted 1 , 6 - diphenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis .", "entity": [{"entity": "1 , 6 - diphenylnaphthalenes", "entity_type": "Chemical", "pos": [93, 121]}], "task": "NER"}
{"text": "In addition , the effect of select 1 , 6 - diphenylnaphthalenes on the polymerization dynamics of S . aureus FtsZ and mammalian beta - tubulin was also assessed .", "entity": [{"entity": "1 , 6 - diphenylnaphthalenes", "entity_type": "Chemical", "pos": [35, 63]}], "task": "NER"}
{"text": "The presence of a basic functional group or a quaternary ammonium substituent on the 6 - phenylnaphthalene was required for significant antibacterial activity .", "entity": [{"entity": "quaternary ammonium", "entity_type": "Chemical", "pos": [46, 65]}, {"entity": "6 - phenylnaphthalene", "entity_type": "Chemical", "pos": [85, 106]}], "task": "NER"}
{"text": "Diphenylnaphthalene derivatives that were active as antibiotics , did exert a pronounced effect on bacterial FtsZ polymerization and do not appear to cross - react with mammalian tubulin to any significant degree .", "entity": [{"entity": "Diphenylnaphthalene", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "Characterization of the 5 - hydroxymethylcytosine - specific DNA restriction endonucleases .", "entity": [{"entity": "5 - hydroxymethylcytosine", "entity_type": "Chemical", "pos": [24, 49]}], "task": "NER"}
{"text": "In T4 bacteriophage , 5 - hydroxymethylcytosine ( 5hmC ) is incorporated into DNA during replication .", "entity": [{"entity": "5 - hydroxymethylcytosine", "entity_type": "Chemical", "pos": [22, 47]}, {"entity": "5hmC", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "In response , bacteria may have developed modification - dependent type IV restriction enzymes to defend the cell from T4 - like infection .", "entity": [], "task": "NER"}
{"text": "PvuRts1I was the first identified restriction enzyme to exhibit specificity toward hmC over 5 - methylcytosine ( 5mC ) and cytosine .", "entity": [{"entity": "hmC", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "5 - methylcytosine", "entity_type": "Chemical", "pos": [92, 110]}, {"entity": "5mC", "entity_type": "Chemical", "pos": [113, 116]}, {"entity": "cytosine", "entity_type": "Chemical", "pos": [123, 131]}], "task": "NER"}
{"text": "By using PvuRts1I as the original member , we identified and characterized a number of homologous proteins .", "entity": [], "task": "NER"}
{"text": "Most enzymes exhibited similar cutting properties to PvuRts1I , creating a double - stranded cleavage on the 3 ' side of the modified cytosine .", "entity": [{"entity": "cytosine", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "In addition , for efficient cutting , the enzymes require two cytosines 21 - 22 - nt apart and on opposite strands where one cytosine must be modified .", "entity": [{"entity": "cytosines", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "cytosine", "entity_type": "Chemical", "pos": [125, 133]}], "task": "NER"}
{"text": "Interestingly , the specificity determination unveiled a new layer of complexity where the enzymes not only have specificity for 5 - beta - glucosylated hmC ( 5 beta ghmC ) but also 5 - alpha - glucosylated hmC ( 5 alpha ghmC ) .", "entity": [{"entity": "5 - beta - glucosylated hmC", "entity_type": "Chemical", "pos": [129, 156]}, {"entity": "5 beta ghmC", "entity_type": "Chemical", "pos": [159, 170]}, {"entity": "5 - alpha - glucosylated hmC", "entity_type": "Chemical", "pos": [182, 210]}, {"entity": "5 alpha ghmC", "entity_type": "Chemical", "pos": [213, 225]}], "task": "NER"}
{"text": "In some cases , the enzymes are inhibited by 5 beta ghmC , whereas in others they are inhibited by 5 alpha ghmC .", "entity": [{"entity": "5 beta ghmC", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "5 alpha ghmC", "entity_type": "Chemical", "pos": [99, 111]}], "task": "NER"}
{"text": "These observations indicate that the position of the sugar ring relative to the base is a determining factor in the substrate specificity of the PvuRts1I homologues .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [53, 58]}], "task": "NER"}
{"text": "Lastly , we envision that the unique properties of select PvuRts1I homologues will permit their use as an additive or alternative tool to map the hydroxymethylome .", "entity": [], "task": "NER"}
{"text": "Chirality sensing using stereodynamic probes with distinct electronic circular dichroism output .", "entity": [], "task": "NER"}
{"text": "Circular dichroism ( CD ) spectroscopy is one of the most useful techniques for the stereochemical analysis of chiral biopolymers and fine chemicals .", "entity": [], "task": "NER"}
{"text": "It has become invaluable for the assignment of the absolute configuration , the study of conformational isomers , and the determination of racemization kinetics of CD active chiral compounds .", "entity": [], "task": "NER"}
{"text": "Molecular interactions between a nonracemic chiral substrate and a chromophoric , CD - silent probe that is achiral or exists as a racemic mixture of rapidly interconverting enantiomeric conformations or configurations can induce a strong , characteristic chiroptical readout .", "entity": [], "task": "NER"}
{"text": "A covalent or noncovalent binding event that coincides with a well - defined asymmetric induction process can effectively imprint the chiral information of the substrate on the stereodynamic sensor and thus generate intense Cotton effects in the UV region of the latter .", "entity": [], "task": "NER"}
{"text": "The probe can thus function as a stereochemical reporter unit and analysis of the CD spectrum often provides accurate information about the absolute configuration and enantiomeric composition of the substrate used .", "entity": [], "task": "NER"}
{"text": "In this review , recent developments in circular dichroism analysis of chiral compounds with stereodynamic probes are described and particular emphasis is given to sensor design , chiral induction processes and applications scope .", "entity": [], "task": "NER"}
{"text": "The induction of mitochondria - mediated apoptosis in cancer cells by ruthenium ( ii ) asymmetric complexes .", "entity": [{"entity": "ruthenium ( ii )", "entity_type": "Chemical", "pos": [70, 86]}], "task": "NER"}
{"text": "Four ruthenium ( ii ) asymmetric complexes , [ Ru ( bpy ) 2 ( PAIDH ) ] ( 2 + ) ( bpy = 2 , 2 ' - bipyridine , PAIDH = 2 - pyridyl - 1H - anthra [ 1 , 2 - d ] imidazole - 6 , 11 - dione , ) , [ Ru ( phen ) 2 ( PAIDH ) ] ( 2 + ) ( phen = 1 , 10 - phenanthroline , ) , [ Ru ( dmp ) 2 ( PAIDH ) ] ( 2 + ) ( dmp = 4 , 7 - dimethyl - 1 , 10 - phenanthroline , ) and [ Ru ( dip ) 2 ( PAIDH ) ] ( 2 + ) ( dip = 4 , 7 - diphenyl - 1 , 10 - phenanthroline , ) , have been synthesized and characterized .", "entity": [{"entity": "ruthenium ( ii )", "entity_type": "Chemical", "pos": [5, 21]}, {"entity": "[ Ru ( bpy ) 2 ( PAIDH ) ] ( 2 + )", "entity_type": "Chemical", "pos": [45, 79]}, {"entity": "bpy", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "2 , 2 ' - bipyridine", "entity_type": "Chemical", "pos": [88, 108]}, {"entity": "PAIDH", "entity_type": "Chemical", "pos": [111, 116]}, {"entity": "2 - pyridyl - 1H - anthra [ 1 , 2 - d ] imidazole - 6 , 11 - dione", "entity_type": "Chemical", "pos": [119, 185]}, {"entity": "[ Ru ( phen ) 2 ( PAIDH ) ] ( 2 + )", "entity_type": "Chemical", "pos": [192, 227]}, {"entity": "phen", "entity_type": "Chemical", "pos": [230, 234]}, {"entity": "1 , 10 - phenanthroline", "entity_type": "Chemical", "pos": [237, 260]}, {"entity": "[ Ru ( dmp ) 2 ( PAIDH ) ] ( 2 + )", "entity_type": "Chemical", "pos": [267, 301]}, {"entity": "dmp", "entity_type": "Chemical", "pos": [304, 307]}, {"entity": "4 , 7 - dimethyl - 1 , 10 - phenanthroline", "entity_type": "Chemical", "pos": [310, 352]}, {"entity": "[ Ru ( dip ) 2 ( PAIDH ) ] ( 2 + )", "entity_type": "Chemical", "pos": [361, 395]}, {"entity": "dip", "entity_type": "Chemical", "pos": [398, 401]}, {"entity": "4 , 7 - diphenyl - 1 , 10 - phenanthroline", "entity_type": "Chemical", "pos": [404, 446]}], "task": "NER"}
{"text": "These complexes displayed potent anti - proliferation activity against various cancer cell lines and had high selectivity between tumor cells and normal cells .", "entity": [], "task": "NER"}
{"text": "HeLa cells exhibited the highest sensitivity to complex , accounting for the greatest cellular uptake .", "entity": [], "task": "NER"}
{"text": "Complex was shown to accumulate preferentially in the mitochondria of HeLa cells and induced apoptosis via the mitochondrial pathway , which involved ROS generation , mitochondrial membrane potential depolarisation , and Bcl - 2 and caspase family members activation .", "entity": [], "task": "NER"}
{"text": "These results demonstrated that complex induced cancer cell apoptosis by acting on mitochondrial pathways .", "entity": [], "task": "NER"}
{"text": "Mechanisms of RAS / beta - catenin interactions .", "entity": [], "task": "NER"}
{"text": "Signaling through the WNT / beta - catenin and the RAS ( rat sarcoma ) / MAPK ( mitogen - activated protein kinase ) pathways plays a key role in the regulation of various physiological cellular processes including proliferation , differentiation , and cell death .", "entity": [], "task": "NER"}
{"text": "Aberrant mutational activation of these signaling pathways is closely linked to the development of cancer in many organs , in humans as well as in laboratory animals .", "entity": [], "task": "NER"}
{"text": "Over the past years , more and more evidence for a close linkage of the two oncogenic signaling cascades has accumulated .", "entity": [], "task": "NER"}
{"text": "Using different experimental approaches , model systems , and experimental conditions , a variety of molecular mechanisms have been identified by which signal transduction through WNT / beta - catenin and RAS interact , either in a synergistic or an antagonistic manner .", "entity": [], "task": "NER"}
{"text": "Mechanisms of interaction comprise an upstream crosstalk at the level of pathway - activating ligands and their receptors , interrelations of cytosolic kinases involved in either pathways , as well as interaction in the nucleus related to the joint regulation of target gene transcription .", "entity": [], "task": "NER"}
{"text": "Here , we present a comprehensive review of the current knowledge on the interaction of RAS / MAPK - and WNT / beta - catenin - driven signal transduction in mammalian cells .", "entity": [], "task": "NER"}
{"text": "Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease .", "entity": [], "task": "NER"}
{"text": "Pharmacological approaches directed toward Alzheimer disease are diversifying in parallel with a growing number of promising targets .", "entity": [], "task": "NER"}
{"text": "Investigations on the microtubule - associated protein tau yielded innovative targets backed by recent findings about the central role of tau in numerous neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "In this review , we summarize the recent evolution in the development of nonpeptidic small molecules tau aggregation inhibitors ( TAGIs ) and their advancement toward clinical trials .", "entity": [], "task": "NER"}
{"text": "The compounds are classified according to their chemical structures , providing correlative insights into their pharmacology .", "entity": [], "task": "NER"}
{"text": "Overall , shared structure - activity traits are emerging , as well as specific binding modes related to their ability to engage in hydrogen bonding .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [132, 140]}], "task": "NER"}
{"text": "Medicinal chemistry efforts on TAGIs together with encouraging in vivo data argue for successful translation to the clinic .", "entity": [], "task": "NER"}
{"text": "Optimization of Chloronitrobenzamides ( CNBs ) as Therapeutic Leads for Human African Trypanosomiasis ( HAT ) .", "entity": [{"entity": "Chloronitrobenzamides", "entity_type": "Chemical", "pos": [16, 37]}, {"entity": "CNBs", "entity_type": "Chemical", "pos": [40, 44]}], "task": "NER"}
{"text": "We previously reported the discovery of the activity of chloronitrobenzamides ( CNBs ) against bloodstream forms of Trypanosoma brucei .", "entity": [{"entity": "chloronitrobenzamides", "entity_type": "Chemical", "pos": [56, 77]}, {"entity": "CNBs", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "Herein we disclose extensive structure - activity relationship and structure - property relationship studies aimed at identification of tractable early leads for clinical development .", "entity": [], "task": "NER"}
{"text": "These studies revealed a promising lead compound , 17b , that exhibited nanomolar potency against T . brucei ( EC50 = 27 nM for T . b . brucei , 7 nM for T . b . rhodesiense , and 2 nM for T . b . gambiense ) with excellent selectivity for parasite cells relative to mammalian cell lines ( EC50 > 25 mu M ) .", "entity": [], "task": "NER"}
{"text": "In addition compound 17b displayed suitable physiochemical characteristics and microsomal stability ( t1 / 2 > 4 h for human and mouse ) to justify pursuing in vivo studies .", "entity": [], "task": "NER"}
{"text": "Adsorption of Primary Substituted Hydrocarbons onto Solid Gallium Substrates .", "entity": [{"entity": "Hydrocarbons", "entity_type": "Chemical", "pos": [34, 46]}, {"entity": "Gallium", "entity_type": "Chemical", "pos": [58, 65]}], "task": "NER"}
{"text": "Adsorption of a series of primary substituted hydrocarbons ( RX ; C18H37PO ( OH ) 2 ( ODPA ) , C17H35COOH , C18H37OH , C18H37NH2 , and C18H37SH ) onto solid gallium substrates with and without UV / ozone treatment was studied using contact angle goniometry , spectroscopic ellipsometry , and cyclic voltammetry ( CV ) .", "entity": [{"entity": "hydrocarbons", "entity_type": "Chemical", "pos": [46, 58]}, {"entity": "C18H37PO ( OH ) 2", "entity_type": "Chemical", "pos": [66, 83]}, {"entity": "ODPA", "entity_type": "Chemical", "pos": [86, 90]}, {"entity": "C17H35COOH", "entity_type": "Chemical", "pos": [95, 105]}, {"entity": "C18H37OH", "entity_type": "Chemical", "pos": [108, 116]}, {"entity": "C18H37NH2", "entity_type": "Chemical", "pos": [119, 128]}, {"entity": "C18H37SH", "entity_type": "Chemical", "pos": [135, 143]}, {"entity": "gallium", "entity_type": "Chemical", "pos": [157, 164]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [198, 203]}], "task": "NER"}
{"text": "UV / ozone treatment offered a hydrophilic surface ( water contact angle ( theta ( water ) ) less than 10 degrees ) , reflecting the formation of a surface oxide layer with the maximum thickness of ca .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [5, 10]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [156, 161]}], "task": "NER"}
{"text": "1 nm and possibly the removal of surface contaminants .", "entity": [], "task": "NER"}
{"text": "Upon immersion in a toluene solution of a RX , theta ( water ) increased due to adsorption of the RX onto gallium substrates .", "entity": [{"entity": "toluene", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "gallium", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "In particular , UV / ozone - treated gallium substrates ( UV - Ga ) immersed in an ODPA solution exhibited theta ( water ) close to 105 degrees .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [21, 26]}, {"entity": "gallium", "entity_type": "Chemical", "pos": [37, 44]}, {"entity": "Ga", "entity_type": "Chemical", "pos": [63, 65]}, {"entity": "ODPA", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "The ellipsometric thickness of the adsorbed ODPA layer was ca .", "entity": [{"entity": "ODPA", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "2 . 4 nm , and CV data measured in an acetonitrile solution showed significant inhibition of redox reaction on the substrate surface .", "entity": [{"entity": "acetonitrile", "entity_type": "Chemical", "pos": [38, 50]}], "task": "NER"}
{"text": "These results indicate the formation of a densely packed ODPA monolayer on UV - Ga .", "entity": [{"entity": "ODPA", "entity_type": "Chemical", "pos": [57, 61]}, {"entity": "Ga", "entity_type": "Chemical", "pos": [80, 82]}], "task": "NER"}
{"text": "The coverage of a C17H35COOH layer adsorbed onto UV - Ga was lower , as shown by smaller theta ( water ) ( ca . 99 degrees ) , smaller ellipsometric thickness ( ca . 1 . 3 nm ) , and smaller electrode reaction inhibition .", "entity": [{"entity": "C17H35COOH", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "Ga", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "Adsorption of the other RX onto UV - Ga was weaker , as indicated by smaller theta ( water ) ( 82 degrees - 92 degrees ) .", "entity": [{"entity": "Ga", "entity_type": "Chemical", "pos": [37, 39]}], "task": "NER"}
{"text": "ODPA did not strongly adsorb onto UV - untreated gallium substrates , suggesting that the ODPA adsorption mainly originates from hydrogen bond interaction of a phosphonate group with surface oxide .", "entity": [{"entity": "ODPA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "gallium", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "ODPA", "entity_type": "Chemical", "pos": [90, 94]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [129, 137]}, {"entity": "phosphonate", "entity_type": "Chemical", "pos": [160, 171]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [191, 196]}], "task": "NER"}
{"text": "These results will provide a means for controlling the surface properties of oxide - coated gallium that play an essential role in monolayer conductivity measurements and electroanalytical applications .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [77, 82]}, {"entity": "gallium", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "Diarylheptanoids and Flavonoids from Viscum album Inhibit LPS - Stimulated Production of Pro - inflammatory Cytokines in Bone Marrow - Derived Dendritic Cells .", "entity": [{"entity": "Diarylheptanoids", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "Flavonoids", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "Three new diarylheptanoids , ( 3S , 5R ) - 3 - hydroxy - 5 - methoxy - 1 , 7 - bis ( 4 - hydroxyphenyl ) - 6E - heptene ( 1 ) , ( 3S , 5S ) - 3 - hydroxy - 5 - methoxy - 1 , 7 - bis ( 4 - hydroxyphenyl ) - 6E - heptene ( 2 ) , and ( 3S ) - 3 - hydroxy - 1 , 7 - bis ( 4 - hydroxyphenyl ) - 6E - hepten - 5 - one ( 3 ) , four new flavonoid glycosides , 3 , 7 , 3 ' - tri - O - methylquercetin - 4 ' - O - beta - d - apiofuranosyl - ( 1 --> 2 ) - O - beta - d - glucopyranoside ( 4 ) , 7 , 3 ' - di - O - methylquercetin - 4 ' - O - beta - d - glucopyranosyl - 3 - O - [ 6 ''' - ( 3 - hydroxy - 3 - methylglutaroyl ) ] - alpha - d - glucopyranoside ( 5 ) , 7 , 3 ' - di - O - methylquercetin - 4 ' - O - beta - d - glucopyranosyl - 3 - O - [ ( 6 ' ' ' ' ' --> 5 ' ' ' ' ) - O - 1 ' ' ' ' ' - ( sinap - 4 - yl ) - beta - d - glucopyranosyl - 6 ''' - ( 3 - hydroxy - 3 - methylglutaroyl ) ] - alpha - d - glucopyranoside ( 6 ) , and ( 2S ) - 5 - hydroxy - 7 , 3 ' - dimethoxyflavanone - 4 ' - O - beta - d - apiofuranosyl - ( 1 --> 5 ) - O - beta - d - apiofuranosyl - ( 1 --> 2 ) - O - beta - d - glucopyranoside ( 9 ) , and 17 known compounds were isolated from the leaves and twigs of Viscum album .", "entity": [{"entity": "diarylheptanoids", "entity_type": "Chemical", "pos": [10, 26]}, {"entity": "( 3S , 5R ) - 3 - hydroxy - 5 - methoxy - 1 , 7 - bis ( 4 - hydroxyphenyl ) - 6E - heptene", "entity_type": "Chemical", "pos": [29, 119]}, {"entity": "( 3S , 5S ) - 3 - hydroxy - 5 - methoxy - 1 , 7 - bis ( 4 - hydroxyphenyl ) - 6E - heptene", "entity_type": "Chemical", "pos": [128, 218]}, {"entity": "( 3S ) - 3 - hydroxy - 1 , 7 - bis ( 4 - hydroxyphenyl ) - 6E - hepten - 5 - one", "entity_type": "Chemical", "pos": [231, 311]}, {"entity": "flavonoid glycosides", "entity_type": "Chemical", "pos": [329, 349]}, {"entity": "3 , 7 , 3 ' - tri - O - methylquercetin - 4 ' - O - beta - d - apiofuranosyl - ( 1 --> 2 ) - O - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [352, 475]}, {"entity": "7 , 3 ' - di - O - methylquercetin - 4 ' - O - beta - d - glucopyranosyl - 3 - O - [ 6 ''' - ( 3 - hydroxy - 3 - methylglutaroyl ) ] - alpha - d - glucopyranoside", "entity_type": "Chemical", "pos": [484, 646]}, {"entity": "7 , 3 ' - di - O - methylquercetin - 4 ' - O - beta - d - glucopyranosyl - 3 - O - [ ( 6 ' ' ' ' ' --> 5 ' ' ' ' ) - O - 1 ' ' ' ' ' - ( sinap - 4 - yl ) - beta - d - glucopyranosyl - 6 ''' - ( 3 - hydroxy - 3 - methylglutaroyl ) ] - alpha - d - glucopyranoside", "entity_type": "Chemical", "pos": [655, 916]}, {"entity": "( 2S ) - 5 - hydroxy - 7 , 3 ' - dimethoxyflavanone - 4 ' - O - beta - d - apiofuranosyl - ( 1 --> 5 ) - O - beta - d - apiofuranosyl - ( 1 --> 2 ) - O - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [929, 1109]}], "task": "NER"}
{"text": "Compounds 1 , 4 , and 19 significantly inhibited LPS - stimulated production of TNF - alpha , IL - 6 , and IL - 12p40 with IC50 values ranging from 0 . 09 +/- 0 . 01 to 8 . 96 +/- 0 . 45 mu M .", "entity": [], "task": "NER"}
{"text": "( + ) - Medioresinol ( 13 ) showed inhibitory effects on LPS - stimulated production of IL - 12p40 with an IC50 value of 2 . 00 +/- 0 . 15 mu M .", "entity": [{"entity": "( + ) - Medioresinol", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "Ultrathin 2D Coordination Polymer Nanosheets by Surfactant - Mediated Synthesis .", "entity": [], "task": "NER"}
{"text": "Low - dimensional nanostructures offer a host of intriguing properties which are distinct from those of the bulk material , owing to size - confinement effects and amplified surface areas .", "entity": [], "task": "NER"}
{"text": "Here , we report on the scalable , bottom - up synthesis of ultrathin coordination polymer nanosheets via surfactant - mediated synthesis and subsequent exfoliation .", "entity": [], "task": "NER"}
{"text": "Layers of a two - dimensional ( 2D ) zinc coordination polymer are self - assembled in the interlamellar space of a reverse microemulsion mesophase into stacks of nanosheets interleaved with cethyltrimethylammonium bromide ( CTAB ) at regular intervals , thus giving rise to a lamellar hybrid mesostructure with a lattice period of ~ 8 nm and an underlying highly crystalline substructure .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [37, 41]}, {"entity": "cethyltrimethylammonium bromide", "entity_type": "Chemical", "pos": [191, 222]}, {"entity": "CTAB", "entity_type": "Chemical", "pos": [225, 229]}], "task": "NER"}
{"text": "The basic structural motif is composed of 2D acetato - benzimidazolato - zinc layers of tetrahedrally coordinated zinc joined together by anionic acetate and benzimidazolate ligands .", "entity": [{"entity": "acetato - benzimidazolato - zinc", "entity_type": "Chemical", "pos": [45, 77]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [114, 118]}, {"entity": "acetate", "entity_type": "Chemical", "pos": [146, 153]}, {"entity": "benzimidazolate", "entity_type": "Chemical", "pos": [158, 173]}], "task": "NER"}
{"text": "The hierarchical structure was studied by PXRD , TEM , EDX , EELS , AFM , and solid - state NMR spectroscopy , revealing a high level of order on both the atomic and mesoscale , suggesting fairly strong interactions along the organic - inorganic hybrid interface .", "entity": [], "task": "NER"}
{"text": "Exfoliation of the hybrid material in organic solvents such as THF and chloroform yields sheet - and belt - like nanostructures with lateral sizes between 10 ' s and 100 ' s of nanometers and a height of about 10 nm measured by AFM , which precisely maps the basal spacing of the lamellar mesostructure ; further exfoliation results in nanobelts with minimum sizes around 4 nm .", "entity": [{"entity": "THF", "entity_type": "Chemical", "pos": [63, 66]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [71, 81]}], "task": "NER"}
{"text": "Finally , the sheetlike nanostructures behave as morphological chameleons , transforming into highly regular multiwalled coordination polymer nanotubes upon treatment with organic solvents .", "entity": [], "task": "NER"}
{"text": "Computational study of the coordination of methane to first row transition metal dication complexes .", "entity": [{"entity": "methane", "entity_type": "Chemical", "pos": [43, 50]}, {"entity": "transition metal dication complexes", "entity_type": "Chemical", "pos": [64, 99]}], "task": "NER"}
{"text": "The coordination of methane , the first step in methane activation , to coordinately unsaturated first row transition metal dication complexes has been studied computationally to determine the most stable metal - methane interaction .", "entity": [{"entity": "methane", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "methane", "entity_type": "Chemical", "pos": [48, 55]}, {"entity": "transition metal dication complexes", "entity_type": "Chemical", "pos": [107, 142]}, {"entity": "methane", "entity_type": "Chemical", "pos": [213, 220]}], "task": "NER"}
{"text": "The geometries and the vibrational frequencies of the encounter complexes [ M ( pyridine ) 2 ( CH4 ) ] ( 2 + ) have been determined using density functional theory with the omega B97XD hybrid functional and triple - zeta basis sets .", "entity": [{"entity": "[ M ( pyridine ) 2 ( CH4 ) ] ( 2 + )", "entity_type": "Chemical", "pos": [74, 110]}], "task": "NER"}
{"text": "The structure is dependent on the metal center ; for the early transition metals eta ( 3 ) coordination is favored , whereas eta ( 2 ) is more favorable for the later transition metals .", "entity": [{"entity": "transition metals", "entity_type": "Chemical", "pos": [63, 80]}, {"entity": "transition metals", "entity_type": "Chemical", "pos": [167, 184]}], "task": "NER"}
{"text": "The periodic trend in methane binding energies in the [ M ( pyridine ) 2 ( CH4 ) ] ( 2 + ) complexes follows the trend in electron affinity until the Mn complex but then exhibits decreasing energies from Fe to Zn .", "entity": [{"entity": "methane", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "[ M ( pyridine ) 2 ( CH4 ) ] ( 2 + )", "entity_type": "Chemical", "pos": [54, 90]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [150, 152]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [204, 206]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [210, 212]}], "task": "NER"}
{"text": "This is attributed to increasing Pauli repulsion and ligand - ligand repulsion .", "entity": [], "task": "NER"}
{"text": "For the most stable complex , [ Cr ( pyridine ) 2 ( CH4 ) ] ( 2 + ) , the structures , energies , and spin states of the key intermediates and products in the oxidative addition / reductive elimination pathway have been investigated .", "entity": [{"entity": "[ Cr ( pyridine ) 2 ( CH4 ) ] ( 2 + )", "entity_type": "Chemical", "pos": [30, 67]}], "task": "NER"}
{"text": "It is found that the reaction is thermodynamically favorable and indicates that two - state reactivity may play an important role in lowering the energy of the hydridomethyl intermediate .", "entity": [{"entity": "hydridomethyl", "entity_type": "Chemical", "pos": [160, 173]}], "task": "NER"}
{"text": "Synergistic interactions of epigallocatechin gallate and oxytetracycline against various drug resistant Staphylococcus aureus strains in vitro .", "entity": [{"entity": "epigallocatechin gallate", "entity_type": "Chemical", "pos": [28, 52]}, {"entity": "oxytetracycline", "entity_type": "Chemical", "pos": [57, 72]}], "task": "NER"}
{"text": "Epigallocatechin gallate ( EGCG ) , the major catechin contained in tea leaves , is known to possess the synergistic anti - staphylococcal activity in combination with various beta - lactam antibiotics and tetracycline .", "entity": [{"entity": "Epigallocatechin gallate", "entity_type": "Chemical", "pos": [0, 24]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "catechin", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "beta - lactam", "entity_type": "Chemical", "pos": [176, 189]}, {"entity": "tetracycline", "entity_type": "Chemical", "pos": [206, 218]}], "task": "NER"}
{"text": "In the present study , we explored the in vitro combinatory effect of EGCG in combination with oxytetracycline against eight standard strains and clinical isolates of Staphylococcus aureus , including erythromycin , methicillin and tetracycline resistant strains .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [70, 74]}, {"entity": "oxytetracycline", "entity_type": "Chemical", "pos": [95, 110]}, {"entity": "erythromycin", "entity_type": "Chemical", "pos": [201, 213]}, {"entity": "methicillin", "entity_type": "Chemical", "pos": [216, 227]}, {"entity": "tetracycline", "entity_type": "Chemical", "pos": [232, 244]}], "task": "NER"}
{"text": "The minimum inhibitory concentrations were determined by the broth microdilution assay and the data were evaluated according to the sum of fractional inhibitory concentrations ( sum FIC ) .", "entity": [], "task": "NER"}
{"text": "Our results showed synergistic and additive interactions against all S . aureus strains tested ( sum FIC 0 . 288 - 0 . 631 ) , two of which were multidrug resistant .", "entity": [], "task": "NER"}
{"text": "According to our best knowledge , it is the first report on the EGCG synergy with oxytetracycline .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [64, 68]}, {"entity": "oxytetracycline", "entity_type": "Chemical", "pos": [82, 97]}], "task": "NER"}
{"text": "Considering its significant synergistic antimicrobial effect and low toxicity , we suggest EGCG as a promising compound for the development of new anti - staphylococcal formulations .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "Orally bioavailable and brain - penetrant pyridazine and pyridine - derived gamma - secretase modulators reduced amyloidogenic A beta peptides in vivo .", "entity": [{"entity": "pyridazine", "entity_type": "Chemical", "pos": [42, 52]}, {"entity": "pyridine", "entity_type": "Chemical", "pos": [57, 65]}], "task": "NER"}
{"text": "Accumulation of amyloid beta ( A beta ) in brain is a pathological hallmark of Alzheimer ' s disease ( AD ) .", "entity": [], "task": "NER"}
{"text": "A beta is generated after sequential cleavage of its parental molecule , amyloid precursor protein ( APP ) , by beta - and gamma - secretases .", "entity": [], "task": "NER"}
{"text": "Inhibition of gamma - secretase activity is an effective approach for the reduction of A beta levels .", "entity": [], "task": "NER"}
{"text": "Since gamma - secretase targets many different substrates , selective inhibition of its cleavage of APP is believed to be critical in order to avoid undesirable side effects .", "entity": [], "task": "NER"}
{"text": "gamma - Secretase modulator ( GSM ) shifts the cleavage site on APP and production of amyloidogenic to non - amyloidogenic A beta fragments .", "entity": [], "task": "NER"}
{"text": "Since GSMs only modulate and do not block cleavage of gamma - secretase substrates , they are believed less likely to produce untoward adverse reactions .", "entity": [], "task": "NER"}
{"text": "Here , we report in vivo A beta - lowering profiles of a pyridazine and a pyridine - derived GSM : GSM - C ( Wan et al . , 2011a ) and GSM - D ( Wan et al . , 2011b ) .", "entity": [{"entity": "pyridazine", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "pyridine", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "Both compounds reduced A beta 40 and A beta 42 productions , increased shorter A beta fragments , and had little effect on Notch signaling ( ~ 100 - fold selective ) .", "entity": [], "task": "NER"}
{"text": "They had excellent oral bioavailability ( 97 . 8 % for GSM - C , ~ 100 % for GSM - D ) and good brain permeability ( free brain to free blood AUC ratio of 0 . 41 and 1 . 10 for GSM - C and GSM - D , respectively ) .", "entity": [], "task": "NER"}
{"text": "Oral administration of these compounds in both acute and sub - chronic conditions reduced A beta levels in plasma and brain in rats in a dose - and time - dependent manner .", "entity": [], "task": "NER"}
{"text": "Therefore , GSM - C and GSM - D represent two GSMs that are orally bioavailable and brain - permeable .", "entity": [], "task": "NER"}
{"text": "They could serve as excellent tools in the investigation of the role of A beta peptides in AD pathogenesis .", "entity": [], "task": "NER"}
{"text": "Research on cholinesterases in the Soviet Union and Russia : A historical perspective .", "entity": [], "task": "NER"}
{"text": "Research on cholinesterases and effects of their inhibition in the USSR and Russia since 1930 - 1940s till present is exposed in historical aspects .", "entity": [], "task": "NER"}
{"text": "The first physiological and toxicological effects of cholinesterase inhibition were reported by Alexander Ginetsinsky during World War II , when academic institutions were evacuated from Leningrad to Kazan .", "entity": [], "task": "NER"}
{"text": "The main scientific schools that initiated research on chemistry , enzymology and physiology of cholinesterases and their inhibitors were leaded by Alexandr and Boris Arbuzovs , Victor Rozengart , Viktor Yakovlev , Michael Michelson , Martin Kabachnik , Mikhail Voronkov , Ivan Knunyants , Alexandr Bretskin and others .", "entity": [], "task": "NER"}
{"text": "They investigated the main physiological effects of cholinesterase inhibitors , and analyzed the catalytic mechanisms of cholinesterases and related enzymes .", "entity": [], "task": "NER"}
{"text": "Their contributions are landmarks in the history of cholinesterase research .", "entity": [], "task": "NER"}
{"text": "At the present time revival of research on cholinesterases in different universities and institutes is vivid , in particular at the Moscow State University , research institutes of Russian Academy of Sciences and Kazan Scientific Center .", "entity": [], "task": "NER"}
{"text": "Protective effect of bark and empty pod extracts from Acacia auriculiformis against paracetamol intoxicated liver injury and alloxan induced type II diabetes .", "entity": [{"entity": "paracetamol", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "alloxan", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "The present study is designed to decipher a clinical evidence and biochemical support for hepatoprotective and antidiabetic efficacy of Acacia auriculiformis by its bark and empty pods .", "entity": [], "task": "NER"}
{"text": "Animal models with paracetamol intoxicated liver injury and alloxan induced diabetes were used in a 7 and 14days trial respectively .", "entity": [{"entity": "paracetamol", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "alloxan", "entity_type": "Chemical", "pos": [60, 67]}], "task": "NER"}
{"text": "The interventions were tested at 200 and 400mg / kg b . w . for bark extract ; 100 and 200mg / kg b . w . for empty pod extract .", "entity": [], "task": "NER"}
{"text": "Both interventions restored the liver function markers ( alanine transaminase : ALT , aspartate transaminase : AST , alkaline phosphatase : ALP , total bilirubin and total protein ) and hepatic antioxidants ( superoxide dismutase : SOD , catalase : CAT , reduced glutathione : GSH and glutathione peroxidase : GPx ) to the normal levels than elevated levels noticed on paracetamol control at P < 0 . 001 .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [86, 95]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [152, 161]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [209, 219]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [263, 274]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [277, 280]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [285, 296]}, {"entity": "paracetamol", "entity_type": "Chemical", "pos": [369, 380]}], "task": "NER"}
{"text": "Reversal of hepatoarchitecture has also been registered and the hepatoprotection is comparable to the reference drug silymarin .", "entity": [{"entity": "silymarin", "entity_type": "Chemical", "pos": [117, 126]}], "task": "NER"}
{"text": "Similarly , substantial elevations of blood glucose , distorted lipid profile ( total cholesterol : TC , triglycerides : TGs , high density lipoprotein cholesterol : HDL - C and low density lipoprotein cholesterol : LDL - C ) and kidney function signs ( creatinine and urea ) have been refurbished to the desirable levels on par with the standard antidiabetic glibenclamide .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [44, 51]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [86, 97]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [105, 118]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [152, 163]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [202, 213]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [254, 264]}, {"entity": "urea", "entity_type": "Chemical", "pos": [269, 273]}, {"entity": "glibenclamide", "entity_type": "Chemical", "pos": [360, 373]}], "task": "NER"}
{"text": "The results signify the importance of bark and empty pod extracts of A . auriculiformis as good therapeutic candidates for liver injury and diabetes .", "entity": [], "task": "NER"}
{"text": "The influence of study design and sex - differences on results from developmental neurotoxicity studies of bisphenol A , implications for toxicity testing .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [107, 118]}], "task": "NER"}
{"text": "Developmental neurotoxicity ( DNT ) of bisphenol A ( BPA ) has been investigated in a large number of studies .", "entity": [{"entity": "bisphenol A", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "BPA", "entity_type": "Chemical", "pos": [53, 56]}], "task": "NER"}
{"text": "However , there are discrepancies in the results reported between the studies .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex - differences in the sensitivity of certain endpoints or tests used in DNT - studies .", "entity": [], "task": "NER"}
{"text": "Forty - four DNT studies of BPA were identified from the open literature .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "Details about study design and results from each study , as well as the criteria for DNT testing according to the standardized OECD test guideline ( TG ) 426 , were collected in a database .", "entity": [], "task": "NER"}
{"text": "This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426 .", "entity": [], "task": "NER"}
{"text": "Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results .", "entity": [], "task": "NER"}
{"text": "The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426 , such as anxiety - related , social and sexual behaviors , especially at very low doses and in female offspring .", "entity": [], "task": "NER"}
{"text": "On the other hand relatively few studies observed any effects on motor activity , which is commonly used in screening for neurotoxic effects in regulatory testing .", "entity": [], "task": "NER"}
{"text": "However , varied and to some extent seemingly contradictory results have been reported in these studies , especially for endpoints related to motor activity and anxiety and exploration .", "entity": [], "task": "NER"}
{"text": "Many studies were also poorly reported , limiting these analyses .", "entity": [], "task": "NER"}
{"text": "No strong conclusions could be drawn from the multivariate analyses .", "entity": [], "task": "NER"}
{"text": "A few factors of study design , such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results .", "entity": [], "task": "NER"}
{"text": "In conclusion , this analysis suggests that DNT - studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA , and possibly other potential endocrine disruptors , especially in female offspring .", "entity": [{"entity": "BPA", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "High - throughput quantification of the mechanical competence of murine femora - A highly automated approach for large - scale genetic studies .", "entity": [], "task": "NER"}
{"text": "Animal models are widely used to gain insight into the role of genetics on bone structure and function .", "entity": [], "task": "NER"}
{"text": "One of the main strategies to map the genes regulating specific traits is called quantitative trait loci ( QTL ) analysis , which generally requires a very large number of animals ( often more than 1000 ) to reach statistical significance .", "entity": [], "task": "NER"}
{"text": "QTL analysis for mechanical traits has been mainly based on experimental mechanical testing , which , in view of the large number of animals , is time consuming .", "entity": [], "task": "NER"}
{"text": "Hence , the goal of the present work was to introduce an automated method for large - scale high - throughput quantification of the mechanical properties of murine femora .", "entity": [], "task": "NER"}
{"text": "Specifically , our aims were , first , to develop and validate an automated method to quantify murine femoral bone stiffness .", "entity": [], "task": "NER"}
{"text": "Second , to test its high - throughput capabilities on murine femora from a large genetic study , more specifically , femora from two growth hormone ( GH ) deficient inbred strains of mice ( B6 - lit / lit and C3 . B6 - lit / lit ) and their first ( F1 ) and second ( F2 ) filial offsprings .", "entity": [], "task": "NER"}
{"text": "Automated routines were developed to convert micro - computed tomography ( micro - CT ) images of femora into micro - finite element ( micro - FE ) models .", "entity": [], "task": "NER"}
{"text": "The method was experimentally validated on femora from C57BL / 6J and C3H / HeJ mice : for both inbred strains the micro - FE models closely matched the experimentally measured bone stiffness when using a single tissue modulus of 13 . 06GPa .", "entity": [], "task": "NER"}
{"text": "The mechanical analysis of the entire dataset ( n = 1990 ) took approximately 44 CPU hours on a supercomputer .", "entity": [], "task": "NER"}
{"text": "In conclusion , our approach , in combination with QTL analysis could help to locate genes directly involved in controlling bone mechanical competence .", "entity": [], "task": "NER"}
{"text": "Pediatric insecticide chalk exposures reported to Texas poison centers .", "entity": [], "task": "NER"}
{"text": "The pesticide Miraculous Insecticide Chalk ( TM ) is illegal in the United States but can be obtained through a variety of sources .", "entity": [], "task": "NER"}
{"text": "Because it is a stick similar in appearance to common blackboard chalk , children might play with it and put it in their mouths .", "entity": [], "task": "NER"}
{"text": "All Miraculous Insecticide Chalk exposures involving children 5 years or younger reported to Texas poison centers during 2000 - 2010 were identified .", "entity": [], "task": "NER"}
{"text": "The distribution by selected demographic and clinical factors was calculated .", "entity": [], "task": "NER"}
{"text": "Of the total 188 exposures , the mean age was 1 . 5 years ( range 6 months - 5 years ) and 60 . 6 % were male .", "entity": [], "task": "NER"}
{"text": "Ingestions were reported in 97 . 3 % of the exposures , and these were reported to involve at most one stick of the chalk .", "entity": [], "task": "NER"}
{"text": "The lowest exposure rates per 100 , 000 population of 5 years or younger were reported in the Public Health Regions in northern and eastern Texas ( 0 . 00 - 2 . 30 ) and the highest rates in the Public Health Regions in southern and western Texas ( 19 . 08 - 39 . 50 ) .", "entity": [], "task": "NER"}
{"text": "Of the 187 exposures not involving other substances , 96 . 8 % were known or expected to result in at most minor effects , and 71 . 1 % were managed on site ( at residence ) .", "entity": [], "task": "NER"}
{"text": "Synthesis and application of FePt / CNTs nanocomposite as a sensor and novel amide ligand as a mediator for simultaneous determination of glutathione , nicotinamide adenine dinucleotide and tryptophan .", "entity": [{"entity": "FePt", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "amide", "entity_type": "Chemical", "pos": [77, 82]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [138, 149]}, {"entity": "nicotinamide adenine dinucleotide", "entity_type": "Chemical", "pos": [152, 185]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [190, 200]}], "task": "NER"}
{"text": "In this study , we report the synthesis and application of a FePt / CNTs nanocomposite as a highly sensitive sensor and novel amide ligand ( 9 , 10 - dihydro - 9 , 10 - ethanoanthracene - 11 , 12 - dicarboximido ) - 4 - ethylbenzene - 1 , 2 - diol as a mediator for the determination of glutathione ( GSH ) , nicotinamide adenine dinucleotide ( NADH ) and tryptophan ( Trp ) .", "entity": [{"entity": "FePt", "entity_type": "Chemical", "pos": [61, 65]}, {"entity": "amide", "entity_type": "Chemical", "pos": [126, 131]}, {"entity": "( 9 , 10 - dihydro - 9 , 10 - ethanoanthracene - 11 , 12 - dicarboximido ) - 4 - ethylbenzene - 1 , 2 - diol", "entity_type": "Chemical", "pos": [139, 247]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [287, 298]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [301, 304]}, {"entity": "nicotinamide adenine dinucleotide", "entity_type": "Chemical", "pos": [309, 342]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [345, 349]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [356, 366]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [369, 372]}], "task": "NER"}
{"text": "The synthesized materials were characterized with different methods such as NMR , IR spectroscopy , TEM , XRD , FESEM , cyclic voltammetry , electrochemical impedance spectroscopy and square wave voltammetry ( SWV ) .", "entity": [], "task": "NER"}
{"text": "The modified electrode exhibited a potent and persistent electron mediating behavior followed by well - separated oxidation peaks of GSH , NADH and Trp .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [133, 136]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [139, 143]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "The peak currents were linearly dependent on GSH , NADH and Trp concentrations in the range of 0 . 08 - 220 , 1 . 0 - 400 and 5 . 0 - 500 mu mol L ( - 1 ) , with detection limits of 0 . 05 , 0 . 8 and 1 . 0 mu mol L ( - 1 ) , respectively .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [51, 55]}, {"entity": "Trp", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "The modified electrode was used for the determination of these compounds in real samples .", "entity": [], "task": "NER"}
{"text": "Channel Size Conversion of Phi29 DNA - Packaging Nanomotor for Discrimination of Single - and Double - Stranded Nucleic Acids .", "entity": [], "task": "NER"}
{"text": "Nanopores have been utilized to detect the conformation and dynamics of polymers , including DNA and RNA .", "entity": [], "task": "NER"}
{"text": "Biological pores are extremely reproducible at the atomic level with uniform channel sizes .", "entity": [], "task": "NER"}
{"text": "The channel of the bacterial virus phi29 DNA - packaging motor is a natural conduit for the transportation of double - stranded DNA ( dsDNA ) and has the largest diameter among the well - studied biological channels .", "entity": [], "task": "NER"}
{"text": "The larger channel facilitates translocation of dsDNA and offers more space for further channel modification and conjugation .", "entity": [], "task": "NER"}
{"text": "Interestingly , the relatively large wild - type channel , which translocates dsDNA , cannot detect single - stranded nucleic acids ( ssDNA or ssRNA ) under the current experimental conditions .", "entity": [], "task": "NER"}
{"text": "Herein , we reengineered this motor channel by removing the internal loop segment of the channel .", "entity": [], "task": "NER"}
{"text": "The modification resulted in two classes of channels .", "entity": [], "task": "NER"}
{"text": "One class was the same size as the wild - type channel , while the other class had a cross - sectional area about 60 % of the wild - type .", "entity": [], "task": "NER"}
{"text": "This smaller channel was able to detect the real - time translocation of single - stranded nucleic acids at single - molecule level .", "entity": [], "task": "NER"}
{"text": "While the wild - type connector exhibited a one - way traffic property with respect to dsDNA translocation , the loop - deleted connector was able to translocate ssDNA and ssRNA with equal competencies from both termini .", "entity": [], "task": "NER"}
{"text": "This finding of size alterations in reengineered motor channels expands the potential application of the phi29 DNA - packaging motor in nanomedicine , nanobiotechnology , and high - throughput single - pore DNA sequencing .", "entity": [], "task": "NER"}
{"text": "Columnar Cell Variant of Papillary Thyroid Carcinoma : A Study of Ten Cases with Emphasis On CDX - 2 Expression .", "entity": [], "task": "NER"}
{"text": "Background : Columnar cell variant is a recognized rare variant of papillary thyroid carcinoma associated with an uncertain clinical course .", "entity": [], "task": "NER"}
{"text": "This variant has two sub variants , and one is regarded as a more aggressive form in comparison to the more common classical and follicular variants .", "entity": [], "task": "NER"}
{"text": "These tumors have morphological resemblance with endometrial or colonic adenocarcinoma .", "entity": [], "task": "NER"}
{"text": "CDX2 , a transcription factor of the caudal homeobox family , plays a key role in intestinal development and differentiation and it is widely used as a marker to detect adenocarcinoma of intestinal and colonic origin .", "entity": [], "task": "NER"}
{"text": "CDX2 has been rarely reported in papillary thyroid carcinoma .", "entity": [], "task": "NER"}
{"text": "Methods : We studied ten cases of columnar cell variant of papillary thyroid carcinoma .", "entity": [], "task": "NER"}
{"text": "The histological , architectural , and cytological features fulfilled the diagnostic criteria of the columnar cell variant of papillary thyroid carcinoma as defined by the current WHO classification .", "entity": [], "task": "NER"}
{"text": "Ten patients ( 6M : 4F ) ranging from 32 to 90 years of age ( mean 58 . 3 years ) presented with tumors classified as indolent ( 4 cases ) or aggressive ( 6 cases ) ; 3 with BRAFV600E mutation .", "entity": [], "task": "NER"}
{"text": "All cases were - Catenin negative .", "entity": [], "task": "NER"}
{"text": "The Ki - 67 proliferative index was up to 50 % .", "entity": [], "task": "NER"}
{"text": "All cases were TTF - 1 positive .", "entity": [], "task": "NER"}
{"text": "Using paraffin embedded blocks , immunohistochemistry for CDX2 was performed to evaluate the reactivity of this antibody to this variant of papillary thyroid carcinoma .", "entity": [], "task": "NER"}
{"text": "Results : Nuclear positivity for CDX2 was detected in one out of the ten cases studied ( 10 % ) ; the other nine cases did not express CDX2 .", "entity": [], "task": "NER"}
{"text": "Conclusion : Only one of our cases showed nuclear positivity for CDX2 , therefore our study failed to confirm this as a marker for columnar cell variant of papillary thyroid carcinoma .", "entity": [], "task": "NER"}
{"text": "The absence of CDX2 in the majority of the cases does not support the theory of CDX2 playing a role in the intestinal phenotype of these tumors .", "entity": [], "task": "NER"}
{"text": "KEYWORDS : Papillary Thyroid Carcinoma , CDX - 2 , Columnar Cell , Immunohistochemistry .", "entity": [], "task": "NER"}
{"text": "Iodine Status in Pregnant Women in the United States : National Children ' s Study and National Health and Nutrition Examination Survey .", "entity": [{"entity": "Iodine", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Background : This report presents iodine data from NHANES and from a sample of pregnant women in the National Children ' s Study ( NCS ) Vanguard Study .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [34, 40]}], "task": "NER"}
{"text": "Methods : UI was measured in a one third subsample of NHANES 2005 - 2006 , and 2009 - 2010 participants and in all 2007 - 2008 participants age six years and older .", "entity": [], "task": "NER"}
{"text": "These measurements are representative of the general U . S . population .", "entity": [], "task": "NER"}
{"text": "UI was also measured in a convenience sample of 501 pregnant women enrolled in the NCS initial Vanguard Study from seven study sites across the U . S .", "entity": [], "task": "NER"}
{"text": "Results : NHANES median UI concentration in 2009 - 2010 ( 144 micro g / L ) was significantly lower than in 2007 - 2008 ( 164 micro g / L ) .", "entity": [], "task": "NER"}
{"text": "Non - Hispanic blacks had the lowest UI concentrations ( 131 micro g / L ) compared to non - Hispanic whites or Hispanics ( 147 and 148 micro g / L , respectively ) .", "entity": [], "task": "NER"}
{"text": "The median for all pregnant women in NHANES 2005 - 2010 was less than adequate ( 129 micro g / L ) , the third trimester women had UI concentrations that were adequate ( median UI 172 micro g / L ) .", "entity": [], "task": "NER"}
{"text": "Third trimester women participating in the NCS study similarly had an adequate level of iodine intake , with a median UI concentration of 167 micro g / L .", "entity": [{"entity": "iodine", "entity_type": "Chemical", "pos": [88, 94]}], "task": "NER"}
{"text": "Furthermore , NCS median UI concentrations varied by geographic location .", "entity": [], "task": "NER"}
{"text": "Conclusions : Dairy , but not salt , seafood or grain consumption , was significantly positively associated with median UI concentration in women of childbearing age .", "entity": [], "task": "NER"}
{"text": "Pregnant women in their third trimester in the NHANES 2005 - 2010 had adequate median UI concentrations , but pregnant women in NHANES who were in their first or second trimesters had median UI concentrations that were less than adequate .", "entity": [], "task": "NER"}
{"text": "Non - Hispanic black pregnant women from both the NHANES 2005 - 20010 and the NCS consistently had lower UI median concentrations than non - Hispanic whites or Hispanics .", "entity": [], "task": "NER"}
{"text": "The use of U - 500 regular insulin in the management of patients with obesity and insulin resistance .", "entity": [], "task": "NER"}
{"text": "The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin .", "entity": [], "task": "NER"}
{"text": "This article reviews the published literature on the properties of U - 500 insulin and its use in clinical practice .", "entity": [], "task": "NER"}
{"text": "U - 500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U - 100 insulin .", "entity": [], "task": "NER"}
{"text": "Evidence for its use in clinical practice rests on retrospective case series , which suggests that the use of U - 500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control .", "entity": [], "task": "NER"}
{"text": "To prevent insulin dosing and administration errors , great care must be taken in providing staff and patient education , and in developing policies for the management of patients on U - 500 insulin who are admitted to hospital .", "entity": [], "task": "NER"}
{"text": "The use of insulin analogues in pregnancy .", "entity": [], "task": "NER"}
{"text": "Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes .", "entity": [], "task": "NER"}
{"text": "The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy .", "entity": [], "task": "NER"}
{"text": "Insulin lispro and insulin aspart are safe in pregnancy and may improve post - prandial glycaemic control in women with type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "However , a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short - acting analogue where the woman ' s diabetes is well controlled with human insulin .", "entity": [], "task": "NER"}
{"text": "There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended .", "entity": [], "task": "NER"}
{"text": "Most studies of insulin glargine in pregnancy are small , retrospective and include women with pre - existing diabetes and gestational diabetes .", "entity": [], "task": "NER"}
{"text": "There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control .", "entity": [], "task": "NER"}
{"text": "A head - to - head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ , fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [166, 173]}], "task": "NER"}
{"text": "The greater evidence base supports the use of insulin detemir as the first line long - acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin .", "entity": [], "task": "NER"}
{"text": "There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low .", "entity": [], "task": "NER"}
{"text": "Synthesis and evaluation of cholecystokinin trimers : a multivalent approach to pancreatic cancer detection and treatment .", "entity": [], "task": "NER"}
{"text": "In the quest for novel tools for early detection and treatment of cancer , we propose the use of multimers targeting overexpressed receptors at the cancer cell surface .", "entity": [], "task": "NER"}
{"text": "Indeed , multimers are prone to create multivalent interactions , more potent and specific than their corresponding monovalent versions , thus enabling the potential for early detection .", "entity": [], "task": "NER"}
{"text": "There is a lack of tools for early detection of pancreatic cancer , one of the deadliest forms of cancer , but CCK2 - R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells .", "entity": [], "task": "NER"}
{"text": "In this Letter , we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2 - R .", "entity": [], "task": "NER"}
{"text": "Anti - influenza active and low toxic N - phenyl - substituted beta - amidoamidines structurally related to natural antibiotic amidinomycin .", "entity": [{"entity": "N - phenyl - substituted beta - amidoamidines", "entity_type": "Chemical", "pos": [38, 83]}, {"entity": "amidinomycin", "entity_type": "Chemical", "pos": [127, 139]}], "task": "NER"}
{"text": "A set of racemic N - phenyl - substituted beta - amidoamidines hydrochlorides 4 , which are structurally related to natural antiviral agent amidinomycin ( 1 ) , was synthesized in four steps starting from methacryloyl anilide ( 5 ) .", "entity": [{"entity": "racemic N - phenyl - substituted beta - amidoamidines hydrochlorides", "entity_type": "Chemical", "pos": [9, 77]}, {"entity": "amidinomycin", "entity_type": "Chemical", "pos": [140, 152]}, {"entity": "methacryloyl anilide", "entity_type": "Chemical", "pos": [205, 225]}], "task": "NER"}
{"text": "In the final step of the synthetic route , an uncommon monoacylation of beta - aminoamidine 8 at the less reactive beta - phenylamino - group took place .", "entity": [{"entity": "beta - aminoamidine", "entity_type": "Chemical", "pos": [72, 91]}, {"entity": "beta - phenylamino", "entity_type": "Chemical", "pos": [115, 133]}], "task": "NER"}
{"text": "To rationalize this result , a mechanism which involves initial acylation at the more active amidine - function followed by intramolecular acyl - group transfer to beta - phenylamino - group was suggested .", "entity": [{"entity": "amidine", "entity_type": "Chemical", "pos": [93, 100]}, {"entity": "acyl", "entity_type": "Chemical", "pos": [139, 143]}, {"entity": "beta - phenylamino", "entity_type": "Chemical", "pos": [164, 182]}], "task": "NER"}
{"text": "All three beta - amidoamidines 4d - f bearing long linear aliphatic chain ( from n - C8H17 to n - C12H25 ) revealed significant in vitro activity against influenza A virus ( H3N2 ) and modest cytotoxicity .", "entity": [{"entity": "beta - amidoamidines", "entity_type": "Chemical", "pos": [10, 30]}, {"entity": "n - C8H17", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "n - C12H25", "entity_type": "Chemical", "pos": [94, 104]}], "task": "NER"}
{"text": "The in vitro antiviral potency of 4d , e is 6 - 20 times greater than that of commercial rimantadine with lower EC50 values and higher therapeutic index .", "entity": [{"entity": "rimantadine", "entity_type": "Chemical", "pos": [89, 100]}], "task": "NER"}
{"text": "The non - toxic in vivo compounds 4d - f showed a beneficial protective effect in influenza A ( H3N2 ) infected mice .", "entity": [], "task": "NER"}
{"text": "Peripubertal female athletes in high - impact sports show improved bone mass acquisition and bone geometry .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : Intensive physical training may have a sport - dependent effect on bone mass acquisition .", "entity": [], "task": "NER"}
{"text": "This cross - sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone .", "entity": [], "task": "NER"}
{"text": "MATERIALS / METHODS : Eighty girls from 10 . 7 to 18 . 0years old ( mean 13 . 83 +/- 1 . 97 ) were recruited : 20 artistic gymnasts ( AG ; high - impact activity ) , 20 rhythmic gymnasts ( RG ; medium - impact activity ) , 20 swimmers ( SW , no - impact activity ) , and 20 age - matched controls ( CON ; leisure physical activity < 3h / wk ) .", "entity": [], "task": "NER"}
{"text": "Areal bone mineral density ( aBMD ) was determined using DEXA .", "entity": [], "task": "NER"}
{"text": "Hip structural analysis applied at the femur evaluated cross - sectional area ( CSA , cm ( 2 ) ) , section modulus ( Z , cm ( 3 ) ) , and buckling ratio .", "entity": [], "task": "NER"}
{"text": "Bone turnover markers and OPG / RANKL levels were analyzed .", "entity": [], "task": "NER"}
{"text": "RESULTS : AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius .", "entity": [], "task": "NER"}
{"text": "RG had higher aBMD than SW and CON only in the femoral region .", "entity": [], "task": "NER"}
{"text": "CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON .", "entity": [], "task": "NER"}
{"text": "In RG only , endocortical diameter and width were reduced , while Z was only increased in AG compared with SW and CON .", "entity": [], "task": "NER"}
{"text": "Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status .", "entity": [], "task": "NER"}
{"text": "All groups showed similar OPG concentrations , while RANKL concentrations increased with age and were decreased in SW .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : High - impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period , although the bone health benefits seem to be more marked after menarche .", "entity": [], "task": "NER"}
{"text": "Differential Expression of Human Cytochrome P450 Enzymes from the CYP3A Subfamily in the Brains of Alcoholics and Drug Free Controls .", "entity": [{"entity": "Alcoholics", "entity_type": "Chemical", "pos": [99, 109]}], "task": "NER"}
{"text": "Cytochrome P450 ( P450 , CYP ) enzymes are responsible for the metabolism of most commonly used drugs .", "entity": [], "task": "NER"}
{"text": "Amongst these enzymes , CYP3A forms mediate the clearance of around 40 - 50 % of drugs and may also play roles in the biotransformation of endogenous compounds .", "entity": [], "task": "NER"}
{"text": "CYP3A forms are expressed both in the liver and extrahepatically .", "entity": [], "task": "NER"}
{"text": "However little is known about the expression of CYP3A proteins in specific regions of the human brain .", "entity": [], "task": "NER"}
{"text": "In this study , form - selective antibodies raised to CYP3A4 and CYP3A5 were utilized to characterize the expression of these forms in the human brain .", "entity": [], "task": "NER"}
{"text": "Both CYP3A4 and CYP3A5 immunoreactivity was found to varying extents in the microsomal fractions of cortex , hippocampus , basal ganglia , amygdala and cerebellum .", "entity": [], "task": "NER"}
{"text": "However , only CYP3A4 expression was observed in the mitochondrial fractions of these brain regions .", "entity": [], "task": "NER"}
{"text": "N - terminal sequencing confirmed the principal antigen detected by the anti - CYP3A4 antibody in cortical microsomes to be CYP3A4 .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "Immunohistochemical analysis revealed that CYP3A4 and CYP3A5 expression was primarily localized in the soma and axonal hillock of neurons and varied according to cell type and cell layer within brain regions .", "entity": [], "task": "NER"}
{"text": "Finally , analysis of the frontal cortex of chronic alcohol abusers revealed elevated expression of CYP3A4 in microsomal but not mitochondrial fractions ; CYP3A5 expression was unchanged .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [52, 59]}], "task": "NER"}
{"text": "The site - specific expression of CYP3A4 and CYP3A5 in the human brain may have implications for the role of these enzymes in both normal brain physiology and the response to drugs .", "entity": [], "task": "NER"}
{"text": "Polybrominated Dibenzo - p - dioxins ( PBDDs ) , Dibenzofurans ( PBDFs ) and Biphenyls ( PBBs ) - Inclusion in the Toxicity Equivalency Factor Concept for Dioxin - like Compounds -", "entity": [{"entity": "Polybrominated Dibenzo - p - dioxins", "entity_type": "Chemical", "pos": [0, 36]}, {"entity": "PBDDs", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "Dibenzofurans", "entity_type": "Chemical", "pos": [49, 62]}, {"entity": "PBDFs", "entity_type": "Chemical", "pos": [65, 70]}, {"entity": "Biphenyls", "entity_type": "Chemical", "pos": [77, 86]}, {"entity": "PBBs", "entity_type": "Chemical", "pos": [89, 93]}, {"entity": "Dioxin", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "In 2011 a joint World Health Organization ( WHO ) and United Nations Environment Programme ( UNEP ) expert consultation took place , during which the possible inclusion of brominated analogues of the dioxin - like compounds in the WHO Toxicity Equivalency Factor ( TEF ) scheme were evaluated .", "entity": [{"entity": "dioxin", "entity_type": "Chemical", "pos": [200, 206]}], "task": "NER"}
{"text": "The expert panel concluded that polybrominated dibenzo - p - dioxins ( PBDDs ) , dibenzofurans ( PBDFs ) , and some dioxin - like biphenyls ( dl - PBBs ) may contribute significantly in daily human background exposure to the total dioxin toxic equivalencies ( TEQs ) .", "entity": [{"entity": "polybrominated dibenzo - p - dioxins", "entity_type": "Chemical", "pos": [32, 68]}, {"entity": "PBDDs", "entity_type": "Chemical", "pos": [71, 76]}, {"entity": "dibenzofurans", "entity_type": "Chemical", "pos": [81, 94]}, {"entity": "PBDFs", "entity_type": "Chemical", "pos": [97, 102]}, {"entity": "dioxin", "entity_type": "Chemical", "pos": [116, 122]}, {"entity": "biphenyls", "entity_type": "Chemical", "pos": [130, 139]}, {"entity": "PBBs", "entity_type": "Chemical", "pos": [147, 151]}, {"entity": "dioxin", "entity_type": "Chemical", "pos": [231, 237]}], "task": "NER"}
{"text": "These compounds are also commonly found in the aquatic environment .", "entity": [], "task": "NER"}
{"text": "Available data for fish toxicity were evaluated for possible inclusion in the WHO - UNEP TEF scheme ( Van den Berg et al . , 1998 ) .", "entity": [], "task": "NER"}
{"text": "Because of the limited database it was decided not to derive specific WHO - UNEP TEFs for fish , but for ecotoxicological risk assessment the use of specific relative effect potencies ( REPs ) from fish embryo assays is recommended .", "entity": [], "task": "NER"}
{"text": "Based on the limited mammalian REP database for these brominated compounds , it was concluded that sufficient differentiation from the present TEF values of the chlorinated analogues ( Van den Berg et al . , 2005 ) was not possible .", "entity": [], "task": "NER"}
{"text": "However , the REPs for PBDDs , PBDFs , and non - ortho dl - PBBs in mammals closely follow those of the chlorinated analogues , at least within one order of magnitude .", "entity": [{"entity": "PBDDs", "entity_type": "Chemical", "pos": [23, 28]}, {"entity": "PBDFs", "entity_type": "Chemical", "pos": [31, 36]}, {"entity": "PBBs", "entity_type": "Chemical", "pos": [60, 64]}], "task": "NER"}
{"text": "Therefore , the use of similar interim TEF values for brominated and chlorinated congeners for human risk assessment is recommended , pending more detailed information in the future .", "entity": [], "task": "NER"}
{"text": "Yeast Proteome Variations Reveal Different Adaptive Responses to Grape Must Fermentation .", "entity": [], "task": "NER"}
{"text": "Saccharomyces cerevisiae and S . uvarum are two domesticated species of the Saccharomyces sensu stricto clade that diverged around 100 Ma after whole - genome duplication .", "entity": [], "task": "NER"}
{"text": "Both have retained many duplicated genes associated with glucose fermentation and are characterized by the ability to achieve grape must fermentation .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [57, 64]}], "task": "NER"}
{"text": "Nevertheless , these two species differ for many other traits , indicating that they underwent different evolutionary histories .", "entity": [], "task": "NER"}
{"text": "To determine how the evolutionary histories of S . cerevisiae and S . uvarum are mirrored on the proteome , we analyzed the genetic variability of the proteomes of domesticated strains of these two species by quantitative mass spectrometry .", "entity": [], "task": "NER"}
{"text": "Overall , 445 proteins were quantified .", "entity": [], "task": "NER"}
{"text": "Massive variations of protein abundances were found , that clearly differentiated the two species .", "entity": [], "task": "NER"}
{"text": "Abundance variations in specific metabolic pathways could be related to phenotypic traits known to discriminate the two species .", "entity": [], "task": "NER"}
{"text": "In addition , proteins encoded by duplicated genes were shown to be differently recruited in each species .", "entity": [], "task": "NER"}
{"text": "Comparing the strain differentiation based on the proteome variability to those based on the phenotypic and genetic variations further revealed that the strains of S . uvarum and some strains of S . cerevisiae displayed similar fermentative performances despite strong proteomic and genomic differences .", "entity": [], "task": "NER"}
{"text": "Altogether , these results indicate that the ability of S . cerevisae and S . uvarum to complete grape must fermentation arose through different evolutionary roads , involving different metabolic pathways and duplicated genes .", "entity": [], "task": "NER"}
{"text": "Dexamethasone - mediated changes in adipose triacylglycerol metabolism are exaggerated , not diminished , in the absence of a functional GR dimerization domain .", "entity": [{"entity": "Dexamethasone", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "triacylglycerol", "entity_type": "Chemical", "pos": [44, 59]}], "task": "NER"}
{"text": "The glucocorticoid ( GC ) receptor ( GR ) has multiple effector mechanisms , including dimerization - mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein - protein interactions .", "entity": [], "task": "NER"}
{"text": "Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti - inflammatory effects .", "entity": [], "task": "NER"}
{"text": "The GR ( dim / dim ) mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression .", "entity": [], "task": "NER"}
{"text": "To understand the role of GR dimerization - dependent targets in multiple tissues , we measured metabolic fluxes through several disease - relevant GC target pathways using heavy water labeling and mass spectrometry in wild - type and GR ( dim / dim ) mice administered the potent GC dexamethasone ( DEX ) .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [284, 297]}, {"entity": "DEX", "entity_type": "Chemical", "pos": [300, 303]}], "task": "NER"}
{"text": "Absolute triglyceride synthesis was increased in both wild - type and GR ( dim / dim ) mice by DEX in the inguinal and epididymal fat depots .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [9, 21]}, {"entity": "DEX", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "GR ( dim / dim ) mice showed an exaggerated response to DEX in both depots .", "entity": [{"entity": "DEX", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "De novo lipogenesis was also greatly increased in both depots in response to DEX in GR ( dim / dim ) , but not wild - type mice .", "entity": [{"entity": "DEX", "entity_type": "Chemical", "pos": [77, 80]}], "task": "NER"}
{"text": "In contrast , the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild - type compared with GR ( dim / dim ) mice .", "entity": [{"entity": "DEX", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "Wild - type mice were more sensitive to DEX - dependent decreases in insulin sensitivity than GR ( dim / dim ) mice .", "entity": [{"entity": "DEX", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "Wild - type and GR ( dim / dim ) mice were equally sensitive to DEX - dependent decreases in muscle protein synthesis .", "entity": [{"entity": "DEX", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Chronic elevation of GCs in GR ( dim / dim ) mice results in severe runting and lethality .", "entity": [], "task": "NER"}
{"text": "In conclusion , some metabolic effects of GC treatment are exaggerated in adipose tissue of GR ( dim / dim ) mice , suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully .", "entity": [], "task": "NER"}
{"text": "X - box binding protein 1 is essential for insulin regulation of pancreatic alpha cell function .", "entity": [], "task": "NER"}
{"text": "Type 2 diabetes mellitus ( T2D ) patients often exhibit hyperglucagonemia despite hyperglycemia suggesting defective alpha - cell function .", "entity": [], "task": "NER"}
{"text": "While endoplasmic reticulum ( ER ) stress has been suggested to underlie beta - cell dysfunction in T2D , its role in alpha - cell biology remains unclear .", "entity": [], "task": "NER"}
{"text": "X - box binding protein 1 ( XBP1 ) is a transcription factor that plays a crucial role in the unfolded protein response ( UPR ) and its deficiency in beta - cells has been reported to impair insulin secretion leading to glucose intolerance .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [220, 227]}], "task": "NER"}
{"text": "To evaluate the role of XBP1 in alpha - cells , we created complementary in vivo ( alpha - cell specific XBP1 knockout ( alpha XBPKO ) mice ) and in vitro ( stable XBP1 knock down alpha - cell line , alpha XBPKD ) models .", "entity": [], "task": "NER"}
{"text": "alpha XBPKO mice exhibited glucose intolerance , mild insulin resistance and an inability to suppress glucagon secretion following glucose stimulation .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [27, 34]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [131, 138]}], "task": "NER"}
{"text": "alpha XBPKD cells exhibited activation of IRE1 , an upstream activator of XBP1 , leading to phosphorylation of JNK .", "entity": [], "task": "NER"}
{"text": "Interestingly , insulin treatment of alpha XBPKD cells reduced tyrosine phosphorylation of IRS - 1 ( pY ( 896 ) ) , and phosphorylation of Akt , while enhancing serine phosphorylation ( pS ( 307 ) ) of IRS - 1 .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [63, 71]}, {"entity": "serine", "entity_type": "Chemical", "pos": [161, 167]}], "task": "NER"}
{"text": "Consequently the alpha XBPKD cells exhibited blunted suppression of glucagon secretion following insulin treatment in the presence of high glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "Together , these data indicate that XBP1 deficiency in pancreatic alpha - cells induces altered insulin signaling and dysfunctional glucagon secretion .", "entity": [], "task": "NER"}
{"text": "Fabrication and multifunction integration of microfluidic chips by femtosecond laser direct writing .", "entity": [], "task": "NER"}
{"text": "In the pursuit of modern microfluidic chips with multifunction integration , micronanofabrication techniques play an increasingly important role .", "entity": [], "task": "NER"}
{"text": "Despite the fact that conventional fabrication approaches such as lithography , imprinting and soft lithography have been widely used for the preparation of microfluidic chips , it is still challenging to achieve complex microfluidic chips with multifunction integration .", "entity": [], "task": "NER"}
{"text": "Therefore , novel micronanofabrication approaches that could be used to achieve this end are highly desired .", "entity": [], "task": "NER"}
{"text": "As a powerful 3D processing tool , femtosecond laser fabrication shows great potential to endow general microfluidic chips with multifunctional units .", "entity": [], "task": "NER"}
{"text": "In this review , we briefly introduce the fundamental principles of femtosecond laser micronanofabrication .", "entity": [], "task": "NER"}
{"text": "With the help of laser techniques , both the preparation and functionalization of advanced microfluidic chips are summarized .", "entity": [], "task": "NER"}
{"text": "Finally , the current challenges and future perspective of this dynamic field are discussed based on our own opinion .", "entity": [], "task": "NER"}
{"text": "LDL Cholesterol Goals in High - Risk Patients : How Low Do We Go and How Do We Get There ?", "entity": [{"entity": "Cholesterol", "entity_type": "Chemical", "pos": [4, 15]}], "task": "NER"}
{"text": "It is widely recognised that low - density lipoprotein cholesterol ( LDL - C ) is one of the most important and modifiable risk factors for cardiovascular disease ( CVD ) .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "Statins ( HMG - CoA reductase inhibitors ) have consistently been shown to decrease both LDL - C and CVD risk in almost all patient categories , with the exception of heart and kidney failure as well as advanced aortic stenosis .", "entity": [{"entity": "HMG - CoA", "entity_type": "Chemical", "pos": [10, 19]}], "task": "NER"}
{"text": "As a consequence , statins have become the cornerstone in current prevention guidelines .", "entity": [], "task": "NER"}
{"text": "In patients who do not reach the LDL - C target , combination therapy with additional LDL - C lowering drugs ( e . g . ezetimibe , bile acid sequestrants or fibrates ) should be considered .", "entity": [{"entity": "ezetimibe", "entity_type": "Chemical", "pos": [119, 128]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [131, 140]}, {"entity": "fibrates", "entity_type": "Chemical", "pos": [157, 165]}], "task": "NER"}
{"text": "Guidelines provide different LDL - C levels to strive for , depending on the CVD risk .", "entity": [], "task": "NER"}
{"text": "In this review , we describe the rationale for these LDL - C targets and how these goals might be reached by current and future therapies .", "entity": [], "task": "NER"}
{"text": "The clinical characteristics at diagnosis of type 2 diabetes in a multi - ethnic population : the South London Diabetes cohort ( SOUL - D ) .", "entity": [], "task": "NER"}
{"text": "AIMS / HYPOTHESIS : This study aimed to investigate the clinical features of newly diagnosed type 2 diabetes in an urban multi - ethnic cohort .", "entity": [], "task": "NER"}
{"text": "METHODS : A population - based cross - sectional design was used .", "entity": [], "task": "NER"}
{"text": "People diagnosed with type 2 diabetes in the preceding 6 months were recruited from primary care practices in three adjacent inner - city boroughs of South London , serving a population in which 20 % of residents are of black African or Caribbean ethnicity .", "entity": [], "task": "NER"}
{"text": "Sociodemographic and biomedical data were collected by standardised clinical assessment and from medical records .", "entity": [], "task": "NER"}
{"text": "Multiple logistic regression methods were used to report associations between ethnicity and diabetes - complication status .", "entity": [], "task": "NER"}
{"text": "RESULTS : From 96 general practices , 1 , 506 patients were recruited .", "entity": [], "task": "NER"}
{"text": "Their mean age was 55 . 6 ( +/- 11 . 07 ) years , 55 % were men , 60 % were asymptomatic at diagnosis and 51 % , 38 % and 11 % were of white , black and South Asian / other ethnicity , respectively .", "entity": [], "task": "NER"}
{"text": "Compared with white participants , black and South Asian / other participants were : younger ( mean age 58 . 9 [ +/- 10 . 09 ] , 52 . 4 [ +/- 11 . 19 ] and 51 . 5 [ +/- 10 . 42 ] years , respectively ; p < 0 . 0001 ) ; less likely to have neuropathy ( 10 . 1 % , 3 . 6 % and 4 . 4 % ; p < 0 . 0001 ) or report coronary artery disease ( 12 . 7 % , 4 . 8 % and 7 . 3 % ; p < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "In logistic regression , compared with white participants , black participants had lower levels of macrovascular complications ( OR 0 . 52 , 95 % CI 0 . 32 , 0 . 84 ; p = 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "Male sex was independently associated with microvascular disease ( OR 1 . 69 , 95 % CI 1 . 26 , 2 . 28 ; p < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS / INTERPRETATION : The prevalence of complications at time of diagnosis was lower than expected , especially in black and South Asian / other ethnic groups .", "entity": [], "task": "NER"}
{"text": "However , in multi - ethnic inner - city populations , onset of type 2 diabetes occurred almost 10 years earlier in non - white populations than in white participants , predicating a prolonged morbidity .", "entity": [], "task": "NER"}
{"text": "Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Mitochondrial glutathione pool is vital in protecting cells against oxidative stress as the majority of the cellular reactive oxygen species are generated in mitochondria .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [126, 132]}], "task": "NER"}
{"text": "Oxidative stress is implicated as a causative factor in neuronal death in neurodegenerative disorders .", "entity": [], "task": "NER"}
{"text": "We hypothesized that depletion of mitochondrial glutathione leads to mitochondrial dysfunction and apoptotic death of SK - N - SH ( human neuroblastoma ) cells and investigated the neuroprotective strategies against GSH depletion .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [216, 219]}], "task": "NER"}
{"text": "SK - N - SH cells were treated with two distinct inhibitors of glutathione metabolism : L - buthionine - ( S , R ) - sulfoximine ( BSO ) and ethacrynic acid ( EA ) .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [63, 74]}, {"entity": "L - buthionine - ( S , R ) - sulfoximine", "entity_type": "Chemical", "pos": [88, 128]}, {"entity": "BSO", "entity_type": "Chemical", "pos": [131, 134]}, {"entity": "ethacrynic acid", "entity_type": "Chemical", "pos": [141, 156]}], "task": "NER"}
{"text": "EA treatment caused depletion of both the total and mitochondrial glutathione ( while BSO had no effect on mitochondrial glutathione ) , enhanced rotenone - induced ROS production , and reduced the viability of SK - N - SH cells .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [66, 77]}, {"entity": "BSO", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [121, 132]}, {"entity": "rotenone", "entity_type": "Chemical", "pos": [146, 154]}], "task": "NER"}
{"text": "Glutathione depletion by BSO or EA demonstrated positive features of mitochondria - mediated apoptosis in neuroblastoma cell death .", "entity": [{"entity": "Glutathione", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "BSO", "entity_type": "Chemical", "pos": [25, 28]}], "task": "NER"}
{"text": "Prevention of apoptosis by Bcl2 overexpression or use of antioxidant ebselen did not confer neuroprotection .", "entity": [{"entity": "ebselen", "entity_type": "Chemical", "pos": [69, 76]}], "task": "NER"}
{"text": "Co - culture with U - 87 ( human glioblastoma ) cells protected SK - N - SH cells from the cell death .", "entity": [], "task": "NER"}
{"text": "Our data suggest that depletion of mitochondrial glutathione leads to mitochondrial dysfunction and apoptosis .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "The study indicates that preventing mitochondrial glutathione depletion could become a novel strategy for the development of neuroprotective therapeutics in neurodegenerative disorders .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "Structure of dipeptides having N - terminal selenocysteine residues : a DFT study in gas and aqueous phase .", "entity": [{"entity": "dipeptides", "entity_type": "Chemical", "pos": [13, 23]}, {"entity": "N", "entity_type": "Chemical", "pos": [31, 32]}, {"entity": "selenocysteine", "entity_type": "Chemical", "pos": [44, 58]}], "task": "NER"}
{"text": "Over the last few decades , dipeptides as well as their analogues have served as important model systems for the computational studies concerning the structure of protein and energetics of protein folding .", "entity": [{"entity": "dipeptides", "entity_type": "Chemical", "pos": [28, 38]}], "task": "NER"}
{"text": "Here , we present a density functional structural study on a set of seven dipeptides having N - terminal selenocysteine residues ( the component in the C - terminus is varied with seven different combinations viz . Ala , Phe , Glu , Thr , Asn , Arg and Sec ) in gas and simulated aqueous phase using a polarizable continuum model ( PCM ) .", "entity": [{"entity": "dipeptides", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "N", "entity_type": "Chemical", "pos": [92, 93]}, {"entity": "selenocysteine", "entity_type": "Chemical", "pos": [105, 119]}, {"entity": "C", "entity_type": "Chemical", "pos": [152, 153]}, {"entity": "Ala", "entity_type": "Chemical", "pos": [215, 218]}, {"entity": "Phe", "entity_type": "Chemical", "pos": [221, 224]}, {"entity": "Glu", "entity_type": "Chemical", "pos": [227, 230]}, {"entity": "Thr", "entity_type": "Chemical", "pos": [233, 236]}, {"entity": "Asn", "entity_type": "Chemical", "pos": [239, 242]}, {"entity": "Arg", "entity_type": "Chemical", "pos": [245, 248]}, {"entity": "Sec", "entity_type": "Chemical", "pos": [253, 256]}], "task": "NER"}
{"text": "The molecular geometries of the dipeptides are fully optimized at B3LYP / 6 - 311 + + G ( d , p ) level and subsequent frequency calculations confirm them as true minima .", "entity": [{"entity": "dipeptides", "entity_type": "Chemical", "pos": [32, 42]}], "task": "NER"}
{"text": "The effects of solvation and identity of the varying C - terminal residue on the energetics , structural features of the peptide planes , values of the psi and phi dihedrals , geometry around the alpha - carbon atoms and theoretically predicted vibrational spectra of the dipeptides are investigated .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [53, 54]}, {"entity": "alpha - carbon", "entity_type": "Chemical", "pos": [196, 210]}, {"entity": "dipeptides", "entity_type": "Chemical", "pos": [272, 282]}], "task": "NER"}
{"text": "Two types of intramolecular H - bonds , namely N ... H - N and O ... H - C , are found to play important roles in influencing the planarity of the peptide planes and geometry around the alpha - carbon atoms of the dipeptides .", "entity": [{"entity": "H", "entity_type": "Chemical", "pos": [28, 29]}, {"entity": "N", "entity_type": "Chemical", "pos": [47, 48]}, {"entity": "H - N", "entity_type": "Chemical", "pos": [53, 58]}, {"entity": "O", "entity_type": "Chemical", "pos": [63, 64]}, {"entity": "H - C", "entity_type": "Chemical", "pos": [69, 74]}, {"entity": "alpha - carbon", "entity_type": "Chemical", "pos": [186, 200]}, {"entity": "dipeptides", "entity_type": "Chemical", "pos": [214, 224]}], "task": "NER"}
{"text": "The identity of the varying C - terminal residue influences the values of phi , planarity of the peptide planes and geometry around the C7 alpha - carbon atoms while the solvation effects are evident on the values of bond lengths and bond angles of the amide planes .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [28, 29]}, {"entity": "alpha - carbon", "entity_type": "Chemical", "pos": [139, 153]}, {"entity": "amide", "entity_type": "Chemical", "pos": [253, 258]}], "task": "NER"}
{"text": "The Role of Traditional Chinese Medicines in Osteogenesis and Angiogenesis .", "entity": [], "task": "NER"}
{"text": "The article aims to review various Traditional Chinese Medicines ( TCMs ) with both osteogenic and angiogenic effects , alone and in combination , and to consider whether these TCMs promote osteogenesis via angiogenesis and vascular endothelial growth factor ( VEGF ) .", "entity": [], "task": "NER"}
{"text": "Each of the TCMs involving in osteogenesis was searched through PubMed and CBMdisc using its Latin name and English name , and keywords such as ' osteogenesis ' , ' bone ' , ' osteoblast ' , ' angiogenesis ' , ' VEGF ' were used .", "entity": [], "task": "NER"}
{"text": "A total of 241 articles were screened from PubMed and CBMdisc .", "entity": [], "task": "NER"}
{"text": "The articles were only chosen if they discussed the relationship of the TCMs with bone formation and / or angiogenesis .", "entity": [], "task": "NER"}
{"text": "Twenty - seven articles were chosen , of which 16 were in English and 11 were in Chinese with English abstract .", "entity": [], "task": "NER"}
{"text": "As a result , the TCMs ( Danshen or Salvia miltiorrhiza Bunge , Danggui or Angelica sinensis , Astragalus membranaceus Bunge or Huangqi , and Ge Gan or Puerarin radix ) that have a relationship with both osteogenesis and angiogenesis were screened out .", "entity": [], "task": "NER"}
{"text": "It is found that the aforementioned TCMs enhance angiogenesis and osteogenesis .", "entity": [], "task": "NER"}
{"text": "They show a positive effect on bone formation , and the possible mechanisms may be related to their ability to promote angiogenesis via an effect on substances such as VEGF .", "entity": [], "task": "NER"}
{"text": "Nickel sulfide / nitrogen - doped graphene composites : phase - controlled synthesis and high performance anode materials for lithium ion batteries .", "entity": [{"entity": "Nickel sulfide", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "nitrogen - doped graphene", "entity_type": "Chemical", "pos": [17, 42]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Phase - controlled nickel sulfide ( Ni3 S4 and NiS1 . 03 ) nanoparticle ( NP ) / nitrogen - doped graphene ( NG ) composites are prepared through a facile one - pot hydrothermal process .", "entity": [{"entity": "nickel sulfide", "entity_type": "Chemical", "pos": [19, 33]}, {"entity": "Ni3 S4", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "NiS1 . 03", "entity_type": "Chemical", "pos": [47, 56]}, {"entity": "nitrogen - doped graphene", "entity_type": "Chemical", "pos": [81, 106]}], "task": "NER"}
{"text": "The composites show ultrahigh capacity retentions of 98 . 87 % and 95 . 94 % for Ni3 S4 / NG and NiS1 . 03 / NG electrodes , respectively , as anode materials for lithium ion batteries .", "entity": [{"entity": "Ni3 S4", "entity_type": "Chemical", "pos": [81, 87]}, {"entity": "NiS1 . 03", "entity_type": "Chemical", "pos": [97, 106]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "( 1 ) H and ( 13 ) C NMR analysis of 2 - acetamido - 3 - mercapto - 3 - methyl - N - aryl - butanamides and 2 - acetamido - 3 - methyl - 3 - nitrososulfanyl - N - aryl - butanamide derivatives .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "2 - acetamido - 3 - mercapto - 3 - methyl - N - aryl - butanamides", "entity_type": "Chemical", "pos": [37, 103]}, {"entity": "2 - acetamido - 3 - methyl - 3 - nitrososulfanyl - N - aryl - butanamide", "entity_type": "Chemical", "pos": [108, 180]}], "task": "NER"}
{"text": "The complete assignment of the ( 1 ) H and ( 13 ) C NMR spectra of various 2 - acetamido - 3 - mercapto - 3 - methyl - N - aryl - butanamides and 2 - acetamide - 3 - methyl - 3 - nitrososulfanyl - N - aryl - butanamides with p - methoxy , o - chloro and m - chloro substituents is reported .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [43, 51]}, {"entity": "2 - acetamido - 3 - mercapto - 3 - methyl - N - aryl - butanamides", "entity_type": "Chemical", "pos": [75, 141]}, {"entity": "2 - acetamide - 3 - methyl - 3 - nitrososulfanyl - N - aryl - butanamides", "entity_type": "Chemical", "pos": [146, 219]}, {"entity": "p - methoxy", "entity_type": "Chemical", "pos": [225, 236]}, {"entity": "o - chloro", "entity_type": "Chemical", "pos": [239, 249]}, {"entity": "m - chloro", "entity_type": "Chemical", "pos": [254, 264]}], "task": "NER"}
{"text": "Targeting protein - protein interactions within the cyclic AMP signaling system as a therapeutic strategy for cardiovascular disease .", "entity": [{"entity": "cyclic AMP", "entity_type": "Chemical", "pos": [52, 62]}], "task": "NER"}
{"text": "The cAMP signaling system can trigger precise physiological cellular responses that depend on the fidelity of many protein - protein interactions , which act to bring together signaling intermediates at defined locations within cells .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [4, 8]}], "task": "NER"}
{"text": "In the heart , cAMP participates in the fine control of excitation - contraction coupling , hence , any disregulation of this signaling cascade can lead to cardiac disease .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [15, 19]}], "task": "NER"}
{"text": "Due to the ubiquitous nature of the cAMP pathway , general inhibitors of cAMP signaling proteins such as PKA , EPAC and PDEs would act non - specifically and universally , increasing the likelihood of serious ' off target ' effects .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [36, 40]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "Recent advances in the discovery of peptides and small molecules that disrupt the protein - protein interactions that underpin cellular targeting of cAMP signaling proteins are described and discussed .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [149, 153]}], "task": "NER"}
{"text": "Identification of Transglutaminase Substrates from Porcine Nucleus Pulposus as Potential Amplifiers in Cross - Linking Cell Scaffolds .", "entity": [], "task": "NER"}
{"text": "Nucleus pulposus from the porcine intervertebral disc was separated chromatographically to discover substrates of microbial transglutaminase .", "entity": [], "task": "NER"}
{"text": "Highly purified proteins were prepared , among them type II collagen , the major protein of the nucleus pulposus .", "entity": [], "task": "NER"}
{"text": "Determination of substrates was performed by transglutaminase - mediated incorporation of biotinylated probes displaying several glutamine and lysine donor proteins .", "entity": [{"entity": "glutamine", "entity_type": "Chemical", "pos": [129, 138]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [143, 149]}], "task": "NER"}
{"text": "Type II collagen was only labeled if smaller nucleus pulposus proteins were present .", "entity": [], "task": "NER"}
{"text": "One of the modulating proteins was serotransferrin , a lysine donor substrate of bacterial transglutaminase .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [55, 61]}], "task": "NER"}
{"text": "An additional substrate was the carboxy - terminal propeptide of type II collagen , chondrocalcin .", "entity": [{"entity": "carboxy", "entity_type": "Chemical", "pos": [32, 39]}], "task": "NER"}
{"text": "Chondrocalcin , a regulator of type II collagen fibrillogenesis , occurs abundantly in juvenile cartilage and nucleus pulposus .", "entity": [], "task": "NER"}
{"text": "Accordingly , the protein may be regarded as an excellent additive for the preparation of injectable stem cells in nucleus pulposus - like matrices cross - linked by microbial transglutaminase .", "entity": [], "task": "NER"}
{"text": "From synaptic spines to nuclear signaling : nuclear and synaptic actions of the amyloid precursor protein .", "entity": [], "task": "NER"}
{"text": "Despite intensive studies of the secretase - mediated processing of the amyloid precursor protein ( APP ) to form the amyloid beta - peptide ( A beta ) , in relation to Alzheimer ' s disease ( AD ) , no new therapeutic agents have reached the clinics based on reducing A beta levels through the use of secretase inhibitors or immunotherapy .", "entity": [], "task": "NER"}
{"text": "Furthermore , the normal neuronal functions of APP and its various metabolites still remain under - investigated and unclear .", "entity": [], "task": "NER"}
{"text": "Here , we highlight emerging areas of APP function that may provide new insights into synaptic development , cognition , and gene regulation .", "entity": [], "task": "NER"}
{"text": "By modulating expression levels of endogenous APP in primary cortical neurons , the frequency and amplitude of calcium oscillations is modified , implying a key role for APP in maintaining neuronal calcium homeostasis essential for synaptic transmission .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [111, 118]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [198, 205]}], "task": "NER"}
{"text": "Disruption of this homeostatic mechanism predisposes to aging and AD .", "entity": [], "task": "NER"}
{"text": "Synaptic spine loss is a feature of neurogeneration resulting in learning and memory deficits , and emerging evidence indicates a role for APP , probably mediated via one or more of its metabolites , in spine structure and functions .", "entity": [], "task": "NER"}
{"text": "The intracellular domain of APP ( AICD ) has also emerged as a key epigenetic regulator of gene expression controlling a diverse range of genes , including APP itself , the amyloid - degrading enzyme neprilysin , and aquaporin - 1 .", "entity": [], "task": "NER"}
{"text": "A fuller understanding of the physiological and pathological actions of APP and its metabolic network could provide new opportunities for therapeutic intervention in AD .", "entity": [], "task": "NER"}
{"text": "The effect of rituximab on thyroid function and autoimmunity .", "entity": [], "task": "NER"}
{"text": "no abstract required .", "entity": [], "task": "NER"}
{"text": "Pyridone Alkaloids from a Marine - Derived Fungus , Stagonosporopsis cucurbitacearum , and Their Activities against Azole - Resistant Candida albicans .", "entity": [{"entity": "Pyridone Alkaloids", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "Azole", "entity_type": "Chemical", "pos": [116, 121]}], "task": "NER"}
{"text": "Four new 4 - hydroxy - 2 - pyridone alkaloids , didymellamides A - D ( 1 - 4 ) , were isolated from the marine - derived fungus Stagonosporopsis cucurbitacearum .", "entity": [{"entity": "4 - hydroxy - 2 - pyridone alkaloids", "entity_type": "Chemical", "pos": [9, 45]}, {"entity": "didymellamides A - D", "entity_type": "Chemical", "pos": [48, 68]}], "task": "NER"}
{"text": "The structures of 1 - 4 were elucidated from spectroscopic data ( NMR , MS , and IR ) , and the absolute configuration of 1 was determined by X - ray diffraction analysis .", "entity": [], "task": "NER"}
{"text": "Didymellamide A ( 1 ) exhibited antifungal activity against azole - resistant Candida albicans .", "entity": [{"entity": "Didymellamide A", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "azole", "entity_type": "Chemical", "pos": [60, 65]}], "task": "NER"}
{"text": "Chemical composition and antioxidant activity of dried powder formulations of Agaricus blazei and Lentinus edodes .", "entity": [], "task": "NER"}
{"text": "Several mushroom species have been pointed out as sources of antioxidant compounds , in addition to their important nutritional value .", "entity": [], "task": "NER"}
{"text": "Agaricus blazei and Lentinus edodes are among the most studied species all over the world , but those studies focused on their fruiting bodies instead of other presentations , such as powdered preparations , used as supplements .", "entity": [], "task": "NER"}
{"text": "In the present work the chemical composition ( nutrients and bioactive compounds ) and antioxidant activity ( free radical scavenging activity , reducing power and lipid peroxidation inhibition ) of dried powder formulations of the mentioned mushroom species ( APF and LPF , respectively ) were evaluated .", "entity": [], "task": "NER"}
{"text": "Powder formulations of both species revealed the presence of essential nutrients , such as proteins , carbohydrates and unsaturated fatty acids .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [102, 115]}, {"entity": "unsaturated fatty acids", "entity_type": "Chemical", "pos": [120, 143]}], "task": "NER"}
{"text": "Furthermore , they present a low fat content ( < 2g / 100g ) and can be used in low - calorie diets , just like the mushrooms fruiting bodies .", "entity": [], "task": "NER"}
{"text": "APF showed higher antioxidant activity and higher content of tocopherols and phenolic compounds ( 124 and 770 mu g / 100g , respectively ) than LPF ( 32 and 690 mu g / 100g ) .", "entity": [{"entity": "tocopherols", "entity_type": "Chemical", "pos": [61, 72]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [77, 85]}], "task": "NER"}
{"text": "Both formulations could be used as antioxidant sources to prevent diseases related to oxidative stress .", "entity": [], "task": "NER"}
{"text": "The antioxidants in oils heated at frying temperature , whether natural or added , could protect against postprandial oxidative stress in obese people .", "entity": [], "task": "NER"}
{"text": "We have investigated the effects of the intake of oils heated at frying temperature in order to find an oil model for deep - frying that prevents postprandial oxidative stress .", "entity": [], "task": "NER"}
{"text": "Twenty obese people received four breakfasts following a randomised crossover design consisting of different oils ( virgin olive oil ( VOO ) , sunflower oil ( SFO ) , and a mixed seed oil ( SFO / canola oil ) with added dimethylpolysiloxane ( SOX ) or natural antioxidants from olives ( SOP ) ) , which were subjected to 20 heating cycles .", "entity": [{"entity": "dimethylpolysiloxane", "entity_type": "Chemical", "pos": [220, 240]}, {"entity": "SOX", "entity_type": "Chemical", "pos": [243, 246]}, {"entity": "SOP", "entity_type": "Chemical", "pos": [287, 290]}], "task": "NER"}
{"text": "The intake of SFO - breakfast reduced plasma GSH levels and the GSH / GSSG ratio , increased protein carbonyl levels , and induced a higher gene expression of the different NADPH - oxidase subunits , Nrf2 - Keap1 activation , gene expression of the antioxidant enzymes in peripheral blood mononuclear cells and antioxidant plasma activities than the intake of the breakfasts prepared with VOO , SOP and SOX .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [70, 74]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [101, 109]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [173, 178]}, {"entity": "SOP", "entity_type": "Chemical", "pos": [395, 398]}, {"entity": "SOX", "entity_type": "Chemical", "pos": [403, 406]}], "task": "NER"}
{"text": "Oils with phenolic compounds , whether natural ( VOO ) or artificially added ( SOP ) , or with artificial antioxidant ( SOX ) , could reduce postprandial oxidative stress compared with sunflower oil .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "SOP", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "SOX", "entity_type": "Chemical", "pos": [120, 123]}], "task": "NER"}
{"text": "Rapid monitoring of heat - accelerated reactions in vegetable oils using direct analysis in real time ionization coupled with high resolution mass spectrometry .", "entity": [], "task": "NER"}
{"text": "Transmission - mode direct analysis in real time ionization coupled with high resolution mass spectrometry ( TM - DART - HRMS ) was used to monitor chemical changes in various vegetable oils ( olive , rapeseed , soybean and sunflower oil ) during their thermally - induced oxidation .", "entity": [], "task": "NER"}
{"text": "This novel instrumental approach enabled rapid fingerprinting of examined samples and detection of numerous sample components , such as triacylglycerols ( TAGs ) , phytosterols , free fatty acids ( FFA ) , and their respective oxidation products .", "entity": [{"entity": "triacylglycerols", "entity_type": "Chemical", "pos": [136, 152]}, {"entity": "TAGs", "entity_type": "Chemical", "pos": [155, 159]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [179, 195]}, {"entity": "FFA", "entity_type": "Chemical", "pos": [198, 201]}], "task": "NER"}
{"text": "Mass spectra obtained from DART were processed with the use of principal component analysis ( PCA ) in order to assess the compositional differences between heated and non - heated samples .", "entity": [], "task": "NER"}
{"text": "Good correlation was observed between the normalized intensities of the pre - selected ion corresponding to mono - oxidized TAG and ' classic ' criterion represented by the levels of TAG polymers determined by high performance - size exclusion chromatography with refractometric detection ( HP - SEC - RID ) .", "entity": [{"entity": "TAG", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [183, 186]}], "task": "NER"}
{"text": "Calcium hydroxy palmitate : possible precursor phase in calcium precipitation by palmitate .", "entity": [{"entity": "Calcium hydroxy palmitate", "entity_type": "Chemical", "pos": [0, 25]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [81, 90]}], "task": "NER"}
{"text": "Calcium ( II ) precipitates with palmitate ( Pal ( - ) ) , a process affecting calcium absorption in the gut , in a first - order reaction , as followed by a calcium electrode in neutral aqueous solution for excess of calcium ( II ) , with a rate constant showing a minimum at physiological ionic strength of 0 . 32 +/- 0 . 09 d ( - 1 ) at 25 degrees C with a stoichiometry of 1 . 79 +/- 0 . 03 , lower than the expected 1 : 2 .", "entity": [{"entity": "Calcium ( II )", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "Pal ( - )", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [158, 165]}, {"entity": "calcium ( II )", "entity_type": "Chemical", "pos": [218, 232]}], "task": "NER"}
{"text": "During ageing of precipitate , pH increases in the supernatant , while pH decreases for precipitation with excess of palmitate .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [117, 126]}], "task": "NER"}
{"text": "Increasing pH , as in some aged food products , decreases the solubility , and Ksp ( ' ) = [ Ca ( 2 + ) ] [ Pal ( - ) ] [ OH ( - ) ] is found constant rather than Ksp = [ Ca ( 2 + ) ] [ Pal ( - ) ] ( 2 ) in agreement with an initial precipitation of Ca ( OH ) ( Pal ) , which slowly may convert into Ca ( Pal ) 2 . Ca ( OH ) ( Pal ) has a solubility minimum at physiological ionic strength with Ksp ( ' ) = ( 1 . 4 +/- 0 . 4 ) 10 ( - 16 ) M ( 3 ) .", "entity": [{"entity": "Ca ( 2 + ) ] [ Pal ( - ) ] [ OH ( - )", "entity_type": "Chemical", "pos": [93, 130]}, {"entity": "[ Ca ( 2 + ) ] [ Pal ( - ) ] ( 2 )", "entity_type": "Chemical", "pos": [169, 203]}, {"entity": "Ca ( OH ) ( Pal )", "entity_type": "Chemical", "pos": [250, 267]}, {"entity": "Ca ( Pal ) 2 . Ca ( OH ) ( Pal )", "entity_type": "Chemical", "pos": [300, 332]}], "task": "NER"}
{"text": "X - ray diffraction showed a d - spacing of 44 . 15 A ( different from 45 . 2 A reported for Ca ( Pal ) 2 ) , and infrared spectroscopy confirmed the presence of a hydroxy group .", "entity": [{"entity": "Ca ( Pal ) 2", "entity_type": "Chemical", "pos": [93, 105]}, {"entity": "hydroxy", "entity_type": "Chemical", "pos": [164, 171]}], "task": "NER"}
{"text": "Sensory quality and compositional characteristics of blackcurrant juices produced by different processes .", "entity": [], "task": "NER"}
{"text": "Effects of enzymatic and non - enzymatic juice pressing on key orosensory and chemical quality factors of blackcurrant juices were studied in laboratory scale using berries of five different cultivars ( Mortti , Mikael , Marski , Ola and Breed15 ) .", "entity": [], "task": "NER"}
{"text": "Enzymatic processing increased the juice yield by 10 - 22 % and the content of various phenolic compounds in juice by 4 - 10 - fold as compared to the non - enzymatic process .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Higher intensity of the mouth - drying astringency of the enzyme - aided juice was the most significant orosensory difference between the processes .", "entity": [], "task": "NER"}
{"text": "Juices of different blackcurrant cultivars varied in sweetness , sourness and bitterness .", "entity": [], "task": "NER"}
{"text": "The most intensive sensory attributes of the juices were sourness and puckering astringency regardless of processing method .", "entity": [], "task": "NER"}
{"text": "They correlated positively with each other and were contributed by acid content and pH .", "entity": [], "task": "NER"}
{"text": "In enzyme - aided juices , the contents of flavonol glycosides and hydroxycinnamic acids were associated with mouth - drying astringency , and sugar / acid ratio correlated with sweetness .", "entity": [{"entity": "flavonol glycosides", "entity_type": "Chemical", "pos": [43, 62]}, {"entity": "hydroxycinnamic acids", "entity_type": "Chemical", "pos": [67, 88]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [143, 148]}], "task": "NER"}
{"text": "These correlations were less clear in non - enzyme juices possibly due to lower content of phenolic compounds and the high content of pectin .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "Nuclear positioning .", "entity": [], "task": "NER"}
{"text": "The nucleus is the largest organelle and is commonly depicted in the center of the cell .", "entity": [], "task": "NER"}
{"text": "Yet during cell division , migration , and differentiation , it frequently moves to an asymmetric position aligned with cell function .", "entity": [], "task": "NER"}
{"text": "We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it .", "entity": [], "task": "NER"}
{"text": "The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins .", "entity": [], "task": "NER"}
{"text": "Finally , we discuss how nuclear position may influence cellular organization and signaling pathways .", "entity": [], "task": "NER"}
{"text": "Antibodies targeting extracellular domain of connexins for studies of hemichannels .", "entity": [], "task": "NER"}
{"text": "Hemichannels are transmembrane channels composed of either a connexin or pannexin hexamer .", "entity": [], "task": "NER"}
{"text": "The docking of the extracellular domains of connexin hemichannels contributed by neighboring cells forms a gap junction channel that joins the cytoplasm of adjacent cells .", "entity": [], "task": "NER"}
{"text": "Connexins are expressed ubiquitously in different organs , but some subtypes are expressed exclusively in certain tissues and tumors .", "entity": [], "task": "NER"}
{"text": "Both gap junction channels and hemichannels participate in diverse physiological and pathological responses .", "entity": [], "task": "NER"}
{"text": "However , the lack of specific reagents that inhibit only gap junction channels or hemichannels is a challenge that makes it different to discern the specific roles of either channel .", "entity": [], "task": "NER"}
{"text": "Fortunately , the available information regarding the connexin sequence , secondary and tertiary structure , and their biochemical and physiological properties permits the development of strategies to block exclusively the hemichannel activity exclusively , with no effect on gap junction activity .", "entity": [], "task": "NER"}
{"text": "This task is accomplished through the use of specifics antibodies that target the extracellular sites of desired connexin subtype .", "entity": [], "task": "NER"}
{"text": "However , the underlying mechanism of how antibodies targeting extracellular connexin epitopes actually inhibit hemichannels remains unknown .", "entity": [], "task": "NER"}
{"text": "Although these antibodies are being used for detecting and blocking of hemichannels in normal and tumor cells , they can also be potentially used for tissue - specific treatment and drug delivery in clinical applications .", "entity": [], "task": "NER"}
{"text": "In this article , we will first review the literature concerning the structure of connexins and the unique properties of extracellular loop domains of the connexins .", "entity": [], "task": "NER"}
{"text": "Furthermore , we will discuss briefly the development of connexin ( Cx ) 43 ( E2 ) antibody , a specific antibody which detects the second extracellular loop of Cx43 and specifically prevents the opening of Cx43 hemichannels .", "entity": [], "task": "NER"}
{"text": "We will then summarize the reported studies of specific reagents used for the inhibition of connexin hemichannels including antibodies developed against extracellular loop domains .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' Connexin based channels ' .", "entity": [], "task": "NER"}
{"text": "Identification of pyrrolo [ 2 , 3 - g ] indazoles as new Pim kinase inhibitors .", "entity": [{"entity": "pyrrolo [ 2 , 3 - g ] indazoles", "entity_type": "Chemical", "pos": [18, 49]}], "task": "NER"}
{"text": "The synthesis and Pim kinase inhibition potency of a new series of pyrrolo [ 2 , 3 - g ] indazole derivatives is described .", "entity": [{"entity": "pyrrolo [ 2 , 3 - g ] indazole", "entity_type": "Chemical", "pos": [67, 97]}], "task": "NER"}
{"text": "The results obtained in this preliminary structure - activity relationship study pointed out that sub - micromolar Pim - 1 and Pim - 3 inhibitory potencies could be obtained in this series , more particularly for compounds 10 and 20 , showing that pyrrolo [ 2 , 3 - g ] indazole scaffold could be used for the development of new potent Pim kinase inhibitors .", "entity": [{"entity": "pyrrolo [ 2 , 3 - g ] indazole", "entity_type": "Chemical", "pos": [248, 278]}], "task": "NER"}
{"text": "Molecular modeling experiments were also performed to study the binding mode of these compounds in Pim - 3 ATP - binding pocket .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "The bizarre pharmacology of the ATP release channel pannexin1 .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Pannexins were originally thought to represent a second and redundant family of gap junction proteins in addition to the well characterized connexins .", "entity": [], "task": "NER"}
{"text": "However , it is now evident that pannexins function as unapposed membrane channels and the major role of Panx1 is that of an ATP release channel .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [125, 128]}], "task": "NER"}
{"text": "Despite the contrasting functional roles , connexins , innexins and pannexins share pharmacological properties .", "entity": [], "task": "NER"}
{"text": "Most gap junction blockers also attenuate the function of Panx1 , including carbenoxolone , mefloquine and flufenamic acid .", "entity": [{"entity": "carbenoxolone", "entity_type": "Chemical", "pos": [76, 89]}, {"entity": "mefloquine", "entity_type": "Chemical", "pos": [92, 102]}, {"entity": "flufenamic acid", "entity_type": "Chemical", "pos": [107, 122]}], "task": "NER"}
{"text": "However , in contrast to connexin based gap junction channels , Panx1 channel activity can be attenuated by several groups of drugs hitherto considered very specific for other proteins .", "entity": [], "task": "NER"}
{"text": "The drugs affecting Panx1 channels include several transport inhibitors , chloride channel blockers , mitochondrial inhibitors , P2X7 receptor ligands , inflammasome inhibitors and malaria drugs .", "entity": [{"entity": "chloride", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "These observations indicate that Panx1 may play an extended role in a wider spectrum of physiological functions .", "entity": [], "task": "NER"}
{"text": "Alternatively , Panx1 may share structural domains with other proteins , not readily revealed by sequence alignments .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' Connexin based channels '", "entity": [], "task": "NER"}
{"text": "Angiotensin - ( 1 - 7 ) inhibits autophagy in the brain of spontaneously hypertensive rats .", "entity": [], "task": "NER"}
{"text": "Autophagy is an important cellular process that mediates lysosomal degradation of damaged organelles , which is activated in response to a variety of stress - related diseases , including hypertension .", "entity": [], "task": "NER"}
{"text": "The basal level of autophagy plays an important role in the maintenance of cellular homeostasis , whereas excessive autophagic activity leads to cell death and is considered as a contributing factor to several disorders .", "entity": [], "task": "NER"}
{"text": "Recent works have demonstrated that Angiotensin - ( 1 - 7 ) [ Ang - ( 1 - 7 ) ] exerted its neuroprotective effects by modulating classic components of renin - angiotensin system associated with reducing oxidative stress and apoptosis in brains of spontaneously hypertensive rats ( SHRs ) .", "entity": [], "task": "NER"}
{"text": "However , the effect of Ang - ( 1 - 7 ) on autophagic activity in brain of hypertensive individual remains unclear .", "entity": [], "task": "NER"}
{"text": "In this study , Wistar - Kyoto rats received intracerebroventricular ( I . C . V . ) infusion of artificial cerebrospinal fluid ( aCSF ) while SHRs received I . C . V . infusion of aCSF , Ang - ( 1 - 7 ) , Mas receptor antagonist A - 779 , or angiotensin II type 2 receptor antagonist PD123319 for 4 weeks .", "entity": [{"entity": "A - 779", "entity_type": "Chemical", "pos": [230, 237]}, {"entity": "PD123319", "entity_type": "Chemical", "pos": [285, 293]}], "task": "NER"}
{"text": "Brain tissues were collected and analyzed by western blotting analysis , immunofluorescence assay , and transmission electron microscopic examination .", "entity": [], "task": "NER"}
{"text": "Our study showed that infusion of Ang - ( 1 - 7 ) for 4 weeks inhibited the increase of microtubule - associated protein 1 light chain 3 ( LC3 ) - II and Beclin - 1 levels , as well as the autophagosome formation in SHR brain .", "entity": [], "task": "NER"}
{"text": "Meanwhile , the reduction of p62 expression in SHR brain was also reversed by Ang - ( 1 - 7 ) .", "entity": [], "task": "NER"}
{"text": "Of note , the anti - autophagic effects of Ang - ( 1 - 7 ) were independent of blood pressure reduction and can be inhibited by A - 779 and PD123319 .", "entity": [{"entity": "A - 779", "entity_type": "Chemical", "pos": [128, 135]}, {"entity": "PD123319", "entity_type": "Chemical", "pos": [140, 148]}], "task": "NER"}
{"text": "These findings suggest that treatment with Ang - ( 1 - 7 ) may be useful to prevent hypertension - induced excessive autophagic activation in brain .", "entity": [], "task": "NER"}
{"text": "Steroidal glycosides from the bulbs of Fritillaria meleagris and their cytotoxic activities .", "entity": [{"entity": "Steroidal glycosides", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "Steroidal glycosides ( 1 - 18 ) , including 10 new compounds ( 1 - 10 ) , were isolated from the bulbs of Fritillaria meleagris ( Liliaceae ) .", "entity": [{"entity": "Steroidal glycosides", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "The structures of the new compounds were determined by two - dimensional ( 2D ) NMR analysis , and by hydrolytic cleavage followed by spectroscopic and chromatographic analysis .", "entity": [], "task": "NER"}
{"text": "The isolated compounds and their aglycones were evaluated for cytotoxic activity against HL - 60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells .", "entity": [], "task": "NER"}
{"text": "Morphological observation and flow cytometry analysis showed that 5 beta - spirostanol glycoside ( 2 ) and a cholestane derivative ( 17a ) induced apoptotic cell death in HL - 60 cells through different mechanisms of action .", "entity": [{"entity": "5 beta - spirostanol glycoside", "entity_type": "Chemical", "pos": [66, 96]}, {"entity": "cholestane", "entity_type": "Chemical", "pos": [109, 119]}], "task": "NER"}
{"text": "Furthermore , the ( 22R ) - spirosolanol glycoside ( 11 ) selectively induced apoptosis in A549 cells without affecting the caspase - 3 activity level .", "entity": [{"entity": "( 22R ) - spirosolanol glycoside", "entity_type": "Chemical", "pos": [18, 50]}], "task": "NER"}
{"text": "Arrhythmogenic effect of a crude extract from sea anemone Condylactis gigantea : Possible involvement of rErg1 channels .", "entity": [], "task": "NER"}
{"text": "Sea anemones possess a number of peptide toxins that target ion channels which provide powerful tools to study the molecular basis of diverse signaling pathways .", "entity": [], "task": "NER"}
{"text": "It is also acknowledged that currents through Erg1 K ( + ) channels in cardiac myocytes are important for electrical stability of the heart and alterations in its activity has been linked to the onset of a potentially life - threatening heart condition named long QT syndrome type 2 .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "Here , we report that a crude extract from sea anemone Condylactis gigantea significantly increases the QT interval and has arrhythmogenic effects in the rat heart .", "entity": [], "task": "NER"}
{"text": "Furthermore , a bioassay - guided purification procedure allowed the isolation of a chromatographic fraction containing a major component with a molecular mass of 4478 Da from the crude extract , which causes a significant inhibition of whole - cell patch - clamp currents through recombinant Erg1 channels , responsible of the rapid delayed rectifying current crucial for electrical activity in the heart .", "entity": [], "task": "NER"}
{"text": "Further studies could provide relevant information on the molecular mechanism of C . gigantea peptide toxins which represent promising tools in studying the physiology of diverse ion channels .", "entity": [], "task": "NER"}
{"text": "Delivery of definable number of drug or growth factor loaded poly ( dl - lactic acid - co - glycolic acid ) microparticles within human embryonic stem cell derived aggregates .", "entity": [{"entity": "poly ( dl - lactic acid - co - glycolic acid )", "entity_type": "Chemical", "pos": [61, 107]}], "task": "NER"}
{"text": "Embryoid bodies ( EBs ) generated from embryonic stem cells are used to study processes of differentiation within a three dimensional ( 3D ) cell environment .", "entity": [], "task": "NER"}
{"text": "In many instances however , EBs are dispersed to single cell suspensions with a subsequent monolayer culture .", "entity": [], "task": "NER"}
{"text": "Moreover , where the 3D integrity of an EB is maintained , cytokines or drugs of interest to stimulate differentiation are often added directly to the culture medium at fixed concentrations and effects are usually limited to the outer layers of the EB .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to create an EB model with localised drug and or growth factor delivery directly within the EB .", "entity": [], "task": "NER"}
{"text": "Using poly ( DL - lactic acid - co - glycolic acid ) microparticles ( MPs ) with an average diameter of 13 mu m , we have demonstrated controllable incorporation of defined numbers of MPs within human ES cell derived EBs , down to 1 MP per EB .", "entity": [{"entity": "poly ( DL - lactic acid - co - glycolic acid )", "entity_type": "Chemical", "pos": [6, 52]}], "task": "NER"}
{"text": "This was achieved by coating MPs with human ES cell lysate and centrifugation of specific ratios of ES cells and MPs to form 3D aggregates .", "entity": [], "task": "NER"}
{"text": "Using MPs loaded with simvastatin ( pro or active drug ) or BMP - 2 , we have demonstrated osteogenic differentiation within the 3D aggregates , maintained in culture for up to 21days , and quantified by real time QPCR for osteocalcin .", "entity": [{"entity": "simvastatin", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "Immunostaining for RUNX2 and osteocalcin , and also histochemical staining with picrosirius red to demonstrate collage type 1 and Alizarin red to demonstrate calcium / mineralisation further demonstrated osteogenic differentiation and revealed regional staining associated with the locations of MPs within the aggregates .", "entity": [{"entity": "Alizarin red", "entity_type": "Chemical", "pos": [130, 142]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [158, 165]}], "task": "NER"}
{"text": "We also demonstrated endothelial differentiation within human ES cell - derived aggregates using VEGF loaded MPs .", "entity": [], "task": "NER"}
{"text": "In conclusion , we demonstrate an effective and reliable approach for engineering stem aggregates with definable number of MPs within the 3D cellular structure .", "entity": [], "task": "NER"}
{"text": "We also achieved localised osteogenic and endothelial differentiation associated with MPs releasing encapsulated drug molecules or cytokines directly within the cell aggregate .", "entity": [], "task": "NER"}
{"text": "This provides a powerful tool for controlling and investigating differentiation within 3D cell cultures and has applications to drug delivery , drug discovery , stem cell biology , tissue engineering and regenerative medicine .", "entity": [], "task": "NER"}
{"text": "Raft forming system - An upcoming approach of gastroretentive drug delivery system .", "entity": [], "task": "NER"}
{"text": "In recent era various technologies have been made in research and development of controlled release oral drug delivery system to overcome various physiological difficulties such as variation in gastric retention and emptying time .", "entity": [], "task": "NER"}
{"text": "To overcome this drawback and to maximize the oral absorption of various drugs , novel drug delivery systems have been developed .", "entity": [], "task": "NER"}
{"text": "Gastroretentive drug delivery system is facing many challenges which can be overcome by upcoming newly emerging approach i . e . raft forming system .", "entity": [], "task": "NER"}
{"text": "The purpose of writing this review is to focus on recent development of stomach specific floating drug delivery system to circumvent the difficulties associated with formulation design .", "entity": [], "task": "NER"}
{"text": "Various gastroretentive approaches that have been developed till now are also discussed .", "entity": [], "task": "NER"}
{"text": "The present study provides valuable information & highlights advances in this raft forming system .", "entity": [], "task": "NER"}
{"text": "This review attempts to discuss various factors like physiological factors , physicochemical factors and formulation factors to be considered in the development of the raft forming system .", "entity": [], "task": "NER"}
{"text": "Different types of smart polymers used for their formulation have also been summarized .", "entity": [], "task": "NER"}
{"text": "The review focuses on the mechanism , formulation and development of the raft forming system .", "entity": [], "task": "NER"}
{"text": "This review also summarizes the studies to evaluate the performance and application of these systems .", "entity": [], "task": "NER"}
{"text": "The study finally highlights advantages , disadvantages , and marketed preparation of the raft forming system .", "entity": [], "task": "NER"}
{"text": "Analysis of the enhanced oral bioavailability of fenofibrate lipid formulations in fasted humans using an in vitro - in silico - in vivo approach .", "entity": [{"entity": "fenofibrate", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Lipid - based formulations have established a significant role in the formulation of poorly soluble drugs for oral administration .", "entity": [], "task": "NER"}
{"text": "In order to better understand their potential advantages over solid oral dosage forms , we studied the solubility and dissolution / precipitation characteristics of three self - microemulsifying drug delivery system ( SMEDDS ) formulations and one suspension of micronized fenofibrate in lipid excipients , for which pharmacokinetic studies had already been reported in the open literature .", "entity": [{"entity": "fenofibrate", "entity_type": "Chemical", "pos": [273, 284]}], "task": "NER"}
{"text": "The in vitro dispersion / dissolution studies were carried out in biorelevant media using USP II apparatus .", "entity": [], "task": "NER"}
{"text": "These were followed up by in silico simulations using STELLA (R) software , in which not only dispersion / dissolution , but also the precipitation and re - dissolution of fenofibrate was taken into account .", "entity": [{"entity": "fenofibrate", "entity_type": "Chemical", "pos": [172, 183]}], "task": "NER"}
{"text": "While unformulated drug exhibited poor solubility ( 0 . 22 mu g / mL in FaSSGF and 4 . 31 mu g / mL in FaSSIF - V2 ( PO4 ) ) and dissolved less than 2 % in dissolution tests , the solubility of fenofibrate in the presence of the lipid excipients increased dramatically ( e . g . , to 65 . 44 mu g / mL in the presence of the Myritol 318 / TPGS / Tween 80 SMEDDS ) and there was an attendant increase in the dissolution ( over 80 % from capsules containing the Myritol 318 / TPGS / Tween 80 SMEDDS and about 20 % from the dispersion of fenofibrate in lipid excipients ) .", "entity": [{"entity": "V2 ( PO4 )", "entity_type": "Chemical", "pos": [112, 122]}, {"entity": "fenofibrate", "entity_type": "Chemical", "pos": [194, 205]}, {"entity": "Myritol 318", "entity_type": "Chemical", "pos": [325, 336]}, {"entity": "TPGS", "entity_type": "Chemical", "pos": [339, 343]}, {"entity": "Tween 80", "entity_type": "Chemical", "pos": [346, 354]}, {"entity": "Myritol 318", "entity_type": "Chemical", "pos": [460, 471]}, {"entity": "TPGS", "entity_type": "Chemical", "pos": [474, 478]}, {"entity": "Tween 80", "entity_type": "Chemical", "pos": [481, 489]}, {"entity": "fenofibrate", "entity_type": "Chemical", "pos": [535, 546]}], "task": "NER"}
{"text": "For the four lipid - based fenofibrate formulations studied , combining in vitro data in biorelevant media with in silico simulation resulted in accurate prediction of the in vivo human plasma profiles .", "entity": [{"entity": "fenofibrate", "entity_type": "Chemical", "pos": [27, 38]}], "task": "NER"}
{"text": "The point estimates of Cmax and AUC ratio calculated from the in silico and in vivo plasma profiles fell within the 0 . 8 - 1 . 25 range for the SMEDDS solution and capsule formulations , suggesting an accurate simulation of the in vivo profiles .", "entity": [], "task": "NER"}
{"text": "This similarity was confirmed by calculation of the respective f2 factors .", "entity": [], "task": "NER"}
{"text": "Sensitivity analysis of the simulation profiles revealed that the SMEDDS formulations had virtually removed any dependency of absorption on the dissolution rate in the small intestine , whereas for the dispersion in lipid excipients , this barrier remained .", "entity": [], "task": "NER"}
{"text": "Such results pave the way to optimizing the performance of oral lipid - based formulations via an in vitro - in silico - in vivo approach .", "entity": [], "task": "NER"}
{"text": "Evaluation of the pharmacodynamics and pharmacokinetics of brucine following transdermal administration .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "Before the design of brucine - containing transdermal formulations , the pharmacodynamics and pharmacokinetics of brucine following transdermal administration should be evaluated .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [21, 28]}, {"entity": "brucine", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "In this study , the effect of addition of ethanol on solubility of bruicne was investigated and 20 % ethanol was added into PBS to obtain 10mg / mL brucine solution .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "bruicne", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [101, 108]}, {"entity": "brucine", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "Then three transdermal doses ( 10 , 20 and 40mg / kg ) were administered to mice to evaluate pharmacological activity .", "entity": [], "task": "NER"}
{"text": "It had been demonstrated that brucine possessed analgesic and anti - inflammatory activity in a dose - dependent manner .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Cytotoxicities of brucine against various tumor cells including skin tumor cell were also compared in vitro .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [18, 25]}], "task": "NER"}
{"text": "Brucine was found to possess antitumor activity in a concentration and time - dependent manner and gastrointestinal tumor cells seemed to be more sensitive to brucine .", "entity": [{"entity": "Brucine", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "brucine", "entity_type": "Chemical", "pos": [159, 166]}], "task": "NER"}
{"text": "Then in vitro skin permeation behavior and in vivo pharmacokinetics following transdermal administration were further investigated .", "entity": [], "task": "NER"}
{"text": "The cumulative amounts of brucine across mouse skin in vitro were found to be higher than 90 % .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [26, 33]}], "task": "NER"}
{"text": "The absolute bioavailability of brucine was determined to be 40 . 83 % .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [32, 39]}], "task": "NER"}
{"text": "And compared with intravenous administration , MRT and T1 / 2 values were increased about 8 ~ 12 - fold by transdermal route .", "entity": [], "task": "NER"}
{"text": "Moreover , fluctuations of drug levels were found to be significantly decreased in tissues , especially in brain .", "entity": [], "task": "NER"}
{"text": "Finally , no dermal toxicity of brucine was observed .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [32, 39]}], "task": "NER"}
{"text": "The results of this study indicated that transdermal administration might be beneficial for the sustained efficacy and reduced toxicity of brucine .", "entity": [{"entity": "brucine", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "The vascular protective properties of kinsenoside isolated from Anoectochilus roxburghii under high glucose condition .", "entity": [{"entity": "kinsenoside", "entity_type": "Chemical", "pos": [38, 49]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "Anoectochilus roxburghii is a traditional Chinese herb used for the treatment of diabetes and some other diseases .", "entity": [], "task": "NER"}
{"text": "The vascular protective effect of its major active ingredient , kinsenoside , in high glucose conditions was investigated in in vivo and in vitro experiments .", "entity": [{"entity": "kinsenoside", "entity_type": "Chemical", "pos": [64, 75]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [86, 93]}], "task": "NER"}
{"text": "In in vivo tests , kinsenoside ( 50 and 100mg / kg ) efficiently lowered blood glucose and cholesterol levels and it enhanced the oxidation resistance of diabetic mice induced by streptozotocin .", "entity": [{"entity": "kinsenoside", "entity_type": "Chemical", "pos": [19, 30]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [91, 102]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [179, 193]}], "task": "NER"}
{"text": "In the in vitro assay , kinsenoside ( 20 and 50 mu g / mL ) markedly inhibited changes in various biochemical substances ( nitric oxide ( NO ) , lactic dehydrogenase ( LDH ) , superoxide dismutase ( SOD ) , and catalase ( CAT ) ) in human umbilical vein endothelial cells ( HUVECs ) damaged by high glucose ( 35mM ) and restored vascular endothelial structure by balancing the matrix metalloproteinases - the tissue inhibitors of matrix metalloproteinases ( MMP - TIMP ) system .", "entity": [{"entity": "kinsenoside", "entity_type": "Chemical", "pos": [24, 35]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [123, 135]}, {"entity": "NO", "entity_type": "Chemical", "pos": [138, 140]}, {"entity": "lactic", "entity_type": "Chemical", "pos": [145, 151]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [176, 186]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [299, 306]}], "task": "NER"}
{"text": "The vascular protective effects of kinsenoside were speculated to be attributed to oxidative stress inhibition and the reduction of nuclear factor kappa B ( NF - kappa B ) mRNA expression levels in high glucose conditions .", "entity": [{"entity": "kinsenoside", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [203, 210]}], "task": "NER"}
{"text": "Moreover , histological examination , including hematoxylin - eosin ( H & E ) staining , masson trichrome ( Masson ) staining , and periodic Schiff - methenamine ( PASM ) staining , greatly supported the morphological and functional amelioration of diabetes - related changes in mice aortas after kinsenoside ( 20 and 50 mu g / mL ) treatment .", "entity": [{"entity": "hematoxylin", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "eosin", "entity_type": "Chemical", "pos": [62, 67]}, {"entity": "methenamine", "entity_type": "Chemical", "pos": [150, 161]}, {"entity": "kinsenoside", "entity_type": "Chemical", "pos": [297, 308]}], "task": "NER"}
{"text": "These results indicated that kinsenoside might be a promising agent for the treatment of diabetic vascular disease .", "entity": [{"entity": "kinsenoside", "entity_type": "Chemical", "pos": [29, 40]}], "task": "NER"}
{"text": "The application of a DNA - based identification technique to over - the - counter herbal medicines .", "entity": [], "task": "NER"}
{"text": "Reliable methods to identify medicinal plant material are becoming more important in an increasingly regulated market place .", "entity": [], "task": "NER"}
{"text": "DNA - based methods have been recognised as a valuable tool in this area with benefits such as being unaffected by the age of the plant material , growth conditions and harvesting techniques .", "entity": [], "task": "NER"}
{"text": "It is possible that the methods of production used for medicinal plant products will degrade or remove DNA .", "entity": [], "task": "NER"}
{"text": "So how applicable are these techniques to processed medicinal plant products ?", "entity": [], "task": "NER"}
{"text": "A simple PCR - based identification technique has been developed for St .", "entity": [], "task": "NER"}
{"text": "John ' s Wort , Hypericum perforatum L .", "entity": [], "task": "NER"}
{"text": "Thirteen St .", "entity": [], "task": "NER"}
{"text": "John ' s Wort products were purchased including capsules , tablets and tinctures .", "entity": [], "task": "NER"}
{"text": "DNA was extracted from each product , and the species specific PCR test conducted .", "entity": [], "task": "NER"}
{"text": "DNA was successfully extracted from all thirteen products , using a fast and efficient modified method for extracting DNA from tinctures .", "entity": [], "task": "NER"}
{"text": "Only four products yielded the full length ITS region ( 850bp ) due to the quality of the DNA .", "entity": [], "task": "NER"}
{"text": "All of the products tested positive for H . perforatum DNA .", "entity": [], "task": "NER"}
{"text": "DNA - based identification methods can complement existing methods of authentication .", "entity": [], "task": "NER"}
{"text": "This paper shows that these methods are applicable to a wide range of processed products , provided that they are designed to account for the possibility of DNA degradation .", "entity": [], "task": "NER"}
{"text": "Bioactive carbazole alkaloids from Murraya koenigii ( L . ) Spreng .", "entity": [{"entity": "carbazole alkaloids", "entity_type": "Chemical", "pos": [10, 29]}], "task": "NER"}
{"text": "Four new carbazole alkaloids ( 1 - 4 ) and fourteen known carbazole alkaloids ( 5 - 18 ) were isolated from Murraya koenigii .", "entity": [{"entity": "carbazole alkaloids", "entity_type": "Chemical", "pos": [9, 28]}, {"entity": "carbazole alkaloids", "entity_type": "Chemical", "pos": [58, 77]}], "task": "NER"}
{"text": "Their structures were elucidated on the basis of extensive spectroscopic analysis .", "entity": [], "task": "NER"}
{"text": "Compounds 4 , 6 , 16 , and 17 ( 10 mu M ) had moderate hepatoprotective activities against d - galactosamine - induced HL - 7702 cell damage .", "entity": [{"entity": "d - galactosamine", "entity_type": "Chemical", "pos": [91, 108]}], "task": "NER"}
{"text": "Compounds 11 , 12 and 18 showed significant PTP1B inhibitory activity with IC50 values of 1 . 773 , 1 . 875 and 2 . 286 mu M , respectively .", "entity": [], "task": "NER"}
{"text": "Curcumin attenuates allergic airway inflammation by regulation of CD4 ( + ) CD25 ( + ) regulatory T cells ( Tregs ) / Th17 balance in ovalbumin - sensitized mice .", "entity": [{"entity": "Curcumin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin ( OVA ) - induced allergic inflammation in a mouse model of allergic asthma .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "Asthma mice model was established by ovalbumin .", "entity": [], "task": "NER"}
{"text": "A total of 60 mice were randomly assigned to six experimental groups : control , model , dexamethasone ( 2mg / kg ) , and curcumin ( 50mg / kg , 100mg / kg , 200mg / kg ) .", "entity": [{"entity": "dexamethasone", "entity_type": "Chemical", "pos": [89, 102]}, {"entity": "curcumin", "entity_type": "Chemical", "pos": [122, 130]}], "task": "NER"}
{"text": "Airway resistance ( Raw ) was measured by the forced oscillation technique , differential cell count in BAL fluid ( BALF ) was measured by Wright - Giemsa staining , histological assessment was measured by hematoxylin and eosin ( HE ) staining , BALF levels of Treg / Th17 cytokines were measured by enzyme - linked immunosorbent assay , Treg cells and Th17 cells were evaluated by flow cytometry ( FCM ) .", "entity": [{"entity": "hematoxylin", "entity_type": "Chemical", "pos": [206, 217]}, {"entity": "eosin", "entity_type": "Chemical", "pos": [222, 227]}], "task": "NER"}
{"text": "Our study demonstrated that curcumin inhibited OVA - induced increases in eosinophil count ; interleukin ( IL ) - 17A level were recovered in bronchoalveolar lavage fluid increased IL - 10 level in bronchoalveolar lavage fluid .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [28, 36]}], "task": "NER"}
{"text": "Histological studies demonstrated that curcumin substantially inhibited OVA - induced eosinophilia in lung tissue .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "Flow cytometry ( FCM ) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "The results in vivo show ovalbumin - induced significantly broke Treg / Th17 balance ; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg / Th17 balance .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [41, 49]}], "task": "NER"}
{"text": "Identification , assessment and management of \" endocrine disruptors \" in wildlife in the EU substance legislation - Discussion paper from the German Federal Environment Agency ( UBA ) .", "entity": [], "task": "NER"}
{"text": "A discussion paper was developed by a panel of experts of the German Federal Environment Agency ( UBA ) contributing to the on - going debate on the identification , assessment and management of endocrine disruptors with a view to protect wildlife according to the EU substance legislation ( plant protection products , biocides , industrial chemicals ) .", "entity": [], "task": "NER"}
{"text": "Based on a critical synthesis of the state - of - the - art regarding regulatory requirements , testing methods , assessment schemes , decision - making criteria and risk management options , we advise an appropriate and consistent implementation of this important subject into existing chemicals legislation in Europe .", "entity": [], "task": "NER"}
{"text": "Our proposal for a balanced risk management of endocrine disruptors essentially advocates transparent regulatory decision making based on a scientifically robust weight of evidence approach and an adequate risk management consistent across different legislations .", "entity": [], "task": "NER"}
{"text": "With respect to the latter , a more explicit consideration of the principle of proportionality of regulatory decision making and socio - economic benefits in the on - going debate is further encouraged .", "entity": [], "task": "NER"}
{"text": "The C - Terminal Region of Cytoplasmic Polyadenylation Element Binding Protein Is a ZZ Domain with Potential for Protein - Protein Interactions .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}], "task": "NER"}
{"text": "Cytoplasmic polyadenylation element binding protein ( CPEB ) provides temporal and spatial control of protein synthesis required for early development and neuronal synaptic plasticity .", "entity": [], "task": "NER"}
{"text": "CPEB regulates protein expression by inhibiting polyadenylation of selected mRNA transcripts , which prevents binding of the ribosome for protein synthesis .", "entity": [], "task": "NER"}
{"text": "Two RNA recognition motif domains and a C - terminal binuclear zinc - binding domain are required for mRNA binding , but the zinc - binding domain is not required for sequence - specific recognition of the targeted mRNA transcript .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [40, 41]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [125, 129]}], "task": "NER"}
{"text": "The structure and function of the zinc - binding domain of CPEB are unknown .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "The C - terminal region of CPEB may participate in assembly of the ribonucleoprotein complex that includes the scaffold protein , Symplekin , and the cleavage and polyadenylation specificity factor .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}], "task": "NER"}
{"text": "Sumoylation of Symplekin is required for polyadenylation , and both cleavage and polyadenylation specificity factor and poly ( A ) polymerase are sumoylated .", "entity": [], "task": "NER"}
{"text": "The foreshortened poly ( A ) tail is maintained by poly ( A ) ribonuclease , which associates with CPEB .", "entity": [], "task": "NER"}
{"text": "While zinc - binding domains are renowned for nucleic acid recognition , binuclear zinc - binding structural motifs , such as LIM ( Lin - 11 , Isl - 1 , Mec - 3 ) , RING ( really interesting new gene ) , PHD ( plant homeodomain ) and ZZ ( ZZ - type zinc finger ) domains , participate in protein - protein interactions .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [249, 253]}], "task": "NER"}
{"text": "Here , we report the solution structure of the C - terminal zinc - binding domain of CPEB1 ( CPEB1 - ZZ ) , which has a cross - braced zinc binding topology .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [47, 48]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [60, 64]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [135, 139]}], "task": "NER"}
{"text": "The structural similarity to other ZZ domains suggests that the CPEB1 - ZZ domain recruits sumoylated proteins during assembly of the ribonucleoprotein complex prior to mRNA export from the nucleus .", "entity": [], "task": "NER"}
{"text": "Characterization of monomeric and multimeric snake neurotoxins and other bioactive proteins from the venom of the lethal Australian common copperhead ( Austrelaps superbus ) .", "entity": [], "task": "NER"}
{"text": "Envenomation by Australian copperheads results mainly in muscle paralysis largely attributed to the presence of postsynaptic alpha - neurotoxins .", "entity": [], "task": "NER"}
{"text": "However , poorly reversible neurotoxic effects suggest that these venoms may contain snake presynaptic phospholipase A2 neurotoxins ( SPANs ) that irreversibly inhibit neurotransmitter release .", "entity": [], "task": "NER"}
{"text": "Using size - exclusion liquid chromatography , the present study isolated the first multimeric SPAN complex from the venom of the Australian common copperhead , Austrelaps superbus .", "entity": [], "task": "NER"}
{"text": "The multimeric SPAN P - elapitoxin - As1a ( P - EPTX - As1a ) along with two novel monomeric SPANs and a new postsynaptic alpha - neurotoxin were then pharmacologically characterized using the chick biventer cervicis nerve - muscle preparation .", "entity": [], "task": "NER"}
{"text": "All SPANs inhibited nerve - evoked twitch contractions at the neuromuscular junction without inhibiting contractile responses to cholinergic agonists or KCl .", "entity": [{"entity": "KCl", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "These actions are consistent with a prejunctional action to inhibit neurotransmitter release , without direct myotoxicity .", "entity": [], "task": "NER"}
{"text": "Furthermore , the multimeric P - EPTX - As1a caused tetanic ' fade ' in muscle tension under high frequency nerve stimulation , and produced a triphasic alteration to neurotransmitter release .", "entity": [], "task": "NER"}
{"text": "These actions have been previously noted with other multimeric SPAN complexes such as taipoxin .", "entity": [], "task": "NER"}
{"text": "Moreover , the neurotoxic alpha - subunit of P - EPTX - As1a shows high homology to taipoxin alpha - chain .", "entity": [], "task": "NER"}
{"text": "Several other coagulopathic and myotoxic high mass proteins including a class PIII snake venom metalloproteinase , C - type lectin , l - amino acid oxidase , acetylcholinesterase and phospholipase B were also identified that may contribute to the overall toxicity of A . superbus venom .", "entity": [{"entity": "l - amino acid", "entity_type": "Chemical", "pos": [133, 147]}], "task": "NER"}
{"text": "In conclusion , clinicians should be aware that early antivenom intervention might be necessary to prevent the onset of irreversible presynaptic neurotoxicity caused by multimeric and monomeric SPANs and that A . superbus venom is potentially capable of producing coagulopathic and myotoxic effects .", "entity": [], "task": "NER"}
{"text": "Analysis by liquid chromatography - mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7 ( Delta 3 - 5 / T93M ) mouse : A model of Smith - Lemli - Opitz syndrome .", "entity": [{"entity": "sterols", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "oxysterols", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "In this study the sterol and oxysterol profile of newborn brain from the Dhcr7 ( Delta 3 - 5 / T93M ) mouse model of Smith - Lemli - Opitz syndrome ( SLOS ) has been investigated .", "entity": [{"entity": "sterol", "entity_type": "Chemical", "pos": [18, 24]}, {"entity": "oxysterol", "entity_type": "Chemical", "pos": [29, 38]}], "task": "NER"}
{"text": "This is a viable mouse model which is compound heterozygous containing one null allele and one T93M mutation on Dhcr7 .", "entity": [], "task": "NER"}
{"text": "We find the SLOS mouse has reduced levels of cholesterol and desmosterol and increased levels of 7 - and 8 - dehydrocholesterol and of 7 - and 8 - dehydrodesmosterol in brain compared to the wild type .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "desmosterol", "entity_type": "Chemical", "pos": [61, 72]}, {"entity": "7 - and 8 - dehydrocholesterol", "entity_type": "Chemical", "pos": [97, 127]}, {"entity": "7 - and 8 - dehydrodesmosterol", "entity_type": "Chemical", "pos": [135, 165]}], "task": "NER"}
{"text": "The profile of enzymatically formed oxysterols in the SLOS mouse resembles that in the wild type but the level of 24S - hydroxycholesterol , the dominating cholesterol metabolite , is reduced in a similar proportion to that of cholesterol .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [114, 138]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [156, 167]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [227, 238]}], "task": "NER"}
{"text": "A number of oxysterols abundant in the SLOS mouse are probably derived from 7 - dehydrocholesterol , however , the mechanism of their formation is unclear .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "7 - dehydrocholesterol", "entity_type": "Chemical", "pos": [76, 98]}], "task": "NER"}
{"text": "Interrelationship between ATP - binding cassette transporters and oxysterols .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [26, 29]}, {"entity": "oxysterols", "entity_type": "Chemical", "pos": [66, 76]}], "task": "NER"}
{"text": "ATP - binding cassette ( ABC ) transporters constitute a ubiquitous superfamily of membrane proteins responsible for the translocation of several substances across membranes using the chemical energy provided by ATP hydrolysis .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [212, 215]}], "task": "NER"}
{"text": "ABC transporters participate in many physiological and pathophysiological processes , including cholesterol and lipid transportation and multidrug resistance .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [96, 107]}], "task": "NER"}
{"text": "Oxysterols are the products of cholesterol oxidation , formed by both enzymatic and non - enzymatic mechanisms .", "entity": [{"entity": "Oxysterols", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [31, 42]}], "task": "NER"}
{"text": "The role of oxysterols in cholesterol metabolism and several diseases has been widely investigated , but many questions remain to be answered .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [26, 37]}], "task": "NER"}
{"text": "Several lines of evidence link ABC transporter functions with cholesterol and oxysterol metabolism .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [62, 73]}, {"entity": "oxysterol", "entity_type": "Chemical", "pos": [78, 87]}], "task": "NER"}
{"text": "This review discusses ABC transporters , oxysterols , and how they interact with each other .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [41, 51]}], "task": "NER"}
{"text": "Donor substrate specificity of bovine kidney gamma - glutamyltransferase .", "entity": [], "task": "NER"}
{"text": "The enzyme gamma - glutamyltransferase ( GGT ) catalyzes the hydrolysis of the gamma - glutamyl isopeptide bond of glutathione conjugates ( donor substrates ) , releasing glutamic acid , or the transfer of the donor ' s gamma - glutamyl group to an acceptor substrate , such as a dipeptide .", "entity": [{"entity": "gamma - glutamyl", "entity_type": "Chemical", "pos": [11, 27]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [115, 126]}, {"entity": "glutamic acid", "entity_type": "Chemical", "pos": [171, 184]}, {"entity": "gamma - glutamyl", "entity_type": "Chemical", "pos": [220, 236]}, {"entity": "dipeptide", "entity_type": "Chemical", "pos": [280, 289]}], "task": "NER"}
{"text": "The specificity of GGT for xenobiotic donor substrates has not been fully characterized .", "entity": [], "task": "NER"}
{"text": "The transpeptidation activity of bovine kidney GGT was measured with glycylglycine as the acceptor substrate and several glutathione conjugate donor substrates , representative of detoxication products of polycyclic aromatic xenobiotics .", "entity": [{"entity": "glycylglycine", "entity_type": "Chemical", "pos": [69, 82]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "HPLC separation with UV detection was used for quantitation .", "entity": [], "task": "NER"}
{"text": "The commonly - used chromogenic substrate gamma - glutamyl - p - nitroanilide was also tested .", "entity": [{"entity": "gamma - glutamyl - p - nitroanilide", "entity_type": "Chemical", "pos": [42, 77]}], "task": "NER"}
{"text": "Michaelis constants ( Km ) were obtained for 4 - nitrobenzylglutathione ( 0 . 075mM ) , 2 , 4 - dinitrophenylglutathione ( 0 . 30mM ) , 4 - methylbiphenylylglutathione ( 0 . 12mM ) , 1 - menaphthylglutathione ( 0 . 23mM ) , and 9 - methylanthracenylglutathione ( 0 . 22mM ) , indicating a trend towards higher values for bulkier substrates .", "entity": [{"entity": "4 - nitrobenzylglutathione", "entity_type": "Chemical", "pos": [45, 71]}, {"entity": "2 , 4 - dinitrophenylglutathione", "entity_type": "Chemical", "pos": [88, 120]}, {"entity": "4 - methylbiphenylylglutathione", "entity_type": "Chemical", "pos": [136, 167]}, {"entity": "1 - menaphthylglutathione", "entity_type": "Chemical", "pos": [183, 208]}, {"entity": "9 - methylanthracenylglutathione", "entity_type": "Chemical", "pos": [228, 260]}], "task": "NER"}
{"text": "These results provide insight into the capacity of GGT to act in the biotransformation of aromatic compounds , many of which are of toxicological importance .", "entity": [], "task": "NER"}
{"text": "Anti - fibrotic effects of puerarin on CCl4 - induced hepatic fibrosis in rats possibly through the regulation of PPAR - gamma expression and inhibition of PI3K / Akt pathway .", "entity": [{"entity": "puerarin", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [39, 43]}], "task": "NER"}
{"text": "Hepatic fibrosis ( HF ) is a chronic disease , which primarily leads to liver unregulated metabolism .", "entity": [], "task": "NER"}
{"text": "In this study , we aimed to investigate the therapeutic effects of puerarin ( PR ) , an active ingredient from kudzu root , on CCl4 - induced HF rats .", "entity": [{"entity": "puerarin", "entity_type": "Chemical", "pos": [67, 75]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [127, 131]}], "task": "NER"}
{"text": "PR effectively ameliorated the liver metabolic function , resulting in reduced serum enzymatic activities of alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , total - bilirubin ( T - bilirubin ) , extracellular matrix ( ECM ) contents and increased levels of albumin , total - protein ( T - protein ) in HF rats .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [109, 116]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [144, 153]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [189, 198]}, {"entity": "bilirubin", "entity_type": "Chemical", "pos": [205, 214]}], "task": "NER"}
{"text": "Similarly , pathological examination showed that the CCl4 - lesioned liver was mitigated by PR treatments .", "entity": [{"entity": "CCl4", "entity_type": "Chemical", "pos": [53, 57]}], "task": "NER"}
{"text": "Meanwhile , we also detected significantly reduced levels of hydroxyproline ( Hyp ) , type III precollagen ( PCIII ) and collagen I ( Col I ) in the liver tissue of HF rats , whereas the peroxisome proliferator - activated receptor - gamma ( PPAR - gamma ) expression was effectively increased .", "entity": [{"entity": "hydroxyproline", "entity_type": "Chemical", "pos": [61, 75]}, {"entity": "Hyp", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "Moreover , the expression of tissue inhibitor of metal protease - 1 ( TIMP - 1 ) was decreased , while the expression of matrix metalloproteinase - 2 ( MMP - 2 ) was increased .", "entity": [], "task": "NER"}
{"text": "In addition , the expression of p - PI3K and p - Akt was significantly down - regulated by PR treatments .", "entity": [], "task": "NER"}
{"text": "Taken together , PR could attenuate the CCl4 - induced toxicity in the hepatocytes of HF rats .", "entity": [{"entity": "CCl4", "entity_type": "Chemical", "pos": [40, 44]}], "task": "NER"}
{"text": "It played a protective role in the liver tissue probably through regulating the PPAR - gamma expression and blocking the PI3K / Akt pathway to inhibit the excessive deposition of collagen .", "entity": [], "task": "NER"}
{"text": "Dietary exposure of juvenile female mice to polyhalogenated seafood contaminants ( HBCD , BDE - 47 , PCB - 153 , TCDD ) : Comparative assessment of effects in potential target tissues .", "entity": [{"entity": "HBCD", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "BDE - 47", "entity_type": "Chemical", "pos": [90, 98]}, {"entity": "PCB - 153", "entity_type": "Chemical", "pos": [101, 110]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [113, 117]}], "task": "NER"}
{"text": "Fish represents source of nutrients and major dietary vehicle of lipophilic persistent contaminants .", "entity": [], "task": "NER"}
{"text": "The study compared the effects of two legacy and two emerging fish pollutants ( Hexabromocyclododecane HBCD ; 2 , 2 ' , 4 , 4 ' - Tetrabromodiphenyl ether BDE - 47 ; 2 , 2 ' , 4 , 4 ' , 5 , 5 ' - Hexachlorobiphenyl PCB - 153 ; 2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - doxin TCDD ) in juvenile female mice exposed through a salmon based rodent diet for 28days ( dietary doses : HBCD 199mg / kg bw / day ; BDE - 47 450 mu g / kg bw / day ; PCB - 153 195 mu g / kg bw / day ; TCDD 90ng / kg bw / day ) .", "entity": [{"entity": "Hexabromocyclododecane", "entity_type": "Chemical", "pos": [80, 102]}, {"entity": "HBCD", "entity_type": "Chemical", "pos": [103, 107]}, {"entity": "2 , 2 ' , 4 , 4 ' - Tetrabromodiphenyl ether", "entity_type": "Chemical", "pos": [110, 154]}, {"entity": "BDE - 47", "entity_type": "Chemical", "pos": [155, 163]}, {"entity": "2 , 2 ' , 4 , 4 ' , 5 , 5 ' - Hexachlorobiphenyl", "entity_type": "Chemical", "pos": [166, 214]}, {"entity": "PCB - 153", "entity_type": "Chemical", "pos": [215, 224]}, {"entity": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - doxin", "entity_type": "Chemical", "pos": [227, 273]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [274, 278]}, {"entity": "HBCD", "entity_type": "Chemical", "pos": [377, 381]}, {"entity": "BDE - 47", "entity_type": "Chemical", "pos": [404, 412]}, {"entity": "PCB - 153", "entity_type": "Chemical", "pos": [438, 447]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [473, 477]}], "task": "NER"}
{"text": "Dose levels were comparable to previously reported developmental Lowest Observed Adverse Effect Levels .", "entity": [], "task": "NER"}
{"text": "None of the treatments elicited signs of overt toxicity , but HBCD increased relative liver weight .", "entity": [{"entity": "HBCD", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "All compounds caused changes in liver , thymus and thyroid ; spleen was affected by BDE - 47 and PCB - 153 ; no effects were seen in uterus and adrenals .", "entity": [{"entity": "BDE - 47", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "PCB - 153", "entity_type": "Chemical", "pos": [97, 106]}], "task": "NER"}
{"text": "Strongest effects in thyroid follicles were elicited by PCB - 153 , in thymus and liver by BDE - 47 .", "entity": [{"entity": "PCB - 153", "entity_type": "Chemical", "pos": [56, 65]}, {"entity": "BDE - 47", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "HBCD and BDE - 47 induced liver fatty changes , but appeared to be less potent in the other tissues .", "entity": [{"entity": "HBCD", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "BDE - 47", "entity_type": "Chemical", "pos": [9, 17]}], "task": "NER"}
{"text": "HBCD , BDE - 47 and TCDD increased serum testosterone levels and the testosterone / estradiol ratio , suggesting a potential involvement of pathways related to sex steroid biosynthesis and / or metabolism .", "entity": [{"entity": "HBCD", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "BDE - 47", "entity_type": "Chemical", "pos": [7, 15]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [20, 24]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [69, 81]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [84, 93]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [164, 171]}], "task": "NER"}
{"text": "The results support the role of toxicological studies on juvenile rodents in the hazard characterization of chemicals , due to endocrine and / or immune effects .", "entity": [], "task": "NER"}
{"text": "Gambogic acid inhibits angiogenesis through inhibiting PHD2 - VHL - HIF - 1 alpha pathway .", "entity": [{"entity": "Gambogic acid", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Our previous studies revealed that gambogic acid ( GA ) , the major active ingredient of gamboge , possessed antiangiogenic activities .", "entity": [{"entity": "gambogic acid", "entity_type": "Chemical", "pos": [35, 48]}], "task": "NER"}
{"text": "In this study , we further explored the mechanism of inhibition effects of GA in tumor angiogenesis .", "entity": [], "task": "NER"}
{"text": "The results of luciferase , RT - PCR , and ELISA assays indicated that GA significantly decreased transcription activation , mRNA expression , and secretion of VEGF in hypoxia .", "entity": [], "task": "NER"}
{"text": "We detected that GA had no effect on mRNA level of HIF - 1 alpha which targets VEGF gene , but the increase of HIF - 1 alpha protein expression in hypoxia was repressed by GA , which can be reversed by proteasomal inhibitor MG132 and siRNA of VHL .", "entity": [], "task": "NER"}
{"text": "But GA exhibited no effect on expression of VHL both in normoxia and hypoxia .", "entity": [], "task": "NER"}
{"text": "HIF prolyl hydroxylases ( PHD enzymes ) act as oxygen sensors regulating HIF , and hence angiogenesis .", "entity": [{"entity": "prolyl", "entity_type": "Chemical", "pos": [4, 10]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "Our results showed that GA potentially enhanced level of PHD2 , the most important HIF hydroxylase , and showed no effect on PHD1 and PHD3 .", "entity": [], "task": "NER"}
{"text": "Transient transfection of siRNA of PHD2 could eliminate GA - induced VEGF secretion increase .", "entity": [], "task": "NER"}
{"text": "Growth of HepG2 xenografts in BALB / cA nude mice was inhibited by GA and angiogenesis was repressed significantly in tumor xenografts by immunohistochemical staining of CD - 31 , a vascular endothelial marker , accompanied with decrease of HIF - 1 alpha and increase of PHD2 expression in tissue extracts .", "entity": [], "task": "NER"}
{"text": "This work provides the demonstration that GA shows anti - angiogenic effects via inhibiting PHD2 - VHL - HIF - 1 alpha pathway .", "entity": [], "task": "NER"}
{"text": "Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus .", "entity": [{"entity": "Coumarins", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "benzimidazoles", "entity_type": "Chemical", "pos": [29, 43]}, {"entity": "ribofuranosides", "entity_type": "Chemical", "pos": [54, 69]}], "task": "NER"}
{"text": "A new compound library that contained 20 hinged benzimidazole - coumarin hybrids and their beta - d - ribofuranosides was established .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [48, 61]}, {"entity": "coumarin", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "beta - d - ribofuranosides", "entity_type": "Chemical", "pos": [91, 117]}], "task": "NER"}
{"text": "The anti - hepatitis C virus ( HCV ) activity of all novel coumarin derivatives , which were obtained by use of organic synthetic methods , was tested .", "entity": [{"entity": "coumarin", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "Two of these hybrids exhibited appealing EC50 values of as low as 3 . 0 and 5 . 5 mu M .", "entity": [], "task": "NER"}
{"text": "The best selectivity index was 14 .", "entity": [], "task": "NER"}
{"text": "The incorporation of a d - ribofuranose into the hinged hybrids provided the corresponding nucleosides with the beta configuration , one of which inhibited HCV replication with an EC50 value of 20 mu M .", "entity": [{"entity": "d - ribofuranose", "entity_type": "Chemical", "pos": [23, 39]}, {"entity": "nucleosides", "entity_type": "Chemical", "pos": [91, 102]}], "task": "NER"}
{"text": "Additionally , the structure - activity relationship is elucidated on the basis of the functional groups that were attached to the nuclei of benzimidazole , coumarin , and ribofuranose of the hybrids .", "entity": [{"entity": "benzimidazole", "entity_type": "Chemical", "pos": [141, 154]}, {"entity": "coumarin", "entity_type": "Chemical", "pos": [157, 165]}, {"entity": "ribofuranose", "entity_type": "Chemical", "pos": [172, 184]}], "task": "NER"}
{"text": "The protective role of l - carnitine against cylindrospermopsin - induced oxidative stress in tilapia ( Oreochromis niloticus ) .", "entity": [{"entity": "l - carnitine", "entity_type": "Chemical", "pos": [23, 36]}, {"entity": "cylindrospermopsin", "entity_type": "Chemical", "pos": [45, 63]}], "task": "NER"}
{"text": "Cylindrospermopsin ( CYN ) is one of the most important cyanotoxins in terms of both human health and environmental quality and is produced by several different species of cyanobacteria , including Aphanizomenon ovalisporum .", "entity": [{"entity": "Cylindrospermopsin", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "CYN", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "The principal mechanisms of action of CYN involve inhibition of protein and glutathione synthesis .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [38, 41]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [76, 87]}], "task": "NER"}
{"text": "In addition , CYN - mediated genotoxicity results from DNA fragmentation .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "The results of both in vivo and in vitro studies suggest that oxidative stress also plays a significant role in CYN pathogenesis in fish .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [112, 115]}], "task": "NER"}
{"text": "We investigated the protective effects of l - carnitine ( LC ) pre - treatment on A . ovalisporum - induced oxidative stress in cells containing CYN and deoxy - CYN , or pure standard CYN , in tilapia ( Oreochromis niloticus ) that had been acutely exposed via oral administration .", "entity": [{"entity": "l - carnitine", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "CYN", "entity_type": "Chemical", "pos": [145, 148]}, {"entity": "deoxy - CYN", "entity_type": "Chemical", "pos": [153, 164]}, {"entity": "CYN", "entity_type": "Chemical", "pos": [184, 187]}], "task": "NER"}
{"text": "Various oxidative stress markers , including lipid peroxidation ( LPO ) , protein oxidation , DNA oxidation , and the ratio of reduced glutathione to oxidised glutathione ( GSH / GSSG ) , and the activities of NADPH oxidase , superoxide dismutase ( SOD ) , catalase ( CAT ) , and gamma - glutamyl - cysteine synthetase ( gamma - GCS ) , were evaluated in the livers and kidneys of fish in the absence and presence of 400 or 880mgLC / kgfish / day during a 21 day period prior to CYN - intoxication .", "entity": [{"entity": "reduced glutathione", "entity_type": "Chemical", "pos": [127, 146]}, {"entity": "oxidised glutathione", "entity_type": "Chemical", "pos": [150, 170]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [173, 176]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [179, 183]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [210, 215]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [226, 236]}, {"entity": "gamma - glutamyl - cysteine", "entity_type": "Chemical", "pos": [280, 307]}, {"entity": "CYN", "entity_type": "Chemical", "pos": [479, 482]}], "task": "NER"}
{"text": "The results of our study demonstrated for the first time the beneficial antioxidant effects of LC dietary supplementation on oxidative stress status in fish .", "entity": [], "task": "NER"}
{"text": "No pro - oxidant effects were detected at any of the LC doses assayed , suggesting that LC is a chemoprotectant that reduces hepatic and renal oxidative stress and may be effective when used for the prophylaxis and treatment of CYN - related intoxication in fish .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [228, 231]}], "task": "NER"}
{"text": "A child exposed to primidone not prescribed for her .", "entity": [{"entity": "primidone", "entity_type": "Chemical", "pos": [19, 28]}], "task": "NER"}
{"text": "A 7 . 5 - year - old girl who was treated with phenobarbital ( PHB ) for epilepsy was admitted with decreased levels of consciousness .", "entity": [{"entity": "phenobarbital", "entity_type": "Chemical", "pos": [47, 60]}, {"entity": "PHB", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "She had been known to have high PHB levels of unknown cause , without symptoms .", "entity": [{"entity": "PHB", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "Her PHB levels were very high , as expected , but primidone levels were also detected although she and her parents denied history of primidone administration .", "entity": [{"entity": "PHB", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "primidone", "entity_type": "Chemical", "pos": [50, 59]}, {"entity": "primidone", "entity_type": "Chemical", "pos": [133, 142]}], "task": "NER"}
{"text": "We wished to rule out intentional unprescribed use of primidone .", "entity": [{"entity": "primidone", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "Our retrospective review showed 3 other children with high PHB concentrations where primidone was also detected when PHB levels were over 130 mu mol / L .", "entity": [{"entity": "PHB", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "primidone", "entity_type": "Chemical", "pos": [84, 93]}, {"entity": "PHB", "entity_type": "Chemical", "pos": [117, 120]}], "task": "NER"}
{"text": "Complementary studies confirmed that high - dose PHB can convert to its prodrug primidone , which has not been reported previously .", "entity": [{"entity": "PHB", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "primidone", "entity_type": "Chemical", "pos": [80, 89]}], "task": "NER"}
{"text": "Systematic review of population pharmacokinetic analyses of imatinib and relationships with treatment outcomes .", "entity": [{"entity": "imatinib", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "Several population pharmacokinetic ( PPK ) analyses of the anticancer drug imatinib have been performed to investigate different patient populations and covariate effects .", "entity": [{"entity": "imatinib", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "The present analysis offers a systematic qualitative and quantitative summary and comparison of those .", "entity": [], "task": "NER"}
{"text": "Its primary objective was to provide useful information for evaluating the expectedness of imatinib plasma concentration measurements in the frame of therapeutic drug monitoring .", "entity": [{"entity": "imatinib", "entity_type": "Chemical", "pos": [91, 99]}], "task": "NER"}
{"text": "The secondary objective was to review clinically important concentration - effect relationships to provide help in evaluating the potential suitability of plasma concentration values .", "entity": [], "task": "NER"}
{"text": "Nine PPK models describing total imatinib plasma concentration were identified .", "entity": [{"entity": "imatinib", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "Parameter estimates were standardized to common covariate values whenever possible .", "entity": [], "task": "NER"}
{"text": "Predicted median exposure ( C min ) was derived by simulations and ranged between models from 555 to 1388 ng / mL ( grand median : 870 ng / mL and interquartile \" reference \" range : 520 - 1390 ng / mL ) .", "entity": [], "task": "NER"}
{"text": "Covariates of potential clinical importance ( up to 30 % change in pharmacokinetic predicted by at least 1 model ) included body weight , albumin , alpha 1 acid glycoprotein , and white blood cell count .", "entity": [], "task": "NER"}
{"text": "Various other covariates were included but were statistically not significant or seemed clinically less important or physiologically controversial .", "entity": [], "task": "NER"}
{"text": "Concentration - response relationships had more importance below the average reference range and concentration - toxicity relationships above .", "entity": [], "task": "NER"}
{"text": "Therapeutic drug monitoring - guided dosage adjustment seems justified for imatinib , but a formal predictive therapeutic range remains difficult to propose in the absence of prospective target concentration intervention trials .", "entity": [{"entity": "imatinib", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "To evaluate the expectedness of a drug concentration measurement in practice , this review allows comparison of the measurement either to the average reference range or to a specific range accounting for individual patient characteristics .", "entity": [], "task": "NER"}
{"text": "For future research , external PPK model validation or meta - model development should be considered .", "entity": [], "task": "NER"}
{"text": "Enteropathogenic Escherichia coli - induced macrophage inhibitory cytokine 1 mediates cancer cell survival : an in vitro implication of infection - linked tumor dissemination .", "entity": [], "task": "NER"}
{"text": "Mucosally adherent Escherichia coli is frequently observed in intestinal surface of patients with colorectal cancer , but rarely in healthy control .", "entity": [], "task": "NER"}
{"text": "Particularly , enteropathogenic Escherichia coli ( EPEC ) is known to be closely associated with colorectal carcinogenesis in human .", "entity": [], "task": "NER"}
{"text": "In this study , one consequence of EPEC infection in human intestinal cancer cells was induction of macrophage inhibitory cytokine 1 ( MIC - 1 ) , which is a multifunctional cytokine with biological activities involved in cancer cell growth , differentiation and migration .", "entity": [], "task": "NER"}
{"text": "The present investigation assessed the involvement of MIC - 1 protein in EPEC infection - mediated cancer cell survival .", "entity": [], "task": "NER"}
{"text": "The challenge with EPEC induced cancer cell detachment via cytoskeleton rearrangement , which was positively associated with induced MIC - 1 expression .", "entity": [], "task": "NER"}
{"text": "Moreover , MIC - 1 also mediated RhoA GTPase - linked survival of the detached cancer cells .", "entity": [], "task": "NER"}
{"text": "Blocking of MIC - 1 or RhoA activity increased cellular apoptosis of the detached cancer cells .", "entity": [], "task": "NER"}
{"text": "In terms of signaling pathway , MIC - 1 triggered transforming growth factor beta - activated kinase 1 ( TAK1 ) , which enhanced expression of RhoA GTPase .", "entity": [], "task": "NER"}
{"text": "We conclude that EPEC enhances MIC - 1 gene expression in the human intestinal cancer cells , which can be associated with enhanced tumor cell resistance to anchorage - dependent tumor cell death via enhanced TAK1 and RhoA GTPase . Oncogene advance online publication , 18 March 2013 ; doi : 10 . 1038 / onc . 2012 . 508 .", "entity": [], "task": "NER"}
{"text": "The regulatory roles of phosphatases in cancer .", "entity": [], "task": "NER"}
{"text": "The relevance of potentially reversible post - translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology .", "entity": [], "task": "NER"}
{"text": "Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases , including different types of cancer , though phosphatases are relatively under - studied .", "entity": [], "task": "NER"}
{"text": "Loss of phosphatases such as PTEN ( phosphatase and tensin homologue deleted on chromosome 10 ) , a known tumour suppressor , across tumour types lends credence to the development of phosphatidylinositol 3 - - kinase inhibitors alongside the use of phosphatase expression as a biomarker , though phase 3 trial data are lacking .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [183, 203]}], "task": "NER"}
{"text": "In this review , we give an updated report on phosphatase dysregulation linked to organ - specific malignancies . Oncogene advance online publication , 18 March 2013 ; doi : 10 . 1038 / onc . 2013 . 80 .", "entity": [], "task": "NER"}
{"text": "Sol - gel nanoglues for an organic binder - free TiO2 nanofiber anode for lithium ion batteries .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [49, 53]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "A TiO2 nanofiber anode is glued using a sol - gel reaction to improve cycle performance and Coulombic efficiencies .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [2, 6]}], "task": "NER"}
{"text": "The hydrolysis - condensation process produces TiO2 nanoglues consisting of TiO2 nanoparticles , providing strong adhesion between nanofibers and the current collector as well as between nanofibers , rendering favourable transporting properties of electrons and Li ions in the TiO2 nanofiber electrode , and eventually leading to the excellent performance of Li ion batteries exhibiting an excellent initial Coulombic efficiency ( ~ 85 % ) , cycle performance up to 100 cycles , and high rate capability ( 60 % at 5 C ) .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [47, 51]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [76, 80]}, {"entity": "Li", "entity_type": "Chemical", "pos": [262, 264]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [277, 281]}, {"entity": "Li", "entity_type": "Chemical", "pos": [359, 361]}], "task": "NER"}
{"text": "Cellular effects of manufactured nanoparticles : effect of adsorption ability of nanoparticles .", "entity": [], "task": "NER"}
{"text": "Nanoparticles are important industrial materials .", "entity": [], "task": "NER"}
{"text": "However , many nanoparticles show biological effects , including toxic activity .", "entity": [], "task": "NER"}
{"text": "Metal ion release is the most important factor affecting the biological effects of nanoparticles .", "entity": [], "task": "NER"}
{"text": "In addition , nanoparticles have large adsorption ability .", "entity": [], "task": "NER"}
{"text": "The adsorption ability , in particular protein adsorption to nanoparticles , has an effect on cellular uptake and cellular metabolisms .", "entity": [], "task": "NER"}
{"text": "Moreover , the adsorption ability of nanoparticles causes artificial effects in in vitro systems .", "entity": [], "task": "NER"}
{"text": "Consequently , accurate determination of released or secreted proteins such as lactate dehydrogenase and cytokines adsorbed to nanoparticles is affected .", "entity": [{"entity": "lactate", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "In addition , artificial effects cause overestimation or underestimation of the cytotoxicity of nanoparticles .", "entity": [], "task": "NER"}
{"text": "Therefore , measurement of the protein adsorption of nanoparticles is important .", "entity": [], "task": "NER"}
{"text": "Some methods for the determination of the adsorption to nanoparticles have been suggested .", "entity": [], "task": "NER"}
{"text": "The flow field - flow fractionation method is one of the efficient techniques for determining proteins on the surface of nanoparticles .", "entity": [], "task": "NER"}
{"text": "The cellular effects caused by nanoparticles should be carefully considered .", "entity": [], "task": "NER"}
{"text": "Xanthohumol attenuates tumour cell - mediated breaching of the lymphendothelial barrier and prevents intravasation and metastasis .", "entity": [{"entity": "Xanthohumol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Health beneficial effects of xanthohumol have been reported , and basic research provided evidence for anti - cancer effects .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [29, 40]}], "task": "NER"}
{"text": "Furthermore , xanthohumol was shown to inhibit the migration of endothelial cells .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Therefore , this study investigated the anti - metastatic potential of xanthohumol .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [71, 82]}], "task": "NER"}
{"text": "MCF - 7 breast cancer spheroids which are placed on lymphendothelial cells ( LECs ) induce \" circular chemorepellent - induced defects \" ( CCIDs ) in the LEC monolayer resembling gates for intravasating tumour bulks at an early step of lymph node colonisation .", "entity": [], "task": "NER"}
{"text": "NF - kappa B reporter - , EROD - , SELE - , 12 ( S ) - HETE - and adhesion assays were performed to investigate the anti - metastatic properties of xanthohumol .", "entity": [{"entity": "12 ( S ) - HETE", "entity_type": "Chemical", "pos": [44, 59]}, {"entity": "xanthohumol", "entity_type": "Chemical", "pos": [148, 159]}], "task": "NER"}
{"text": "Western blot analyses were used to elucidate the mechanisms inhibiting CCID formation .", "entity": [], "task": "NER"}
{"text": "Xanthohumol inhibited the activity of CYP , SELE and NF - kB and consequently , the formation of CCIDs at low micromolar concentrations .", "entity": [{"entity": "Xanthohumol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "More specifically , xanthohumol affected ICAM - 1 expression and adherence of MCF - 7 cells to LECs , which is a prerequisite for CCID formation .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [20, 31]}], "task": "NER"}
{"text": "Furthermore , markers of epithelial - to - mesenchymal transition ( EMT ) and of cell mobility such as paxillin , MCL2 and S100A4 were suppressed by xanthohumol .", "entity": [{"entity": "xanthohumol", "entity_type": "Chemical", "pos": [149, 160]}], "task": "NER"}
{"text": "Xanthohumol attenuated tumour cell - mediated defects at the lymphendothelial barrier and inhibited EMT - like effects thereby providing a mechanistic explanation for the anti - intravasative / anti - metastatic properties of xanthohumol .", "entity": [{"entity": "Xanthohumol", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "xanthohumol", "entity_type": "Chemical", "pos": [226, 237]}], "task": "NER"}
{"text": "Gas - phase structures and thermochemistry of neutral histidine and its conjugated acid and base .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "Extensive exploration of the conformational space of neutral , protonated and deprotonated histidine has been conducted at the G4MP2 level .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [91, 100]}], "task": "NER"}
{"text": "Theoretical protonation and deprotonation thermochemistry as well as heats of formation of gaseous histidine and its ionized forms have been calculated at the G4 level considering either the most stable conformers or an equilibrium population of conformers at 298 K .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [99, 108]}], "task": "NER"}
{"text": "These theoretical results were compared to evaluated experimental determinations .", "entity": [], "task": "NER"}
{"text": "Recommended proton affinity and protonation entropy deduced from these comparisons are PA ( His ) = 980 kJ mol ( - 1 ) and Delta pS ( His ) ~ 0 J mol ( - 1 ) K ( - 1 ) , thus leading to a gas - phase basicity value of GB ( His ) = 947 . 5 kJ mol ( - 1 ) .", "entity": [{"entity": "His", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "His", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "His", "entity_type": "Chemical", "pos": [223, 226]}], "task": "NER"}
{"text": "Similarly , gas phase acidity parameters are Delta acidH ( o ) ( His ) = 1373 kJ mol ( - 1 ) , Delta acidS ( His ) ~ 10 J mol ( - 1 ) K ( - 1 ) and Delta acidG ( o ) ( His ) = 1343 kJ mol ( - 1 ) .", "entity": [{"entity": "His", "entity_type": "Chemical", "pos": [65, 68]}, {"entity": "His", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "His", "entity_type": "Chemical", "pos": [168, 171]}], "task": "NER"}
{"text": "Computed G4 heats of formation values are equal to - 290 , 265 and - 451 kJ mol ( - 1 ) for gaseous neutral histidine and its protonated and deprotonated forms , respectively .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [108, 117]}], "task": "NER"}
{"text": "The present computational data correct , and complete , previous thermochemical parameter estimates proposed for gas - phase histidine and its acido - basic properties .", "entity": [], "task": "NER"}
{"text": "Maternal perinatal diet induces developmental programming of bone architecture .", "entity": [], "task": "NER"}
{"text": "Maternal high - fat ( HF ) diet can alter offspring metabolism via perinatal developmental programming .", "entity": [], "task": "NER"}
{"text": "This study tests the hypothesis that maternal HF diet also induces perinatal programming of offspring bone mass and strength .", "entity": [], "task": "NER"}
{"text": "We compared skeletal acquisition in pups from C57Bl / 6J mice fed HF or normal diet from preconception through lactation .", "entity": [], "task": "NER"}
{"text": "Three - week - old male and female pups from HF ( HF - N ) and normal mothers ( N - N ) were weaned onto normal diet .", "entity": [], "task": "NER"}
{"text": "Outcomes at 14 and 26 weeks of age included body mass , body composition , whole - body bone mineral content ( WBBMC ) via peripheral dual - energy X - ray absorptiometry , femoral cortical and trabecular architecture via microcomputed tomography , and glucose tolerance .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [253, 260]}], "task": "NER"}
{"text": "Female HF - N had normal body mass and glucose tolerance , with lower body fat ( % ) but higher serum leptin at 14 weeks vs . N - N ( P < 0 . 05 for both ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "WBBMC was 12 % lower at 14 weeks and 5 % lower at 26 weeks , but trabecular bone volume fraction was 20 % higher at 14 weeks in female HF - N vs . N - N ( P < 0 . 05 for all ) .", "entity": [], "task": "NER"}
{"text": "Male HF - N had normal body mass and mildly impaired glucose tolerance , with lower body fat ( % ) at 14 weeks and lower serum leptin at 26 weeks vs . N - N ( P < 0 . 05 for both ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [53, 60]}], "task": "NER"}
{"text": "Serum insulin was higher at 14 weeks and lower at 26 weeks in HF - N vs . N - N ( P < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Trabecular BV / TV was 34 % higher and cortical bone area was 6 % higher at 14 weeks vs . N - N ( P < 0 . 05 for both ) .", "entity": [], "task": "NER"}
{"text": "These data suggest that maternal HF diet has complex effects on offspring bone , supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis .", "entity": [], "task": "NER"}
{"text": "LIM - homeodomain Transcription Factor Isl - 1 Mediates the Effect of Leptin on Insulin Secretion in Mice .", "entity": [], "task": "NER"}
{"text": "In addition to the well known regulating effects of leptin on energy balance and glucose homeostasis through the central nervous system , circulating leptin has a direct effect on pancreatic islet and insulin secretion through its receptor ( OBRb ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [81, 88]}], "task": "NER"}
{"text": "The LIM - homeodomain transcription factor Isl - 1 is expressed in all classes of pancreatic endocrine cells and is involved in regulating both islet development and insulin secretion .", "entity": [], "task": "NER"}
{"text": "Both OBRb and Isl - 1 mutations result in obesity - related diabetes .", "entity": [], "task": "NER"}
{"text": "However , the interactions and physiological significance of leptin and Isl - 1 in pancreatic islets remain to be established .", "entity": [], "task": "NER"}
{"text": "Here , we show that most of leptin target cells in pancreatic islets and NIT beta cells express Isl - 1 .", "entity": [], "task": "NER"}
{"text": "Both in vivo and in vitro results demonstrate that leptin suppresses Isl - 1 expression and insulin secretion in islet in physiological and pathophysiological conditions , e . g . high fat diet .", "entity": [], "task": "NER"}
{"text": "This effect of leptin on insulin secretion is lost in leptin receptor - defective db / db and Isl - 1 - inducible knock - out mice .", "entity": [], "task": "NER"}
{"text": "We conclude that the action of leptin on insulin secretion is at least partly mediated by Isl - 1 .", "entity": [], "task": "NER"}
{"text": "Another new finding of this study is that Isl - 1 acts as a direct downstream target of leptin signaling molecule STAT3 to influence the effect of leptin on insulin secretion , whereas inversely , insulin has feedback regulating effects on Isl - 1 expression through JAK - STAT3 pathway .", "entity": [], "task": "NER"}
{"text": "These findings are crucial for understanding the mechanisms regulating insulin secretion and metabolism in related diseases , such as obesity and type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Testicular function and fertility in men with Klinefelter syndrome : a review .", "entity": [], "task": "NER"}
{"text": "Klinefelter syndrome , 47 , XXY ( KS ) , is the most frequent sex chromosome aberration in males , affecting 1 in 660 newborn boys .", "entity": [], "task": "NER"}
{"text": "The syndrome is characterized by testicular destruction with extensive fibrosis and hyalinization of the seminiferous tubules resulting in small testes , hypergonadotropic hypogonadism , and azoospermia in the majority of cases .", "entity": [], "task": "NER"}
{"text": "Until recently , infertility was considered an untreatable condition in KS .", "entity": [], "task": "NER"}
{"text": "However , with the development of new advanced assisted reproductive techniques such as testicular sperm extraction ( TESE ) combined with ICSI it seems that KS patients should no longer be labelled as infertile .", "entity": [], "task": "NER"}
{"text": "Especially , microdissection ( micro ) - TESE has proved to be an advantageous procedure for the identification of testicular spermatozoa in KS .", "entity": [], "task": "NER"}
{"text": "The aim of this review was to describe current knowledge on the testicular changes occurring in KS , the associated changes in reproductive hormones and spermatogenesis , and the existing possibilities of biological fatherhood in 47 , XXY patients .", "entity": [], "task": "NER"}
{"text": "Inhibition of Protein Misfolding / Aggregation Using Polyglutamine Binding Peptide QBP1 as a Therapy for the Polyglutamine Diseases .", "entity": [{"entity": "Polyglutamine", "entity_type": "Chemical", "pos": [53, 66]}, {"entity": "Polyglutamine", "entity_type": "Chemical", "pos": [109, 122]}], "task": "NER"}
{"text": "Protein misfolding and aggregation in the brain have been recognized to be crucial in the pathogenesis of various neurodegenerative diseases , including Alzheimer ' s , Parkinson ' s , and the polyglutamine ( polyQ ) diseases , which are collectively called the \" protein misfolding diseases \" .", "entity": [{"entity": "polyglutamine", "entity_type": "Chemical", "pos": [193, 206]}, {"entity": "polyQ", "entity_type": "Chemical", "pos": [209, 214]}], "task": "NER"}
{"text": "In the polyQ diseases , an abnormally expanded polyQ stretch in the responsible proteins causes the proteins to misfold and aggregate , eventually resulting in neurodegeneration .", "entity": [{"entity": "polyQ", "entity_type": "Chemical", "pos": [7, 12]}, {"entity": "polyQ", "entity_type": "Chemical", "pos": [47, 52]}], "task": "NER"}
{"text": "Hypothesizing that polyQ protein misfolding and aggregation could be inhibited by molecules specifically binding to the expanded polyQ stretch , we identified polyQ binding peptide 1 ( QBP1 ) .", "entity": [{"entity": "polyQ", "entity_type": "Chemical", "pos": [19, 24]}, {"entity": "polyQ", "entity_type": "Chemical", "pos": [129, 134]}, {"entity": "polyQ", "entity_type": "Chemical", "pos": [159, 164]}], "task": "NER"}
{"text": "We show that QBP1 does , indeed , inhibit misfolding and aggregation of the expanded polyQ protein in vitro .", "entity": [{"entity": "polyQ", "entity_type": "Chemical", "pos": [85, 90]}], "task": "NER"}
{"text": "Furthermore overexpression of QBP1 by the crossing of transgenic animals inhibits neurodegeneration in Drosophila models of the polyQ diseases .", "entity": [{"entity": "polyQ", "entity_type": "Chemical", "pos": [128, 133]}], "task": "NER"}
{"text": "We also introduce our attempts to deliver QBP1 into the brain by administration using viral vectors and protein transduction domains .", "entity": [], "task": "NER"}
{"text": "Interestingly , recent data suggest that QBP1 can also inhibit the misfolding / aggregation of proteins responsible for other protein misfolding diseases , highlighting the potential of QBP1 as a general therapeutic molecule for a wide range of neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "We hope that in the near future , aggregation inhibitor - based drugs will be developed and bring relief to patients suffering from these currently intractable protein misfolding diseases .", "entity": [], "task": "NER"}
{"text": "The Pharmacokinetics and Pharmacodynamics of Zaleplon Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers .", "entity": [{"entity": "Zaleplon", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "Pharmacokinetics , pharmacodynamics , safety , and tolerability of inhaled zaleplon were assessed in healthy volunteers .", "entity": [{"entity": "zaleplon", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "Forty participants received 0 . 5 , 1 , 2 , or 4 mg zaleplon or placebo as a thermally generated aerosol in a randomized , double - blind , parallel - group , dose escalation study .", "entity": [{"entity": "zaleplon", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Blood was collected up to 24 hours after dosing , and sedation was assessed up to 8 hours .", "entity": [], "task": "NER"}
{"text": "Following inhalation , the observed median time to maximum plasma concentrations ( 25 % , 75 % ) was 1 . 89 ( 1 . 45 , 3 . 08 ) minutes and the mean ( SD ) elimination half - life was 1 . 24 ( 0 . 24 ) hours .", "entity": [], "task": "NER"}
{"text": "The equilibration half - life for sedation ( t1 / 2 ke0 ) was 1 . 16 ( 0 . 62 , 2 . 17 ) minutes .", "entity": [], "task": "NER"}
{"text": "The zaleplon AUC was dose proportional across doses , with a slope ( 90 % confidence interval ) of log - AUC versus log - dose of 0 . 92 ( 0 . 82 , 1 . 02 ) .", "entity": [{"entity": "zaleplon", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "No clinically significant changes were noted in laboratory values , vital signs , or spirometry .", "entity": [], "task": "NER"}
{"text": "The most common adverse events were dizziness , somnolence , euphoria , headache , and visual disturbance .", "entity": [], "task": "NER"}
{"text": "Zaleplon inhalation represents a safe , well - tolerated means of rapidly achieving effective plasma concentrations .", "entity": [{"entity": "Zaleplon", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Exposure - Exposure Relationship of Tocilizumab , an Anti - IL - 6 Receptor Monoclonal Antibody , in a Large Population of Patients With Rheumatoid Arthritis .", "entity": [], "task": "NER"}
{"text": "Relationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies .", "entity": [], "task": "NER"}
{"text": "Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints ( DAS28 ) and American College of Rheumatology ( ACR ) criteria and with a decrease in inflammation markers .", "entity": [], "task": "NER"}
{"text": "A population pharmacokinetic / pharmacodynamic ( PKPD ) model was developed to describe data from 2 studies .", "entity": [], "task": "NER"}
{"text": "An indirect - response model with a sigmoid Emax ( maximal drug effect ) inhibitory drug effect on DAS28 \" production \" rate adequately described the relationship between tocilizumab concentration and DAS28 .", "entity": [], "task": "NER"}
{"text": "Mean minimum serum tocilizumab concentration at steady state was greater than the EC50 ( concentration at which 50 % of Emax on DAS28 is reached ) with the 8 - mg / kg dose but not with the 4 - mg / kgdose .", "entity": [], "task": "NER"}
{"text": "Simulations within a large rheumatoid arthritis ( RA ) population showed that DAS remission rates were 38 % for 8 mg / kg and 24 % for 4 mg / kg .", "entity": [], "task": "NER"}
{"text": "Tocilizumab was more potent in RA patients with higher baseline interleukin - 6 levels , but this effect was not clinically significant .", "entity": [], "task": "NER"}
{"text": "Other covariates ( eg , presence of neutralizing antitocilizumab antibodies ) did not demonstrate a clinically meaningful effect on tocilizumab DAS28 dose - response relationships .", "entity": [], "task": "NER"}
{"text": "These data support clinical observations that tocilizumab 8 mg / kg is more effective than 4 mg / kg in reducing disease activity .", "entity": [], "task": "NER"}
{"text": "Sclerostin and bone strength in women in their 10 ( th ) decade of life .", "entity": [], "task": "NER"}
{"text": "Sclerostin is a potent inhibitor of bone formation but has been shown to correlate positively with areal bone mineral density ( aBMD ) .", "entity": [], "task": "NER"}
{"text": "Little is known about its relationship to parameters of bone strength and volumentric BMD ( vBMD ) as measured by peripheral quantitative computed tomography ( pQCT ) .", "entity": [], "task": "NER"}
{"text": "We measured both serum sclerostin and parameters of tibial bone size and strength by pQCT to characterize this relationship .", "entity": [], "task": "NER"}
{"text": "Our study population consisted of 223 Caucasian and 35 African American women ( mean age 87 ) from the Study of Osteoporotic Fractures ( SOF ) cohort , who had usable pQCT scans of the tibia at sites 4 % ( T4 % ) , 33 % ( T33 % ) , and 66 % ( T66 % ) from the ankle .", "entity": [], "task": "NER"}
{"text": "Analysis of covariance was used to test for differences in age - adjusted means of aBMD , pQCT variables , and serum biomarkers across sclerostin quartiles .", "entity": [], "task": "NER"}
{"text": "Black women had significantly lower median sclerostin ( 34 . 3 pmol / L ) than white women ( 48 . 5 pmol / L ) ( p = 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Women in the highest sclerostin quartile had 7 - 14 . 5 % higher hip aBMD and pQCT parameters of vBMD and bone size than those in the lowest quartile in multivariate models adjusting for age , race , weight , height and diabetes .", "entity": [], "task": "NER"}
{"text": "The association of sclerostin with parameters of bone strength differed dramatically between T33 % and T66 % sites .", "entity": [], "task": "NER"}
{"text": "At T66 % , women in the highest sclerostin quartile had pQCT strength parameters 9 . 4 - 15 . 3 % greater than the lowest quartile , whereas no trend was found for the T33 % site .", "entity": [], "task": "NER"}
{"text": "Our results suggest paradoxical associations between circulating sclerostin and bone size , density and strength .", "entity": [], "task": "NER"}
{"text": "Interplay of Octahedral Tilts and Polar Order in BiFeO3 Films .", "entity": [{"entity": "BiFeO3", "entity_type": "Chemical", "pos": [49, 55]}], "task": "NER"}
{"text": "Heterointerface stabilization of a distinct nonpolar BiFeO3 phase occurs simultaneously with changes in octahedral tilts .", "entity": [{"entity": "BiFeO3", "entity_type": "Chemical", "pos": [53, 59]}], "task": "NER"}
{"text": "The resulting phase arises via suppression of polarization by a structural order parameter and can thus be identified as anti - ferroelectric ( Fe displacements - bottom panel ) .", "entity": [{"entity": "Fe", "entity_type": "Chemical", "pos": [144, 146]}], "task": "NER"}
{"text": "The phase is metastable and can be switched into a polar ferroelectric state ( top panel ) under an applied electric bias .", "entity": [], "task": "NER"}
{"text": "Cobalt chloride speciation , mechanisms of cytotoxicity on human pulmonary cells , and synergistic toxicity with zinc .", "entity": [{"entity": "Cobalt chloride", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [113, 117]}], "task": "NER"}
{"text": "Cobalt is used in numerous industrial sectors , leading to occupational diseases , particularly by inhalation .", "entity": [{"entity": "Cobalt", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Cobalt - associated mechanisms of toxicity are far from being understood and information that could improve knowledge in this area is required .", "entity": [{"entity": "Cobalt", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "We investigated the impact of a soluble cobalt compound , CoCl ( 2 ) . 6H ( 2 ) O , on the BEAS - 2B lung epithelial cell line , as well as its impact on metal homeostasis .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [40, 46]}, {"entity": "CoCl ( 2 ) . 6H ( 2 ) O", "entity_type": "Chemical", "pos": [58, 81]}], "task": "NER"}
{"text": "Cobalt speciation in different culture media , in particular soluble and precipitated cobalt species , was investigated via theoretical and analytical approaches .", "entity": [{"entity": "Cobalt", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "cobalt", "entity_type": "Chemical", "pos": [86, 92]}], "task": "NER"}
{"text": "The cytotoxic effects of cobalt on the cells were assessed .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [25, 31]}], "task": "NER"}
{"text": "Upon exposure of BEAS - 2B cells to cobalt , intracellular accumulation of cobalt and zinc was demonstrated using direct in situ microchemical analysis based on ion micro - beam techniques and analysis after cell lysis by inductively coupled plasma mass spectrometry ( ICP - MS ) .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "cobalt", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [86, 90]}], "task": "NER"}
{"text": "Microchemical imaging revealed that cobalt was rather homogeneously distributed in the nucleus and in the cytoplasm whereas zinc was more abundant in the nucleus .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [36, 42]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [124, 128]}], "task": "NER"}
{"text": "The modulation of zinc homeostasis led to the evaluation of the effect of combined cobalt and zinc exposure .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "cobalt", "entity_type": "Chemical", "pos": [83, 89]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [94, 98]}], "task": "NER"}
{"text": "In this case , a clear synergistic increase in toxicity was observed as well as a substantial increase in zinc content within cells .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [106, 110]}], "task": "NER"}
{"text": "Western blots performed under the same coexposure conditions revealed a decrease in ZnT1 expression , suggesting that cobalt could inhibit zinc release through the modulation of ZnT1 .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [118, 124]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "Overall , this study highlights the potential hazard to lung function , of combined exposure to cobalt and zinc .", "entity": [{"entity": "cobalt", "entity_type": "Chemical", "pos": [96, 102]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "Boosting Immunity to Small Tumor - Associated Carbohydrates with Bacteriophage Q beta Capsids .", "entity": [{"entity": "Carbohydrates", "entity_type": "Chemical", "pos": [46, 59]}], "task": "NER"}
{"text": "The development of an effective immunotherapy is an attractive strategy toward cancer treatment .", "entity": [], "task": "NER"}
{"text": "Tumor associated carbohydrate antigens ( TACAs ) are overexpressed on a variety of cancer cell surfaces , which present tempting targets for anticancer vaccine development .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [17, 29]}], "task": "NER"}
{"text": "However , such carbohydrates are often poorly immunogenic .", "entity": [{"entity": "carbohydrates", "entity_type": "Chemical", "pos": [15, 28]}], "task": "NER"}
{"text": "To overcome this challenge , we show here that the display of a very weak TACA , the monomeric Tn antigen , on bacteriophage Q beta virus - like particles elicits powerful humoral responses to the carbohydrate .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [197, 209]}], "task": "NER"}
{"text": "The effects of adjuvants , antigen display pattern , and vaccine dose on the strength and subclasses of antibody responses were established .", "entity": [], "task": "NER"}
{"text": "The local density of antigen rather than the total amount of antigen administered was found to be crucial for induction of high Tn - specific IgG titers .", "entity": [], "task": "NER"}
{"text": "The ability to display antigens in an organized and high density manner is a key advantage of virus - like particles such as Q beta as vaccine carriers .", "entity": [], "task": "NER"}
{"text": "Glycan microarray analysis showed that the antibodies generated were highly selective toward Tn antigens .", "entity": [], "task": "NER"}
{"text": "Furthermore , Q beta elicited much higher levels of IgG antibodies than other types of virus - like particles , and the IgG antibodies produced reacted strongly with the native Tn antigens on human leukemia cells .", "entity": [], "task": "NER"}
{"text": "Thus , Q beta presents a highly attractive platform for the development of carbohydrate - based anticancer vaccines .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [75, 87]}], "task": "NER"}
{"text": "Cell Durotaxis on Polyelectrolyte Multilayers with Photogenerated Gradients of Modulus .", "entity": [], "task": "NER"}
{"text": "Behaviors of rat aortic smooth muscle ( A7r5 ) and human osteosarcoma ( U2OS ) cells on photo - cross - linked polyelectrolyte multilayers ( PEMUs ) with uniform , or gradients of , moduli were investigated .", "entity": [], "task": "NER"}
{"text": "The PEMUs were built layer - by - layer with the polycation poly ( allylamine hydrochloride ) ( PAH ) and a polyanion poly ( acrylic acid ) ( PAA ) that was modified with photoreactive 4 - ( 2 - hydroxyethoxy ) benzophenone ( PAABp ) .", "entity": [{"entity": "poly ( allylamine hydrochloride )", "entity_type": "Chemical", "pos": [60, 93]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [96, 99]}, {"entity": "poly ( acrylic acid )", "entity_type": "Chemical", "pos": [118, 139]}, {"entity": "PAA", "entity_type": "Chemical", "pos": [142, 145]}, {"entity": "4 - ( 2 - hydroxyethoxy ) benzophenone", "entity_type": "Chemical", "pos": [185, 223]}], "task": "NER"}
{"text": "PEMUs with different uniform and gradients of modulus were generated by varying the time of uniform ultraviolet light exposure and by exposure through optical density gradient filters .", "entity": [], "task": "NER"}
{"text": "Analysis of adhesion , morphology , cytoskeletal organization , and motility of the cells on the PEMUs revealed that A7r5 cells established a polarized orientation toward increasing modulus on shallow modulus gradients ( approximately 4 . 7 MPa mm ( - 1 ) ) and durotaxed toward stiffer regions on steeper gradients ( approximately 55 MPa mm ( - 1 ) ) .", "entity": [], "task": "NER"}
{"text": "In contrast , U2OS cells exhibited little orientation or durotaxis on modulus gradients .", "entity": [], "task": "NER"}
{"text": "These results demonstrate the utility of photo - cross - linked PEMUs to direct vascular and osteoblast cell behavior , a potential application for PEMU coatings on biomedical implants .", "entity": [], "task": "NER"}
{"text": "New selective inhibitors of MMP - 13 for inflammatory diseases : a patent evaluation ( W02012151158 ) .", "entity": [], "task": "NER"}
{"text": "A series of compounds incorporating an aromatic scaffold based on isoxazolines were prepared in the patent application ( WO2012151158 ) .", "entity": [{"entity": "isoxazolines", "entity_type": "Chemical", "pos": [66, 78]}], "task": "NER"}
{"text": "The new compounds from the patent are defined to be biologically active metabolites , prodrugs , isomers , stereoisomers , solvates , hydrates and pharmaceutically acceptable salts , they are claimed to be useful for treating immunological conditions because of their inhibitory activities on matrix metalloproteinase ( MMP - 13 ) , although no specific MMP - 13 inhibition data or other rationale to explain their biological effects is provided .", "entity": [], "task": "NER"}
{"text": "The compounds have a broad potential utility with osteoarthritis , rheumatoid arthritis , juvenile arthritis , psoriatic arthritis , degenerative joint disease or systemic lupus erythematosus among the likely preferred indications .", "entity": [], "task": "NER"}
{"text": "Increased Levels of Inosine in a Mouse Model of Inflammation .", "entity": [{"entity": "Inosine", "entity_type": "Chemical", "pos": [20, 27]}], "task": "NER"}
{"text": "One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen , nitrogen , and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage , with these chemical mediators causing damage that ultimately leads to cell death and mutation .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [92, 98]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [101, 109]}, {"entity": "halogen", "entity_type": "Chemical", "pos": [116, 123]}], "task": "NER"}
{"text": "To determine the most biologically deleterious chemistries of inflammation , we previously assessed products across the spectrum of DNA damage arising in inflamed tissues in the SJL mouse model nitric oxide overproduction ( Pang et al . ( 2007 ) Carcinogenesis 28 , 1807 - 1813 ) .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [194, 206]}], "task": "NER"}
{"text": "Among the anticipated DNA damage chemistries , we observed significant changes only in lipid peroxidation - derived etheno adducts .", "entity": [{"entity": "etheno", "entity_type": "Chemical", "pos": [116, 122]}], "task": "NER"}
{"text": "We have now developed an isotope - dilution , liquid chromatography - coupled , tandem quadrupole mass spectrometric method to quantify representative species across the spectrum of RNA damage products predicted to arise at sites of inflammation , including nucleobase deamination ( xanthosine and inosine ) , oxidation ( 8 - oxoguanosine ) , and alkylation ( 1 , N ( 6 ) - ethenoadenosine ) .", "entity": [{"entity": "nucleobase", "entity_type": "Chemical", "pos": [258, 268]}, {"entity": "xanthosine", "entity_type": "Chemical", "pos": [283, 293]}, {"entity": "inosine", "entity_type": "Chemical", "pos": [298, 305]}, {"entity": "8 - oxoguanosine", "entity_type": "Chemical", "pos": [322, 338]}, {"entity": "1 , N ( 6 ) - ethenoadenosine", "entity_type": "Chemical", "pos": [360, 389]}], "task": "NER"}
{"text": "Application of the method to the liver , spleen , and kidney from the SJL mouse model revealed generally higher levels of oxidative background RNA damage than was observed in DNA in control mice .", "entity": [], "task": "NER"}
{"text": "However , compared to control mice , RcsX treatment to induce nitric oxide overproduction resulted in significant increases only in inosine and only in the spleen .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [62, 74]}, {"entity": "inosine", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "Further , the nitric oxide synthase inhibitor , N - methylarginine , did not significantly affect the levels of inosine in control and RcsX - treated mice .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "N - methylarginine", "entity_type": "Chemical", "pos": [48, 66]}, {"entity": "inosine", "entity_type": "Chemical", "pos": [112, 119]}], "task": "NER"}
{"text": "The differences between DNA and RNA damage in the same animal model of inflammation point to possible influences from DNA repair , RcsX - induced alterations in adenosine deaminase activity , and differential accessibility of DNA and RNA to reactive oxygen and nitrogen species as determinants of nucleic acid damage during inflammation .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [161, 170]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [250, 256]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [261, 269]}], "task": "NER"}
{"text": "Comprehensive Experimental and Computational Analysis of Binding Energy Hot Spots at the NF - kappa B Essential Modulator / IKK beta Protein - Protein Interface .", "entity": [], "task": "NER"}
{"text": "We report a comprehensive analysis of binding energy hot spots at the protein - protein interaction ( PPI ) interface between nuclear factor kappa B ( NF - kappa B ) essential modulator ( NEMO ) and I kappa B kinase subunit beta ( IKK beta ) , an interaction that is critical for NF - kappa B pathway signaling , using experimental alanine scanning mutagenesis and also the FTMap method for computational fragment screening .", "entity": [], "task": "NER"}
{"text": "The experimental results confirm that the previously identified NEMO binding domain ( NBD ) region of IKK beta contains the highest concentration of hot - spot residues , the strongest of which are W739 , W741 , and L742 ( Delta Delta G = 4 . 3 , 3 . 5 , and 3 . 2 kcal / mol , respectively ) .", "entity": [], "task": "NER"}
{"text": "The region occupied by these residues defines a potentially druggable binding site on NEMO that extends for ~ 16 A to additionally include the regions that bind IKK beta L737 and F734 .", "entity": [], "task": "NER"}
{"text": "NBD residues D738 and S740 are also important for binding but do not make direct contact with NEMO , instead likely acting to stabilize the active conformation of surrounding residues .", "entity": [], "task": "NER"}
{"text": "We additionally found two previously unknown hot - spot regions centered on IKK beta residues L708 / V709 and L719 / I723 .", "entity": [], "task": "NER"}
{"text": "The computational approach successfully identified all three hot - spot regions on IKK beta .", "entity": [], "task": "NER"}
{"text": "Moreover , the method was able to accurately quantify the energetic importance of all hot - spot residues involving direct contact with NEMO .", "entity": [], "task": "NER"}
{"text": "Our results provide new information to guide the discovery of small - molecule inhibitors that target the NEMO / IKK beta interaction .", "entity": [], "task": "NER"}
{"text": "They additionally clarify the structural and energetic complementarity between \" pocket - forming \" and \" pocket - occupying \" hot - spot residues , and further validate computational fragment mapping as a method for identifying hot spots at PPI interfaces .", "entity": [], "task": "NER"}
{"text": "Targeting TRP Channels in Airway Disorders .", "entity": [], "task": "NER"}
{"text": "Novel effective therapeutic agents are actively sought for the treatment of a broad spectrum of respiratory diseases which collectively significantly impact on mortality , morbidity and quality of life of hundreds of millions of people world - wide .", "entity": [], "task": "NER"}
{"text": "These include asthma , allergic rhinitis , chronic obstructive pulmonary disease , cough , idiopathic pulmonary fibrosis , pulmonary arterial hypertension , cystic fibrosis and acute lung injury .", "entity": [], "task": "NER"}
{"text": "TRP channels are broadly distributed throughout the respiratory tract and play an important physiological role in sensing and subsequently responding to a wide variety of stimuli , for example temperature , osmolarity and oxidant stress .", "entity": [], "task": "NER"}
{"text": "In the context of respiratory disease however TRP channel function may be altered , eg : under conditions of oxidative stress , inflammation , hypoxia and mechanical stress .", "entity": [], "task": "NER"}
{"text": "In addition there is evidence that the expression / activity of TRP channels can be affected in the disease setting .", "entity": [], "task": "NER"}
{"text": "Modulators of TRP channel function are therefore under investigation for a range of diseases including disorders of the respiratory system .", "entity": [], "task": "NER"}
{"text": "Several excellent review articles have discussed in detail evidence that modulation of specific TRP channels may be of benefit in specific respiratory diseases .", "entity": [], "task": "NER"}
{"text": "In this article we have taken the approach of reviewing evidence that modulation of TRP channel function may be able to affect common and over - lapping characteristic features of respiratory diseases , for example bronchoconstriction , airways hyper - responsiveness , cough , airways inflammation , mucus hyper - secretion , exacerbations , lung injury , hypoxia and airways re - modelling .", "entity": [], "task": "NER"}
{"text": "The therapeutic potential of TRP channel modulators , the status of these agents in the clinic along with the challenges posed in this rapidly advancing field are also discussed in this review .", "entity": [], "task": "NER"}
{"text": "The hemodynamics of septic shock : a historical perspective .", "entity": [], "task": "NER"}
{"text": "In the late 19th century , it was already known that severe infections could be associated with cardiovascular collapse , a fact essentially attributed to cardiac failure .", "entity": [], "task": "NER"}
{"text": "A major experimental work in the rabbit , published by Romberg and P a ssler in 1899 , shifted attention to disturbed peripheral vascular tone as the mechanism of hypotension in these conditions .", "entity": [], "task": "NER"}
{"text": "In the first half of the 20th century , great progresses were made in the pathophysiologic understanding of hemorrhagic and traumatic shocks , while researchers devoted relatively little attention to septic shock .", "entity": [], "task": "NER"}
{"text": "Progress in the hemodynamic understanding of septic shock resumed with the advent of critical care units .", "entity": [], "task": "NER"}
{"text": "The hyperdynamic state was recognized in the late fifties and early sixties .", "entity": [], "task": "NER"}
{"text": "The present short review ends with landmark studies by Max Harry Weil , demonstrating the importance of venous pooling , and John H . Siegel , which introduced the concept of deficient peripheral utilization of oxygen , inspiring later work on the microvascular disturbances of septic shock .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [211, 217]}], "task": "NER"}
{"text": "Effect of Enzyme Concentration of the Morphology and Properties of Enzymatically Triggered Peptide Hydrogels .", "entity": [], "task": "NER"}
{"text": "We have recently shown that thermolysine , a protease enzyme obtained from Bacillus thermoproteolyticus rokko , can be used to trigger the gelation of FEFK ( F , phenylalanine ; E , glutamic acid ; K , lysine ) tetrapeptides through reverse hydrolysis and formation of longer peptide sequences , mainly octapeptides , that self - assemble readily .", "entity": [{"entity": "phenylalanine", "entity_type": "Chemical", "pos": [162, 175]}, {"entity": "glutamic acid", "entity_type": "Chemical", "pos": [182, 195]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [202, 208]}], "task": "NER"}
{"text": "In this article we investigate the effect of enzyme concentration on the morphology and properties of enzymatically triggered peptide hydrogels using HPLC , FTIR , real - time SAXS , TEM , and shear rheology .", "entity": [], "task": "NER"}
{"text": "We have shown that the enzyme concentration , Cenz , does not affect the final composition of the samples .", "entity": [], "task": "NER"}
{"text": "Instead , this is dictated by the initial tetrapeptide concentration , C0 , suggesting the existence of a chemical equilibrium .", "entity": [], "task": "NER"}
{"text": "We went on to show that Cenz does not affect the self - assembly of these peptides at a molecular level either nor the structure of the fibrillar network formed at the nanometer scale .", "entity": [], "task": "NER"}
{"text": "Interestingly , the mechanical properties were found to be affected by Cenz , where the shear moduli of the hydrogels were found to increase with increasing Cenz .", "entity": [], "task": "NER"}
{"text": "These results suggest that morphological differences between the hydrogels at the microscale are at the origin of their difference in mechanical properties .", "entity": [], "task": "NER"}
{"text": "In this paper , we propose a morphological model in which denser network regions are found around the enzymes , resulting in the creation of heterogeneous networks .", "entity": [], "task": "NER"}
{"text": "These were confirmed by TEM measurements .", "entity": [], "task": "NER"}
{"text": "The existence of these denser network regions will result in the reinforcement of the hydrogels , thus , explaining the high shear moduli obtained increasing Cenz .", "entity": [], "task": "NER"}
{"text": "Evaluation of Constituents of Piper retrofractum Fruits on Neurotrophic Activity .", "entity": [], "task": "NER"}
{"text": "Three new compounds , 1 - 3 , together with 22 known compounds , were isolated from the fruits of Piper retrofractum .", "entity": [], "task": "NER"}
{"text": "The structures of the new compounds were elucidated on the basis of spectroscopic data analysis and comparison with literature values .", "entity": [], "task": "NER"}
{"text": "Compound 1 was found to enhance the neurite outgrowth of NGF - mediated PC12 cells at concentrations ranging from 0 . 1 to 10 mu M .", "entity": [], "task": "NER"}
{"text": "' Bacoside B ' - the need remains for establishing identity .", "entity": [{"entity": "Bacoside B", "entity_type": "Chemical", "pos": [2, 12]}], "task": "NER"}
{"text": "Bacopa monnieri is fast gaining popularity for its beneficial effects on cognition and memory .", "entity": [], "task": "NER"}
{"text": "The active constituents of the plant were putatively identified as ' bacosides A and B ' in older publications .", "entity": [{"entity": "bacosides A and B", "entity_type": "Chemical", "pos": [69, 86]}], "task": "NER"}
{"text": "Subsequently ' bacoside A ' was identified as a mixture of four saponins [ bacoside A3 ( 1 ) , bacopaside II ( 2 ) , bacopasaponin C ( 3 ) and the jujobogenin isomer of the latter ( 4 ) ] and was considered as part of major constituents of the herb along with bacopaside I ( 5 ) .", "entity": [{"entity": "bacoside A", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "bacoside A3", "entity_type": "Chemical", "pos": [75, 86]}, {"entity": "bacopaside II", "entity_type": "Chemical", "pos": [95, 108]}, {"entity": "bacopasaponin C", "entity_type": "Chemical", "pos": [117, 132]}, {"entity": "jujobogenin", "entity_type": "Chemical", "pos": [147, 158]}, {"entity": "bacopaside I", "entity_type": "Chemical", "pos": [260, 272]}], "task": "NER"}
{"text": "These major saponins now form part of analytical monographs in many Pharmacopoeia .", "entity": [{"entity": "saponins", "entity_type": "Chemical", "pos": [12, 20]}], "task": "NER"}
{"text": "However identity of ' bacoside B ' still appears controversial with seemingly contradictory information available in the scientific literature .", "entity": [{"entity": "bacoside B", "entity_type": "Chemical", "pos": [22, 32]}], "task": "NER"}
{"text": "At the same time quality of many extracts and herbal products derived from the plant is still being determined based on the content of ' bacosides A and B ' .", "entity": [{"entity": "bacosides A and B", "entity_type": "Chemical", "pos": [137, 154]}], "task": "NER"}
{"text": "We have elaborated these issues in this article along with our recommendations to move forward towards achieving scientific clarity on the subject .", "entity": [], "task": "NER"}
{"text": "Interpretation of the margin of exposure for genotoxic carcinogens - Elicitation of expert knowledge about the form of the dose response curve at human relevant exposures .", "entity": [], "task": "NER"}
{"text": "The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to \" as low as reasonably achievable / practicable \" ( ALARA / P ) .", "entity": [], "task": "NER"}
{"text": "However , whilst this remains the preferred risk management option , it does not provide guidance on the urgency or extent of risk management actions necessary .", "entity": [], "task": "NER"}
{"text": "To address this , the \" Margin of Exposure \" ( MOE ) approach has been proposed .", "entity": [], "task": "NER"}
{"text": "The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure .", "entity": [], "task": "NER"}
{"text": "However , interpretation of the MOE requires implicit or explicit consideration of the shape of the dose - response curve at human relevant exposures .", "entity": [], "task": "NER"}
{"text": "In a structured elicitation exercise , we captured expert opinion on available scientific evidence for low dose - response relationships for genotoxic carcinogens .", "entity": [], "task": "NER"}
{"text": "This allowed assessment of : available evidence for the nature of dose - response relationships at human relevant exposures ; the generality of judgments about such dose - response relationships ; uncertainties affecting judgments on the nature of such dose - response relationships ; and whether this last should differ for different classes of genotoxic carcinogens .", "entity": [], "task": "NER"}
{"text": "Elicitation results reflected the variability in experts ' views on the form of the dose - response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship .", "entity": [], "task": "NER"}
{"text": "Inhibitory effects of in vivo oxidized high - density lipoproteins on platelet aggregation : evidence from patients with abetalipoproteinemia .", "entity": [], "task": "NER"}
{"text": "There is evidence that high - density lipoproteins ( HDLs ) may regulate platelet function , but disparate results exist regarding the effects of oxidized HDLs on platelets .", "entity": [], "task": "NER"}
{"text": "The objective of our study was to determine the role of in vivo oxidized HDLs on platelet aggregation .", "entity": [], "task": "NER"}
{"text": "Platelet aggregation and redox status were investigated in 5 patients with abetalipoproteinemia ( ABLP ) or homozygous hypobetalipoproteinemia , two rare metabolic diseases characterized by the absence of apolipoprotein B - containing lipoproteins , compared to 5 control subjects .", "entity": [], "task": "NER"}
{"text": "Platelets isolated from plasma of patients with ABLP aggregated 4 to 10 times more than control platelets , depending on the agonist .", "entity": [], "task": "NER"}
{"text": "By contrast , no differences in the extent of platelet aggregation were observed between ABLP platelet - rich plasma ( PRP ) and control PRP , suggesting the presence of a protective factor in ABLP plasma .", "entity": [], "task": "NER"}
{"text": "ABLP HDLs inhibited agonist - induced platelet aggregation by binding to SR - BI , while control HDLs had no effect .", "entity": [], "task": "NER"}
{"text": "On the other hand , lipoprotein - deficient plasma from patients with ABLP did not inhibit platelet aggregation .", "entity": [], "task": "NER"}
{"text": "Severe oxidative stress was evidenced in patients with ABLP .", "entity": [], "task": "NER"}
{"text": "Compared to control HDLs , ABLP HDLs showed a 40 % decrease of alpha - tocopherol and an 11 - fold increased malondialdehyde concentration .", "entity": [{"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [63, 81]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [109, 124]}], "task": "NER"}
{"text": "These results demonstrate that in vivo oxidized HDLs do not lose their antiaggregatory properties despite oxidation . - Calzada , C . , V e ricel , E . , Colas , R . , Guillot , N . , El Khoury , G . , Drai , J . , Sassolas , A . , Peretti , N . , Ponsin , G . , Lagarde , M . , Moulin , P .", "entity": [], "task": "NER"}
{"text": "A genome - wide association study of bronchodilator response in asthmatics .", "entity": [], "task": "NER"}
{"text": "Reversibility of airway obstruction in response to beta 2 - agonists is highly variable among asthmatics , which is partially attributed to genetic factors .", "entity": [], "task": "NER"}
{"text": "In a genome - wide association study of acute bronchodilator response ( BDR ) to inhaled albuterol , 534 290 single - nucleotide polymorphisms ( SNPs ) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations .", "entity": [{"entity": "albuterol", "entity_type": "Chemical", "pos": [89, 98]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [118, 128]}], "task": "NER"}
{"text": "The primary replication phase included 1397 polymorphisms in three asthma trials ( pooled n = 764 ) .", "entity": [], "task": "NER"}
{"text": "The second replication phase tested 13 SNPs in three additional asthma populations ( n = 241 , n = 215 and n = 592 ) .", "entity": [], "task": "NER"}
{"text": "An intergenic SNP on chromosome 10 , rs11252394 , proximal to several excellent biological candidates , significantly replicated ( P = 1 . 98 x 10 ( - 7 ) ) in the primary replication trials .", "entity": [], "task": "NER"}
{"text": "An intronic SNP ( rs6988229 ) in the collagen ( COL22A1 ) locus also provided strong replication signals ( P = 8 . 51 x 10 ( - 6 ) ) .", "entity": [], "task": "NER"}
{"text": "This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics . The Pharmacogenomics Journal advance online publication , 19 March 2013 ; doi : 10 . 1038 / tpj . 2013 . 5 .", "entity": [], "task": "NER"}
{"text": "Differential tolerance to copper , but no evidence of population - level genetic differences in a widely - dispersing native barnacle .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [26, 32]}], "task": "NER"}
{"text": "Despite many estuaries having high levels of metal pollution , species are found to persist in these stressful environments .", "entity": [], "task": "NER"}
{"text": "Populations of estuarine invertebrates exposed to toxic concentrations of such metals may be under selection .", "entity": [], "task": "NER"}
{"text": "However , in species with a wide - dispersal potential , any short - term results of localized selection may be counteracted by external recruitment from populations not under selection .", "entity": [], "task": "NER"}
{"text": "The barnacle Amphibalanus variegatus is found in nearshore coastal environments as well as sheltered embayments and estuaries , including metal - impacted estuaries , from New South Wales , Australia to Western Australia .", "entity": [], "task": "NER"}
{"text": "The fertilised eggs of A . variegatus are brooded internally and released as larvae ( nauplii ) , which remain in the water - column for ~ 14 days before settling .", "entity": [], "task": "NER"}
{"text": "Hence the species has a considerable dispersal capacity .", "entity": [], "task": "NER"}
{"text": "The purpose of this study was to examine whether populations of A . variegatus from metal - impacted sites , displayed a greater tolerance to a toxicant ( copper ) than reference populations .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "Adult barnacles where collected from twenty sites within two metal - impacted and fourteen sites within two reference estuaries .", "entity": [], "task": "NER"}
{"text": "Within 24 h , adults were induced to spawn and the offspring were exposed to copper in a laboratory assay .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "Larvae collected from the metal - impacted estuaries demonstrated a greater tolerance to copper compared to those from reference sites .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "To determine if selection / localised in the metal impacted sites was occurring , the genetic structure of populations at three sites was examined using an AFLP methodology .", "entity": [], "task": "NER"}
{"text": "No evidence of unique population identity and or selection ( outlier loci ) was detected suggesting that : ( 1 ) the tolerance displayed in the assay was derived from acclimation during development ; and / or ( 2 ) that the populations are open preventing the fixation of any unique alleles .", "entity": [], "task": "NER"}
{"text": "Diurnal pituitary - adrenal activity during schedule - induced polydipsia of water and ethanol in cynomolgus monkeys ( Macaca fascicularis ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [87, 94]}], "task": "NER"}
{"text": "RATIONALE : Intermittent delivery of an important commodity ( e . g . , food pellets ) generates excessive behaviors as an adjunct to the schedule of reinforcement ( adjunctive behaviors ) that are hypothesized to be due to conflict between engaging and escaping a situation where reinforcement is delivered , but at suboptimal rates .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : This study characterized the endocrine correlates during schedule - induced polydipsia of water and ethanol using a longitudinal approach in non - human primates .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [113, 120]}], "task": "NER"}
{"text": "METHODS : Plasma adrenocorticotropic hormone ( ACTH ) and cortisol were measured in samples from awake cynomolgus monkeys ( Macaca fascicularis , 11 adult males ) obtained at the onset , mid - day , and offset of their 12 - h light cycle .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [58, 66]}], "task": "NER"}
{"text": "The monkeys were induced to drink water and ethanol ( 4 % w / v , in water ) using a fixed time ( FT ) 300 - s interval schedule of pellet delivery .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "The induction fluid changed every 30 sessions in the following order : water , 0 . 5 g / kg ethanol , 1 . 0 g / kg ethanol , and 1 . 5 g / kg ethanol .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [115, 122]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [142, 149]}], "task": "NER"}
{"text": "Following induction , ethanol and water were concurrently available for 22 h / day .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [22, 29]}], "task": "NER"}
{"text": "RESULTS : The FT 300 - s schedule gradually increased ACTH , but not cortisol , during water induction to a plateau sustained throughout ethanol induction in every monkey .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [69, 77]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [137, 144]}], "task": "NER"}
{"text": "Upon termination of the schedule , ACTH decreased to baseline and cortisol below baseline .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "Diurnal ACTH and cortisol were unrelated to the dose of ethanol , but ACTH rhythm flattened at 0 . 5 g / kg / day and remained flattened .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "CONCLUSIONS : The coincidence of elevated ACTH with the initial experience of drinking to intoxication may have altered the mechanisms involved in the transition to heavy drinking .", "entity": [], "task": "NER"}
{"text": "Repressive Epigenetic Changes at the Mglu2 Promoter in Frontal Cortex of 5 - HT2A Knockout Mice .", "entity": [], "task": "NER"}
{"text": "Serotonin 5 - HT2A and metabotropic glutamate 2 ( mGlu2 ) are G protein - coupled receptors suspected in the pathophysiology of psychiatric disorders such as schizophrenia , depression and suicide .", "entity": [{"entity": "Serotonin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [36, 45]}], "task": "NER"}
{"text": "Previous findings demonstrate that mGlu2 mRNA expression is down - regulated in brain cortical regions of 5 - HT2A knockout ( KO ) mice .", "entity": [], "task": "NER"}
{"text": "However , the molecular mechanism responsible for this alteration remains unknown .", "entity": [], "task": "NER"}
{"text": "We show here repressive epigenetic changes at the promoter region of the mGlu2 gene in frontal cortex of 5 - HT2A - KO mice .", "entity": [], "task": "NER"}
{"text": "Disruption of 5 - HT2A receptor - dependent signaling in mice was associated with decreased acetylation of histone H3 ( H3ac ) and H4 ( H4ac ) , and increased tri - methylation of histone H3 at lysine 27 ( H3K27me3 ) at the mGlu2 promoter - epigenetic changes that correlate with transcriptional repression .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [194, 200]}], "task": "NER"}
{"text": "Neither methylation of histone H3 at lysine 4 ( H3K4me1 / 2 / 3 ) nor tri - methylation of histone H3 at lysine 9 ( H3K9me3 ) was affected .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [37, 43]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [105, 111]}], "task": "NER"}
{"text": "We found that Egr1 , a transcription factor whose promoter activity was positively regulated by the 5 - HT2A receptor agonist TCB - 2 , binds less to the mGlu2 promoter in frontal cortex of 5 - HT2A - KO as compared to wild - type mice .", "entity": [{"entity": "TCB - 2", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Furthermore , expression of mGlu2 was increased by viral - mediated gene transfer of Flag - tagged Egr1 in mouse frontal cortex .", "entity": [], "task": "NER"}
{"text": "Together , these observations suggest that 5 - HT2A receptor - dependent signaling epigenetically affects mGlu2 transcription in mouse frontal cortex .", "entity": [], "task": "NER"}
{"text": "Relationship of Dehydroepiandrosterone Sulfate with Overweight and Insulin Sensitivity in 12 - 16 - Year - old Spanish Children .", "entity": [{"entity": "Dehydroepiandrosterone Sulfate", "entity_type": "Chemical", "pos": [16, 46]}], "task": "NER"}
{"text": "DHEA - S is the most abundant steroid hormone in human circulation .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Although a relationship of DHEA - S with obesity - related diseases has been reported , the metabolic role of this hormone remains unclear , particularly in children .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "In our study , we have investigated the relationship of DHEA - S levels with anthropometric variables , insulin , HOMA , and free fatty acids in adolescents .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [125, 141]}], "task": "NER"}
{"text": "The study sample included 812 healthy 12 - 16 - year - old children ( 383 boys and 429 girls ) .", "entity": [], "task": "NER"}
{"text": "Plasma DHEA - S was determined by RIA , insulin concentrations by IRMA , and free fatty acids by using a commercial kit .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [7, 15]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [77, 93]}], "task": "NER"}
{"text": "Insulin resistance was estimated using the HOMA index .", "entity": [], "task": "NER"}
{"text": "No significant differences in plasma DHEA - S levels were found between sexes .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "DHEA - S levels in overweight children were significantly higher than in normal - weight children .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "DHEA - S levels were significantly correlated with weight and BMI after adjusting for age .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Significant positive correlations between DHEA - S and free fatty acids levels were found after adjusting for age and BMI , particularly in boys , but not between DHEA - S levels and insulin or HOMA in either gender .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [55, 71]}, {"entity": "DHEA - S", "entity_type": "Chemical", "pos": [163, 171]}], "task": "NER"}
{"text": "DHEA - S levels in 12 - 16 - year - old children are correlated with weight and BMI independently of age .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "We failed to find any association between DHEA - S and insulin levels , but we did find a - significant correlation between DHEA - S and free fatty acids levels , suggesting that its association with free fatty acids may be related to the onset of the association of DHEA - S with insulin resi - stance .", "entity": [{"entity": "DHEA - S", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "DHEA - S", "entity_type": "Chemical", "pos": [124, 132]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [137, 153]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [200, 216]}, {"entity": "DHEA - S", "entity_type": "Chemical", "pos": [267, 275]}], "task": "NER"}
{"text": "Dammarane - type saponins from heat - processed Gynostemma pentaphyllum show fortified activity against A549 cells .", "entity": [{"entity": "Dammarane", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "saponins", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "An ethanol extract from heat - processed Gynostemma pentaphyllum showed more potent cytotoxic activity against human lung adenocarcinoma A549 cells than that of raw G . pentaphyllum .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [3, 10]}], "task": "NER"}
{"text": "Four constituents were isolated from heat - processed G . pentaphyllum using resin HP - 20 , silica gel and reversed ODS column chromatography .", "entity": [{"entity": "silica gel", "entity_type": "Chemical", "pos": [93, 103]}], "task": "NER"}
{"text": "They were identified by mass and NMR spectra as damulin A and damulin B , gypenoside L and gypenoside LI , respectively .", "entity": [{"entity": "damulin A", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "damulin B", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "gypenoside L", "entity_type": "Chemical", "pos": [74, 86]}, {"entity": "gypenoside LI", "entity_type": "Chemical", "pos": [91, 104]}], "task": "NER"}
{"text": "To evaluate the efficacy of these four constituents , the MTT cytotoxicity assay was performed using A549 cells .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "Based on the structure of these four constituents , the results indicate that the hydroxyl group in C - 2 and double bond in C20 ( 21 ) and C20 ( 22 ) positions are of importance in inhibition of A549 cell proliferation .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [82, 90]}], "task": "NER"}
{"text": "Two new tirucallane triterpenoids from the leaves of Aquilaria sinensis .", "entity": [{"entity": "tirucallane triterpenoids", "entity_type": "Chemical", "pos": [8, 33]}], "task": "NER"}
{"text": "Two new tirucallane triterpenoids , aquilacallanes A - B ( 1 - 2 ) , together with 15 known compounds ( 3 - 17 ) were isolated from the leaves of Aquilaria sinensis .", "entity": [{"entity": "tirucallane triterpenoids", "entity_type": "Chemical", "pos": [8, 33]}, {"entity": "aquilacallanes A - B", "entity_type": "Chemical", "pos": [36, 56]}], "task": "NER"}
{"text": "The structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses .", "entity": [], "task": "NER"}
{"text": "All compounds were evaluated for their cytotoxic activity against five human cancer cell lines .", "entity": [], "task": "NER"}
{"text": "The known compounds , ursolic acid ( 7 ) and 5 , 7 , 4 ' - trimethoxyflavone ( 14 ) , exhibited weak cytotoxic activity against some cells .", "entity": [{"entity": "ursolic acid", "entity_type": "Chemical", "pos": [22, 34]}, {"entity": "5 , 7 , 4 ' - trimethoxyflavone", "entity_type": "Chemical", "pos": [45, 76]}], "task": "NER"}
{"text": "Free radical reactions in two dimensions : a case study on photochlorination of graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [80, 88]}], "task": "NER"}
{"text": "Graphene , a two - dimensional giant - molecule of sp ( 2 ) - bonded carbon atoms , provides a perfect platform for studying free radical reaction chemistry in two - dimensions , which holds promise to control the chemical functionality of graphene .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [69, 75]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [240, 248]}], "task": "NER"}
{"text": "Free - radical photochlorination of graphene is used as an example to investigate the thickness , stacking order , and single - and double - side dependent reactivity in graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [170, 178]}], "task": "NER"}
{"text": "Anomalously low reactivity is observed in the photochlorination of AB - stacked bilayer graphene in comparison with that of few - layer graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [88, 96]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Double - sided chlorination of graphene shows higher reactivity and chlorine coverage than single - sided reaction .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [31, 39]}, {"entity": "chlorine", "entity_type": "Chemical", "pos": [68, 76]}], "task": "NER"}
{"text": "It is also experimentally and theoretically demonstrated that chlorine free radicals at low coverage prefer to form a stable charge - transfer complex with graphene , which highly enhances graphene ' s conductivity and simultaneously generates a pseudo - bandgap through noninvasive doping .", "entity": [{"entity": "chlorine", "entity_type": "Chemical", "pos": [62, 70]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [156, 164]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [189, 197]}], "task": "NER"}
{"text": "Moreover , the initial accumulation of chlorine radicals is considered as the rate - determining step of photochlorination of graphene .", "entity": [{"entity": "chlorine", "entity_type": "Chemical", "pos": [39, 47]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [126, 134]}], "task": "NER"}
{"text": "Enhanced Replication of R5 HIV - 1 Isolates in vitro by a Small - Molecule Reagent Targeting HIV - 1 Protease .", "entity": [], "task": "NER"}
{"text": "Chemical enhancement : Designed to target HIV - 1 protease , a novel gamma - hydroxyphosphonate has been found to significantly enhance viral replication in a panel of clinically relevant R5 HIV - 1 isolates .", "entity": [{"entity": "gamma - hydroxyphosphonate", "entity_type": "Chemical", "pos": [69, 95]}], "task": "NER"}
{"text": "This unexpected result constitutes the first instance of a small molecule capable of doing this , and it has implications for the preparation and use of R5 isolates in vaccine and drug development .", "entity": [], "task": "NER"}
{"text": "Synthesis and evaluation of stable substrate analogs as potential modulators of cyclodiphosphate synthase IspF .", "entity": [{"entity": "cyclodiphosphate", "entity_type": "Chemical", "pos": [80, 96]}], "task": "NER"}
{"text": "Stable IspF substrate analogs were synthesized .", "entity": [], "task": "NER"}
{"text": "In the presence of substrate analogs , the E . coli IspF - MEP complex shows activities distinct from IspF , and bisphosphonates ( BP ) behave differently than their diphosphate ( DP ) counterparts .", "entity": [{"entity": "MEP", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "bisphosphonates", "entity_type": "Chemical", "pos": [113, 128]}, {"entity": "diphosphate", "entity_type": "Chemical", "pos": [166, 177]}], "task": "NER"}
{"text": "Bisphosphonate analogs activate and / or stabilize IspF , and only the closest structural substrate analog weakly inhibits the IspF - MEP complex .", "entity": [{"entity": "Bisphosphonate", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "MEP", "entity_type": "Chemical", "pos": [134, 137]}], "task": "NER"}
{"text": "Scopoletin and Scopolin Isolated from Artemisia iwayomogi Suppress Differentiation of Osteoclastic Macrophage RAW 264 . 7 Cells by Scavenging Reactive Oxygen Species .", "entity": [{"entity": "Scopoletin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "Scopolin", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "Oxygen", "entity_type": "Chemical", "pos": [151, 157]}], "task": "NER"}
{"text": "Artemisia iwayomogi has been used as a folk medicine for treating various diseases including inflammatory and immune - related diseases .", "entity": [], "task": "NER"}
{"text": "Scopoletin ( 1 ) and scopolin ( 2 ) were isolated from this species .", "entity": [{"entity": "Scopoletin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "scopolin", "entity_type": "Chemical", "pos": [21, 29]}], "task": "NER"}
{"text": "Scopoletin ( 1 ) showed more potent peroxyl radical - scavenging capacity , reducing capacity , and cellular antioxidant capacity compared to scopolin ( 2 ) .", "entity": [{"entity": "Scopoletin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "peroxyl", "entity_type": "Chemical", "pos": [36, 43]}, {"entity": "scopolin", "entity_type": "Chemical", "pos": [142, 150]}], "task": "NER"}
{"text": "The inhibitory effect of 1 on the receptor activator of nuclear factor kappa B ligand - induced osteoclastic differentiation of RAW 264 . 7 macrophage cells was also more potent than that of 2 .", "entity": [], "task": "NER"}
{"text": "The production of general reactive oxygen species ( ROS ) and superoxide anions during differentiation of preosteoclastic RAW 264 . 7 cells into osteoclasts was attenuated by compounds 1 and 2 .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [35, 41]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [62, 72]}], "task": "NER"}
{"text": "These findings indicate that the suppressive effects of 1 and 2 on the differentiation of preosteoclastic RAW 264 . 7 cells is partially due to their intracellular antioxidant capacity , as they can scavenge ROS and play an important signaling role in the differentiation process .", "entity": [], "task": "NER"}
{"text": "Acoustics as a Tool for Better Characterization of Ionic Liquids : A Comparative Study of 1 - Alkyl - 3 - methylimidazolium Bis [ ( trifluoromethyl ) sulfonyl ] imide Room - Temperature Ionic Liquids .", "entity": [{"entity": "1 - Alkyl - 3 - methylimidazolium Bis [ ( trifluoromethyl ) sulfonyl ] imide", "entity_type": "Chemical", "pos": [90, 166]}], "task": "NER"}
{"text": "Acoustic properties of three ( 1 - ethyl - , 1 - butyl - , and 1 - octyl - ) 1 - alkyl - 3 - methylimidazolium bis [ ( trifluoromethyl ) sulfonyl ] imide room - temperature ionic liquids are reported and discussed .", "entity": [{"entity": "1 - ethyl", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "1 - butyl", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "1 - octyl", "entity_type": "Chemical", "pos": [63, 72]}, {"entity": "1 - alkyl - 3 - methylimidazolium bis [ ( trifluoromethyl ) sulfonyl ] imide", "entity_type": "Chemical", "pos": [77, 153]}], "task": "NER"}
{"text": "The speeds of sound in RTILs were measured as a function of temperature in the range 288 - 323 K by means of a sing around method .", "entity": [], "task": "NER"}
{"text": "The densities and isobaric heat capacities were determined from 288 . 15 to 363 . 15 K and from 293 . 15 to 323 . 15 K , respectively .", "entity": [], "task": "NER"}
{"text": "The related properties , like isentropic and isothermal compressibilities , isobaric coefficients of thermal expansion , molar isochoric heat capacities , and internal pressures , were calculated .", "entity": [], "task": "NER"}
{"text": "It was found that for some ionic liquids , temperature dependence of isobaric coefficients of thermal expansion is small and negative .", "entity": [], "task": "NER"}
{"text": "All investigations were completed by the ultrasound absorption coefficient measurements in 1 - ethyl - and 1 - octyl - 3 - methylimidazolium bis [ ( trifluoromethyl ) sulfonyl ] imide as a function of frequency from 10 to 300 MHz at temperatures 293 . 15 - 298 . 15 K .", "entity": [{"entity": "1 - ethyl - and 1 - octyl - 3 - methylimidazolium bis [ ( trifluoromethyl ) sulfonyl ] imide", "entity_type": "Chemical", "pos": [91, 183]}], "task": "NER"}
{"text": "The ultrasound absorption spectra indicate relaxation frequencies in the megahertz range .", "entity": [], "task": "NER"}
{"text": "Ectopic Thyroid Tissue in the Adrenal Gland : Report of 2 Cases with Pathogenetic Implications .", "entity": [], "task": "NER"}
{"text": "Background : Ectopic thyroid tissue is usually found anywhere along the embryonic descent pathway of the medial thyroid anlage from the tongue to the trachea ( W o lfler area ) .", "entity": [], "task": "NER"}
{"text": "However , ectopic thyroid tissue in the adrenal gland ( ETTAG ) is not easy to understand on the basis of thyroid embryology ; because it is so rare , the possibility of metastasis should first be considered .", "entity": [], "task": "NER"}
{"text": "Here , we describe 2 cases of ETTAG with pathogenetic implications and review the literature .", "entity": [], "task": "NER"}
{"text": "Patient findings : Two cases of ETTAG presented as incidental cystic adrenal masses in adult females , one having a congenital hernia of Morgagni .", "entity": [], "task": "NER"}
{"text": "The ETTAG was histologically indistinguishable from normal orthotopic thyroid tissue , and its follicular nature was confirmed by immunohistochemical positivity for thyroglobulin , thyroperoxidase , thyroid transcription factor - 1 ( TTF - 1 / Titf - 1 / Nkx2 . 1 ) , cytokeratin ( CK ) AE1 / AE3 , CK 7 , pendrin , human sodium iodide symporter ( hNIS ) , paired box gene 8 ( PAX8 ) and FOXE1 ( TTF - 2 ) , as well as positivity for the messenger RNA of the thyroglobulin gene by in situ hybridization analysis .", "entity": [{"entity": "sodium iodide", "entity_type": "Chemical", "pos": [322, 335]}], "task": "NER"}
{"text": "No C cells ( negativity for calcitonin , cromogranin and synaptophysin ) were present .", "entity": [], "task": "NER"}
{"text": "Neither BRAF nor KRAS mutations were detected with real - time polymerase chain reaction analysis .", "entity": [], "task": "NER"}
{"text": "Further work - up did not show evidence of thyroid malignancy .", "entity": [], "task": "NER"}
{"text": "Summary : ETTAG is a rare finding , with only 7 cases reported ; women are much more frequently affected than men ( 8 : 1 ) and it usually clinically presents in the fifth decade ( mean age : 54 , range : 38 - 67 ) as a cystic adrenal mass incidentally discovered on abdominal ultrasonography and / or in computed tomography images .", "entity": [], "task": "NER"}
{"text": "ETTAG is composed of normal follicular cells without C cells .", "entity": [], "task": "NER"}
{"text": "The expression of some transcription factors ( TTF - 1 , PAX8 and FOXE1 ) involved in development and / or migration of the medial thyroid anlage is preserved .", "entity": [], "task": "NER"}
{"text": "Coexistence of a congenital hernia of Morgagni in one patient suggests an over - descent of medial thyroid anlage derived cells in its pathogenesis .", "entity": [], "task": "NER"}
{"text": "Conclusion : Although ETTAG pathogenesis remains unknown , the lack of C cells together with the coexistence of a congenital defect of the anterior diaphragm ( hernia of Morgagni ) in one of our patients could suggest an over - descent of medial thyroid anlagen derived cells in the origin of this heterotopia .", "entity": [], "task": "NER"}
{"text": "Dendrimer Driven Self - Assembly of SPR Active Silver - Gold Nanohybrids .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "A fourth generation PAMAM dendrimer has been successfully employed for the development of a single step synthesis strategy for self - assembled Ag - Au nanohybrid structures .", "entity": [{"entity": "PAMAM", "entity_type": "Chemical", "pos": [20, 25]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [144, 146]}, {"entity": "Au", "entity_type": "Chemical", "pos": [149, 151]}], "task": "NER"}
{"text": "The surface plasmon resonance properties and the degree of self - assembly of the nanohybrid are strongly correlated with the stoichiometry of the metals which gives rise to enhanced plasmonic properties .", "entity": [], "task": "NER"}
{"text": "The enhanced plasmonic response of the nanohybrids is modeled and is validated experimentally in a model HRP ( horseradish peroxidise ) bioassay carried out on an SPR - based biochip platform .", "entity": [], "task": "NER"}
{"text": "H3O2 Bridging Ligand in a Metal - Organic Framework .", "entity": [{"entity": "H3O2", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Insight into the Aqua - Hydroxo <--> Hydroxyl Equilibrium : A Combined Experimental and Theoretical Study .", "entity": [{"entity": "Aqua - Hydroxo", "entity_type": "Chemical", "pos": [17, 31]}, {"entity": "Hydroxyl", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "A metal - organic framework ( MOF ) bearing the aqua - hydroxo species ( O2H3 ) ( - ) in the framework , as well as the processes that govern the equilibrium aqua - hydroxo ( O2H3 ) ( - ) <--> hydroxyl ( OH ) in Sc - MOFs , are studied experimentally and theoretically .", "entity": [{"entity": "aqua - hydroxo", "entity_type": "Chemical", "pos": [48, 62]}, {"entity": "( O2H3 ) ( - )", "entity_type": "Chemical", "pos": [71, 85]}, {"entity": "aqua - hydroxo", "entity_type": "Chemical", "pos": [158, 172]}, {"entity": "( O2H3 ) ( - )", "entity_type": "Chemical", "pos": [173, 187]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [193, 201]}, {"entity": "OH", "entity_type": "Chemical", "pos": [204, 206]}, {"entity": "Sc", "entity_type": "Chemical", "pos": [212, 214]}], "task": "NER"}
{"text": "Computational studies were employed to determine the relative energies for the two compounds that coexist under certain hydrothermal conditions at pH < 2 . 8 .", "entity": [], "task": "NER"}
{"text": "The thermodynamically more stable [ Sc3 ( 3 , 5 - DSB ) 2 ( mu - O2H3 ) ( mu - OH ) 2 ( H2O ) 2 ] ( from now on , ( O2H3 ) Sc - MOF ; 3 , 5 - DSB = 3 , 5 - disulfobenzoic acid ) was obtained as a pure and stable phase .", "entity": [{"entity": "[ Sc3 ( 3 , 5 - DSB ) 2 ( mu - O2H3 ) ( mu - OH ) 2 ( H2O ) 2 ]", "entity_type": "Chemical", "pos": [34, 97]}, {"entity": "( O2H3 ) Sc", "entity_type": "Chemical", "pos": [114, 125]}, {"entity": "3 , 5 - DSB", "entity_type": "Chemical", "pos": [134, 145]}, {"entity": "3 , 5 - disulfobenzoic acid", "entity_type": "Chemical", "pos": [148, 175]}], "task": "NER"}
{"text": "It was impossible to isolate [ Sc3 ( 3 , 5 - DSB ) 2 ( mu - OH ) 3 ( H2O ) 4 ] as a pure phase , as it turned out to be the precursor of ( O2H3 ) Sc - MOF .", "entity": [{"entity": "[ Sc3 ( 3 , 5 - DSB ) 2 ( mu - OH ) 3 ( H2O ) 4 ]", "entity_type": "Chemical", "pos": [29, 78]}, {"entity": "( O2H3 ) Sc", "entity_type": "Chemical", "pos": [137, 148]}], "task": "NER"}
{"text": "Additionally , a third compound that appears at pH between 3 . 5 and 4 , [ Sc3 ( 3 , 5 - DSB ) ( mu - OH ) 6 ( H2O ) ] and a fourth , [ Sc ( 3 , 5 - DSB ) ( Phen ) ( H2O ) ] ( H2O ) , in whose formula neither OH groups nor H3O2 ( - ) anions appear , are reported for comparative purposes .", "entity": [{"entity": "[ Sc3 ( 3 , 5 - DSB ) ( mu - OH ) 6 ( H2O ) ]", "entity_type": "Chemical", "pos": [73, 118]}, {"entity": "[ Sc ( 3 , 5 - DSB ) ( Phen ) ( H2O ) ] ( H2O )", "entity_type": "Chemical", "pos": [134, 181]}, {"entity": "OH", "entity_type": "Chemical", "pos": [209, 211]}, {"entity": "H3O2 ( - )", "entity_type": "Chemical", "pos": [223, 233]}], "task": "NER"}
{"text": "A study of the ( O2H3 ) Sc - MOF electronic structure , and some heterogeneous catalytic tests in cyanosilylation of aldehydes reactions , are also reported .", "entity": [{"entity": "( O2H3 ) Sc", "entity_type": "Chemical", "pos": [15, 26]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [117, 126]}], "task": "NER"}
{"text": "Identification of benzofurano [ 3 , 2 - d ] pyrimidin - 2 - ones , a new series of HIV - 1 nucleotide - competing reverse transcriptase inhibitors .", "entity": [{"entity": "benzofurano [ 3 , 2 - d ] pyrimidin - 2 - ones", "entity_type": "Chemical", "pos": [18, 64]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [91, 101]}], "task": "NER"}
{"text": "Screening of our sample collection led to the identification of a set of benzofurano [ 3 , 2 - d ] pyrimidine - 2 - one hits acting as nucleotide - competing HIV - 1 reverse transcriptase inhibitiors ( NcRTI ) .", "entity": [{"entity": "benzofurano [ 3 , 2 - d ] pyrimidine - 2 - one", "entity_type": "Chemical", "pos": [73, 119]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [135, 145]}], "task": "NER"}
{"text": "Significant improvement in antiviral potency was achieved when substituents were introduced at positions N1 , C4 , C7 and C8 on the benzofuranopyrimidone scaffold .", "entity": [{"entity": "benzofuranopyrimidone", "entity_type": "Chemical", "pos": [132, 153]}], "task": "NER"}
{"text": "The series was optimized from low micromolar enzymatic activity against HIV - 1 RT and no antiviral activity to low nanomolar antiviral potency .", "entity": [], "task": "NER"}
{"text": "Further profiling of inhibitor 30 showed promising overall in vitro properties and also demonstrated that its potency was maintained against viruses resistant to the other major classes of HIV - 1 RT inhibitors .", "entity": [], "task": "NER"}
{"text": "Is there a link between neutrophil - lymphocyte ratio and microvascular complications in geriatric diabetic patients ?", "entity": [], "task": "NER"}
{"text": "Background : Chronic inflammation plays an important role on development and progression of type 2 diabetes through immunologic inflammatory mechanisms .", "entity": [], "task": "NER"}
{"text": "Neutrophil to lymphocyte ratio ( NLR ) is a new , simple and cheap marker of subclinical inflammation .", "entity": [], "task": "NER"}
{"text": "NLR has recently been used as a systemic inflammation marker in chronic diseases as well as a predictor of prognosis in cardiovascular diseases and malignancies .", "entity": [], "task": "NER"}
{"text": "Aim : The objective of the present study was to investigate the relationship between NLR and microvascular complications of diabetes mellitus in elderly population .", "entity": [], "task": "NER"}
{"text": "Subjects and methods : Two hundred and forty - two patients with DM ( 145 diabetic patients with complications , 97 diabetic patients without complications ) and 218 control subjects were enrolled in this study .", "entity": [], "task": "NER"}
{"text": "NLR and microvascular complications because of diabetes mellitus were evaluated and compared with other inflammatory markers .", "entity": [], "task": "NER"}
{"text": "Results : NLR was higher in the diabetic group ( 2 . 21 +/- 1 . 14 ) than in the controls ( 2 . 18 +/- 0 . 76 ) .", "entity": [], "task": "NER"}
{"text": "Furthermore , there was a statistically significant difference between NLR levels in diabetic patients with and without complications ( 2 . 46 +/- 1 . 26 vs . 2 . 04 +/- 0 . 51 , respectively ; P < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "The results of the multiple logistic regression analysis depicted that NLR is also an independent predictor for microvascular complications ( OR = 2 . 217 ; 95 % = 1 . 086 - 4 . 526 , P = 0 . 029 ) .", "entity": [], "task": "NER"}
{"text": "ROC curve analysis suggested that the optimum NLR cut - off point for microvascular complication was 2 . 89 with 96 . 72 % specificity , 94 . 4 % positive predictive value .", "entity": [], "task": "NER"}
{"text": "Conclusion : Increased NLR levels may be associated with microvascular complications of diabetes mellitus in the elderly population .", "entity": [], "task": "NER"}
{"text": "High density lipoprotein as a source of cholesterol for adrenal steroidogenesis : a study in individuals with low plasma HDL - C .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [40, 51]}], "task": "NER"}
{"text": "Few studies have addressed the delivery of lipoprotein - derived cholesterol to the adrenals for steroid production in humans .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [65, 76]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [97, 104]}], "task": "NER"}
{"text": "While there is evidence against a role for low - density lipoprotein ( LDL ) , it is unresolved whether high density lipoprotein ( HDL ) contributes to adrenal steroidogenesis .", "entity": [], "task": "NER"}
{"text": "To study this , steroid hormone profiles in urine were assessed in male subjects suffering from functional mutations in ATP binding cassette transporter A1 ( ABCA1 ) ( n = 24 ) , lecithin : cholesterol acyltransferase ( LCAT ) ( n = 40 ) , as well as in 11 subjects with low HDL cholesterol ( HDL - C ) without ABCA1 / LCAT mutations .", "entity": [{"entity": "steroid hormone", "entity_type": "Chemical", "pos": [16, 31]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [120, 123]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [190, 201]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [279, 290]}], "task": "NER"}
{"text": "HDL - C levels were 39 % lower in the ABCA1 , LCAT , and low HDL - C groups compared with controls ( all P < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "In all groups with low HDL - C levels , urinary excretion of 17 - ketogenic steroids was reduced by 33 % , 27 % , and 32 % compared with controls ( all P < 0 . 04 ) .", "entity": [{"entity": "17 - ketogenic steroids", "entity_type": "Chemical", "pos": [61, 84]}], "task": "NER"}
{"text": "In seven carriers of either type of mutation , adrenocorticotropic hormone ( ACTH ) stimulation did not reveal differences from normolipidemic controls .", "entity": [], "task": "NER"}
{"text": "In conclusion , this study shows that basal but not stimulated corticosteroid metabolism is attenuated in subjects with low HDL - C , irrespective of its molecular origin .", "entity": [], "task": "NER"}
{"text": "These findings lend support to a role for HDL as a cholesterol donor for basal adrenal steroidogenesis in humans .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [51, 62]}], "task": "NER"}
{"text": "Redox - and pH - Responsive Cysteamine - Modified Poly ( aspartic acid ) Showing a Reversible Sol - Gel Transition .", "entity": [{"entity": "Cysteamine", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "Poly ( aspartic acid )", "entity_type": "Chemical", "pos": [50, 72]}], "task": "NER"}
{"text": "Synthesis and characterization of a pH - and redox - sensitive hydrogel of poly ( aspartic acid ) are reported .", "entity": [{"entity": "poly ( aspartic acid )", "entity_type": "Chemical", "pos": [75, 97]}], "task": "NER"}
{"text": "Reversible gelation and dissolution are achieved both in dimethylformamide and in aqueous medium via a thiol - disulphide interconversion in the side chain of the polymers .", "entity": [{"entity": "dimethylformamide", "entity_type": "Chemical", "pos": [57, 74]}, {"entity": "thiol - disulphide", "entity_type": "Chemical", "pos": [103, 121]}], "task": "NER"}
{"text": "Structural changes are confirmed by Raman microscopy and rheological measurements .", "entity": [], "task": "NER"}
{"text": "Injectable aqueous solutions of thiolated poly ( aspartic acid ) can be converted into mechanically stable gels by oxidation , which can be useful for drug encapsulation and targeted delivery .", "entity": [{"entity": "thiolated poly ( aspartic acid )", "entity_type": "Chemical", "pos": [32, 64]}], "task": "NER"}
{"text": "Reduction - facilitated release of an entrapped drug from disulphide cross - linked hydrogels is studied .", "entity": [{"entity": "disulphide", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "Diarylheptanoids from Alnus glutinosa Bark and Their Chemoprotective Effect on Human Lymphocytes DNA .", "entity": [{"entity": "Diarylheptanoids", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "A study of secondary metabolites from the bark of Alnus glutinosa led to the isolation of fourteen diarylheptanoids : oregonin ( 1 ) , platyphylloside ( 2 ) , rubranoside A ( 3 ) , rubranoside B ( 4 ) , hirsutanonol ( 5 ) , hirsutenone ( 6 ) , hirsutanonol - 5 - O - beta - D - glucopyranoside ( 7 ) , platyphyllonol - 5 - O - beta - D - xylopyranoside ( 8 ) , aceroside VII ( 9 ) , alnuside A ( 10 ) , alnuside B ( 11 ) , 1 , 7 - bis - ( 3 , 4 - dihydoxyphenyl ) - 5 - hydroxy - heptane - 3 - O - beta - D - xylopyranoside ( 12 ) , ( 5S ) - 1 - ( 4 - hydroxyphenyl ) - 7 - ( 3 , 4 - dihydroxyphenyl ) - 5 - O - beta - D - glucopyranosyl - heptan - 3 - one ( 13 ) , and ( 5S ) - 1 , 7 - bis - ( 3 , 4 - dihydroxyphenyl ) - 5 - O - beta - D - [ 6 - ( 3 , 4 - dimethoxycinnamoylglucopyranosyl ) ] - heptan - 3 - one ( 14 ) .", "entity": [{"entity": "diarylheptanoids", "entity_type": "Chemical", "pos": [99, 115]}, {"entity": "oregonin", "entity_type": "Chemical", "pos": [118, 126]}, {"entity": "platyphylloside", "entity_type": "Chemical", "pos": [135, 150]}, {"entity": "rubranoside A", "entity_type": "Chemical", "pos": [159, 172]}, {"entity": "rubranoside B", "entity_type": "Chemical", "pos": [181, 194]}, {"entity": "hirsutanonol", "entity_type": "Chemical", "pos": [203, 215]}, {"entity": "hirsutenone", "entity_type": "Chemical", "pos": [224, 235]}, {"entity": "hirsutanonol - 5 - O - beta - D - glucopyranoside", "entity_type": "Chemical", "pos": [244, 293]}, {"entity": "platyphyllonol - 5 - O - beta - D - xylopyranoside", "entity_type": "Chemical", "pos": [302, 352]}, {"entity": "aceroside VII", "entity_type": "Chemical", "pos": [361, 374]}, {"entity": "alnuside A", "entity_type": "Chemical", "pos": [383, 393]}, {"entity": "alnuside B", "entity_type": "Chemical", "pos": [403, 413]}, {"entity": "1 , 7 - bis - ( 3 , 4 - dihydoxyphenyl ) - 5 - hydroxy - heptane - 3 - O - beta - D - xylopyranoside", "entity_type": "Chemical", "pos": [423, 523]}, {"entity": "( 5S ) - 1 - ( 4 - hydroxyphenyl ) - 7 - ( 3 , 4 - dihydroxyphenyl ) - 5 - O - beta - D - glucopyranosyl - heptan - 3 - one", "entity_type": "Chemical", "pos": [533, 656]}, {"entity": "( 5S ) - 1 , 7 - bis - ( 3 , 4 - dihydroxyphenyl ) - 5 - O - beta - D - [ 6 - ( 3 , 4 - dimethoxycinnamoylglucopyranosyl ) ] - heptan - 3 - one", "entity_type": "Chemical", "pos": [670, 813]}], "task": "NER"}
{"text": "All of the diarylheptanoids , except 1 and 5 , were found in A . glutinosa for the first time , while 13 and 14 were new compounds .", "entity": [{"entity": "diarylheptanoids", "entity_type": "Chemical", "pos": [11, 27]}], "task": "NER"}
{"text": "The structures were determined by spectroscopic techniques : 1D and 2D NMR , HR - ESI - MS , FTIR , UV , and CD .", "entity": [], "task": "NER"}
{"text": "All isolated compounds were analyzed for an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using the cytokinesis - block micronucleus assay .", "entity": [], "task": "NER"}
{"text": "The majority of them , including the new compounds 13 and 14 , exerted a pronounced effect in decreasing DNA damage in human lymphocytes .", "entity": [], "task": "NER"}
{"text": "Diarylheptanoids 1 , 2 , 5 , 13 , and 14 at a concentration of 1 micro g / mL decreased the frequency of micronuclei by 52 . 8 % , 43 . 8 % , 63 . 6 % , 44 . 4 % , and 56 . 0 % , respectively , exerting a much stronger effect than the synthetic protector amifostine ( 17 . 2 % , c = 1 micro g / mL ) .", "entity": [{"entity": "Diarylheptanoids", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "amifostine", "entity_type": "Chemical", "pos": [255, 265]}], "task": "NER"}
{"text": "Edge - to - Edge Assembled Graphene Oxide Aerogels with Outstanding Mechanical Performance and Superhigh Chemical Activity .", "entity": [{"entity": "Graphene Oxide", "entity_type": "Chemical", "pos": [27, 41]}], "task": "NER"}
{"text": "Aerogels , an extremely important aggregation state of various self - assembled nanoscale building blocks , have great potential in fields ranging from energy storage to thermal insulation .", "entity": [], "task": "NER"}
{"text": "However , the porosity of aerogels makes them mechanically weak in most cases , and the chemical activity of the resulting aerogel needs consideration .", "entity": [], "task": "NER"}
{"text": "Herein , chemically crosslinked graphene oxide ( GO ) 3D aerogels with large specific surface areas ( up to 850 m ( 2 ) g ( - 1 ) ) , outstanding mechanical performance ( up to 20 MPa Young ' s modulus , 1 MPa yield strength and 45 J g ( - 1 ) specific energy adsorption ) , and superhigh chemical activity ( toward some reducing gases such as H2 S , HI , and SO2 ) , are fabricated by assembling 2D GO sheets edge - to - edge into uniform , 3D hydrogel networks with subsequent supercritical fluid drying .", "entity": [{"entity": "graphene oxide", "entity_type": "Chemical", "pos": [32, 46]}, {"entity": "H2 S", "entity_type": "Chemical", "pos": [344, 348]}, {"entity": "HI", "entity_type": "Chemical", "pos": [351, 353]}, {"entity": "SO2", "entity_type": "Chemical", "pos": [360, 363]}], "task": "NER"}
{"text": "These aerogels are superior to other 3D frameworks ( e . g . graphene aerogels ) assembled via partial overlapping of the basal planes of the 2D building blocks .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [61, 69]}], "task": "NER"}
{"text": "Mastoid Obliteration Using Three - Dimensional Composite Scaffolds Consisting of Polycaprolactone / beta - Tricalcium Phosphate / Collagen Nanofibers : An In Vitro and In Vivo Study .", "entity": [{"entity": "Polycaprolactone", "entity_type": "Chemical", "pos": [81, 97]}, {"entity": "beta - Tricalcium Phosphate", "entity_type": "Chemical", "pos": [100, 127]}], "task": "NER"}
{"text": "Two different composite scaffolds , solid - freeform - fabricated PCL / beta - TCP supplemented with and without collagen nanofibers are fabricated .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [72, 82]}], "task": "NER"}
{"text": "These scaffolds are evaluated whether a combination of collagen nanofibers with PCL / beta - TCP can promote osteogenesis in a mastoid obliteration .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [80, 83]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [86, 96]}], "task": "NER"}
{"text": "To assess the effects of the cellular activities of osteoblast - like - cells ( MG63 ) , SEM images and MTT assays are conducted .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [104, 107]}], "task": "NER"}
{"text": "Experimental mastoid obliteration is performed using guinea pigs that are divided group A ( PCL / beta - TCP / collagen - nanofiber scaffold ) and group B ( PCL / beta - TCP scaffold ) .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [98, 108]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [157, 160]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [163, 173]}], "task": "NER"}
{"text": "The results reveal that PCL / beta - TCP / collagen scaffold provide much broader cell attachment sites than PCL / beta - TCP scaffold .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "PCL", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [115, 125]}], "task": "NER"}
{"text": "The micro - CT and fluorescent microscopy results reveal that the acceleration of early new bone formation within the pores and scaffold itself at week 4 post - operation is more effective in group A .", "entity": [], "task": "NER"}
{"text": "In addition , based on the results of the histological and micro - CT at 12 weeks post - surgery , the effective regeneration of bone in the PCL / beta - TCP / collagen scaffold is appeared .", "entity": [{"entity": "PCL", "entity_type": "Chemical", "pos": [141, 144]}, {"entity": "beta - TCP", "entity_type": "Chemical", "pos": [147, 157]}], "task": "NER"}
{"text": "Anticonvulsant / antiepileptic carbonic anhydrase inhibitors : a patent review .", "entity": [], "task": "NER"}
{"text": "Introduction : An epileptic seizure is a transient occurrence of signs and / or symptoms due to abnormal excessive or synchronous neuronal activity in the brain .", "entity": [], "task": "NER"}
{"text": "The International League Against Epilepsy classifies seizures in two broad categories : partial ( localized to one cerebral hemisphere ) and generalized ( localized to both cerebral hemispheres ) .", "entity": [], "task": "NER"}
{"text": "One indirect pathway for the treatment of epilepsy includes the inhibition of carbonic anhydrase ( CA ) , thereby increasing CO2 levels in the brain .", "entity": [{"entity": "CO2", "entity_type": "Chemical", "pos": [125, 128]}], "task": "NER"}
{"text": "Areas covered : Carbonic anhydrases ( EC 4 . 2 . 1 . 1 ) are ubiquitous metalloenzymes that catalyze the reversible hydration / dehydration of CO2 / HCO3 ( - ) , respectively .", "entity": [{"entity": "CO2", "entity_type": "Chemical", "pos": [143, 146]}, {"entity": "HCO3 ( - )", "entity_type": "Chemical", "pos": [149, 159]}], "task": "NER"}
{"text": "CA inhibitors ( CAIs ) such as acetazolamide , methazolamide , topiramate , zonisamide , and sulthiame can reduce seizures through perturbation of the CO2 equilibrium and / or the inhibition of ion channels .", "entity": [{"entity": "acetazolamide", "entity_type": "Chemical", "pos": [31, 44]}, {"entity": "methazolamide", "entity_type": "Chemical", "pos": [47, 60]}, {"entity": "topiramate", "entity_type": "Chemical", "pos": [63, 73]}, {"entity": "zonisamide", "entity_type": "Chemical", "pos": [76, 86]}, {"entity": "sulthiame", "entity_type": "Chemical", "pos": [93, 102]}, {"entity": "CO2", "entity_type": "Chemical", "pos": [151, 154]}], "task": "NER"}
{"text": "This review focuses on the mechanism of epilepsy , CA catalysis , and recent developments in the treatment of epilepsy using CAIs .", "entity": [], "task": "NER"}
{"text": "Expert opinion : Based on the observed active - site binding interactions of CAIs in crystal structures and their respective inhibition constants , structure - activity relationships can be mapped .", "entity": [], "task": "NER"}
{"text": "Various CAIs along with novel techniques to administer them have been patented in the last four years .", "entity": [], "task": "NER"}
{"text": "However , epilepsy continues to be a path less traveled when it comes to CAIs .", "entity": [], "task": "NER"}
{"text": "A major area of research must focus toward the design of isoform - specific inhibitors using analogs of existing CAIs .", "entity": [], "task": "NER"}
{"text": "Serotonin - kynurenine hypothesis of depression : historical overview and recent developments .", "entity": [{"entity": "Serotonin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "kynurenine", "entity_type": "Chemical", "pos": [12, 22]}], "task": "NER"}
{"text": "This mini - review focuses on the studies of late Prof .", "entity": [], "task": "NER"}
{"text": "IP Lapin ( 1903 - 2012 ) and his research team on the role of methoxyindole and kynurenine ( KYN ) pathways of tryptophan ( TRP ) metabolism in the pathogenesis of depression and action mechanisms of antidepressant effect .", "entity": [{"entity": "methoxyindole", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "kynurenine", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "KYN", "entity_type": "Chemical", "pos": [93, 96]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [111, 121]}, {"entity": "TRP", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "In the late 60s of the last century Prof .", "entity": [], "task": "NER"}
{"text": "IP Lapin suggested that \" intensification of central serotoninergic processes is a determinant of the thymoleptic ( mood elevating ) component \" while \" activation of noradrenergic processes is responsible for psychoenergetic and motor - stimulating component of the clinical antidepressant effect \" .", "entity": [], "task": "NER"}
{"text": "The cause of serotonin deficiency in depression was attributed to the shunt of TRP \" metabolism away from serotonin production towards KYN production \" due to cortisol - induced activation of liver enzyme , tryptophan 2 , 3 - dioxygenase , the rate - limiting enzyme of TRP - KYN pathway .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "TRP", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [106, 115]}, {"entity": "KYN", "entity_type": "Chemical", "pos": [135, 138]}, {"entity": "cortisol", "entity_type": "Chemical", "pos": [159, 167]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [207, 217]}, {"entity": "TRP", "entity_type": "Chemical", "pos": [270, 273]}, {"entity": "KYN", "entity_type": "Chemical", "pos": [276, 279]}], "task": "NER"}
{"text": "Prof .", "entity": [], "task": "NER"}
{"text": "Lapin suggested and discovered that KYN and its metabolites affect brain functions , and proposed the role of neurokynurenines in pathogenesis of depression and action mechanisms of antidepressant effect ( kynurenine hypothesis ) .", "entity": [{"entity": "KYN", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "kynurenine", "entity_type": "Chemical", "pos": [115, 125]}], "task": "NER"}
{"text": "Further research suggested the antidepressant and cognition - enhancing effects of post - serotonin metabolite , N - acetylserotonin ( NAS ) , an agonist to tyrosine kinase B ( TrkB ) receptor ; and link between depression and chronic inflammation - associated disorders ( e . g . , insulin resistance , hepatitis C virus ) via inflammation - induced activation of indoleamine 2 , 3 - dioxygenase , brain located rate - limiting enzyme of TRY - KYN metabolism .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [90, 99]}, {"entity": "N - acetylserotonin", "entity_type": "Chemical", "pos": [113, 132]}, {"entity": "NAS", "entity_type": "Chemical", "pos": [135, 138]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [157, 165]}, {"entity": "indoleamine", "entity_type": "Chemical", "pos": [365, 376]}, {"entity": "TRY", "entity_type": "Chemical", "pos": [439, 442]}, {"entity": "KYN", "entity_type": "Chemical", "pos": [445, 448]}], "task": "NER"}
{"text": "NAS and kynurenines might be the targets for prevention and treatment of depression and associated conditions .", "entity": [{"entity": "NAS", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "kynurenines", "entity_type": "Chemical", "pos": [8, 19]}], "task": "NER"}
{"text": "Insulin - Like Growth Factor Binding Protein 2 ( IGFBP - 2 ) Promotes Growth and Survival of Breast Epithelial Cells : Novel Regulation of the Estrogen Receptor .", "entity": [{"entity": "Estrogen", "entity_type": "Chemical", "pos": [143, 151]}], "task": "NER"}
{"text": "In breast tumors IGF binding protein - 2 ( IGFBP - 2 ) is elevated , and the presence of IGFBP - 2 has been shown to correlate with malignancy .", "entity": [], "task": "NER"}
{"text": "However , how IGFBP - 2 contributes to the malignant state is still unclear .", "entity": [], "task": "NER"}
{"text": "Silencing IGFBP - 2 blocked cell proliferation and in MCF - 7 cells increased cell death , indicating that IGFBP - 2 was acting in both a mitogenic and a survival capacity .", "entity": [], "task": "NER"}
{"text": "Exogenous IGFBP - 2 acting via integrin receptors to reduce phosphatase and tensin homolog deleted from chromosome 10 ( PTEN ) levels protected these cells against death induced by various chemotherapeutic agents .", "entity": [], "task": "NER"}
{"text": "This was dependent on a functional estrogen receptor ( ER ) - alpha because silencing ER - alpha blocked the ability of IGFBP - 2 to confer cell survival .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "Loss of IGFBP - 2 increased levels of PTEN and improved chemosensitivity of the cells , confirming its role as a survival factor .", "entity": [], "task": "NER"}
{"text": "Silencing IGFBP - 2 had no effect on the response to IGF - II , but responses to estrogen and tamoxifen were no longer observed due to loss of ER - alpha , which could be prevented by the inhibition of PTEN .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [81, 89]}, {"entity": "tamoxifen", "entity_type": "Chemical", "pos": [94, 103]}], "task": "NER"}
{"text": "Conversely , exogenous IGFBP - 2 increased ER - alpha mRNA and protein in both normal and cancer cells via its interaction with integrin receptors .", "entity": [], "task": "NER"}
{"text": "These actions of IGFBP - 2 on ER - alpha involved the IGF - I receptor and activation of phosphatidylinositol 3 - kinase in the cancer cells but were independent of this in normal breast cells .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [89, 109]}], "task": "NER"}
{"text": "The production of IGFBP - 2 by breast cancer cells enhances their proliferative potential , increases their survival , and protects them against chemotherapy - induced death .", "entity": [], "task": "NER"}
{"text": "IGFBP - 2 not only modulates IGFs and directly regulates PTEN but also has a role in maintaining ER - alpha expression .", "entity": [], "task": "NER"}
{"text": "Involvement of serotonin mechanism in methamphetamine - induced chronic pulmonary toxicity in rats .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [38, 53]}], "task": "NER"}
{"text": "The widest distribution and the highest uptake of methamphetamine ( MA ) in the human body occurred in the lungs , so that more and more attention should be paid to MA - induced pulmonary toxicity .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [50, 65]}], "task": "NER"}
{"text": "MA induces the release of serotonin , which is an important mediator in pulmonary disease .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [26, 35]}], "task": "NER"}
{"text": "The purpose of this study is to investigate the chronic response of the lung to MA and its potential mechanism in rats .", "entity": [], "task": "NER"}
{"text": "Models of the chronic toxicity of MA were established with MA of 5 mg / kg and 10 mg / kg ( intraperitoneally , twice per day ) for 5 weeks .", "entity": [], "task": "NER"}
{"text": "It was found that the high dose of MA induced rat pulmonary toxicity : crowded lung parenchyma , thickened septum , reduced number of alveolar sacs , inflammatory cell infiltration , and pulmonary arteriolar remodeling .", "entity": [], "task": "NER"}
{"text": "In addition , MA resulted in a significant increase in the lung serotonin concentration and the marked upregulation of tryptophan hydroxylase 1 , vesicular monoamine transporter 2 , serotonin transporter , and downregulation of monoamine oxidase - A .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [64, 73]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [119, 129]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [182, 191]}, {"entity": "monoamine", "entity_type": "Chemical", "pos": [228, 237]}], "task": "NER"}
{"text": "These findings suggest that MA induced chronic pulmonary toxicity , which is concerned with the elevated serotonin concentration in rat lungs by increased synthesis , reduced metabolism , augmented accumulation , and promoted release of serotonin .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [105, 114]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [237, 246]}], "task": "NER"}
{"text": "Transforming growth factor beta 1 and monocyte chemoattractant protein - 1 as prognostic markers of diabetic nephropathy .", "entity": [], "task": "NER"}
{"text": "We aimed to find the relationship between serum transforming growth factor beta 1 ( TGF - beta 1 ) and urinary monocyte chemoattractant protein - 1 ( MCP - 1 ) throughout the course of diabetic nephropathy ( DN ) and to assess the relationship between both levels and other parameters of renal injury such as albumin / creatinine ratio and estimated glomerular filtration rate ( eGFR ) .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [319, 329]}], "task": "NER"}
{"text": "Serum TGF - beta 1 , urinary MCP - 1 , eGFR , and glycosylated hemoglobin ( HbA1c ) were measured in 60 patients with type II diabetes mellitus with different degrees of nephropathy ( 20 patients with normoalbuminuria , 20 patients with microalbuminuria , and 20 patients with macroalbuminuria ) and compared with 20 matched healthy control subjects .", "entity": [], "task": "NER"}
{"text": "Both the levels of serum TGF - beta 1 and urinary MCP - 1 were significantly higher in patients with micro - and macroalbuminuria ( 137 . 8 +/- 69 . 5 and 329 . 25 +/- 41 . 46 ng / dl , respectively , for TGF - beta 1 and 167 . 41 +/- 50 . 23 and 630 . 87 +/- 318 . 10 ng / g creatinine , respectively , for MCP - 1 ) compared with normoalbuminuric patients and healthy controls ( 33 . 25 +/- 17 . 5 and 29 . 64 +/- 10 . 57 ng / dl , respectively , for TGF - beta 1 and 63 . 85 +/- 21 . 15 and 61 . 50 +/- 24 . 81 ng / g creatinine , respectively , for MCP - 1 ; p < 0 . 001 ) .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [276, 286]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [521, 531]}], "task": "NER"}
{"text": "There was a positive significant correlation between the levels of serum TGF - beta 1 and those of urinary MCP - 1 ( r = 0 . 73 , p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "Also , serum TGF - beta 1 and urinary MCP - 1 correlated positively with HbA1c ( r = 0 . 49 and 0 . 55 , respectively , p < 0 . 05 for both ) and inversely with eGFR ( r = - 0 . 69 and - 0 . 60 , respectively , p < 0 . 001 for both ) .", "entity": [], "task": "NER"}
{"text": "We can conclude that serum TGF - beta 1 and urinary MCP - 1 can be used as the markers for detection of progression of DN .", "entity": [], "task": "NER"}
{"text": "Antagonizing TGF - beta 1 and MCP - 1 might be helpful in attenuating the progression of nephropathy in diabetic patients .", "entity": [], "task": "NER"}
{"text": "Efficacy of D - penicillamine , a sequestering acetaldehyde agent , in the prevention of alcohol relapse - like drinking in rats .", "entity": [{"entity": "D - penicillamine", "entity_type": "Chemical", "pos": [12, 29]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [47, 59]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "RATIONALE : Nowadays , very few approved anti - relapse treatments for alcoholism exist , and their overall efficacy can be considered moderate .", "entity": [], "task": "NER"}
{"text": "An exciting rationale drug development opportunity for the treatment of chronic alcoholism is the use of acetaldehyde sequestering agents .", "entity": [{"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [105, 117]}], "task": "NER"}
{"text": "Although these compounds are able to attenuate or prevent most of the behavioral and neurochemical effects of ethanol , the efficacy of acetaldehyde sequestration , by using agents such as D - penicillamine ( DP ) , in relapse prevention has not been studied yet .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [110, 117]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [136, 148]}, {"entity": "D - penicillamine", "entity_type": "Chemical", "pos": [189, 206]}], "task": "NER"}
{"text": "OBJECTIVES : The aim of this study was to analyze the effects of DP treatment on the alcohol deprivation effect ( ADE ) in long - term ethanol - experienced rats as a model of relapse behavior and measure drug plasma and brain levels during treatment .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [135, 142]}], "task": "NER"}
{"text": "METHODS : Rats were subcutaneously implanted with mini - osmotic pumps delivering 0 , 0 . 25 , or 1 mg / h of DP during 1 week .", "entity": [], "task": "NER"}
{"text": "The efficacy to prevent ADE was determined .", "entity": [], "task": "NER"}
{"text": "DP plasma and brain levels achieved during its subcutaneous administration were measured .", "entity": [], "task": "NER"}
{"text": "In a second experiment , animals received bilateral infusions of 0 or 1 . 5 mu g / h of DP directly into pVTA , and the appearance of ADE was evaluated .", "entity": [], "task": "NER"}
{"text": "RESULTS : One milligram per hour , but not 0 . 25 mg / h , DP infusion prevented ADE and reduced the total ethanol preference in animals .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [107, 114]}], "task": "NER"}
{"text": "DP plasma concentrations associated with ADE suppression were around 3 - 4 mu g / ml , and brain DP levels in these conditions were about 2 - 3 % of those found in plasma .", "entity": [], "task": "NER"}
{"text": "Intra - pVTA DP administration also suppressed ADE .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : DP is able to prevent alcohol - relapse - like drinking in rats suggesting that this drug may be a useful new tool in the management of relapse in alcohol - dependent patients .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [35, 42]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [160, 167]}], "task": "NER"}
{"text": "Sublethal silver and NaCl toxicity in Daphnia magna : a comparative study of standardized chronic endpoints and progeny phototaxis .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "NaCl", "entity_type": "Chemical", "pos": [21, 25]}], "task": "NER"}
{"text": "Behavioral bioassays with the model freshwater cladoceran Daphnia magna have the potential to serve as nontraditional but sensitive endpoints of sublethal stress .", "entity": [], "task": "NER"}
{"text": "However , few studies have examined the comparative sensitivity of neonate phototaxis perturbations to standardized endpoints commonly employed in chronic toxicity testing protocols .", "entity": [], "task": "NER"}
{"text": "Even less understood are the consequences of prenatal exposure on neonate phototactic behavior .", "entity": [], "task": "NER"}
{"text": "Here , we tested the hypothesis that D . magna neonate phototaxis is a more sensitive endpoint over a chronic study period than mortality and reproduction .", "entity": [], "task": "NER"}
{"text": "D . magna 21 day studies were conducted with model stressors of sodium chloride and dissolved silver .", "entity": [{"entity": "sodium chloride", "entity_type": "Chemical", "pos": [64, 79]}, {"entity": "silver", "entity_type": "Chemical", "pos": [94, 100]}], "task": "NER"}
{"text": "Phototaxis assays of progeny response to relative light changes in small water columns were conducted for each brood .", "entity": [], "task": "NER"}
{"text": "Significant differences in neonate phototactic behavior were observed among treatment level broods , suggesting that maternal exposure to sublethal levels of NaCl and Ag + impacted offspring .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [158, 162]}, {"entity": "Ag +", "entity_type": "Chemical", "pos": [167, 171]}], "task": "NER"}
{"text": "In fact , progeny phototactic response was significantly affected at or below 21 - day LOEC thresholds for fecundity in broods 2 , 3 , 5 and 6 of the NaCl experiment and in broods 2 , 4 , 5 and 6 of the dissolved Ag + study .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [150, 154]}, {"entity": "Ag +", "entity_type": "Chemical", "pos": [213, 217]}], "task": "NER"}
{"text": "Because neonate phototaxis was generally more sensitive than standardized fecundity thresholds , we suggest employing neonate phototaxis as an ecologically important endpoint in future ecological risk assessments .", "entity": [], "task": "NER"}
{"text": "Parathyroid Hormone ( PTH ) and PTH - Related Peptide Domains Contributing to Activation of Different PTH Receptor - Mediated Signaling Pathways .", "entity": [], "task": "NER"}
{"text": "Parathyroid hormone ( PTH ) and parathyroid hormone related peptide ( PTHrP ) , acting through the osteoblast PTH1R , play important roles in bone remodeling .", "entity": [], "task": "NER"}
{"text": "Intermittent administration of PTH ( 1 - 34 ) ( teriparatide ) leads to bone formation while continuous administration paradoxically leads to bone resorption .", "entity": [], "task": "NER"}
{"text": "Activation of PTH1R promotes regulation of multiple signaling pathways , including Gs / cAMP / PKA , Gq / calcium / PKC , beta - arrestin recruitment and ERK1 / 2 phosphorylation as well as receptor internalization but their role in promoting anabolic and catabolic actions of PTH ( 1 - 34 ) are unclear .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [88, 92]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "In the present investigation , a collection of PTH ( 1 - 34 ) and PTHrP ( 1 - 34 ) peptide analogs were evaluated in orthogonal hPTH1R functional assays capturing Gs - and Gq - signaling , beta - arrestin recruitment , ERK1 / 2 phosphorylation and receptor internalization to further define patterns of of PTH1R signaling they stimulate and to further establish peptide domains contributing to agonist activity .", "entity": [], "task": "NER"}
{"text": "Results indicate that both N - and C - terminal domains are critical for activation of signaling pathways .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [27, 28]}, {"entity": "C", "entity_type": "Chemical", "pos": [35, 36]}], "task": "NER"}
{"text": "However , modifications of both regions leads to more substantial decreases in agonist potency and efficacy to stimulate Gq - signaling , beta - arrestin recruitment , ERK1 / 2 phosphorylation and receptor internalization than to stimulate Gs .", "entity": [], "task": "NER"}
{"text": "The substantial contribution of the peptide C - terminal domain in activation of hPTH1R - signaling suggests a role in positioning of the peptide N - terminal region into the receptor J - domain .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [44, 45]}, {"entity": "N", "entity_type": "Chemical", "pos": [146, 147]}], "task": "NER"}
{"text": "Several PTH and PTHrP peptide analogs evaluated in this study promote different patterns of biased agonist signaling and may serve as useful tools to further elucidate therapeutically relevant PTH1R signaling in osteoblasts .", "entity": [], "task": "NER"}
{"text": "With a better understanding of therapeutically relevant signaling , novel biased peptides with desired signaling could be designed for safer and more effective treatment of osteoporosis .", "entity": [], "task": "NER"}
{"text": "Substituted 7 - Amino - 5 - thio - thiazolo [ 4 , 5 - d ] pyrimidines as Potent and Selective Antagonists of the Fractalkine Receptor ( CX3CR1 ) .", "entity": [{"entity": "7 - Amino - 5 - thio - thiazolo [ 4 , 5 - d ] pyrimidines", "entity_type": "Chemical", "pos": [12, 69]}], "task": "NER"}
{"text": "We have developed two parallel series , A and B , of CX3CR1 antagonists for the treatment of multiple sclerosis .", "entity": [], "task": "NER"}
{"text": "By modifying the substituents on the 7 - amino - 5 - thio - thiazolo [ 4 , 5 - d ] pyrimidine core structure , we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor .", "entity": [{"entity": "7 - amino - 5 - thio - thiazolo [ 4 , 5 - d ] pyrimidine", "entity_type": "Chemical", "pos": [37, 93]}], "task": "NER"}
{"text": "The structure - activity relationships showed that a leucinol moiety attached to the core - structure in the 7 - position together with alpha - methyl branched benzyl derivatives in the 5 - position displayed promising affinity , and selectivity as well as physicochemical properties , as exemplified by compounds 18a and 24h .", "entity": [{"entity": "leucinol", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "alpha - methyl", "entity_type": "Chemical", "pos": [136, 150]}, {"entity": "benzyl", "entity_type": "Chemical", "pos": [160, 166]}], "task": "NER"}
{"text": "We show the preparation of the first potent and selective orally available CX3CR1 antagonists .", "entity": [], "task": "NER"}
{"text": "Therapeutic Agents Triggering Nonapoptotic Cancer Cell Death .", "entity": [], "task": "NER"}
{"text": "It is widely recognized that the evasion of apoptotic cell death is one of the hallmarks of cancer .", "entity": [], "task": "NER"}
{"text": "For many years cytotoxic agents have been developed to target apoptotic cell death as a main method of treating cancer .", "entity": [], "task": "NER"}
{"text": "However , the occurrence of cellular defects involving the apoptotic machinery in many cancers has resulted in an acquired resistance to apoptotic cell death , undermining the effectiveness of chemotherapeutic agents .", "entity": [], "task": "NER"}
{"text": "Over the past decade , research has revealed a growing number of cell death pathways that are not dependent on apoptosis .", "entity": [], "task": "NER"}
{"text": "In addition , compounds specifically triggering these alternative cell death pathways have been identified and explored as novel cancer treatment options .", "entity": [], "task": "NER"}
{"text": "These novel anticancer agents are critically discussed by the authors , and therefore , the current Perspective represents a resource for a practicing medicinal chemist looking for new opportunities to combat cancers resistant to the established proapoptotic therapeutic agents .", "entity": [], "task": "NER"}
{"text": "Constraint Network Analysis ( CNA ) : A Python Software Package for Efficiently Linking Biomacromolecular Structure , Flexibility , ( Thermo - ) Stability , and Function .", "entity": [], "task": "NER"}
{"text": "For deriving maximal advantage from information on biomacromolecular flexibility and rigidity , results from rigidity analyses must be linked to biologically relevant characteristics of a structure .", "entity": [], "task": "NER"}
{"text": "Here , we describe the Python - based software package Constraint Network Analysis ( CNA ) developed for this task .", "entity": [], "task": "NER"}
{"text": "CNA functions as a front - and backend to the graph - based rigidity analysis software FIRST .", "entity": [], "task": "NER"}
{"text": "CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it ( I ) provides a refined modeling of thermal unfolding simulations that also considers the temperature - dependence of hydrophobic tethers , ( II ) allows performing rigidity analyses on ensembles of network topologies , either generated from structural ensembles or by using the concept of fuzzy noncovalent constraints , and ( III ) computes a set of global and local indices for quantifying biomacromolecular stability .", "entity": [], "task": "NER"}
{"text": "This leads to more robust results from rigidity analyses and extends the application domain of rigidity analyses in that phase transition points ( \" melting points \" ) and unfolding nuclei ( \" structural weak spots \" ) are determined automatically .", "entity": [], "task": "NER"}
{"text": "Furthermore , CNA robustly handles small - molecule ligands in general .", "entity": [], "task": "NER"}
{"text": "Such advancements are important for applying rigidity analysis to data - driven protein engineering and for estimating the influence of ligand molecules on biomacromolecular stability .", "entity": [], "task": "NER"}
{"text": "CNA maintains the efficiency of FIRST such that the analysis of a single protein structure takes a few seconds for systems of several hundred residues on a single core .", "entity": [], "task": "NER"}
{"text": "These features make CNA an interesting tool for linking biomacromolecular structure , flexibility , ( thermo - ) stability , and function .", "entity": [], "task": "NER"}
{"text": "CNA is available from http : / / cpclab . uni - duesseldorf . de / software for nonprofit organizations .", "entity": [], "task": "NER"}
{"text": "Novel Plasmodium falciparum Maurer ' s clefts protein families implicated in the release of infectious merozoites .", "entity": [], "task": "NER"}
{"text": "The pathogenicity of the most deadly human malaria parasite , Plasmodium falciparum , relies on the export of virulence factors to the surface of infected erythrocytes .", "entity": [], "task": "NER"}
{"text": "A novel membrane compartment , referred to as Maurer ' s clefts , is transposed to the host erythrocyte , acting as a marshal platform in the red blood cell cytoplasm , for exported parasite proteins addressed to the host cell plasma membrane .", "entity": [], "task": "NER"}
{"text": "We report here the characterization of three new P . falciparum multigene families organized in 9 highly conserved clusters with the Pfmc - 2tm genes in the subtelomeric regions of parasite ' s chromosomes and expressed at early trophozoite stages .", "entity": [], "task": "NER"}
{"text": "Like the PfMC - 2TM proteins , the PfEPF1 , 3 and 4 proteins encoded by these families are exported to the Maurer ' s clefts , as peripheral or integral proteins of the Maurer ' s cleft membrane and largely exposed to the red cell cytosolic face of this membrane .", "entity": [], "task": "NER"}
{"text": "A promoter titration approach was used to question the biological roles of these P . falciparum - specific exported proteins .", "entity": [], "task": "NER"}
{"text": "Using the Pfepf1 family promoter , we observed the specific downregulation of all four families , correlating with the inefficient release of merozoites while the parasite intra - erythrocytic maturation and Maurer ' s clefts morphology were not impacted .", "entity": [], "task": "NER"}
{"text": "Ultrafast Spectroscopy of Quantum Confined States in a Single CdSe Nanowire .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "We measure for the first time transient absorption spectra of individual CdSe nanowires with about 10 nm diameter .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "Confinement of the carrier wave functions leads to discrete states which can be described by a six - band effective mass model .", "entity": [], "task": "NER"}
{"text": "Combining transient absorption and luminescence spectroscopy allows us to track the excitation dynamics in the visible and near - infrared spectral range .", "entity": [], "task": "NER"}
{"text": "About 10 % of all absorbed photons lead to an excitation of the lowest energy state .", "entity": [], "task": "NER"}
{"text": "Of these excitations , less than 1 % lead to a photon in the optical far - field .", "entity": [], "task": "NER"}
{"text": "Almost all emission is reabsorbed by other parts of the nanowire .", "entity": [], "task": "NER"}
{"text": "These findings might explain the low overall quantum efficiency of CdSe nanowires .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "1 , 4 , 2 - Benzo / pyridodithiazine 1 , 1 - Dioxides Structurally Related to the ATP - Sensitive Potassium Channel Openers 1 , 2 , 4 - Benzo / pyridothiadiazine 1 , 1 - Dioxides Exert a Myorelaxant Activity Linked to a Distinct Mechanism of Action .", "entity": [{"entity": "1 , 4 , 2 - Benzo / pyridodithiazine 1 , 1 - Dioxides", "entity_type": "Chemical", "pos": [0, 53]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "Potassium", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "1 , 2 , 4 - Benzo / pyridothiadiazine 1 , 1 - Dioxides", "entity_type": "Chemical", "pos": [124, 178]}], "task": "NER"}
{"text": "The synthesis of diversely substituted 3 - alkyl / aralkyl / arylamino - 1 , 4 , 2 - benzodithiazine 1 , 1 - dioxides and 3 - alkylaminopyrido [ 4 , 3 - e ] - 1 , 4 , 2 - dithiazine 1 , 1 - dioxides is described .", "entity": [{"entity": "3 - alkyl / aralkyl / arylamino - 1 , 4 , 2 - benzodithiazine 1 , 1 - dioxides", "entity_type": "Chemical", "pos": [39, 117]}, {"entity": "3 - alkylaminopyrido [ 4 , 3 - e ] - 1 , 4 , 2 - dithiazine 1 , 1 - dioxides", "entity_type": "Chemical", "pos": [122, 198]}], "task": "NER"}
{"text": "Their biological activities on pancreatic beta - cells and on smooth muscle cells were compared to those of the reference ATP - sensitive potassium channel ( KATP channel ) openers diazoxide and 7 - chloro - 3 - isopropylamino - 4H - 1 , 2 , 4 - benzothiadiazine 1 , 1 - dioxide .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [122, 125]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [138, 147]}, {"entity": "diazoxide", "entity_type": "Chemical", "pos": [181, 190]}, {"entity": "7 - chloro - 3 - isopropylamino - 4H - 1 , 2 , 4 - benzothiadiazine 1 , 1 - dioxide", "entity_type": "Chemical", "pos": [195, 278]}], "task": "NER"}
{"text": "The aim was to assess the impact on biological activities of the replacement of the 1 , 2 , 4 - thiadiazine ring by an isosteric 1 , 4 , 2 - dithiazine ring .", "entity": [{"entity": "1 , 2 , 4 - thiadiazine", "entity_type": "Chemical", "pos": [84, 107]}, {"entity": "1 , 4 , 2 - dithiazine", "entity_type": "Chemical", "pos": [129, 151]}], "task": "NER"}
{"text": "Most of the dithiazine analogues were found to be inactive on the pancreatic tissue , although some compounds bearing a 1 - phenylethylamino side chain at the 3 - position exerted a marked myorelaxant activity .", "entity": [{"entity": "dithiazine", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "1 - phenylethylamino", "entity_type": "Chemical", "pos": [120, 140]}], "task": "NER"}
{"text": "Such an effect did not appear to be related to the opening of KATP channels but rather reflected a mechanism of action similar to that of calcium channel blockers .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "Tightly related 3 - ( 1 - phenylethyl ) sulfanyl - 4H - 1 , 2 , 4 - benzothiadiazine 1 , 1 - dioxides were also found to exert a pronounced myorelaxant activity , resulting from both a KATP channel activation and a calcium channel blocker mechanism .", "entity": [{"entity": "3 - ( 1 - phenylethyl ) sulfanyl - 4H - 1 , 2 , 4 - benzothiadiazine 1 , 1 - dioxides", "entity_type": "Chemical", "pos": [16, 101]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [215, 222]}], "task": "NER"}
{"text": "The present work highlights the critical importance of an intracyclic NH group at the 4 - position , as well as an exocyclic NH group linked to the 3 - position of the benzo - and pyridothiadiazine dioxides , for activity on KATP channels .", "entity": [{"entity": "NH", "entity_type": "Chemical", "pos": [70, 72]}, {"entity": "NH", "entity_type": "Chemical", "pos": [125, 127]}, {"entity": "benzo - and pyridothiadiazine dioxides", "entity_type": "Chemical", "pos": [168, 206]}], "task": "NER"}
{"text": "Discovery of 3 , 3 ' - diindolylmethanes as potent antileishmanial agents .", "entity": [{"entity": "3 , 3 ' - diindolylmethanes", "entity_type": "Chemical", "pos": [13, 40]}], "task": "NER"}
{"text": "An efficient protocol for synthesis of 3 , 3 ' - diindolylmethanes using recyclable Fe - pillared interlayered clay ( Fe - PILC ) catalyst under aqueous medium has been developed .", "entity": [{"entity": "3 , 3 ' - diindolylmethanes", "entity_type": "Chemical", "pos": [39, 66]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [84, 86]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [118, 120]}], "task": "NER"}
{"text": "All synthesized 3 , 3 ' - diindolylmethanes showed promising antileishmanial activity against Leishmania donovani promastigotes as well as axenic amastigotes .", "entity": [{"entity": "3 , 3 ' - diindolylmethanes", "entity_type": "Chemical", "pos": [16, 43]}], "task": "NER"}
{"text": "Structure - activity relationship analysis revealed that nitroaryl substituted diindolylmethanes showed potent antileishmanial activity .", "entity": [{"entity": "nitroaryl substituted diindolylmethanes", "entity_type": "Chemical", "pos": [57, 96]}], "task": "NER"}
{"text": "The 4 - nitrophenyl linked 3 , 3 ' - diindolylmethane 8g was found to be the most potent antileishmanial analog showing IC50 values of 7 . 88 and 8 . 37 mu M against both L . donovani promastigotes and amastigotes , respectively .", "entity": [{"entity": "4 - nitrophenyl linked 3 , 3 ' - diindolylmethane", "entity_type": "Chemical", "pos": [4, 53]}], "task": "NER"}
{"text": "Further , a pharmacophore based QSAR model was established to understand the crucial molecular features of 3 , 3 ' - diindolylmethanes essential for potent antileishmanial activity .", "entity": [{"entity": "3 , 3 ' - diindolylmethanes", "entity_type": "Chemical", "pos": [107, 134]}], "task": "NER"}
{"text": "These compounds also exhibited promising antifungal activity against Cryptococcus neoformans , wherein fluorophenyl substituted 3 , 3 ' - diindolylmethanes were found to be most potent antifungal agents .", "entity": [{"entity": "fluorophenyl substituted 3 , 3 ' - diindolylmethanes", "entity_type": "Chemical", "pos": [103, 155]}], "task": "NER"}
{"text": "Developed synthetic protocol will be useful for economical and eco - friendly synthesis of potent antileishmanial and antifungal 3 , 3 ' - diindolylmethane class of compounds .", "entity": [{"entity": "3 , 3 ' - diindolylmethane", "entity_type": "Chemical", "pos": [129, 155]}], "task": "NER"}
{"text": "Synthesis and selected immunological properties of substituted quino [ 3 , 2 - b ] benzo [ 1 , 4 ] thiazines .", "entity": [{"entity": "quino [ 3 , 2 - b ] benzo [ 1 , 4 ] thiazines", "entity_type": "Chemical", "pos": [63, 108]}], "task": "NER"}
{"text": "A new type of azaphenothiazines - tetracyclic quino [ 3 , 2 - b ] benzo [ 1 , 4 ] thiazines , possessing common substituents ( H , CH3 , Cl , Br , F , CF3 , SCH3 ) in positions 8 - 10 and pharmacophoric aminoalkyl substituents in position 6 , were obtained from diquinodithiin and 2 , 2 ' - dichloro - 3 , 3 ' - diquinolinyl disulfide in several - step syntheses .", "entity": [{"entity": "azaphenothiazines", "entity_type": "Chemical", "pos": [14, 31]}, {"entity": "tetracyclic quino [ 3 , 2 - b ] benzo [ 1 , 4 ] thiazines", "entity_type": "Chemical", "pos": [34, 91]}, {"entity": "H", "entity_type": "Chemical", "pos": [127, 128]}, {"entity": "CH3", "entity_type": "Chemical", "pos": [131, 134]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [137, 139]}, {"entity": "Br", "entity_type": "Chemical", "pos": [142, 144]}, {"entity": "F", "entity_type": "Chemical", "pos": [147, 148]}, {"entity": "CF3", "entity_type": "Chemical", "pos": [151, 154]}, {"entity": "SCH3", "entity_type": "Chemical", "pos": [157, 161]}, {"entity": "aminoalkyl", "entity_type": "Chemical", "pos": [203, 213]}, {"entity": "diquinodithiin", "entity_type": "Chemical", "pos": [262, 276]}, {"entity": "2 , 2 ' - dichloro - 3 , 3 ' - diquinolinyl disulfide", "entity_type": "Chemical", "pos": [281, 334]}], "task": "NER"}
{"text": "Sixty one compounds , grouped as the 6H , 6 - dialkylaminoalkyl , 6 - acylaminoalkyl and sulfonylaminoalkyl derivatives , were tested for cytotoxicity , their effects on phytohemagglutin A ( PHA ) - induced proliferative response of human peripheral blood mononuclear cells ( PBMC ) and lipopolysaccharide ( LPS ) - induced tumor necrosis factor alpha ( TNF - alpha ) production by these cells .", "entity": [{"entity": "6 - dialkylaminoalkyl", "entity_type": "Chemical", "pos": [42, 63]}, {"entity": "6 - acylaminoalkyl", "entity_type": "Chemical", "pos": [66, 84]}, {"entity": "sulfonylaminoalkyl", "entity_type": "Chemical", "pos": [89, 107]}], "task": "NER"}
{"text": "The compounds exhibited differential inhibitory activities in these tests and significantly varied in terms of cytotoxicity .", "entity": [], "task": "NER"}
{"text": "The most promising compounds were tested for growth inhibition of leukemia L - 1210 cells , colon cancer SV - 948 cells and epidermal carcinoma A - 341 cells .", "entity": [], "task": "NER"}
{"text": "The most active compounds exhibited anticancer activity against these cell lines comparable to that of cisplatin .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [103, 112]}], "task": "NER"}
{"text": "The structure - activity relationship of the compounds were discussed .", "entity": [], "task": "NER"}
{"text": "Fisetin regulates obesity by targeting mTORC1 signaling .", "entity": [{"entity": "Fisetin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Fisetin , a flavonol present in vegetables and fruits , possesses antioxidative and anti - inflammatory properties .", "entity": [{"entity": "Fisetin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "flavonol", "entity_type": "Chemical", "pos": [12, 20]}], "task": "NER"}
{"text": "In this study , we have demonstrated that fisetin prevents diet - induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 ( mTORC1 ) , a central mediator of cellular growth , cellular proliferation and lipid biosynthesis .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [141, 150]}], "task": "NER"}
{"text": "To evaluate whether fisetin regulates mTORC1 signaling , we investigated the phosphorylation and kinase activity of the 70 - kDa ribosomal protein S6 kinase 1 ( S6K1 ) and mTORC1 in 3T3 - L1 preadipocytes .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [20, 27]}], "task": "NER"}
{"text": "Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time - and concentration - dependent manner .", "entity": [{"entity": "Fisetin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "To further our understanding of how fisetin negatively regulates mTORC1 signaling , we analyzed the phosphorylation of S6K1 , mTOR and Akt in fisetin - treated TSC2 - knockdown cells .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [36, 43]}, {"entity": "fisetin", "entity_type": "Chemical", "pos": [142, 149]}], "task": "NER"}
{"text": "The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt - dependent manner .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity .", "entity": [], "task": "NER"}
{"text": "Fisetin treatment inhibited adipocyte differentiation , consistent with the negative effect of fisetin on mTOR .", "entity": [{"entity": "Fisetin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "fisetin", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity , suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "fisetin", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [165, 178]}], "task": "NER"}
{"text": "Fisetin supplementation in mice fed a high - fat diet ( HFD ) significantly attenuated HFD - induced increases in body weight and white adipose tissue .", "entity": [{"entity": "Fisetin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "We also observed that fisetin efficiently suppressed the phosphorylation of Akt , S6K1 and mTORC1 in adipose tissue .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [22, 29]}], "task": "NER"}
{"text": "Collectively , these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3 - L1 preadipocytes and obesity in HFD - fed mice .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "Therefore , fisetin may be a useful phytochemical agent for attenuating diet - induced obesity .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [12, 19]}], "task": "NER"}
{"text": "Structural elucidation of possible lutein oxidation products mediated through peroxyl radical inducer 2 , 2 ' - Azobis ( 2 - methylpropionamidine ) dihydrochloride : Antioxidant and cytotoxic influence of oxidized lutein in HeLa cells .", "entity": [{"entity": "lutein", "entity_type": "Chemical", "pos": [35, 41]}, {"entity": "peroxyl", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "2 , 2 ' - Azobis ( 2 - methylpropionamidine ) dihydrochloride", "entity_type": "Chemical", "pos": [102, 163]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [214, 220]}], "task": "NER"}
{"text": "Aim of this study was to elucidate lutein oxidation products mediated through peroxyl radical inducer 2 , 2 ' - Azobis ( 2 - methylpropionamidine ) dihydrochloride ( AAPH ) and to study antioxidant and cytotoxic effects of oxidized lutein using liposome and HeLa cells .", "entity": [{"entity": "lutein", "entity_type": "Chemical", "pos": [35, 41]}, {"entity": "peroxyl", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "2 , 2 ' - Azobis ( 2 - methylpropionamidine ) dihydrochloride", "entity_type": "Chemical", "pos": [102, 163]}, {"entity": "AAPH", "entity_type": "Chemical", "pos": [166, 170]}, {"entity": "oxidized lutein", "entity_type": "Chemical", "pos": [223, 238]}], "task": "NER"}
{"text": "Lutein ( 20 mu mol ) with AAPH ( 5mM ) in liposome ' s was incubated at 37 degrees C in dark for 3h , oxidized lutein products were characterized by LC - MS ( APCI ( + ) ) and studied for their free radical scavenging activity and cytotoxic effects in terms of cell viability , cellular glutathione , and malondialdehyde levels .", "entity": [{"entity": "Lutein", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "AAPH", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "oxidized lutein", "entity_type": "Chemical", "pos": [102, 117]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [287, 298]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [305, 320]}], "task": "NER"}
{"text": "AAPH mediated lutein fragmented ions were identified as 551 ( M ( + ) + H ( + ) - H2O ) , 391 ( M ( + ) + H ( + ) + O2 - C22H32O ) and 276 ( M ( + ) + H ( + ) + O2 - C12H20O ) and its isomers as 13 - Z lutein , 13 - Z zeaxanthin , 13 ' - Z zeaxanthin and all - E zeaxanthin .", "entity": [{"entity": "AAPH", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [72, 79]}, {"entity": "H2O", "entity_type": "Chemical", "pos": [82, 85]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [106, 113]}, {"entity": "O2 - C22H32O", "entity_type": "Chemical", "pos": [116, 128]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [151, 158]}, {"entity": "O2 - C12H20O", "entity_type": "Chemical", "pos": [161, 173]}, {"entity": "13 - Z lutein", "entity_type": "Chemical", "pos": [195, 208]}, {"entity": "13 - Z zeaxanthin", "entity_type": "Chemical", "pos": [211, 228]}, {"entity": "13 ' - Z zeaxanthin", "entity_type": "Chemical", "pos": [231, 250]}, {"entity": "all - E zeaxanthin", "entity_type": "Chemical", "pos": [255, 273]}], "task": "NER"}
{"text": "Free radical scavenging activity of oxidized lutein was higher by 32 . 7 % ( IC50 , 2 . 64 mu g ) than lutein ( IC50 , 5 . 28 mu g ) .", "entity": [{"entity": "oxidized lutein", "entity_type": "Chemical", "pos": [36, 51]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "Oxidized lutein lowered the lipid peroxidation ( 21 % ) , HeLa cells viability ( 22 % ) and glutathione levels ( 32 % ) than lutein .", "entity": [{"entity": "Oxidized lutein", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [92, 103]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [125, 131]}], "task": "NER"}
{"text": "To conclude , the oxidized lutein may be highly reactive , since oxidation by AAPH results in peroxyl radical ions , which can react with conjugated polyene chain of lutein that could lead to higher antioxidant and cytotoxic effects on HeLa cells .", "entity": [{"entity": "oxidized lutein", "entity_type": "Chemical", "pos": [18, 33]}, {"entity": "AAPH", "entity_type": "Chemical", "pos": [78, 82]}, {"entity": "peroxyl", "entity_type": "Chemical", "pos": [94, 101]}, {"entity": "polyene", "entity_type": "Chemical", "pos": [149, 156]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "Tricyclic thiazoles are a new class of angiogenesis inhibitors .", "entity": [{"entity": "Tricyclic thiazoles", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "Tricyclic thiazoleamine derivatives that were identified as hits in a screen against human umbilical vein endothelial cell proliferation were subjected to a structure - activity relationship study .", "entity": [{"entity": "Tricyclic thiazoleamine", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "Two structurally superimposable scaffolds - 4H - thiochromeno [ 4 , 3 - d ] thiazol - 2 - amine and 5 , 6 - dihydro - 4H - benzo [ 6 , 7 ] cyclohepta [ 1 , 2 - d ] thiazol - 2 - amine derivatives - yielded low - micromolar inhibitors , and two among them 37 and 43 also exhibited antiangiogenic activity in an endothelial tube formation assay .", "entity": [{"entity": "4H - thiochromeno [ 4 , 3 - d ] thiazol - 2 - amine", "entity_type": "Chemical", "pos": [44, 95]}, {"entity": "5 , 6 - dihydro - 4H - benzo [ 6 , 7 ] cyclohepta [ 1 , 2 - d ] thiazol - 2 - amine", "entity_type": "Chemical", "pos": [100, 183]}], "task": "NER"}
{"text": "Thus , 37 and 43 can serve as leads to develop a novel class of antiangiogenic agents .", "entity": [], "task": "NER"}
{"text": "Neuroprotective effect of sulforaphane in 6 - hydroxydopamine - lesioned mouse model of Parkinson ' s disease .", "entity": [{"entity": "sulforaphane", "entity_type": "Chemical", "pos": [26, 38]}, {"entity": "6 - hydroxydopamine", "entity_type": "Chemical", "pos": [42, 61]}], "task": "NER"}
{"text": "Parkinson ' s disease ( PD ) is characterized by the selective loss of dopaminergic nigrostriatal neurons , which leads to disabling motor disturbances .", "entity": [], "task": "NER"}
{"text": "Sulforaphane ( SFN ) , found in cruciferous vegetables , is a potent indirect antioxidant and recent advances have shown its neuroprotective activity in various experimental models of neurodegeneration .", "entity": [{"entity": "Sulforaphane", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "SFN", "entity_type": "Chemical", "pos": [15, 18]}], "task": "NER"}
{"text": "This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to 6 - hydroxydopamine ( 6 - OHDA ) .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [52, 55]}, {"entity": "6 - hydroxydopamine", "entity_type": "Chemical", "pos": [128, 147]}, {"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [150, 158]}], "task": "NER"}
{"text": "For this purpose , mice were treated with SFN ( 5mg / kg twice a week ) for four weeks after the unilateral intrastriatal injection of 6 - OHDA .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [135, 143]}], "task": "NER"}
{"text": "The increase in 6 - OHDA - induced rotations and deficits in motor coordination were ameliorated significantly by SFN treatment .", "entity": [{"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "SFN", "entity_type": "Chemical", "pos": [114, 117]}], "task": "NER"}
{"text": "In addition , SFN protected 6 - OHDA - induced apoptosis via blocking DNA fragmentation and caspase - 3 activation .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [28, 36]}], "task": "NER"}
{"text": "These results were further supported by immunohistochemical findings in the substantia nigra that showed that SFN protected neurons from neurotoxic effects of 6 - OHDA .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [110, 113]}, {"entity": "6 - OHDA", "entity_type": "Chemical", "pos": [159, 167]}], "task": "NER"}
{"text": "The neuroprotective effect of SFN may be attributed to its ability to enhance glutathione levels and its dependent enzymes ( glutathione - S - transferase and glutathione reductase ) and to modulate neuronal survival pathways , such as ERK1 / 2 , in the brain of mice .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [78, 89]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [125, 136]}, {"entity": "S", "entity_type": "Chemical", "pos": [139, 140]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [159, 170]}], "task": "NER"}
{"text": "These results suggest that SFN may potentially be effective in slowing down the progression of idiopathic PD by the modulation of oxidative stress and apoptotic machinery .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "Oxidative DNA damage corresponds to the long term survival of human cells treated with silver nanoparticles .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [87, 93]}], "task": "NER"}
{"text": "We examined the relation between DNA damage and the clonogenic potential of 3 human cell lines , HepG2 , HT29 and A549 , treated with bare 20nm or 200nm silver nanoparticles ( AgNPs ) .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [153, 159]}], "task": "NER"}
{"text": "The endpoints examined were the DNA breakage estimated by the comet assay , the oxidative base damage recognized by formamido - pyrimidine glycosylase ( FPG ) and estimated with the FPG + comet assay , and the frequencies of histone gamma H2AX foci and micronuclei .", "entity": [{"entity": "formamido - pyrimidine", "entity_type": "Chemical", "pos": [116, 138]}], "task": "NER"}
{"text": "Each cell line studied had a different pattern of DNA breakage and base damage versus the NPs concentration and time of treatment .", "entity": [], "task": "NER"}
{"text": "The overall pattern of DNA breakage and base damage induction corresponded to the intracellular generation of reactive oxygen species .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [119, 125]}], "task": "NER"}
{"text": "There was no increase in the frequencies of histone gamma H2AX foci and micronuclei as compared to those in the untreated cells .", "entity": [], "task": "NER"}
{"text": "The reported experiments suggest that only the oxidative DNA damage corresponds to the loss of the clonogenic ability of cells treated with AgNPs .", "entity": [], "task": "NER"}
{"text": "Detecting genome - wide gene transcription profiles associated with high pollution burden in the critically endangered European eel .", "entity": [], "task": "NER"}
{"text": "The European eel illustrates an example of a critically endangered fish species strongly affected by human stressors throughout its life cycle , in which pollution is considered to be one of the factors responsible for the decline of the stock .", "entity": [], "task": "NER"}
{"text": "The objective of our study was to better understand the transcriptional response of European eels chronically exposed to pollutants in their natural environment .", "entity": [], "task": "NER"}
{"text": "A total of 42 pre - migrating ( silver ) female eels from lowly , highly and extremely polluted environments in Belgium and , for comparative purposes , a lowly polluted habitat in Italy were measured for polychlorinated biphenyls ( PCBs ) , organochlorine pesticides ( OCPs ) and brominated flame retardants ( BFRs ) .", "entity": [{"entity": "polychlorinated biphenyls", "entity_type": "Chemical", "pos": [205, 230]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [233, 237]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [242, 256]}], "task": "NER"}
{"text": "Multipollutant level of bioaccumulation was linked to their genome - wide gene transcription using an eel - specific array of 14 , 913 annotated cDNAs .", "entity": [], "task": "NER"}
{"text": "Shared responses to pollutant exposure were observed when comparing the highly polluted site in Belgium with the relatively clean sites in Belgium and Italy .", "entity": [], "task": "NER"}
{"text": "First , an altered pattern of transcription of genes was associated with detoxification , with a novel European eel CYP3A gene and gluthatione S - transferase transcriptionally up - regulated .", "entity": [{"entity": "gluthatione", "entity_type": "Chemical", "pos": [131, 142]}, {"entity": "S", "entity_type": "Chemical", "pos": [143, 144]}], "task": "NER"}
{"text": "Second , an altered pattern of transcription of genes associated with the oxidative phosphorylation pathway , with the following genes involved in the generation of ATP being transcriptionally down - regulated in individuals from the highly polluted site : NADH dehydrogenase , succinate dehydrogenase , ubiquinol - cytochrome c reductase , cytochrome c oxidase and ATP synthase .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [165, 168]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [257, 261]}, {"entity": "succinate", "entity_type": "Chemical", "pos": [278, 287]}, {"entity": "ubiquinol", "entity_type": "Chemical", "pos": [304, 313]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [366, 369]}], "task": "NER"}
{"text": "Although we did not measure metabolism directly , seeing that the transcription level of many genes encoding enzymes involved in the mitochondrial respiratory chain and oxidative phosphorylation were down - regulated in the highly polluted site suggests that pollutants may have a significant effect on energy metabolism in these fish .", "entity": [], "task": "NER"}
{"text": "Large - scale synthesis and in situ functionalization of Zn3P2 and Zn4Sb3 nanowire powders .", "entity": [{"entity": "Zn3P2", "entity_type": "Chemical", "pos": [57, 62]}, {"entity": "Zn4Sb3", "entity_type": "Chemical", "pos": [67, 73]}], "task": "NER"}
{"text": "A simple method for the large - scale synthesis of gram quantities of compound semiconductor nanowires without the need for any external catalysts or templates is presented .", "entity": [], "task": "NER"}
{"text": "This method is demonstrated using zinc phosphide ( Zn3P2 ) and zinc antimonide ( beta - Zn4Sb3 ) nanowires as example systems .", "entity": [{"entity": "zinc phosphide", "entity_type": "Chemical", "pos": [34, 48]}, {"entity": "Zn3P2", "entity_type": "Chemical", "pos": [51, 56]}, {"entity": "zinc antimonide", "entity_type": "Chemical", "pos": [63, 78]}, {"entity": "Zn4Sb3", "entity_type": "Chemical", "pos": [88, 94]}], "task": "NER"}
{"text": "Large - scale synthesis of Zn3P2 and Zn4Sb3 nanowire powders was accomplished using a hot - walled chemical vapor deposition chamber by transporting phosphorus and antimony , respectively , via the vapor phase onto heated zinc foils .", "entity": [{"entity": "Zn3P2", "entity_type": "Chemical", "pos": [27, 32]}, {"entity": "Zn4Sb3", "entity_type": "Chemical", "pos": [37, 43]}, {"entity": "phosphorus", "entity_type": "Chemical", "pos": [149, 159]}, {"entity": "antimony", "entity_type": "Chemical", "pos": [164, 172]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [222, 226]}], "task": "NER"}
{"text": "The zinc foils were rolled concentrically into coils to maximize the substrate surface area , and consequently , the nanowire yield .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [4, 8]}], "task": "NER"}
{"text": "Using this method , 250 mg of Zn3P2 nanowires were obtained on 480 cm ( 2 ) of zinc foil in a span of 45 minutes .", "entity": [{"entity": "Zn3P2", "entity_type": "Chemical", "pos": [30, 35]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "Furthermore , a process of exposing the synthesized nanowires to a vapor of organic functional molecules immediately after their synthesis and before their removal from the vacuum chamber was developed to obtain large quantities of surface functionalized nanowire powders .", "entity": [], "task": "NER"}
{"text": "This in situ vapor - phase functionalization procedure passivated the nanowire surfaces without adversely affecting their morphology or dimensions .", "entity": [], "task": "NER"}
{"text": "Our studies revealed that both 4 - aminothiophenol and 3 - propanedithiol functionalized Zn3P2 nanowires were stable over a 120 day duration without any agglomeration or degradation .", "entity": [{"entity": "4 - aminothiophenol", "entity_type": "Chemical", "pos": [31, 50]}, {"entity": "3 - propanedithiol", "entity_type": "Chemical", "pos": [55, 73]}, {"entity": "Zn3P2", "entity_type": "Chemical", "pos": [89, 94]}], "task": "NER"}
{"text": "This method of mass producing nanowires can also be extended to other binary semiconductors .", "entity": [], "task": "NER"}
{"text": "Loss of Survivin influences liver regeneration and is associated with impaired Aurora B function .", "entity": [], "task": "NER"}
{"text": "The chromosomal passenger complex ( CPC ) acts as a key regulator of mitosis , preventing asymmetric segregation of chromosomal material into daughter cells .", "entity": [], "task": "NER"}
{"text": "The CPC is composed of three non - enzymatic components termed Survivin , the inner centromere protein ( INCENP ) and Borealin , and an enzymatic component , Aurora B kinase .", "entity": [], "task": "NER"}
{"text": "Survivin is necessary for the appropriate separation of sister chromatids during mitosis and is involved in liver regeneration , but its role in regenerative processes is incompletely elucidated .", "entity": [], "task": "NER"}
{"text": "Whether Survivin , which is classified as an inhibitor of apoptosis protein ( IAP ) based on domain composition , also has a role in apoptosis is controversial .", "entity": [], "task": "NER"}
{"text": "The present study examined the in vivo effects of Survivin ablation in the liver and during liver regeneration after 70 % hepatectomy in a hepatocyte - specific knockout mouse model .", "entity": [], "task": "NER"}
{"text": "The absence of Survivin caused a reduction in the number of hepatocytes in the liver , together with an increase in cell volume , macronucleation and polyploidy , but no changes in apoptosis .", "entity": [], "task": "NER"}
{"text": "During liver regeneration , mitosis of hepatocytes was associated with mislocalization of the members of the CPC , which were no longer detectable at the centromere despite an unchanged protein amount .", "entity": [], "task": "NER"}
{"text": "Furthermore , the loss of survivin in regenerating hepatocytes was associated with reduced levels of phosphorylated Histone H3 at serine 28 and abolished phosphorylation of CENP - A and Hec1 at serine 55 , which is a consequence of decreased Aurora B kinase activity .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [130, 136]}, {"entity": "serine", "entity_type": "Chemical", "pos": [194, 200]}], "task": "NER"}
{"text": "These data indicate that Survivin expression determines hepatocyte number during liver development and liver regeneration .", "entity": [], "task": "NER"}
{"text": "Lack of Survivin causes mislocalization of the CPC members in combination with reduced Aurora B activity , leading to impaired phosphorylation of its centromeric target proteins and inappropriate cytokinesis .", "entity": [], "task": "NER"}
{"text": "Predictive factors of sensitivity to elisidepsin , a novel kahalalide f - derived marine compound .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [37, 48]}, {"entity": "kahalalide f", "entity_type": "Chemical", "pos": [59, 71]}], "task": "NER"}
{"text": "Elisidepsin ( PM02734 , Irvalec (R) ) is a synthetic marine - derived cyclic peptide of the Kahalalide F family currently in phase II clinical development .", "entity": [{"entity": "Elisidepsin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "PM02734", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "Irvalec", "entity_type": "Chemical", "pos": [24, 31]}, {"entity": "Kahalalide F", "entity_type": "Chemical", "pos": [92, 104]}], "task": "NER"}
{"text": "Elisidepsin was shown to induce rapid oncosis in ErbB3 - expressing cells .", "entity": [{"entity": "Elisidepsin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Other predictive factors of elisidepsin sensitivity remained unknown .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "A panel of 23 cancer cell lines of different origin was assessed for elisidepsin cytotoxicity and correlated with mutational state , mRNA and protein expression of selected genes .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [69, 80]}], "task": "NER"}
{"text": "Elisidepsin showed potent and broad cytotoxic effects in our cancer cell line panel , being active at concentrations ranging from 0 . 4 to 2 mu M that may be relevant for clinical settings .", "entity": [{"entity": "Elisidepsin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "We have shown that elisidepsin is more active in cells harboring epithelial phenotype with high E - cadherin and low vimentin expression .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [19, 30]}], "task": "NER"}
{"text": "In addition , high ErbB3 and Muc1 expression was correlated with sensitivity to elisidepsin , whereas the presence of KRAS activating mutations was associated with resistance .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "In DU - PM cells with acquired resistance to elisidepsin , ErbB3 expression was decreased , while Bcl2 was increased .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [45, 56]}], "task": "NER"}
{"text": "DU - PM cells displayed higher sensitivity to ErbB1 - inhibitors suggesting possible cross - talk of ErbB1 and ErbB3 signaling pathways .", "entity": [], "task": "NER"}
{"text": "Combinations of elisidepsin with lapatinib and several chemotherapies including 5 - FU and oxaliplatin resulted in synergistic effects that offer the potential of clinical use of elisidepsin in combination settings .", "entity": [{"entity": "elisidepsin", "entity_type": "Chemical", "pos": [16, 27]}, {"entity": "lapatinib", "entity_type": "Chemical", "pos": [33, 42]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [80, 86]}, {"entity": "oxaliplatin", "entity_type": "Chemical", "pos": [91, 102]}, {"entity": "elisidepsin", "entity_type": "Chemical", "pos": [179, 190]}], "task": "NER"}
{"text": "Gold nanoparticle - enhanced luminescence of silicon quantum dots co - encapsulated in polymer nanoparticles .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "The preparation of two - component polymer composite nanoparticles encapsulating both Si quantum dots ( SiQDs ) and Au nanoparticles ( AuNPs ) by a single step miniemulsion polymerization of divinylbenzene is described .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [86, 88]}, {"entity": "Au", "entity_type": "Chemical", "pos": [116, 118]}, {"entity": "divinylbenzene", "entity_type": "Chemical", "pos": [191, 205]}], "task": "NER"}
{"text": "This simple and robust method affords well - defined polymer composite nanoparticles with mean diameters in a range of 100 - 200 nm and with narrow polydispersity indices as determined by dynamic light scattering and transmission electron microscopy .", "entity": [], "task": "NER"}
{"text": "The successful encapsulation of AuNPs within poly ( divinylbenzene ) was confirmed by UV - visible spectroscopy and from TEM images .", "entity": [{"entity": "poly ( divinylbenzene )", "entity_type": "Chemical", "pos": [45, 68]}], "task": "NER"}
{"text": "Plasmon - enhanced fluorescence of the luminescence of the SiQDs by AuNPs encapsulated within the polymer composite nanoparticles was evaluated by confocal microspectroscopy , and luminescence enhancements of up to 15 times were observed .", "entity": [], "task": "NER"}
{"text": "These observations indicate that the luminescence of the SiQDs is enhanced by the proximity of the AuNPs .", "entity": [], "task": "NER"}
{"text": "The polymer composite nanoparticles were successfully ink - jet printed onto a glass substrate , which demonstrates that these composites are processable in printing applications .", "entity": [], "task": "NER"}
{"text": "Novel Phosphorylation and Ubiquitination Sites Regulate Reactive Oxygen Species - dependent Degradation of Anti - apoptotic c - FLIP Protein .", "entity": [{"entity": "Oxygen", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "The cytosolic protein c - FLIP ( cellular Fas - associated death domain - like interleukin 1 beta - converting enzyme inhibitory protein ) is an inhibitor of death receptor - mediated apoptosis that is up - regulated in a variety of cancers , contributing to apoptosis resistance .", "entity": [], "task": "NER"}
{"text": "Several compounds found to restore sensitivity of cancer cells to TRAIL , a TNF family death ligand with promising therapeutic potential , act by targeting c - FLIP ubiquitination and degradation by the proteasome .", "entity": [], "task": "NER"}
{"text": "The generation of reactive oxygen species ( ROS ) has been implicated in c - FLIP protein degradation .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [27, 33]}], "task": "NER"}
{"text": "However , the mechanism by which ROS post - transcriptionally regulate c - FLIP protein levels is not well understood .", "entity": [], "task": "NER"}
{"text": "We show here that treatment of prostate cancer PPC - 1 cells with the superoxide generators menadione , paraquat , or buthionine sulfoximine down - regulates c - FLIP long ( c - FLIPL ) protein levels , which is prevented by the proteasome inhibitor MG132 .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [70, 80]}, {"entity": "menadione", "entity_type": "Chemical", "pos": [92, 101]}, {"entity": "paraquat", "entity_type": "Chemical", "pos": [104, 112]}, {"entity": "buthionine sulfoximine", "entity_type": "Chemical", "pos": [118, 140]}, {"entity": "MG132", "entity_type": "Chemical", "pos": [250, 255]}], "task": "NER"}
{"text": "Furthermore , pretreatment of PPC - 1 cells with a ROS scavenger prevented ubiquitination and loss of c - FLIPL protein induced by menadione or paraquat .", "entity": [{"entity": "menadione", "entity_type": "Chemical", "pos": [131, 140]}, {"entity": "paraquat", "entity_type": "Chemical", "pos": [144, 152]}], "task": "NER"}
{"text": "We identified lysine 167 as a novel ubiquitination site of c - FLIPL important for ROS - dependent degradation .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [14, 20]}], "task": "NER"}
{"text": "We also identified threonine 166 as a novel phosphorylation site and demonstrate that Thr - 166 phosphorylation is required for ROS - induced Lys - 167 ubiquitination .", "entity": [{"entity": "threonine", "entity_type": "Chemical", "pos": [19, 28]}, {"entity": "Thr", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "Lys", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "The mutation of either Thr - 166 or Lys - 167 was sufficient to stabilize c - FLIP protein levels in PPC - 1 , HEK293T , and HeLa cancer cells treated with menadione or paraquat .", "entity": [{"entity": "Thr", "entity_type": "Chemical", "pos": [23, 26]}, {"entity": "Lys", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "menadione", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "paraquat", "entity_type": "Chemical", "pos": [169, 177]}], "task": "NER"}
{"text": "Accordingly , expression of c - FLIP T166A or K167R mutants protected cells from ROS - mediated sensitization to TRAIL - induced cell death .", "entity": [], "task": "NER"}
{"text": "Our findings reveal novel ROS - dependent post - translational modifications of the c - FLIP protein that regulate its stability , thus impacting sensitivity of cancer cells to TRAIL .", "entity": [], "task": "NER"}
{"text": "Nicotine - , tobacco particulate matter - and methamphetamine - produced locomotor sensitisation in rats .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [46, 61]}], "task": "NER"}
{"text": "RATIONALE : Repeated nicotine exposure produces a weak and transient sensitised locomotor response in rats .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [21, 29]}], "task": "NER"}
{"text": "Since tobacco smoke contains thousands of non - nicotine chemical constituents , these could alter the sensitised response .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "OBJECTIVES : This study aims to compare the magnitude , persistence and spatial distribution of locomotor sensitisation produced by repeated doses of nicotine , aqueous tobacco particulate matter ( TPM ) and a positive methamphetamine control .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [150, 158]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [219, 234]}], "task": "NER"}
{"text": "METHODS : Male Sprague - Dawley rats received five nicotine ( 0 . 0 , 0 . 2 or 0 . 4 mg / kg ) , TPM ( containing 0 . 2 or 0 . 4 mg / kg nicotine ) or methamphetamine ( 0 . 5 mg / kg ) injections every second day , followed by a 4 - day withdrawal before the first challenge ( Challenge 1 , C1 ) .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [137, 145]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [151, 166]}], "task": "NER"}
{"text": "The animals were re - challenged again at 15 days post C1 to test for the persistence of sensitisation ( Challenge 2 , C2 ) .", "entity": [], "task": "NER"}
{"text": "RESULTS : There were no major differences in sensitisation profile between nicotine and TPM .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "At the lowest 0 . 2 mg / kg nicotine / TPM dose , however , small differences emerged on select test days .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [28, 36]}], "task": "NER"}
{"text": "CONCLUSIONS : The results indicated that the non - nicotinic agents in TPM did not greatly impact the nicotine - produced locomotor - sensitised response .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "These findings might suggest that the differential pharmacological properties of TPM do not have major clinical significance .", "entity": [], "task": "NER"}
{"text": "Alternatively , the locomotor model might not expose effects of non - nicotinic constituents , and furthermore , might not closely relate to human tobacco dependence .", "entity": [], "task": "NER"}
{"text": "Different reward - related behavioural models should also be utilised to assess potential effects of non - nicotinic constituents before a role in dependence is discounted .", "entity": [], "task": "NER"}
{"text": "Treatment of Primary Chronic Glomerulonephritis with Rehmannia Glutinosa Acteosides in Combination with the Angiotensin Receptor Blocker Irbesartan : A Randomized Controlled Trial .", "entity": [{"entity": "Acteosides", "entity_type": "Chemical", "pos": [73, 83]}, {"entity": "Irbesartan", "entity_type": "Chemical", "pos": [137, 147]}], "task": "NER"}
{"text": "This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis .", "entity": [{"entity": "acteosides", "entity_type": "Chemical", "pos": [73, 83]}, {"entity": "irbesartan", "entity_type": "Chemical", "pos": [142, 152]}], "task": "NER"}
{"text": "A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group ( Rehmannia glutinosa acteosides , two 200 - mg capsules , bid ; and irbesartan , one 150 - mg tablet , qd ) or the control group ( irbesartan , one 150 - mg tablet , qd ) .", "entity": [{"entity": "acteosides", "entity_type": "Chemical", "pos": [185, 195]}, {"entity": "irbesartan", "entity_type": "Chemical", "pos": [232, 242]}, {"entity": "irbesartan", "entity_type": "Chemical", "pos": [295, 305]}], "task": "NER"}
{"text": "The primary outcome was 24 - h urinary protein .", "entity": [], "task": "NER"}
{"text": "Secondary outcome measures included blood pressure , estimated glomerular filtration rate , erythrocyturia , serum alanine aminotransferase , aspartate transaminase and electrolytes .", "entity": [{"entity": "alanine", "entity_type": "Chemical", "pos": [115, 122]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [142, 151]}], "task": "NER"}
{"text": "After 8 weeks of treatment , the treatment group showed a mean reduction in 24 - h proteinuria of 36 . 42 % compared to baseline , which was significantly higher than the mean reduction from baseline of 27 . 97 % in the control group ( P = 0 . 0278 ) . Adverse drug reactions occurred at a similarly low rate in the treatment group ( 0 . 4 % ) and control group ( 1 . 2 % , P = 0 . 3724 ) .", "entity": [], "task": "NER"}
{"text": "In the treatment of chronic glomerulonephritis , the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone .", "entity": [{"entity": "acteosides", "entity_type": "Chemical", "pos": [88, 98]}, {"entity": "irbesartan", "entity_type": "Chemical", "pos": [103, 113]}, {"entity": "irbesartan", "entity_type": "Chemical", "pos": [159, 169]}], "task": "NER"}
{"text": "6 - Gingerol Inhibits Rosiglitazone - Induced Adipogenesis in 3T3 - L1 Adipocytes .", "entity": [{"entity": "6 - Gingerol", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "Rosiglitazone", "entity_type": "Chemical", "pos": [22, 35]}], "task": "NER"}
{"text": "We investigated the effects of 6 - gingerol ( ( S ) - 5 - hydroxy - 1 - ( 4 - hydroxy - 3 - methoxyphenyl ) - 3 - decanone ) on the inhibition of rosiglitazone ( RGZ ) - induced adipogenesis in 3T3 - L1 cells .", "entity": [{"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [31, 43]}, {"entity": "( S ) - 5 - hydroxy - 1 - ( 4 - hydroxy - 3 - methoxyphenyl ) - 3 - decanone", "entity_type": "Chemical", "pos": [46, 122]}, {"entity": "rosiglitazone", "entity_type": "Chemical", "pos": [146, 159]}, {"entity": "RGZ", "entity_type": "Chemical", "pos": [162, 165]}], "task": "NER"}
{"text": "The morphological changes were photographed based on staining lipid accumulation by Oil - Red O in RGZ ( 1 micro mol / l ) - treated 3T3 - L1 cells without or with various concentrations of 6 - gingerol on differentiation day 8 .", "entity": [{"entity": "Oil - Red O", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "RGZ", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [190, 202]}], "task": "NER"}
{"text": "Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction .", "entity": [{"entity": "triglycerides", "entity_type": "Chemical", "pos": [16, 29]}], "task": "NER"}
{"text": "Differentiated cells were lysed to detect mRNA and protein levels of adipocyte - specific transcription factors by real - time reverse transcription - polymerase chain reaction and Western blot analysis , respectively .", "entity": [], "task": "NER"}
{"text": "6 - gingerol ( 50 micro mol / l ) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ - induced adipocyte differentiation in 3T3 - L1 cells .", "entity": [{"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "RGZ", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "The triglyceride accumulation induced by RGZ in differentiated 3T3 - L1 cells was also reduced by 6 - gingerol ( 50 micro mol / l ) .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "RGZ", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [98, 110]}], "task": "NER"}
{"text": "Treatment of differentiated 3T3 - L1 cells with 6 - gingerol ( 50 micro mol / l ) antagonized RGZ - induced gene expression of peroxisome proliferator - activated receptor ( PPAR ) gamma and CCAAT / enhancer - binding protein alpha .", "entity": [{"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [48, 60]}, {"entity": "RGZ", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "Additionally , the increased levels of mRNA and protein in adipocyte - specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3 - L1 cells were decreased upon treatment with 6 - gingerol .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [113, 123]}, {"entity": "RGZ", "entity_type": "Chemical", "pos": [144, 147]}, {"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [201, 213]}], "task": "NER"}
{"text": "Our data suggests that 6 - gingerol may be beneficial in obesity , by reducing adipogenesis partly through the down - regulating PPAR gamma activity .", "entity": [{"entity": "6 - gingerol", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "Multisite quantitative ultrasound for the prediction of fractures over five years of follow - up : The Canadian Multicentre Osteoporosis Study .", "entity": [], "task": "NER"}
{"text": "This study assessed the ability of multisite quantitative ultrasound ( mQUS ) to predict fracture over a five - year follow - up .", "entity": [], "task": "NER"}
{"text": "Participants were a subset of the Canadian Multicentre Osteoporosis Study .", "entity": [], "task": "NER"}
{"text": "mQUS - assessed speed of sound ( SOS in m / s ) at three sites ( distal radius , tibia and phalanx ) and extensive questionnaires were completed , after which participants were followed for five years and incident fractures recorded .", "entity": [], "task": "NER"}
{"text": "Two survival analyses were completed for each site - a univariate analysis and an adjusted multivariate analysis controlling for age , anti - resorptive use , femoral neck bone mineral density , number of diseases , previous fractures , BMI , parental history of hip fracture , current smoking , current alcoholic drinks > 3 per day , current using glucocorticoids , and rheumatoid arthritis diagnosis ( variables from the FRAX 10 - year fracture risk assessment tool ) .", "entity": [{"entity": "alcoholic", "entity_type": "Chemical", "pos": [304, 313]}], "task": "NER"}
{"text": "The unit of change for regression analyses was one standard deviation for all measurement sites , specific to site and sex .", "entity": [], "task": "NER"}
{"text": "Separate analyses were completed for all clinical fractures , non - vertebral fractures and hip fractures by sex .", "entity": [], "task": "NER"}
{"text": "There were 2633 women and 1108 men included and they experienced 204 incident fractures over five years ( 5 . 5 % fractured ) .", "entity": [], "task": "NER"}
{"text": "Univariate models revealed statistically significant ( p < 0 . 05 ) predictive ability of mQUS for all three measurement sites for women alone for all three fracture types ( one standard deviation decrease in SOS was associated with a 52 - 130 % increase in the risk of fracture ) , but not for the men ' s group .", "entity": [], "task": "NER"}
{"text": "The adjusted model found that measures at the distal radius and tibia in the women ' s group could significantly ( p < 0 . 05 ) predict all clinical fractures and non - vertebral fractures within the next five years ( one standard deviation decrease in SOS was associated with a 25 - 31 % increase in the risk of fracture ) .", "entity": [], "task": "NER"}
{"text": "mQUS provided significant five - year clinical fracture prediction in women , independent of bone mineral density and other significant risk factors for fracture , when measured at the distal radius and tibia sites .", "entity": [], "task": "NER"}
{"text": "Library construction and biological evaluation of enmein - type diterpenoid analogues as potential anticancer agents .", "entity": [{"entity": "enmein", "entity_type": "Chemical", "pos": [50, 56]}, {"entity": "diterpenoid", "entity_type": "Chemical", "pos": [64, 75]}], "task": "NER"}
{"text": "A library of promising enmein - type 14 - O - diterpenoid derivatives was constructed from a commercially available kaurene - type oridonin by practical and efficient synthetic methods .", "entity": [{"entity": "enmein", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "14 - O - diterpenoid", "entity_type": "Chemical", "pos": [37, 57]}, {"entity": "kaurene", "entity_type": "Chemical", "pos": [116, 123]}, {"entity": "oridonin", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines .", "entity": [], "task": "NER"}
{"text": "The IC50 values are similar to or improved over those of the parent molecule and paclitaxel , the latter of which was used as a positive control .", "entity": [{"entity": "paclitaxel", "entity_type": "Chemical", "pos": [81, 91]}], "task": "NER"}
{"text": "Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel - 7402 cells to better understand its mode of action .", "entity": [], "task": "NER"}
{"text": "Moreover , compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer ( MGC - 803 mice ) .", "entity": [], "task": "NER"}
{"text": "These results warrant further preclinical investigations of these diterpenoid - based analogues as potential novel anticancer chemotherapeutics .", "entity": [{"entity": "diterpenoid", "entity_type": "Chemical", "pos": [66, 77]}], "task": "NER"}
{"text": "PHARMACODYNAMIC EFFECTS OF A D - AMINO ACID OXIDASE INHIBITOR INDICATE A SPINAL SITE OF ACTION IN RAT MODELS OF NEUROPATHIC PAIN .", "entity": [{"entity": "D - AMINO ACID", "entity_type": "Chemical", "pos": [29, 43]}], "task": "NER"}
{"text": "Inhibition of D - amino acid oxidase ( DAAO ) activity is a potential target for the treatment of chronic pain .", "entity": [{"entity": "D - amino acid", "entity_type": "Chemical", "pos": [14, 28]}], "task": "NER"}
{"text": "Here we characterized the effects of systemic administration of the DAAO inhibitor 4H - furo [ 3 , 2 - b ] pyrrole - 5 - carboxylic acid ( SUN ) in rat models of neuropathic and inflammatory pain .", "entity": [{"entity": "4H - furo [ 3 , 2 - b ] pyrrole - 5 - carboxylic acid", "entity_type": "Chemical", "pos": [83, 136]}, {"entity": "SUN", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "Oral administration of SUN dose - dependently attenuated tactile allodynia induced by ligation of the L5 spinal nerve ( SNL ) , and similarly reversed thermal hyperalgesia produced by chronic constriction injury ( CCI ) .", "entity": [{"entity": "SUN", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "In addition , SUN was efficacious against Complete Freund ' s Adjuvant ( CFA ) - induced thermal hyperalgesia .", "entity": [{"entity": "SUN", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "In these models , maximal reversal of pain - related behaviors corresponded with maximum rates - of - increase in brain and plasma D - serine concentrations , indicative of full inhibition of DAAO activity .", "entity": [{"entity": "D - serine", "entity_type": "Chemical", "pos": [131, 141]}], "task": "NER"}
{"text": "To investigate the possible site ( s ) of action , we recorded spontaneous nerve activity and mechanically - evoked responses of central spinal cord dorsal horn neurons and compared these to spontaneous activity of peripheral dorsal root filaments in anesthetized SNL model animals .", "entity": [], "task": "NER"}
{"text": "Oral SUN reduced spontaneous activity in both central and peripheral recordings at doses and pretreatment times that corresponded to reduced mechanical allodynia in behavioral experiments .", "entity": [{"entity": "SUN", "entity_type": "Chemical", "pos": [5, 8]}], "task": "NER"}
{"text": "Following i . v . administration of SUN , the onset of action for this central effect was rapid ( maximal effects within 30 minutes ) , but was abolished by severing afferent inputs to the dorsal horn .", "entity": [{"entity": "SUN", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "Overall , these results indicate that inhibition of DAAO in peripheral afferent - spinal circuits reduced spontaneous neuronal activity to attenuate pain - related behaviors in rat models of neuropathic and inflammatory pain .", "entity": [], "task": "NER"}
{"text": "Synthesis and Structure - Activity Relationships of 5 , 6 , 7 - Substituted Pyrazolopyrimidines : Discovery of a Novel TSPO PET Ligand for Cancer Imaging .", "entity": [{"entity": "5 , 6 , 7 - Substituted Pyrazolopyrimidines", "entity_type": "Chemical", "pos": [52, 95]}], "task": "NER"}
{"text": "Focused library synthesis and structure - activity relationship development of 5 , 6 , 7 - substituted pyrazolopyrimidines led to the discovery of 2 - ( 5 , 7 - diethyl - 2 - ( 4 - ( 2 - fluoroethoxy ) phenyl ) pyrazolo [ 1 , 5 - a ] pyrimidin - 3 - yl ) - N , N - diethylacetamide ( 6b ) , a novel translocator protein ( TSPO ) ligand exhibiting a 36 - fold enhancement in affinity compared to another pyrazolopyrimidine - based TSPO ligand , 6a ( DPA - 714 ) .", "entity": [{"entity": "5 , 6 , 7 - substituted pyrazolopyrimidines", "entity_type": "Chemical", "pos": [79, 122]}, {"entity": "2 - ( 5 , 7 - diethyl - 2 - ( 4 - ( 2 - fluoroethoxy ) phenyl ) pyrazolo [ 1 , 5 - a ] pyrimidin - 3 - yl ) - N , N - diethylacetamide", "entity_type": "Chemical", "pos": [147, 281]}, {"entity": "pyrazolopyrimidine", "entity_type": "Chemical", "pos": [403, 421]}, {"entity": "DPA - 714", "entity_type": "Chemical", "pos": [449, 458]}], "task": "NER"}
{"text": "Radiolabeling with fluorine - 18 ( ( 18 ) F ) facilitated production of 2 - ( 5 , 7 - diethyl - 2 - ( 4 - ( 2 - [ ( 18 ) F ] fluoroethoxy ) phenyl ) pyrazolo [ 1 , 5 - a ] pyrimidin - 3 - yl ) - N , N - diethylacetamide ( ( 18 ) F - 6b ) in high radiochemical yield and specific activity .", "entity": [{"entity": "fluorine - 18", "entity_type": "Chemical", "pos": [19, 32]}, {"entity": "( 18 ) F", "entity_type": "Chemical", "pos": [35, 43]}, {"entity": "2 - ( 5 , 7 - diethyl - 2 - ( 4 - ( 2 - [ ( 18 ) F ] fluoroethoxy ) phenyl ) pyrazolo [ 1 , 5 - a ] pyrimidin - 3 - yl ) - N , N - diethylacetamide", "entity_type": "Chemical", "pos": [72, 219]}, {"entity": "( 18 ) F", "entity_type": "Chemical", "pos": [222, 230]}], "task": "NER"}
{"text": "In vivo studies of ( 18 ) F - 6b were performed which illuminated this agent as an improved probe for molecular imaging of TSPO - expressing cancers .", "entity": [{"entity": "( 18 ) F", "entity_type": "Chemical", "pos": [19, 27]}], "task": "NER"}
{"text": "A new sesquiterpene from the mangrove endophytic fungus Aspergillus terreus ( No . GX7 - 3B ) .", "entity": [{"entity": "sesquiterpene", "entity_type": "Chemical", "pos": [6, 19]}], "task": "NER"}
{"text": "A new compound 1 ( named botryosphaerin F ) , along with other three known compounds 2 ( 13 , 14 , 15 , 16 - tetranorlabd - 7 - ene - 19 , 6b : 12 , 17 - diolide ) , 3 ( botryosphaerin B ) and 4 ( LL - Z1271 beta ) , has been isolated from the mangrove fungus Aspergillus terreus ( No . GX7 - 3B ) .", "entity": [{"entity": "botryosphaerin F", "entity_type": "Chemical", "pos": [25, 41]}, {"entity": "13 , 14 , 15 , 16 - tetranorlabd - 7 - ene - 19 , 6b : 12 , 17 - diolide", "entity_type": "Chemical", "pos": [89, 161]}, {"entity": "botryosphaerin B", "entity_type": "Chemical", "pos": [170, 186]}, {"entity": "LL - Z1271 beta", "entity_type": "Chemical", "pos": [197, 212]}], "task": "NER"}
{"text": "The structure of the new compound was established by analysis of spectroscopic data .", "entity": [], "task": "NER"}
{"text": "The hypothetical biogenic relationship of four sesquiterpene analogues was also described in this paper .", "entity": [{"entity": "sesquiterpene", "entity_type": "Chemical", "pos": [47, 60]}], "task": "NER"}
{"text": "Furthermore , in the cytotoxicity assays , compound 1 showed potent inhibiting activity towards MCF - 7 and HL - 60 cancer cell lines with 50 % inhibition of cell growth ( IC50 ) values of 4 . 49 and 3 . 43 mu M , respectively , and compound 4 exhibited promising activity against HL - 60 cell line with an IC50 value of 0 . 6 mu M .", "entity": [], "task": "NER"}
{"text": "Comparison of transcriptomic signature of post - Chernobyl and post - radiotherapy thyroid tumors .", "entity": [], "task": "NER"}
{"text": "Background : We previously identified two highly discriminating and predictive radiation - induced transcriptomic signatures by comparing series of sporadic and post - radiotherapy thyroid tumors ( 322 - gene signature ) , and by re - analyzing a previously published dataset of sporadic and post - Chernobyl thyroid tumors ( 106 - gene signature ) .", "entity": [], "task": "NER"}
{"text": "The aim of the present work was 1 ) to compare the two signatures in terms of gene expression deregulations and molecular features / pathways and 2 ) to test the capacity of the post - radiotherapy signature in classifying the post - Chernobyl series of tumors and reciprocally of the post Chernobyl signature in classifying the post - radiotherapy induced tumors .", "entity": [], "task": "NER"}
{"text": "Methods : We now explored if post - radiotherapy and post - Chernobyl thyroid papillary carcinomas ( PTC ) display common molecular features by comparing molecular pathways deregulated in the two tumor series and test the potential of gene subsets of the post - radiotherapy signature to classify the post - Chernobyl series ( 14 sporadic and 12 post - Chernobyl PTC ) , and reciprocally of gene subsets of the post - Chernobyl signature to classify the post - radiotherapy series ( 15 sporadic and 12 post - radiotherapy PTC ) , by using conventional Principal Component Analysis .", "entity": [], "task": "NER"}
{"text": "Results : We found that the 5 genes common to the two signatures classified the learning / training tumors ( used to search these signatures ) of both the post - radiotherapy ( 7 PTC ) and the post - Chernobyl ( 6 PTC ) thyroid tumor series as compared with the sporadic tumors ( 7 sporadic PTC in each series ) .", "entity": [], "task": "NER"}
{"text": "Importantly , these 5 genes were also effective for classifying independent series of post - radiotherapy ( 5 PTC ) and post - Chernobyl ( 6 PTC ) tumors compared to independent series of sporadic tumors ( 8 PTC and 6 PTC , respectively ) ( testing tumors ) Moreover , part of each post - radiotherapy ( 32 genes ) and post - Chernobyl signature ( 16 genes ) cross - classified the respective series of thyroid tumors .", "entity": [], "task": "NER"}
{"text": "Finally , several molecular pathways deregulated in post - Chernobyl tumors matched those found to be deregulated in post - radiotherapy tumors .", "entity": [], "task": "NER"}
{"text": "Conclusions Overall , our data suggest that thyroid tumors that developed following either external exposure or internal 131I contamination shared common molecular features , related to DNA repair , oxidative and endoplasmic reticulum stresses , allowing their classification as radiation - induced tumors in comparison with sporadic counterparts , independently of doses and dose rates , which suggests there may be a \" general \" radiation - induced signature of thyroid tumors .", "entity": [], "task": "NER"}
{"text": "Baeckein E , a new bioactive C - methylated biflavonoid from the roots of Baeckea frutescens .", "entity": [{"entity": "Baeckein E", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "C - methylated biflavonoid", "entity_type": "Chemical", "pos": [29, 55]}], "task": "NER"}
{"text": "A phytochemical study of Baeckea frutescens afforded a new biflavonoid named as baeckein E ( 1 ) , along with four known C - methylated flavonols , baeckeins A ( 2 ) and B ( 3 ) , 6 - methylquercetin ( 6 ) and 6 - methylquercetin - 4 ' - O - beta - d - glucopyranoside ( 7 ) , and two known biflavonoids baeckeins C ( 4 ) and D ( 5 ) .", "entity": [{"entity": "biflavonoid", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "baeckein E", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "C - methylated flavonols", "entity_type": "Chemical", "pos": [121, 145]}, {"entity": "baeckeins A", "entity_type": "Chemical", "pos": [148, 159]}, {"entity": "6 - methylquercetin", "entity_type": "Chemical", "pos": [180, 199]}, {"entity": "6 - methylquercetin - 4 ' - O - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [210, 268]}, {"entity": "baeckeins C", "entity_type": "Chemical", "pos": [304, 315]}], "task": "NER"}
{"text": "The structure of compound 1 was elucidated on the basis of spectroscopic analysis , including HR - ESI - MS , 1D and 2D NMR spectra , and the absolute configurations of C - 2 and C - 3 for compound 1 were assigned by circular dichroism spectrometry combined with quantum chemical calculations .", "entity": [], "task": "NER"}
{"text": "The antioxidant and cytoprotective activities of compounds 1 - 7 were also investigated .", "entity": [], "task": "NER"}
{"text": "Controlled Assembly of Gold Nanoparticles through Antibody Recognition : Study and Utilizing the Effect of Particle Size on Interparticle Distance .", "entity": [], "task": "NER"}
{"text": "An assembly of gold nanoparticle through the recognition of unmodified antibody was developed .", "entity": [], "task": "NER"}
{"text": "The use of peptide ( Cys - Ala - Leu - Asn - Asn ) as ligands to stabilize and functionalize gold nanoparticles provides technical and operational convenience .", "entity": [{"entity": "Cys - Ala - Leu - Asn - Asn", "entity_type": "Chemical", "pos": [21, 48]}], "task": "NER"}
{"text": "These peptide - capped particles in different sizes are recognized by antibody and assembly to form dimers and expanded hybrid material by controlling the conditions .", "entity": [], "task": "NER"}
{"text": "The interparticle spacing of these assemblies was well studied with small - angle X - ray scattering measurements , and it was found that the interparticle spacing is inversely dependent on the particle size .", "entity": [], "task": "NER"}
{"text": "This relationship of interparticle spacing and particle size is closely related to the structure of antibody linker .", "entity": [], "task": "NER"}
{"text": "Therefore , analyzing the interparticle spacing of assemblies can reveal the equilibrium configuration of IgG .", "entity": [], "task": "NER"}
{"text": "Based on the investigation , the Fab - Fab angle of IgG is obtained to be =~ 102 degrees and the Fab arms are =~ 7 . 8 nm .", "entity": [], "task": "NER"}
{"text": "These results provide new experimental data on the structure of flexible IgG .", "entity": [], "task": "NER"}
{"text": "Time - split cross - validation as a method for estimating the goodness of prospective prediction .", "entity": [], "task": "NER"}
{"text": "Cross - validation is a common method to validate a QSAR model .", "entity": [], "task": "NER"}
{"text": "In cross - validation , some compounds are held out as a test set , while the remaining compounds form a training set .", "entity": [], "task": "NER"}
{"text": "A model is built from the training set , and the test set compounds are predicted on that model .", "entity": [], "task": "NER"}
{"text": "The agreement of the predicted and observed activity values of the test set ( measured by , say , R ( 2 ) ) is an estimate of the self - consistency of the model and is sometimes taken as an indication of the predictivity of the model .", "entity": [], "task": "NER"}
{"text": "This estimate of predictivity can be optimistic or pessimistic compared to true prospective prediction , depending how compounds in the test set are selected .", "entity": [], "task": "NER"}
{"text": "Here , we show that time - split selection gives an R ( 2 ) that is more like that of true prospective prediction than the R ( 2 ) from random selection ( too optimistic ) or from our analog of leave - class - out selection ( too pessimistic ) .", "entity": [], "task": "NER"}
{"text": "Time - split selection should be used in addition to random selection as a standard for cross - validation in QSAR model building .", "entity": [], "task": "NER"}
{"text": "Discovery of oxysterol - derived pharmacological chaperones for NPC1 : implication for the existence of second sterol - binding site .", "entity": [{"entity": "oxysterol", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [111, 117]}], "task": "NER"}
{"text": "Niemann - Pick type C1 ( NPC1 ) is a polytopic endosomal membrane protein required for efflux of LDL - derived cholesterol from endosomes , and mutations of this protein are associated with Niemann - Pick disease type C , a fatal neurodegenerative disease .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [111, 122]}], "task": "NER"}
{"text": "At least one prevalent mutation ( I1061T ) has been shown to cause a folding defect , which results in failure of endosomal localization , leading to a loss - of - function phenotype .", "entity": [], "task": "NER"}
{"text": "Here , we show that several oxysterols and their derivatives act as pharmacological chaperones ; binding of these compounds to I1061T NPC1 corrects the localization / maturation defect of the mutant protein .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [28, 38]}], "task": "NER"}
{"text": "Further , these compounds alleviate intracellular cholesterol accumulation in patient - derived fibroblasts , suggesting that they may have therapeutic potential .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "These oxysterol derivatives bind to a domain of NPC1 that is different from the known N - terminal sterol - binding domain ; i . e . , there is an additional sterol - binding site on NPC1 .", "entity": [{"entity": "oxysterol", "entity_type": "Chemical", "pos": [6, 15]}, {"entity": "N", "entity_type": "Chemical", "pos": [48, 49]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [99, 105]}, {"entity": "sterol", "entity_type": "Chemical", "pos": [158, 164]}], "task": "NER"}
{"text": "Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks .", "entity": [], "task": "NER"}
{"text": "The Y - family of DNA polymerases support of translesion DNA synthesis ( TLS ) associated with stalled DNA replication by DNA damage .", "entity": [], "task": "NER"}
{"text": "Recently , a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo .", "entity": [], "task": "NER"}
{"text": "Here we show that mouse polymerase kappa ( Pol kappa ) could accumulate at laser - induced sites of damage in vivo resembling polymerases eta and iota .", "entity": [], "task": "NER"}
{"text": "The recruitment was mediated through Pol kappa C - terminus which contains the PCNA - interacting peptide , ubiquitin zinc finger motif 2 and nuclear localization signal .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [47, 48]}, {"entity": "zinc", "entity_type": "Chemical", "pos": [118, 122]}], "task": "NER"}
{"text": "Interestingly , this recruitment was significantly reduced in MSH2 - deficient LoVo cells and Rad18 - depleted cells .", "entity": [], "task": "NER"}
{"text": "We further observed that Pol kappa - deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single - strand break repair and double - strand break repair .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [101, 105]}], "task": "NER"}
{"text": "We speculate that Pol kappa may have an important role in strand break repair following oxidative stress in vivo .", "entity": [], "task": "NER"}
{"text": "In silico identification of poly ( ADP - ribose ) polymerase - 1 inhibitors and their chemosensitizing effects against cisplatin - resistant human gastric cancer cells .", "entity": [{"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [28, 49]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [119, 128]}], "task": "NER"}
{"text": "Poly ( ADP - ribose ) polymerase - 1 ( PARP - 1 ) enzyme is involved in the repair of DNA damages made by certain anticancer agents .", "entity": [{"entity": "Poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [0, 21]}], "task": "NER"}
{"text": "It is suggested that PARP - 1 inhibitors potentiate the cytotoxic effects and circumvent the resistance of DNA - modifying anticancer agents such as cisplatin .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [149, 158]}], "task": "NER"}
{"text": "In this study , we conducted virtual screening of Korea Chemical Bank database targeting PARP - 1 and identified several potent PARP - 1 inhibitors with submicromolar IC50 values ( 77 - 79nM ) .", "entity": [], "task": "NER"}
{"text": "We then examined the chemosensitization of cisplatin by pre - treatment of PARP - 1 inhibitors in cisplatin - resistant human gastric cancer cells .", "entity": [{"entity": "cisplatin", "entity_type": "Chemical", "pos": [43, 52]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "Our results show that PARP - 1 inhibitors suppress the formation of poly ( ADP - ribose ) and enhance the cytotoxicity of cisplatin .", "entity": [{"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [68, 89]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [122, 131]}], "task": "NER"}
{"text": "Activation of PPAR gamma is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress .", "entity": [{"entity": "hydroxysafflor yellow A", "entity_type": "Chemical", "pos": [41, 64]}], "task": "NER"}
{"text": "Oxidative stress caused hepatic fibrosis by activating hepatic stellate cells ( HSCs ) , which were implemented by depressing PPAR gamma activation .", "entity": [], "task": "NER"}
{"text": "Hydroxysafflor yellow A ( HSYA ) as a nature active ingredient with antioxidant capacity was able to effectively attenuate oxidative stress mediated injury .", "entity": [{"entity": "Hydroxysafflor yellow A", "entity_type": "Chemical", "pos": [0, 23]}, {"entity": "HSYA", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "So it will be very interesting to study effect of HSYA on HSCs activation and liver fibrosis , and reveal the role of PPAR gamma . CCl4 and H2O2 were used to mimic oxidative stress mediated hepatic injury in vitro and in vivo respectively .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [131, 135]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "The anti - fibrosis effects of HSYA were evaluated and its mechanisms were disclosed by applying western blot , histopathological analysis , flow cytometry , RT - PCR and ELISA .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [31, 35]}], "task": "NER"}
{"text": "Our results showed that HSCs activation and proliferation could be induced by oxidative stress , and the expressive levels of TGF - beta 1 and TIMP - 1 , the serum levels of ALT , AST , HA , LN , III - C and IV - C were also enhanced by oxidative stress , which is correlated with liver fibrosis ( p < 0 . 05 or p < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "HSYA was able to effectively inhibit oxidative stress mediated hepatic injury by increasing the activities of antioxidant enzymes , up regulating the expression of PPAR gamma and MMP - 2 , and down regulating the expression of TGF - beta 1 and TIMP - 1 , and reducing alpha - SMA level .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The protective effect of HSYA can be significantly attenuated by GW9662 via blocking PPAR gamma ( p < 0 . 05 or p < 0 . 01 ) .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [25, 29]}, {"entity": "GW9662", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "Taken together , these results demonstrate that HSYA is able to significantly protect the liver from oxidative stress , which requires for HSYA to stimulate PPAR gamma activity , reduce cell proliferation and suppress ECM synthesis .", "entity": [{"entity": "HSYA", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "HSYA", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "Targeting kinases : a new approach to treating inflammatory rheumatic diseases .", "entity": [], "task": "NER"}
{"text": "After two decades of research and development activity focussed on orally active kinase inhibitors , the first such drug ( the JAK inhibitor Xeljanz , tofacitinib ) was approved by the FDA in November 2012 for the treatment of rheumatoid arthritis ( RA ) .", "entity": [{"entity": "Xeljanz", "entity_type": "Chemical", "pos": [141, 148]}, {"entity": "tofacitinib", "entity_type": "Chemical", "pos": [151, 162]}], "task": "NER"}
{"text": "There is an intense activity in many companies both on expanding the utility of JAK inhibitors in other auto - immune indications and in discovering inhibitors of the JAK family with different and more selective profiles .", "entity": [], "task": "NER"}
{"text": "Progress is also being made with orally active Syk inhibitors .", "entity": [], "task": "NER"}
{"text": "One such inhibitor ( fostamatinib ) is currently in large - scale phase 3 trials , and there are others in clinical development .", "entity": [{"entity": "fostamatinib", "entity_type": "Chemical", "pos": [21, 33]}], "task": "NER"}
{"text": "The last two to three years have been transformative for kinase inhibitors in auto - immune diseases , as several inhibitors have finally progressed beyond phase 2 trials after so many failures on other targets .", "entity": [], "task": "NER"}
{"text": "Thus , there are new treatment options for RA patients beyond existing oral DMARDs and parenteral biologics .", "entity": [], "task": "NER"}
{"text": "An Ancient Transcription Factor Initiates the Burst of piRNA Production during Early Meiosis in Mouse Testes .", "entity": [], "task": "NER"}
{"text": "Animal germ cells produce PIWI - interacting RNAs ( piRNAs ) , small silencing RNAs that suppress transposons and enable gamete maturation .", "entity": [], "task": "NER"}
{"text": "Mammalian transposon - silencing piRNAs accumulate early in spermatogenesis , whereas pachytene piRNAs are produced later during postnatal spermatogenesis and account for > 95 % of all piRNAs in the adult mouse testis .", "entity": [], "task": "NER"}
{"text": "Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm , but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known .", "entity": [], "task": "NER"}
{"text": "Here , we show that the transcription factor A - MYB initiates pachytene piRNA production .", "entity": [], "task": "NER"}
{"text": "A - MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors including MIWI , the protein through which pachytene piRNAs function .", "entity": [], "task": "NER"}
{"text": "A - MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feedforward loop that ensures the robust accumulation of pachytene piRNAs .", "entity": [], "task": "NER"}
{"text": "This regulatory circuit , which can be detected in rooster testes , likely predates the divergence of birds and mammals .", "entity": [], "task": "NER"}
{"text": "Structure of the Polycomb Group Protein PCGF1 in Complex with BCOR Reveals Basis for Binding Selectivity of PCGF Homologs .", "entity": [], "task": "NER"}
{"text": "Polycomb - group RING finger homologs ( PCGF1 , PCGF2 , PCGF3 , PCGF4 , PCGF5 , and PCGF6 ) are critical components in the assembly of distinct Polycomb repression complex 1 ( PRC1 ) - related complexes .", "entity": [], "task": "NER"}
{"text": "Here , we identify a protein interaction domain in BCL6 corepressor , BCOR , which binds the RING finger - and WD40 - associated ubiquitin - like ( RAWUL ) domain of PCGF1 ( NSPC1 ) and PCGF3 but not of PCGF2 ( MEL18 ) or PCGF4 ( BMI1 ) .", "entity": [], "task": "NER"}
{"text": "Because of the selective binding , we have named this domain PCGF Ub - like fold discriminator ( PUFD ) .", "entity": [], "task": "NER"}
{"text": "The structure of BCOR PUFD bound to PCGF1 reveals that ( 1 ) PUFD binds to the same surfaces as observed for a different Polycomb group RAWUL domain and ( 2 ) the ability of PUFD to discriminate among RAWULs stems from the identity of specific residues within these interaction surfaces .", "entity": [], "task": "NER"}
{"text": "These data show the molecular basis for determining the binding preference for a PCGF homolog , which ultimately helps determine the identity of the larger PRC1 - like assembly .", "entity": [], "task": "NER"}
{"text": "Characterization of the first K ( + ) channel blockers from the venom of the Moroccan scorpion Buthus occitanus Paris .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "The availability of a large variety of specific blockers , which inhibit different K ( + ) currents , would help to elucidate their differences in physiological function .", "entity": [{"entity": "K ( + )", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "Short peptide toxins isolated from scorpion venoms are able to block voltage - dependent or Ca ( 2 + ) - activated K ( + ) channels .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [92, 102]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [115, 122]}], "task": "NER"}
{"text": "Here , we have studied the venom of the Moroccan scorpion Buthus occitanus Paris ( BoP ) in order to find new peptides , which could enlarge our structure - function relationship knowledge on the Kv1 . 3 blocker Kaliotoxin ( KTX ) that belongs to the alpha - KTx3 . 1 family .", "entity": [], "task": "NER"}
{"text": "Indeed and since more a decade , KTX is widely used by international investigators because it exhibits a quite sharp specificity and a high - affinity for the Kv1 . 3 channel , which is not only a neuronal channel but also a therapeutic target for diverse autoimmune diseases such as multiple sclerosis , type 1 diabetes , and rheumatoid arthritis .", "entity": [], "task": "NER"}
{"text": "The BoP venom was first investigated using HPLC and MALDI - TOF / MS .", "entity": [], "task": "NER"}
{"text": "Further , the HPLC fractions were screened by ELISA with antibodies raised against KTX .", "entity": [], "task": "NER"}
{"text": "These antibodies recognized at least three components toxic in mice by intracerebroventricular injection .", "entity": [], "task": "NER"}
{"text": "They were further pharmacologically characterized by competition using ( 125 ) I - KTX bound to its specific binding sites on rat brain synaptosomes .", "entity": [{"entity": "( 125 ) I", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "A single component ( 4161 Da ) inhibited totally the ( 125 ) I - KTX binding and with high - affinity ( IC50 = 0 . 1 nM ) , while the two other components poorly competed with ( IC50 > 100 nM ) .", "entity": [{"entity": "( 125 ) I", "entity_type": "Chemical", "pos": [53, 62]}], "task": "NER"}
{"text": "These toxins were sequenced in full by Edman ' s degradation .", "entity": [], "task": "NER"}
{"text": "The high - affinity ligand ( BoPKTX ) shares 86 % sequence identity with KTX and was classified as toxin alpha - KTx3 . 17 .", "entity": [], "task": "NER"}
{"text": "The two others peptides ( BoP1 and BoP2 , 4093 Da and 4121 Da , respectively ) only differ by a Lys / Arg mutation .", "entity": [{"entity": "Lys", "entity_type": "Chemical", "pos": [96, 99]}, {"entity": "Arg", "entity_type": "Chemical", "pos": [102, 105]}], "task": "NER"}
{"text": "Their amino acid sequences were related to Martentoxin , which has been characterized from the Chinese scorpion Buthus martenzi Karch and described as both a BKCa and Kv1 . 3 blocker .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [6, 16]}], "task": "NER"}
{"text": "Accordingly , they belong to the alpha - KTx16 family .", "entity": [], "task": "NER"}
{"text": "Towards the bioequivalence of pressurised metered dose inhalers 1 : Design and characterisation of aerodynamically equivalent beclomethasone dipropionate inhalers with and without glycerol as a non - volatile excipient .", "entity": [{"entity": "beclomethasone dipropionate", "entity_type": "Chemical", "pos": [126, 153]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [180, 188]}], "task": "NER"}
{"text": "A series of semi - empirical equations were utilised to design two solution based pressurised metered dose inhaler ( pMDI ) formulations , with equivalent aerosol performance but different physicochemical properties .", "entity": [], "task": "NER"}
{"text": "Both inhaler formulations contained the drug , beclomethasone dipropionate ( BDP ) , a volatile mixture of ethanol co - solvent and propellant ( hydrofluoroalkane - HFA ) .", "entity": [{"entity": "beclomethasone dipropionate", "entity_type": "Chemical", "pos": [47, 74]}, {"entity": "BDP", "entity_type": "Chemical", "pos": [77, 80]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [107, 114]}, {"entity": "hydrofluoroalkane", "entity_type": "Chemical", "pos": [145, 162]}, {"entity": "HFA", "entity_type": "Chemical", "pos": [165, 168]}], "task": "NER"}
{"text": "However , one formulation was designed such that the emitted aerosol particles contained BDP and glycerol , a common inhalation particle modifying excipient , in a 1 : 1 mass ratio .", "entity": [{"entity": "BDP", "entity_type": "Chemical", "pos": [89, 92]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "By modifying the formulation parameters , including actuator orifice , HFA and metering volumes , it was possible to produce two formulations ( glycerol - free and glycerol - containing ) which had identical mass median aerodynamic diameters ( 2 . 4 mu m +/- 0 . 1 and 2 . 5 mu m +/- 0 . 2 ) , fine particle dose ( >= 5 mu m ; 66 mu g +/- 6 and 68 mu g +/- 2 ) and fine particle fractions ( 28 % +/- 2 % and 30 % +/- 1 % ) , respectively .", "entity": [{"entity": "HFA", "entity_type": "Chemical", "pos": [71, 74]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [144, 152]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [164, 172]}], "task": "NER"}
{"text": "These observations demonstrate that it is possible to engineer formulations that generate aerosol particles with very different compositions to have similar emitted dose and in vitro deposition profiles , thus making them equivalent in terms of aerosol performance .", "entity": [], "task": "NER"}
{"text": "Analysis of the physicochemical properties of each formulation identified significant differences in terms of morphology , thermal properties and drug dissolution of emitted particles .", "entity": [], "task": "NER"}
{"text": "The particles produced from both formulations were amorphous ; however , the formulation containing glycerol generated particles with a porous structure , while the glycerol - free formulation generated particles with a primarily spherical morphology .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [100, 108]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [165, 173]}], "task": "NER"}
{"text": "Furthermore , the glycerol - containing particles had a significantly lower dissolution rate ( 7 . 8 % +/- 2 . 1 % , over 180min ) compared to the glycerol - free particles ( 58 . 0 % +/- 2 . 9 % , over 60min ) when measured using a Franz diffusion cell .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [18, 26]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [147, 155]}], "task": "NER"}
{"text": "It is hypothesised that the presence of glycerol in the emitted aerosol particles altered solubility and drug transport , which may have implications for BDP pharmacokinetics after deposition in the respiratory tract .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [40, 48]}, {"entity": "BDP", "entity_type": "Chemical", "pos": [154, 157]}], "task": "NER"}
{"text": "5 - HT1A receptors direct the orientation of plasticity in layer 5 pyramidal neurons of the mouse prefrontal cortex .", "entity": [], "task": "NER"}
{"text": "Several psychiatric disorders involving the prefrontal cortex ( PFC ) are associated with a dysfunction of 5 - HT1A receptors ( 5 - HT1AR ) .", "entity": [], "task": "NER"}
{"text": "These receptors , located on interneurons and pyramidal neurons , may influence neuronal excitability through a regulation of the balance between excitation ( E ) and inhibition ( I ) .", "entity": [], "task": "NER"}
{"text": "Patch - clamp recordings in mouse cortical slices were performed to determine the modulatory role of 5 - HT1AR on the excitability and the synaptic plasticity of layer 5 pyramidal neurons ( L5PyNs ) of the PFC .", "entity": [], "task": "NER"}
{"text": "This was done by a comparison of postsynaptic currents evoked by electrical stimulation in layer 2 / 3 of 5 - HT1AR - KO and wild - type ( WT ) mice .", "entity": [], "task": "NER"}
{"text": "We observed that the E - I balance was significantly changed from 20 % E - 80 % I in WT mice to 23 % E - 77 % I in 5 - HT1AR - KO mice , demonstrating that 5 - HT1ARs contribute to the control of the balance between excitation and inhibition .", "entity": [], "task": "NER"}
{"text": "Furthermore , we show that interfering with 5 - HT1AR reduced the magnitude of the long term potentiation of excitation ( eLTP ) ( induced by high frequency stimulation ) .", "entity": [], "task": "NER"}
{"text": "In addition , we show that 5 - HT1ARs determine the orientation of the synaptic plasticity towards LTP or LTD or no plasticity through the modulation of NMDAR - mediated currents .", "entity": [], "task": "NER"}
{"text": "Our data point out to a unique role of 5 - HT1A postsynaptic receptors in PFC to adapt the functional plasticity of L5PyNs towards LTP , LTD or no plasticity .", "entity": [], "task": "NER"}
{"text": "This brings a new way to intervene on neuronal networks of the PFC in anxiety disorders and schizophrenia .", "entity": [], "task": "NER"}
{"text": "Baicalein attenuates bleomycin - induced pulmonary fibrosis in rats through inhibition of miR - 21 .", "entity": [{"entity": "Baicalein", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "bleomycin", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Currently , there is no satisfactory treatment for pulmonary fibrosis , and effective agents urgently need to be developed .", "entity": [], "task": "NER"}
{"text": "The aim of the present study was to investigate the effects of baicalein on bleomycin - induced pulmonary fibrosis , and the novel mechanisms involved in the anti - fibrosis effects .", "entity": [{"entity": "baicalein", "entity_type": "Chemical", "pos": [63, 72]}, {"entity": "bleomycin", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Pulmonary fibrosis was induced by a single intratracheal instillation of 5 mg / kg bleomycin .", "entity": [{"entity": "bleomycin", "entity_type": "Chemical", "pos": [83, 92]}], "task": "NER"}
{"text": "Two bleomycin - treated groups were orally administered daily with 50 and 100 mg / kg of baicalein from day 1 to 28 .", "entity": [{"entity": "bleomycin", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "baicalein", "entity_type": "Chemical", "pos": [89, 98]}], "task": "NER"}
{"text": "The results showed baicalein decreased hydroxyproline content and alpha - SMA levels and increased lung index .", "entity": [{"entity": "baicalein", "entity_type": "Chemical", "pos": [19, 28]}, {"entity": "hydroxyproline", "entity_type": "Chemical", "pos": [39, 53]}], "task": "NER"}
{"text": "Histopathological examinations demonstrated baicalein could obviously lower the degree of alveolitis and lung fibrosis .", "entity": [{"entity": "baicalein", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "The total antioxidant capacity in bleomycin - treated rats with baicalein was also remarkably higher than in those without baicalein .", "entity": [{"entity": "bleomycin", "entity_type": "Chemical", "pos": [34, 43]}, {"entity": "baicalein", "entity_type": "Chemical", "pos": [64, 73]}, {"entity": "baicalein", "entity_type": "Chemical", "pos": [123, 132]}], "task": "NER"}
{"text": "Baicalein remarkably decreased miR - 21 levels and inhibited the increased expression of TGF - beta 1 and p - Smad - 2 / 3 in bleomycin - treated rats .", "entity": [{"entity": "Baicalein", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "bleomycin", "entity_type": "Chemical", "pos": [126, 135]}], "task": "NER"}
{"text": "Baicalein can attenuate bleomycin - induced pulmonary fibrosis .", "entity": [{"entity": "Baicalein", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "bleomycin", "entity_type": "Chemical", "pos": [24, 33]}], "task": "NER"}
{"text": "The attenuation is partly achieved by improving antioxidant activity , alleviating inflammation , repressing miR - 21 , and inhibiting TGF - beta / Smad signaling .", "entity": [], "task": "NER"}
{"text": "Quercetin and epigallocatechin - 3 - gallate effect on the anisotropy of model membranes with cholesterol .", "entity": [{"entity": "Quercetin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [14, 44]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "Cell membrane fluidity , which can be altered by oxidative stress , plays an important role in the cell physiology .", "entity": [], "task": "NER"}
{"text": "Flavonoids are among the most studied food substances that prevent and / or reduce oxidative stress , but their action mechanisms are far from being understood .", "entity": [{"entity": "Flavonoids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "We performed a study on the effect of quercetin and epigallocatechin - 3 - gallate on 2 - Dimyristoyl - sn - glycero - 3 - phosphocholine small unilamellar vesicles ( SUVs ) with different amounts of cholesterol , using Laurdan as a fluorescent probe , to put into evidence the perturbations of the phospholipid membrane fluidity and local lipid order in an attempt to decipher the action mechanism of the flavonoids at the cell membrane level .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [52, 82]}, {"entity": "2 - Dimyristoyl - sn - glycero - 3 - phosphocholine", "entity_type": "Chemical", "pos": [86, 137]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [200, 211]}, {"entity": "Laurdan", "entity_type": "Chemical", "pos": [220, 227]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [406, 416]}], "task": "NER"}
{"text": "Results indicate that polyphenols modulate the transition from the gel phase to the liquid crystalline phase of SUVs in all studied membranes .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "SUVs with cholesterol have by themselves higher phase transition temperature and the presence of polyphenols stabilizes further the membrane .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [10, 21]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [97, 108]}], "task": "NER"}
{"text": "Quercetin has a dose - dependent effect on the fluidity and local order of the lipid membranes , whilst epigallocatechin - 3 - gallate action is not dose - dependent , the differences being attributable to the hydrophobic / hydrophilic character of the substances .", "entity": [{"entity": "Quercetin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [104, 134]}], "task": "NER"}
{"text": "The findings are discussed within the frame of earlier reports on the effect of polyphenols on artificial membranes .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "Cytotoxic mechanism of Piper gaudichaudianum Kunth essential oil and its major compound nerolidol .", "entity": [{"entity": "nerolidol", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "Piper gaudichaudianum Kunth is used in popular medicine as anti - inflamatory and against liver disorders .", "entity": [], "task": "NER"}
{"text": "One of the most studied components of the plant is the essential oil for which chemical analysis revealed ( E ) - nerolidol as major compound .", "entity": [{"entity": "( E ) - nerolidol", "entity_type": "Chemical", "pos": [106, 123]}], "task": "NER"}
{"text": "Recently , we have shown that P . gaudichaudianum essential oil possesses strong cytotoxic effects in mammalian V79 cells .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to analyze the cytotoxicity and mutagenicity of P . gaudichaudianum essential oil and nerolidol using Saccharomyces cerevisiae as model study .", "entity": [{"entity": "nerolidol", "entity_type": "Chemical", "pos": [112, 121]}], "task": "NER"}
{"text": "Treatment of the XV185 - 14c and N123 strains with essential oil and nerolidol led to cytotoxicity but did not induce mutagenicity .", "entity": [{"entity": "nerolidol", "entity_type": "Chemical", "pos": [69, 78]}], "task": "NER"}
{"text": "Our results revealed an important role of base excision repair ( BER ) as the ntg1 , ntg2 , apn1 and apn2 mutants showed pronounced sensitivity to essential oil and nerolidol .", "entity": [{"entity": "nerolidol", "entity_type": "Chemical", "pos": [165, 174]}], "task": "NER"}
{"text": "In the absence of superoxide dismutase ( in sod1 Delta mutant strain ) sensitivity to the essential oil and nerolidol increased indicating that this oil and nerolidol are generating reactive oxygen species ( ROS ) .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "nerolidol", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "nerolidol", "entity_type": "Chemical", "pos": [157, 166]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [191, 197]}], "task": "NER"}
{"text": "The ROS production was confirmed by DCF - DA probing assay in Sod - deficient strains .", "entity": [{"entity": "DCF - DA", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "From this , we conclude that the observed cytotoxicity to P . gaudichaudianum essential oil and nerolidol is mainly related to ROS and DNA single strand breaks generated by the presence of oxidative lesions .", "entity": [{"entity": "nerolidol", "entity_type": "Chemical", "pos": [96, 105]}], "task": "NER"}
{"text": "Differential effects of acute and chronic zinc ( Zn ) exposure on hepatic lipid deposition and metabolism in yellow catfish Pelteobagrus fulvidraco .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [42, 46]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [49, 51]}], "task": "NER"}
{"text": "The present study is conducted to determine the potential mechanisms of Zn on hepatic lipid deposition and metabolism for yellow catfish Pelteobagrus fulvidraco with 8 - week chronic exposure to low Zn levels ( Zn levels : 0 . 05 , 0 . 35 and 0 . 86mg / l Zn , respectively ) and 96 - h acute exposure to a high Zn level ( Zn level : 4 . 71mg / l Zn , respectively ) .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [72, 74]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [199, 201]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [211, 213]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [256, 258]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [312, 314]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [323, 325]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [347, 349]}], "task": "NER"}
{"text": "For that purpose , hepatic lipid deposition and Zn accumulation , hepatic carnitine palmitoyltransferase I ( CPT I ) and lipoprotein lipase ( LPL ) activities , and the hepatic mRNA expression of ten genes involved in lipid metabolism are determined .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [48, 50]}, {"entity": "carnitine", "entity_type": "Chemical", "pos": [74, 83]}], "task": "NER"}
{"text": "Chronic ( 8 weeks ) exposure to low Zn levels apparently increases hepatic lipid content , hepatosomatic index ( HSI ) ( P < 0 . 05 ) and LPL activity , and reduces hepatic CPT I activity .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [36, 38]}], "task": "NER"}
{"text": "In contrast , the acute ( 96h ) exposure to high Zn level reduces hepatic lipid content , HSI and LPL activity , and increases CPT I activity .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [49, 51]}], "task": "NER"}
{"text": "The change of mRNA levels of genes related to lipid metabolism is Zn concentration - dependent .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [66, 68]}], "task": "NER"}
{"text": "Pearson correlations among mRNA expression levels , lipid content , CPT I and LPL activities in liver are also observed in yellow catfish with the 8 - week chronic Zn exposure .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [164, 166]}], "task": "NER"}
{"text": "For the first time , our study demonstrates the effect of waterborne Zn exposure on lipid metabolism at the molecular levels in fish , which may contribute to understanding the mechanism of Zn - induced hepatic toxicity in fish .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [69, 71]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [190, 192]}], "task": "NER"}
{"text": "The force of the spontaneously contracting zebrafish heart , in the assessment of cardiovascular toxicity : Application on adriamycin .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [123, 133]}], "task": "NER"}
{"text": "The heart of the zebrafish has been used extensively to assess the cardiotoxic effect of compounds , using the frequency of heart contractions as the main index of cardiac response to drugs .", "entity": [], "task": "NER"}
{"text": "In this study , the force and the frequency generated by the spontaneously contracting zebrafish heart , isolated in saline , were found to be 0 . 87 +/- 0 . 05mN and 1 . 54 +/- 0 . 03Hz ( n = 6 ) respectively within the first hour of recording .", "entity": [], "task": "NER"}
{"text": "Both values of force and frequency remained constant for over 8h .", "entity": [], "task": "NER"}
{"text": "The advantage of prolonged vitality in the assessment of cardiovascular toxicity was shown using the well - known anticancer drug adriamycin , which has severe cardiotoxic side effects .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [130, 140]}], "task": "NER"}
{"text": "At 10 . 0 mu M there was a 21 . 05 +/- 4 . 42 % ( p = 0 . 02 , n = 4 ) decrease in the force of contraction , while the frequency was not affected after 3h treatment ( p > 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "At 50 . 0 and 100 . 0 mu M there was a 33 . 24 +/- 3 . 0 and 46 . 6 +/- 4 . 80 % irreversible decrease in force ( p < 0 . 05 , n = 4 ) , while a 18 . 02 +/- 4 . 07 % and 16 . 16 +/- 4 . 07 % reversible increase was observed in the frequency ( p = 0 . 02 , n = 4 ) .", "entity": [], "task": "NER"}
{"text": "These contradictory positive chronotropic and negative inotropic responses indicate the strong inhibitory effect of adriamycin on ventricular cardiomyocytes and its excitatory effects on auto - rhythmical pacemaker cells .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [116, 126]}], "task": "NER"}
{"text": "If heart frequency was the only parameter used to assess the cardiotoxic effect of adriamycin , at the above range of concentrations , this compound would have been classified as non - cardiotoxic .", "entity": [{"entity": "adriamycin", "entity_type": "Chemical", "pos": [83, 93]}], "task": "NER"}
{"text": "Potentiation of morphine - induced mechanical antinociception by sigma 1 receptor inhibition : Role of peripheral sigma 1 receptors .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [16, 24]}], "task": "NER"}
{"text": "We studied the modulation of morphine - induced mechanical antinociception and side effects by sigma 1 receptor inhibition .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Both wild - type ( WT ) and sigma 1 receptor knockout ( sigma 1 - KO ) mice showed similar responses to paw pressure ( 100 - 600 g ) .", "entity": [], "task": "NER"}
{"text": "The systemic ( subcutaneous ) or local ( intraplantar ) administration of sigma 1 antagonists ( BD - 1063 , BD - 1047 , NE - 100 and S1RA ) was devoid of antinociceptive effects in WT mice .", "entity": [{"entity": "BD - 1063", "entity_type": "Chemical", "pos": [96, 105]}, {"entity": "BD - 1047", "entity_type": "Chemical", "pos": [108, 117]}, {"entity": "NE - 100", "entity_type": "Chemical", "pos": [120, 128]}, {"entity": "S1RA", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "However , sigma 1 - KO mice exhibited an enhanced mechanical antinociception in response to systemic morphine ( 1 - 16 mg / kg ) .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "Similarly , systemic treatment of WT mice with sigma 1 antagonists markedly potentiated morphine - induced antinociception , and its effects were reversed by the selective sigma 1 agonist PRE - 084 .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [88, 96]}, {"entity": "PRE - 084", "entity_type": "Chemical", "pos": [188, 197]}], "task": "NER"}
{"text": "Although the local administration of morphine ( 50 - 200 mu g ) was devoid of antinociceptive effects in WT mice , it induced dose - dependent antinociception in sigma 1 - KO mice .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "This effect was limited to the injected paw .", "entity": [], "task": "NER"}
{"text": "Enhancement of peripheral morphine antinociception was replicated in WT mice locally co - administered with sigma 1 antagonists and the opioid .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [26, 34]}], "task": "NER"}
{"text": "None of the sigma 1 antagonists tested enhanced morphine - antinociception in sigma 1 - KO mice , confirming a sigma 1 - mediated action .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "Morphine - induced side - effects ( hyperlocomotion and inhibition of gastrointestinal transit ) were unaltered in sigma 1 - KO mice .", "entity": [{"entity": "Morphine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "These results cannot be explained by a direct interaction of sigma 1 ligands with mu - opioid receptors or adaptive changes of mu - receptors in sigma 1 - KO mice , given that [ ( 3 ) H ] DAMGO binding in forebrain , spinal cord , and hind - paw skin membranes was unaltered in mutant mice , and none of the sigma 1 drugs tested bound to mu - opioid receptors .", "entity": [{"entity": "[ ( 3 ) H ] DAMGO", "entity_type": "Chemical", "pos": [176, 193]}], "task": "NER"}
{"text": "These results show that sigma 1 receptor inhibition potentiates morphine - induced mechanical analgesia but not its acute side effects , and that this enhanced analgesia can be induced at peripheral level .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "Accumulation of phenolic compounds in in vitro cultures and wild plants of Lavandula viridis L ' H e r and their antioxidant and anti - cholinesterase potential .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [16, 24]}], "task": "NER"}
{"text": "In this study , we evaluated the phenolic profile , antioxidant and anti - cholinesterase potential of different extracts from wild plants and in vitro cultures of Lavandula viridis L ' H e r .", "entity": [], "task": "NER"}
{"text": "The HPLC - DAD analysis allowed the identification and quantification of 3 - O - caffeoylquinic , 4 - O - caffeoylquinic , 5 - O - caffeoylquinic and rosmarinic acids , and luteolin and pinocembrin .", "entity": [{"entity": "3 - O - caffeoylquinic , 4 - O - caffeoylquinic , 5 - O - caffeoylquinic and rosmarinic acids", "entity_type": "Chemical", "pos": [73, 166]}, {"entity": "luteolin", "entity_type": "Chemical", "pos": [173, 181]}, {"entity": "pinocembrin", "entity_type": "Chemical", "pos": [186, 197]}], "task": "NER"}
{"text": "Water / ethanol extract from in vitro cultures contained the highest amount of the identified phenolic compounds ( 51652 . 92mg / kg ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [8, 15]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [94, 102]}], "task": "NER"}
{"text": "To investigate the antioxidant activity we used Trolox equivalent antioxidant capacity , oxygen radical absorbance capacity , Fe ( 2 + ) chelation activity and the inhibition of Fe ( 2 + ) - induced lipid peroxidation in mouse brain homogenates ( in vitro ) .", "entity": [{"entity": "Trolox", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [89, 95]}, {"entity": "Fe ( 2 + )", "entity_type": "Chemical", "pos": [126, 136]}, {"entity": "Fe ( 2 + )", "entity_type": "Chemical", "pos": [178, 188]}], "task": "NER"}
{"text": "Overall , all the extracts from both wild plants and in vitro cultures exhibited ability to scavenge free radicals , to chelate Fe ( 2 + ) and to protect against lipid peroxidation .", "entity": [{"entity": "Fe ( 2 + )", "entity_type": "Chemical", "pos": [128, 138]}], "task": "NER"}
{"text": "In addition , the extracts from L . viridis were active in inhibiting both acetylcholinesterase and butyrylcholinesterase ( Ellman ' s method ) .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that L . viridis in vitro cultures represent a promising alternative for the production of active metabolites with antioxidant and anti - cholinesterase activity .", "entity": [], "task": "NER"}
{"text": "Hypocholesterolemic effect of daily fisetin supplementation in high fat fed Sprague - Dawley rats .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [36, 43]}], "task": "NER"}
{"text": "We aimed to test whether fisetin could modulate cholesterol homeostasis in rats with diet - induced hypercholesterolemia , and further investigated the underlying mechanisms by which fisetin exerts its cholesterol lowering effect .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "fisetin", "entity_type": "Chemical", "pos": [183, 190]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [202, 213]}], "task": "NER"}
{"text": "Blood lipid profile , hepatic cholesterol content , as well as gene expressions in cholesterol metabolism were examined .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [30, 41]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "Elevated levels of total cholesterol and LDL - cholesterol , along with hepatic cholesterol content in a high fat group were found to be significantly reduced by fisetin .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [80, 91]}, {"entity": "fisetin", "entity_type": "Chemical", "pos": [162, 169]}], "task": "NER"}
{"text": "The high fat diet significantly decreased hepatic mRNA levels of LDLR , SREBP2 , HMGCR and PCSK9 in comparison to the control diet , however , fisetin did not further elicit any changes in mRNA levels of the same genes .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [143, 150]}], "task": "NER"}
{"text": "The high fat diet dramatically increased the transcript levels of CYP7A1 , which was subsequently reversed by the fisetin .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "In HepG2 cells , fisetin was found to increase the levels of a nuclear form of SREBP2 and LDLR .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [17, 24]}], "task": "NER"}
{"text": "In conclusion , fisetin supplementation displayed hypocholesterolemic effects by modulating the expression of genes associated with cholesterol and bile acid metabolism .", "entity": [{"entity": "fisetin", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [54, 65]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [148, 157]}], "task": "NER"}
{"text": "Phenolic compounds from Jacaranda caroba ( Vell . ) A .", "entity": [{"entity": "Phenolic", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "DC . : Approaches to neurodegenerative disorders .", "entity": [], "task": "NER"}
{"text": "Diseases affecting the central nervous system are spread throughout the world .", "entity": [], "task": "NER"}
{"text": "As so , more efficient and safe neuroprotective drugs are required .", "entity": [], "task": "NER"}
{"text": "The present study describes , for the first time , the phenolic composition and bioactivity of Jacaranda caroba ( Vell . ) A .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "DC , a species whose infusion is consumed as traditional medicine .", "entity": [], "task": "NER"}
{"text": "The HPLC - DAD - ESI / MS ( n ) analysis revealed the presence of four dicaffeoyl acid derivatives and nine flavonoids , comprising quercetin , kaempferol and isorhamnetin derivatives .", "entity": [{"entity": "dicaffeoyl acid", "entity_type": "Chemical", "pos": [71, 86]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [108, 118]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [132, 141]}, {"entity": "kaempferol", "entity_type": "Chemical", "pos": [144, 154]}, {"entity": "isorhamnetin", "entity_type": "Chemical", "pos": [159, 171]}], "task": "NER"}
{"text": "Twelve compounds are described for the first time in Jacaranda genus .", "entity": [], "task": "NER"}
{"text": "Although isorhamnetin - 3 - O - rhmanoside - 7 , 4 ' - di - O - glucoside and quercetin - 3 - O - ( 2 - pentosyl ) hexoside are the main metabolites in both aqueous and hydromethanolic extracts , qualitative and quantitative differences were found between them .", "entity": [{"entity": "isorhamnetin - 3 - O - rhmanoside - 7 , 4 ' - di - O - glucoside", "entity_type": "Chemical", "pos": [9, 73]}, {"entity": "quercetin - 3 - O - ( 2 - pentosyl ) hexoside", "entity_type": "Chemical", "pos": [78, 123]}], "task": "NER"}
{"text": "Aqueous extract is richer in dicaffeoyl acid derivatives .", "entity": [{"entity": "dicaffeoyl acid", "entity_type": "Chemical", "pos": [29, 44]}], "task": "NER"}
{"text": "Both extracts proved to be strong radicals ' scavengers and effective monoamine - oxidase A inhibitors , but showed weak protection against cholinesterases ' activity .", "entity": [{"entity": "monoamine", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "The results highlight the value of J . caroba as a source of health - promoting antioxidants and antidepressant compounds .", "entity": [], "task": "NER"}
{"text": "The mycotoxin T - 2 inhibits hepatic cytochrome P4503A activity in pigs .", "entity": [{"entity": "mycotoxin T - 2", "entity_type": "Chemical", "pos": [4, 19]}], "task": "NER"}
{"text": "Mycotoxins are toxic metabolites produced by fungi that readily colonize crops .", "entity": [], "task": "NER"}
{"text": "After ingestion , these mycotoxins can compromise intestinal health , and once entering the blood stream , even affect the liver and its metabolizing enzymes .", "entity": [], "task": "NER"}
{"text": "It was therefore the aim of the present study to investigate the effect of T - 2 toxin , an emerging and potent Fusarium mycotoxin , on the enzymatic activity of cytochrome P4503A ( CYP3A ) metabolizing enzymes in the liver of pigs .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "In addition , a yeast - derived feed additive that claims to bind T - 2 toxin was included in the study to evaluate its efficacy .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [66, 77]}], "task": "NER"}
{"text": "Our results demonstrated that a 14 - days intake of T - 2 toxin contaminated feed at a dose of 903 mu g / kg feed , whether or not combined with the mycotoxin binder , results in a substantial inhibition of the CYP3A activity in the liver of pigs .", "entity": [{"entity": "T - 2 toxin", "entity_type": "Chemical", "pos": [52, 63]}], "task": "NER"}
{"text": "This result may be of importance for animal health , the pharmacokinetics and the withdrawal time of drugs that are substrate of CYP3A enzymes , and consequently can be a threat for public health with respect to tissue residues of these drugs .", "entity": [], "task": "NER"}
{"text": "Metabolism Studies of Unformulated Internally [ 3H ] - labeled siRNAs in Mice .", "entity": [{"entity": "3H", "entity_type": "Chemical", "pos": [48, 50]}], "task": "NER"}
{"text": "Absorption , distribution , metabolism , and excretion properties of two unformulated model siRNAs were determined using a single internal [ ( 3 ) H ] - radiolabeling procedure , where the full - length oligonucleotides were radiolabeled by Br / ( 3 ) H - exchange .", "entity": [{"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [141, 148]}, {"entity": "Br", "entity_type": "Chemical", "pos": [241, 243]}, {"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [246, 253]}], "task": "NER"}
{"text": "Tissue distribution , excretion , and mass balance of radioactivity were investigated in male CD - 1 mice , following a single intravenous administration of the [ ( 3 ) H ] - siRNAs , at a target dose level of 5 mg / kg .", "entity": [{"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "Quantitative whole - body autoradiography ( QWBA ) and liquid scintillation counting techniques were used to determine tissue distribution .", "entity": [], "task": "NER"}
{"text": "Radiochromatogram profiles were determined in plasma , tissue extracts and urine .", "entity": [], "task": "NER"}
{"text": "Metabolites were separated by liquid chromatography and identified by radiodetection and high - resolution accurate mass spectrometry .", "entity": [], "task": "NER"}
{"text": "In general , there was little difference in the distribution of total radiolabeled components after administration of the two unformulated [ ( 3 ) H ] - siRNAs .", "entity": [{"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [141, 148]}], "task": "NER"}
{"text": "The radioactivity was rapidly and widely distributed throughout the body , and remained detectable in all tissues investigated at later time points ( 24 and 48 hours for [ ( 3 ) H ] - MRP4 and [ ( 3 ) H ] - SSB siRNA , respectively ) .", "entity": [{"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [172, 179]}, {"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [195, 202]}], "task": "NER"}
{"text": "After an initial rapid decline , concentrations of total radiolabeled components in dried blood declined at a much slower rate .", "entity": [], "task": "NER"}
{"text": "A nearly complete mass balance was obtained for the [ ( 3 ) H ] - SSB siRNA and renal excretion was the main route of elimination ( 38 % ) .", "entity": [{"entity": "( 3 ) H", "entity_type": "Chemical", "pos": [54, 61]}], "task": "NER"}
{"text": "The metabolism of the two model siRNAs was rapid and extensive .", "entity": [], "task": "NER"}
{"text": "Five minutes after administration , no parent compound could be detected in plasma .", "entity": [], "task": "NER"}
{"text": "Instead , radiolabeled nucleosides resulting from nuclease hydrolysis were observed .", "entity": [{"entity": "nucleosides", "entity_type": "Chemical", "pos": [23, 34]}], "task": "NER"}
{"text": "In the metabolism profiles obtained from various tissues only radiolabeled nucleosides were found , suggesting that siRNAs are rapidly metabolized and that the distribution pattern of total radiolabeled components can be ascribed to small molecular weight metabolites .", "entity": [{"entity": "nucleosides", "entity_type": "Chemical", "pos": [75, 86]}], "task": "NER"}
{"text": "Enhanced broadband and omnidirectional performance of Cu ( In , Ga ) Se2 solar cells with ZnO functional nanotree arrays .", "entity": [{"entity": "Cu ( In , Ga ) Se2", "entity_type": "Chemical", "pos": [54, 72]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [90, 93]}], "task": "NER"}
{"text": "An effective approach is demonstrated for enhancing photoelectric conversion of Cu ( In , Ga ) Se2 ( CIGS ) solar cells with three - dimensional ZnO nanotree arrays .", "entity": [{"entity": "Cu ( In , Ga ) Se2", "entity_type": "Chemical", "pos": [80, 98]}, {"entity": "CIGS", "entity_type": "Chemical", "pos": [101, 105]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [145, 148]}], "task": "NER"}
{"text": "Under a simulated one - sun condition , cells with ZnO nanotree arrays enhance the short - circuit current density by 10 . 62 % .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "The omnidirectional anti - reflection of CIGS solar cells with various ZnO nanostructures is also investigated .", "entity": [{"entity": "CIGS", "entity_type": "Chemical", "pos": [41, 45]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [71, 74]}], "task": "NER"}
{"text": "The solar - spectrum weighted reflectance is approximately less than 5 % for incident angles of up to 60 degrees and for the wavelengths primarily from 400 nm to 1000 nm .", "entity": [], "task": "NER"}
{"text": "This enhancement in light harvesting is attributable to the gradual refractive index profile between the ZnO nanostructures and air .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [105, 108]}], "task": "NER"}
{"text": "Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens .", "entity": [], "task": "NER"}
{"text": "RATIONALE : The nucleus accumbens ( NAc ) is a site critical for the actions of many drugs of abuse .", "entity": [], "task": "NER"}
{"text": "Psychoactive compounds , such as N - methyl - D - aspartate receptor ( NMDAR ) antagonists , modify gamma ( 40 - 90 ) and high frequency oscillations ( HFO , 130 - 180 Hz ) in local field potentials ( LFPs ) recorded in the NAc .", "entity": [{"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [33, 59]}], "task": "NER"}
{"text": "Lysergic acid diethylamide ( LSD ) and 2 , 5 - dimethoxy - 4 - iodoamphetamine ( DOI ) are serotonergic hallucinogens and activation of 5HT2A receptors likely underlies their hallucinogenic effects .", "entity": [{"entity": "Lysergic acid diethylamide", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "LSD", "entity_type": "Chemical", "pos": [29, 32]}, {"entity": "2 , 5 - dimethoxy - 4 - iodoamphetamine", "entity_type": "Chemical", "pos": [39, 78]}, {"entity": "DOI", "entity_type": "Chemical", "pos": [81, 84]}], "task": "NER"}
{"text": "Whether these compounds can also modulate LFP oscillations in the NAc is unclear .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : This study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT2A receptors mediate the effects observed .", "entity": [], "task": "NER"}
{"text": "METHODS : LFPs were recorded from the NAc of freely moving rats .", "entity": [], "task": "NER"}
{"text": "Drugs were administered intraperitoneally .", "entity": [], "task": "NER"}
{"text": "RESULTS : LSD ( 0 . 03 - 0 . 3 mg / kg ) and DOI ( 0 . 5 - 2 . 0 mg / kg ) increased the power and reduced the frequency of HFO .", "entity": [{"entity": "LSD", "entity_type": "Chemical", "pos": [10, 13]}, {"entity": "DOI", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "In contrast , the hallucinogens produced a robust reduction in the power of low ( 40 - 60 Hz ) , but not high gamma oscillations ( 70 - 90 Hz ) .", "entity": [], "task": "NER"}
{"text": "MDL 11939 ( 1 . 0 mg / kg ) , a 5HT2A receptor antagonist , fully reversed the changes induced by DOI on HFO but only partially for the low gamma band .", "entity": [{"entity": "MDL 11939", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "DOI", "entity_type": "Chemical", "pos": [98, 101]}], "task": "NER"}
{"text": "Equivalent increases in HFO power were observed after TCB - 2 ( 5HT2A receptor agonist , 0 . 1 - 1 . 5 mg / kg ) , but not CP 809101 ( 5H2C receptor agonist , 0 . 1 - 3 mg / kg ) .", "entity": [{"entity": "TCB - 2", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "CP 809101", "entity_type": "Chemical", "pos": [123, 132]}], "task": "NER"}
{"text": "Notably , hallucinogen - induced increases in HFO power were smaller than those produced by ketamine ( 25 mg / kg ) .", "entity": [{"entity": "ketamine", "entity_type": "Chemical", "pos": [92, 100]}], "task": "NER"}
{"text": "CONCLUSIONS : Serotonergic hallucinogen - induced changes in HFO and gamma are mediated , at least in part , by stimulation of 5HT2A receptors .", "entity": [], "task": "NER"}
{"text": "Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed .", "entity": [], "task": "NER"}
{"text": "Inhibition of Ebola Virus Infection : Identification of Niemann - Pick C1 as the Target by Optimization of a Chemical Probe .", "entity": [], "task": "NER"}
{"text": "A high throughput screen identified adamantane dipeptide 1 as an inhibitor of Ebola virus ( EboV ) infection .", "entity": [{"entity": "adamantane", "entity_type": "Chemical", "pos": [36, 46]}], "task": "NER"}
{"text": "Hit - to - lead optimization to determine the structure - activity relationship ( SAR ) identified the more potent EboV inhibitor 2 and a photoaffinity labeling agent 3 .", "entity": [], "task": "NER"}
{"text": "These anti - viral compounds were employed to identify the target as Niemann - Pick C1 ( NPC1 ) , a host protein that binds the EboV glycoprotein and is essential for infection .", "entity": [], "task": "NER"}
{"text": "These studies establish NPC1 as a promising target for anti - viral therapy .", "entity": [], "task": "NER"}
{"text": "The Arf GAP AGAP2 Interacts with beta Arrestin2 and Regulates beta 2 - Adrenergic Receptor Recycling and Erk Activation .", "entity": [], "task": "NER"}
{"text": "AGAP2 is a multidomain Arf GAP ( ADP ribosylation factor - directed GTPase - activating protein ) that was shown to promote the fast - recycling of transferrin receptors .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "Here , we tested the hypothesis that AGAP2 regulates trafficking of beta 2 - adrenergic receptors .", "entity": [], "task": "NER"}
{"text": "We found that AGAP2 formed a complex with beta Arrestin1 and beta Arrestin2 , proteins that are known to regulate beta 2 - adrenergic receptor signaling and trafficking .", "entity": [], "task": "NER"}
{"text": "AGAP2 colocalized with beta Arrestin2 on the plasma membrane , and knockdown of AGAP2 expression reduced plasma membrane association of beta Arrestin2 upon beta 2 - adrenergic receptor activation .", "entity": [], "task": "NER"}
{"text": "AGAP2 also colocalized with internalized beta 2 - adrenergic receptors on endosomes , and overexpression of AGAP2 slowed accumulation of beta 2 - adrenergic receptor in the perinuclear recycling endosomes .", "entity": [], "task": "NER"}
{"text": "On the contrary , knockdown of AGAP2 expression prevented recycling of beta 2 - adrenergic receptor back to the plasma membrane .", "entity": [], "task": "NER"}
{"text": "In addition , AGAP2 formed a complex with endogenous Erk and overexpression of AGAP2 potentiated Erk phosphorylation induced by beta 2 - adrenergic receptors .", "entity": [], "task": "NER"}
{"text": "Taken together , these results support the hypothesis that AGAP2 plays a role in the signaling and recycling of beta 2 - adrenergic receptors .", "entity": [], "task": "NER"}
{"text": "Identification of the first synthetic inhibitors of the type II transmembrane serine protease TMPRSS2 suitable for inhibition of influenza virus activation .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [78, 84]}], "task": "NER"}
{"text": "TMPRSS2 is a multidomain type II transmembrane serine protease that cleaves the surface glycoprotein hemagglutinin ( HA ) of influenza viruses with monobasic cleavage site , which is a prerequisite for virus fusion and propagation .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "Furthermore , it activates the fusion protein F of the human metapneumovirus and the spike protein S of the SARS coronavirus .", "entity": [], "task": "NER"}
{"text": "Increased TMPRSS2 expression was also described in several tumor entities .", "entity": [], "task": "NER"}
{"text": "Therefore , TMPRSS2 emerged as a potential target for drug design .", "entity": [], "task": "NER"}
{"text": "The catalytic domain of TMPRSS2 was expressed in E . coli and used for an inhibitor screen with previously synthesized inhibitors of various trypsin - like serine proteases .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [156, 162]}], "task": "NER"}
{"text": "Two inhibitor types were identified , which inhibit TMPRSS2 in the nanomolar range .", "entity": [], "task": "NER"}
{"text": "The first series comprises substrate analogue inhibitors containing a 4 - amidinobenzylamide moiety in P1 position , whereby some of these analogues possess inhibition constants around 20 nM .", "entity": [{"entity": "4 - amidinobenzylamide", "entity_type": "Chemical", "pos": [70, 92]}], "task": "NER"}
{"text": "An improved potency was found for second type derived from sulfonylated 3 - amindinophenylalanylamide derivates .", "entity": [{"entity": "sulfonylated 3 - amindinophenylalanylamide", "entity_type": "Chemical", "pos": [59, 101]}], "task": "NER"}
{"text": "The most potent derivative of this series inhibits TMPRSS2 with a Ki value of 0 . 9 nM and showed an efficient blockage of influenza virus propagation in human airway epithelial cells .", "entity": [], "task": "NER"}
{"text": "Based on the inhibitor studies a series of new fluorogenic substrates containing a d - arginine residue in P3 position was synthesized , some of them were efficiently cleaved by TMPRSS2 .", "entity": [{"entity": "d - arginine", "entity_type": "Chemical", "pos": [83, 95]}], "task": "NER"}
{"text": "Broken Symmetry Quantum Hall States in Dual - Gated ABA Trilayer Graphene .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "ABA - stacked trilayer graphene is a unique 2D electron system with mirror reflection symmetry and unconventional quantum Hall effect .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "We present low - temperature transport measurements on dual - gated suspended trilayer graphene in the quantum Hall ( QH ) regime .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "We observe QH plateaus at filling factors nu = - 8 , - 2 , 2 , 6 , and 10 , which is in agreement with the full - parameter tight binding calculations .", "entity": [], "task": "NER"}
{"text": "In high magnetic fields , odd - integer plateaus are also resolved , indicating almost complete lifting of the 12 - fold degeneracy of the lowest Landau level ( LL ) .", "entity": [], "task": "NER"}
{"text": "Under an out - of - plane electric field E _|_ , we observe degeneracy breaking and transitions between QH plateaus .", "entity": [], "task": "NER"}
{"text": "Interestingly , depending on its direction , E _|_ selectively breaks the LL degeneracies in the electron - doped or hole - doped regimes .", "entity": [], "task": "NER"}
{"text": "Our results underscore the rich interaction - induced phenomena in trilayer graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "Coarse - grained model for predicting RNA folding thermodynamics .", "entity": [], "task": "NER"}
{"text": "We present a thermodynamically robust coarse - grained model to simulate folding of RNA in monovalent salt solutions .", "entity": [], "task": "NER"}
{"text": "The model includes stacking , hydrogen bond , and electrostatic interactions as fundamental components in describing the stability of RNA structures .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "The stacking interactions are parametrized using a set of nucleotide - specific parameters , which were calibrated against the thermodynamic measurements for single - base stacks and base - pair stacks .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "All hydrogen bonds are assumed to have the same strength , regardless of their context in the RNA structure .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "The ionic buffer is modeled implicitly , using the concept of counterion condensation and the Debye - H u ckel theory .", "entity": [], "task": "NER"}
{"text": "The three adjustable parameters in the model were determined by fitting the experimental data for two RNA hairpins and a pseudoknot .", "entity": [], "task": "NER"}
{"text": "A single set of parameters provides good agreement with thermodynamic data for the three RNA molecules over a wide range of temperatures and salt concentrations .", "entity": [], "task": "NER"}
{"text": "In the process of calibrating the model , we establish the extent of counterion condensation onto the single - stranded RNA backbone .", "entity": [], "task": "NER"}
{"text": "The reduced backbone charge is independent of the ionic strength and is 60 % of the RNA bare charge at 37 degrees C .", "entity": [], "task": "NER"}
{"text": "Our model can be used to predict the folding thermodynamics for any RNA molecule in the presence of monovalent ions .", "entity": [], "task": "NER"}
{"text": "Supramolecular Structure of TTBC J - Aggregates in Solution and on Surface .", "entity": [{"entity": "TTBC", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "The aggregation behavior of cationic 5 , 5 ' , 6 , 6 ' - tetrachloro - 1 , 1 ' , 3 , 3 ' - tetraethylbenzimidacarbocyanine with chloride ( TTBC - Cl ) or iodide counterions ( TTBC - I ) in aqueous solution is investigated by absorption , linear dichroism , and fluorescence spectroscopies , as well as cryogenic transmission electron microscopy ( cryo - TEM ) and atomic force microscopy ( AFM ) .", "entity": [{"entity": "5 , 5 ' , 6 , 6 ' - tetrachloro - 1 , 1 ' , 3 , 3 ' - tetraethylbenzimidacarbocyanine", "entity_type": "Chemical", "pos": [37, 122]}, {"entity": "chloride", "entity_type": "Chemical", "pos": [128, 136]}, {"entity": "TTBC - Cl", "entity_type": "Chemical", "pos": [139, 148]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [154, 160]}, {"entity": "TTBC - I", "entity_type": "Chemical", "pos": [175, 183]}], "task": "NER"}
{"text": "TTBC - Cl is found to form J - aggregates with a classical Davydov - split absorption band ( type I spectrum ) even under different preparation conditions .", "entity": [{"entity": "TTBC - Cl", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "These aggregates remain stable for months .", "entity": [], "task": "NER"}
{"text": "Unlike the chloride salt , the iodide salt TTBC - I forms two different types of J - aggregates depending on the pH of the aqueous solution .", "entity": [{"entity": "chloride", "entity_type": "Chemical", "pos": [11, 19]}, {"entity": "iodide", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "TTBC - I", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "The TTBC - I aggregates prepared in pure water ( pH = 6 ) are characterized by a single redshifted absorption band ( type III spectrum ) , whereas those prepared in alkaline solution at pH = 13 show a typical Davydov - split ( type I ) absorption band .", "entity": [{"entity": "TTBC - I", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "Despite differences in counterions , preparation method , stability , and spectroscopic behavior , cryo - TEM reveals an identical tubular architecture for all these J - aggregates .", "entity": [], "task": "NER"}
{"text": "Among the new structure models discussed here is a cylindrical brickwork layer of dye molecules for single - banded J - aggregates ( type III ) .", "entity": [], "task": "NER"}
{"text": "For Davydov - split aggregates ( type I ) , a molecular herringbone - like pattern is proposed instead .", "entity": [], "task": "NER"}
{"text": "Moreover , absorption spectra have revealed an additional single redshifted absorption band ( type II spectrum ) that is assigned to a surface aggregate and is induced by a specific interaction of the dye cation with the negatively charged cuvette wall .", "entity": [], "task": "NER"}
{"text": "AFM measurements of analogous preparations on negatively charged mica surfaces have supported this interpretation and revealed the formation of monolayered sheet structures .", "entity": [], "task": "NER"}
{"text": "Synthesis of indolyl - 3 - acetonitrile derivatives and their inhibitory effects on nitric oxide and PGE2 productions in LPS - induced RAW 264 . 7 cells .", "entity": [{"entity": "indolyl - 3 - acetonitrile", "entity_type": "Chemical", "pos": [13, 39]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [84, 96]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [101, 105]}], "task": "NER"}
{"text": "Arvelexin is one of major constituents of Brassica rapa that exerts anti - inflammatory activities .", "entity": [{"entity": "Arvelexin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Several indolyl - 3 - acetonitrile derivatives were synthesized as arvelexin analogs and evaluated for their abilities to inhibit NO and PGE2 productions in LPS - induced RAW 264 . 7 cells .", "entity": [{"entity": "indolyl - 3 - acetonitrile", "entity_type": "Chemical", "pos": [8, 34]}, {"entity": "arvelexin", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "NO", "entity_type": "Chemical", "pos": [130, 132]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [137, 141]}], "task": "NER"}
{"text": "Of the indolyl - 3 - acetonitriles synthesized , compound 2k , which possesses a hydroxyl group at C - 7 position of the indole ring and an N - methyl substituent , more potently inhibited NO and PGE2 productions and was less cytotoxic than arvelexin on macrophage cells .", "entity": [{"entity": "indolyl - 3 - acetonitriles", "entity_type": "Chemical", "pos": [7, 34]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [81, 89]}, {"entity": "indole", "entity_type": "Chemical", "pos": [121, 127]}, {"entity": "N - methyl", "entity_type": "Chemical", "pos": [140, 150]}, {"entity": "NO", "entity_type": "Chemical", "pos": [189, 191]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [196, 200]}, {"entity": "arvelexin", "entity_type": "Chemical", "pos": [241, 250]}], "task": "NER"}
{"text": "Discovery of a synthetic Aminopeptidase N inhibitor LB - 4b as a potential anticancer agent .", "entity": [{"entity": "LB - 4b", "entity_type": "Chemical", "pos": [52, 59]}], "task": "NER"}
{"text": "APN inhibitors have been considered as potential anticancer agents for years .", "entity": [], "task": "NER"}
{"text": "LB - 4b is the first synthetic APN inhibitor to be evaluated for both of its anti - invasion and anti - angiogenesis effects .", "entity": [{"entity": "LB - 4b", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "As a potent synthetic APN inhibitor ( IC50 = 850nM , versus bestatin of 8 . 1 mu M ) , LB - 4b was determined to have more significant block effects to cancer cell invasion and angiogenesis than bestatin .", "entity": [{"entity": "bestatin", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "LB - 4b", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "bestatin", "entity_type": "Chemical", "pos": [195, 203]}], "task": "NER"}
{"text": "Besides , it is able to be easily synthesized with a high total yield , while the reported synthetic methods of bestatin are much more complex .", "entity": [{"entity": "bestatin", "entity_type": "Chemical", "pos": [112, 120]}], "task": "NER"}
{"text": "Atropa acuminata Royle Ex Lindl . blunts production of pro - inflammatory mediators eicosanoids . , leukotrienes , cytokines in vitro and in vivo models of acute inflammatory responses .", "entity": [{"entity": "eicosanoids", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "leukotrienes", "entity_type": "Chemical", "pos": [100, 112]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Atropa acuminata Royle Ex Lindl . has been widely used in folk medicine for several inflammatory disorders such as arthritis , asthma , conjunctivitis , encephalitis , pancreatitis , peritonitis , acute infections and neuroinflammatory disorders .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : Our aim was to evaluate Atropa acuminata for its anti - inflammatory properties and to delineate its possible mechanism of action on the modulation of the inflammatory mediators .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : We investigated the inhibitory action of ethanolic extract of Atropa acuminata ( AAEE ) on production of NO , TNF - alpha and IL - 1 beta in lipopolysaccharide ( LPS ) - stimulated RAW264 . 7 cells and also assayed it for COX 1 / 2 and 5 - LOX inhibitory activities .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [129, 131]}], "task": "NER"}
{"text": "Next AAEE was tested in acute inflammatory animal models . , carragenean induced rat paw edema , carragenean induce pleurisy in rats and vascular permeability in mice and the effects on NO , PGE2 and LTB4 production in the pleural fluid and paw exudates were evaluated .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [186, 188]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [191, 195]}], "task": "NER"}
{"text": "In addition the effects on leukocyte migration and exudation and vascular permeability were also observed .", "entity": [], "task": "NER"}
{"text": "RESULTS : Our findings summarized novel anti - inflammatory mechanisms for Atropa acuminata based on dual in vitro cyclooxygenase 1 / 2 / and 5 - Lipoxygenase inhibitory activities and also significant downregulation of nitric oxide ( NO ) and pro - inflammatory cytokin ( TNF - alpha and Il - 1 beta ) release in LPS - stimulated RAW 246 . 7 macrophage cell line .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [220, 232]}, {"entity": "NO", "entity_type": "Chemical", "pos": [235, 237]}], "task": "NER"}
{"text": "In acute inflammatory models in vivo ( carragenean induced edema , carragenean induced pleurisy in rats and vascular permeability in mice ) , AAEE exhibited an extensive diverse mechanism for anti - inflammatory properties .", "entity": [], "task": "NER"}
{"text": "This was indicated on the basis of dose dependent suppression of multi targeted inflammatory mediators . , NO , TNF - alpha and IL - 1 beta , eicosanoids . , PGE2 and leukotrienes . , LTB4 along with significantly decreased leucocyte migration , exudation and decreased vascular permeability .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [107, 109]}, {"entity": "eicosanoids", "entity_type": "Chemical", "pos": [142, 153]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [158, 162]}, {"entity": "leukotrienes", "entity_type": "Chemical", "pos": [167, 179]}], "task": "NER"}
{"text": "These effects were more potent and prolonged than traditional NSAIDS , thereby indicating fewer side effects .", "entity": [], "task": "NER"}
{"text": "AAEE was found to be safe for long term administration , as confirmed by the results of acute toxicity studies and MTT assay .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "The complex mode of action of the herbs was attributed possibly due to the high polyphenolic , flavanol and flavonoid content present in the extracts as observed by means of quantitative screening for phytochemicals .", "entity": [{"entity": "polyphenolic", "entity_type": "Chemical", "pos": [80, 92]}, {"entity": "flavanol", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [108, 117]}], "task": "NER"}
{"text": "CONCLUSION : Our study provides scientific evidence to support the traditional anti - inflammatory uses of Atropa acuminata and is probably due to inhibitory effects on multiple inflammatory mediators which indicates a promising potential for the development of a strong anti - inflammatory agent from this plant .", "entity": [], "task": "NER"}
{"text": "Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse .", "entity": [{"entity": "Morphine", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "Ethanol", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "The chronic use of opioids in humans , accompanied by the development of tolerance , is a dangerous phenomenon in its own right .", "entity": [], "task": "NER"}
{"text": "However chronic opioid use is often made more dangerous by the co - consumption of other substances .", "entity": [], "task": "NER"}
{"text": "It has been observed that the blood level of opioids in postmortem analyses of addicts , who consumed ethanol along with the opioid , was much less than that observed in individuals that died from opioids alone .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [26, 33]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [88, 95]}], "task": "NER"}
{"text": "In the present study , we report that ethanol significantly and dose - dependently reduced the antinociceptive tolerance produced by morphine and the cross tolerance between DAMGO and morphine in the mouse tail - flick test .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [133, 141]}, {"entity": "DAMGO", "entity_type": "Chemical", "pos": [174, 179]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [184, 192]}], "task": "NER"}
{"text": "The reversal of morphine tolerance was partially blocked by both the GABAA receptor blocker bicuculline and by the GABAB receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "bicuculline", "entity_type": "Chemical", "pos": [92, 103]}, {"entity": "phaclofen", "entity_type": "Chemical", "pos": [138, 147]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [225, 232]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [236, 244]}], "task": "NER"}
{"text": "Diazepam , like ethanol , decreased morphine tolerance .", "entity": [{"entity": "Diazepam", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "However , this inhibition was reversed by the GABAA antagonist bicuculline but not by the GABAB antagonist phaclofen .", "entity": [{"entity": "bicuculline", "entity_type": "Chemical", "pos": [63, 74]}, {"entity": "phaclofen", "entity_type": "Chemical", "pos": [107, 116]}], "task": "NER"}
{"text": "These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [81, 88]}], "task": "NER"}
{"text": "Physiological costs and carry - over effects of avian interspecific brood parasitism influence reproductive tradeoffs .", "entity": [], "task": "NER"}
{"text": "Although models of co - evolution between brood parasites and their hosts primarily focus upon the cost to hosts in the current reproductive bout , the impact of brood parasitism may carry over to future reproductive attempts by altering resource allocation .", "entity": [], "task": "NER"}
{"text": "Glucocorticoid stress hormones help mediate resource allocation to reproduction , yet they have rarely been examined in brood parasitic systems .", "entity": [], "task": "NER"}
{"text": "Here we determined if shifts in parental care and corticosterone had carry - over effects on future reproductive effort in the rufous - and - white wren ( Thryophilus rufalbus ) , a host of the Central American striped cuckoo ( Tapera naevia ) .", "entity": [{"entity": "corticosterone", "entity_type": "Chemical", "pos": [50, 64]}], "task": "NER"}
{"text": "We found that parasitized parents had significantly higher stress - induced , but not baseline , corticosterone than natural parents during the fledgling stage , which was associated with changes in parental care .", "entity": [{"entity": "corticosterone", "entity_type": "Chemical", "pos": [97, 111]}], "task": "NER"}
{"text": "The high investment in current reproduction while parasitized may be due to the value of fledged chicks in tropical systems .", "entity": [], "task": "NER"}
{"text": "This maladaptive response by parasitized parents was associated with delayed re - nesting and a reduced likelihood of nesting in the subsequent breeding season .", "entity": [], "task": "NER"}
{"text": "Although a reduction in future reproductive effort can result from a combination of factors , this work suggests that fitness costs of brood parasitism are mediated by changes in corticosterone and parental care behavior that carry over into subsequent breeding seasons .", "entity": [{"entity": "corticosterone", "entity_type": "Chemical", "pos": [179, 193]}], "task": "NER"}
{"text": "The short course in toxinology : Training the trainers .", "entity": [], "task": "NER"}
{"text": "Clinical toxinology is the medical discipline dealing with the diagnosis , treatment and prevention of toxin diseases caused by exposure to venomous animals and poisonous animals , plants and mushrooms .", "entity": [], "task": "NER"}
{"text": "Currently there is no national or international organisation accrediting or training doctors in this discipline .", "entity": [], "task": "NER"}
{"text": "A few courses covering some aspects of clinical toxinology exist , either with limited curricula , or with only a minor clinical focus , or with a very regional , non - global focus .", "entity": [], "task": "NER"}
{"text": "The only comprehensive clinical toxinology course is the one provided in Adelaide , Australia , running regularly since 1997 .", "entity": [], "task": "NER"}
{"text": "Hundreds of doctors from many nations have attended the course since 1997 .", "entity": [], "task": "NER"}
{"text": "This course covers venomous animals , poisonous animals , plants and mushrooms , from a full global perspective , with an international faculty and an exit exam .", "entity": [], "task": "NER"}
{"text": "Though lasting only one week , extensive pre - reading material is mandated .", "entity": [], "task": "NER"}
{"text": "The current Course Handbook is about 500 pages .", "entity": [], "task": "NER"}
{"text": "Emphasis is on clinically relevant information and is focused on the needs of doctors treating cases .", "entity": [], "task": "NER"}
{"text": "While it is expected that attendees will have , or acquire , direct experience managing cases of toxin disease and will use the knowledge and skills gained in the course in direct patient care , they may also act as resource people in their home region / nation to promote increased skills in clinical toxinology amongst the wider medical workforce .", "entity": [], "task": "NER"}
{"text": "This course may form the nucleus from which IST can develop a global accredited training scheme in clinical toxinology .", "entity": [], "task": "NER"}
{"text": "Such a scheme will require input from diverse global regions and will be far more comprehensive and over a much longer time than the current Short Course , though likely will incorporate the Short Course in some way , or a derivative of it .", "entity": [], "task": "NER"}
{"text": "Two novel saponins of 20 , 26 - epoxy derivatives of pseudojujubogenin from the seeds of Hovenia trichocarpa .", "entity": [{"entity": "saponins", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "20 , 26 - epoxy", "entity_type": "Chemical", "pos": [22, 37]}, {"entity": "pseudojujubogenin", "entity_type": "Chemical", "pos": [53, 70]}], "task": "NER"}
{"text": "Two new saponins of 20 , 26 - epoxy derivatives of pseudojujubogenin , hoduloside XI ( 1 ) and hoduloside XII ( 2 ) were isolated from the seeds of Hovenia trichocarpa .", "entity": [{"entity": "saponins", "entity_type": "Chemical", "pos": [8, 16]}, {"entity": "20 , 26 - epoxy", "entity_type": "Chemical", "pos": [20, 35]}, {"entity": "pseudojujubogenin", "entity_type": "Chemical", "pos": [51, 68]}, {"entity": "hoduloside XI", "entity_type": "Chemical", "pos": [71, 84]}, {"entity": "hoduloside XII", "entity_type": "Chemical", "pos": [95, 109]}], "task": "NER"}
{"text": "The structures of the new compounds were established by extensive NMR experiments and chemical methods .", "entity": [], "task": "NER"}
{"text": "Hoduloside XI was confirmed to be 3 - O - { beta - d - glucopyranosyl ( 1 --> 3 ) - [ beta - d - xylopyranosyl ( 1 --> 2 ) ] - alpha - l - arabinopyranosyl } - 20 , 26 - epoxypseudojujubogenin .", "entity": [{"entity": "Hoduloside XI", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "3 - O - { beta - d - glucopyranosyl ( 1 --> 3 ) - [ beta - d - xylopyranosyl ( 1 --> 2 ) ] - alpha - l - arabinopyranosyl } - 20 , 26 - epoxypseudojujubogenin", "entity_type": "Chemical", "pos": [34, 192]}], "task": "NER"}
{"text": "Hoduloside XII was identified as 3 - O - { beta - d - xylopyranose ( 1 --> 2 ) glucopyranosyl ( 1 --> 3 ) [ rhamnopyranose ( 1 --> 2 ) ] beta - d - glucopyranosyl } - 20 , 26 - epoxypseudojujubogenin .", "entity": [{"entity": "Hoduloside XII", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "3 - O - { beta - d - xylopyranose ( 1 --> 2 ) glucopyranosyl ( 1 --> 3 ) [ rhamnopyranose ( 1 --> 2 ) ] beta - d - glucopyranosyl } - 20 , 26 - epoxypseudojujubogenin", "entity_type": "Chemical", "pos": [33, 199]}], "task": "NER"}
{"text": "The in vitro cytotoxic activity of compounds 1 and 2 was assayed .", "entity": [], "task": "NER"}
{"text": "They displayed inhibitive activities against human cancer cell lines HL60 and K562 .", "entity": [], "task": "NER"}
{"text": "Antinociceptive effect and gastroprotective mechanisms of 3 , 5 - diprenyl - 4 - hydroxyacetophenone from Ageratina pichinchensis .", "entity": [{"entity": "3 , 5 - diprenyl - 4 - hydroxyacetophenone", "entity_type": "Chemical", "pos": [58, 100]}], "task": "NER"}
{"text": "The present study aimed to evaluate the antinociceptive activity ( in inflammatory and neuropathic pain models ) and gastroprotective effect of the 3 , 5 - diprenyl - 4 - hydroxyacetophenone ( HYDP ) , isolated from Ageratina pichinchensis .", "entity": [{"entity": "3 , 5 - diprenyl - 4 - hydroxyacetophenone", "entity_type": "Chemical", "pos": [148, 190]}, {"entity": "HYDP", "entity_type": "Chemical", "pos": [193, 197]}], "task": "NER"}
{"text": "The gastroprotective activity of this plant was previously reported by our workgroup , finding encesanescin to be one active compound .", "entity": [{"entity": "encesanescin", "entity_type": "Chemical", "pos": [95, 107]}], "task": "NER"}
{"text": "The present results show that HYDP reduced nociception in a dose - dependent manner in carrageenan and L5 / L6 spinal nerve ligation , with efficacies of 72 . 6 and 57 . 1 % , respectively , at doses of 100 and 562mg / kg .", "entity": [{"entity": "HYDP", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "HYDP also showed gastroprotective activity in the model of ethanol - induced gastric lesion , with a 75 . 59 % maximum inhibition of ulcers at a dose of 100mg / kg .", "entity": [{"entity": "HYDP", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "This gastroprotective effect was attenuated by N ( G ) - nitro - l - arginine methyl ester , indomethacin and N - ethylmaleimide , indicating that NO , prostaglandins and sulfhydryl groups are involved in the mechanisms of action .", "entity": [{"entity": "N ( G ) - nitro - l - arginine methyl ester", "entity_type": "Chemical", "pos": [47, 90]}, {"entity": "indomethacin", "entity_type": "Chemical", "pos": [93, 105]}, {"entity": "N - ethylmaleimide", "entity_type": "Chemical", "pos": [110, 128]}, {"entity": "NO", "entity_type": "Chemical", "pos": [147, 149]}, {"entity": "prostaglandins", "entity_type": "Chemical", "pos": [152, 166]}, {"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [171, 181]}], "task": "NER"}
{"text": "This is the first evidence , to our knowledge , of the antinociceptive and gastroprotective activities of HYDP .", "entity": [{"entity": "HYDP", "entity_type": "Chemical", "pos": [106, 110]}], "task": "NER"}
{"text": "The effect of sodium selenite on lead induced cognitive dysfunction .", "entity": [{"entity": "sodium selenite", "entity_type": "Chemical", "pos": [14, 29]}], "task": "NER"}
{"text": "The effect of lead ( Pb ) on spatial memory and hippocampal long - term potentiation ( LTP ) as a key risk factor has been widely recognized and the oxidative damage has been proposed as a possible mechanism of lead neurotoxicity .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [21, 23]}], "task": "NER"}
{"text": "Selenium ( Se ) is a nutritionally essential trace element with known antioxidant potential .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Se", "entity_type": "Chemical", "pos": [11, 13]}], "task": "NER"}
{"text": "In this study we investigated the effect and the underlying mechanisms of Se supplementary on Pb induced cognition and synaptic plasticity impairment .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [74, 76]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [94, 96]}], "task": "NER"}
{"text": "Lactating Sprague - Dawley rats ( SD rats ) were randomly divided to four groups : 0ppm lead acetate ( Pb ) ; 0ppm Pb and 0 . 2ppm sodium selenite ( Se ) ; 100ppm Pb ; 100ppm Pb and 0 . 2ppm Se .", "entity": [{"entity": "lead acetate", "entity_type": "Chemical", "pos": [88, 100]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [103, 105]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [115, 117]}, {"entity": "sodium selenite", "entity_type": "Chemical", "pos": [131, 146]}, {"entity": "Se", "entity_type": "Chemical", "pos": [149, 151]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [163, 165]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [175, 177]}, {"entity": "Se", "entity_type": "Chemical", "pos": [191, 193]}], "task": "NER"}
{"text": "Lactating rats were treated with or without Pb and / or Se throughout lactation until weaning .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [44, 46]}, {"entity": "Se", "entity_type": "Chemical", "pos": [56, 58]}], "task": "NER"}
{"text": "The levels of hippocampal LTP , the spatial memory , the apoptosis of hippocampal neurons , the levels of lactate dehydrogenase ( LDH ) release , and the serum level of superoxide dismutase ( SOD ) and malondialdehyde ( MDA ) were assayed .", "entity": [{"entity": "lactate", "entity_type": "Chemical", "pos": [106, 113]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [169, 179]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [202, 217]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [220, 223]}], "task": "NER"}
{"text": "It had been observed that in Pb group the spatial memory , the induce level of LTP , the serum SOD level decreased , the LDH release level , the neurons apoptosis level , the serum MDA level increased , while in the Se supplements groups , the spatial memory , the induce level of LTP increased significantly .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [181, 184]}, {"entity": "Se", "entity_type": "Chemical", "pos": [216, 218]}], "task": "NER"}
{"text": "Compared with the Pb group , Se supplements shown down regulated the level of LDH , the neurons apoptosis and the serum MDA , and up regulated the level of serum SOD .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "Se", "entity_type": "Chemical", "pos": [29, 31]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [120, 123]}], "task": "NER"}
{"text": "We could draw the conclusion that Se supplements could alleviate toxic effect of lead on hippocampal LTP and spatial memory .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [34, 36]}], "task": "NER"}
{"text": "The treated with selenium around 0 . 2ppm may protect against spatial memory dysfunction induced by lead exposure .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "A critical examination of best dose analysis for determining cognitive - enhancing potential of drugs : studies with rhesus monkeys and computer simulations .", "entity": [], "task": "NER"}
{"text": "RATIONALE : Best dose analysis involves identifying the dose associated with the greatest improvement in performance for each subject and comparing performances associated with these individually determined best doses to control performances .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The current experiments were conducted to examine whether significant best dose effects might result from the selective analysis of data rather than an actual drug effect .", "entity": [], "task": "NER"}
{"text": "METHODS : Experiment 1 examined the effects of nicotine and methylphenidate on delayed matching - to - sample ( DMTS ) and self - ordered spatial search ( SOSS ) performances in rhesus monkeys ( DMTS : n = 7 ; SOSS : n = 6 ) to determine the validity and reliability of best dose effects .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [47, 55]}, {"entity": "methylphenidate", "entity_type": "Chemical", "pos": [60, 75]}], "task": "NER"}
{"text": "Experiment 2 used Monte Carlo computer simulations to estimate the likelihood of obtaining a significant outcome when the best dose method was applied to randomly generated data sets for which no difference existed .", "entity": [], "task": "NER"}
{"text": "RESULTS : Significant effects were obtained when the best dose analysis was applied to performances from nondrug sessions , and best dose performances were not significantly different from the best nondrug performances .", "entity": [], "task": "NER"}
{"text": "The doses identified as best doses from two nicotine dose - response curve determinations were unrelated , and the improvement associated with the best dose observed during the first dose - response curve determination was not reliable when the dose was administered repeatedly .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "Finally , there was a high likelihood of obtaining a statistically significant difference when no real difference existed .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Best dose analysis for the identification of potential therapeutic agents should be replaced by single - subject designs .", "entity": [], "task": "NER"}
{"text": "Exposure of Bacillus subtilis to mercury induces accumulation of shorter tRNA Cys species .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [33, 40]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "RNA processing is an essential pathway in the regulation of genetic expression in the cell .", "entity": [], "task": "NER"}
{"text": "In this work , Bacillus subtilis was used to understand the effects of mercury on the mechanism of tRNA metabolism .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "The CVAAS ( cold vapor atomic absorption spectroscopy ) method revealed that from the addition of HgCl2 ( 0 . 75 mu g ml ( - 1 ) ) during the bacterial exponential phase , ca .", "entity": [{"entity": "HgCl2", "entity_type": "Chemical", "pos": [98, 103]}], "task": "NER"}
{"text": "48 % of the added mercury was taken up by the cells .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [18, 25]}], "task": "NER"}
{"text": "This led to an immediate reduction in the rate of cell division .", "entity": [], "task": "NER"}
{"text": "During this response , we observed accumulation of species shorter than mature tRNA ( Cys ) over a 10 h period .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "We did not observe this accumulation for another five tRNAs analyzed .", "entity": [], "task": "NER"}
{"text": "tRNA processing is largely dependent on RNase R and PNPase in B . subtilis .", "entity": [], "task": "NER"}
{"text": "Thus , when the exonuclease PNPase was absent , we found that the shorter tRNA ( Cys ) species increased and mature tRNA ( Cys ) decreased after mercury addition , but this proportion changed during the time analyzed .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "Cys", "entity_type": "Chemical", "pos": [123, 126]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [145, 152]}], "task": "NER"}
{"text": "However , in the absence of RNase R and PNPase the accumulation of the shorter tRNA ( Cys ) was more pronounced and the mature form was not recovered .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "In the single rnr mutant strain the shorter tRNA ( Cys ) was not observed .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "All together , we provide in vivo evidence that PNPase and RNase R are indispensable in controlling tRNA ( Cys ) quality in the presence of mercury .", "entity": [{"entity": "Cys", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [140, 147]}], "task": "NER"}
{"text": "Insights into the adsorption and energy transfer of Ag clusters on the AgCl ( 100 ) surface .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [71, 75]}], "task": "NER"}
{"text": "It is fundamental to uncover the real adsorption properties of Ag clusters on an AgCl surface and the energy transfer mechanisms at the interface to understand the highly active photocatalytic performance and the stability of the plasmonic photocatalyst Ag @ AgCl .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [63, 65]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [81, 85]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [254, 256]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [259, 263]}], "task": "NER"}
{"text": "Based on density functional theory calculations we provide valuable insights into the binding nature of Ag clusters on AgCl surface , where the binding between Ag atoms in the cluster and on the surface plays a decisive role in determining the most stable adsorption configurations .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [104, 106]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [119, 123]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [160, 162]}], "task": "NER"}
{"text": "Our results demonstrate that there is energy transfer from the plasmonic metals to substrate .", "entity": [], "task": "NER"}
{"text": "The hot holes excited by the decay of surface plasmon resonance on the metals can diffuse into the Cl ions in the outermost two layers of the surface producing highly oxidative Cl atoms .", "entity": [{"entity": "Cl", "entity_type": "Chemical", "pos": [99, 101]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [177, 179]}], "task": "NER"}
{"text": "The dipole - dipole interaction between the plasmonic metal clusters and substrate Cl ions can also generate electron - hole pairs in the surface layers .", "entity": [{"entity": "Cl", "entity_type": "Chemical", "pos": [83, 85]}], "task": "NER"}
{"text": "It is deduced that the positively charged nature of adsorbed clusters acting as electron trapping centers and reduction sites plays a crucial role in keeping the stability of the Ag @ AgCl system during the photocatalytic process .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [179, 181]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [184, 188]}], "task": "NER"}
{"text": "Finally , the validity of the cluster adsorption model for energy transfer is verified with respect to the nucleation and aggregation process of Ag atoms on the AgCl surface and a detailed description of the formation and evolution of Ag nanoparticles on an AgCl surface is provided .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [145, 147]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [161, 165]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [235, 237]}, {"entity": "AgCl", "entity_type": "Chemical", "pos": [258, 262]}], "task": "NER"}
{"text": "The present study may be helpful for understanding and designing this novel plasmonic photocatalyst and can be useful for investigating other relevant photocatalysts as well .", "entity": [], "task": "NER"}
{"text": "Diagnostic performance of ( 99m ) Tc - MIBI scan in predicting the malignancy of thyroid nodules : a meta - analysis .", "entity": [{"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [26, 43]}], "task": "NER"}
{"text": "Several studies have investigated the diagnostic performance of ( 99m ) Tc - MIBI scan in the evaluation of thyroid nodules suspicious for malignancy with conflicting results .", "entity": [{"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [64, 81]}], "task": "NER"}
{"text": "The aim of our study is to meta - analyze published data on this topic .", "entity": [], "task": "NER"}
{"text": "A comprehensive literature search of studies published through December 2012 regarding the diagnostic performance of ( 99m ) Tc - MIBI scan in the evaluation of thyroid nodules suspicious for malignancy was carried out .", "entity": [{"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [117, 134]}], "task": "NER"}
{"text": "Pooled sensitivity and specificity of ( 99m ) Tc - MIBI scan on a per lesion - based analysis and the area under the ROC curve were calculated .", "entity": [{"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [38, 55]}], "task": "NER"}
{"text": "Pathological reports of thyroid nodules were considered as reference standard .", "entity": [], "task": "NER"}
{"text": "Twenty - one studies were included in the meta - analysis .", "entity": [], "task": "NER"}
{"text": "Pooled sensitivity and specificity of ( 99m ) Tc - MIBI scan in detecting malignant thyroid nodules were 85 . 1 % [ 95 % confidence interval ( 95 % CI ) : 81 . 1 - 88 . 5 % ] and 45 . 7 % ( 95 % CI : 42 . 7 - 48 . 7 % ) , respectively , on a per lesion - based analysis , irrespective of eventual results of previous technetium pertechnetate ( ( 99m ) TcO4 ) or iodine - 123 ( ( 123 ) I ) scan .", "entity": [{"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [38, 55]}, {"entity": "technetium pertechnetate", "entity_type": "Chemical", "pos": [317, 341]}, {"entity": "( 99m ) TcO4", "entity_type": "Chemical", "pos": [344, 356]}, {"entity": "iodine - 123", "entity_type": "Chemical", "pos": [362, 374]}, {"entity": "( 123 ) I", "entity_type": "Chemical", "pos": [377, 386]}], "task": "NER"}
{"text": "The area under the ROC curve was 0 . 78 .", "entity": [], "task": "NER"}
{"text": "A sub - analysis restricted to data on hypofunctioning nodules on ( 99m ) TcO4 or ( 123 ) I scans was performed : pooled sensitivity and specificity of ( 99m ) Tc - MIBI scan in these nodules were 82 . 1 % ( 95 % CI : 77 . 2 - 86 . 3 % ) and 62 . 8 % ( 95 % CI : 58 . 9 - 66 . 7 % ) , respectively , on a per lesion - based analysis .", "entity": [{"entity": "( 99m ) TcO4", "entity_type": "Chemical", "pos": [66, 78]}, {"entity": "( 123 ) I", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [152, 169]}], "task": "NER"}
{"text": "The area under the ROC curve was 0 . 81 .", "entity": [], "task": "NER"}
{"text": "( 99m ) Tc - MIBI scan is a sensitive diagnostic tool in predicting the malignancy of thyroid nodules .", "entity": [{"entity": "( 99m ) Tc - MIBI", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Therefore , this imaging method could be helpful in patients with thyroid nodules in which malignancy is suspected on the basis of conventional diagnostic techniques .", "entity": [], "task": "NER"}
{"text": "Higher specificity can be reached when hypofunctioning thyroid nodules are considered .", "entity": [], "task": "NER"}
{"text": "Synthesis , antimicrobial evaluation and molecular modelling of novel sulfonamides carrying a biologically active quinazoline nucleus .", "entity": [{"entity": "sulfonamides", "entity_type": "Chemical", "pos": [70, 82]}, {"entity": "quinazoline", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "A novel series of quinazolines 5 - 10 , triazoloquinazolines 11 - 17 and triazinoquinazoline 19 bearing a biologically active sulfonamide moiety were synthesized , utilizing methyl 2 - isothiocyanato benzoate 2 .", "entity": [{"entity": "quinazolines", "entity_type": "Chemical", "pos": [18, 30]}, {"entity": "triazoloquinazolines", "entity_type": "Chemical", "pos": [40, 60]}, {"entity": "triazinoquinazoline", "entity_type": "Chemical", "pos": [73, 92]}, {"entity": "sulfonamide", "entity_type": "Chemical", "pos": [126, 137]}, {"entity": "methyl 2 - isothiocyanato benzoate", "entity_type": "Chemical", "pos": [174, 208]}], "task": "NER"}
{"text": "Some of the newly synthesized compounds revealed promising bacterial growth inhibition , compared with the ampicillin , as the reference drug .", "entity": [{"entity": "ampicillin", "entity_type": "Chemical", "pos": [107, 117]}], "task": "NER"}
{"text": "A LigandScout approach - generated pharmacophore model for the Staph aureus bacteria growth inhibition was done .", "entity": [], "task": "NER"}
{"text": "The degree of fitting of the test set compounds ( 3 , 4 , 6 , 8 , 11 , 17 ) to the generated hypothetical model revealed a qualitative measure of the more or less microbial inhibition of Staphylococcus aureus .", "entity": [], "task": "NER"}
{"text": "Compounds ( 7 , 8 , 10 , 12 , 15 , 17 and 22 ) , which revealed significant activity , are able to effectively satisfy the proposed pharmacophore geometry , using the energy accessible conformers ( E conf < 20 kcal / mol ) .", "entity": [], "task": "NER"}
{"text": "Agreement Between ICU Clinicians and Electrophysiology Cardiologists on the Decision to Initiate a QTc - interval Prolonging Medication in Critically Ill Patients with Potential Risk Factors for Torsade de Pointes : A Comparative , Case - Based Evaluation .", "entity": [], "task": "NER"}
{"text": "STUDY OBJECTIVES : To measure concordance between different intensive care unit ( ICU ) clinicians and a consensus group of electrophysiology ( EP ) cardiologists for use of a common rate - corrected QT interval ( QTc ) - prolonging medication in cases containing different potential risk factor ( s ) for torsade de pointes ( TdP ) .", "entity": [], "task": "NER"}
{"text": "DESIGN : Prospective case - based evaluation .", "entity": [], "task": "NER"}
{"text": "SETTING : Academic medical center with 320 beds .", "entity": [], "task": "NER"}
{"text": "SUBJECTS : Medical house staff ( MDs ) and ICU nurses ( RNs ) from one center and select critical care pharmacists ( PHs ) .", "entity": [], "task": "NER"}
{"text": "INTERVENTION : Completion of a survey containing 10 hypothetical ICU cases in which patients had agitated delirium for which a psychiatrist recommended intravenous haloperidol 5 mg every 6 hours .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [164, 175]}], "task": "NER"}
{"text": "Each case contained different potential risk factor ( s ) for TdP in specific combinations .", "entity": [], "task": "NER"}
{"text": "A group of five EP cardiologists agreed that haloperidol use was safe in five cases and not safe in five cases .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [45, 56]}], "task": "NER"}
{"text": "MEASUREMENTS AND MAIN RESULTS : For each case , participants were asked to document whether they would administer haloperidol , to provide a rationale for their decision , and to state their level of confidence in that decision .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "Most clinicians ( 92 of 115 [ 80 % ] ) invited to participate completed the cases .", "entity": [], "task": "NER"}
{"text": "Among the five cases where EP cardiologists agreed that haloperidol was not safe , 29 % of respondents felt that haloperidol was safe .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [56, 67]}, {"entity": "haloperidol", "entity_type": "Chemical", "pos": [113, 124]}], "task": "NER"}
{"text": "Conversely , in the five cases where EP cardiologists felt haloperidol was safe , 21 % of respondents believed that it was not safe .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "Overall respondent - EP cardiologist agreement for haloperidol use across the 10 cases was moderate ( kappa = 0 . 51 ) .", "entity": [{"entity": "haloperidol", "entity_type": "Chemical", "pos": [51, 62]}], "task": "NER"}
{"text": "MDs and PHs were in agreement with the EP cardiologists more than RNs ( p = 0 . 03 ) .", "entity": [], "task": "NER"}
{"text": "Interprofessional variability existed for the TdP risk factors each best identified .", "entity": [], "task": "NER"}
{"text": "Clinician confidence correlated with EP cardiologist concordance for MDs ( p = 0 . 002 ) and PHs ( p = 0 . 0002 ) , but not for RNs ( p = 0 . 69 ) .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : When evaluating use of a QTc interval - prolonging medication , ICU clinicians often fail to identify the TdP risk factors that EP cardiologists feel should prevent its use .", "entity": [], "task": "NER"}
{"text": "Clinician - EP cardiologist concordance varies by the specific risk factor ( s ) for TdP and the ICU professional conducting the assessment .", "entity": [], "task": "NER"}
{"text": "High - Purity Prostate Circulating Tumor Cell Isolation by a Polymer Nanofiber - Embedded Microchip for Whole Exome Sequencing .", "entity": [], "task": "NER"}
{"text": "Handpick single cancer cells : A modified NanoVelcro Chip is coupled with ArcturusXT laser capture microdissection ( LCM ) technology to enable the detection and isolation of single circulating tumor cells ( CTCs ) from patients with prostate cancer ( PC ) .", "entity": [], "task": "NER"}
{"text": "This new approach paves the way for conducting next - generation sequencing ( NGS ) on single CTCs .", "entity": [], "task": "NER"}
{"text": "Rapid Improvement of Diabetes After Gastric Bypass Surgery : Is It the Diet or Surgery ?", "entity": [], "task": "NER"}
{"text": "OBJECTIVEImprovements in diabetes after Roux - en - Y gastric bypass ( RYGB ) often occur days after surgery .", "entity": [], "task": "NER"}
{"text": "Surgically induced hormonal changes and the restrictive postoperative diet are proposed mechanisms .", "entity": [], "task": "NER"}
{"text": "We evaluated the contribution of caloric restriction versus surgically induced changes to glucose homeostasis in the immediate postoperative period . RESEARCH DESIGN AND METHODSPatients with type 2 diabetes planning to undergo RYGB participated in a prospective two - period study ( each period involved a 10 - day inpatient stay and periods were separated by a minimum of 6 weeks of wash - out ) in which patients served as their own controls .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [90, 97]}], "task": "NER"}
{"text": "The presurgery period consisted of diet alone .", "entity": [], "task": "NER"}
{"text": "The postsurgery period was matched in all aspects ( daily matched diet ) and included RYGB surgery .", "entity": [], "task": "NER"}
{"text": "Glucose measurements were performed every 4 h throughout the study .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "A mixed meal challenge test was performed before and after each period . RESULTSTen patients completed the study and had the following characteristics : age , 53 . 2 years ( 95 % CI , 48 . 0 - 58 . 4 ) ; BMI , 51 . 2 kg / m ( 2 ) ( 46 . 1 - 56 . 4 ) ; diabetes duration , 7 . 4 years ( 4 . 8 - 10 . 0 ) ; and HbA1c , 8 . 52 % ( 7 . 08 - 9 . 96 ) .", "entity": [], "task": "NER"}
{"text": "Patients lost 7 . 3 kg ( 8 . 1 - 6 . 5 ) during the presurgery period versus 4 . 0 kg ( 6 . 2 - 1 . 7 ) during the postsurgery period ( P = 0 . 01 between periods ) .", "entity": [], "task": "NER"}
{"text": "Daily glycemia in the presurgery period was significantly lower ( 1 , 293 . 58 mg / dL * day [ 1 , 096 . 83 - 1 , 490 . 33 ) vs . 1 , 478 . 80 mg / dL * day [ 1 , 277 . 47 - 1 , 680 . 13 ] ) compared with the postsurgery period ( P = 0 . 02 between periods ) .", "entity": [], "task": "NER"}
{"text": "The improvements in the fasting and maximum poststimulation glucose and 6 - h glucose area under the curve ( primary outcome ) were similar during both periods . CONCLUSIONSGlucose homeostasis improved in response to a reduced caloric diet , with a greater effect observed in the absence of surgery as compared with after RYGB .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "CONCLUSIONSGlucose", "entity_type": "Chemical", "pos": [162, 180]}], "task": "NER"}
{"text": "These findings suggest that reduced calorie ingestion can explain the marked improvement in diabetes control observed after RYGB .", "entity": [], "task": "NER"}
{"text": "Structural basis for activation of ZAP - 70 by phosphorylation of the SH2 - kinase linker .", "entity": [], "task": "NER"}
{"text": "Serial activation of the tyrosine kinases Lck and ZAP - 70 initiates signaling downstream of the T - cell receptor .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "We had previously reported the structure of an autoinhibited ZAP - 70 variant in which two regulatory tyrosine residues ( 315 and 319 ) in the SH2 - kinase linker were replaced by phenylalanine .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "phenylalanine", "entity_type": "Chemical", "pos": [180, 193]}], "task": "NER"}
{"text": "We now present the crystal structure of ZAP - 70 in which Tyr 315 and Tyr 319 are not mutated , leading to the recognition of a five - residue sequence register error in the SH2 - kinase linker of the original crystallographic model .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [58, 61]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "The revised model identifies distinct roles for these two tyrosines .", "entity": [{"entity": "tyrosines", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "As seen in a recently reported structure of the related tyrosine kinase Syk , Tyr 315 of ZAP - 70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain , and the integrity of this interface would be lost upon engagement of doubly - phosphorylated peptides by the SH2 domains .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "Tyr 319 is not necessarily dislodged by SH2 engagement , which activates ZAP - 70 by only ~ 5 - fold in vitro .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "In contrast , phosphorylation by Lck activates ZAP - 70 by ~ 100 - fold .", "entity": [], "task": "NER"}
{"text": "This difference is due to the ability of Tyr 319 to suppress ZAP - 70 activity even when the SH2 domains are dislodged from the kinase domain , providing stringent control of ZAP - 70 activity downstream of Lck .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "Laser welding of ruptured intestinal tissue using plasmonic polypeptide nanocomposite solders .", "entity": [], "task": "NER"}
{"text": "Approximately 1 . 5 million people suffer from colorectal cancer and inflammatory bowel disease in the United States .", "entity": [], "task": "NER"}
{"text": "Occurrence of leakage following standard surgical anastomosis in intestinal and colorectal surgery is common and can cause infection leading to life - threatening consequences .", "entity": [], "task": "NER"}
{"text": "In this report , we demonstrate that plasmonic nanocomposites , generated from elastin - like polypeptides ( ELPs ) cross - linked with gold nanorods , can be used to weld ruptured intestinal tissue upon exposure to near - infrared ( NIR ) laser irradiation .", "entity": [], "task": "NER"}
{"text": "Mechanical properties of these nanocomposites can be modulated based on the concentration of gold nanorods embedded within the ELP matrix .", "entity": [], "task": "NER"}
{"text": "We employed photostable , NIR - absorbing cellularized and noncellularized GNR - ELP nanocomposites for ex vivo laser welding of ruptured porcine small intestines .", "entity": [], "task": "NER"}
{"text": "Laser welding using the nanocomposites significantly enhanced the tensile strength , leakage pressure , and bursting pressure of ruptured intestinal tissue .", "entity": [], "task": "NER"}
{"text": "This , in turn , provided a liquid - tight seal against leakage of luminal liquid from the intestine and resulting bacterial infection .", "entity": [], "task": "NER"}
{"text": "This study demonstrates the utility of laser tissue welding using plasmonic polypeptide nanocomposites and indicates the translational potential of these materials in intestinal and colorectal repair .", "entity": [], "task": "NER"}
{"text": "Bioinspired Water - Enhanced Mechanical Gradient Nanocomposite Films That Mimic the Architecture and Properties of the Squid Beak .", "entity": [], "task": "NER"}
{"text": "Inspired by the water - enhanced mechanical gradient character of the squid beak , we herein report a nanocomposite that mimics both the architecture and properties of this interesting natural material .", "entity": [], "task": "NER"}
{"text": "Similar to the squid beak , we have developed nanocomposites where the degree of cross - linking is controlled along the length of the film .", "entity": [], "task": "NER"}
{"text": "In this study , we utilized tunicate cellulose nanocrystals as the nanofiller that are functionalized with allyl moieties .", "entity": [{"entity": "allyl", "entity_type": "Chemical", "pos": [107, 112]}], "task": "NER"}
{"text": "Using photoinduced thiol - ene chemistry , we have been able to cross - link the CNC nanofiller .", "entity": [{"entity": "thiol", "entity_type": "Chemical", "pos": [19, 24]}], "task": "NER"}
{"text": "In the dry state where strong CNC interactions can occur , only a small mechanical contrast is observed between the cross - linked and uncross - linked samples .", "entity": [], "task": "NER"}
{"text": "However , when the films are exposed to water , which \" switches off \" the noncovalent CNC interactions , a significant mechanical contrast is observed between the same films .", "entity": [], "task": "NER"}
{"text": "For example , at 20 wt % CNC ( in the dry film ) , an increase in wet modulus from 60 to 300 MPa ( ~ 500 % increase ) is observed after photoirradiation .", "entity": [], "task": "NER"}
{"text": "Furthermore , we show that the wet modulus can be controlled by altering the UV exposure time which allows access to mechanical gradient films .", "entity": [], "task": "NER"}
{"text": "Multitarget Global Sensitivity Analysis of n - Butanol Combustion .", "entity": [{"entity": "n - Butanol", "entity_type": "Chemical", "pos": [43, 54]}], "task": "NER"}
{"text": "A model for the combustion of butanol is studied using a recently developed theoretical method for the systematic improvement of the kinetic mechanism .", "entity": [{"entity": "butanol", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "The butanol mechanism includes 1446 reactions , and we demonstrate that it is straightforward and computationally feasible to implement a full global sensitivity analysis incorporating all the reactions .", "entity": [{"entity": "butanol", "entity_type": "Chemical", "pos": [4, 11]}], "task": "NER"}
{"text": "In addition , we extend our previous analysis of ignition - delay targets to include species targets .", "entity": [], "task": "NER"}
{"text": "The combination of species and ignition targets leads to multitarget global sensitivity analysis , which allows for a more complete mechanism validation procedure than we previously implemented .", "entity": [], "task": "NER"}
{"text": "The inclusion of species sensitivity analysis allows for a direct comparison between reaction pathway analysis and global sensitivity analysis .", "entity": [], "task": "NER"}
{"text": "Design , Synthesis , Biological Evaluation , and Docking Studies of ( S ) - Phenylalanine Derivatives with a 2 - Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors .", "entity": [{"entity": "( S ) - Phenylalanine", "entity_type": "Chemical", "pos": [68, 89]}, {"entity": "2 - Cyanopyrrolidine", "entity_type": "Chemical", "pos": [109, 129]}], "task": "NER"}
{"text": "A novel series of ( S ) - phenylalanine derivatives with a 2 - cyanopyrrolidine moiety were designed and synthesized through a rational drug design strategy .", "entity": [{"entity": "( S ) - phenylalanine", "entity_type": "Chemical", "pos": [18, 39]}, {"entity": "2 - cyanopyrrolidine", "entity_type": "Chemical", "pos": [59, 79]}], "task": "NER"}
{"text": "Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 ( DPP - 4 ) inhibitors , among them , the cyclopropyl - substituted phenylalanine derivative 11h displayed the most potent DPP - 4 inhibitory activity with an IC50 value of 0 . 247 mu M .", "entity": [{"entity": "cyclopropyl - substituted phenylalanine", "entity_type": "Chemical", "pos": [135, 174]}], "task": "NER"}
{"text": "In addition , molecular docking analysis of the representative compounds 11h , 11k , and 15a were performed , which not only revealed the impact of binding modes on DPP - 4 inhibitory activity , but also provided additional methodological values for design and optimization .", "entity": [], "task": "NER"}
{"text": "HISTONE DEACETYLASE INHIBITION AFFECTS SODIUM IODIDE SYMPORTER ( NIS ) EXPRESSION AND INDUCES (1) (3) (1) I CYTOTOXICITY IN ANAPLASTIC THYROID CANCER CELLS .", "entity": [{"entity": "SODIUM IODIDE", "entity_type": "Chemical", "pos": [39, 52]}, {"entity": "(1) (3) (1) I", "entity_type": "Chemical", "pos": [94, 107]}], "task": "NER"}
{"text": "Background : Anaplastic thyroid cancers ( ATC ) represent only 1 - 2 % of all thyroid tumors , but they account for up to 50 % of the mortality .", "entity": [], "task": "NER"}
{"text": "Treatment of differentiated thyroid carcinomas is well standardized and the use of radioiodine represents an essential step ; in contrast , there is no standardized therapeutic approach for anaplastic tumors and their prognosis is poor .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [83, 94]}], "task": "NER"}
{"text": "The resistance of anaplastic thyroid cancer to radioiodine treatment is principally due to the absence of expression of the sodium iodide symporter ( NIS ) , mainly due to epigenetic silencing .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "sodium iodide", "entity_type": "Chemical", "pos": [124, 137]}], "task": "NER"}
{"text": "The acetylation status of histones is involved in the epigenetic control of gene expression and is usually disrupted in advanced thyroid cancer .", "entity": [], "task": "NER"}
{"text": "Histone deacetylase inhibitors have been demonstrated as potent anticancer drugs with several different effects on cell viability and differentiation .", "entity": [], "task": "NER"}
{"text": "Methods : Stabilized anaplastic thyroid cancer cell lines ( BHT - 101 and CAL - 62 ) and primary cultures from patients who underwent thyroidectomy for anaplastic thyroid cancer were treated with the histone deacetylase inhibitor LBH589 .", "entity": [{"entity": "LBH589", "entity_type": "Chemical", "pos": [230, 236]}], "task": "NER"}
{"text": "After treatment , we evaluated the expression and function of NIS .", "entity": [], "task": "NER"}
{"text": "Gene expression was evaluated by real - time PCR ( RT - PCR ) ; NIS promoter activity was determined with a luciferase reporter assay ; and protein expression was assessed through immunofluorescence .", "entity": [], "task": "NER"}
{"text": "We tested the protein function by 125I uptake and efflux experiments ; finally the cytotoxic effect of 131I was determined with a clonogenic assay .", "entity": [{"entity": "125I", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "131I", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "Results : Our results demonstrate that treatment with LBH589 leads to NIS RNA expression as shown by RT - PCR and luciferase assay , and to protein expression as determined by immunofluorescence in vitro and by immunohistochemistry in xenograft tumors .", "entity": [{"entity": "LBH589", "entity_type": "Chemical", "pos": [54, 60]}], "task": "NER"}
{"text": "Moreover , 125I uptake and efflux experiments show the correct protein function and iodine retention , that translate into cytotoxicity effects , as demonstrated by a clonogenic assay with 131I .", "entity": [{"entity": "125I", "entity_type": "Chemical", "pos": [11, 15]}, {"entity": "iodine", "entity_type": "Chemical", "pos": [84, 90]}, {"entity": "131I", "entity_type": "Chemical", "pos": [189, 193]}], "task": "NER"}
{"text": "Conclusions : This study supplies a new potential strategy for the treatment of ATC by modifying gene expression with the aim of inducing responsiveness towards radioiodine therapy .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [161, 172]}], "task": "NER"}
{"text": "Adhesion and Nanomechanics of Pili from the Probiotic Lactobacillus rhamnosus GG .", "entity": [], "task": "NER"}
{"text": "Knowledge of the mechanisms by which bacterial pili adhere to host cells and withstand external forces is critical to our understanding of their functional roles and offers exciting avenues in biomedicine for controlling the adhesion of bacterial pathogens and probiotics .", "entity": [], "task": "NER"}
{"text": "While much progress has been made in the nanoscale characterization of pili from Gram - negative bacteria , the adhesive and mechanical properties of Gram - positive bacterial pili remain largely unknown .", "entity": [], "task": "NER"}
{"text": "Here , we use single - molecule atomic force microscopy to unravel the binding mechanism of pili from the probiotic Gram - positive bacterium Lactobacillus rhamnosus GG ( LGG ) .", "entity": [], "task": "NER"}
{"text": "First , we show that SpaC , the key adhesion protein of the LGG pilus , is a multifunctional adhesin with broad specificity .", "entity": [], "task": "NER"}
{"text": "SpaC forms homophilic trans - interactions engaged in bacterial aggregation and specifically binds mucin and collagen , two major extracellular components of host epithelial layers .", "entity": [], "task": "NER"}
{"text": "Homophilic and heterophilic interactions display similar binding strengths and dissociation rates .", "entity": [], "task": "NER"}
{"text": "Next , pulling experiments on living bacteria demonstrate that LGG pili exhibit two unique mechanical responses , that is , zipper - like adhesion involving multiple SpaC molecules distributed along the pilus length and nanospring properties enabling pili to resist high force .", "entity": [], "task": "NER"}
{"text": "These mechanical properties may represent a generic mechanism among Gram - positive bacterial pili for strengthening adhesion and withstanding shear stresses in the natural environment .", "entity": [], "task": "NER"}
{"text": "The single - molecule experiments presented here may help us to design molecules capable of promoting or inhibiting bacterial - host interactions .", "entity": [], "task": "NER"}
{"text": "Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish : A tool for examining OH - BDE toxicity to early life stages .", "entity": [{"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [51, 66]}, {"entity": "OH - BDE", "entity_type": "Chemical", "pos": [146, 154]}], "task": "NER"}
{"text": "Polybrominated diphenyl ethers ( PBDEs ) and their oxidative metabolites ( hydroxylated PBDEs ; OH - BDEs ) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish .", "entity": [{"entity": "Polybrominated diphenyl ethers", "entity_type": "Chemical", "pos": [0, 30]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [33, 38]}, {"entity": "hydroxylated PBDEs", "entity_type": "Chemical", "pos": [75, 93]}, {"entity": "OH - BDEs", "entity_type": "Chemical", "pos": [96, 105]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [184, 199]}], "task": "NER"}
{"text": "The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish ( Danio rerio ) , and to determine the effects of an OH - BDE on their expression .", "entity": [{"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [113, 128]}, {"entity": "OH - BDE", "entity_type": "Chemical", "pos": [217, 225]}], "task": "NER"}
{"text": "While RT - PCR can provide quantitative data on gene expression , it lacks spatial sensitivity to examine localized gene expression ; and , isolation of organs from zebrafish embryos is technically difficult , if not impossible .", "entity": [], "task": "NER"}
{"text": "For this reason , the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo .", "entity": [], "task": "NER"}
{"text": "While PBDEs and OH - BDEs have been shown to inhibit the activity and expression of deiodionases , a family of enzymes that regulate thyroid hormone concentrations intracellularly , it is unclear whether or not they can affect regional expression of the different isoforms during early development .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [6, 11]}, {"entity": "OH - BDEs", "entity_type": "Chemical", "pos": [16, 25]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [133, 148]}], "task": "NER"}
{"text": "In this study we investigated deiodinase 1 ( Dio1 ) , deiodinase 2 ( Dio2 ) , and deiodinase 3 ( Dio3 ) mRNA expression at the following life stages ( 2 , 8 , and 1k - cells ; 50 % - epiboly , 6 and 18 - somites , 22 , 24 , 48 , 72 hpf and / or 10 dpf ) in zebrafish and found life stage specific expression of these genes that were highly localized .", "entity": [], "task": "NER"}
{"text": "To demonstrate the use of this technique for investigating potential endocrine disrupting effects , zebrafish embryos were exposed to 1 , 10 and 100nM 6 - OH - BDE - 47 .", "entity": [{"entity": "6 - OH - BDE - 47", "entity_type": "Chemical", "pos": [151, 168]}], "task": "NER"}
{"text": "Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct , respectively ( quantified by measuring intensity of coloration using ImageJ analysis software ) were observed , suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment .", "entity": [], "task": "NER"}
{"text": "Our results demonstrate effects of OH - BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages .", "entity": [{"entity": "OH - BDEs", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "Transport Function and Transcriptional Regulation of a Liver - Enriched Human Organic Anion Transporting Polypeptide 2B1 Transcriptional Start Site Variant .", "entity": [], "task": "NER"}
{"text": "Human Organic Anion Transporting Polypeptide 2B1 ( OATP2B1 ) is a membrane transporter that facilitates the cellular uptake of a number of endogenous compounds and drugs .", "entity": [], "task": "NER"}
{"text": "OATP2B1 is widely expressed in tissues including the small intestine , liver , kidney , placenta , heart , skeletal muscle and platelets .", "entity": [], "task": "NER"}
{"text": "Recently , it has been shown that differential promoter usage in tissues results in expression of five OATP2B1 transcriptional start site variants which utilize distinct first exons but share common subsequent exons .", "entity": [], "task": "NER"}
{"text": "These variants are expected to encode either a full length ( OATP2B1 - FL ) or shortened protein lacking 22 N - terminus amino acids ( OATP2B - Short ) .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [108, 109]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "Little is known regarding the transport activity and regulation of OATP2B1 variants with N - terminus truncation .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [89, 90]}], "task": "NER"}
{"text": "Here , using absolute quantitative polymerase chain reaction we find the full length variant is the major form expressed in duodenum but the short variant predominates in liver .", "entity": [], "task": "NER"}
{"text": "Using a transient heterologous cell expression system , we find that the transport activities of the short OATP2B1 variant towards substrates estrone sulfate and rosuvastatin are similar to the well - characterized full length variant .", "entity": [{"entity": "estrone sulfate", "entity_type": "Chemical", "pos": [142, 157]}, {"entity": "rosuvastatin", "entity_type": "Chemical", "pos": [162, 174]}], "task": "NER"}
{"text": "Transcriptional activity screening of the liver enriched OATP2B1 variant promoter identified hepatocyte nuclear factor 4 alpha ( HNF4 alpha ) as a novel transacting factor .", "entity": [], "task": "NER"}
{"text": "With a combination of in silico screening , promoter mutation in cell - based reporter assays , siRNA knockdown and chromatin immunoprecipitation studies , we identified a functional HNF4 alpha binding site close to the transcription start site ( - 17 to - 4 bp ) .", "entity": [], "task": "NER"}
{"text": "We conclude that the major OATP2B1 protein form in liver is transport competent and its hepatic expression is regulated by HNF4 alpha .", "entity": [], "task": "NER"}
{"text": "Genome - wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4 .", "entity": [], "task": "NER"}
{"text": "AIMS / HYPOTHESIS : Most genetic variants identified for type 2 diabetes have been discovered in European populations .", "entity": [], "task": "NER"}
{"text": "We performed genome - wide association studies ( GWAS ) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians .", "entity": [], "task": "NER"}
{"text": "METHODS : We performed a meta - analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent .", "entity": [], "task": "NER"}
{"text": "We followed up the top signals in two independent Southern Han Chinese cohorts ( totalling 10 , 383 cases and 6 , 974 controls ) , and performed in silico replication in multiple populations .", "entity": [], "task": "NER"}
{"text": "RESULTS : We identified CDKN2A / B and four novel type 2 diabetes association signals with p < 1 x 10 ( - 5 ) from the meta - analysis .", "entity": [], "task": "NER"}
{"text": "Thirteen variants within these four loci were followed up in two independent Chinese cohorts , and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11 , 067 cases and 7 , 929 controls ( p meta = 2 . 6 x 10 ( - 8 ) ; OR [ 95 % CI ] 1 . 18 [ 1 . 11 , 1 . 25 ] ) .", "entity": [], "task": "NER"}
{"text": "In silico replication revealed consistent associations across multiethnic groups , including five East Asian populations ( p meta = 2 . 3 x 10 ( - 10 ) ) and a population of European descent ( p = 8 . 6 x 10 ( - 3 ) ) .", "entity": [], "task": "NER"}
{"text": "The rs10229583 risk variant was associated with elevated fasting plasma glucose , impaired beta cell function in controls , and an earlier age at diagnosis for the cases .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [72, 79]}], "task": "NER"}
{"text": "The novel variant lies within an islet - selective cluster of open regulatory elements .", "entity": [], "task": "NER"}
{"text": "There was significant heterogeneity of effect between Han Chinese and individuals of European descent , Malaysians and Indians .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS / INTERPRETATION : Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Disrupting the scaffold to improve focal adhesion kinase - targeted cancer therapeutics .", "entity": [], "task": "NER"}
{"text": "Focal adhesion kinase ( FAK ) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth , invasion , and metastasis .", "entity": [], "task": "NER"}
{"text": "Existing FAK - based therapeutics focus on inhibiting the kinase ' s catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [164, 172]}], "task": "NER"}
{"text": "Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer .", "entity": [], "task": "NER"}
{"text": "ERP evidence suggests executive dysfunction in ecstasy polydrug users .", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [47, 54]}], "task": "NER"}
{"text": "BACKGROUND : Deficits in executive functions such as access to semantic / long - term memory have been shown in ecstasy users in previous research .", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [112, 119]}], "task": "NER"}
{"text": "Equally , there have been many reports of equivocal findings in this area .", "entity": [], "task": "NER"}
{"text": "The current study sought to further investigate behavioural and electro - physiological measures of this executive function in ecstasy users .", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [127, 134]}], "task": "NER"}
{"text": "METHOD : Twenty ecstasy - polydrug users , 20 non - ecstasy - polydrug users and 20 drug - na i ve controls were recruited .", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "ecstasy", "entity_type": "Chemical", "pos": [52, 59]}], "task": "NER"}
{"text": "Participants completed background questionnaires about their drug use , sleep quality , fluid intelligence and mood state .", "entity": [], "task": "NER"}
{"text": "Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography ( EEG ) measures were recorded .", "entity": [], "task": "NER"}
{"text": "RESULTS : Analysis of Variance ( ANOVA ) revealed no between - group differences in behavioural performance on the task .", "entity": [], "task": "NER"}
{"text": "Mixed ANOVA on event - related potential ( ERP ) components P2 , N2 and P3 revealed significant between - group differences in the N2 component .", "entity": [], "task": "NER"}
{"text": "Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between - group differences , generally showing greater negativity at occipito - parietal electrodes in ecstasy users compared to drug - na i ve controls .", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [197, 204]}], "task": "NER"}
{"text": "Despite absence of behavioural differences , differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy - polydrug users .", "entity": [{"entity": "ecstasy", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "In vitro read - through of phenylalanine hydroxylase ( PAH ) nonsense mutations using aminoglycosides : a potential therapy for phenylketonuria .", "entity": [{"entity": "phenylalanine", "entity_type": "Chemical", "pos": [27, 40]}, {"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [86, 101]}], "task": "NER"}
{"text": "Phenylketonuria ( PKU , OMIM 261600 ) is an autosomal recessive inborn error of phenylalanine metabolism , predominantly caused by mutations in the phenylalanine hydroxylase ( PAH ) gene .", "entity": [{"entity": "phenylalanine", "entity_type": "Chemical", "pos": [80, 93]}, {"entity": "phenylalanine", "entity_type": "Chemical", "pos": [148, 161]}], "task": "NER"}
{"text": "Approximately 10 % of patients carry a nonsense mutation , which results in an inactive or unstable truncated protein .", "entity": [], "task": "NER"}
{"text": "In some genetic disorders , including cystic fibrosis and Duchenne muscular dystrophy , restoration of full - length protein has been achieved by aminoglycoside antibiotics , such as gentamicin and G - 418 ( Geneticin ) .", "entity": [{"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [146, 160]}, {"entity": "gentamicin", "entity_type": "Chemical", "pos": [183, 193]}, {"entity": "G - 418", "entity_type": "Chemical", "pos": [198, 205]}, {"entity": "Geneticin", "entity_type": "Chemical", "pos": [208, 217]}], "task": "NER"}
{"text": "More recently , nonsense read - through has been induced at greater rates using a non - aminoglycoside drug , PTC124 ( Ataluren ) , which has the advantage of being non - toxic in contrast to the antibiotics .", "entity": [{"entity": "aminoglycoside", "entity_type": "Chemical", "pos": [88, 102]}, {"entity": "PTC124", "entity_type": "Chemical", "pos": [110, 116]}, {"entity": "Ataluren", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "The efficacy of read - through induced by three compounds , aminoglycosides G418 and gentamicin , and PTC124 were evaluated for four nonsense mutations of PAH in an in vitro expression system in two mammalian cell lines ( COS - 7 and HEK293 ) .", "entity": [{"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [60, 75]}, {"entity": "G418", "entity_type": "Chemical", "pos": [76, 80]}, {"entity": "gentamicin", "entity_type": "Chemical", "pos": [85, 95]}, {"entity": "PTC124", "entity_type": "Chemical", "pos": [102, 108]}], "task": "NER"}
{"text": "The production of full - length PAH was investigated using western blotting and the functionality confirmed by enzyme activity .", "entity": [], "task": "NER"}
{"text": "Gentamicin and G - 418 induced read - through of nonsense PAH mutations in HEK293 cells .", "entity": [{"entity": "Gentamicin", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "G - 418", "entity_type": "Chemical", "pos": [15, 22]}], "task": "NER"}
{"text": "The read - through product partially restored enzymatic activity , which was significantly less than that of wild - type , but comparable to a missense mutation of PAH associated with less severe forms of PKU .", "entity": [], "task": "NER"}
{"text": "Treatment with PTC124 up to 100 mu M did not result in full - length PAH polypeptide .", "entity": [{"entity": "PTC124", "entity_type": "Chemical", "pos": [15, 21]}], "task": "NER"}
{"text": "Nonsense read - through drugs are a potential form of treatment for PKU , although the high dosage of aminoglycosides used is not appropriate in a clinical setting .", "entity": [{"entity": "aminoglycosides", "entity_type": "Chemical", "pos": [102, 117]}], "task": "NER"}
{"text": "In vitro studies with new non - toxic read - through agents as well as in vivo studies would also be essential to determine the extent of read - through required to restore normal phenylalanine levels .", "entity": [{"entity": "phenylalanine", "entity_type": "Chemical", "pos": [180, 193]}], "task": "NER"}
{"text": "Implication of circulating omentin - 1 level on the arterial stiffening in type 2 diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "Omentin - 1 is an adipokine implicated in diabetes , inflammation , and cardiovascular disease .", "entity": [], "task": "NER"}
{"text": "However , no prospective studies have examined the impact of circulating omentin - 1 levels on arterial stiffening in patients with type 2 diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "For the purpose of this study , we recruited 120 patients with type 2 diabetes mellitus and measured serum omentin - 1 , adiponectin , and high - sensitivity C - reactive protein levels as well as other cardiovascular risk factors .", "entity": [], "task": "NER"}
{"text": "Arterial stiffness was assessed by brachial ankle pulse wave velocity ( baPWV ) .", "entity": [], "task": "NER"}
{"text": "An increase in the level of circulating omentin - 1 over a period of 1 year was positively correlated with changes in levels of HbA1c and serum adiponectin as well as baPWV .", "entity": [], "task": "NER"}
{"text": "Subjects with higher baseline serum omentin - 1 levels tended to have a reduced arterial stiffness after 1 year ( P for linear trend = 0 . 03 ) .", "entity": [], "task": "NER"}
{"text": "In the group with increased baPWV after 1 year , the magnitude of increase of circulating omentin - 1 levels was significantly higher than in the group with a lower baPWV after 1 year ( 134 . 3 [ 16 . 6 , 277 . 1 ] ng / mL vs . 15 . 9 [ - 67 . 6 , 145 . 7 ] ng / mL , P < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "Multiple stepwise logistic regression analysis revealed that an increase in systolic blood pressure and an increase in serum omentin - 1 level were independently correlated with arterial stiffening , even after adjusting for other cardiovascular risk factors and medication history .", "entity": [], "task": "NER"}
{"text": "Baseline serum omentin - 1 levels can predict arterial stiffness changes occurring within a year .", "entity": [], "task": "NER"}
{"text": "Furthermore , changes in serum omentin - 1 levels after a year can function as independent markers of arterial stiffening in patients with type 2 diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "High - Grade Prostatic Intraepithelial Neoplasia ( HGPIN ) and topographical distribution in 1 , 374 prostatectomy specimens : Existence of HGPIN near prostate cancer .", "entity": [], "task": "NER"}
{"text": "PURPOSE : High - grade prostatic intraepithelial neoplasia ( HGPIN ) is believed to be a precursor of prostate cancer ( PCa ) .", "entity": [], "task": "NER"}
{"text": "This study evaluated whether HGPIN was located close to PCa in whole radical prostatectomy specimens ( RPSs ) .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : We evaluated 1 , 374 prostate specimens from 1999 to 2010 using a cMDX - based map model of the prostate .", "entity": [], "task": "NER"}
{"text": "The distribution of 10 , 439 PCa foci was analyzed and visualized on a heat map .", "entity": [], "task": "NER"}
{"text": "The color gradient of the heat map was reduced to six colors representing the frequency classification of the relative frequency of PCa using an image posterization effect .", "entity": [], "task": "NER"}
{"text": "We defined 22 regions in the prostate according to the frequency of PCa occurrence .", "entity": [], "task": "NER"}
{"text": "Seven hundred ninety RPSs containing 6 , 374 PCa foci and 4 , 502 HGPIN foci were evaluated .", "entity": [], "task": "NER"}
{"text": "The topographical association between PCa and HGPIN in the RPSs was analyzed by estimating the frequencies of PCa and HGPIN in 22 regions .", "entity": [], "task": "NER"}
{"text": "A logistic regression analysis was performed to assess the odds ratios of HGPIN for the presence of PCa in 22 regions .", "entity": [], "task": "NER"}
{"text": "RESULTS : Fifty - eight percent of PCa specimens included HGPIN and had significantly more favorable Gleason scores , lower PSA levels and smaller relative tumor volumes than isolated PCa specimens .", "entity": [], "task": "NER"}
{"text": "HGPIN ( 68 % ) and PCa ( 69 % ) were predominantly localized to the apical half of the prostate .", "entity": [], "task": "NER"}
{"text": "HGPIN was mainly concentrated in the peripheral zone medial to regions with high PCa frequencies .", "entity": [], "task": "NER"}
{"text": "Upon logistic regression analysis , HGPIN was a significant predictor of PCa co - existence in 11 regions .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : HGPIN was located adjacent to PCa in whole RPSs .", "entity": [], "task": "NER"}
{"text": "PCa concomitant with HGPIN had more favorable pathologic features than isolated PCa .", "entity": [], "task": "NER"}
{"text": "The Joubert Syndrome Associated Missense Mutation ( V443D ) in the Abelson - helper Integration Site 1 ( AHI1 ) Protein Alters Its Localization and Protein - Protein Interactions .", "entity": [], "task": "NER"}
{"text": "Mutations in AHI1 cause Joubert syndrome ( JBTS ) , a neurodevelopmental ciliopathy , characterized by midbrain - hindbrain malformations and motor / cognitive deficits .", "entity": [], "task": "NER"}
{"text": "Here , we show that primary cilia ( PC ) formation is decreased in fibroblasts from individuals with JBTS and AHI1 mutations .", "entity": [], "task": "NER"}
{"text": "Most missense mutations in AHI1 , causing JBTS , occur in known protein domains , however , a common V443D mutation in AHI1 is found in a region with no known protein motifs .", "entity": [], "task": "NER"}
{"text": "We show that cells transfected with AHI1 - V443D , or a new JBTS - causing mutation , AHI1 - R351L , have aberrant localization of AHI1 at the basal bodies of PC and at cell - cell junctions , likely through decreased binding of mutant AHI1 to NPHP1 ( another JBTS - causing protein ) .", "entity": [], "task": "NER"}
{"text": "The AHI1 - V443D mutation causes decreased AHI1 stability , since there is a 50 % reduction in AHI1 - V443D protein levels compared to wildtype AHI1 .", "entity": [], "task": "NER"}
{"text": "Huntingtin - associated protein - 1 ( Hap1 ) is a regulatory protein that binds Ahi1 , and Hap1 knockout mice have been reported to have JBTS - like phenotypes , suggesting a role for Hap1 in ciliogenesis .", "entity": [], "task": "NER"}
{"text": "Fibroblasts and neurons with Hap1 deficiency form PC with normal growth factor - induced ciliary signaling , indicating that the Hap1 JBTS - phenotype is likely not through effects at PC .", "entity": [], "task": "NER"}
{"text": "These results also suggest that the binding of Ahi1 and Hap1 may not be critical for ciliary function .", "entity": [], "task": "NER"}
{"text": "However , we show that HAP1 has decreased binding to AHI1 - V443D indicating that this altered binding could be responsible for the JBTS - like phenotype through an unknown pathway .", "entity": [], "task": "NER"}
{"text": "Thus , these JBTS - associated missense mutations alter their subcellular distribution and protein interactions , compromising functions of AHI1 in cell polarity and cilium - mediated signaling , thereby contributing to JBTS .", "entity": [], "task": "NER"}
{"text": "Bioimaging real - time PXR - dependent mdr1a gene regulation in mdr1a . fLUC reporter mice .", "entity": [], "task": "NER"}
{"text": "The MDR1 gene encodes P - glycoprotein , a transmembrane drug efflux transporter that confers multidrug resistance in cancer cells and affects drug pharmacokinetics by virtue of its expression in the liver , kidney , and colon .", "entity": [], "task": "NER"}
{"text": "Nuclear receptors SXR and CAR are possible master regulators of xenobiotic - inducible MDR1 expression in drug processing organs , but the mechanism of MDR1 regulation has yet to be directly demonstrated in vivo .", "entity": [], "task": "NER"}
{"text": "Moreover , it has previously been impossible to determine the sustained or cumulative effect of repeated doses of xenobiotics on in vivo MDR1 expression .", "entity": [], "task": "NER"}
{"text": "We previously reported a mouse model containing firefly luciferase ( fLUC ) knocked into the mdr1a genomic locus , allowing non - invasive bioimaging of intestinal mdr1a gene expression in live animals .", "entity": [], "task": "NER"}
{"text": "In the current study , we crossed mdr1a . fLUC mice into the pxr knockout ( pxr ( - / - ) ) genetic background and injected mice with pregnenolone - 16 alpha - carbonitrile ( PCN ) , a strong PXR ligand , and two therapeutically relevant taxanes , paclitaxel and docetaxel .", "entity": [{"entity": "pregnenolone - 16 alpha - carbonitrile", "entity_type": "Chemical", "pos": [134, 172]}, {"entity": "PCN", "entity_type": "Chemical", "pos": [175, 178]}, {"entity": "taxanes", "entity_type": "Chemical", "pos": [238, 245]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [248, 258]}, {"entity": "docetaxel", "entity_type": "Chemical", "pos": [263, 272]}], "task": "NER"}
{"text": "All three agents induced mdr1a . fLUC expression ( bioluminescence ) , but only PCN and docetaxel appeared to act primarily via PXR .", "entity": [{"entity": "PCN", "entity_type": "Chemical", "pos": [80, 83]}, {"entity": "docetaxel", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "Luminescence returned to baseline by 24 - 48 hrs after drug injection and was re - inducible over two additional rounds of drug dosing in pxr ( + / + ) mice .", "entity": [], "task": "NER"}
{"text": "TCPOBOP , a CAR ligand , modestly induced mdr1a . fLUC in pxr ( + / + ) and pxr ( - / - ) strains , consistent with CAR ' s minor role in mdr1a regulation .", "entity": [{"entity": "TCPOBOP", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Collectively , these results demonstrate that the mdr1a . fLUC bioimaging model can capture changes in mdr1 gene expression under conditions of repeated xenobiotic treatment in vivo and that it can be used to probe the mechanism of gene regulation in response to different xenobiotic agents .", "entity": [], "task": "NER"}
{"text": "SpecDis : quantifying the comparison of calculated and experimental electronic circular dichroism spectra .", "entity": [], "task": "NER"}
{"text": "This article outlines theory and practice of the comparison of calculated and experimental electronic circular dichroism ( ECD ) curves to determine the absolute configuration of chiral molecules .", "entity": [], "task": "NER"}
{"text": "The focus is on the evaluation of excited - state calculations giving hints at the identification of the correct bandwidth and the application of the so - called \" UV shift \" as a correction factor .", "entity": [], "task": "NER"}
{"text": "A similarity factor is introduced , which helps to quantify the degree of matching of curves .", "entity": [], "task": "NER"}
{"text": "In addition , a few common errors are described that can be made during the measurements of ECD and UV spectra - and advice is given of how to avoid these mistakes .", "entity": [], "task": "NER"}
{"text": "All equations mentioned in the article are implemented in our SpecDis software , which has been developed to rapidly compare calculated ECD and UV curves with experimental ones , and to produce graphics in publication quality .", "entity": [], "task": "NER"}
{"text": "O - heterocyclic embeurekols from Embellisia eureka , an endophyte of Cladanthus arabicus .", "entity": [{"entity": "O - heterocyclic embeurekols", "entity_type": "Chemical", "pos": [0, 28]}], "task": "NER"}
{"text": "Three new polyketides ( ( - ) - 1 , ( + ) - 1 , and 2 ) were isolated from the EtOAc extract of the fungus Embellisia eureka , an endophyte of the Moroccan plant Cladanthus arabicus ( Asteraceae ) .", "entity": [{"entity": "EtOAc", "entity_type": "Chemical", "pos": [79, 84]}], "task": "NER"}
{"text": "The structures of these new compounds were determined on the basis of one - and two - dimensional NMR spectroscopy as well as by high - resolution mass spectrometry .", "entity": [], "task": "NER"}
{"text": "The absolute configurations of ( - ) - 1 , ( + ) - 1 , and 2 were determined by TDDFT ECD calculations of solution conformers , online HPLC - ECD analysis , and the modified Mosher method .", "entity": [], "task": "NER"}
{"text": "Increased activin bioavailability enhances hepatic insulin sensitivity while inducing hepatic steatosis in male mice .", "entity": [], "task": "NER"}
{"text": "The development of insulin resistance is tightly linked to fatty liver disease and is considered a major health concern worldwide , although their mechanistic relationship remains controversial .", "entity": [], "task": "NER"}
{"text": "Activin has emerging roles in nutrient homeostasis but its metabolic effects on hepatocytes remain unknown .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated the effects of increased endogenous activin bioactivity on hepatic nutrient homeostasis by creating mice with inactivating mutations that deplete the circulating activin antagonists , follistatin like - 3 ( FSTL3 ) or the follistatin 315 isoform ( FST315 ; FST288 - only mice ) .", "entity": [], "task": "NER"}
{"text": "We investigated liver histology and lipid content , hepatic insulin sensitivity , and metabolic gene expression including the HepG2 cell and primary hepatocyte response to activin treatment .", "entity": [], "task": "NER"}
{"text": "Both FSTL3KO and FST288 - only mice had extensive hepatic steatosis and elevated hepatic triglyceride ( TG ) content .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [89, 101]}], "task": "NER"}
{"text": "Unexpectedly , insulin signaling , as assessed by phospho - AKT , was enhanced in both mouse models .", "entity": [], "task": "NER"}
{"text": "Pretreatment of HepG2 cells with activin A increased their response to subsequent insulin challenge .", "entity": [], "task": "NER"}
{"text": "Gene expression analysis suggests that increased lipid uptake , enhanced de novo lipid synthesis , decreased lipolysis and / or enhanced glucose uptake contribute to increased hepatic TG content in these models .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [137, 144]}], "task": "NER"}
{"text": "However , activin treatment recapitulated only some of these gene changes suggesting that increased activin bioactivity may be only partially responsible for this phenotype .", "entity": [], "task": "NER"}
{"text": "Nevertheless , our results indicate that activin enhances hepatocyte insulin response which ultimately leads to hepatic steatosis despite the increased insulin sensitivity .", "entity": [], "task": "NER"}
{"text": "Thus , regulation of activin bioactivity is critical for maintaining normal liver lipid homeostasis and response to insulin while activin agonists may be useful for increasing liver insulin sensitivity .", "entity": [], "task": "NER"}
{"text": "Calculation of Electron Transfer Rates Using Mixed Quantum Classical Approaches : Nonadiabatic Limit and Beyond .", "entity": [], "task": "NER"}
{"text": "We investigate the applicability of the Ehrenfest and surface hopping methods to calculate electron transfer rates using the spin - boson model with different parameters .", "entity": [], "task": "NER"}
{"text": "Rate constants are obtained from short time dynamics performed in both the diabatic and adiabatic basis sets .", "entity": [], "task": "NER"}
{"text": "Numerical results and theoretical analysis show that these two methods can be reasonably accurate in the nonadiabatic limit , by staying close to an approximate Fermi ' s golden rule .", "entity": [], "task": "NER"}
{"text": "Beyond the nonadiabatic limit , the calculated mixed quantum classical rates are compared with numerical exact results , and similar accuracy was found as in the nonadiabatic limit .", "entity": [], "task": "NER"}
{"text": "The relation between the current finding and recent studies using the surface hopping method based on long time dynamics is also discussed .", "entity": [], "task": "NER"}
{"text": "It is found that the short time dynamics could be more accurate in calculating rate constants using the mixed quantum classical methods .", "entity": [], "task": "NER"}
{"text": "Effect of surface charge density on the affinity of oxide nanoparticles for the vapor - water interface .", "entity": [{"entity": "oxide", "entity_type": "Chemical", "pos": [52, 57]}], "task": "NER"}
{"text": "Using in - situ X - ray photoelectron spectroscopy at the vapor - water interface , the affinity of nanometer - sized silica colloids to adsorb at the interface is shown to depend on colloid surface charge density .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [118, 124]}], "task": "NER"}
{"text": "In aqueous suspensions at pH 10 corrected Debye - H u ckel theory for surface complexation calculations predict that smaller silica colloids have increased negative surface charge density that originates from enhanced screening of deprotonated silanol groups ( = Si - O ( - ) ) by counterions in the condensed ion layer .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [125, 131]}, {"entity": "silanol", "entity_type": "Chemical", "pos": [244, 251]}, {"entity": "= Si - O ( - )", "entity_type": "Chemical", "pos": [261, 275]}], "task": "NER"}
{"text": "The increased negative surface charge density results in an electrostatic repulsion from the vapor - water interface that is seen to a lesser extent for larger particles that have a reduced charge density in the XPS measurements .", "entity": [], "task": "NER"}
{"text": "We compare the results and interpretation of the in - situ XPS and corrected Debye - H u ckel theory for surface complexation calculations with traditional surface tension measurements .", "entity": [], "task": "NER"}
{"text": "Our results show that controlling the surface charge density of colloid particles can regulate their adsorption to the interface between two dielectrics .", "entity": [], "task": "NER"}
{"text": "Two - dimensional penning ionization electron spectroscopy of open - shell metallocenes : outer valence ionic States of vanadocene and nickelocene .", "entity": [{"entity": "metallocenes", "entity_type": "Chemical", "pos": [75, 87]}, {"entity": "vanadocene", "entity_type": "Chemical", "pos": [120, 130]}, {"entity": "nickelocene", "entity_type": "Chemical", "pos": [135, 146]}], "task": "NER"}
{"text": "In order to investigate outer valence ionic states of open - shell metallocenes , we have applied two - dimensional collision - energy / electron - energy - resolved Penning ionization electron spectroscopy ( 2D - PIES ) upon collision with metastable He * ( 2 ( 3 ) S ) excited atoms as well as a high level ab initio molecular orbital calculation ( the partial third - order quasiparticle theory of the electron propagator ( P3 ) ) to ionization from neutral ground states of vanadocene ( ( 4 ) A2g ) and nickelocene ( ( 3 ) A2g ) .", "entity": [{"entity": "metallocenes", "entity_type": "Chemical", "pos": [67, 79]}, {"entity": "He", "entity_type": "Chemical", "pos": [252, 254]}, {"entity": "vanadocene", "entity_type": "Chemical", "pos": [478, 488]}, {"entity": "nickelocene", "entity_type": "Chemical", "pos": [507, 518]}], "task": "NER"}
{"text": "Assignments of observed Penning ionization electron / He I ultraviolet photoelectron spectra were consistent with the P3 calculation results for ionization of alpha and beta spin electrons except for electron correlation bands observed by PIES .", "entity": [{"entity": "He", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "Negative collision energy dependence of partial Penning ionization cross - sections ( CEDPICS ) indicate attractive interaction with He * ( 2 ( 3 ) S ) around the molecule .", "entity": [{"entity": "He", "entity_type": "Chemical", "pos": [133, 135]}], "task": "NER"}
{"text": "Results by model potential calculation utilizing Li ( 2 ( 2 ) S ) instead of He * ( 2 ( 3 ) S ) for interaction between He * ( 2 ( 3 ) S ) and open - shell metallocenes do not explain the strong negative CEDPICS of the bands observed in PIES .", "entity": [{"entity": "Li", "entity_type": "Chemical", "pos": [49, 51]}, {"entity": "He", "entity_type": "Chemical", "pos": [77, 79]}, {"entity": "He", "entity_type": "Chemical", "pos": [120, 122]}, {"entity": "metallocenes", "entity_type": "Chemical", "pos": [156, 168]}], "task": "NER"}
{"text": "Antifreeze ( Glyco ) protein Mimetic Behavior of Poly ( vinyl alcohol ) : Detailed Structure Ice Recrystallization Inhibition Activity Study .", "entity": [{"entity": "Poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [49, 71]}], "task": "NER"}
{"text": "This manuscript reports a detailed study on the ability of poly ( vinyl alcohol ) to act as a biomimetic surrogate for antifreeze ( glyco ) proteins , with a focus on the specific property of ice - recrystallization inhibition ( IRI ) .", "entity": [{"entity": "poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [59, 81]}], "task": "NER"}
{"text": "Despite over 40 years of study , the underlying mechanisms that govern the action of biological antifreezes are still poorly understood , which is in part due to their limited availability and challenging synthesis .", "entity": [], "task": "NER"}
{"text": "Poly ( vinyl alcohol ) ( PVA ) has been shown to display remarkable ice recrystallization inhibition activity despite its major structural differences to native antifreeze proteins .", "entity": [{"entity": "Poly ( vinyl alcohol )", "entity_type": "Chemical", "pos": [0, 22]}, {"entity": "PVA", "entity_type": "Chemical", "pos": [25, 28]}], "task": "NER"}
{"text": "Here , controlled radical polymerization is used to synthesize well - defined PVA , which has enabled us to obtain the first quantitative structure - activity relationships , to probe the role of molecular weight and comonomers on IRI activity .", "entity": [{"entity": "PVA", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "Crucially , it was found that IRI activity is \" switched on \" when the polymer chain length increases from 10 and 20 repeat units .", "entity": [], "task": "NER"}
{"text": "Substitution of the polymer side chains with hydrophilic or hydrophobic units was found to diminish activity .", "entity": [], "task": "NER"}
{"text": "Hydrophobic modifications to the backbone were slightly more tolerated than side chain modifications , which implies an unbroken sequence of hydroxyl units is necessary for activity .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "These results highlight that , although hydrophobic domains are key components of IRI activity , the random inclusion of addition hydrophobic units does not guarantee an increase in activity and that the actual polymer conformation is important .", "entity": [], "task": "NER"}
{"text": "Skin Sensitization of Epoxyaldehydes : Importance of Conjugation .", "entity": [{"entity": "Epoxyaldehydes", "entity_type": "Chemical", "pos": [22, 36]}], "task": "NER"}
{"text": "Structure - activity relationship ( SAR ) models are important tools for predicting the skin sensitization potential of new compounds without animal testing .", "entity": [], "task": "NER"}
{"text": "In compounds possessing a structural alert ( aldehyde ) and an activation alert ( double bond ) , it is important to consider bioactivation / autoxidation ( e . g . , epoxidation ) .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "In the present study , we have explored a series of aldehydes with regard to contact allergy .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "The chemical reactivity of these 6 aldehydes toward a model hexapeptide was investigated , and their skin sensitization potencies were evaluated using the local lymph node assay ( LLNA ) .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [35, 44]}], "task": "NER"}
{"text": "Overall , we observed a similar trend for the in vitro reactivity and the in vivo sensitization potency for the structural analogues in this study .", "entity": [], "task": "NER"}
{"text": "The highly reactive conjugated aldehydes ( alpha , beta - unsaturated aldehydes and 2 , 3 - epoxyaldehydes ) are sensitizing moieties , while nonconjugated aldehydes and nonterminal aliphatic epoxides show low reactivity and low sensitization potency .", "entity": [{"entity": "aldehydes", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "alpha , beta - unsaturated aldehydes", "entity_type": "Chemical", "pos": [43, 79]}, {"entity": "2 , 3 - epoxyaldehydes", "entity_type": "Chemical", "pos": [84, 106]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "epoxides", "entity_type": "Chemical", "pos": [192, 200]}], "task": "NER"}
{"text": "Our data show the importance of not only double bond conjugation to aldehyde but also epoxide - aldehyde conjugation .", "entity": [{"entity": "aldehyde", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "epoxide", "entity_type": "Chemical", "pos": [86, 93]}, {"entity": "aldehyde", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "The observations indicate that the formation of nonconjugated epoxides by bioactivation or autoxidation is not sufficient to significantly increase the sensitization potency of weakly sensitizing parent compounds .", "entity": [{"entity": "epoxides", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD .", "entity": [], "task": "NER"}
{"text": "The helicase PcrA unwinds DNA during asymmetric replication of plasmids , acting with an initiator protein , in our case RepD .", "entity": [], "task": "NER"}
{"text": "Detailed kinetics of PcrA activity were measured using bulk solution and a single - molecule imaging technique to investigate the oligomeric state of the active helicase complex , its processivity and the mechanism of unwinding .", "entity": [], "task": "NER"}
{"text": "By tethering either DNA or PcrA to a microscope coverslip surface , unwinding of both linear and natural circular plasmid DNA by PcrA / RepD was followed in real - time using total internal reflection fluorescence microscopy .", "entity": [], "task": "NER"}
{"text": "Visualization was achieved using a fluorescent single - stranded DNA - binding protein .", "entity": [], "task": "NER"}
{"text": "The single - molecule data show that PcrA , in combination with RepD , can unwind plasmid lengths of DNA in a single run , and that PcrA is active as a monomer .", "entity": [], "task": "NER"}
{"text": "Although the average rate of unwinding was similar in single - molecule and bulk solution assays , the single - molecule experiments revealed a wide distribution of unwinding speeds by different molecules .", "entity": [], "task": "NER"}
{"text": "The average rate of unwinding was several - fold slower than the PcrA translocation rate on single - stranded DNA , suggesting that DNA unwinding may proceed via a partially passive mechanism .", "entity": [], "task": "NER"}
{"text": "However , the fastest dsDNA unwinding rates measured in the single - molecule unwinding assays approached the PcrA translocation speed measured on ssDNA .", "entity": [], "task": "NER"}
{"text": "Mechanisms of the anti - proliferative and anti - inflammatory effects of the herbal fixed combination STW 5 ( Iberogast ( (R) ) ) on colon adenocarcinoma ( HT29 ) cells in vitro .", "entity": [], "task": "NER"}
{"text": "INTRODUCTION : Several conventional pharmaceuticals like non - steroidal anti - inflammatory drugs ( NSAIDS ) or selective cyclooxygenase - 2 ( COX - 2 ) inhibitors have been demonstrated to exert anti - proliferative effects and to induce apoptosis in a variety of cell lines , e . g . colon , stomach , or prostate cancer cells .", "entity": [], "task": "NER"}
{"text": "STW 5 ( Iberogast ( (R) ) ) , a combination of nine plant extracts , is widely used in the treatment of gastrointestinal disorders , including functional dyspepsia and irritable bowel syndrome for which the involvement of an inflammatory etiology is discussed .", "entity": [], "task": "NER"}
{"text": "To investigate the possible anti - proliferative effects , STW 5 and its components have been tested by using the colon - carcinoma cell line HT - 29 .", "entity": [], "task": "NER"}
{"text": "The analyses have been performed in comparison to acetylsalicylic acid ( ASA ) and diclofenac ( Diclo ) , which are well - known to reduce colon carcinoma risk .", "entity": [{"entity": "acetylsalicylic acid", "entity_type": "Chemical", "pos": [50, 70]}, {"entity": "ASA", "entity_type": "Chemical", "pos": [73, 76]}, {"entity": "diclofenac", "entity_type": "Chemical", "pos": [83, 93]}, {"entity": "Diclo", "entity_type": "Chemical", "pos": [96, 101]}], "task": "NER"}
{"text": "RESULTS : STW 5 showed significant anti - proliferative and pro - apoptotic effects on HT - 29 cancer cells , similar to NSAIDs under test .", "entity": [], "task": "NER"}
{"text": "However , using the LDH assay , STW 5 revealed significantly lower cytotoxicity than Diclo at same concentrations .", "entity": [{"entity": "Diclo", "entity_type": "Chemical", "pos": [85, 90]}], "task": "NER"}
{"text": "In contrast to NSAIDs , STW 5 induced COX - 1 / COX - 2 , caspase - 3 and Bax mRNA expressions in HT - 29 and blocked LPS mediated translocation of the NF - kappa B p65 from the cytoplasm into the nucleus in PMA - differentiated THP - 1 macrophages .", "entity": [{"entity": "PMA", "entity_type": "Chemical", "pos": [208, 211]}], "task": "NER"}
{"text": "These effects might be relevant , e . g . for prevention of undesirable side effects like gastric erosions .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : Our data suggest that the pro - apoptotic effect of STW 5 on HT - 29 cells is involving multiple targets and is possibly due to an activation of the caspase cascade via mitochondrial destabilization .", "entity": [], "task": "NER"}
{"text": "Active concentrations of STW 5 are , in relation to therapeutic doses , comparable to those of ASA and Diclo , suggesting a similar favorable effect on colon carcinoma risk .", "entity": [{"entity": "ASA", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "Diclo", "entity_type": "Chemical", "pos": [103, 108]}], "task": "NER"}
{"text": "Cajaninstilbene acid ( CSA ) exerts cytoprotective effects against oxidative stress through the Nrf2 - dependent antioxidant pathway .", "entity": [{"entity": "Cajaninstilbene acid", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "CSA", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "Cajaninstilbene acid ( CSA ) , an active compound separated from pigeon pea leaves , possesses the highly efficient antioxidant activities .", "entity": [{"entity": "Cajaninstilbene acid", "entity_type": "Chemical", "pos": [0, 20]}, {"entity": "CSA", "entity_type": "Chemical", "pos": [23, 26]}], "task": "NER"}
{"text": "Transcription factor nuclear factor - erythroid 2 - related factor 2 ( Nrf2 ) is an important regulator of cellular oxidative stress .", "entity": [], "task": "NER"}
{"text": "This study examined the role of Nrf2 in CSA - mediated antioxidant effects on human hepatocarcinoma ( HepG2 ) cell line .", "entity": [{"entity": "CSA", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "The generation of reactive oxygen species ( ROS ) upon H2O2 and CSA treatment was lower than that of H2O2 alone .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [27, 33]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "CSA", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [101, 105]}], "task": "NER"}
{"text": "CSA activated Nrf2 as evaluated by Western blotting .", "entity": [{"entity": "CSA", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "A luciferase reporter assay also demonstrated that CSA - activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the antioxidant response element ( ARE ) enhancer sequence .", "entity": [{"entity": "CSA", "entity_type": "Chemical", "pos": [51, 54]}], "task": "NER"}
{"text": "Our study indicated that treatment of HepG2 cells with CSA induces Nrf2 - dependent ARE activity and gene expression of heme oxygenase - 1 ( HO - 1 ) , NAD ( P ) H quinone oxidoreductase 1 ( NQO1 ) , and glutamate - cysteine ligase modifier subunits by activation of PI3K / AKT , ERK and JNK signaling pathways .", "entity": [{"entity": "CSA", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "heme", "entity_type": "Chemical", "pos": [120, 124]}, {"entity": "NAD ( P ) H", "entity_type": "Chemical", "pos": [152, 163]}, {"entity": "quinone", "entity_type": "Chemical", "pos": [164, 171]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [204, 213]}, {"entity": "cysteine", "entity_type": "Chemical", "pos": [216, 224]}], "task": "NER"}
{"text": "Inhibition of Nrf2 by siRNA reduced CSA - induced upregulation of these Nrf2 - related enzymes .", "entity": [{"entity": "CSA", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "These results suggest that the Nrf2 / ARE pathway plays an important role in the regulation of CSA - mediated antioxidant effects in HepG2 cells .", "entity": [{"entity": "CSA", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "Enantiocomplementary access to carba - analogs of C - nucleoside derivatives by recombinant Baeyer - Villiger monooxygenases .", "entity": [{"entity": "C - nucleoside", "entity_type": "Chemical", "pos": [50, 64]}], "task": "NER"}
{"text": "A novel and stereoselective synthetic route towards carba - C - nucleosides was investigated applying an enantiodivergent biooxidation strategy by two different Baeyer - Villiger monooxygenases .", "entity": [{"entity": "carba - C - nucleosides", "entity_type": "Chemical", "pos": [52, 75]}], "task": "NER"}
{"text": "Within only three chemo - enzymatic steps it was possible to introduce four chiral centers starting from commercially available non - chiral starting material .", "entity": [], "task": "NER"}
{"text": "Use of asenapine in clinical practice for the management of bipolar mania .", "entity": [{"entity": "asenapine", "entity_type": "Chemical", "pos": [7, 16]}], "task": "NER"}
{"text": "Bipolar disorder is a chronic mental illness associated with high levels of somatic morbidity , comorbidity and mortality .", "entity": [], "task": "NER"}
{"text": "Treatment guidelines for bipolar mania generally recommend initiating first - line therapy with a second - generation antipsychotic or mood stabiliser , either alone or in combination .", "entity": [], "task": "NER"}
{"text": "Asenapine is a second - generation antipsychotic with a unique receptor binding profile , licensed for the treatment of manic episodes in adults with bipolar I disorder .", "entity": [{"entity": "Asenapine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "' Real - world ' data are needed to complement evidence from clinical trials , in order to provide clinicians with pragmatic information regarding the likely risks and benefits of using a new agent in clinical practice .", "entity": [], "task": "NER"}
{"text": "Evidence from real - world case reports demonstrates that - as in clinical trials - asenapine is effective in treating mania and mixed episodes associated with bipolar I disorder , whether used as monotherapy or in combination with a mood stabiliser .", "entity": [{"entity": "asenapine", "entity_type": "Chemical", "pos": [84, 93]}], "task": "NER"}
{"text": "It has a rapid onset of antimanic effect and an early improvement is associated with treatment outcome .", "entity": [], "task": "NER"}
{"text": "Asenapine also shows promise in controlling depressive symptoms and clinically challenging mixed states .", "entity": [{"entity": "Asenapine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Asenapine has a favourable tolerability profile , compared with other first - line agents , having a minimal impact on weight and metabolic parameters .", "entity": [{"entity": "Asenapine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Asenapine should be considered a first - line treatment option for adults with bipolar I disorder .", "entity": [{"entity": "Asenapine", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Force nanoscopy of cell mechanics and cell adhesion .", "entity": [], "task": "NER"}
{"text": "Cells are constantly exposed to mechanical stimuli in their environment and have several evolved mechanisms to sense and respond to these cues .", "entity": [], "task": "NER"}
{"text": "It is becoming increasingly recognized that many cell types , from bacteria to mammalian cells , possess a diverse set of proteins to translate mechanical cues into biochemical signalling and to mediate cell surface interactions such as cell adhesion .", "entity": [], "task": "NER"}
{"text": "Moreover , the mechanical properties of cells are involved in regulating cell function as well as serving as indicators of disease states .", "entity": [], "task": "NER"}
{"text": "Importantly , the recent development of biophysical tools and nanoscale methods has facilitated a deeper understanding of the role that physical forces play in modulating cell mechanics and cell adhesion .", "entity": [], "task": "NER"}
{"text": "Here , we discuss how atomic force microscopy ( AFM ) has recently been used to investigate cell mechanics and cell adhesion at the single - cell and single - molecule levels .", "entity": [], "task": "NER"}
{"text": "This knowledge is critical to our understanding of the molecular mechanisms that govern mechanosensing , mechanotransduction , and mechanoresponse in living cells .", "entity": [], "task": "NER"}
{"text": "While pushing living cells with the AFM tip provides a means to quantify their mechanical properties and examine their response to nanoscale forces , pulling single surface proteins with a functionalized tip allows one to understand their role in sensing and adhesion .", "entity": [], "task": "NER"}
{"text": "The combination of these nanoscale techniques with modern molecular biology approaches , genetic engineering and optical microscopies provides a powerful platform for understanding the sophisticated functions of the cell surface machinery , and its role in the onset and progression of complex diseases .", "entity": [], "task": "NER"}
{"text": "Geographical differences in the prevalence of chronic polypharmacy in older people : eleven years of the EPIFARM - Elderly Project .", "entity": [], "task": "NER"}
{"text": "PURPOSE : To compare the geographical differences in the prevalence of chronic polypharmacy in community - dwelling older people over 11 years .", "entity": [], "task": "NER"}
{"text": "METHODS : This study analyzed nearly two million patients aged 65 - 94 years recorded in the Drug Administrative Database of the Lombardy Region ( Northern Italy ) from 2000 to 2010 .", "entity": [], "task": "NER"}
{"text": "Chronic polypharmacy was defined as taking five or more drugs in 1 month for at least 6 months ( consecutive or not ) in a year .", "entity": [], "task": "NER"}
{"text": "RESULTS : There was a significant spatial autocorrelation that increased at the municipality level from 2000 ( Moran ' s I Index = 0 . 26 , z score = 16 . 91 , p < 0 . 0001 ) to 2010 ( Moran ' s I Index = 0 . 36 , z score = 23 . 78 , p < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "Clusters of high ( Z ( G ) > 1 . 96 ) and low ( Z ( G ) < - 1 . 96 ) prevalence rates of chronic polypharmacy were found and were not influenced by age .", "entity": [], "task": "NER"}
{"text": "Chronic polypharmacy weakly correlated with hospital admission ( 2000 : rho = 0 . 08 , p = 0 . 0032 ; 2005 : rho = 0 . 11 , p < 0 . 0001 ; 2010 : rho = 0 . 18 , p < 0 . 0001 ) , but not with mortality .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : There were geographical differences in the prevalence of older people with chronic polypharmacy that were only partly explained by health indicators .", "entity": [], "task": "NER"}
{"text": "Targeted activities on prescription practice to ensure that the prescribing of chronic polypharmacy is appropriate are required .", "entity": [], "task": "NER"}
{"text": "The effects of gender difference on monocrotaline - induced pulmonary hypertension in rats .", "entity": [{"entity": "monocrotaline", "entity_type": "Chemical", "pos": [36, 49]}], "task": "NER"}
{"text": "The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline ( MCT ) - induced pulmonary hypertension in rat .", "entity": [{"entity": "monocrotaline", "entity_type": "Chemical", "pos": [117, 130]}, {"entity": "MCT", "entity_type": "Chemical", "pos": [133, 136]}], "task": "NER"}
{"text": "The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated .", "entity": [{"entity": "MCT", "entity_type": "Chemical", "pos": [113, 116]}], "task": "NER"}
{"text": "For this purpose , the right ventricular pressures ( RVPs ) and right ventricular / heart weight ( HW ) ratios were compared between groups and the glutathione ( GSH ) level and superoxide dismutase ( SOD ) , catalase ( CAT ) and glutathione - S - transferase ( GST ) activities were determined in lung and liver tissue samples of rats .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [148, 159]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [162, 165]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [178, 188]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [230, 241]}, {"entity": "S", "entity_type": "Chemical", "pos": [244, 245]}], "task": "NER"}
{"text": "RVP and right ventricular / HW ratios significantly increased in the MCT group compared to the control group .", "entity": [{"entity": "MCT", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "In the MCT group , RVP was significantly higher in males than females .", "entity": [{"entity": "MCT", "entity_type": "Chemical", "pos": [7, 10]}], "task": "NER"}
{"text": "MCT - induced pulmonary hypertension resulted in decreased GSH level , decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats .", "entity": [{"entity": "MCT", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [59, 62]}], "task": "NER"}
{"text": "In addition , the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "The results of the present study , that antioxidant enzyme activities were different between the groups , highlight the possible role of oxidative stress in the pathogenesis of MCT - induced pulmonary hypertension in rats .", "entity": [{"entity": "MCT", "entity_type": "Chemical", "pos": [177, 180]}], "task": "NER"}
{"text": "Moreover , the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT - induced pulmonary hypertension in males compared to females .", "entity": [{"entity": "MCT", "entity_type": "Chemical", "pos": [138, 141]}], "task": "NER"}
{"text": "Injection of ropivacaine into the subarachnoid changes the ultrastructure and proteome of the rat spinal cord .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [13, 24]}], "task": "NER"}
{"text": "In the present study , we investigated the impact of 1 . 0 % ropivacaine on the ultrastructure and proteome of the rat spinal cord .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [61, 72]}], "task": "NER"}
{"text": "Rats received three injections ( 90 - min intervals , 0 . 2 mL / kg ) of 0 . 9 % NaCl , 0 . 5 % ropivacaine or 1 . 0 % ropivacaine via an implanted intrathecal catheter .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [81, 85]}, {"entity": "ropivacaine", "entity_type": "Chemical", "pos": [96, 107]}, {"entity": "ropivacaine", "entity_type": "Chemical", "pos": [119, 130]}], "task": "NER"}
{"text": "Transmission electron microscopy was performed to exam the ultrastructure of the spinal cord .", "entity": [], "task": "NER"}
{"text": "Two - dimensional electrophoresis followed by mass spectrometry identification were carried out to investigate the proteome .", "entity": [], "task": "NER"}
{"text": "In the rats administered 1 . 0 % ropivacaine , deformed organelles , detached myelinated nerve fiber layer , and incomplete inner and outer shaft membranes were observed in the spinal cord and posterior root shrunken nuclei .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [33, 44]}], "task": "NER"}
{"text": "Furthermore , in the rat spinal cord 1 . 0 % ropivacaine induced the down - regulation of voltage - dependent anion channel 2 ( VDAC2 ) and mitochondrial pyruvate dehydrogenase subunit alpha ( ODPA ) , the upregulation of myelin basic protein ( MBP ) , the disappearance of myelin transcription factor 1 ( MYT1 ) and the appearance of heat shock protein 25 ( HSP25 ) .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "pyruvate", "entity_type": "Chemical", "pos": [154, 162]}], "task": "NER"}
{"text": "Little change was observed in the 0 . 5 % ropivacaine or control groups .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [42, 53]}], "task": "NER"}
{"text": "Our results suggest that 1 . 0 % ropivacaine treatment led to neurotoxicity , as shown by ultrastructural and proteomic changes in the rat spinal cord .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [33, 44]}], "task": "NER"}
{"text": "Specific proteins were identified that are implicated in 1 . 0 % ropivacaine - induced neurotoxicity .", "entity": [{"entity": "ropivacaine", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "Temperature Dependence and Energetics of Single Ions at the Aqueous Liquid - Vapor Interface .", "entity": [], "task": "NER"}
{"text": "We investigate temperature - dependence of free energetics with two single halide anions , I - and Cl - , crossing the aqueous liquid - vapor interface through molecular dynamics simulations .", "entity": [{"entity": "halide", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "I", "entity_type": "Chemical", "pos": [91, 92]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [99, 101]}], "task": "NER"}
{"text": "The result shows that I - has a modest surface stability of 0 . 5 kcal / mol at 300 K and the stability decreases as the temperature increases , indicating the surface adsorption process for the anion is entropically disfavored .", "entity": [{"entity": "I", "entity_type": "Chemical", "pos": [22, 23]}], "task": "NER"}
{"text": "In contrast , Cl - shows no such surface state at all temperatures .", "entity": [{"entity": "Cl", "entity_type": "Chemical", "pos": [14, 16]}], "task": "NER"}
{"text": "Decomposition of free energetics reveals that water - water interactions provide a favorable enthalpic contribution , while the desolvation of ion induces an increase in free energy .", "entity": [], "task": "NER"}
{"text": "Calculations of surface fluctuations demonstrate that I - generates significantly greater interfacial fluctuations compared to Cl - .", "entity": [{"entity": "I", "entity_type": "Chemical", "pos": [54, 55]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [127, 129]}], "task": "NER"}
{"text": "The fluctuation is attributed to the malleability of the solvation shells , which allows for more long - ranged perturbations and solvent density redistribution induced by I - as the anion approaches the liquid - vapor interface .", "entity": [{"entity": "I", "entity_type": "Chemical", "pos": [172, 173]}], "task": "NER"}
{"text": "The increase in temperature of the solvent enhances the inherent thermally - excited fluctuations and consequently reduces the relative contribution from anion to surface fluctuations , which is consistent with the decrease in surface - stability of I - .", "entity": [{"entity": "I", "entity_type": "Chemical", "pos": [250, 251]}], "task": "NER"}
{"text": "Our results indicate a strong correlation with induced interfacial fluctuations and anion surface stability ; moreover , resulting temperature dependent behavior of induced fluctuations suggests the possibility of a critical level of induced fluctuations associated with surface stability .", "entity": [], "task": "NER"}
{"text": "Molecular Mechanism of the Inhibition of EGCG on the Alzheimer A beta 1 - 42 Dimer .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Growing evidence supports that amyloid beta ( A beta ) oligomers are the major causative agents leading to neural cell death in Alzheimer ' s disease .", "entity": [], "task": "NER"}
{"text": "The polyphenol ( - ) - epigallocatechin gallate ( EGCG ) was recently reported to inhibit A beta fibrillization and redirect A beta aggregation into unstructured , off - pathway oligomers .", "entity": [{"entity": "polyphenol", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "( - ) - epigallocatechin gallate", "entity_type": "Chemical", "pos": [15, 47]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "Given the experimental challenge to characterize the structures of A beta / EGCG complexes , we performed extensive atomistic replica exchange molecular dynamics simulations of A beta 1 - 42 dimer in the present and absence of EGCG in explicit solvent .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [76, 80]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [227, 231]}], "task": "NER"}
{"text": "Our equilibrium A beta dimeric structures free of EGCG are consistent with the collision cross section from ion - mobility mass spectrometry and the secondary structure composition from circular dichroism experiment .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "In the presence of EGCG , the A beta structures are characterized by increased inter - center - of - mass distances , reduced interchain and intrachain contacts , reduced beta - sheet content , and increased coil and alpha - helix contents .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [19, 23]}], "task": "NER"}
{"text": "Analysis of the free energy surfaces reveals that the A beta dimer with EGCG adopts new conformations , affecting therefore its propensity to adopt fibril - prone states .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [72, 76]}], "task": "NER"}
{"text": "Overall , this study provides , for the first time , insights on the equilibrium structures of A beta 1 - 42 dimer in explicit aqueous solution and an atomic picture of the EGCG - mediated conformational change on A beta dimer .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [173, 177]}], "task": "NER"}
{"text": "Lipopolysaccharide Interactions of C - Terminal Peptides from Human Thrombin .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [35, 36]}], "task": "NER"}
{"text": "Interactions with bacterial lipopolysaccharide ( LPS ) , both in aqueous solution and in lipid membranes , were investigated for a series of amphiphilic peptides derived from the C - terminal region of human thrombin , using ellipsometry , dual polarization interferometry , fluorescence spectroscopy , circular dichroism ( CD ) , dynamic light scattering , and z - potential measurements .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [179, 180]}], "task": "NER"}
{"text": "The ability of these peptides to block endotoxic effects caused by LPS , monitored through NO production in macrophages , was compared to peptide binding to LPS and its endotoxic component lipid A , and to size , charge , and secondary structure of peptide / LPS complexes .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [91, 93]}], "task": "NER"}
{"text": "While the antiendotoxic peptide GKY25 ( GKYGFYTHVFRLKKWIQKVIDQFGE ) displayed significant binding to both LPS and lipid A , so did two control peptides with either selected D - amino acid substitutions or with maintained composition but scrambled sequence , both displaying strongly attenuated antiendotoxic effects .", "entity": [{"entity": "D - amino acid", "entity_type": "Chemical", "pos": [173, 187]}], "task": "NER"}
{"text": "Hence , the extent of LPS or lipid A binding is not the sole discriminant for the antiendotoxic effect of these peptides .", "entity": [], "task": "NER"}
{"text": "In contrast , helix formation in peptide / LPS complexes correlates to the antiendotoxic effect of these peptides and is potentially linked to this functionality .", "entity": [], "task": "NER"}
{"text": "Preferential binding to LPS over lipid membrane was furthermore demonstrated for these peptides and preferential binding to the lipid A moiety within LPS inferred .", "entity": [], "task": "NER"}
{"text": "Structural Changes in Cytochrome c Oxidase Induced by Binding of Sodium and Calcium Ions : An ATR - FTIR Study .", "entity": [{"entity": "Sodium", "entity_type": "Chemical", "pos": [65, 71]}, {"entity": "Calcium", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "Attenuated total reflection Fourier transform infrared ( ATR - FTIR ) spectroscopy was used to investigate the binding of Na ( + ) and Ca ( 2 + ) cations to bovine cytochrome c oxidase in its fully oxidized and partially reduced , cyanide - ligated ( a ( 2 + ) a3 ( 3 + ) - CN ) ( mixed valence ) forms .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [122, 130]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [135, 145]}, {"entity": "cyanide", "entity_type": "Chemical", "pos": [231, 238]}, {"entity": "CN", "entity_type": "Chemical", "pos": [274, 276]}], "task": "NER"}
{"text": "These ions induced distinctly different IR binding spectra , indicating that the induced structural changes are different .", "entity": [], "task": "NER"}
{"text": "Despite this , their binding spectra were mutually exclusive , confirming their known competitive binding behavior .", "entity": [], "task": "NER"}
{"text": "Dissociation constants for Na ( + ) and Ca ( 2 + ) with the oxidized enzyme were 1 . 2 mM and 11 mu M , respectively and Na ( + ) binding appeared to involve cooperative binding of two Na ( + ) .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [40, 50]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [121, 129]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [185, 193]}], "task": "NER"}
{"text": "Ca ( 2 + ) binding induced a large IR spectrum , with prominent amide I / II polypeptide changes , bandshifts assigned to carboxylate and an arginine , and a number of bandshifts of heme a .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "amide", "entity_type": "Chemical", "pos": [64, 69]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [122, 133]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [141, 149]}, {"entity": "heme a", "entity_type": "Chemical", "pos": [182, 188]}], "task": "NER"}
{"text": "The Na ( + ) - induced binding spectrum showed much weaker amide I / II and heme a changes but had similar shifts assignable to carboxylate and arginine residues .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "amide", "entity_type": "Chemical", "pos": [59, 64]}, {"entity": "heme a", "entity_type": "Chemical", "pos": [76, 82]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [128, 139]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [144, 152]}], "task": "NER"}
{"text": "Yeast CcO also displayed a calcium - induced IR and UV / visible binding spectra , though of lower intensities .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "This was attributed to the difficulty in fully depleting Ca ( 2 + ) from its binding site , as has been found with bacterial CcOs .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [57, 67]}], "task": "NER"}
{"text": "The implications of Ca ( 2 + ) / Na ( + ) ion binding are discussed in terms of structure and possible modulation of core catalytic function .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [33, 41]}], "task": "NER"}
{"text": "NMDA receptor - dependent function and plasticity in inhibitory circuits .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "NMDA receptors have been known to play a central role in long - term potentiation at glutamatergic synapses in principal cells for thirty years .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "In contrast , their roles in the development and activity - dependent plasticity of synapses in inhibitory circuits have only recently begun to be understood .", "entity": [], "task": "NER"}
{"text": "Progress has , to a great extent , been hampered by the extensive diversity of GABAergic cell types in the CNS .", "entity": [], "task": "NER"}
{"text": "However , anatomical , immunohistochemical and electrophysiological methods have allowed distinct types to be identified , with the result that consistent patterns of synaptic plasticity have begun to emerge .", "entity": [], "task": "NER"}
{"text": "This review summarizes recent evidence on the role of NMDA receptors in the development and plasticity of GABAergic synapses on principal cells and of glutamatergic synapses on identified interneurons .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [54, 58]}], "task": "NER"}
{"text": "A major challenge is to understand how NMDA receptors affect the routing of information in healthy inhibitory circuits , and how changes in NMDA receptor function may contribute to altered circuit function in disorders such as schizophrenia .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [39, 43]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "This article is part of a Special Issue entitled \" Glutamate receptor - dependent synaptic plasticity \" .", "entity": [{"entity": "Glutamate", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "Nanocarrier systems for oral drug delivery : Do we really need them ?", "entity": [], "task": "NER"}
{"text": "In particular since the last two decades there is constantly increasing interest in nanocarrier systems .", "entity": [], "task": "NER"}
{"text": "They are utilized in order to overcome the major challenges being associated with this route of administration - namely poor solubility ( I ) , poor permeability ( II ) and poor GI - stability ( III ) .", "entity": [], "task": "NER"}
{"text": "In order to improve drug solubility nanonization of the API , the use of solid lipid nanoparticles and porous adsorbent particles have shown great potential .", "entity": [], "task": "NER"}
{"text": "Nanocrystals and selfnanoemulsifying drug delivery systems ( SNEDDS ) resulted already in numerous marketed drug products .", "entity": [], "task": "NER"}
{"text": "Moreover , proof - of - principle studies for nanocarrier systems providing enhanced oral drug uptake are available .", "entity": [], "task": "NER"}
{"text": "By providing a comparatively more intimate contact with the absorption membrane , a prolonged GI - residence time and / or exhibiting permeation enhancing properties , oral absorption can be strongly improved .", "entity": [], "task": "NER"}
{"text": "Likely because of safety considerations and because of insufficiently high bioavailability improvements ( < 5 - fold ) , however , a commercial interest in these systems is limited .", "entity": [], "task": "NER"}
{"text": "Poor GI - stability can be overcome by incorporating the drug in nanocarrier systems providing a protective effect towards an enzymatic attack in the GI - tract .", "entity": [], "task": "NER"}
{"text": "Furthermore , as nanocarrier systems can at least to some extent diffuse into the mucus gel layer releasing their payload there , a presystemic metabolism of the drug on the way between the delivery system and the absorption membrane can be excluded .", "entity": [], "task": "NER"}
{"text": "Future trends are mainly focusing on carrier systems capable of not just improving solubility but providing also controlled drug release as well as on nanocarrier systems capable of efficiently permeating the mucus gel layer without destroying it .", "entity": [], "task": "NER"}
{"text": "Amino acids as co - amorphous stabilizers for poorly water soluble drugs - Part 1 : Preparation , stability and dissolution enhancement .", "entity": [{"entity": "Amino acids", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Poor aqueous solubility of an active pharmaceutical ingredient ( API ) is one of the most pressing problems in pharmaceutical research and development because up to 90 % of new API candidates under development are poorly water soluble .", "entity": [], "task": "NER"}
{"text": "These drugs usually have a low and variable oral bioavailability , and therefore an unsatisfactory therapeutic effect .", "entity": [], "task": "NER"}
{"text": "One of the most promising approaches to increase dissolution rate and solubility of these drugs is the conversion of a crystalline form of the drug into its respective amorphous form , usually by incorporation into hydrophilic polymers , forming glass solutions .", "entity": [], "task": "NER"}
{"text": "However , this strategy only led to a small number of marketed products usually because of inadequate physical stability of the drug ( crystallization ) .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated a fundamentally different approach to stabilize the amorphous form of drugs , namely the use of amino acids as small molecular weight excipients that form specific molecular interactions with the drug resulting in co - amorphous forms .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [128, 139]}], "task": "NER"}
{"text": "The two poorly water soluble drugs carbamazepine and indomethacin were combined with amino acids from the binding sites of the biological receptors of these drugs .", "entity": [{"entity": "carbamazepine", "entity_type": "Chemical", "pos": [35, 48]}, {"entity": "indomethacin", "entity_type": "Chemical", "pos": [53, 65]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [85, 96]}], "task": "NER"}
{"text": "Mixtures of drug and the amino acids arginine , phenylalanine , tryptophan and tyrosine were prepared by vibrational ball milling .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "phenylalanine", "entity_type": "Chemical", "pos": [48, 61]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [64, 74]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "Solid - state characterization with X - ray powder diffraction ( XRPD ) and differential scanning calorimetry ( DSC ) revealed that the various blends could be prepared as homogeneous , single phase co - amorphous formulations indicated by the appearance of an amorphous halo in the XRPD diffractograms and a single glass transition temperature ( Tg ) in the DSC measurements .", "entity": [], "task": "NER"}
{"text": "In addition , the Tgs of the co - amorphous mixtures were significantly increased over those of the individual drugs .", "entity": [], "task": "NER"}
{"text": "The drugs remained chemically stable during the milling process and the co - amorphous formulations were generally physically stable over at least 6months at 40 degrees C under dry conditions .", "entity": [], "task": "NER"}
{"text": "The dissolution rate of all co - amorphous drug - amino acid mixtures was significantly increased over that of the respective crystalline and amorphous pure drugs .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [50, 60]}], "task": "NER"}
{"text": "Amino acids thus appear as promising excipients to solve challenges connected with the stability and dissolution of amorphous drugs .", "entity": [{"entity": "Amino acids", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Dysfunctions of the translational machinery in digestive glands of mussels exposed to mercury ions .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [86, 93]}], "task": "NER"}
{"text": "Mercury is an element naturally occurring in the biosphere , but is also released into the environment by human activities , such as mining , smelting , and industrial discharge .", "entity": [{"entity": "Mercury", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Mercury is a biologically harmful element and any exposure of living organisms mainly due to contamination , can cause severe or even lethal side effects .", "entity": [{"entity": "Mercury", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In every form detected , elemental , inorganic , or organic , mercury exhibits toxicity associated with induced oxidative stress .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [62, 69]}], "task": "NER"}
{"text": "Although the genotoxicity of mercury has been well demonstrated in mussels , little is known about its toxic effects on the translational machinery at the molecular level .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "To investigate possible effects , we exposed the common mussel Mytilus galloprovincialis in seawater supplemented by 30 mu g / L Hg ( 2 + ) for 15 days .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [129, 139]}], "task": "NER"}
{"text": "We observed that Hg ( 2 + ) was significantly accumulated in the digestive glands of mussels , reaching a level around 80 mu g / g tissue ( dry weight ) at the 15th day of exposure .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "Exposure of mussels to Hg ( 2 + ) resulted in failure of redox homeostasis , as reflected on lipid peroxidation levels and superoxide dismutase activity in glands , and micronucleus frequency in gills .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [123, 133]}], "task": "NER"}
{"text": "Extracts from digestive glands after 15 - day exposure to Hg ( 2 + ) exhibited decreased tRNA aminoacylation ability and , moreover , a 70 % reduction in the ability of 40S ribosomal subunits to form the 48S initiation ribosomal complex .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "A similar reduction was detected in the ability of ribosomes to translocate peptidyl - tRNA from the A - site to the P - site , an observation coinciding with the notion that regulation of protein synthesis by Hg ( 2 + ) mainly occurs at the initiation and elongation stages of translation .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [210, 220]}], "task": "NER"}
{"text": "A - site binding , peptidyl transferase activity , and termination of peptide chain synthesis underwent less pronounced but measurable reductions , a finding which explains why poly ( Phe ) - synthesis in ribosomes isolated from exposed mussels is reduced by 70 % .", "entity": [{"entity": "poly ( Phe )", "entity_type": "Chemical", "pos": [177, 189]}], "task": "NER"}
{"text": "In conclusion , Hg ( 2 + ) apart from being a genotoxic ion acts as a modulator of protein synthesis in mussels , an observation probably related with its ability to induce oxidative stress .", "entity": [{"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [16, 26]}], "task": "NER"}
{"text": "Analysis of MC - LR and MC - RR in tissue from freshwater fish ( Tinca tinca ) and crayfish ( Procambarus clarkii ) in tench ponds ( C a ceres , Spain ) by liquid chromatography - mass spectrometry ( LC - MS ) .", "entity": [], "task": "NER"}
{"text": "In the present study a new method has been developed and validated for detecting free microcystins ( MCs ) ( MC - RR , MC - LR and MC - YR ) by liquid chromatography - mass spectrometry ( LC - MS ) in the cyprinid Tinca tinca and in the crayfish Procambarus clarkii collected from three ponds in Extremadura ( Spain ) where the presence of the cyanobacteria species Microcystis aeruginosa and Anabaena spiroides has been confirmed .", "entity": [{"entity": "microcystins", "entity_type": "Chemical", "pos": [86, 98]}, {"entity": "MC - RR", "entity_type": "Chemical", "pos": [109, 116]}, {"entity": "MC - LR", "entity_type": "Chemical", "pos": [119, 126]}, {"entity": "MC - YR", "entity_type": "Chemical", "pos": [131, 138]}], "task": "NER"}
{"text": "Once the method had been validated , free MCs were determined in fish ( tench , T . tinca ) and crayfish from different ponds in order to understand how they are bioaccumulated through the food web .", "entity": [], "task": "NER"}
{"text": "MCs were not detected in any of the fish samples analyzed .", "entity": [], "task": "NER"}
{"text": "It was confirmed that P . clarkii accumulated MCs in their tissues without losing their organoleptic characteristics , with MC - LR ( 2 . 3 - 18 . 1 mu g MC - LR / g body weight ) being the predominant MC variant detected in all the crayfish samples .", "entity": [{"entity": "MC - LR", "entity_type": "Chemical", "pos": [124, 131]}, {"entity": "MC - LR", "entity_type": "Chemical", "pos": [154, 161]}], "task": "NER"}
{"text": "MC - RR was measured in 50 % of the samples analyzed , ranging between 1 . 4 and 7 . 8 mu g MC - RR / g body weight and no MC - YR was detected .", "entity": [{"entity": "MC - RR", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "MC - RR", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "MC - YR", "entity_type": "Chemical", "pos": [123, 130]}], "task": "NER"}
{"text": "The results indicated that crayfish can accumulate free MCs in higher quantities than tench that live in ponds contaminated by toxic cyanobacteria species , and emphasized the need for regular monitoring if the health risks associated with their consumption are to be avoided .", "entity": [], "task": "NER"}
{"text": "Lead , mercury , and cadmium in blood and their relation to diet among Swedish adults .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [7, 14]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [21, 28]}], "task": "NER"}
{"text": "The aim of the present study was to examine the body burden of lead ( Pb ) , mercury ( Hg ) , and cadmium ( Cd ) in blood among Swedish adults and the association between blood levels , diet and other lifestyle factors .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [70, 72]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [87, 89]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [98, 105]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [108, 110]}], "task": "NER"}
{"text": "The study was based on a subgroup ( n = 273 ) of the national survey Riksmaten 2010 - 2011 ( 4 - day food records and questionnaire ) .", "entity": [], "task": "NER"}
{"text": "Lead , Hg , and Cd were measured in whole blood , and Cd additionally in urine , by mass or fluorescence spectrometry methods .", "entity": [{"entity": "Hg", "entity_type": "Chemical", "pos": [7, 9]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [16, 18]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [54, 56]}], "task": "NER"}
{"text": "The median values ( 5 - 95th percentiles ) of the metals in blood were as follows ; Pb : 13 . 4 ( 5 . 8 - 28 . 6 ) mu g / L , Hg : 1 . 13 ( 0 . 31 - 3 . 45 ) mu g / L , and Cd : 0 . 19 ( 0 . 09 - 1 . 08 ) mu g / L .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [84, 86]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [126, 128]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [173, 175]}], "task": "NER"}
{"text": "All three metals increased with increasing age .", "entity": [], "task": "NER"}
{"text": "Lead levels in blood were positively associated with intakes of game and alcohol , Hg was related to fish intake , and blood Cd related to smoking and low iron stores and to a low meat intake .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [73, 80]}, {"entity": "Hg", "entity_type": "Chemical", "pos": [83, 85]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [125, 127]}, {"entity": "iron", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "Body burdens of the studied metals were generally below health based reference values , but several individuals had blood Pb levels above the reference point for possible nephrotoxic and developmental neurotoxic effects .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [122, 124]}], "task": "NER"}
{"text": "As health effects cannot be excluded , individuals with high Pb exposure should aim at decreasing their body burden , both from food and from other exposure routes .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [61, 63]}], "task": "NER"}
{"text": "The involvement of heme oxygenase 1 but not nitric oxide synthase 2 in a hepatoprotective action of quercetin in lipopolysaccharide - induced hepatotoxicity of d - galactosamine sensitized rats .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [19, 23]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [44, 56]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [100, 109]}, {"entity": "d - galactosamine", "entity_type": "Chemical", "pos": [160, 177]}], "task": "NER"}
{"text": "The objective of this study was to evaluate potential hepatoprotective capabilities of quercetin in relation to its modulation of the HO - 1 and NOS - 2 activities in an experimental model of fulminant liver failure .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [87, 96]}], "task": "NER"}
{"text": "Liver insult was induced by in vivo administration of d - galactosamine ( d - GalN , 400mg / kg , i . p . ) and lipopolysaccharide ( LPS , 10 mu g / kg , i . p . ) .", "entity": [{"entity": "d - galactosamine", "entity_type": "Chemical", "pos": [54, 71]}, {"entity": "d - GalN", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "The effects of quercetin ( 50mg / kg , i . p ) on d - GalN toxicity was evaluated by standard biochemical , RT - PCR and Western blot methods .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "d - GalN", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "Administration of d - GalN / LPS combination resulted in significantly higher plasma levels of aminotransferases , as well as increased mRNA and protein expressions of both HO - 1 and NOS - 2 enzymes .", "entity": [{"entity": "d - GalN", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "Quercetin exhibited cytoprotective effects on the liver , as evidenced by decreased aminotransferase plasma levels .", "entity": [{"entity": "Quercetin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Additionally , quercetin treatment in d - GalN / LPS treated rats significantly increased HO - 1 mRNA and its protein expressions .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "d - GalN", "entity_type": "Chemical", "pos": [38, 46]}], "task": "NER"}
{"text": "On the contrary , quercetin did not exhibit any significant effects on the levels of nitrites , and NOS - 2 mRNA and protein expressions in d - GalN / LPS treated rats .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [18, 27]}, {"entity": "nitrites", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "d - GalN", "entity_type": "Chemical", "pos": [140, 148]}], "task": "NER"}
{"text": "Quercetin when given alone did not have any significant changes on liver enzymes nor HO - 1 and NOS - 2 mRNA and protein expressions .", "entity": [{"entity": "Quercetin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "It can be concluded that the quercetin ' s induction of HO - 1 and its byproducts , without concomitant NOS - 2 activity reduction , is among mechanisms contributing to the hepatoprotective effect in d - GalN / LPS hepatotoxicity .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "d - GalN", "entity_type": "Chemical", "pos": [200, 208]}], "task": "NER"}
{"text": "Apoptotic and proinflammatory effect of combustion - generated organic nanoparticles in endothelial cells .", "entity": [], "task": "NER"}
{"text": "Air pollution exposure in industrialized cities is associated with an increased risk of morbidity and mortality attributed to cardiovascular diseases .", "entity": [], "task": "NER"}
{"text": "Combustion exhausts emitted from motor vehicles and industries represent a major source of nanoparticles in the atmosphere .", "entity": [], "task": "NER"}
{"text": "Flame - generated organic carbon nanoparticles ( OC NPs ) provide interesting model nanoparticles that simulate fresh combustion emissions near roadways or combustion sources .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [26, 32]}], "task": "NER"}
{"text": "These model nanoparticles can be produced by controlling flame operating conditions and used to test possible toxicological mechanisms responsible for the observed health effects .", "entity": [], "task": "NER"}
{"text": "OC NPs were used to investigate their possible effect on endothelial cells ( EC ) growth and production of proinflammatory lipid mediators .", "entity": [], "task": "NER"}
{"text": "Results indicated a dose and time - dependent reduction in cell viability following incubation of EC with OC NPs for 24 and 48h .", "entity": [], "task": "NER"}
{"text": "Fluorescence - activated cell sorting revealed that EC treated with OC NPs showed a cell proliferation index significantly lower than that of control cells and an increased apoptotic cell death .", "entity": [], "task": "NER"}
{"text": "The annexin assay confirmed the increased apoptotic cell death .", "entity": [], "task": "NER"}
{"text": "Moreover , OC NPs also induced a time - dependent increase of proinflammatory lysophospholipid production .", "entity": [], "task": "NER"}
{"text": "These results , establishing that OC NPs induce EC proinflammatory lysophosholipid production and apoptotic cell death , provide the first evidence of the detrimental effect of OC NPs on EC .", "entity": [], "task": "NER"}
{"text": "Discovery of adamantane based highly potent HDAC inhibitors .", "entity": [{"entity": "adamantane", "entity_type": "Chemical", "pos": [13, 23]}], "task": "NER"}
{"text": "Herein , we report the development of highly potent HDAC inhibitors for the treatment of cancer .", "entity": [], "task": "NER"}
{"text": "A series of adamantane and nor - adamantane based HDAC inhibitors were designed , synthesized and screened for the inhibitory activity of HDAC .", "entity": [{"entity": "adamantane", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "adamantane", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "A number of compounds exhibited GI50 of 10 - 100 nM in human HCT116 , NCI - H460 and U251 cancer cells , in vitro .", "entity": [], "task": "NER"}
{"text": "Compound 32 displays efficacy in human tumour animal xenograft model .", "entity": [], "task": "NER"}
{"text": "EZETIMIBE INCREASES HEPATIC IRON LEVELS IN MICE FED A HIGH - FAT DIET .", "entity": [{"entity": "EZETIMIBE", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "IRON", "entity_type": "Chemical", "pos": [28, 32]}], "task": "NER"}
{"text": "Accumulating evidence suggests that ezetimibe may be a promising agent for treatment of non - alcoholic fatty liver disease and steatohepatitis ( NAFLD / NASH ) .", "entity": [{"entity": "ezetimibe", "entity_type": "Chemical", "pos": [36, 45]}], "task": "NER"}
{"text": "Phlebotomy and dietary iron restriction reduces serum transaminase in NAFLD / NASH patients .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [23, 27]}], "task": "NER"}
{"text": "Recent studies showed that mutual effects exist between lipid metabolism and iron metabolism .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "Accordingly , the effects of ezetimibe on iron metabolism were examined in mice fed a high - fat diet with or without iron .", "entity": [{"entity": "ezetimibe", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "iron", "entity_type": "Chemical", "pos": [42, 46]}, {"entity": "iron", "entity_type": "Chemical", "pos": [118, 122]}], "task": "NER"}
{"text": "C57BL / 6 mice were fed the following diets for 12 weeks .", "entity": [], "task": "NER"}
{"text": "Experiment 1 : 1 ) a control diet ; C 2 ) C plus ezetimibe ( 0 . 3mg / day ; 4 weeks ) ; CE 3 ) a high - fat diet ; H 4 ) H plus ezetimibe ; HE .", "entity": [{"entity": "ezetimibe", "entity_type": "Chemical", "pos": [49, 58]}, {"entity": "ezetimibe", "entity_type": "Chemical", "pos": [129, 138]}], "task": "NER"}
{"text": "Experiment 2 : 1 ) C containing carbonyl iron ( average ; 22 . 4mg / day ; 6 weeks ) ; CI 2 ) CI plus ezetimibe ; CIE 3 ) H containing carbonyl iron ; HI 4 ) HI plus ezetimibe ; HIE .", "entity": [{"entity": "carbonyl iron", "entity_type": "Chemical", "pos": [32, 45]}, {"entity": "ezetimibe", "entity_type": "Chemical", "pos": [102, 111]}, {"entity": "carbonyl iron", "entity_type": "Chemical", "pos": [135, 148]}, {"entity": "ezetimibe", "entity_type": "Chemical", "pos": [166, 175]}], "task": "NER"}
{"text": "Blood , livers , and duodenum were removed after 12 weeks .", "entity": [], "task": "NER"}
{"text": "In Experiment 1 , hepatic iron levels were higher in HE than H , whereas there was no difference between C and CE .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "Hepatic mRNA expression of transferrin receptor 1 and 2 , ferritins , and hepcidin were increased more in CE than C , and in HE than H .", "entity": [], "task": "NER"}
{"text": "In duodenum , DMT1 , ferritinH , and hephaestin mRNA levels were increased in CE compared to C .", "entity": [], "task": "NER"}
{"text": "In Experiment 2 , hepatic iron concentrations were higher in HIE than HI .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "Hepatic mRNA expression of ferritinL and hepcidin were increased in HIE compared to HI .", "entity": [], "task": "NER"}
{"text": "In duodenum , ferritinL mRNA was increased in HIE compared to CIE .", "entity": [], "task": "NER"}
{"text": "Ezetimibe induced hepatic iron uptake transporter expression in mice fed a high - fat diet , causing increased hepatic iron concentrations .", "entity": [{"entity": "Ezetimibe", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "iron", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "iron", "entity_type": "Chemical", "pos": [119, 123]}], "task": "NER"}
{"text": "Astaxanthin Suppresses MPP + - Induced Oxidative Damage in PC12 Cells through a Sp1 / NR1 Signaling Pathway .", "entity": [{"entity": "Astaxanthin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "MPP +", "entity_type": "Chemical", "pos": [23, 28]}], "task": "NER"}
{"text": "Objective : To investigate astaxanthin ( ATX ) neuroprotection , and its mechanism , on a 1 - methyl - 4 - phenyl - pyridine ion ( MPP + ) - induced cell model of Parkinson ' s disease .", "entity": [{"entity": "astaxanthin", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "ATX", "entity_type": "Chemical", "pos": [41, 44]}, {"entity": "1 - methyl - 4 - phenyl - pyridine", "entity_type": "Chemical", "pos": [90, 124]}, {"entity": "MPP +", "entity_type": "Chemical", "pos": [131, 136]}], "task": "NER"}
{"text": "Methods : Mature , differentiated PC12 cells treated with MPP + were used as an in vitro cell model .", "entity": [{"entity": "MPP +", "entity_type": "Chemical", "pos": [58, 63]}], "task": "NER"}
{"text": "The MTT assay was used to investigate cell viability after ATX treatment , and western blot analysis was used to observe Sp1 ( activated transcription factor 1 ) and NR1 ( NMDA receptor subunit 1 ) protein expression , real - time PCR was used to monitor Sp1 and NR1 mRNA , and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1 .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "ATX", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [172, 176]}], "task": "NER"}
{"text": "Results : PC12 cell viability was significantly reduced by MPP + treatment .", "entity": [{"entity": "MPP +", "entity_type": "Chemical", "pos": [59, 64]}], "task": "NER"}
{"text": "The expression of Sp1 and NR1 mRNA and protein were increased compared with the control ( p < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "Following co - treatment with ATX and MPP + , cell viability was significantly increased , and Sp1 and NR1 mRNA and protein were decreased , compared with the MPP + groups ( p < 0 . 01 ) .", "entity": [{"entity": "ATX", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "MPP +", "entity_type": "Chemical", "pos": [38, 43]}, {"entity": "MPP +", "entity_type": "Chemical", "pos": [159, 164]}], "task": "NER"}
{"text": "In addition , mithracycin A protected PC12 cells from oxidative stress caused by MPP + by specifically inhibiting the expression of Sp1 .", "entity": [{"entity": "mithracycin A", "entity_type": "Chemical", "pos": [14, 27]}, {"entity": "MPP +", "entity_type": "Chemical", "pos": [81, 86]}], "task": "NER"}
{"text": "Moreover , cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer .", "entity": [{"entity": "ATX", "entity_type": "Chemical", "pos": [49, 52]}], "task": "NER"}
{"text": "Conclusion : ATX inhibited oxidative stress induced by MPP + in PC12 cells , via the SP1 / NR1 signaling pathway .", "entity": [{"entity": "ATX", "entity_type": "Chemical", "pos": [13, 16]}, {"entity": "MPP +", "entity_type": "Chemical", "pos": [55, 60]}], "task": "NER"}
{"text": "p38 Mitogen Activated Protein Kinase Regulates the Nuclear Receptor CAR to Activate the CYP2B6 Gene .", "entity": [], "task": "NER"}
{"text": "The constitutive active / androstane receptor ( CAR ) regulates hepatic drug metabolism by activating genes such as cytochrome P450 ( CYP ) and certain transferases .", "entity": [{"entity": "androstane", "entity_type": "Chemical", "pos": [26, 36]}], "task": "NER"}
{"text": "p38 mitogen activated protein kinase ( MAPK ) is highly activated in human primary hepatocytes but barely in human hepatoma cell - lines including HepG2 cells .", "entity": [], "task": "NER"}
{"text": "Liganded - CAR induced CYP2B6 mRNA in human primary hepatocytes far more effectively than in HepG2 cells ectopically expressing CAR .", "entity": [], "task": "NER"}
{"text": "Here , we have now found that activation of p38 MAPK by anisomycin potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand - treated human primary hepatocytes .", "entity": [{"entity": "anisomycin", "entity_type": "Chemical", "pos": [56, 66]}], "task": "NER"}
{"text": "siRNA knockdown of p38 MAPK abrogated the ability of anisomycin to synergistically induce CYP2B6 mRNA .", "entity": [{"entity": "anisomycin", "entity_type": "Chemical", "pos": [53, 63]}], "task": "NER"}
{"text": "In addition to CYP2B6 , anisomycin co - treatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not CYP3A4 or UDP - glucuronosyltransferase 1A1 mRNAs .", "entity": [{"entity": "anisomycin", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [119, 122]}], "task": "NER"}
{"text": "Thus , activated p38 MAPK is required for liganded - CAR to selectively activate a set of genes that encode drug metabolizing enzymes .", "entity": [], "task": "NER"}
{"text": "Our present results suggest that CAR - mediated induction of these enzymes can not be understood by ligand binding alone because the specificity and magnitude of induction are co - determined by a given cell signaling such as p38 MAPK ; both physiological and pathophysiological states of cell signaling may have a strong impact in hepatic drug metabolizing capability during therapeutic treatments .", "entity": [], "task": "NER"}
{"text": "Insulin - like Factor 3 promotes wound healing at the ocular surface .", "entity": [], "task": "NER"}
{"text": "Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis .", "entity": [], "task": "NER"}
{"text": "We studied the presence and functional role of insulin - like factor 3 ( INSL3 ) and its cognate receptor RXFP2 at the ocular surface and in tears .", "entity": [], "task": "NER"}
{"text": "Expression of human INSL3 and RXFP2 was determined in tissues of the ocular surface , lacrimal apparatus , in human corneal ( HCE ) , conjunctival ( HCjE ) , sebaceous ( SC ) epithelial cell lines and in human tears by RT - PCR and ELISA .", "entity": [], "task": "NER"}
{"text": "We investigated effects of human recombinant ( hr ) INSL3 on cell proliferation and cell migration and the influence of hrINSL3 on the expression of MMP2 , - 9 , - 13 and TIMP1 and - 2 was quantified by real - time PCR and ELISA in HCE , HCjE and SC cells .", "entity": [], "task": "NER"}
{"text": "We used a C57BL / 6 mouse corneal defect model to elucidate the effect of topical application of hrINSL3 on corneal wound healing .", "entity": [], "task": "NER"}
{"text": "INSL3 and RXFP2 transcripts and INSL3 protein were detected in all tissues and cell lines investigated .", "entity": [], "task": "NER"}
{"text": "Significantly higher concentrations of INSL3 were detected in tears from male vs . female volunteers .", "entity": [], "task": "NER"}
{"text": "Stimulation of HCE , HCjE and SC with hrINSL3 significantly increased cell proliferation in HCjE and SC and migration of HCjE .", "entity": [], "task": "NER"}
{"text": "Treatment with hrINSL3 for 24 h regulated MMP2 , TIMP1 and TIMP2 expression .", "entity": [], "task": "NER"}
{"text": "The local application of hrINSL3 onto denuded corneal surface resulted in significantly accelerated corneal wound healing in mice .", "entity": [], "task": "NER"}
{"text": "These findings suggest a novel and gender specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis and determined a novel role for hrINSL3 in corneal wound healing .", "entity": [], "task": "NER"}
{"text": "Amphetamine , past and present - a pharmacological and clinical perspective .", "entity": [{"entity": "Amphetamine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Amphetamine was discovered over 100 years ago .", "entity": [{"entity": "Amphetamine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Since then , it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder ( ADHD ) and narcolepsy .", "entity": [], "task": "NER"}
{"text": "This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [86, 97]}], "task": "NER"}
{"text": "Amphetamine ' s diverse pharmacological actions translate not only into therapeutic efficacy , but also into the production of adverse events and liability for recreational abuse .", "entity": [{"entity": "Amphetamine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Accordingly , the balance of benefit / risk is the key challenge for its clinical use .", "entity": [], "task": "NER"}
{"text": "The review charts advances in pharmaceutical development from the introduction of once - daily formulations of amphetamine through to lisdexamfetamine , which is the first d - amphetamine prodrug approved for the management of ADHD in children , adolescents and adults .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [111, 122]}, {"entity": "lisdexamfetamine", "entity_type": "Chemical", "pos": [134, 150]}, {"entity": "d - amphetamine", "entity_type": "Chemical", "pos": [172, 187]}], "task": "NER"}
{"text": "The unusual metabolic route for lisdexamfetamine to deliver d - amphetamine makes an important contribution to its pharmacology .", "entity": [{"entity": "lisdexamfetamine", "entity_type": "Chemical", "pos": [32, 48]}, {"entity": "d - amphetamine", "entity_type": "Chemical", "pos": [60, 75]}], "task": "NER"}
{"text": "How lisdexamfetamine ' s distinctive pharmacokinetic / pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed .", "entity": [{"entity": "lisdexamfetamine", "entity_type": "Chemical", "pos": [4, 20]}], "task": "NER"}
{"text": "Strategic use of conformational bias and structure based design to identify potent JAK3 inhibitors with improved selectivity against the JAK family and the kinome .", "entity": [], "task": "NER"}
{"text": "Using a structure based design approach we have identified a series of indazole substituted pyrrolopyrazines , which are potent inhibitors of JAK3 .", "entity": [{"entity": "indazole", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "pyrrolopyrazines", "entity_type": "Chemical", "pos": [92, 108]}], "task": "NER"}
{"text": "Intramolecular electronic repulsion was used as a strategy to induce a strong conformational bias within the ligand .", "entity": [], "task": "NER"}
{"text": "Compounds bearing this conformation participated in a favorable hydrophobic interaction with a cysteine residue in the JAK3 binding pocket , which imparted high selectivity versus the kinome and improved selectivity within the JAK family .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "Copper - catalyzed diastereoselective arylation of tryptophan derivatives : total synthesis of ( + ) - naseseazines a and B .", "entity": [{"entity": "Copper", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [51, 61]}, {"entity": "( + ) - naseseazines a and B", "entity_type": "Chemical", "pos": [95, 123]}], "task": "NER"}
{"text": "A copper - catalyzed arylation of tryptophan derivatives is reported .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [2, 8]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "The reaction proceeds with high site - and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials .", "entity": [{"entity": "aryl pyrroloindoline", "entity_type": "Chemical", "pos": [75, 95]}], "task": "NER"}
{"text": "The utility of this transformation is highlighted in the five - step syntheses of the natural products ( + ) - naseseazine A and B .", "entity": [{"entity": "( + ) - naseseazine A and B", "entity_type": "Chemical", "pos": [103, 130]}], "task": "NER"}
{"text": "Surface Engineering of Ultrafine Cellulose Nanofibrils toward Polymer Nanocomposite Materials .", "entity": [], "task": "NER"}
{"text": "Surface grafting of crystalline and ultrafine cellulose nanofibrils with poly ( ethylene glycol ) ( PEG ) chains via ionic bonds was achieved by a simple ion - exchange treatment .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [73, 97]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [100, 103]}], "task": "NER"}
{"text": "The PEG - grafted cellulose nanofibrils exhibited nanodispersibility in organic solvents such as chloroform , toluene , and tetrahydrofuran .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [4, 7]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "toluene", "entity_type": "Chemical", "pos": [110, 117]}, {"entity": "tetrahydrofuran", "entity_type": "Chemical", "pos": [124, 139]}], "task": "NER"}
{"text": "Then , the PEG - grafted cellulose nanofibril / chloroform dispersion and poly ( l - lactide ) ( PLLA ) / chloroform solution were mixed , and the PEG - grafted cellulose nanofibril / PLLA composite films with various blend ratios were prepared by casting the mixtures on a plate and drying .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [11, 14]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [48, 58]}, {"entity": "poly ( l - lactide )", "entity_type": "Chemical", "pos": [74, 94]}, {"entity": "PLLA", "entity_type": "Chemical", "pos": [97, 101]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [106, 116]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [147, 150]}, {"entity": "PLLA", "entity_type": "Chemical", "pos": [184, 188]}], "task": "NER"}
{"text": "The tensile strength , Young ' s modulus , and work of fracture of the composite films were remarkably improved , despite low cellulose addition levels ( < 1 wt % ) .", "entity": [], "task": "NER"}
{"text": "The highly efficient nanocomposite effect was explained in terms of achievement of nanodispersion states of the PEG - grafted cellulose nanofibrils in the PLLA matrix .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [112, 115]}, {"entity": "PLLA", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "Moreover , some attractive interactions mediated by the PEG chains were likely to be formed between the cellulose nanofibrils and PLLA molecules in the composites , additionally enhancing the efficient nanocomposite effect .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [56, 59]}, {"entity": "PLLA", "entity_type": "Chemical", "pos": [130, 134]}], "task": "NER"}
{"text": "Small Molecule Regulation of Protein Conformation by Binding in the Flap of HIV Protease .", "entity": [], "task": "NER"}
{"text": "The fragment indole - 6 - carboxylic acid ( 1F1 ) , previously identified as a flap site binder in a fragment - based screen against HIV protease ( PR ) , has been cocrystallized with pepstatin - inhibited PR and with apo - PR .", "entity": [{"entity": "indole - 6 - carboxylic acid", "entity_type": "Chemical", "pos": [13, 41]}, {"entity": "pepstatin", "entity_type": "Chemical", "pos": [184, 193]}], "task": "NER"}
{"text": "Another fragment , 3 - indolepropionic acid ( 1F1 - N ) , predicted by AutoDock calculations and confirmed in a novel inhibition of nucleation crystallization assay , exploits the same interactions in the flap site in two crystal structures .", "entity": [{"entity": "3 - indolepropionic acid", "entity_type": "Chemical", "pos": [19, 43]}], "task": "NER"}
{"text": "Both 1F1 and 1F1 - N bind to the closed form of apo - PR and to pepstatin : PR .", "entity": [{"entity": "pepstatin", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "In solution , 1F1 and 1F1 - N raise the Tm of apo - PR by 3 . 5 - 5 degrees C as assayed by differential scanning fluorimetry ( DSF ) and show equivalent low - micromolar binding constants to both apo - PR and pepstatin : PR , assayed by backscattering interferometry ( BSI ) .", "entity": [{"entity": "pepstatin", "entity_type": "Chemical", "pos": [210, 219]}], "task": "NER"}
{"text": "The observed signal intensities in BSI are greater for each fragment upon binding to apo - PR than to pepstatin - bound PR , consistent with greater conformational change in the former binding event .", "entity": [{"entity": "pepstatin", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "Together , these data indicate that fragment binding in the flap site favors a closed conformation of HIV PR .", "entity": [], "task": "NER"}
{"text": "Improving the Catalytic Activity of Semiconductor Nanocrystals through Selective Domain Etching .", "entity": [], "task": "NER"}
{"text": "Colloidal chemistry offers an assortment of synthetic tools for tuning the shape of semiconductor nanocrystals .", "entity": [], "task": "NER"}
{"text": "While many nanocrystal architectures can be obtained directly via colloidal growth , other nanoparticle morphologies require alternative processing strategies .", "entity": [], "task": "NER"}
{"text": "Here , we show that chemical etching of colloidal nanoparticles can facilitate the realization of nanocrystal shapes that are topologically inaccessible by hot - injection techniques alone .", "entity": [], "task": "NER"}
{"text": "The present methodology is demonstrated by synthesizing a two - component CdSe / CdS nanoparticle dimer , constructed in a way that both CdSe and CdS semiconductor domains are exposed to the external environment .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [74, 78]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [137, 141]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [146, 149]}], "task": "NER"}
{"text": "This structural morphology is highly desirable for catalytic applications as it enables both reductive and oxidative reactions to occur simultaneously on dissimilar nanoparticle surfaces .", "entity": [], "task": "NER"}
{"text": "Hydrogen production tests confirmed the improved catalytic activity of CdSe / CdS dimers , which was enhanced 3 - 4 times upon etching treatment .", "entity": [{"entity": "Hydrogen", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [71, 75]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "We expect that the demonstrated application of etching to shaping of colloidal heteronanocrystals can become a common methodology in the synthesis of charge - separating nanocrystals , leading to advanced nanoparticles architectures for applications in areas of photocatalysis , photovoltaics , and light detection .", "entity": [], "task": "NER"}
{"text": "Synergistic effects of diosmetin with erythromycin against ABC transporter over - expressed methicillin - resistant Staphylococcus aureus ( MRSA ) RN4220 / pUL5054 and inhibition of MRSA pyruvate kinase .", "entity": [{"entity": "diosmetin", "entity_type": "Chemical", "pos": [23, 32]}, {"entity": "erythromycin", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "methicillin", "entity_type": "Chemical", "pos": [92, 103]}, {"entity": "pyruvate", "entity_type": "Chemical", "pos": [187, 195]}], "task": "NER"}
{"text": "Increasing prevalence of methicillin - resistant Staphylococcus aureus ( MRSA ) worldwide with limited therapeutic options is a growing public health concern .", "entity": [{"entity": "methicillin", "entity_type": "Chemical", "pos": [25, 36]}], "task": "NER"}
{"text": "Natural products have been shown to possess antibacterial actions against MRSA .", "entity": [], "task": "NER"}
{"text": "Flavonoids from natural products have been shown to possess antibacterial actions against MRSA by antagonizing its resistance mechanisms .", "entity": [{"entity": "Flavonoids", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Diosmin and diosmetin are natural flavonoids found in a variety of citrus fruits .", "entity": [{"entity": "Diosmin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "diosmetin", "entity_type": "Chemical", "pos": [12, 21]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [34, 44]}], "task": "NER"}
{"text": "The aim of this study was to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and the in vitro enzymatic activity of a newly discovered MRSA drug target , pyruvate kinase ( PK ) .", "entity": [{"entity": "diosmin", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "diosmetin", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "pyruvate", "entity_type": "Chemical", "pos": [181, 189]}], "task": "NER"}
{"text": "By using a panel of MRSA strains with known resistant mechanisms , neither diosmin nor diosmetin was shown to possess direct antibacterial activities against all tested MRSA strains .", "entity": [{"entity": "diosmin", "entity_type": "Chemical", "pos": [75, 82]}, {"entity": "diosmetin", "entity_type": "Chemical", "pos": [87, 96]}], "task": "NER"}
{"text": "However , in checkerboard assay , we found that diosmetin together with erythromycin , could synergistically inhibit the growth of ABC - pump overexpressed MRSA - RN4220 / pUL5054 , and time kill assay also showed that the antibacterial activities of diosmetin with erythromycin were bactericidal .", "entity": [{"entity": "diosmetin", "entity_type": "Chemical", "pos": [48, 57]}, {"entity": "erythromycin", "entity_type": "Chemical", "pos": [72, 84]}, {"entity": "diosmetin", "entity_type": "Chemical", "pos": [251, 260]}, {"entity": "erythromycin", "entity_type": "Chemical", "pos": [266, 278]}], "task": "NER"}
{"text": "Diosmetin was further shown to significantly suppress the MRSA PK activities in a dose dependent manner .", "entity": [{"entity": "Diosmetin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "In conclusion , the inhibition of MRSA PK by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux pump which might contribute to the antibacterial actions of diosmetin against MRSA .", "entity": [{"entity": "diosmetin", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [85, 88]}, {"entity": "diosmetin", "entity_type": "Chemical", "pos": [181, 190]}], "task": "NER"}
{"text": "Endothelin - 3 Expression in the Subfornical Organ Enhances the Sensitivity of Nax , the Brain Sodium - Level Sensor , to Suppress Salt Intake .", "entity": [{"entity": "Sodium", "entity_type": "Chemical", "pos": [95, 101]}], "task": "NER"}
{"text": "Salt homeostasis is essential to survival , but brain mechanisms for salt - intake control have not been fully elucidated .", "entity": [], "task": "NER"}
{"text": "Here , we found that the sensitivity of Nax channels to [ Na ( + ) ] o is dose - dependently enhanced by endothelin - 3 ( ET - 3 ) .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [58, 66]}], "task": "NER"}
{"text": "Nax channels began to open when [ Na ( + ) ] o exceeded ~ 150 mM without ET - 3 , but opened fully at a physiological [ Na ( + ) ] o ( 135 - 145 mM ) with 1 nM ET - 3 .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [34, 42]}, {"entity": "Na ( + )", "entity_type": "Chemical", "pos": [120, 128]}], "task": "NER"}
{"text": "Importantly , ET - 3 was expressed in the subfornical organ ( SFO ) along with Nax , and the level was robustly increased by dehydration .", "entity": [], "task": "NER"}
{"text": "Pharmacological experiments revealed that endothelin receptor B ( ETBR ) signaling is involved in this modulation of Nax gating through protein kinase C and ERK1 / 2 activation . ETBR agonists increased the firing rate of GABAergic neurons via lactate in the SFO , and an ETBR antagonist attenuated salt aversion during dehydration .", "entity": [{"entity": "lactate", "entity_type": "Chemical", "pos": [244, 251]}], "task": "NER"}
{"text": "These results indicate that ET - 3 expression in the SFO is tightly coupled with body - fluid homeostasis through modulation of the [ Na ( + ) ] o sensitivity of Nax .", "entity": [{"entity": "Na ( + )", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "Pharmacological study of a new Asp49 phospholipase A2 ( Bbil - TX ) isolated from Bothriopsis bilineata smargadina ( forest viper ) venom in vertebrate neuromuscular preparations .", "entity": [], "task": "NER"}
{"text": "The neuromuscular activity of Bbil - TX , a PLA2 with catalytic activity isolated from Bothriopsis bilineata smargadina venom , was examined in chick biventer cervicis ( BC ) and mouse phrenic nerve - diaphragm ( PND ) preparations .", "entity": [], "task": "NER"}
{"text": "In BC preparations , Bbil - TX ( 0 . 5 - 10 mu g / ml ) caused time - and concentration - dependent blockade that was not reversed by washing ; the times for 50 % blockade were 87 +/- 7 , 41 +/- 7 and 19 +/- 2 min ( mean +/- SEM ; n = 4 - 6 ) for 1 , 5 and 10 mu g / ml , respectively .", "entity": [], "task": "NER"}
{"text": "Muscle contractures to exogenous ACh and KCl were unaffected .", "entity": [{"entity": "ACh", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "KCl", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "The toxin ( 10 mu g / ml ) also did not affect the twitch - tension of directly - stimulated , curarized ( 10 mu g / ml ) BC preparations .", "entity": [], "task": "NER"}
{"text": "However , Bbil - TX ( 10 mu g / ml ) produced mild morphological alterations ( edematous and / or hyperchromic fibers ) in BC ; there was also a progressive release of CK ( from 116 +/- 17 IU / ml ( basal ) to 710 +/- 91 IU / ml after 45 min ) .", "entity": [], "task": "NER"}
{"text": "Bbil - TX ( 5 mu g / ml ) - induced blockade was markedly inhibited at 22 - 24 degrees C and pretreatment with p - bromophenacyl bromide ( p - BPB ) abolished the neuromuscular blockade .", "entity": [{"entity": "p - bromophenacyl bromide", "entity_type": "Chemical", "pos": [111, 136]}, {"entity": "p - BPB", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "Bbil - TX ( 3 - 30 mu g / ml , n = 4 - 6 ) caused partial time - and concentration - dependent blockade in PND preparations ( 52 +/- 2 % at the highest concentration ) .", "entity": [], "task": "NER"}
{"text": "Bbil - TX ( 30 mu g / ml ) also markedly reduced the MEPPs frequency [ from 26 +/- 2 . 5 ( basal ) to 10 +/- 1 after 60 min ; n = 5 ; p < 0 . 05 ] and the quantal content [ from 94 +/- 14 ( basal ) to 24 +/- 3 after 60 min ; n = 5 ; p < 0 . 05 ] of PND preparations , but caused only minor depolarization of the membrane resting potential [ from - 80 +/- 1 mV ( basal ) to - 66 +/- 2 mV after 120 min ; n = 5 ; p < 0 . 05 ] , with no significant change in the depolarizing response to exogenous carbachol .", "entity": [{"entity": "carbachol", "entity_type": "Chemical", "pos": [495, 504]}], "task": "NER"}
{"text": "These results show that Bbil - TX is a presynaptic PLA2 that contributes to the neuromuscular blockade caused by B .", "entity": [], "task": "NER"}
{"text": "b . smargadina venom .", "entity": [], "task": "NER"}
{"text": "Selenium and mercury molar ratios in commercial fish from New Jersey and Illinois : Variation within species and relevance to risk communication .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [13, 20]}], "task": "NER"}
{"text": "There is an emerging consensus that people consuming large amounts of fish with selenium : mercury ratios below 1 are at higher risk from mercury toxicity .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [80, 88]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [91, 98]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [138, 145]}], "task": "NER"}
{"text": "As the relative amount of selenium increases compared to mercury , risk may be lowered , but it is unclear how much excess selenium is required .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [26, 34]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [123, 131]}], "task": "NER"}
{"text": "It would be useful if the selenium : mercury ratio was relatively consistent within a species , but this has not been the case in our studies of wild - caught fish .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [26, 34]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [37, 44]}], "task": "NER"}
{"text": "Since most people in developed countries and urban areas obtain their fish and other seafood commercially , we examined selenium : mercury molar ratios in commercial fish purchased in stores and fish markets in central New Jersey and Chicago .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [120, 128]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [131, 138]}], "task": "NER"}
{"text": "There was substantial interspecific and intraspecific variation in molar ratios .", "entity": [], "task": "NER"}
{"text": "Across species the selenium : mercury molar ratio decreased with increasing mean mercury levels , but selenium variation also contributed to the ratio .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [81, 88]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [102, 110]}], "task": "NER"}
{"text": "Few samples had selenium : mercury molar ratios below 1 , but there was a wide range in ratios , complicating the interpretation for use in risk management and communication .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "Before ratios can be used in risk management , more information is needed on mercury : selenium interactions and mutual bioavailability , and on the relationship between molar ratios and health outcomes .", "entity": [{"entity": "mercury", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Further , people who are selenium deficient may be more at risk from mercury toxicity than others .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "mercury", "entity_type": "Chemical", "pos": [69, 76]}], "task": "NER"}
{"text": "Synthesis and biological evaluation of prodrugs of 2 - fluoro - 2 - deoxyribose - 1 - phosphate and 2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate .", "entity": [{"entity": "2 - fluoro - 2 - deoxyribose - 1 - phosphate", "entity_type": "Chemical", "pos": [51, 95]}, {"entity": "2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate", "entity_type": "Chemical", "pos": [100, 150]}], "task": "NER"}
{"text": "We report in this Letter the synthesis of prodrugs of 2 - fluoro - 2 - deoxyarabinose - 1 - phosphate and 2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate .", "entity": [{"entity": "2 - fluoro - 2 - deoxyarabinose - 1 - phosphate", "entity_type": "Chemical", "pos": [54, 101]}, {"entity": "2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate", "entity_type": "Chemical", "pos": [106, 156]}], "task": "NER"}
{"text": "We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2 - deoxyribose , and we discover that introduction of fluorine atoms on the 2 position of 2 - deoxyribose enables the phosphorylation step : in fact , the stability of the prodrugs increases with the degree of 2 - fluorination .", "entity": [{"entity": "2 - deoxyribose", "entity_type": "Chemical", "pos": [94, 109]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [149, 157]}, {"entity": "2 - deoxyribose", "entity_type": "Chemical", "pos": [185, 200]}], "task": "NER"}
{"text": "Stability studies of produgs of 2 - fluoro - 2 - deoxyribose - 1 - phosphate and 2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate in acidic and neutral conditions were conducted to confirm our observation .", "entity": [{"entity": "2 - fluoro - 2 - deoxyribose - 1 - phosphate", "entity_type": "Chemical", "pos": [32, 76]}, {"entity": "2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate", "entity_type": "Chemical", "pos": [81, 131]}], "task": "NER"}
{"text": "Biological evaluation of prodrugs of 2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate for antiviral and cytotoxic activity is reported .", "entity": [{"entity": "2 , 2 - difluoro - 2 - deoxyribose - 1 - phosphate", "entity_type": "Chemical", "pos": [37, 87]}], "task": "NER"}
{"text": "Oxidation - specific epitopes and immunological responses : Translational biotheranostic implications for atherosclerosis .", "entity": [], "task": "NER"}
{"text": "Oxidation - specific epitopes ( OSE ) , present on oxidized LDL ( OxLDL ) , apoptotic cells , cell debris and modified proteins in the vessel wall , accumulate in response to hypercholesterolemia , and generate potent pro - inflammatory , disease - specific antigens .", "entity": [], "task": "NER"}
{"text": "They represent an important class of ' danger associated molecular patterns ' ( DAMPs ) , against which a concerted innate immune response is directed .", "entity": [], "task": "NER"}
{"text": "OSE are recognized by innate ' pattern recognition receptors ' , such as scavenger receptors present on dendritic cells and monocyte / macrophages , as well as by innate proteins , such as IgM natural antibodies and soluble proteins , such as C - reactive protein and complement factor H .", "entity": [], "task": "NER"}
{"text": "These innate immune responses provide a first line of defense against atherosclerosis - specific DAMPs , and engage adaptive immune responses , provided by T and B - 2 cells , which provide a more specific and definitive response .", "entity": [], "task": "NER"}
{"text": "Such immune responses are ordinarily directed to remove foreign pathogens , such as those found on microbial pathogens , but when persistent or maladaptive , lead to host damage .", "entity": [], "task": "NER"}
{"text": "In this context , atherosclerosis can be considered as a systemic chronic inflammatory disease initiated by the accumulation of OSE type DAMPs and perpetuated by maladaptive response of the innate and adaptive immune system .", "entity": [], "task": "NER"}
{"text": "Understanding this paradigm leads to new approaches to defining cardiovascular risk and suggests new modes of therapy .", "entity": [], "task": "NER"}
{"text": "Therefore , OSE have become potential targets of diagnostic and therapeutic agents .", "entity": [], "task": "NER"}
{"text": "Human and murine OSE - targeting antibodies have been developed and are now being used as biomarkers in human studies and experimentally in translational applications of non - invasive molecular imaging of oxidation - rich plaques and immunotherapeutics .", "entity": [], "task": "NER"}
{"text": "Posttranslational mechanisms modulating the expression of the cytochrome P450 1A1 gene by methylmercury in HepG2 cells : A role of heme oxygenase - 1 .", "entity": [{"entity": "methylmercury", "entity_type": "Chemical", "pos": [90, 103]}, {"entity": "heme", "entity_type": "Chemical", "pos": [131, 135]}], "task": "NER"}
{"text": "Recently we demonstrated the ability of mercuric chloride ( Hg ( 2 + ) ) in human hepatoma HepG2 cells to significantly decrease the TCDD - mediated induction of Cytochrome P450 1A1 ( CYP1A1 ) mRNA , protein , and catalytic activity levels .", "entity": [{"entity": "mercuric chloride", "entity_type": "Chemical", "pos": [40, 57]}, {"entity": "Hg ( 2 + )", "entity_type": "Chemical", "pos": [60, 70]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [133, 137]}], "task": "NER"}
{"text": "In this study we investigated the effect of methylmercury ( MeHg ) on CYP1A1 in HepG2 cells .", "entity": [{"entity": "methylmercury", "entity_type": "Chemical", "pos": [44, 57]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [60, 64]}], "task": "NER"}
{"text": "For this purpose , cells were co - exposed to MeHg and TCDD and the expression of CYP1A1 mRNA , protein , and catalytic activity levels were determined .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [46, 50]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [55, 59]}], "task": "NER"}
{"text": "Our results showed that MeHg did not alter the TCDD - mediated induction of CYP1A1 mRNA , or protein levels ; however it was able to significantly decrease CYP1A1 catalytic activity levels in a concentration - dependent manner .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [24, 28]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [47, 51]}], "task": "NER"}
{"text": "Importantly , this inhibition was specific to CYP1A1and was not radiated to other aryl hydrocarbon receptor ( AhR ) - regulated genes , as MeHg induced NAD ( P ) H : quinone oxidoreductase 1 mRNA and protein levels .", "entity": [{"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [82, 98]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [139, 143]}, {"entity": "NAD ( P ) H", "entity_type": "Chemical", "pos": [152, 163]}, {"entity": "quinone", "entity_type": "Chemical", "pos": [166, 173]}], "task": "NER"}
{"text": "Mechanistically , the inhibitory effect of MeHg on the induction of CYP1A1 coincided with an increase in heme oxygenase - 1 ( HO - 1 ) mRNA levels .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "heme", "entity_type": "Chemical", "pos": [105, 109]}], "task": "NER"}
{"text": "Furthermore , the inhibition of HO - 1 activity , by tin mesoporphyrin , caused a complete restoration of MeHg - mediated inhibition of CYP1A1 activity , induced by TCDD .", "entity": [{"entity": "tin mesoporphyrin", "entity_type": "Chemical", "pos": [53, 70]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [106, 110]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [165, 169]}], "task": "NER"}
{"text": "In addition , transfection of HepG2 cells with siRNA targeting the human HO - 1 gene reversed the MeHg - mediated inhibition of TCDD - induced CYP1A1 .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [98, 102]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [128, 132]}], "task": "NER"}
{"text": "In conclusion , this study demonstrated that MeHg inhibited the TCDD - mediated induction of CYP1A1 through a posttranslational mechanism and confirms the role of HO - 1 in a MeHg - mediated effect .", "entity": [{"entity": "MeHg", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [64, 68]}, {"entity": "MeHg", "entity_type": "Chemical", "pos": [175, 179]}], "task": "NER"}
{"text": "Molecular Basis of SMC ATPase Activation : Role of Internal Structural Changes of the Regulatory Subcomplex ScpAB .", "entity": [], "task": "NER"}
{"text": "In many bacteria , a homodimer of structural - maintenance - of - chromosomes proteins associates with two regulatory subunits ( known as ScpA and ScpB ) , assembling a protein complex that plays a crucial role in chromosome organization and segregation .", "entity": [], "task": "NER"}
{"text": "It remains poorly understood , however , how this complex might work at the mechanistic level .", "entity": [], "task": "NER"}
{"text": "Here , we report crystal structures of the ScpAB core complex that display a highly unusual structure in which the central segment of ScpA winds around an asymmetrically oriented ScpB dimer .", "entity": [], "task": "NER"}
{"text": "The two C - terminal domains of the ScpB dimer primarily interact with different regions of ScpA with different affinities .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [8, 9]}], "task": "NER"}
{"text": "Moreover , flexible interdomain regions of ScpB contribute to a dynamic folding process of the ScpAB subcomplex .", "entity": [], "task": "NER"}
{"text": "Together with other genetic and biochemical assays , we provide evidence that internal structural changes of the ScpAB subcomplex are tightly coupled with activation of the structural - maintenance - of - chromosomes ATPase .", "entity": [], "task": "NER"}
{"text": "Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model .", "entity": [], "task": "NER"}
{"text": "Biodegradable oligo ( poly ( ethylene glycol ) fumarate ) ( OPF ) composite hydrogels have been investigated for the delivery of growth factors ( GFs ) with the aid of gelatin microparticles ( GMPs ) and stem cell populations for osteochondral tissue regeneration .", "entity": [{"entity": "oligo ( poly ( ethylene glycol ) fumarate )", "entity_type": "Chemical", "pos": [14, 57]}, {"entity": "OPF", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "In this study , a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor - beta 3 ( TGF - beta 3 ) with varying release kinetics and / or insulin - like growth factor - 1 ( IGF - 1 ) on osteochondral tissue regeneration in a rabbit full - thickness osteochondral defect model .", "entity": [{"entity": "OPF", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "The four groups investigated included ( i ) a blank control ( no GFs ) , ( ii ) GMP - loaded IGF - 1 alone , ( iii ) GMP - loaded IGF - 1 and gel - loaded TGF - beta 3 , and ( iv ) GMP - loaded IGF - 1 and GMP - loaded TGF - beta 3 in OPF composite hydrogels .", "entity": [{"entity": "OPF", "entity_type": "Chemical", "pos": [235, 238]}], "task": "NER"}
{"text": "The results of an in vitro release study demonstrated that TGF - beta 3 release kinetics could be modulated by the GF incorporation method .", "entity": [], "task": "NER"}
{"text": "At 12weeks post - implantation , the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring .", "entity": [], "task": "NER"}
{"text": "All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control .", "entity": [], "task": "NER"}
{"text": "Single delivery of IGF - 1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF - 1 and TGF - beta 3 , independent of the TGF - beta 3 release kinetics .", "entity": [], "task": "NER"}
{"text": "The results suggest that although the dual delivery of TGF - beta 3 and IGF - 1 may not synergistically enhance the quality of engineered tissue , the delivery of IGF - 1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications .", "entity": [], "task": "NER"}
{"text": "Fishing and knockout of bioactive compounds using a combination of high - speed counter - current chromatography ( HSCCC ) and preparative HPLC for evaluating the holistic efficacy and interaction of the components of Herba Epimedii .", "entity": [], "task": "NER"}
{"text": "Due to the complex chemical compositions and pharmacological effects of traditional Chinese medicines , we developed a strategy based on fishing and knockout of bioactive compounds using a combination of high - speed counter - current chromatography ( HSCCC ) and preparative HPLC for evaluating the holistic activity and interaction of the components of Herba Epimedii .", "entity": [], "task": "NER"}
{"text": "First , osteoblast target cell extraction was used for preliminary screening of the potential bioactive compounds of Herba Epimedii .", "entity": [], "task": "NER"}
{"text": "Second , the bioactive compounds identified ( epimedin A , epimedin B , epimedin C and icariin ) were fished and knocked out using high - speed counter - current chromatography and preparative HPLC .", "entity": [{"entity": "epimedin A", "entity_type": "Chemical", "pos": [46, 56]}, {"entity": "epimedin B", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "epimedin C", "entity_type": "Chemical", "pos": [72, 82]}, {"entity": "icariin", "entity_type": "Chemical", "pos": [87, 94]}], "task": "NER"}
{"text": "Third , the bioactivity of resulting fractions was assessed by determining their influence on cell proliferation and differentiation , thereby allowing for an evaluation of their interaction . The pharmacodynamic contribution ratio of each bioactive compound to the efficacy of the herbal medicine could then be comprehensively and intuitively determined based on the spectra - activity correlations ( VIP values ) of the tested compositions using partial least - squares regression ( PLS - R ) , through which the reliability of the screening and isolation of bioactive compounds by the target cell extraction technique were verified .", "entity": [], "task": "NER"}
{"text": "The proposed strategy is a useful approach with potential application in other traditional Chinese medicines .", "entity": [], "task": "NER"}
{"text": "Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [48, 58]}], "task": "NER"}
{"text": "The neurospecific cholesterol 24 - hydroxylase converts excess brain cholesterol into 24S - hydroxycholesterol ( 24OHC ) which , via the liver X receptor ( LXR ) , can increase the expression and synthesis of astrocyte ApoE .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [69, 80]}, {"entity": "24S - hydroxycholesterol", "entity_type": "Chemical", "pos": [86, 110]}, {"entity": "24OHC", "entity_type": "Chemical", "pos": [113, 118]}], "task": "NER"}
{"text": "24OHC effluxes directly from brain into plasma where it is considered an indicator of brain cholesterol turnover .", "entity": [{"entity": "24OHC", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [92, 103]}], "task": "NER"}
{"text": "It is reduced in neurodegenerative disease states proportionally to the severity of disease and the degree of brain atrophy .", "entity": [], "task": "NER"}
{"text": "In the early phases of active disease , a higher rate of turnover may result in transitory increases in plasma 24OHC .", "entity": [{"entity": "24OHC", "entity_type": "Chemical", "pos": [111, 116]}], "task": "NER"}
{"text": "Less than 1 % of the total brain excretion of 24OHC occurs via the cerebrospinal fluid ( CSF ) whereas almost all 27 - hydroxycholesterol ( 27OHC ) excretion is dependent on the function of the blood - cerebrospinal fluid barrier .", "entity": [{"entity": "24OHC", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "27 - hydroxycholesterol", "entity_type": "Chemical", "pos": [114, 137]}, {"entity": "27OHC", "entity_type": "Chemical", "pos": [140, 145]}], "task": "NER"}
{"text": "Iincreased CSF oxysterols were found in patients with neurodegenerative and neuroinflammatory diseases in the presence of barrier dysfunction .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [15, 25]}], "task": "NER"}
{"text": "In neurodegeneration , free cholesterol released from dying cells may engulf neurons .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "Cholesterol also increases Amyloid beta ( A beta ) deposition and tau pathology .", "entity": [{"entity": "Cholesterol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "ApoE , 24OHC , tau and soluble APP were correlated in Alzheimer disease ( AD ) samples .", "entity": [{"entity": "24OHC", "entity_type": "Chemical", "pos": [7, 12]}], "task": "NER"}
{"text": "Excess of cholesterol converted into 24OHC may up - regulate ApoE synthesis which is a scavenger for A beta and Tau .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [10, 21]}, {"entity": "24OHC", "entity_type": "Chemical", "pos": [37, 42]}], "task": "NER"}
{"text": "In AD this protective mechanism seems to be inefficient , probably due to the presence of high concentrations of 27OHC , microvascular dysfunction and the decreased efficiency of ApoE4 as lipid transporter and A beta scavenger .", "entity": [{"entity": "27OHC", "entity_type": "Chemical", "pos": [113, 118]}], "task": "NER"}
{"text": "24OHC itself was cytotoxic .", "entity": [{"entity": "24OHC", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Analysis of side chain oxysterols in the CSF is likely to provided useful information about cholesterol metabolism and ApoE function in the pathogenesis of AD .", "entity": [{"entity": "oxysterols", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [92, 103]}], "task": "NER"}
{"text": "Anti - inflammatory and antioxidant properties of hydroalcoholic crude extract from Casearia sylvestris Sw .", "entity": [], "task": "NER"}
{"text": "( Salicaceae ) .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Casearia sylvestris Sw .", "entity": [], "task": "NER"}
{"text": "is widely used in popular medicine to treat inflammatory conditions .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : To investigate the anti - inflammatory and antioxidant properties of hydroalcoholic crude extract ( HCE ) taken from Casearia sylvestris Sw .", "entity": [], "task": "NER"}
{"text": "METHODS AND RESULTS : The effect of the HCE from this plant ( 3 - 300mg / kg ) on the reduction of inflammatory response to carrageenan was investigated in pleurisy in rats ( intrapleural , 2 % in 0 . 2mL ) or paw edema in mice ( intraplantar , 300 mu g / 20 mu L , right hind paw ) .", "entity": [], "task": "NER"}
{"text": "The plant anti - inflammatory action was assessed by its capability in inhibiting cell migration , enzymatic activity of myeloperoxidase ( MPO ) and production of nitrite / nitrate or edema .", "entity": [{"entity": "nitrite", "entity_type": "Chemical", "pos": [163, 170]}, {"entity": "nitrate", "entity_type": "Chemical", "pos": [173, 180]}], "task": "NER"}
{"text": "The in vitro antioxidant activity of this extract against lipid peroxidation and damage to proteins was assessed as possible pathways to contribute as anti - inflammatory mechanisms .", "entity": [], "task": "NER"}
{"text": "Carrageenan - induced hind paw edema ( 739 . 3 +/- 11 . 9 mu m ) was reduced by HCE ( 30mg / kg : 462 . 8 +/- 28 . 38 mu m ) to similar extents as dexametasone ( 365 . 1 +/- 16 . 7 ) .", "entity": [{"entity": "dexametasone", "entity_type": "Chemical", "pos": [147, 159]}], "task": "NER"}
{"text": "In pleurisy , treatment of the animals with HCE ( 100mg / kg : 0 . 010 +/- 0 . 001mU / mg of protein ) also reduced MPO activity augmented by carrageenan ( 0 . 020 +/- 0 . 001mU / mg of protein ) as well as leukocytes migration ( carrageenan : 17 . 8890 +/- 2 . 3900leukocytes / mL , HCE 100mg / kg : 7 . 0880 +/- 9631leukocytes / mL ) .", "entity": [], "task": "NER"}
{"text": "Significant effects were also observed in animals treated with different doses of HCE in biochemical tests for oxidative stress analysis .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : The anti - inflammatory and antioxidant effects of HCE from Casearia sylvestris Sw . suggests a potential therapeutic benefit of this plant in treatment of inflammatory conditions .", "entity": [], "task": "NER"}
{"text": "Ethanol extract of Adiantum capillus - veneris L . suppresses the production of inflammatory mediators by inhibiting NF - kappa B activation .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Adiantum capillus - veneris L .", "entity": [], "task": "NER"}
{"text": "is a wildly distributed plant species and has been extensively used in south of China as traditional folk medicine for the treatment of inflammatory diseases .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : To investigate the anti - inflammatory effect of ethanolic extracts of Adiantum capillus - veneris L . and the involvement of NF - kappa B signaling in the regulation of inflammation .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : The plant ethanolic extracts were initially tested against lipopolysaccharide ( LPS ) - induced prostaglandin E2 ( PGE2 ) production in RAW264 . 7 mouse macrophages , and interleukin 6 ( IL - 6 ) and tumor necrosis factor ( TNF ) production in human U937 monocytes .", "entity": [{"entity": "prostaglandin E2", "entity_type": "Chemical", "pos": [120, 136]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [139, 143]}], "task": "NER"}
{"text": "The effect of the plant extracts on the transcription factor nuclear factor kappa B ( NF - kappa B ) pathway was evaluated in TNF - alpha stimulated HepG2 cells by luciferase gene reporter assay and Western blotting at the transcriptional and translational levels .", "entity": [], "task": "NER"}
{"text": "Subsequently , the inhibition of NF - kappa B downstream gene expression ( IL - 8 and ICAM - 1 ) by the plant extracts was assessed via quantitative real time polymerase chain reaction ( qPCR ) .", "entity": [], "task": "NER"}
{"text": "Lastly , the anti - inflammatory activities of the plant extracts in vivo were evaluated by testing spleen index and NF - kappa B related protein expression in LPS - stimulated CD1 mice .", "entity": [], "task": "NER"}
{"text": "RESULTS : The plant ethanolic extracts effectively suppressed PGE2 , IL - 6 and TNF release with an IC50 less than 50 mu g / ml .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "Moreover , luciferase expression could be specifically blocked in HepG2 cells , not in HEK293 cells , showing that the plant extracts displayed a cell - specific pattern on NF - kappa B gene transcription .", "entity": [], "task": "NER"}
{"text": "The assayed biological activity also depended on the order of adding TNF - alpha and the plant extracts because the plant extracts could only block the NF - kappa B activation if added earlier but were unable to stop the signal when added after TNF - alpha .", "entity": [], "task": "NER"}
{"text": "However , the plant extracts did not exert any effect on ubiquitination which regulates several steps in the NF - kappa B pathway .", "entity": [], "task": "NER"}
{"text": "Additionally , the plant extracts down - regulated phosphorylation of IKK alpha / beta at S176 / 180 , p38 at T180 / Y182 and p65 at S536 , but not p65 at S276 .", "entity": [], "task": "NER"}
{"text": "This was confirmed by their ability to selectively abrogate the induction of IL - 8 transcription , whereas the ICAM - 1 gene , which is not transcribed selectively by an NF - kappa B complex containing a form of p65 phosphorylated on Ser536 , did not change .", "entity": [{"entity": "Ser536", "entity_type": "Chemical", "pos": [235, 241]}], "task": "NER"}
{"text": "Finally , the plant extracts at 200 mu g / mg could normalize the LPS - induced elevation of spleen index as well as NF - kappa B and p38 activations in CD1 mice .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : The present studies presents the potential utilization of this plant extracts , as a natural resources for the development of an anti - inflammatory medicine .", "entity": [], "task": "NER"}
{"text": "Neuroprotection by steroids after neurotrauma in organotypic spinal cord cultures : A key role for progesterone receptors and steroidal modulators of GABAA receptors .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [99, 111]}], "task": "NER"}
{"text": "Progesterone is neuroprotective after spinal cord injury , however its mechanism of action remains unexplored .", "entity": [{"entity": "Progesterone", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Here we used organotypic spinal cord slice cultures from 3 weeks - old mice to evaluate the mechanisms of neuroprotection by progesterone and its 5 alpha - reduced metabolites .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [125, 137]}], "task": "NER"}
{"text": "In vitro spinal cord injury , using a weight drop model , induced a decrease in the number of motoneurons .", "entity": [], "task": "NER"}
{"text": "This was correlated with an increase in the number of dying cells ( PI ( + ) cells ) and in LDH release .", "entity": [], "task": "NER"}
{"text": "Addition of 10 mu M of progesterone , 5 alpha - dihydroprogesterone ( 5 alpha - DHP ) or allopregnanolone ( 3 alpha , 5 alpha - tetrahydroprogesterone ) to the medium at the time of injury rescued the spinal cord slices from the effects of damage .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [23, 35]}, {"entity": "5 alpha - dihydroprogesterone", "entity_type": "Chemical", "pos": [38, 67]}, {"entity": "5 alpha - DHP", "entity_type": "Chemical", "pos": [70, 83]}, {"entity": "allopregnanolone", "entity_type": "Chemical", "pos": [89, 105]}, {"entity": "3 alpha , 5 alpha - tetrahydroprogesterone", "entity_type": "Chemical", "pos": [108, 150]}], "task": "NER"}
{"text": "Progesterone prevented membrane cell damage , motoneuron loss and cell death .", "entity": [{"entity": "Progesterone", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "These effects were not due to its bioconversion to 5 alpha - DHP nor to allopregnanolone , as supported by the finasteride , an inhibitor of 5 alpha - reductase enzymes , and by the absence of 5 alpha - reduced progesterone metabolites in the slices analyzed by gas chromatography - mass spectrometry .", "entity": [{"entity": "5 alpha - DHP", "entity_type": "Chemical", "pos": [51, 64]}, {"entity": "allopregnanolone", "entity_type": "Chemical", "pos": [72, 88]}, {"entity": "finasteride", "entity_type": "Chemical", "pos": [111, 122]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [211, 223]}], "task": "NER"}
{"text": "The neuroprotective effects of progesterone required PR as they could not be observed in slices from homozygous knockout PR ( - / - ) mice .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [31, 43]}], "task": "NER"}
{"text": "Allopregnanolone treatment was also neuroprotective .", "entity": [{"entity": "Allopregnanolone", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Its effects were not due to its bioconversion back to 5 alpha - DHP , which can activate gene transcription via PR , because they were still observed in slices from knockout PR ( - / - ) mice .", "entity": [{"entity": "5 alpha - DHP", "entity_type": "Chemical", "pos": [54, 67]}], "task": "NER"}
{"text": "Allopregnanolone effects involved GABAA receptors , as they were inhibited by the selective GABAA receptor antagonist Gabazine , in both PR ( + / + ) and PR ( - / - ) mice .", "entity": [{"entity": "Allopregnanolone", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "Gabazine", "entity_type": "Chemical", "pos": [118, 126]}], "task": "NER"}
{"text": "Altogether , these findings identify both PR and GABAA receptors as important targets for neuroprotection by progestagens after spinal cord injury .", "entity": [{"entity": "progestagens", "entity_type": "Chemical", "pos": [109, 121]}], "task": "NER"}
{"text": "Central functional response to the novel peptide cannabinoid , hemopressin .", "entity": [{"entity": "hemopressin", "entity_type": "Chemical", "pos": [63, 74]}], "task": "NER"}
{"text": "Hemopressin is the first peptide ligand to be described for the CB1 cannabinoid receptor .", "entity": [{"entity": "Hemopressin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Hemopressin acts as an inverse agonist in vivo and can cross the blood - brain barrier to both inhibit appetite and induce antinociception .", "entity": [{"entity": "Hemopressin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Despite being highly effective , synthetic CB1 inverse agonists are limited therapeutically due to unwanted , over dampening of central reward pathways .", "entity": [], "task": "NER"}
{"text": "However , hemopressin appears to have its effect on appetite by affecting satiety rather than reward , suggesting an alternative mode of action which might avoid adverse side effects .", "entity": [{"entity": "hemopressin", "entity_type": "Chemical", "pos": [10, 21]}], "task": "NER"}
{"text": "Here , to resolve the neuronal circuitry mediating hemopressin ' s actions , we have combined blood - oxygen - level - dependent , pharmacological - challenge magnetic resonance imaging with c - Fos functional activity mapping to compare brain regions responsive to systemic administration of hemopressin and the synthetic CB1 inverse agonist , AM251 .", "entity": [{"entity": "hemopressin", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [102, 108]}, {"entity": "hemopressin", "entity_type": "Chemical", "pos": [293, 304]}, {"entity": "AM251", "entity_type": "Chemical", "pos": [345, 350]}], "task": "NER"}
{"text": "Using these complementary methods , we demonstrate that hemopressin activates distinct neuronal substrates within the brain , focused mainly on the feeding - related circuits of the mediobasal hypothalamus and in nociceptive regions of the periaqueductal grey ( PAG ) and dorsal raphe ( DR ) .", "entity": [{"entity": "hemopressin", "entity_type": "Chemical", "pos": [56, 67]}], "task": "NER"}
{"text": "In contrast to AM251 , there is a distinct lack of activation of the brain reward centres , such as the ventral tegmental area , nucleus accumbens and orbitofrontal cortex , which normally form a functional activity signature for the central action of synthetic CB1 receptor inverse agonists .", "entity": [{"entity": "AM251", "entity_type": "Chemical", "pos": [15, 20]}], "task": "NER"}
{"text": "Thus , hemopressin modulates the function of key feeding - related brain nuclei of the mediobasal hypothalamus , and descending pain pathways of the PAG and DR , and not higher limbic structures .", "entity": [{"entity": "hemopressin", "entity_type": "Chemical", "pos": [7, 18]}], "task": "NER"}
{"text": "Thus , hemopressin may offer behaviourally selective effects on nociception and appetite , without engaging reward pathways .", "entity": [{"entity": "hemopressin", "entity_type": "Chemical", "pos": [7, 18]}], "task": "NER"}
{"text": "A novel method for preparing complete antigens of gonyautoxin 2 , 3 and their feature of immunogenicity .", "entity": [{"entity": "gonyautoxin 2 , 3", "entity_type": "Chemical", "pos": [50, 67]}], "task": "NER"}
{"text": "In this paper , a novel method was proposed to prepare artificial antigens of gonyaulax parlaytic shellfish toxin 2 and 3 ( GTX2 , 3 ) .", "entity": [{"entity": "GTX2 , 3", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "An intermediate GTX2 , 3 - aldehyde was first synthesized by activating the NH2 group of the 2nd and 8th amino acid residues with three different aldehydes and two artificial complete antigens GTX2 , 3 - aldehyde - bovine serum albumin ( BSA ) and GTX2 , 3 - aldehyde - keyhole limpet hemocyanin ( KLH ) were then prepared by cross - linking the intermediate with BSA or KLH .", "entity": [{"entity": "GTX2 , 3 - aldehyde", "entity_type": "Chemical", "pos": [16, 35]}, {"entity": "NH2", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [146, 155]}, {"entity": "GTX2 , 3 - aldehyde", "entity_type": "Chemical", "pos": [193, 212]}, {"entity": "GTX2 , 3 - aldehyde", "entity_type": "Chemical", "pos": [248, 267]}], "task": "NER"}
{"text": "The successful preparation of the two complete antigens was confirmed by UV spectral scanning , HPLC , production of antibodies with titer of 1 . 28 x 10 ( 4 ) from mice immunized with the two complete antigens , indirect ELISA and Western - blot .", "entity": [], "task": "NER"}
{"text": "In conclusion , the synthesized complete antigens have strong immunogenicity , which provides a solid foundation for preparing GTX2 , 3 monoclonal antibody and rapid detection kit .", "entity": [{"entity": "GTX2 , 3", "entity_type": "Chemical", "pos": [127, 135]}], "task": "NER"}
{"text": "A GLUE uncertainty analysis of a drying model of pharmaceutical granules .", "entity": [], "task": "NER"}
{"text": "A shift from batch processing towards continuous processing is of interest in the pharmaceutical industry .", "entity": [], "task": "NER"}
{"text": "However , this transition requires detailed knowledge and process understanding of all consecutive unit operations in a continuous manufacturing line to design adequate control strategies .", "entity": [], "task": "NER"}
{"text": "This can be facilitated by developing mechanistic models of the multi - phase systems in the process .", "entity": [], "task": "NER"}
{"text": "Since modelling efforts only started recently in this field , uncertainties about the model predictions are generally neglected .", "entity": [], "task": "NER"}
{"text": "However , model predictions have an inherent uncertainty ( i . e . prediction uncertainty ) originating from uncertainty in input data , model parameters , model structure , boundary conditions and software .", "entity": [], "task": "NER"}
{"text": "In this paper , the model prediction uncertainty is evaluated for a model describing the continuous drying of single pharmaceutical wet granules in a six - segmented fluidized bed drying unit , which is part of the full continuous from - powder - to - tablet manufacturing line ( Consigma (TM) , GEA Pharma Systems ) .", "entity": [], "task": "NER"}
{"text": "A validated model describing the drying behaviour of a single pharmaceutical granule in two consecutive phases is used .", "entity": [], "task": "NER"}
{"text": "First of all , the effect of the assumptions at the particle level on the prediction uncertainty is assessed .", "entity": [], "task": "NER"}
{"text": "Secondly , the paper focuses on the influence of the most sensitive parameters in the model .", "entity": [], "task": "NER"}
{"text": "Finally , a combined analysis ( particle level plus most sensitive parameters ) is performed and discussed .", "entity": [], "task": "NER"}
{"text": "To propagate the uncertainty originating from the parameter uncertainty to the model output , the Generalized Likelihood Uncertainty Estimation ( GLUE ) method is used .", "entity": [], "task": "NER"}
{"text": "This method enables a modeller to incorporate the information obtained from the experimental data in the assessment of the uncertain model predictions and to find a balance between model performance and data precision .", "entity": [], "task": "NER"}
{"text": "A detailed evaluation of the obtained uncertainty analysis results is made with respect to the model structure , interactions between parameters and uncertainty boundaries .", "entity": [], "task": "NER"}
{"text": "Liver X receptors : Emerging therapeutic targets for Alzheimer ' s disease .", "entity": [], "task": "NER"}
{"text": "Alzheimer ' s disease ( AD ) is a complex neurodegenerative disorder , typified by the pathological accumulation of beta - amyloid peptides ( A beta ) and neurofibrillary tangles within the brain , culminating to cognitive impairment .", "entity": [], "task": "NER"}
{"text": "Epidemiological and biochemical data have suggested a link between cholesterol content , APP ( amyloid precursor protein ) processing , A beta , inflammation and AD .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [67, 78]}], "task": "NER"}
{"text": "The intricacy of the disease presents considerable challenges for the development of newer therapeutic agents .", "entity": [], "task": "NER"}
{"text": "Liver X receptors ( LXRa and LXR beta ) are oxysterol activated nuclear receptors that play essential role in lipid and glucose homeostasis , steroidogenesis and inflammatory responses .", "entity": [{"entity": "oxysterol", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [120, 127]}], "task": "NER"}
{"text": "LXR signalling impacts the development of AD pathology through multiple pathways .", "entity": [], "task": "NER"}
{"text": "Reports indicate that genetic loss of either lxra or lxr beta in APP / PS1 transgenic mice results in increased amyloid plaque load .", "entity": [], "task": "NER"}
{"text": "Studies also suggest that ligand activation of LXRs in Tg2576 mice enhanced , the expression of genes linked with cholesterol efflux e . g . apoe , abca - 1 , down regulated APP processing and A beta production with significant improvement in memory functions .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "LXR agonists have also depicted to inhibit neuroinflammation through modulation of microglial phagocytosis and by repressing the expression of cox2 , mcp1 and iNos in glial cells .", "entity": [], "task": "NER"}
{"text": "This review summarizes in brief the biology of LXRs , with an emphasis on their probable pathophysiological mechanisms that may elicit the defending role of these receptors in brains of AD patients .", "entity": [], "task": "NER"}
{"text": "Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues , but its effects on brain bioenergetics are less documented .", "entity": [{"entity": "Cocaine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Furthermore , the combination of cocaine and opioids ( speedball ) was also shown to induce mitochondrial dysfunction .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [33, 40]}], "task": "NER"}
{"text": "In this work , we compared the effects of cocaine and / or morphine on the bioenergetics of isolated brain and liver mitochondria , to understand their specific effects in each tissue .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [42, 49]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "Upon energization with complex I substrates , cocaine decreased state - 3 respiration in brain ( but not in liver ) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues , through a direct effect on complex I .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "Morphine presented only slight effects on brain and liver mitochondria , and the combination cocaine + morphine had similar effects to cocaine alone , except for a greater decrease in state - 3 respiration .", "entity": [{"entity": "Morphine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [93, 100]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [103, 111]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [135, 142]}], "task": "NER"}
{"text": "Brain and liver mitochondrial respirations were differentially affected , and liver mitochondria were more prone to proton leak caused by the drugs or their combination .", "entity": [], "task": "NER"}
{"text": "This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues .", "entity": [], "task": "NER"}
{"text": "In summary , cocaine and cocaine + morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria , with specific effects in each tissue .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "In vitro characterisation of the anti - intravasative properties of the marine product heteronemin .", "entity": [{"entity": "heteronemin", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Metastases destroy the function of infested organs and are the main reason of cancer - related mortality .", "entity": [], "task": "NER"}
{"text": "Heteronemin , a natural product derived from a marine sponge , was tested in vitro regarding its properties to prevent tumour cell intravasation through the lymph - endothelial barrier .", "entity": [{"entity": "Heteronemin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In three - dimensional ( 3D ) cell cultures consisting of MCF - 7 breast cancer cell spheroids that were placed on lymph - endothelial cell ( LEC ) monolayers , tumour cell spheroids induce \" circular chemorepellent - induced defects \" ( CCIDs ) in the LEC monolayer ; 12 ( S ) - Hydroxyeicosatetraenoic acid ( 12 ( S ) - HETE ) and NF - kappa B activity are major factors inducing CCIDs , which are entry gates for tumour emboli intravasating the vasculature .", "entity": [{"entity": "12 ( S ) - Hydroxyeicosatetraenoic acid", "entity_type": "Chemical", "pos": [269, 308]}, {"entity": "12 ( S ) - HETE", "entity_type": "Chemical", "pos": [311, 326]}], "task": "NER"}
{"text": "This 3D co - culture is a validated model for the investigation of intravasation mechanisms and of drugs preventing CCID formation and hence lymph node metastasis .", "entity": [], "task": "NER"}
{"text": "Furthermore , Western blot analyses , NF - kappa B reporter , EROD , SELE , 12 ( S ) - HETE , and adhesion assays were performed to investigate the properties of heteronemin .", "entity": [{"entity": "12 ( S ) - HETE", "entity_type": "Chemical", "pos": [76, 91]}, {"entity": "heteronemin", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "Five micromolar heteronemin inhibited the directional movement of LECs and , therefore , the formation of CCIDs , which were induced by MCF - 7 spheroids .", "entity": [{"entity": "heteronemin", "entity_type": "Chemical", "pos": [16, 27]}], "task": "NER"}
{"text": "Furthermore , heteronemin reduced the adhesion of MCF - 7 cells to LECs and suppressed 12 ( S ) - HETE - induced expression of the EMT marker paxillin , which is a regulator of directional cell migration .", "entity": [{"entity": "heteronemin", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "12 ( S ) - HETE", "entity_type": "Chemical", "pos": [87, 102]}], "task": "NER"}
{"text": "The activity of CYP1A1 , which contributed to CCID formation , was also inhibited by heteronemin .", "entity": [{"entity": "heteronemin", "entity_type": "Chemical", "pos": [85, 96]}], "task": "NER"}
{"text": "Hence , heteronemin inhibits important mechanisms contributing to tumour intravasation in vitro and should be tested in vivo .", "entity": [{"entity": "heteronemin", "entity_type": "Chemical", "pos": [8, 19]}], "task": "NER"}
{"text": "Nicotine - Induced Structural Plasticity in Mesencephalic Dopaminergic Neurons Is Mediated by Dopamine D3 Receptors and Akt - mTORC1 Signalling .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Dopamine", "entity_type": "Chemical", "pos": [58, 66]}], "task": "NER"}
{"text": "Though long - term exposure to nicotine is highly addictive , one \" beneficial \" consequence of chronic tobacco use is a reduced risk for Parkinson ' s disease .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [31, 39]}], "task": "NER"}
{"text": "Interestingly , these effects both reflect structural and functional plasticity of brain circuits controlling reward and motor behavior , and specifically recruitment of nicotinic acetylcholine receptors ( nAChR ) in mesencephalic dopaminergic neurons .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [180, 193]}], "task": "NER"}
{"text": "Since the underlying cellular mechanisms are poorly understood , we addressed this issue employing primary cultures of mouse mesencephalic dopaminergic neurons .", "entity": [], "task": "NER"}
{"text": "Exposure to nicotine ( 1 - 10 mu M ) for 72 hr in vitro increased dendritic arborization and soma size in primary cultures .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [12, 20]}], "task": "NER"}
{"text": "These effects were blocked by mecamylamine and dihydro - beta - erythroidine , but not methyllycaconitine .", "entity": [{"entity": "mecamylamine", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "dihydro - beta - erythroidine", "entity_type": "Chemical", "pos": [47, 76]}, {"entity": "methyllycaconitine", "entity_type": "Chemical", "pos": [87, 105]}], "task": "NER"}
{"text": "The involvement of alpha 4 beta 2 nAChR was supported by the lack of nicotine - induced structural remodeling in neurons from alpha 4 null mutant mice ( KO ) .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "Challenge with nicotine triggered phosphorylation of the extracellular signal - regulated kinase ( ERK ) and the thymoma viral proto - oncogene ( Akt ) followed by activation of the mTORC1 - dependent p70 ribosomal S6 protein kinase .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "Upstream pathway blockade using the phosphatidylinositol 3 - kinase inhibitor LY294002 resulted in suppression of nicotine - induced phosphorylations and structural plasticity .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [36, 56]}, {"entity": "LY294002", "entity_type": "Chemical", "pos": [78, 86]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [114, 122]}], "task": "NER"}
{"text": "These effects were dependent upon functional DA D3 receptor ( D3R ) since nicotine was inactive both in cultures from D3R KO mice and following pharmacologic blockade with D3R antagonist SB - 277011 - A ( 50 nM ) .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [74, 82]}, {"entity": "SB - 277011 - A", "entity_type": "Chemical", "pos": [187, 202]}], "task": "NER"}
{"text": "Finally , exposure to nicotine in utero ( 5 mg / kg / day for 5 days ) resulted in increased soma area of DAergic neurons of newborn mice , effects not observed in D3KO mice .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [22, 30]}], "task": "NER"}
{"text": "These findings indicate that nicotine - induced structural plasticity in mesencephalic dopaminergic neurons involves alpha 4 beta 2 nAChRs together with dopamine D3R - mediated recruitment of ERK / Akt - mTORC1 signaling .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Macroprolactinemia in hyperprolactinemic infertile women .", "entity": [], "task": "NER"}
{"text": "Hyperprolactinemia occurs in 15 - 20 % of women with menstrual disturbances and 30 - 40 % of infertile women and it can adversely affect the fertility .", "entity": [], "task": "NER"}
{"text": "High molecular weight prolactin ( macroprolactin ) has long been known in hyperprolactinemic fertile women .", "entity": [], "task": "NER"}
{"text": "However , the prevalence of macroprolactinemia in hyperprolactinemic infertile women is not known .", "entity": [], "task": "NER"}
{"text": "This cross - sectional study was carried out during the period of June 2010 and June 2011 at a single tertiary care centre .", "entity": [], "task": "NER"}
{"text": "All women who attended the infertility clinic during this period were screened for hyperprolactinemia and only women with hyperprolactinemia and infertility were further studied for the presence of macroprolactin by polyethylene glycol precipitation assay .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [216, 235]}], "task": "NER"}
{"text": "We compared the clinical , hormonal profile and fertility outcome of infertile women with true hyperprolactinemia and macroprolacinemia using appropriate statistical tests .", "entity": [], "task": "NER"}
{"text": "Of 1 , 163 infertile women , 183 ( 15 . 7 % ) had hyperprolactinemia [ 134 ( 73 % ) had primary infertility and 49 ( 27 % ) had secondary infertility ] .", "entity": [], "task": "NER"}
{"text": "Out of these 183 women with hyperprolactinemia , one had microadenoma , 161 had true idiopathic hyperprolactinemia and 21 ( 11 . 5 % ) women had macroprolactinemia .", "entity": [], "task": "NER"}
{"text": "The prevalence of oligomenorrhea and galactorrhea were significantly higher in patients with true hyperprolactinemia than macroprolactinemia ( 46 vs . 14 % , p < 0 . 008 and 30 vs . 5 % , p = 0 . 01 respectively ) .", "entity": [], "task": "NER"}
{"text": "Twenty - two patients ( 13 . 5 % ) of true hyperprolactinemia and two ( 9 % ) in macroprolactinemia became pregnant during the study period .", "entity": [], "task": "NER"}
{"text": "Prolactin measurement should be a part of routine evaluation of couples referred to infertility clinics .", "entity": [], "task": "NER"}
{"text": "Macroprolactin screening is mandatory when clinical features and serum PRL assay results are conflicting .", "entity": [], "task": "NER"}
{"text": "Patients with macroprolactinemia should be investigated for causes of infertility other than hyperprolactinemia .", "entity": [], "task": "NER"}
{"text": "Theoretical Considerations and Practical Approaches to Address the Effect of Anti - drug Antibody ( ADA ) on Quantification of Biotherapeutics in Circulation .", "entity": [], "task": "NER"}
{"text": "Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic ( PK ) and safety studies of biotherapeutics .", "entity": [], "task": "NER"}
{"text": "One area that has been getting increasing attention recently is in the assessment of \" free \" and \" total \" analyte and the impact of the assay format on those assessments .", "entity": [], "task": "NER"}
{"text": "To compliment these considerations , the authors provide a critical review of available literature and prospectively explore methods to mitigate the potential impact of anti - drug antibody on PK assay measurement .", "entity": [], "task": "NER"}
{"text": "This challenge is of particular interest and importance since biotherapeutic drugs often elicit an immune response , and thus may have a direct impact on quantification of the drug for its PK and safety evaluations .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic characterization of CK2 inhibitor CX - 4945 .", "entity": [{"entity": "CX - 4945", "entity_type": "Chemical", "pos": [50, 59]}], "task": "NER"}
{"text": "Over - expression of protein kinase CK2 is highly linked to the survival of cancer cells and the poor prognosis of patients with cancers .", "entity": [], "task": "NER"}
{"text": "CX - 4945 , a potent and selective orally bioavailable ATP - competitive inhibitor of CK2 , inhibits the oncogenic cellular events such as proliferation and angiogenesis , and the increase of tumor growth in mouse xenograft model .", "entity": [{"entity": "CX - 4945", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "In this study , the pharmacokinetic information about CX - 4945 was provided ; at 10 mu M , CX - 4945 with high stability in human and rat liver microsome exhibited low percentage of inhibition ( < 10 % ) in CYP450 isoforms ( 1A2 , 2C19 , 3A4 ) , but considerable inhibition ( ~ 70 % ) in CYP450 2C9 and 2D6 .", "entity": [{"entity": "CX - 4945", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "CX - 4945", "entity_type": "Chemical", "pos": [92, 101]}], "task": "NER"}
{"text": "In hERG potassium channel inhibition assay , CX - 4945 exhibited relatively low inhibition rate .", "entity": [{"entity": "potassium", "entity_type": "Chemical", "pos": [8, 17]}, {"entity": "CX - 4945", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "Additionally , CX - 4945 showed high MDCK cell permeability ( > 10 x 10 ( - 6 ) cm / s ) and above 98 % of plasma protein binding in the rat .", "entity": [{"entity": "CX - 4945", "entity_type": "Chemical", "pos": [15, 24]}], "task": "NER"}
{"text": "After intravenous administration , Vss ( 1 . 39 l / kg ) and extremely low CL ( 0 . 08 l / kg / h ) were observed .", "entity": [], "task": "NER"}
{"text": "Moreover , orally administrated CX - 4945 showed high bioavailability ( > 70 % ) and these data might be related to the MDCK cell permeability results .", "entity": [{"entity": "CX - 4945", "entity_type": "Chemical", "pos": [32, 41]}], "task": "NER"}
{"text": "Novel 4 - substituted - 2 ( 1H ) - phthalazinone derivatives : synthesis , molecular modeling study and their effects on alpha - receptors .", "entity": [{"entity": "4 - substituted - 2 ( 1H ) - phthalazinone", "entity_type": "Chemical", "pos": [6, 48]}], "task": "NER"}
{"text": "Novel 4 - ( 4 - bromophenyl ) phthalazine derivatives connected via an alkyl spacer to amine or N - substituted piperazine were designed and synthesized as promising alpha - adrenoceptor antagonists .", "entity": [{"entity": "4 - ( 4 - bromophenyl ) phthalazine", "entity_type": "Chemical", "pos": [6, 41]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [71, 76]}, {"entity": "amine", "entity_type": "Chemical", "pos": [87, 92]}, {"entity": "N - substituted piperazine", "entity_type": "Chemical", "pos": [96, 122]}], "task": "NER"}
{"text": "The structures of the phthalazine derivatives were established using elemental and spectral analyses .", "entity": [{"entity": "phthalazine", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "Twelve of the tested compounds displayed significant alpha - blocking activity .", "entity": [], "task": "NER"}
{"text": "Molecular modeling studies were performed to rationalize the biological results .", "entity": [], "task": "NER"}
{"text": "Among the tested compounds , 7j displayed the best - fitting score and the highest in vitro activity .", "entity": [], "task": "NER"}
{"text": "Nickel and Cobalt - Catalyzed Coupling of Alkyl Halides with Alkenes via Heck Reactions and Radical Conjugate Addition .", "entity": [{"entity": "Nickel", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "Cobalt", "entity_type": "Chemical", "pos": [11, 17]}, {"entity": "Alkyl Halides", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "Alkenes", "entity_type": "Chemical", "pos": [61, 68]}], "task": "NER"}
{"text": "Cross - coupling of alkyl halides with alkenes leading to Heck - type and addition products is summarized .", "entity": [{"entity": "alkyl halides", "entity_type": "Chemical", "pos": [20, 33]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "The development of Heck reaction with aliphatic halides although has made significant progress in the past decade and particularly recently , it was much less explored in comparison with the aryl halides .", "entity": [{"entity": "aliphatic halides", "entity_type": "Chemical", "pos": [38, 55]}, {"entity": "aryl halides", "entity_type": "Chemical", "pos": [191, 203]}], "task": "NER"}
{"text": "The use of Ni - and Co - catalyzed protocols allowed efficient Heck coupling of activated and unactivated alkenes with 1 ( o ) , 2 ( o ) and 3 ( o ) alkyl halides .", "entity": [{"entity": "Ni", "entity_type": "Chemical", "pos": [11, 13]}, {"entity": "Co", "entity_type": "Chemical", "pos": [20, 22]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [106, 113]}, {"entity": "alkyl halides", "entity_type": "Chemical", "pos": [149, 162]}], "task": "NER"}
{"text": "In addition , radical conjugate addition to activated alkenes has become a well - established method that has led to efficient construction of many natural products .", "entity": [{"entity": "alkenes", "entity_type": "Chemical", "pos": [54, 61]}], "task": "NER"}
{"text": "The utilization of Ni - and Co - catalyzed strategies would avoid toxic tin reagents , and therefore worth exploring .", "entity": [{"entity": "Ni", "entity_type": "Chemical", "pos": [19, 21]}, {"entity": "Co", "entity_type": "Chemical", "pos": [28, 30]}], "task": "NER"}
{"text": "The recent development of Ni - and Co - catalyzed addition of alkyl halides to alkenes displays much improved reactivity and functional group tolerance .", "entity": [{"entity": "Ni", "entity_type": "Chemical", "pos": [26, 28]}, {"entity": "Co", "entity_type": "Chemical", "pos": [35, 37]}, {"entity": "alkyl halides", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "In this mini - review , we also attempt to overview the mechanisms that are proposed in the reactions , aiming at providing insight into the nickel and cobalt - catalyzed coupling of alkyl halides with alkenes .", "entity": [{"entity": "nickel", "entity_type": "Chemical", "pos": [141, 147]}, {"entity": "cobalt", "entity_type": "Chemical", "pos": [152, 158]}, {"entity": "alkyl halides", "entity_type": "Chemical", "pos": [183, 196]}, {"entity": "alkenes", "entity_type": "Chemical", "pos": [202, 209]}], "task": "NER"}
{"text": "Pyrazolines : a biological review .", "entity": [{"entity": "Pyrazolines", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Pyrazoline is an important five membered nitrogen heterocycle , which has been extensively researched upon .", "entity": [{"entity": "Pyrazoline", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [41, 49]}], "task": "NER"}
{"text": "The ring is quite stable and has inspired chemists to carry out various structural variations in the ring .", "entity": [], "task": "NER"}
{"text": "This has propelled the development of distinct pyrazolines with an array of pharmacological activities viz . anti - inflammatory , analgesic , antimicrobial , anticancer , antidepressant etc .", "entity": [{"entity": "pyrazolines", "entity_type": "Chemical", "pos": [47, 58]}], "task": "NER"}
{"text": "The review aims at highlighting this pharmacological diversity of pyrazolines .", "entity": [{"entity": "pyrazolines", "entity_type": "Chemical", "pos": [66, 77]}], "task": "NER"}
{"text": "The review is a gist of latest work done describing the pharmacological aspects and potential of pyrazoline ring .", "entity": [{"entity": "pyrazoline", "entity_type": "Chemical", "pos": [97, 107]}], "task": "NER"}
{"text": "Nanoscale Imaging of Neutral Atoms with a Pulsed Magnetic Lens .", "entity": [], "task": "NER"}
{"text": "We present a scheme for imaging of neutral atoms to the nanoscale with a pulsed magnetic lens and show its viability through numerical calculations .", "entity": [], "task": "NER"}
{"text": "This scheme achieves focal lengths on the order of several centimeters and focal spots of less than 10 nm .", "entity": [], "task": "NER"}
{"text": "With these results , it is possible to create sub - 10 nm structures on surfaces in a parallel and time - efficient manner .", "entity": [], "task": "NER"}
{"text": "When used with metastable noble gas atoms , and in combination with electron spectroscopy , this scheme can create a chemically sensitive microscope which can probe surfaces on the nanometer scale .", "entity": [], "task": "NER"}
{"text": "In Vitro Fertilization outcomes in treated hypothyroidism .", "entity": [], "task": "NER"}
{"text": "Background : Levothyroxine has been shown to enhance pregnancy outcomes in women with hypothyroidism requiring In Vitro Fertilization ( IVF ) .", "entity": [{"entity": "Levothyroxine", "entity_type": "Chemical", "pos": [13, 26]}], "task": "NER"}
{"text": "However , the precise magnitude of these benefits remains to be determined .", "entity": [], "task": "NER"}
{"text": "In particular , it has yet to be clarified whether levothyroxine may fully overcome the detrimental effects of hypothyroidism or , conversely , whether affected women remain at reduced prognosis for pregnancy outcomes .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [51, 64]}], "task": "NER"}
{"text": "Methods : Patients who underwent IVF - ICSI ( IVF - intracytoplasmic sperm injection ) over a three - year period were reviewed .", "entity": [], "task": "NER"}
{"text": "Cases were deemed eligible if they were diagnosed with clinical or subclinical hypothyroidism and were receiving levothyroxine .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [113, 126]}], "task": "NER"}
{"text": "Controls were two subsequently age - matched euthyroid women for every case .", "entity": [], "task": "NER"}
{"text": "Both cases and controls were selected only if serum TSH was <= 2 . 5 mIU / L .", "entity": [], "task": "NER"}
{"text": "Results : One hundred thirty - seven women with treated hypothyroidism and 274 controls were included .", "entity": [], "task": "NER"}
{"text": "Baseline characteristics of the two study groups were similar with the exception of BMI , which was slightly higher among the cases ( 22 . 9 +/- 3 . 9 versus 21 . 9 +/- 3 . 3 Kg / m2 , p = 0 . 013 ) .", "entity": [], "task": "NER"}
{"text": "Most IVF - ICSI cycle outcome variables were also similar with the exception of a higher rate of cancellation for poor response ( 3 . 6 % versus 0 . 7 % , p = 0 . 04 ) , a longer duration of stimulation ( 10 . 9 +/- 2 . 2 versus 10 . 1 +/- 2 . 0 days , p = 0 . 001 ) , a higher proportion of women failing to obtain viable embryos ( 17 % versus 7 % , p = 0 . 006 ) , and a lower fertilization rate ( 75 % versus 86 % , p = 0 . 017 ) among cases .", "entity": [], "task": "NER"}
{"text": "Conversely , the clinical pregnancy rate per started cycle , the implantation rate and the live birth rate per started cycle did not differ ; they were 36 % and 34 % ( p = 0 . 93 ) , 28 % and 22 % ( p = 0 . 11 ) and 30 % and 27 % ( p = 0 . 50 ) in cases and controls , respectively .", "entity": [], "task": "NER"}
{"text": "Subgroup analyses comparing women with ( n = 79 ) and without ( n = 58 ) thyroid autoimmunity and comparing women who were diagnosed with overt hypothyroidism ( n = 70 ) or subclinical hypothyroidism ( n = 67 ) failed to identify relevant differences .", "entity": [], "task": "NER"}
{"text": "Conclusions : In our population , IVF - ICSI outcome was not significantly hampered in women with adequately treated hypothyroidism .", "entity": [], "task": "NER"}
{"text": "The magnitude of the detected differences in cycle outcome was mild and we failed to document any differences for the most relevant outcomes , i . e . pregnancy rate , implantation rate and delivery rate .", "entity": [], "task": "NER"}
{"text": "In conclusion , adequate levothyroxine treatment maintaining TSH serum levels below 2 . 5 mIU / L may overcome the detrimental effects of hypothyroidism .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [25, 38]}], "task": "NER"}
{"text": "Chronic dietary exposure to chlorpyrifos causes behavioral impairments , low activity of brain membrane - bound acetylcholinesterase , and increased brain acetylcholinesterase - R mRNA .", "entity": [{"entity": "chlorpyrifos", "entity_type": "Chemical", "pos": [28, 40]}], "task": "NER"}
{"text": "Chlorpyrifos ( CPF ) is an organophosphate ( OP ) insecticide that is metabolically activated to the highly toxic chlorpyrifos oxon .", "entity": [{"entity": "Chlorpyrifos", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "CPF", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "organophosphate", "entity_type": "Chemical", "pos": [27, 42]}, {"entity": "chlorpyrifos oxon", "entity_type": "Chemical", "pos": [114, 131]}], "task": "NER"}
{"text": "Dietary exposure is the main route of intoxication for non - occupational exposures .", "entity": [], "task": "NER"}
{"text": "However , only limited behavioral effects of chronic dietary exposure have been investigated .", "entity": [], "task": "NER"}
{"text": "Therefore , male Wistar rats were fed a dose of 5mg / kg / day of CPF for thirty - one weeks .", "entity": [{"entity": "CPF", "entity_type": "Chemical", "pos": [66, 69]}], "task": "NER"}
{"text": "Animals were evaluated in spatial learning and impulsivity tasks after 21 weeks of CPF dietary exposure and one week after exposure ended , respectively .", "entity": [{"entity": "CPF", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "In addition , the degree of inhibition of brain acetylcholinesterase ( AChE ) was evaluated for both the soluble and particulate forms of the enzyme , as well as AChE gene expression .", "entity": [], "task": "NER"}
{"text": "Also , brain acylpeptide hydrolase ( APH ) was investigated as an alternative target for OP - mediated effects .", "entity": [], "task": "NER"}
{"text": "All variables were evaluated at various time points in response to CPF diet and after exposure ended .", "entity": [{"entity": "CPF", "entity_type": "Chemical", "pos": [67, 70]}], "task": "NER"}
{"text": "Results from behavioral procedures suggest cognitive and emotional disorders .", "entity": [], "task": "NER"}
{"text": "Moreover , low levels of activity representing membrane - bound oligomeric forms ( tetramers ) were also observed .", "entity": [], "task": "NER"}
{"text": "In addition , increased brain AChE - R mRNA levels were detected after four weeks of CPF dietary exposure .", "entity": [{"entity": "CPF", "entity_type": "Chemical", "pos": [85, 88]}], "task": "NER"}
{"text": "However , no changes in levels of brain APH were observed among groups .", "entity": [], "task": "NER"}
{"text": "In conclusion , our data point to a relationship between cognitive impairments and changes in AChE forms , specifically to a high inhibition of the particulate form and a modification of alternative splicing of mRNA during CPF dietary exposure .", "entity": [{"entity": "CPF", "entity_type": "Chemical", "pos": [223, 226]}], "task": "NER"}
{"text": "In vitro intestinal and hepatic metabolism of Di ( 2 - ethylhexyl ) phthalate ( DEHP ) in human and rat .", "entity": [{"entity": "Di ( 2 - ethylhexyl ) phthalate", "entity_type": "Chemical", "pos": [46, 77]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "Species and organ differences in the intrinsic clearance and the enzymes involved in the metabolism of DEHP were examined in subcellular fractions of the intestine and liver as well as by recombinant cytochrome P450 ( CYP ) isoforms of human and rat .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "Estimated clearance ( CLint ) of DEHP via esterase - mediated pathway in human intestine was 2 . 4 - fold greater than that in human liver while its value in rat intestine was 1 . 7 - fold less than that in rat liver .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "Ranks of CLint for CYP - mediated oxidation / dealkylation of MEHP were human liver > rat liver > human intestine > rat intestine .", "entity": [{"entity": "MEHP", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "Estimates of CLint for the production of mono ( 2 - ethyl - 5 - hydroxyhexyl ) phthalate and mono ( 2 - ethyl - 5 - oxohexyl ) phthalate by human CYP2C9 ( * ) 1 were 4 . 2 - and 2 . 6 - fold greater than those by rat CYP2C6 , respectively .", "entity": [{"entity": "mono ( 2 - ethyl - 5 - hydroxyhexyl ) phthalate", "entity_type": "Chemical", "pos": [41, 88]}, {"entity": "mono ( 2 - ethyl - 5 - oxohexyl ) phthalate", "entity_type": "Chemical", "pos": [93, 136]}], "task": "NER"}
{"text": "Total CLint via hCYP2C9 ( * ) 3 - mediated oxidation was 1 . 9 - and 2 . 6 - fold less than those by hCYP2C9 ( * ) 2 and 2C9 ( * ) 1 , respectively .", "entity": [], "task": "NER"}
{"text": "Estimated CLint for phthalic acid production by hCYP3A4 was 24 . 5 mu LnmolCYP ( - 1 ) min ( - 1 ) while it was continuously produced by rCYP2C6 and 3A2 via passive mechanism .", "entity": [{"entity": "phthalic acid", "entity_type": "Chemical", "pos": [20, 33]}], "task": "NER"}
{"text": "These species / organ differences in major metabolic pathway and CYP isoforms should be considered for appraisal of the potential adverse health effects of DEHP .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [156, 160]}], "task": "NER"}
{"text": "Electroactive nanoparticle directed assembly of functionalized graphene nanosheets into hierarchical structures with hybrid compositions for flexible supercapacitors .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "Hierarchical structures of hybrid materials with the controlled compositions have been shown to offer a breakthrough for energy storage and conversion .", "entity": [], "task": "NER"}
{"text": "Here , we report the integrative assembly of chemically modified graphene ( CMG ) building blocks into hierarchical complex structures with the hybrid composition for high performance flexible pseudocapacitors .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "The formation mechanism of hierarchical CMG / Nafion / RuO2 ( CMGNR ) microspheres , which is triggered by the cooperative interplay during the in situ synthesis of RuO2 nanoparticles ( NPs ) , was extensively investigated .", "entity": [{"entity": "Nafion", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "RuO2", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "RuO2", "entity_type": "Chemical", "pos": [165, 169]}], "task": "NER"}
{"text": "In particular , the hierarchical CMGNR microspheres consisting of the aggregates of CMG / Nafion ( CMGN ) nanosheets and RuO2 NPs provided large surface area and facile ion accessibility to storage sites , while the interconnected nanosheets offered continuous electron pathways and mechanical integrity .", "entity": [{"entity": "Nafion", "entity_type": "Chemical", "pos": [90, 96]}, {"entity": "RuO2", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "The synergistic effect of CMGNR hybrids on the supercapacitor ( SC ) performance was derived from the hybrid composition of pseudocapacitive RuO2 NPs with the conductive CMGNs as well as from structural features .", "entity": [{"entity": "RuO2", "entity_type": "Chemical", "pos": [141, 145]}], "task": "NER"}
{"text": "Consequently , the CMGNR - SCs showed a specific capacitance as high as 160 F g ( - 1 ) , three - fold higher than that of conventional graphene SCs , and a capacitance retention of > 95 % of the maximum value even after severe bending and 1000 charge - discharge tests due to the structural and compositional features .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Beneficial influence of topical extra virgin olive oil application on an experimental model of penile fracture in rats .", "entity": [], "task": "NER"}
{"text": "Penile fracture ( PF ) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum .", "entity": [], "task": "NER"}
{"text": "In this study , we aimed to investigate the healing influence of topical extra virgin olive oil ( EVOO ) on PF through evaluating levels of some oxidative stress biomarkers for the first time .", "entity": [], "task": "NER"}
{"text": "Histopathological evaluation was also realized .", "entity": [], "task": "NER"}
{"text": "A total of 18 male Sprague - Dawley albino rats were divided into three groups of six rats each as control group , in PF ( alone ) group , and PF + EVOO group .", "entity": [], "task": "NER"}
{"text": "Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control .", "entity": [], "task": "NER"}
{"text": "While in PF ( alone ) group , fracture was formed and the incision was primarily closed , in PF + EVOO group in addition to foregoing processes , EVOO was also administrated topically twice a day for 3 weeks .", "entity": [], "task": "NER"}
{"text": "At the end of the experiment , all rats were killed and penectomy was carried out .", "entity": [], "task": "NER"}
{"text": "While malondialdehyde , myeloperoxidase , lipid hyroperoxide , and total oxidant status significantly ( p < 0 . 05 ) increased , reduced glutathione and total free sulfhydryl groups markedly ( p < 0 . 05 ) decreased in PF ( alone ) group when compared with PF + EVOO group .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [6, 21]}, {"entity": "hyroperoxide", "entity_type": "Chemical", "pos": [48, 60]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [137, 148]}, {"entity": "sulfhydryl", "entity_type": "Chemical", "pos": [164, 174]}], "task": "NER"}
{"text": "Levels of these parameters were reversed to nearly normal values by topical EVOO application .", "entity": [], "task": "NER"}
{"text": "Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF ( alone ) group .", "entity": [], "task": "NER"}
{"text": "Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant , free radical defusing , anti - inflammatory , and antimicrobial effects .", "entity": [], "task": "NER"}
{"text": "Design , Synthesis and Antiviral Activity of 2 - ( 3 - Amino - 4 - piperazinylphenyl ) chromone Derivatives .", "entity": [{"entity": "2 - ( 3 - Amino - 4 - piperazinylphenyl ) chromone", "entity_type": "Chemical", "pos": [45, 95]}], "task": "NER"}
{"text": "Previously , we have confirmed that the antiviral activities of the chromone derivatives were controlled by the type as well as the position of the substituents attached to the chromone core structure .", "entity": [{"entity": "chromone", "entity_type": "Chemical", "pos": [68, 76]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "In the course of our ongoing efforts to optimize the antiviral activity of the chromone derivatives , we have been attempting to derivatize the chromone scaffold via introduction of various substituents .", "entity": [{"entity": "chromone", "entity_type": "Chemical", "pos": [79, 87]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [144, 152]}], "task": "NER"}
{"text": "In this proof - of - concept study , we introduced a 3 - amino - 4 - piperazinylphenyl functionality to the chromone scaffold and evaluated the antiviral activities of the resulting chromone derivatives .", "entity": [{"entity": "3 - amino - 4 - piperazinylphenyl", "entity_type": "Chemical", "pos": [53, 86]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [108, 116]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [182, 190]}], "task": "NER"}
{"text": "The synthesized 2 - ( 3 - amino - 4 - piperazinylphenyl ) - chromones showed severe acute respiratory syndrome - corona virus ( SARS - CoV ) - specific antiviral activity .", "entity": [{"entity": "2 - ( 3 - amino - 4 - piperazinylphenyl ) - chromones", "entity_type": "Chemical", "pos": [16, 69]}], "task": "NER"}
{"text": "In particular , the 2 - pyridinylpiperazinylphenyl substituents provided the resulting chromone derivatives with selective antiviral activity .", "entity": [{"entity": "2 - pyridinylpiperazinylphenyl", "entity_type": "Chemical", "pos": [20, 50]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Taken together , this result indicates the possible pharmacophoric role of the 2 - pyridinylpiperazine functionality attached to the chromone scaffold , which warrants further in - depth structure - activity relationship study .", "entity": [{"entity": "2 - pyridinylpiperazine", "entity_type": "Chemical", "pos": [79, 102]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [133, 141]}], "task": "NER"}
{"text": "Randomly amplified polymorphic - DNA analysis for detecting genotoxic effects of Boron on maize ( Zea mays L . ) .", "entity": [{"entity": "Boron", "entity_type": "Chemical", "pos": [81, 86]}], "task": "NER"}
{"text": "This study was carried out to investigate the genotoxic effect of boron ( B ) on maize using randomly amplified polymorphic DNA ( RAPD ) method .", "entity": [{"entity": "boron", "entity_type": "Chemical", "pos": [66, 71]}, {"entity": "B", "entity_type": "Chemical", "pos": [74, 75]}], "task": "NER"}
{"text": "Experimental design was conducted under 0 , 5 , 10 , 25 , 50 , 100 , 125 , and 150 ppm B exposures , and physiological changes have revealed a sharp decrease in root growth rates from 28 % to 85 % , starting from 25 ppm to 150 ppm , respectively .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [87, 88]}], "task": "NER"}
{"text": "RAPD - polymerase chain reaction ( PCR ) analysis shows that DNA alterations are clearly observed from beginning to 100 ppm .", "entity": [], "task": "NER"}
{"text": "B - induced inhibition in root growth had a positive correlation with DNA alterations .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "Total soluble protein , root and stem lengths , and B content analysis in root and leaves encourage these results as a consequence .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [52, 53]}], "task": "NER"}
{"text": "These preliminary findings reveal that B causes chromosomal aberration and genotoxic effects on maize .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [39, 40]}], "task": "NER"}
{"text": "Meanwhile , usage of RAPD - PCR technique is a suitable biomarker to detect genotoxic effect of B on maize and other crops for the future .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [96, 97]}], "task": "NER"}
{"text": "PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary bladder of female rat .", "entity": [], "task": "NER"}
{"text": "Acute bladder distension causes various morphological and functional changes , in part through altered gene expression .", "entity": [], "task": "NER"}
{"text": "We aimed to investigate the physiological role of PTHrP , which is upregulated in an acute bladder distension model in female rats .", "entity": [], "task": "NER"}
{"text": "In the control Empty group , bladders were kept empty for 6 h , and in the Distension group , bladders were kept distended for 3 h after an artificial storing - voiding cycle for 3 h .", "entity": [], "task": "NER"}
{"text": "In the Distention group bladder , upregulation of transcripts was noted for three genes reported to be upregulated by stretch in the cultured bladder smooth muscle cells ( BSMC ) in vitro .", "entity": [], "task": "NER"}
{"text": "Further transcriptome analysis by microarray identified PTHrP as the 2second highest gene upregulated in Distension group bladder , among more than 27 , 000 genes .", "entity": [], "task": "NER"}
{"text": "Localization of PTHrP and its functional receptor , PTH / PTHrP receptor 1 ( PTH1R ) , were analyzed in the untreated rat bladders and cultured bladder cells using real - time RT - PCR and immunoblotting , which revealed that PTH1R and PTHrP were more predominantly expressed in smooth muscle than in urothelium .", "entity": [], "task": "NER"}
{"text": "Exogenous PTHrP peptide ( 1 - 34 ) increased intracellular cAMP level in cultured BSMC .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [59, 63]}], "task": "NER"}
{"text": "In organ bath study using bladder strips , the PTHrP peptide caused a marked reduction in the amplitude of spontaneous contraction , but caused only modest suppression for carbachol - induced contraction .", "entity": [{"entity": "carbachol", "entity_type": "Chemical", "pos": [172, 181]}], "task": "NER"}
{"text": "In in vivo functional study by cystometrogram , the PTHrP peptide decreased voiding pressure and increased bladder compliance .", "entity": [], "task": "NER"}
{"text": "Thus , PTHrP is a potent endogenous relaxant of bladder contraction , and autocrine or paracrine mechanism of PTHrP - PTH1R axis is a physiologically relevant pathway functioning in the bladder .", "entity": [], "task": "NER"}
{"text": "17 beta - estradiol activates glucose uptake via GLUT4 translocation and PI3K / Akt signaling pathway in MCF - 7 cells .", "entity": [{"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "The relationship between estrogen and some types of breast cancer has been clearly established .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "However , although several studies have demonstrated the relationship between estrogen and glucose uptake via PI3K / Akt in other tissues , not too much is known about the possible cross talk between them for development and maintenance of breast cancer .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [78, 86]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [91, 98]}], "task": "NER"}
{"text": "This study was designed to test the rapid effects of 17 beta - estradiol ( E2 ) or its membrane - impermeable form conjugated with bovine serum albumin ( E2BSA ) on glucose uptake in a positive estrogen receptor ( ER ) breast cancer cell line , through the possible relationship between key components of the PI3K / Akt signaling pathway and acute steroid treatment .", "entity": [{"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [53, 72]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [165, 172]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [194, 202]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [348, 355]}], "task": "NER"}
{"text": "MCF - 7 human breast cancer cells were cultured in standard conditions .", "entity": [], "task": "NER"}
{"text": "Then 10nM of 17 beta - estradiol or estradiol BSA conjugated were administrated before obtaining the cell lysates .", "entity": [{"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [13, 32]}, {"entity": "estradiol", "entity_type": "Chemical", "pos": [36, 45]}], "task": "NER"}
{"text": "To study the glucose uptake , the glucose fluorescent analogue 2 - [ N - ( 7 - nitrobenz - 2 - oxa - 1 , 3 - diazol - 4 - yl ) amino ] - 2 - deoxy - d - glucose was used .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [13, 20]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "2 - [ N - ( 7 - nitrobenz - 2 - oxa - 1 , 3 - diazol - 4 - yl ) amino ] - 2 - deoxy - d - glucose", "entity_type": "Chemical", "pos": [63, 160]}], "task": "NER"}
{"text": "We report an ER - dependent activation of some of the key steps of the PI3K / Akt signaling pathway cascade that leads cells to improve some mechanisms that finally increase glucose uptake capacity .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [174, 181]}], "task": "NER"}
{"text": "Our data suggest that both E2 and E2BSA enhance the entrance of the fluorescent glucose analogue 2 - NBDG , and also activates s PI3K / Akt signaling pathway , leading to translocation of GLUT4 to the plasma membrane in an ER alpha dependent manner .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [80, 87]}, {"entity": "2 - NBDG", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "E2 enhances ER - dependent rapid signaling triggered , partially in the plasma membrane , allowing ER alpha - positive MCF - 7 breast cancer cells to increase glucose uptake , which could be essential to meet the energy demands of the high rate of proliferation .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [159, 166]}], "task": "NER"}
{"text": "The consumption of n - 3 polyunsaturated fatty acids differentially modulates gene expression of peroxisome proliferator - activated receptor alpha and gamma and hypoxia - inducible factor 1 alpha in subcutaneous adipose tissue of obese adolescents .", "entity": [{"entity": "n - 3 polyunsaturated fatty acids", "entity_type": "Chemical", "pos": [19, 52]}], "task": "NER"}
{"text": "The aim of this study was to evaluate the effect of long - chain omega - 3 polyunsaturated fatty acid ( n - 3 PUFA ) supplementation on metabolic state and gene expression in subcutaneous adipose tissues of obese adolescents .", "entity": [{"entity": "omega - 3 polyunsaturated fatty acid", "entity_type": "Chemical", "pos": [65, 101]}, {"entity": "n - 3 PUFA", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "Obese adolescents ( n = 26 , 10 girls and 16 boys ) aged 12 . 4 +/- 2 . 1 years were assigned to a 12 - week regimen of n - 3 PUFA intake .", "entity": [{"entity": "n - 3 PUFA", "entity_type": "Chemical", "pos": [120, 130]}], "task": "NER"}
{"text": "Five times per day , subjects received a food supplement consisting of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ( 3 g per day , 944 mg EPA , and 2 , 088 mg DHA ) .", "entity": [{"entity": "eicosapentaenoic acid", "entity_type": "Chemical", "pos": [71, 92]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [95, 98]}, {"entity": "docosahexaenoic acid", "entity_type": "Chemical", "pos": [105, 125]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [128, 131]}, {"entity": "EPA", "entity_type": "Chemical", "pos": [157, 160]}, {"entity": "DHA", "entity_type": "Chemical", "pos": [178, 181]}], "task": "NER"}
{"text": "Blood parameters were measured , and subcutaneous adipose tissue biopsies were analyzed to determine gene expression at baseline and after 12 weeks .", "entity": [], "task": "NER"}
{"text": "Student ' s t test and the Wilcoxon signed - rank test were used to estimate differences in arithmetic means of pre - and post - dietary supplementation for various anthropometric , biochemical , clinical , and gene expression parameters .", "entity": [], "task": "NER"}
{"text": "After 12 weeks , n - 3 PUFA consumption was associated with decreased body mass index ( 29 . 7 +/- 4 . 6 vs . 27 . 8 +/- 4 . 4 kg / m ( 2 ) ; P < 0 . 001 ) , waist circumference ( 93 . 2 +/- 9 . 9 vs . 90 . 5 +/- 10 . 0 cm ; P < 0 . 003 ) , hip circumference ( 102 . 9 +/- 10 . 9 vs . 101 . 1 +/- 10 . 9 cm ; P < 0 . 014 ) , and blood triglyceride levels ( 220 . 8 +/- 27 . 4 vs . 99 . 7 +/- 32 . 7 mg / dL ; P < 0 . 001 ) .", "entity": [{"entity": "n - 3 PUFA", "entity_type": "Chemical", "pos": [17, 27]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [335, 347]}], "task": "NER"}
{"text": "Fatty acid supplementation / n3 PUFA supplementation was associated with a downregulated expression of the genes encoding PPAR gamma and PGC - 1 alpha ( P < 0 . 001 ) , and an upregulated expression of the genes encoding PPAR alpha ( P < 0 . 007 ) and SREBP1 ( P < 0 . 021 ) .", "entity": [{"entity": "Fatty acid", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "n3 PUFA", "entity_type": "Chemical", "pos": [29, 36]}], "task": "NER"}
{"text": "The expressions of SOD2 ( P < 0 . 04 ) , CAT ( P < 0 . 001 ) , GPX3 ( P < 0 . 032 ) and HIF - 1 alpha protein also decreased .", "entity": [], "task": "NER"}
{"text": "Our study demonstrated that n - 3 PUFA consumption and dietary restriction improved the anthropometric parameters and decreased the triglycerides levels of the adolescents , suggesting a reduction in hypoxia in subcutaneous adipose tissue .", "entity": [{"entity": "n - 3 PUFA", "entity_type": "Chemical", "pos": [28, 38]}, {"entity": "triglycerides", "entity_type": "Chemical", "pos": [132, 145]}], "task": "NER"}
{"text": "Structure of Bradyrhizobium japonicum transcription factor FixK2 unveils sites of DNA binding and oxidation .", "entity": [], "task": "NER"}
{"text": "FixK2 is an important regulatory protein that helps activating a large number of genes for the anoxic and microoxic , endosymbiotic and nitrogen - fixing life styles of the alpha - proteobacterium Bradyrhizobium japonicum .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "FixK2 belongs to the cyclic AMP receptor protein ( CRP ) superfamily .", "entity": [{"entity": "cyclic AMP", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "While most CRP - family members are co - regulated by effector molecules , the activity of FixK2 is negatively controlled by oxidation of its single cysteine ( C183 ) located next to the DNA binding domain , and possibly also by proteolysis .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [149, 157]}], "task": "NER"}
{"text": "Here we report the three - dimensional X - ray structure of FixK2 , a representative of the FixK subgroup of the CRP superfamily .", "entity": [], "task": "NER"}
{"text": "Crystallization succeeded only ( i ) when an oxidation - and protease - insensitive protein variant ( C183S - FixK2His6 ) was used , in which C183 was replaced by serine and the C - terminus fused with a hexa - histidine tag , and ( ii ) when this protein was allowed to form a complex with a 30mer double - strand target DNA .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [163, 169]}, {"entity": "C", "entity_type": "Chemical", "pos": [178, 179]}, {"entity": "hexa - histidine", "entity_type": "Chemical", "pos": [204, 220]}], "task": "NER"}
{"text": "The structure of the FixK2 - DNA complex was solved at a resolution of 1 . 77 A in which the protein formed a homodimer .", "entity": [], "task": "NER"}
{"text": "The precise protein - DNA contacts were identified which led to an affirmation of the canonical target sequence , the so - called FixK2 box .", "entity": [], "task": "NER"}
{"text": "The C - terminus is surface - exposed which might explain its sensitivity to specific cleavage and degradation .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [4, 5]}], "task": "NER"}
{"text": "The oxidation - sensitive C183 is also surface - exposed and in close proximity to DNA .", "entity": [], "task": "NER"}
{"text": "Therefore , we propose a mechanism whereby the oxo - acids generated after oxidation of the cysteine thiol cause an electrostatic repulsion , thus preventing specific DNA binding .", "entity": [{"entity": "oxo - acids", "entity_type": "Chemical", "pos": [47, 58]}, {"entity": "cysteine thiol", "entity_type": "Chemical", "pos": [92, 106]}], "task": "NER"}
{"text": "Nanostructured potential of optical trapping using a plasmonic nanoblock pair .", "entity": [], "task": "NER"}
{"text": "We performed two - dimensional mapping of optical trapping potentials experienced by a 100 nm dielectric particle above a plasmon - resonant gold nanoblock pair with a gap of several nanometers .", "entity": [], "task": "NER"}
{"text": "Our results demonstrate that the potentials have nanoscale spatial structures that reflect the near - field landscape of the nanoblock pair .", "entity": [], "task": "NER"}
{"text": "When an incident polarization parallel to the pair axis is rotated by 90 degrees , a single potential well turns into multiple potential wells separated by a distance smaller than the diffraction limit ; this is associated with super - resolution optical trapping .", "entity": [], "task": "NER"}
{"text": "In addition , we show that the trap stiffness can be enhanced by approximately 3 orders of magnitude compared to that with conventional far - field trapping .", "entity": [], "task": "NER"}
{"text": "Photoinduced and Thermal Denitrogenation of Bulky Triazoline Crystals : Insights into Solid - to - Solid Transformation .", "entity": [{"entity": "Triazoline", "entity_type": "Chemical", "pos": [50, 60]}], "task": "NER"}
{"text": "The photoinduced and thermal denitrogenation of crystalline triazolines with bulky substituents leads to the quantitative formation of aziridines in clean solid - to - solid reactions despite very large structural changes in the transition from reactant to product .", "entity": [{"entity": "triazolines", "entity_type": "Chemical", "pos": [60, 71]}, {"entity": "aziridines", "entity_type": "Chemical", "pos": [135, 145]}], "task": "NER"}
{"text": "Analysis of the reaction progress by powder X - ray diffraction , solid - state ( 13 ) C CPMAS NMR , solid - state FTIR spectroscopy , and thermal analysis has revealed that solid - to - solid reactions proceed either through metastable phases susceptible to amorphization or by mechanisms that involve a reconstructive phase transition that culminates in the formation of the stable phase of the product .", "entity": [{"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [80, 88]}], "task": "NER"}
{"text": "While the key for a solid - to - solid transformation is that the reaction occurs below the eutectic temperature of the reactant and product two - component system , experimental evidence suggests that those reactions will undergo a reconstructive phase transition when they take place above the glass transition temperature .", "entity": [], "task": "NER"}
{"text": "Genetics of serotonin receptors and depression : state of the art .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [12, 21]}], "task": "NER"}
{"text": "Major depression ( MD ) is a major health problem , partly due to the incomplete understanding of the pathogenic mechanisms of the disease .", "entity": [], "task": "NER"}
{"text": "Research efforts have mainly focused on alterations in monoaminergic neurotransmission , especially in relation to the serotonergic system , due to its key role in the regulation of mood and related biological functions .", "entity": [], "task": "NER"}
{"text": "Given the high heritability of MD ( estimated between 31 % and 42 % for unipolar depression ) , genes coding for key regulators of the serotonergic neurotransmission have been considered as optimal candidates .", "entity": [], "task": "NER"}
{"text": "The present review is focused on the role of genes coding for serotonin receptors in MD pathogenesis , since the serotonin transporter and enzymes involved in serotonin metabolism have been reviewed elsewhere .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [113, 122]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [159, 168]}], "task": "NER"}
{"text": "Despite the large number of candidate gene studies focusing on genes coding for serotonin receptors , results have been inconsistent .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [80, 89]}], "task": "NER"}
{"text": "The most replicated findings are the associations between rs6295 ( HTR1A gene ) G allele or G / G genotype and rs6311 ( HTR2A gene ) A allele or A / A genotype and MD or depressive symptoms .", "entity": [], "task": "NER"}
{"text": "Preclinical and imaging / post - mortem studies in humans provide strong support for the involvement of HTR1A and HTR2A genes in MD .", "entity": [], "task": "NER"}
{"text": "Nevertheless , the inconsistency across previous studies clearly suggests that innovative approaches should be designed in order to overcome the limitations of candidate gene studies .", "entity": [], "task": "NER"}
{"text": "To date , the most appealing methodologies seem to be full exome or genome sequencing , genome - wide pathway analyses , endophenotypes , and epigenetic biomarkers .", "entity": [], "task": "NER"}
{"text": "The reported tools may assist in the detection of multiple - loci models , which could potentially explain the high percentage of MD susceptibility ascribed to genetic factors .", "entity": [], "task": "NER"}
{"text": "Key targets and relevant inhibitors for the drug discovery of tuberculosis .", "entity": [], "task": "NER"}
{"text": "Tuberculosis ( TB ) is an infectious disease caused by the pathogen Mycobacterium tuberculosis ( M . tuberculosis ) , killing about two million people worldwide each year .", "entity": [], "task": "NER"}
{"text": "An increase in the prevalence of drug - resistant strains of M . tuberculosis in the past decades has renewed focus on the development of new drugs that can treat both drug - sensitive and resistant TB infections .", "entity": [], "task": "NER"}
{"text": "M . tuberculosis evades the host immune system and drug regimes by entering dormant phase within macrophage .", "entity": [], "task": "NER"}
{"text": "As a consequence , there is a pressing need for new vaccines and antimicrobials to treat persistent infections .", "entity": [], "task": "NER"}
{"text": "As clinically used antibiotics target very few essential functions of mycobacterium , it is rational that identification of new targets that are essential for bacterial growth and survival can serve as starting point for designing of novel drugs to cure both drug - sensitive and resistant TB infections .", "entity": [], "task": "NER"}
{"text": "With the development of molecular biology and structural biology and the availability of the genome sequence of M . tuberculosis , some success has been achieved in the identification of new targets in M . tuberculosis and their relevant inhibitors .", "entity": [], "task": "NER"}
{"text": "This review summarizes about ninety important targets that participate in a range of diverse physiological processes in M . tuberculosis and seven new drugs currently in clinical phase 2 or 3 trials .", "entity": [], "task": "NER"}
{"text": "In addition , promising inhibitors with novel mechanisms of action and clinical vaccine candidates are highlighted .", "entity": [], "task": "NER"}
{"text": "Discovery of the First C - Nucleoside HCV Polymerase Inhibitor ( GS - 6620 ) with Demonstrated Antiviral Response in HCV Infected Patients .", "entity": [{"entity": "C - Nucleoside", "entity_type": "Chemical", "pos": [23, 37]}, {"entity": "GS - 6620", "entity_type": "Chemical", "pos": [65, 74]}], "task": "NER"}
{"text": "Hepatitis C virus ( HCV ) infection presents an unmet medical need requiring more effective treatment options .", "entity": [], "task": "NER"}
{"text": "Nucleoside inhibitors ( NI ) of HCV polymerase ( NS5B ) have demonstrated pan - genotypic activity and durable antiviral response in the clinic , and they are likely to become a key component of future treatment regimens .", "entity": [{"entity": "Nucleoside", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "NI candidates that have entered clinical development thus far have all been N - nucleoside derivatives .", "entity": [{"entity": "N - nucleoside", "entity_type": "Chemical", "pos": [76, 90]}], "task": "NER"}
{"text": "Herein , we report the discovery of a C - nucleoside class of NS5B inhibitors .", "entity": [{"entity": "C - nucleoside", "entity_type": "Chemical", "pos": [38, 52]}], "task": "NER"}
{"text": "Exploration of adenosine analogs in this class identified 1 ' - cyano - 2 ' - C - methyl 4 - aza - 7 , 9 - dideaza adenosine as a potent and selective inhibitor of NS5B .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "1 ' - cyano - 2 ' - C - methyl 4 - aza - 7 , 9 - dideaza adenosine", "entity_type": "Chemical", "pos": [58, 124]}], "task": "NER"}
{"text": "A monophosphate prodrug approach afforded a series of compounds showing submicromolar activity in HCV replicon assays .", "entity": [{"entity": "monophosphate", "entity_type": "Chemical", "pos": [2, 15]}], "task": "NER"}
{"text": "Further pharmacokinetic optimization for sufficient oral absorption and liver triphosphate loading led to identification of a clinical development candidate GS - 6620 .", "entity": [{"entity": "triphosphate", "entity_type": "Chemical", "pos": [78, 90]}, {"entity": "GS - 6620", "entity_type": "Chemical", "pos": [157, 166]}], "task": "NER"}
{"text": "In a phase I clinical study , the potential for potent activity was demonstrated but with high intra - and interpatient pharmacokinetic and pharmacodynamic variability .", "entity": [], "task": "NER"}
{"text": "Cytotoxicity and Modulation of Cancer - Related Signaling by ( Z ) - and ( E ) - 3 , 4 , 3 ' , 5 ' - Tetramethoxystilbene Isolated from Eugenia rigida .", "entity": [{"entity": "( Z ) - and ( E ) - 3 , 4 , 3 ' , 5 ' - Tetramethoxystilbene", "entity_type": "Chemical", "pos": [61, 121]}], "task": "NER"}
{"text": "Bioassay - guided fractionation of the leaves of Eugenia rigida yielded three stilbenes , ( Z ) - 3 , 4 , 3 ' , 5 ' - tetramethoxystilbene ( 1 ) , ( E ) - 3 , 4 , 3 ' , 5 ' - tetramethoxystilbene ( 2 ) , and ( E ) - 3 , 5 , 4 ' - trimethoxystilbene ( 3 ) .", "entity": [{"entity": "stilbenes", "entity_type": "Chemical", "pos": [78, 87]}, {"entity": "( Z ) - 3 , 4 , 3 ' , 5 ' - tetramethoxystilbene", "entity_type": "Chemical", "pos": [90, 138]}, {"entity": "( E ) - 3 , 4 , 3 ' , 5 ' - tetramethoxystilbene", "entity_type": "Chemical", "pos": [147, 195]}, {"entity": "( E ) - 3 , 5 , 4 ' - trimethoxystilbene", "entity_type": "Chemical", "pos": [208, 248]}], "task": "NER"}
{"text": "Their structures were determined using 1D - and 2D - NMR spectroscopy and HRESIMS .", "entity": [], "task": "NER"}
{"text": "The sterically hindered Z - stereoisomer 1 , a new natural product , was prepared by time - dependent photoisomerization of the E - isomer ( 2 ) under UV irradiation at lambda 254 nm , while 2 , 3 , 5 , 7 - tetramethoxyphenanthrene ( 5 ) was identified at lambda 365 nm by UHPLC / APCI - MS and NMR spectroscopy .", "entity": [{"entity": "2 , 3 , 5 , 7 - tetramethoxyphenanthrene", "entity_type": "Chemical", "pos": [191, 231]}], "task": "NER"}
{"text": "Compounds 1 - 3 were tested against a panel of luciferase reporter gene assays that assess the activity of many cancer - related signaling pathways , and the Z - isomer ( 1 ) was found to be more potent than the E - isomer ( 2 ) in inhibiting the activation of Stat3 , Smad3 / 4 , myc , Ets , Notch , and Wnt signaling , with IC50 values between 40 and 80 mu M .", "entity": [], "task": "NER"}
{"text": "However , both compounds showed similar inhibition against Ap - 1 and NF - kappa B signaling .", "entity": [], "task": "NER"}
{"text": "In addition , 1 demonstrated cytotoxic activity toward human leukemia cells , solid tumor cells of epidermal , breast , and cervical carcinomas , and skin melanoma , with IC50 values between 3 . 6 and 4 . 3 mu M , while 2 was weakly active against leukemia , cervical carcinoma , and skin melanoma cells .", "entity": [], "task": "NER"}
{"text": "Interestingly , 2 showed antioxidant activity by inhibition of ROS generation to 50 % at 33 . 3 mu M in PMA - induced HL - 60 cells , while 1 was inactive at 100 mu M ( vs Trolox 1 . 4 mu M ) .", "entity": [{"entity": "PMA", "entity_type": "Chemical", "pos": [104, 107]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [172, 178]}], "task": "NER"}
{"text": "Neoclerodanes as Atypical Opioid Receptor Ligands .", "entity": [{"entity": "Neoclerodanes", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "The neoclerodane diterpene salvinorin A is the major active component of the hallucinogenic mint plant Salvia divinorum Epling and J a tiva ( Lamiaceae ) .", "entity": [{"entity": "neoclerodane diterpene", "entity_type": "Chemical", "pos": [4, 26]}, {"entity": "salvinorin A", "entity_type": "Chemical", "pos": [27, 39]}], "task": "NER"}
{"text": "Since the finding that salvinorin A exerts its potent psychotropic actions through the activation of opioid receptors , the site of action of morphine and related analogues , there has been much interest in elucidating the underlying mechanisms behind its effects .", "entity": [{"entity": "salvinorin A", "entity_type": "Chemical", "pos": [23, 35]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [142, 150]}], "task": "NER"}
{"text": "These effects are particularly remarkable because ( 1 ) salvinorin A is the first reported non - nitrogenous opioid receptor agonist and ( 2 ) its effects are not mediated through the previously investigated targets of psychotomimetics .", "entity": [{"entity": "salvinorin A", "entity_type": "Chemical", "pos": [56, 68]}], "task": "NER"}
{"text": "This Perspective outlines our research program , illustrating a new direction to the development of tools to further elucidate the biological mechanisms of drug tolerance and dependence .", "entity": [], "task": "NER"}
{"text": "The information gained from these efforts is expected to facilitate the design of novel agents to treat pain , drug abuse , and other central nervous system disorders .", "entity": [], "task": "NER"}
{"text": "Formation of a tyrosine adduct involved in lignin degradation by Trametopsis cervina lignin peroxidase : A novel peroxidase activation mechanism .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "Lignin peroxidase ( LiP ) from Trametopsis cervina has an exposed catalytic tyrosine ( Tyr - 181 ) instead of the conserved tryptophan of other lignin - degrading peroxidases .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [76, 84]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "tryptophan", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "Pristine LiP showed a lag period in veratryl alcohol ( VA ) oxidation .", "entity": [{"entity": "veratryl alcohol", "entity_type": "Chemical", "pos": [36, 52]}], "task": "NER"}
{"text": "However , LiP after turnover with H2O2 / VA ( VA - LiP ) lacked this lag , and H2O2 - pretreated LiP ( H2O2 - LiP ) was inactive .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [34, 38]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [79, 83]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "MS analyses revealed that VA - LiP includes one VA molecule covalently bound to the side - chain of Tyr - 181 , whereas H2O2 - LiP contains hydroxylated Tyr - 181 .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [100, 103]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [120, 124]}, {"entity": "Tyr", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "No adduct is formed by the Y171N variant .", "entity": [], "task": "NER"}
{"text": "Molecular docking showed that VA binding is favored by sandwich pi stacking with Tyr - 181 and Phe - 89 .", "entity": [{"entity": "Tyr", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "Phe", "entity_type": "Chemical", "pos": [95, 98]}], "task": "NER"}
{"text": "EPR spectroscopy after peroxide activation of the pretreated LiPs showed other protein radicals than the tyrosine radical found in pristine LiP , which were assigned to a tyrosine / VA adduct radical in VA - LiP and a dihydroxyphenyalanine radical in H2O2 - LiP .", "entity": [{"entity": "peroxide", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [105, 113]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [171, 179]}, {"entity": "dihydroxyphenyalanine", "entity_type": "Chemical", "pos": [218, 239]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [251, 255]}], "task": "NER"}
{"text": "Both radicals are able to oxidize large low redox - potential substrates , but H2O2 - LiP is unable to oxidize high redox - potential substrates .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "Transient - state kinetics showed that the tyrosine / VA adduct strongly promotes ( > 100 - fold ) substrate oxidation by compound II , the rate - limiting step in catalysis .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [43, 51]}], "task": "NER"}
{"text": "The novel activation mechanism is involved in ligninolysis , as demonstrated using lignin model substrates .", "entity": [], "task": "NER"}
{"text": "This is the first report on autocatalytic modification , resulting in functional alteration , among class - II peroxidases .", "entity": [], "task": "NER"}
{"text": "Nrf2 - dependent neuroprotective activity of diterpenoids isolated from Sideritis spp .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [45, 57]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : The species of the genus Sideritis are extensively used in the Mediterranean area in folk medicine for their digestive , antimicrobial , anti - inflammatory and antioxidant properties , among others .", "entity": [], "task": "NER"}
{"text": "Moreover , Sideritis species as tea infusions are popularly known for improving memory function and cognitive ability .", "entity": [], "task": "NER"}
{"text": "Diterpenoids are one of the most abundant and important pharmacological interest of the classes of natural products presented in these medicinal plants .", "entity": [{"entity": "Diterpenoids", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "AIM OF THE STUDY : To determine for the first time the neuroprotective effects , based on their antioxidant properties , of the three isolated major diterpenoids andalusol , conchitriol and lagascatriol in an oxidative stress model .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [149, 161]}, {"entity": "andalusol", "entity_type": "Chemical", "pos": [162, 171]}, {"entity": "conchitriol", "entity_type": "Chemical", "pos": [174, 185]}, {"entity": "lagascatriol", "entity_type": "Chemical", "pos": [190, 202]}], "task": "NER"}
{"text": "MATERIALS AND METHODS : H2O2 was used as oxidant inductor and rat adrenal pheochromocytoma PC12 cells as cellular model .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [24, 28]}], "task": "NER"}
{"text": "Cell viability was measured using MTT and LDH assays , lipid peroxidation was determined by HPLC , GSH and GSSG levels assessed by fluorometric techniques , enzymatic activity and protein expression were determined by spectrofometric techniques and Western blot , respectively .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [34, 37]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "RESULTS : Pretreatments with the three diterpenoids significantly attenuated H2O2 - induced changes in mitochondrial integrity and activity ( MTT assay ) , in cell membrane integrity ( LDH assay ) and in cell morphology .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [39, 51]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [77, 81]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "Moreover , these diterpenoids inhibited intracellular ROS production H2O2 - induced , reduced lipid peroxidation and counteracted GSH / GSSG changes .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [17, 29]}, {"entity": "H2O2", "entity_type": "Chemical", "pos": [69, 73]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [130, 133]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [136, 140]}], "task": "NER"}
{"text": "Furthermore , both activities and protein expression of the endogenous antioxidant enzymes ( CAT , SOD , GR , GPx and HO - 1 ) were increased .", "entity": [], "task": "NER"}
{"text": "The Nrf2 pathway was involved , at least in part , in the protective effects of these diterpenoids .", "entity": [{"entity": "diterpenoids", "entity_type": "Chemical", "pos": [86, 98]}], "task": "NER"}
{"text": "CONCLUSION : These findings suggest that these natural compounds provide significant antioxidant effects in PC12 under for counteracting the oxidative damage H2O2 - induced and their potential role as useful agents for the prevention of those oxidative stress - mediated dementia disorders .", "entity": [{"entity": "H2O2", "entity_type": "Chemical", "pos": [158, 162]}], "task": "NER"}
{"text": "Andalusol was the most active compound among the studied diterpenoids .", "entity": [{"entity": "Andalusol", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "diterpenoids", "entity_type": "Chemical", "pos": [57, 69]}], "task": "NER"}
{"text": "The putative JAK - STAT inhibitor AG490 exacerbates LPS - fever , reduces sickness behavior , and alters the expression of pro - and anti - inflammatory genes in the rat brain .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [34, 39]}], "task": "NER"}
{"text": "The functional significance for activation of inflammatory transcription factors , such as signal transducer and activator of transcription ( STAT3 ) , nuclear factor ( NF ) kappa B or NF - interleukin ( IL ) 6 and their contribution to the induction of brain controlled sickness responses , such as fever , during infection and inflammation is unknown .", "entity": [], "task": "NER"}
{"text": "Using AG490 , previously shown to inhibit the STAT3 - and NF - IL6 - signaling pathway , we therefore investigated the central involvement of these two signaling pathways in mediating sickness behavior , fever and accompanying brain inflammation induced by peripheral lipopolysaccharide ( LPS ) - stimulation .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [6, 11]}], "task": "NER"}
{"text": "Rats pre - treated i . c . v . with AG490 1 h before the i . p .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [36, 41]}], "task": "NER"}
{"text": "LPS - challenge ( 100 mu g / kg ) showed a modestly exaggerated fever , attenuated adipsia and almost unimpaired locomotor activity compared to LPS - controls receiving vehicle ( i . c . v . ) .", "entity": [], "task": "NER"}
{"text": "The LPS - induced anorexia was not altered and AG490 did not have any effect on rats receiving PBS ( i . p . ) .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [47, 52]}], "task": "NER"}
{"text": "We did observe effects of AG490 on STAT3 - signaling at 4 h , while AG490 - mediated changes in brain activity of inflammatory transcription factors at 8 h were not significant .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [26, 31]}, {"entity": "AG490", "entity_type": "Chemical", "pos": [68, 73]}], "task": "NER"}
{"text": "Increased NF - IL6 and suppressor of cytokines 3 mRNA - expression in AG490 / LPS - treated rats were indicative of a compensative activation at 24 h .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [70, 75]}], "task": "NER"}
{"text": "Moreover , a significant decrease in hypothalamic anti - inflammatory IL - 10 - expression and an increase in inflammatory microsomal prostaglandin E synthase ( mPGES ) mRNA - expression 8 h after LPS - injection was revealed in AG490 pre - treated animals compared to solvent - treated LPS - controls .", "entity": [{"entity": "prostaglandin E", "entity_type": "Chemical", "pos": [134, 149]}, {"entity": "AG490", "entity_type": "Chemical", "pos": [229, 234]}], "task": "NER"}
{"text": "In summary , we have shown a dissociation between the effects of central AG490 treatment on fever and components of sickness behavior , which appears to be related to reduced IL - 10 and increased mPGES - expression in the brain .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [73, 78]}], "task": "NER"}
{"text": "Thus , AG490 might have therapeutic potential to reduce sickness behavior .", "entity": [{"entity": "AG490", "entity_type": "Chemical", "pos": [7, 12]}], "task": "NER"}
{"text": "Distinct signaling cascades elicited by different formyl Peptide receptor 2 ( FPR2 ) agonists .", "entity": [{"entity": "formyl", "entity_type": "Chemical", "pos": [50, 56]}], "task": "NER"}
{"text": "The formyl peptide receptor 2 ( FPR2 ) is a remarkably versatile transmembrane protein belonging to the G - protein coupled receptor ( GPCR ) family .", "entity": [{"entity": "formyl", "entity_type": "Chemical", "pos": [4, 10]}], "task": "NER"}
{"text": "FPR2 is activated by an array of ligands , which include structurally unrelated lipids and peptide / proteins agonists , resulting in different intracellular responses in a ligand - specific fashion .", "entity": [], "task": "NER"}
{"text": "In addition to the anti - inflammatory lipid , lipoxin A4 , several other endogenous agonists also bind FPR2 , including serum amyloid A , glucocorticoid - induced annexin 1 , urokinase and its receptor , suggesting that the activation of FPR2 may result in potent pro - or anti - inflammatory responses .", "entity": [{"entity": "lipoxin A4", "entity_type": "Chemical", "pos": [47, 57]}], "task": "NER"}
{"text": "Other endogenous ligands , also present in biological samples , include resolvins , amyloidogenic proteins , such as beta amyloid ( A beta ) - 42 and prion protein ( Prp ) 106 - 126 , the neuroprotective peptide , humanin , antibacterial peptides , annexin 1 - derived peptides , chemokine variants , the neuropeptides , vasoactive intestinal peptide ( VIP ) and pituitary adenylate cyclase activating polypeptide ( PACAP ) - 27 , and mitochondrial peptides .", "entity": [{"entity": "resolvins", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "adenylate", "entity_type": "Chemical", "pos": [373, 382]}], "task": "NER"}
{"text": "Upon activation , intracellular domains of FPR2 mediate signaling to G - proteins , which trigger several agonist - dependent signal transduction pathways , including activation of phospholipase C ( PLC ) , protein kinase C ( PKC ) isoforms , the phosphoinositide 3 - kinase ( PI3K ) / protein kinase B ( Akt ) pathway , the mitogen - activated protein kinase ( MAPK ) pathway , p38MAPK , as well as the phosphorylation of cytosolic tyrosine kinases , tyrosine kinase receptor transactivation , phosphorylation and nuclear translocation of regulatory transcriptional factors , release of calcium and production of oxidants .", "entity": [{"entity": "phosphoinositide", "entity_type": "Chemical", "pos": [247, 263]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [433, 441]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [452, 460]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [588, 595]}], "task": "NER"}
{"text": "FPR2 is an attractive therapeutic target , because of its involvement in a range of normal physiological processes and pathological diseases .", "entity": [], "task": "NER"}
{"text": "Here , we review and discuss the most significant findings on the intracellular pathways and on the cross - communication between FPR2 and tyrosine kinase receptors triggered by different FPR2 agonists .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "Isolation and Structure Elucidation of Three New Dolastanes from the Brown Alga Dilophus spiralis .", "entity": [{"entity": "Dolastanes", "entity_type": "Chemical", "pos": [49, 59]}], "task": "NER"}
{"text": "Three new dolastane diterpenes ( 1 - 3 ) and five previously reported perhydroazulenes were isolated from the organic extracts of the brown alga Dilophus spiralis .", "entity": [{"entity": "dolastane diterpenes", "entity_type": "Chemical", "pos": [10, 30]}, {"entity": "perhydroazulenes", "entity_type": "Chemical", "pos": [70, 86]}], "task": "NER"}
{"text": "The structure elucidation and the assignment of the relative configurations of the isolated natural products were based on extensive analyses of their spectroscopic data , whereas the absolute configuration of metabolite 2 was determined through its chemical conversion to a previously isolated compound of known configuration .", "entity": [], "task": "NER"}
{"text": "A Distal Enhancer Controls Cytokine - dependent Human cPLA2 alpha Gene Expression .", "entity": [], "task": "NER"}
{"text": "Specific control of group IVA cytosolic phospholipase A2 ( cPLA2 alpha or PLA2G4A ) expression modulates arachidonic acid production , thus tightly regulating the downstream effects of pro - and anti - inflammatory eicosanoids .", "entity": [{"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [105, 121]}, {"entity": "eicosanoids", "entity_type": "Chemical", "pos": [215, 226]}], "task": "NER"}
{"text": "The significance of this pathway in human disease is apparent in a range of pathologies from inflammation to tumorigenesis .", "entity": [], "task": "NER"}
{"text": "While much of the regulation of cPLA2 alpha has focused on post - translational phosphorylation of the protein , studies on transcriptional regulation of this gene have focused only on proximal promoter regions .", "entity": [], "task": "NER"}
{"text": "We have identified a DNase I hypersensitive site encompassing a 5 ' distal enhancer element containing a highly conserved consensus AP - 1 site involved in transcriptional activation of cPLA2 alpha by IL - 1 beta .", "entity": [], "task": "NER"}
{"text": "ChIP , knockdown , knockout and overexpression analyses have shown that c - Jun acts both in a negative and positive regulatory role .", "entity": [], "task": "NER"}
{"text": "Transcriptional activation of cPLA2 alpha occurs through the phosphorylation of c - Jun in conjunction with increased association of C / EBP beta with the distal novel enhancer .", "entity": [], "task": "NER"}
{"text": "The association of C / EBP beta with the transcriptional activation complex does not require an obvious DNA binding site .", "entity": [], "task": "NER"}
{"text": "These data provide new and important contributions to the understanding of cPLA2 alpha regulation at the transcriptional level with implications to eicosanoid metabolism , cellular signaling and disease pathogenesis .", "entity": [{"entity": "eicosanoid", "entity_type": "Chemical", "pos": [148, 158]}], "task": "NER"}
{"text": "Ultrahigh - efficiency photocatalysts based on mesoporous Pt - WO3 nanohybrids .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [58, 60]}, {"entity": "WO3", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "A reliable nanocasting method has been developed to synthesize mesoporous hybrids of platinum ( Pt ) nanoparticles decorating tungsten trioxide ( WO3 ) .", "entity": [{"entity": "platinum", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [96, 98]}, {"entity": "tungsten trioxide", "entity_type": "Chemical", "pos": [126, 143]}, {"entity": "WO3", "entity_type": "Chemical", "pos": [146, 149]}], "task": "NER"}
{"text": "The process began with modification of the SBA - 15 template with carbon polymers and Pt nanoparticles accompanied by adsorption of W ( 6 + ) , which was then converted into m - Pt - WO3 composites by heat treatment and subsequent template removal .", "entity": [{"entity": "SBA - 15", "entity_type": "Chemical", "pos": [43, 51]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [86, 88]}, {"entity": "W ( 6 + )", "entity_type": "Chemical", "pos": [132, 141]}, {"entity": "m - Pt - WO3", "entity_type": "Chemical", "pos": [174, 186]}], "task": "NER"}
{"text": "The synthetic strategy can be easily extended to prepare other mesoporous nanohybrids with metal oxide loaded precious metal composites .", "entity": [{"entity": "metal oxide", "entity_type": "Chemical", "pos": [91, 102]}], "task": "NER"}
{"text": "Comprehensive characterizations suggest that the as - developed m - Pt - WO3 nanohybrid exhibits unique properties with mesoporous structure , excellent crystalline structure , and high surface area .", "entity": [{"entity": "m - Pt - WO3", "entity_type": "Chemical", "pos": [64, 76]}], "task": "NER"}
{"text": "When the photocatalytic properties of m - Pt - WO3 nanohybrids were systematically investigated , it was revealed that the m - Pt - WO3 nanohybrids showed great promise for degrading the organic dye under visible light irradiation , which shows an excellent photocatalytic activity that far exceeded those of pure phase mesoporous WO3 and commercial TiO2 ( P25 ) , and was 10 - fold more active than that of the bulk Pt - WO3 catalyst .", "entity": [{"entity": "m - Pt - WO3", "entity_type": "Chemical", "pos": [38, 50]}, {"entity": "m - Pt - WO3", "entity_type": "Chemical", "pos": [123, 135]}, {"entity": "WO3", "entity_type": "Chemical", "pos": [331, 334]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [350, 354]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [417, 419]}, {"entity": "WO3", "entity_type": "Chemical", "pos": [422, 425]}], "task": "NER"}
{"text": "The as - developed synthetic route opens up a new avenue for designing mesoporous hybrid materials for various applications benefiting from the unique porous structure , high surface area , and synergistic effects among constituents .", "entity": [], "task": "NER"}
{"text": "An Active Role for Steroid - binding Globulins : An Update .", "entity": [{"entity": "Steroid", "entity_type": "Chemical", "pos": [19, 26]}], "task": "NER"}
{"text": "It has been 7 years ( can it really be that long ? ) since we co - edited a volume ( # 38 ) of Hormone and Metabolic Research that focused on evidence that steroid - binding globulins play an active role in the actions of steroids .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [156, 163]}, {"entity": "steroids", "entity_type": "Chemical", "pos": [222, 230]}], "task": "NER"}
{"text": "There has been considerable progress in identifying the location , the physiological actions , and of determining the role of binding globulins in the actions of steroids and identifying a membrane - associated receptor for a binding protein since then and this review will discuss this progress .", "entity": [{"entity": "steroids", "entity_type": "Chemical", "pos": [162, 170]}], "task": "NER"}
{"text": "Mechanisms of metal - catalyzed dehydrocoupling reactions .", "entity": [], "task": "NER"}
{"text": "This review summarizes selected mechanistic insight garnered from reactions that form bonds between main group elements with liberation of hydrogen , dehydrocoupling or dehydropolymerization reactions .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "Focus has been made where mechanistic study has been done or provides unique insight as compared to previous work .", "entity": [], "task": "NER"}
{"text": "Thus , a limited number of catalysts and substrates will be discussed , but a broad range of mechanistic features will be noted .", "entity": [], "task": "NER"}
{"text": "A comparative approach considering dehydrocoupling reactions that appear to proceed by certain mechanistic steps is taken here , beginning with steps that are well established and general then moving to those that are newer , at least to this application .", "entity": [], "task": "NER"}
{"text": "Dominant role of molybdenum in the electrochemical deposition of biological macromolecules on metallic surfaces .", "entity": [{"entity": "molybdenum", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "The corrosion of CoCrMo , an alloy frequently used in orthopedic implants , was studied with an electrochemical quartz crystal microbalance ( QCM ) in three physiologically relevant solutions .", "entity": [{"entity": "CoCrMo", "entity_type": "Chemical", "pos": [17, 23]}, {"entity": "quartz", "entity_type": "Chemical", "pos": [112, 118]}], "task": "NER"}
{"text": "Mass changes were measured during potentiodynamic tests , showing material deposition in protein solutions at potential levels that caused mass loss when the proteins were not present .", "entity": [], "task": "NER"}
{"text": "X - ray photoelectron spectroscopy ( XPS ) data indicated that the deposited material was primarily organic and therefore was most likely derived from proteins in the electrolyte .", "entity": [], "task": "NER"}
{"text": "Material deposition consistently occurred at a critical potential and was not dependent on the current density or total charge released into solution .", "entity": [], "task": "NER"}
{"text": "Corrosion studies on pure Co , Cr , and Mo in protein solutions found material deposition only on Mo .", "entity": [{"entity": "Co", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Cr", "entity_type": "Chemical", "pos": [31, 33]}, {"entity": "Mo", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "Mo", "entity_type": "Chemical", "pos": [98, 100]}], "task": "NER"}
{"text": "We hypothesize that organic deposition results from the interaction of Mo ( VI ) with proteins in the surrounding solution .", "entity": [{"entity": "Mo ( VI )", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "The organic layer is reminiscent of tribochemical reaction layers that form on the surface of CoCrMo hip bearings , suggesting that these types of layers can be formed by purely electrochemical means .", "entity": [{"entity": "CoCrMo", "entity_type": "Chemical", "pos": [94, 100]}], "task": "NER"}
{"text": "Spontaneous formation of hydrophobic domains in isolated peptides .", "entity": [], "task": "NER"}
{"text": "Aromatic amino acids are known for their hydrophobicity and the active role they play in protein folding .", "entity": [{"entity": "Aromatic amino acids", "entity_type": "Chemical", "pos": [0, 20]}], "task": "NER"}
{"text": "Here , we investigate the intrinsic propensity of small peptides to form hydrophobic domains in the absence of solvent water molecules .", "entity": [], "task": "NER"}
{"text": "The structures of three aromatic - rich isolated peptides , Ac - Phe - Phe - NH2 ( FF ) , Ac - Trp - Tyr - NH2 ( WY ) , and Ac - Phe - Phe - Phe - NH2 ( FFF ) , all in the gas phase , have been studied by infrared - ultraviolet ( IR / UV ) double resonance laser spectroscopy , aided by dispersion - corrected density functional theory ( DFT - D ) calculations .", "entity": [{"entity": "Ac - Phe - Phe - NH2", "entity_type": "Chemical", "pos": [60, 80]}, {"entity": "Ac - Trp - Tyr - NH2", "entity_type": "Chemical", "pos": [90, 110]}, {"entity": "Ac - Phe - Phe - Phe - NH2", "entity_type": "Chemical", "pos": [124, 150]}], "task": "NER"}
{"text": "Spontaneous formation of hydrophobic domains is systematically observed , whatever the secondary structure adopted by the backbone .", "entity": [], "task": "NER"}
{"text": "Various types of aromatic - aromatic arrangements have been identified and associated to specific secondary structures , illustrating the interplay between the hydrophobic clusters and the backbone .", "entity": [], "task": "NER"}
{"text": "Backbone NH amide groups surrounded by aromatic rings have also been evidenced and are found to contribute significantly to the stabilization of aromatic pairs .", "entity": [{"entity": "NH", "entity_type": "Chemical", "pos": [9, 11]}, {"entity": "amide", "entity_type": "Chemical", "pos": [12, 17]}], "task": "NER"}
{"text": "These results suggest that the formation of aromatic clusters involving contiguous residues might be a very efficient process leading to the formation of hydrophobic domains in the early stages of protein folding , well before a hydrophobic collapse into the tertiary structure .", "entity": [], "task": "NER"}
{"text": "Using genomic data to revisit an early example of reproductive character displacement in Haitian Anolis lizards .", "entity": [], "task": "NER"}
{"text": "The pattern of reproductive character displacement ( RCD ) - in which traits associated with reproductive isolation are more different where two species occur together than where they occur in isolation - is frequently attributed to reinforcement , a process during which natural selection acting against maladaptive mating events leads to enhanced prezygotic isolation between species or incipient species .", "entity": [], "task": "NER"}
{"text": "One of the first studies of RCD to include molecular genetic data was described 40 years ago in a complex of Haitian trunk anole lizards using a small number of allozyme loci .", "entity": [], "task": "NER"}
{"text": "In this example , Anolis caudalis appears to experience divergence in the color and pattern of an extensible throat fan , or dewlap , in areas of contact with closely related species at the northern and southern limits of its range .", "entity": [], "task": "NER"}
{"text": "However , this case study has been largely overlooked for decades ; meanwhile , explanations for geographic variation in dewlap color and pattern have focused primarily on adaptation to local signalling environments .", "entity": [], "task": "NER"}
{"text": "We reinvestigate this example using amplified fragment length polymorphism ( AFLP ) genome scans , mtDNA sequence data , information on dewlap phenotypes and GIS data on environmental variation to test the hypothesis of RCD generated by reinforcement in Haitian trunk anoles .", "entity": [], "task": "NER"}
{"text": "Together , our phenotypic and genetic results are consistent with RCD at the southern and northern limits of the range of A . caudalis .", "entity": [], "task": "NER"}
{"text": "We evaluate the evidence for reinforcement as the explanation for RCD in Haitian trunk anoles , consider alternative explanations and provide suggestions for future work on the relationship between dewlap variation and speciation in Haitian trunk anoles .", "entity": [], "task": "NER"}
{"text": "Sensitive determination of lead , cadmium and nickel in soil , water , vegetable and fruit samples using STAT - FAAS after preconcentration with activated carbon .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "In this study , lead ( Pb ) , cadmium ( Cd ) and nickel ( Ni ) were determined in soil , water , vegetable and fruit samples taken from around oil refinery region in Batman , Turkey .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [23, 25]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [49, 55]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [58, 60]}], "task": "NER"}
{"text": "Digestion procedures for samples were optimized and all optimum parameters were used both in digestion and in determination steps .", "entity": [], "task": "NER"}
{"text": "In order to determine Pb and Cd , slotted tube atom trap ( STAT ) was used to increase the sensitivity in atomic absorption spectrophotometry .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [29, 31]}], "task": "NER"}
{"text": "Preconcentration procedure under the optimum conditions was applied to water , vegetable and fruit samples to determine Pb , Cd and Ni in trace levels .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [120, 122]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [125, 127]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [132, 134]}], "task": "NER"}
{"text": "In soil samples , concentrations of analytes were found in the range of 4 . 0 +/- 0 . 2 - 12 , 000 +/- 60 mg / kg for Pb , 0 . 15 +/- 0 . 01 - 3 . 0 +/- 0 . 1 mg / kg for Cd and 21 +/- 1 - 65 +/- 3 . 4 mg / kg for Ni .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [118, 120]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [171, 173]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [214, 216]}], "task": "NER"}
{"text": "In all water samples , concentration of Ni was expressed as nanogram per milliliter ( ng / mL ) and found to be higher than Pb and Cd levels .", "entity": [{"entity": "Ni", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [124, 126]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [131, 133]}], "task": "NER"}
{"text": "It was observed that Pb , Cd and Ni concentrations varied from both plant to plant and in same plants at different experimental sites .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [26, 28]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [33, 35]}], "task": "NER"}
{"text": "Pb concentrations in vegetable and fruit samples interested varied between 20 +/- 2 and 160 +/- 12 ng / g , and the highest level of Pb was found to be in green pepper taken from 1000 m away from refinery .", "entity": [{"entity": "Pb", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "Pb", "entity_type": "Chemical", "pos": [133, 135]}], "task": "NER"}
{"text": "UVA photoirradiation of benzo [ a ] pyrene metabolites : induction of cytotoxicity , reactive oxygen species , and lipid peroxidation .", "entity": [{"entity": "benzo [ a ] pyrene", "entity_type": "Chemical", "pos": [24, 42]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [94, 100]}], "task": "NER"}
{"text": "Benzo [ a ] pyrene ( BaP ) is a prototype for studying carcinogenesis of polycyclic aromatic hydrocarbons ( PAHs ) .", "entity": [{"entity": "Benzo [ a ] pyrene", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "BaP", "entity_type": "Chemical", "pos": [21, 24]}, {"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [73, 105]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [108, 112]}], "task": "NER"}
{"text": "We have long been interested in studying the phototoxicity of PAHs .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [62, 66]}], "task": "NER"}
{"text": "In this study , we determined that metabolism of BaP by human skin HaCaT keratinocytes resulted in six identified phase I metabolites , for example , BaP trans - 7 , 8 - dihydrodiol ( BaP t - 7 , 8 - diol ) , BaP t - 4 , 5 - diol , BaP t - 9 , 10 - diol , 3 - hydroxybenzo [ a ] pyrene ( 3 - OH - BaP ) , BaP ( 7 , 10 / 8 , 9 ) tetrol , and BaP ( 7 / 8 , 9 , 10 ) tetrol .", "entity": [{"entity": "BaP", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "BaP trans - 7 , 8 - dihydrodiol", "entity_type": "Chemical", "pos": [150, 181]}, {"entity": "BaP t - 7 , 8 - diol", "entity_type": "Chemical", "pos": [184, 204]}, {"entity": "BaP t - 4 , 5 - diol", "entity_type": "Chemical", "pos": [209, 229]}, {"entity": "BaP t - 9 , 10 - diol", "entity_type": "Chemical", "pos": [232, 253]}, {"entity": "3 - hydroxybenzo [ a ] pyrene", "entity_type": "Chemical", "pos": [256, 285]}, {"entity": "3 - OH - BaP", "entity_type": "Chemical", "pos": [288, 300]}, {"entity": "BaP ( 7 , 10 / 8 , 9 ) tetrol", "entity_type": "Chemical", "pos": [305, 334]}, {"entity": "BaP ( 7 / 8 , 9 , 10 ) tetrol", "entity_type": "Chemical", "pos": [341, 370]}], "task": "NER"}
{"text": "The photocytotoxicity of BaP , 3 - OH - BaP , BaP t - 7 , 8 - diol , BaP trans - 7 , 8 - diol - anti - 9 , 10 - epoxide ( BPDE ) , and BaP ( 7 , 10 / 8 , 9 ) tetrol in the HaCaT keratinocytes was examined .", "entity": [{"entity": "BaP", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "3 - OH - BaP", "entity_type": "Chemical", "pos": [31, 43]}, {"entity": "BaP t - 7 , 8 - diol", "entity_type": "Chemical", "pos": [46, 66]}, {"entity": "BaP trans - 7 , 8 - diol - anti - 9 , 10 - epoxide", "entity_type": "Chemical", "pos": [69, 119]}, {"entity": "BPDE", "entity_type": "Chemical", "pos": [122, 126]}, {"entity": "BaP ( 7 , 10 / 8 , 9 ) tetrol", "entity_type": "Chemical", "pos": [135, 164]}], "task": "NER"}
{"text": "When irradiated with 1 . 0 J / cm ( 2 ) UVA light , these compounds when tested at doses of 0 . 1 , 0 . 2 , and 0 . 5 mu M , all induced photocytotoxicity in a dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "When photoirradiation was conducted in the presence of a lipid ( methyl linoleate ) , BaP metabolites , BPDE , and three related PAHs , pyrene , 7 , 8 , 9 , 10 - tetrahydro - BaP trans - 7 , 8 - diol , and 7 , 8 , 9 , 10 - tetrahydro - BaP trans - 9 , 10 - diol , all induced lipid peroxidation .", "entity": [{"entity": "methyl linoleate", "entity_type": "Chemical", "pos": [65, 81]}, {"entity": "BaP", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "BPDE", "entity_type": "Chemical", "pos": [104, 108]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [129, 133]}, {"entity": "pyrene", "entity_type": "Chemical", "pos": [136, 142]}, {"entity": "7 , 8 , 9 , 10 - tetrahydro - BaP trans - 7 , 8 - diol", "entity_type": "Chemical", "pos": [145, 199]}, {"entity": "7 , 8 , 9 , 10 - tetrahydro - BaP trans - 9 , 10 - diol", "entity_type": "Chemical", "pos": [206, 261]}], "task": "NER"}
{"text": "The formation of lipid peroxides by BaP t - 7 , 8 - diol was inhibited by NaN3 and enhanced by deuterated methanol , which suggests that singlet oxygen may be involved in the generation of lipid peroxides .", "entity": [{"entity": "BaP t - 7 , 8 - diol", "entity_type": "Chemical", "pos": [36, 56]}, {"entity": "NaN3", "entity_type": "Chemical", "pos": [74, 78]}, {"entity": "deuterated methanol", "entity_type": "Chemical", "pos": [95, 114]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [145, 151]}], "task": "NER"}
{"text": "The formation of lipid hydroperoxides was partially inhibited by superoxide dismutase ( SOD ) .", "entity": [{"entity": "hydroperoxides", "entity_type": "Chemical", "pos": [23, 37]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [65, 75]}], "task": "NER"}
{"text": "Electron spin resonance spin trapping experiments indicated that both singlet oxygen and superoxide radical anion were generated from UVA photoirradiation of BPDE in a light dose responding manner .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [78, 84]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "BPDE", "entity_type": "Chemical", "pos": [158, 162]}], "task": "NER"}
{"text": "Rapid self - healable poly ( ethylene glycol ) hydrogels formed by selective metal - phosphate interactions .", "entity": [{"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [22, 46]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [85, 94]}], "task": "NER"}
{"text": "Rapid self - healable and biocompatible hydrogels were prepared using the selective formation of metal - ligand interactions between selected metal ions and phosphate end groups of poly ( ethylene glycol ) ( PEG ) .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [157, 166]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [181, 205]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [208, 211]}], "task": "NER"}
{"text": "The phosphate - terminated branch of PEG was synthesized via a substitution reaction of the hydroxyl end groups using phosphoryl chloride .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [92, 100]}, {"entity": "phosphoryl chloride", "entity_type": "Chemical", "pos": [118, 137]}], "task": "NER"}
{"text": "The gelation and gel properties including rheological properties can be tuned by the careful selection of metal ions , branch numbers , and temperature .", "entity": [], "task": "NER"}
{"text": "Especially , the gels rapidly formed by trivalent metal ions such as Fe ( 3 + ) , V ( 3 + ) , Al ( 3 + ) , Ti ( 3 + ) , and Ga ( 3 + ) have relatively small ionic radii .", "entity": [{"entity": "Fe ( 3 + )", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "V ( 3 + )", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "Al ( 3 + )", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "Ti ( 3 + )", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "Ga ( 3 + )", "entity_type": "Chemical", "pos": [124, 134]}], "task": "NER"}
{"text": "The ligand substitution rates also affected the repeatable autonomic healing ability .", "entity": [], "task": "NER"}
{"text": "We have also demonstrated a gel - sol / sol - gel transition by switching the redox states of Fe ( 3 + ) / Fe ( 2 + ) ions .", "entity": [{"entity": "Fe ( 3 + )", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "Fe ( 2 + )", "entity_type": "Chemical", "pos": [107, 117]}], "task": "NER"}
{"text": "Learning from biological systems , the proposed phosphate - metal ion based self - healable hydrogels could become an attractive candidate for various biomedical and environmental applications .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [48, 57]}], "task": "NER"}
{"text": "Soluble Receptor for Advanced Glycation End - Product ( sRAGE ) / Pentosidine Ratio : A Potential Risk Factor Determinant for Type 2 Diabetic Retinopathy .", "entity": [{"entity": "Pentosidine", "entity_type": "Chemical", "pos": [66, 77]}], "task": "NER"}
{"text": "This study aims to investigate potential diabetic retinopathy ( DR ) risk factors by evaluating the circulating levels of pentosidine , soluble receptor for advanced glycation end - product ( sRAGE ) , advanced oxidation protein product ( AOPP ) as well as glutathione peroxidase ( GPx ) and superoxide dismutase ( SOD ) activities in DR patients .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [122, 133]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [257, 268]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [292, 302]}], "task": "NER"}
{"text": "A total of 235 healthy controls , 171 type 2 diabetic without retinopathy ( DNR ) and 200 diabetic retinopathy ( DR ) patients were recruited .", "entity": [], "task": "NER"}
{"text": "Plasma was extracted for the estimation of pentosidine , sRAGE , AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [43, 54]}], "task": "NER"}
{"text": "DNR and DR patients showed significantly higher levels of plasma pentosidine , sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "The sRAGE / pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [12, 23]}], "task": "NER"}
{"text": "Proliferative DR patients had significantly higher levels of plasma pentosidine , sRAGE , AOPP and sRAGE / pentosidine ratio than non - proliferative DR patients .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [68, 79]}, {"entity": "pentosidine", "entity_type": "Chemical", "pos": [107, 118]}], "task": "NER"}
{"text": "High HbA1c level , long duration of diabetes and low sRAGE / pentosidine ratio were determined as the risk factors for DR .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [61, 72]}], "task": "NER"}
{"text": "This study suggests that sRAGE / pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR .", "entity": [{"entity": "pentosidine", "entity_type": "Chemical", "pos": [33, 44]}], "task": "NER"}
{"text": "Dioscin - induced autophagy mitigates cell apoptosis through modulation of PI3K / Akt and ERK and JNK signaling pathways in human lung cancer cell lines .", "entity": [{"entity": "Dioscin", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Our previous study has revealed that dioscin , a compound with anti - inflammatory , lipid - lowering , anticancer and hepatoprotective effects , may induce autophagy in hepatoma cells .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [37, 44]}], "task": "NER"}
{"text": "Autophagy is a lysosomal degradation pathway that is essential for cell survival and tissue homeostasis .", "entity": [], "task": "NER"}
{"text": "In this study , the role of autophagy and related signaling pathways during dioscin - induced apoptosis in human lung cancer cells was investigated .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "Results from 4 ' - 6 - diamidino - 2 - phenylindole and annexin - V / PI double - staining assay showed that caspase - 3 - and caspase - 8 - dependent , and dose - dependent apoptoses were detected after a 24 - h dioscin treatment .", "entity": [{"entity": "4 ' - 6 - diamidino - 2 - phenylindole", "entity_type": "Chemical", "pos": [13, 51]}, {"entity": "dioscin", "entity_type": "Chemical", "pos": [213, 220]}], "task": "NER"}
{"text": "Meanwhile , autophagy was detected as early as 12 h after an exposure to low - dose dioscin , as indicated by an up - regulated expression of LC3 - II and beclin - 1 proteins .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "Blockade of autophagy with bafilomycin A1 or 3 - methyladenine sensitized the A549 and H1299 cells to apoptosis .", "entity": [{"entity": "bafilomycin A1", "entity_type": "Chemical", "pos": [27, 41]}, {"entity": "3 - methyladenine", "entity_type": "Chemical", "pos": [45, 62]}], "task": "NER"}
{"text": "Treatment of A549 and H1299 cells with dioscin caused a dose - dependent increase in ERK1 / 2 and JNK1 / 2 activity , accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [39, 46]}], "task": "NER"}
{"text": "Taken together , this study demonstrated for the first time that autophagy occurred earlier than apoptosis during dioscin - induced human lung cancer cell line apoptosis .", "entity": [{"entity": "dioscin", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "Dioscin - induced autophagy via ERK1 / 2 and JNK1 / 2 pathways may provide a protective mechanism for cell survival against dioscin - induced apoptosis to act as a cytoprotective reaction .", "entity": [{"entity": "Dioscin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "dioscin", "entity_type": "Chemical", "pos": [124, 131]}], "task": "NER"}
{"text": "Cytotoxic and Antibacterial Cembranoids from a South China Sea Soft Coral , Lobophytum sp .", "entity": [{"entity": "Cembranoids", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "Chemical examination of a South China Sea soft coral Lobophytum sp . led to the isolation of three new alpha - methylene - gamma - lactone - containing cembranoids , ( 1R * , 3R * , 4R * , 14R * , 7E , 11E ) - 3 , 4 - epoxycembra - 7 , 11 , 15 ( 17 ) - trien - 16 , 14 - olide ( 1 ) , ( 1R * , 7S * , 14S * , 3E , 11E ) - 7 - hydroperoxycembra - 3 , 8 ( 19 ) , 11 , 15 ( 17 ) - tetraen - 16 , 14 - olide ( 2 ) , and ( 1R * , 7S * , 14S * , 3E , 11E ) - 18 - acetoxy - 7 - hydroperoxycembra - 3 , 8 ( 19 ) , 11 , 15 ( 17 ) - tetraen - 16 , 14 - olide ( 3 ) , along with eleven known analogues 4 - 14 .", "entity": [{"entity": "alpha - methylene - gamma - lactone", "entity_type": "Chemical", "pos": [103, 138]}, {"entity": "cembranoids", "entity_type": "Chemical", "pos": [152, 163]}, {"entity": "( 1R * , 3R * , 4R * , 14R * , 7E , 11E ) - 3 , 4 - epoxycembra - 7 , 11 , 15 ( 17 ) - trien - 16 , 14 - olide", "entity_type": "Chemical", "pos": [166, 276]}, {"entity": "( 1R * , 7S * , 14S * , 3E , 11E ) - 7 - hydroperoxycembra - 3 , 8 ( 19 ) , 11 , 15 ( 17 ) - tetraen - 16 , 14 - olide", "entity_type": "Chemical", "pos": [285, 403]}, {"entity": "( 1R * , 7S * , 14S * , 3E , 11E ) - 18 - acetoxy - 7 - hydroperoxycembra - 3 , 8 ( 19 ) , 11 , 15 ( 17 ) - tetraen - 16 , 14 - olide", "entity_type": "Chemical", "pos": [416, 549]}], "task": "NER"}
{"text": "The structures of the new compounds were elucidated through extensive spectroscopic analysis , including 1D and 2D NMR data .", "entity": [], "task": "NER"}
{"text": "Compounds 1 - 3 exhibited moderate cytotoxic activity against the selected tumor cell lines .", "entity": [], "task": "NER"}
{"text": "Moreover , 2 and 3 were found to be moderate inhibitors against the bacteria S . aureus and S . pneumoniae .", "entity": [], "task": "NER"}
{"text": "Atypical antipsychotics in the treatment of children and adolescents with pervasive developmental disorders .", "entity": [], "task": "NER"}
{"text": "RATIONALE : Autism and related pervasive developmental disorders ( PDD ) are characterized by impairments in social interaction and communication , restricted interests , and repetitive and stereotyped patterns of behavior .", "entity": [], "task": "NER"}
{"text": "Individuals with PDD frequently display irritability and disruptive behaviors including tantrums , self - injurious behavior , and aggression .", "entity": [], "task": "NER"}
{"text": "Atypical antipsychotics are currently the most efficacious pharmacological interventions available for treatment of irritability associated with PDD .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : This article aims to review the body of literature pertaining to the use of atypical antipsychotics in the treatment of patients with PDD .", "entity": [], "task": "NER"}
{"text": "METHODS : A PubMed literature search was conducted using the following key words : autism , pervasive developmental disorders , atypical antipsychotics , risperidone , aripiprazole , quetiapine , ziprasidone , olanzapine , clozapine , paliperidone , iloperidone , asenapine , and lurasidone .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [154, 165]}, {"entity": "aripiprazole", "entity_type": "Chemical", "pos": [168, 180]}, {"entity": "quetiapine", "entity_type": "Chemical", "pos": [183, 193]}, {"entity": "ziprasidone", "entity_type": "Chemical", "pos": [196, 207]}, {"entity": "olanzapine", "entity_type": "Chemical", "pos": [210, 220]}, {"entity": "clozapine", "entity_type": "Chemical", "pos": [223, 232]}, {"entity": "paliperidone", "entity_type": "Chemical", "pos": [235, 247]}, {"entity": "iloperidone", "entity_type": "Chemical", "pos": [250, 261]}, {"entity": "asenapine", "entity_type": "Chemical", "pos": [264, 273]}, {"entity": "lurasidone", "entity_type": "Chemical", "pos": [280, 290]}], "task": "NER"}
{"text": "Search terms were limited to English language , human subjects , and publication from 1999 to present .", "entity": [], "task": "NER"}
{"text": "Relevant references from identified articles were also reviewed .", "entity": [], "task": "NER"}
{"text": "RESULTS : The efficacy and tolerability of risperidone and aripiprazole for the treatment of irritability in autism have been established with multi - site , randomized , controlled trials .", "entity": [{"entity": "risperidone", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "aripiprazole", "entity_type": "Chemical", "pos": [59, 71]}], "task": "NER"}
{"text": "Studies supporting the use of other atypical antipsychotics are either limited in scope or less robust in their findings , though newer agents such as ziprasidone and paliperidone show promise .", "entity": [{"entity": "ziprasidone", "entity_type": "Chemical", "pos": [151, 162]}, {"entity": "paliperidone", "entity_type": "Chemical", "pos": [167, 179]}], "task": "NER"}
{"text": "CONCLUSIONS : Atypical antipsychotics are currently first - line pharmacological agents for the treatment of irritability and associated behaviors in children with PDD .", "entity": [], "task": "NER"}
{"text": "Further placebo - controlled studies are warranted to characterize the efficacy and tolerability of the majority of these medications .", "entity": [], "task": "NER"}
{"text": "There is also a need for the development of novel , targeted drugs with more favorable long - term side effect profiles .", "entity": [], "task": "NER"}
{"text": "Development and Regulation of Biosimilars : Current Status and Future Challenges .", "entity": [], "task": "NER"}
{"text": "Biologic medicinal products developed via rDNA technology as recombinant protein - based medicines that have been in clinical use since the early 1980s as original biopharmaceuticals have greatly contributed to the therapy of severe metabolic and degenerative diseases .", "entity": [], "task": "NER"}
{"text": "The recent expiration of the data protection or patents for most of them created opportunities for the development of copy versions of original biopharmaceuticals with similar biologic activity ( termed biosimilars ) .", "entity": [], "task": "NER"}
{"text": "Production of these new products is expected to meet worldwide demand , promote market competition , maintain the incentives for innovation , and sustain the healthcare systems .", "entity": [], "task": "NER"}
{"text": "The licencing of these products , however , relies on the experience gained with the original biopharmaceuticals .", "entity": [], "task": "NER"}
{"text": "Critical issues related to this class of medicinal products include their terminology ( to avoid confusion with generics and non - innovator copy versions that have not been tested according to the biosimilar guidelines ) , manufacturing , and regulation .", "entity": [], "task": "NER"}
{"text": "The European Union ( EU ) has been the first to establish a regulatory framework for marketing authorization application ( MAA ) and has named these products biosimilars , a term also recently adopted by the US FDA .", "entity": [], "task": "NER"}
{"text": "Unlike the conventional , more common small molecular weight human medicines and chemical generics , protein - based medicines exhibit higher molecular weight , complexity in structure and function that can be affected by changes in the manufacturing process .", "entity": [], "task": "NER"}
{"text": "Therefore , biosimilars represent a relatively heterogeneous class of medicinal products that make their regulation quite challenging .", "entity": [], "task": "NER"}
{"text": "According to the current understanding in the EU , a biosimilar is a copy version of an already authorized biopharmaceutical ( or reference product ) with similar biologic activity , physicochemical characteristics , efficacy , and safety , based on a full comparability exercise at quality , preclinical and clinical level to ensure similar efficacy and safety .", "entity": [], "task": "NER"}
{"text": "Guidance has been provided through several Committee for Medicinal Products for Human Use ( CHMP ) guidelines as well as individual scientific advice requested from the European Medicines Agency ( EMA ) by various companies for the development and regulation of biosimilars .", "entity": [], "task": "NER"}
{"text": "This review is mainly focused on the current status of regulation of biosimilars in the EU as well as on future challenges lying ahead for the improvement of the requirements needed for the marketing authorization of biosimilars .", "entity": [], "task": "NER"}
{"text": "Emphasis is given on the quality requirements concerning these medicinal products ( biologics ) .", "entity": [], "task": "NER"}
{"text": "The evolving role of antifungal susceptibility testing .", "entity": [], "task": "NER"}
{"text": "Although increasing numbers of hospital microbiology laboratories are performing antifungal susceptibility testing ( AST ) , its routine use is uncommon .", "entity": [], "task": "NER"}
{"text": "The utility of AST is founded on the belief that susceptibility ( or resistance ) of an agent allows some prediction of clinical outcome .", "entity": [], "task": "NER"}
{"text": "This review provides an overview of the development of antifungal susceptibility testing methodology , including wild - type minimum inhibitory concentration ( MIC ) distributions , epidemiologic breakpoints , and Interpretive Clinical Breakpoints for antifungal agents .", "entity": [], "task": "NER"}
{"text": "In addition , we examine the current clinical utility of AST and the clinical data support utilized in the development of clinical breakpoints ( CBP ) for common pathogens causing invasive fungal infections .", "entity": [], "task": "NER"}
{"text": "In the treatment of fungal infections , identifying consistent correlations between MICs - or susceptibility category - and clinical outcomes is an ongoing challenge , and current data sets are insufficient for many drugs and pathogens to enable the development , revision , or confirmation of CBPs .", "entity": [], "task": "NER"}
{"text": "Antifungal susceptibility testing is of current value , but further research in many areas is needed before MICs are independently used to guide treatment decisions .", "entity": [], "task": "NER"}
{"text": "Role of Interleukin - 1 Inhibitors in the Management of Gout .", "entity": [], "task": "NER"}
{"text": "Interleukin - 1 ( IL - 1 ) inhibitors potentially have a role as antiinflammatory agents in refractory gout or for patients who are unable to tolerate conventional therapy , such as nonsteroidal antiinflammatory drugs ( NSAIDs ) , colchicine , or glucocorticoids , for acute attacks .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [231, 241]}], "task": "NER"}
{"text": "Additionally , IL - 1 inhibitors may also help patients with polyarticular and tophaceous gout by making them less vulnerable to breakthrough attacks during initiation of chronic urate - lowering treatment , the mainstay of gout therapy .", "entity": [], "task": "NER"}
{"text": "Because evidence highlights the role of proinflammatory cytokine IL - 1 in the inflammation process during an acute gouty attack , IL - 1 inhibitors are used to modulate the pathogenesis of a variety of autoinflammatory diseases , providing support for its potential role in the inflammatory process of gout .", "entity": [], "task": "NER"}
{"text": "After NSAIDs , colchicine , and steroids , IL - 1 inhibitors are beneficial as fourth - line therapy for acute gout attacks due to their high cost and limited clinical experience .", "entity": [{"entity": "colchicine", "entity_type": "Chemical", "pos": [15, 25]}, {"entity": "steroids", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "The IL - 1 inhibitors used in gout are anakinra , canakinumab , and rilonacept .", "entity": [], "task": "NER"}
{"text": "Based on published evidence , anakinra has limited support in the form of anecdotal case reports to justify its use for treating gout .", "entity": [], "task": "NER"}
{"text": "Canakinumab ' s toxic profile in clinical trials precludes its use in treating patients for gout , and rilonacept shows promise with a few well - designed studies to support its use in gout patients initiating urate - lowering treatment .", "entity": [], "task": "NER"}
{"text": "When combined with current traditional therapies , these newer agents present clinicians and patients with more potential treatment options in the difficult - to - treat gout population .", "entity": [], "task": "NER"}
{"text": "Incidence and costs of adverse drug reactions in a tertiary care pediatric intensive care unit .", "entity": [], "task": "NER"}
{"text": "Adverse drug reactions ( ADRs ) increase morbidity , mortality , and hospital costs in children treated in the Pediatric Intensive Care Unit ( PICU ) .", "entity": [], "task": "NER"}
{"text": "Few studies have reported the incidence and risk factors of ADRs in PICU .", "entity": [], "task": "NER"}
{"text": "Our study aimed to evaluate incidence , risk factors , and economic burden of ADRs in PICU .", "entity": [], "task": "NER"}
{"text": "An intensive ADR surveillance was conducted at the PICU of Children ' s Hospital of Michigan between November 1 , 2010 and May 31 , 2011 .", "entity": [], "task": "NER"}
{"text": "A trigger list was used to screen for suspected ADR cases .", "entity": [], "task": "NER"}
{"text": "Of the 697 consecutive PICU admissions reviewed , 13 . 1 % experienced at least one episode of ADR .", "entity": [], "task": "NER"}
{"text": "The ADR incidence was 22 % in patients with cardiovascular ( CV ) surgery and 11 . 5 % in other patients .", "entity": [], "task": "NER"}
{"text": "The most frequently detected ADR was electrolyte imbalance associated with diuretic exposure .", "entity": [], "task": "NER"}
{"text": "Mean age at admission was 4 years ( interquartile range : 9 months - 13 years ) .", "entity": [], "task": "NER"}
{"text": "Risk factors for ADR included young age ( < 1 year ) , Pediatric Risk of Mortality ( PRISM ) score upon admission >= 3 , and administration of >= 16 medications .", "entity": [], "task": "NER"}
{"text": "ADRs increased total ICU costs by 3 . 5 - fold and length of ICU stay by 3 . 8 - fold .", "entity": [], "task": "NER"}
{"text": "Increased ADR surveillance of high risk patients in conjunction with early intervention may reduce drug related morbidity and costs in the PICU .", "entity": [], "task": "NER"}
{"text": "A comparison of bone quality at the distal radius between Asian and Caucasian adolescents and young adults : An HR - pQCT study .", "entity": [], "task": "NER"}
{"text": "Paradoxically , Asians have lower areal bone mineral density , but their rates of hip and wrist fractures are lower than Caucasians .", "entity": [], "task": "NER"}
{"text": "Therefore , we used high - resolution pQCT ( HR - pQCT ) to determine whether differences in bone macro - and microstructure , BMD and bone strength at the distal radius are apparent in Asian ( n = 91 , 53 males , 38 females , 17 . 3 +/- 1 . 5 yrs ) and Caucasian ( n = 89 , 46 males , 43 females , 18 . 1 +/- 1 . 8 yrs ) adolescents and young adults .", "entity": [], "task": "NER"}
{"text": "HR - pQCT outcomes included total BMD ( Tt . BMD ) , trabecular bone volume fraction ( BV / TV ) , trabecular number ( Tb . N ) , thickness ( Tb . Th ) and separation ( Tb . Sp ) .", "entity": [], "task": "NER"}
{"text": "We used an automated segmentation algorithm to determine total bone area ( Tt . Ar ) , cortical BMD ( Ct . BMD ) , porosity ( Ct . Po ) and thickness ( Ct . Th ) , and we applied finite element analysis to HR - pQCT scans to estimate bone strength .", "entity": [], "task": "NER"}
{"text": "We fit sex - specific multivariable regression models to compare bone outcomes between Asians and Caucasians , adjusting for age , age at menarche ( girls ) , lean mass , ulnar length , dietary calcium intake and physical activity .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [194, 201]}], "task": "NER"}
{"text": "In males , after adjusting for covariates , Asians had 11 % greater Tt . BMD , 8 % greater Ct . BMD and 25 % lower Ct . Po than Caucasians ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Also , Asians had 9 % smaller Tt . Ar and 27 % greater Ct . Th ( p < 0 . 01 ) .", "entity": [], "task": "NER"}
{"text": "In females , Asians had smaller Tt . Ar than Caucasians ( 16 % , p < 0 . 001 ) , but this difference was not significant after adjusting for covariates .", "entity": [], "task": "NER"}
{"text": "Asian females had 5 % greater Ct . BMD , 12 % greater Ct . Th and 11 % lower Tb . Sp than Caucasians after adjusting for covariates ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Estimated bone strength did not differ between Asian and Caucasian males or females .", "entity": [], "task": "NER"}
{"text": "Our study supports the notion of compensatory elements of bone structure that sustain bone strength ; smaller bones as observed between those of Asian compared with Caucasian origin , have , on average , more dense , less porous and thicker cortices .", "entity": [], "task": "NER"}
{"text": "Longitudinal studies are needed to determine whether ethnic differences in bone structure exist in childhood , persist into old age and whether they influence fracture risk .", "entity": [], "task": "NER"}
{"text": "Impact of Phytolacca americana Extracts on Gene Expression of Colon Cancer Cells .", "entity": [], "task": "NER"}
{"text": "Native Americans have used Phytolacca americana to treat breast ailments , gastrointestinal disorders , rashes , and inflammation .", "entity": [], "task": "NER"}
{"text": "Some anti - cancer and anti - viral research has been reported on this perennial herb , but none has been published concerning the effects of its extracts on cancer cell genes .", "entity": [], "task": "NER"}
{"text": "In this study , changes in gene expression at the transcription level were evaluated in HCT - 116 colon cancer cells after exposure to P . americana ethanol extract and its water fraction using the Human Cancer Pathway Finder PCR Array .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [149, 156]}], "task": "NER"}
{"text": "Of the genes significantly affected in HCT - 116 cells exposed to the ethanol extract at 3200 micro g / ml , changes in expression of MYC , PLAU , and TEK may benefit the treatment of colon cancer .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "Exposing the cells to 1600 micro g / ml of the water fraction resulted in several gene changes that may also be beneficial in the treatment of colon cancer : NME4 , TEK , and THBS1 .", "entity": [], "task": "NER"}
{"text": "A few genes on this array that are known to play a specific role in colon cancer had activities changed in a way that may be detrimental in the treatment of colon cancer .", "entity": [], "task": "NER"}
{"text": "Further studies should be performed to understand how these changes would impact colon cancer treatment .", "entity": [], "task": "NER"}
{"text": "Furanodiene Presents Synergistic Anti - proliferative Activity With Paclitaxel Via Altering Cell Cycle and Integrin Signaling in 95 - D Lung Cancer Cells .", "entity": [{"entity": "Furanodiene", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "Paclitaxel", "entity_type": "Chemical", "pos": [68, 78]}], "task": "NER"}
{"text": "Furanodiene ( FUR ) is a natural terpenoid isolated from Rhizoma Curcumae , a well - known Chinese medicinal herb that presents anti - proliferative activities in several cancer cell lines .", "entity": [{"entity": "Furanodiene", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "FUR", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "terpenoid", "entity_type": "Chemical", "pos": [33, 42]}], "task": "NER"}
{"text": "Recently , we found that the combined treatment of FUR with paclitaxel ( TAX ) showed synergetic anti - proliferative activities in 95 - D lung cancer cells .", "entity": [{"entity": "FUR", "entity_type": "Chemical", "pos": [51, 54]}, {"entity": "paclitaxel", "entity_type": "Chemical", "pos": [60, 70]}, {"entity": "TAX", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "Herein , we showed that FUR reduced the cell numbers distributed in mitosis phase induced by TAX while increased those in G1 phase .", "entity": [{"entity": "FUR", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "TAX", "entity_type": "Chemical", "pos": [93, 96]}], "task": "NER"}
{"text": "The protein levels of cyclin D1 , cyclin B1 , CDK6 and c - Myc were all down - regulated in the group of combined treatment .", "entity": [], "task": "NER"}
{"text": "The dramatically down - regulated expression of integrin beta 4 , focal adhesion kinase and paxillin might partially contribute to the synergic effect .", "entity": [], "task": "NER"}
{"text": "Though FUR alone obviously induced endoplasmic reticulum stress , this signaling pathway may not contribute to the synergetic anti - proliferative effect as the protein expression of CHOP and BIP was similar in FUR alone and combined treatment group .", "entity": [{"entity": "FUR", "entity_type": "Chemical", "pos": [7, 10]}, {"entity": "FUR", "entity_type": "Chemical", "pos": [211, 214]}], "task": "NER"}
{"text": "A Mineral Extract from red Algae Ameliorates Chronic Spontaneous Colitis in IL - 10 Deficient Mice in a Mouse Strain Dependent Manner .", "entity": [], "task": "NER"}
{"text": "Inflammatory bowel disease is an urgent public health problem with a high incidence in developed countries .", "entity": [], "task": "NER"}
{"text": "Alterations of lifestyle or dietary interventions may attenuate the disease progression and increase the efficacy of current therapies .", "entity": [], "task": "NER"}
{"text": "Here we tested the effect of chronic supplementation with a mineral extract from red marine algae - rich in calcium ( 34 % ) , magnesium , phosphorus , selenium and other trace minerals - in a clinically relevant model of spontaneous enterocolitis , interleukin ( IL ) - 10 ( - / - ) mice .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [108, 115]}, {"entity": "magnesium", "entity_type": "Chemical", "pos": [127, 136]}, {"entity": "phosphorus", "entity_type": "Chemical", "pos": [139, 149]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "The mineral extract was administered in the drinking water of Il10 ( - / - ) mice on C57BL / 6 J and BALB / c strain backgrounds for 25 weeks commencing from 3 to 4 weeks of age .", "entity": [], "task": "NER"}
{"text": "The mineral extract ameliorated the spontaneous development of colitis and severity of disease in Il10 ( - / - ) mice on a C57BL / 6 J background .", "entity": [], "task": "NER"}
{"text": "Mineral extract - treated Il10 ( - / - ) C57BL / 6 J strain mice had significantly reduced mortality , circulating levels of serum Amyloid A and reduced colonic tissue damage .", "entity": [], "task": "NER"}
{"text": "In contrast , comparable treatment of Il10 ( - / - ) mice on a BALB / c background with the mineral extract did not alter the course of colitis .", "entity": [], "task": "NER"}
{"text": "These data demonstrate that chronic supplementation with a natural mineral extract selectively ameliorates spontaneous mild - moderate colitis in Il10 ( - / - ) mice on a C57BL / 6 J , but does not attenuate more moderate - severe colitis in BALB / c strain animals .", "entity": [], "task": "NER"}
{"text": "Expression , purification and proteomic analysis of recombinant histone H4 acetylated at lysine 16 .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "Many histone covalent modifications have been identified and shown to play key regulatory roles in eukaryotic transcription , DNA damage repair , and replication .", "entity": [], "task": "NER"}
{"text": "In vitro experiments designed to understand the mechanistic role of individual modifications require the availability of substantial quantities of pure histones , homogeneously modified at specific residues .", "entity": [], "task": "NER"}
{"text": "We have applied the amber stop codon / suppressor tRNA strategy to the production of histone H4 acetylated at lysine 16 , a particularly important isoform of this histone .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "Our success relies on adapting the H4 DNA sequence to the codon preference of E . coli and on preventing the premature decay of the H4 mRNA .", "entity": [], "task": "NER"}
{"text": "These modifications to the original procedure render it easily applicable to the generation of any covalently modified histone H4 isoform .", "entity": [], "task": "NER"}
{"text": "SiCN : SiCN Nanofibers with a Diameter Below 100 nm Synthesized via Concerted Block Copolymer Formation , Microphase Separation , and Crosslinking ( Small 7 / 2013 ) .", "entity": [{"entity": "SiCN", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "SiCN", "entity_type": "Chemical", "pos": [7, 11]}], "task": "NER"}
{"text": "SiCN fibers with a mean diameter of 50 nm and an aspect ratio of up to 100 are produced in a two - step process by R .", "entity": [{"entity": "SiCN", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Kempe and co - workers .", "entity": [], "task": "NER"}
{"text": "The key step to fabricate the longitudinal and crosssectional views of the mesofibers shown here is a concerted block - copolymer synthesis , microphase separation , and cross linking at 140 degrees C followed by pyrolysis at 1100 degrees C .", "entity": [], "task": "NER"}
{"text": "Inexpensive components like a commercially available silazane and polyethylene are linked .", "entity": [{"entity": "silazane", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "polyethylene", "entity_type": "Chemical", "pos": [66, 78]}], "task": "NER"}
{"text": "The fibers may find application in electronic devices , as components of ceramic matrix composites , as fiber beds in hightemperature nano - filtering like diesel fine dust removal , or as thermally robust and chemically inert catalyst supports .", "entity": [], "task": "NER"}
{"text": "Furthermore , the SiCN nanofibers introduced on page 984 are a promising alternative to ultrathin carbon fibers , due to their oxidation resistance .", "entity": [{"entity": "SiCN", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [98, 104]}], "task": "NER"}
{"text": "Graphene in Light : Design , Synthesis and Applications of Photo - active Graphene and Graphene - Like Materials .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "Graphene", "entity_type": "Chemical", "pos": [74, 82]}, {"entity": "Graphene", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "Graphene functionalized with photo - active units has become one of the most exciting topics of research in the last few years , which remarkably sustains and expands the graphene boom .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [171, 179]}], "task": "NER"}
{"text": "The rise of photo - active graphene in photonics and optoelectronics is evidenced by a spate of recent reports on topics ranging from photodetectors , photovoltaics , and optoelectronics to photocatalysis .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "For these applications , the fabrication of photo - active graphene through appropriate chemical functionalization strategies is essential as pristine graphene has zero bandgap and only weak absorption of photons .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [59, 67]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "Written from the chemists ' point of view , up - to - date chemical functionalization of graphene with various small organic molecules , conjugated polymers , rare - earth components , and inorganic semiconductors is reviewed .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [89, 97]}], "task": "NER"}
{"text": "Particular attention is paid to the development of graphene functionalized with light - harvesting moieties , including materials synthesis , characterization , energy / charge - transfer processes , and applications in photovoltaics .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [51, 59]}], "task": "NER"}
{"text": "Challenges currently faced by researchers and future perspectives in this field are also discussed .", "entity": [], "task": "NER"}
{"text": "Potent Agonists of a Hematopoietic Stem Cell Cytokine Receptor , c - Mpl .", "entity": [], "task": "NER"}
{"text": "Several growth factors feature prominently in the control of hematopoiesis .", "entity": [], "task": "NER"}
{"text": "Thrombopoietin , a class I hematopoietic cytokine , plays critical roles in regulating hematopoietic stem cell numbers and also stimulates the production and differentiation of megakaryocytes , the bone marrow cells that ultimately produce platelets .", "entity": [], "task": "NER"}
{"text": "Thrombopoietin interacts with the c - Mpl cell - surface receptor .", "entity": [], "task": "NER"}
{"text": "Recently , several peptide and small - molecule agonists and antagonists of c - Mpl have been reported .", "entity": [], "task": "NER"}
{"text": "We conducted a bioinformatics and molecular modeling study aimed at understanding the agonist activities of peptides that bind to c - Mpl , and developed new potent peptide agonists with low nanomolar activity .", "entity": [], "task": "NER"}
{"text": "These agonists also show very high activity in human CD34 ( + ) primary cell cultures , and doubled the mean blood platelet counts when injected into mice .", "entity": [], "task": "NER"}
{"text": "Amorphous Ni ( OH ) 2 Nanoboxes : Fast Fabrication and Enhanced Sensing for Glucose .", "entity": [{"entity": "Ni ( OH ) 2", "entity_type": "Chemical", "pos": [10, 21]}, {"entity": "Glucose", "entity_type": "Chemical", "pos": [76, 83]}], "task": "NER"}
{"text": "Inspired by Pearson ' s hard and soft acid - base ( HSAB ) principle , uniform amorphous Ni ( OH ) 2 nanoboxes with intact shell structures and various sizes are quickly fabricated by deliberately selecting S2 O3 ( 2 - ) as the coordinating etchant toward Cu2 O templates and optimizing the reaction conditions .", "entity": [{"entity": "Ni ( OH ) 2", "entity_type": "Chemical", "pos": [89, 100]}, {"entity": "S2 O3 ( 2 - )", "entity_type": "Chemical", "pos": [207, 220]}, {"entity": "Cu2 O", "entity_type": "Chemical", "pos": [256, 261]}], "task": "NER"}
{"text": "It is found that not only the solvent system but also the employing of a surfactant is vital for the fabrication of the nanoboxes .", "entity": [], "task": "NER"}
{"text": "Ni ( OH ) 2 nanoboxes , as an example , demonstrate an improved electrochemical sensing ability for glucose , which might be due to their amorphous and hollow structural features .", "entity": [{"entity": "Ni ( OH ) 2", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "A Thyroxine Absorption Test Followed by Weekly Thyroxine Administration : A Method to Assess Non - Adherence to Treatment .", "entity": [{"entity": "Thyroxine", "entity_type": "Chemical", "pos": [2, 11]}, {"entity": "Thyroxine", "entity_type": "Chemical", "pos": [47, 56]}], "task": "NER"}
{"text": "OBJECTIVE : For patients , who remain hypothyroid despite the administration of what would seem adequate doses of levothyroxine , the underlying cause can be difficult to determine .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [114, 127]}], "task": "NER"}
{"text": "The possibility of a biological cause should first be explored ; however , in the majority of cases poor adherence to medication is likely to be the main cause of treatment failure .", "entity": [], "task": "NER"}
{"text": "When non - adherence is suspected but not volunteered , options to confirm the suspicion are limited .", "entity": [], "task": "NER"}
{"text": "In this study we identified patients for whom known drug and pathological causes of levothyroxine malabsorption were excluded and despite often high doses of levothyroxine , the patients remained hypothyroid .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [84, 97]}, {"entity": "levothyroxine", "entity_type": "Chemical", "pos": [158, 171]}], "task": "NER"}
{"text": "DESIGN : Using a weight - determined oral levothyroxine bolus administration , absorption was initially assessed in twenty - three patients .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [42, 55]}], "task": "NER"}
{"text": "In nearly all patients this was shown to be maximal at 120mins post ingestion .", "entity": [], "task": "NER"}
{"text": "This was then followed by the continued administration of a weekly thyroxine bolus for a four - week period after which TSH and free T4 levels were recorded .", "entity": [{"entity": "thyroxine", "entity_type": "Chemical", "pos": [67, 76]}], "task": "NER"}
{"text": "RESULTS : All patients showed a rise in free T4 at 120mins following the administration of the levothyroxine bolus , with a mean increase of 54 +/- 3 % from baseline .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "Following the treatment period , using an equivalent weekly levothyroxine dose which was significantly less than that of the daily dose taken by the patients before the test , the TSH reduced from baseline in ~ 75 % of cases .", "entity": [{"entity": "levothyroxine", "entity_type": "Chemical", "pos": [60, 73]}], "task": "NER"}
{"text": "CONCLUSION : Using this combination of tests allows significant malabsorptive problems to be first identified , then potential non - adherence to be demonstrated .", "entity": [], "task": "NER"}
{"text": "A management plan can then be implemented to increase adherence , aiming to improve treatment outcomes .", "entity": [], "task": "NER"}
{"text": "Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs .", "entity": [{"entity": "urotensin II", "entity_type": "Chemical", "pos": [50, 62]}], "task": "NER"}
{"text": "Renal expression of the peptide hormone urotensin II ( UII ) and its receptor ( UTR ) are dependent on kidney maturation and anatomical regions .", "entity": [{"entity": "urotensin II", "entity_type": "Chemical", "pos": [40, 52]}, {"entity": "UII", "entity_type": "Chemical", "pos": [55, 58]}], "task": "NER"}
{"text": "However , renal regional hemodynamic effects of UII in neonates are unclear .", "entity": [{"entity": "UII", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "Here , we investigated regional hemodynamic responses to acute intrarenal arterial administration of UII in newborn pigs .", "entity": [{"entity": "UII", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Western immunoblotting and immunofluorescence confirmed UTR expression and membrane localization in newborn pig renal afferent arterioles and afferent arteriolar smooth muscle cells respectively .", "entity": [], "task": "NER"}
{"text": "Intrarenal arterial bolus injections of human UII ( hUII ; 1 - 100 ng / kg ) resulted in a dose - dependent decrease in total renal blood flow ( RBF ) and an increase in mean arterial pressure ( MAP ) and renal vascular resistance ( RVR ) in newborn pigs .", "entity": [], "task": "NER"}
{"text": "Moreover , hUII dose dependently reduced cortical blood flow ( CBF ) but increased medullary blood flow ( MBF ) in the piglets .", "entity": [], "task": "NER"}
{"text": "hUII - induced MAP elevation and hemodynamic changes were inhibited by urantide , a UTR antagonist , but not losartan , a type 1 angiotensin II receptor antagonist .", "entity": [{"entity": "urantide", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "losartan", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "U - 73122 , a phospholipase C ( PLC ) inhibitor , and 2 - aminoethoxydiphenyl borate , an inositol 1 , 4 , 5 trisphosphate ( IP3 ) receptor antagonist , attenuated hUII - induced MAP and RVR elevations , RBF and CBF reductions , but not MBF increase .", "entity": [{"entity": "U - 73122", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "2 - aminoethoxydiphenyl borate", "entity_type": "Chemical", "pos": [54, 84]}, {"entity": "inositol 1 , 4 , 5 trisphosphate", "entity_type": "Chemical", "pos": [90, 122]}], "task": "NER"}
{"text": "These findings indicate that intrarenal arterial administration of hUII elevates blood pressure and induces region - selective renal hemodynamic changes in newborn pigs .", "entity": [], "task": "NER"}
{"text": "Our data also suggest that the PLC / IP3 signaling pathway contributes to hUII - induced alterations in MAP , RBF , RVR , and CBF but not MBF in newborn pigs .", "entity": [], "task": "NER"}
{"text": "Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis .", "entity": [{"entity": "glucosylceramide", "entity_type": "Chemical", "pos": [23, 39]}], "task": "NER"}
{"text": "Hypothalamic neurons are main regulators of energy homeostasis .", "entity": [], "task": "NER"}
{"text": "Neuronal function essentially depends on plasma membrane - located gangliosides .", "entity": [], "task": "NER"}
{"text": "The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase ( GCS ; UDP - glucose : ceramide glucosyltransferase ) .", "entity": [{"entity": "glucosylceramide", "entity_type": "Chemical", "pos": [113, 129]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [147, 150]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [153, 160]}, {"entity": "ceramide", "entity_type": "Chemical", "pos": [163, 171]}], "task": "NER"}
{"text": "As a major mechanism of central nervous system ( CNS ) metabolic control , we demonstrate that GCS - derived gangliosides interacting with leptin receptors ( ObR ) in the neuronal membrane modulate leptin - stimulated formation of signaling metabolites in hypothalamic neurons .", "entity": [], "task": "NER"}
{"text": "Furthermore , ganglioside - depleted hypothalamic neurons fail to adapt their activity ( c - Fos ) in response to alterations in peripheral energy signals .", "entity": [], "task": "NER"}
{"text": "Consequently , mice with inducible forebrain neuron - specific deletion of the UDP - glucose : ceramide glucosyltransferase gene ( Ugcg ) display obesity , hypothermia , and lower sympathetic activity .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "ceramide", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "Recombinant adeno - associated virus ( rAAV ) - mediated Ugcg delivery to the arcuate nucleus ( Arc ) significantly ameliorated obesity , specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis .", "entity": [], "task": "NER"}
{"text": "Dose - dependent pharmacokinetics of bulleyaconitine A in rats .", "entity": [{"entity": "bulleyaconitine A", "entity_type": "Chemical", "pos": [37, 54]}], "task": "NER"}
{"text": "This study was conducted to determine the pharmacokinetic characteristics of bulleyaconitine A ( BLA ) after oral gavage and intravenous administration of BLA at a single dose of 0 . 04 , 0 . 12 , 0 . 36 mg / kg ( oral ) or 0 . 02 mg / kg ( i . v . ) in male Sprague - Dawley rats .", "entity": [{"entity": "bulleyaconitine A", "entity_type": "Chemical", "pos": [77, 94]}, {"entity": "BLA", "entity_type": "Chemical", "pos": [97, 100]}, {"entity": "BLA", "entity_type": "Chemical", "pos": [155, 158]}], "task": "NER"}
{"text": "Plasma concentration profiles were analysed using a non - compartmental pharmacokinetic method .", "entity": [], "task": "NER"}
{"text": "Following i . v . 0 . 02 mg / kg and oral administration 0 . 04 , 0 . 12 or 0 . 36 mg / kg , the geometric mean Cmax values were 19 . 97 , 2 . 11 , 5 . 11 and 11 . 47 ng / ml , respectively ; the corresponding geometric mean AUC ( 0 - t ) values were 10 . 50 , 3 . 19 , 9 . 59 and 18 . 10 ng x h / ml , respectively .", "entity": [], "task": "NER"}
{"text": "The median Tmax values were 0 . 033 , 0 . 167 , 0 . 167 and 0 . 167 h , respectively .", "entity": [], "task": "NER"}
{"text": "The terminal elimination half - lives ( t1 / 2 ) were 1 . 23 , 2 . 48 , 1 . 93 and 2 . 17h , respectively .", "entity": [], "task": "NER"}
{"text": "The results showed that Cmax and AUC ( 0 - t ) increased with increasing doses of BLA .", "entity": [{"entity": "BLA", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "The increase in exposure with increasing dose was lower than expected under conditions of strict proportionality .", "entity": [], "task": "NER"}
{"text": "Anticancer activity of the liposome - encapsulated cyclic dipeptides , cyclo ( His - Gly ) and cyclo ( His - Ala ) .", "entity": [{"entity": "cyclic dipeptides", "entity_type": "Chemical", "pos": [51, 68]}, {"entity": "cyclo ( His - Gly )", "entity_type": "Chemical", "pos": [71, 90]}, {"entity": "cyclo ( His - Ala )", "entity_type": "Chemical", "pos": [95, 114]}], "task": "NER"}
{"text": "Cyclic dipeptides have been well characterized for their biological activity , including antimicrobial and anticancer activities .", "entity": [{"entity": "Cyclic dipeptides", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Cyclo ( His - Gly ) and cyclo ( His - Ala ) have also recently demonstrated significant anticancer activity against a range of cell lines , however , as a result of their physicochemistry , namely high solubility and low lipophilicity , it can be predicted that cellular permeability would be low , making them ideal candidates for liposome drug delivery .", "entity": [{"entity": "Cyclo ( His - Gly )", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "cyclo ( His - Ala )", "entity_type": "Chemical", "pos": [24, 43]}], "task": "NER"}
{"text": "Liposomes were composed of phosphatidylcholine , hydrogenated soy phosphatidylcholine ( HSPC ) , stearylamine , alpha - tocopherol and 1 , 2 - distearoyl - sn - glycero - 3 - phosphoethanolamine - N - [ amino ( polyethylene glycol ) - 2000 ] ( PEG - DSPE ) or folate - polyethylene glycol - cholesteryl hemisuccinate ( F - PEG - CHEMS ) using the thin - film hydration method and characterized for size and encapsulation .", "entity": [{"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [27, 46]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [66, 85]}, {"entity": "stearylamine", "entity_type": "Chemical", "pos": [97, 109]}, {"entity": "alpha - tocopherol", "entity_type": "Chemical", "pos": [112, 130]}, {"entity": "1 , 2 - distearoyl - sn - glycero - 3 - phosphoethanolamine - N - [ amino ( polyethylene glycol ) - 2000 ]", "entity_type": "Chemical", "pos": [135, 241]}, {"entity": "PEG - DSPE", "entity_type": "Chemical", "pos": [244, 254]}, {"entity": "folate - polyethylene glycol - cholesteryl hemisuccinate", "entity_type": "Chemical", "pos": [260, 316]}, {"entity": "F - PEG - CHEMS", "entity_type": "Chemical", "pos": [319, 334]}], "task": "NER"}
{"text": "The cytotoxic activity of the encapsulated cyclic dipeptides was tested against HeLa , low folate HeLa and MCF - 7 cells and found to have limited improvement in activity .", "entity": [{"entity": "cyclic dipeptides", "entity_type": "Chemical", "pos": [43, 60]}, {"entity": "folate", "entity_type": "Chemical", "pos": [91, 97]}], "task": "NER"}
{"text": "However , modification of the polyethylene glycol with folic acid to target folate receptors significantly decreased the IC50 values recorded in all cells lines tested , particularly HeLa cells cultured in media containing physiological concentrations of folic acid with the lowest IC50 being recorded as 0 . 0962 mM for folate - targeted cyclo ( His - Ala ) .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [30, 49]}, {"entity": "folic acid", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "folic acid", "entity_type": "Chemical", "pos": [255, 265]}, {"entity": "folate", "entity_type": "Chemical", "pos": [321, 327]}, {"entity": "cyclo ( His - Ala )", "entity_type": "Chemical", "pos": [339, 358]}], "task": "NER"}
{"text": "Therefore , hydrophilic cyclic dipeptides are ideal candidates for inclusion into targeted drug delivery systems such as liposomes .", "entity": [{"entity": "cyclic dipeptides", "entity_type": "Chemical", "pos": [24, 41]}], "task": "NER"}
{"text": "Biological activities of selected basidiomycetes from Yemen .", "entity": [], "task": "NER"}
{"text": "In a previous paper we demonstrated the results of biological screening of Yemeni basidiomycetes .", "entity": [], "task": "NER"}
{"text": "The present study was aimed to investigate the antimicrobial and the antioxidant activity of further basidiomycetes collected in Yemen .", "entity": [], "task": "NER"}
{"text": "Dichloromethane , methanol and aqueous extracts of the fruiting bodies of 25 species were screened in vitro for their antibacterial activities against three Gram - positive bacteria ( Staphyloccocus aureus , Bacillus subtilis , Micrococcus flavus ) and two Gram - negative bacteria ( Escherichia coli , Pseudomonas aeruginosa ) , against six human fungal pathogens ( Candida albicans , Candida krusei , Aspergillus fumigatus , Mucor sp . , Microsporum gypseum , Trichophyton mentagrophytes ) and against one non human pathogenic fungus ( Candida maltosa ) .", "entity": [{"entity": "Dichloromethane", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [18, 26]}], "task": "NER"}
{"text": "The results indicated that 75 extracts exhibited activity against one or more of the bacteria .", "entity": [], "task": "NER"}
{"text": "The methanol extracts of Agaricus cf . bernardii , Agrocybe pediades , Chlorophyllum molybdites , Coriolopsis polyzona , Ganoderma xylonoides , Pycnoporus sanguineus , Trametes lactinea and Trametes cingulata showed activity against all tested bacteria .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "The highest antibacterial activity was exhibited by methanol extracts from Chlorophyllum molybdites , Ganoderma xylonoides and Trametes cingulata and Agaricus cf . bernardii , Agrocybe pediades , Coriolopsis polyzona , Pycnoporus sanguineus and Trametes lactinea .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "The methanol extracts of Chlorophyllum molybdites , Ganoderma xylonoides and Pycnoporus sanguineus showed considerable antifungal activities against the tested fungal strains .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [4, 12]}], "task": "NER"}
{"text": "Strong antioxidative effects employing the DPPH assay were exhibited by methanol extracts from Chlorophyllum molybdites , Ganoderma xylonoides , Hexagonia velutina , Pycnoporus sanguineus , Trametes lactinea and Trametes cingulata .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [72, 80]}], "task": "NER"}
{"text": "Our previous and presented studies about 48 basidiomycetes collected in Yemen provide evidence that basidiomycetes from the Arabic region so far should attract more attention as potential source for new biologically active agents .", "entity": [], "task": "NER"}
{"text": "Rovibrational Energies of the Hydrocarboxyl Radical from a RCCSD ( T ) Study .", "entity": [{"entity": "Hydrocarboxyl", "entity_type": "Chemical", "pos": [30, 43]}], "task": "NER"}
{"text": "A RCCSD ( T ) / cc - pVQZ potential energy surface is constructed for the HOCO radical in the ground electronic state and used to compute rotation - vibration levels of HOCO and DOCO .", "entity": [{"entity": "HOCO", "entity_type": "Chemical", "pos": [74, 78]}, {"entity": "HOCO", "entity_type": "Chemical", "pos": [169, 173]}, {"entity": "DOCO", "entity_type": "Chemical", "pos": [178, 182]}], "task": "NER"}
{"text": "Two numerical strategies are employed to study in detail the wave function properties .", "entity": [], "task": "NER"}
{"text": "The importance of stretch - bend coupling , such as nu 4 / nu 5 and nu 3 / nu 4 , for the internal dynamics is demonstrated .", "entity": [], "task": "NER"}
{"text": "The rotational constants computed for the vibrational ground state of trans and cis conformers are in good agreement with experimental values .", "entity": [], "task": "NER"}
{"text": "Institutional Profile : Jayne Haines Center for Pharmacogenomics and Drug Safety : educating future generations of healthcare professionals .", "entity": [], "task": "NER"}
{"text": "The Jayne Haines Center for Pharmacogenomics and Drug Safety operates in the Temple University School of Pharmacy and serves as an educational and research facility for professional pharmacy students , graduate students , residents , postdoctoral fellows and faculties .", "entity": [], "task": "NER"}
{"text": "The Center is involved in educational and investigational projects in a setting that includes an inner city research / teaching hospital and the Temple University Schools of Pharmacy , Medicine , Dentistry and Health Professions .", "entity": [], "task": "NER"}
{"text": "The mission of the Haines Center is to facilitate the basic science approach to the problems of pharmacotherapy , and to provide education for future healthcare professionals in the genetics of drug response .", "entity": [], "task": "NER"}
{"text": "With the expanding role of genetic analysis in preventing adverse effects of pharmacotherapy , we are working towards truly personalized pharmacotherapy that fully exploits the advances of modern biomedical science .", "entity": [], "task": "NER"}
{"text": "Antioxidant activity of Tunisian Geranium robertianum L .", "entity": [], "task": "NER"}
{"text": "( Geraniaceae ) .", "entity": [], "task": "NER"}
{"text": "The present investigation focuses on the methanolic extract obtained from Geranium robertianum L .", "entity": [], "task": "NER"}
{"text": "( Geraniaceae ) ( Herb Robert ) , a herbal plant used in traditional medicine for the treatment of human and animal diseases .", "entity": [], "task": "NER"}
{"text": "The antioxidant capacities of the extract were evaluated using 1 , 1 - diphenyl - 2 - picrylhydrazyl radical , beta - carotene / linoleic acid and reducing power and metal chelating activity assays .", "entity": [{"entity": "1 , 1 - diphenyl - 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [63, 100]}, {"entity": "beta - carotene", "entity_type": "Chemical", "pos": [111, 126]}, {"entity": "linoleic acid", "entity_type": "Chemical", "pos": [129, 142]}], "task": "NER"}
{"text": "The amount of total phenolic content , flavonoids and condensed tannins was very high , and the correlation between the antioxidant activity potential and total phenolic level of the extract was pointed out .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "tannins", "entity_type": "Chemical", "pos": [64, 71]}], "task": "NER"}
{"text": "Galactose - Based Amphiphilic Block Copolymers : Synthesis , Micellization , and Bioapplication .", "entity": [{"entity": "Galactose", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Redox - responsive amphiphilic diblock copolymers , poly ( 6 - O - methacryloyl - d - galactopyranose - co - 2 - ( N , N - dimethylaminoethyl ) methacrylate ) - b - poly ( pyridyl disulfide ethyl methylacrylate ) ( P ( MAGP - co - DMAEMA ) - b - PPDSMA ) were obtained by deprotection of poly ( ( 6 - O - methacryloyl - 1 , 2 : 3 , 4 - di - O - isopropylidene - d - galactopyranose ) - co - DMAEMA ) - b - PPDSMA [ P ( MAlpGP - co - DMAEMA ) - b - PPDSMA ] , which were prepared via reversible addition - fragmentation chain transfer ( RAFT ) polymerization of PDSMA using P ( MAlpGP - co - DMAEMA ) as macro - RAFT agent .", "entity": [{"entity": "poly ( 6 - O - methacryloyl - d - galactopyranose - co - 2 - ( N , N - dimethylaminoethyl ) methacrylate ) - b - poly ( pyridyl disulfide ethyl methylacrylate )", "entity_type": "Chemical", "pos": [52, 212]}, {"entity": "P ( MAGP - co - DMAEMA ) - b - PPDSMA", "entity_type": "Chemical", "pos": [215, 252]}, {"entity": "poly ( ( 6 - O - methacryloyl - 1 , 2 : 3 , 4 - di - O - isopropylidene - d - galactopyranose ) - co - DMAEMA ) - b - PPDSMA", "entity_type": "Chemical", "pos": [288, 412]}, {"entity": "P ( MAlpGP - co - DMAEMA ) - b - PPDSMA", "entity_type": "Chemical", "pos": [415, 454]}, {"entity": "PDSMA", "entity_type": "Chemical", "pos": [561, 566]}, {"entity": "P ( MAlpGP - co - DMAEMA )", "entity_type": "Chemical", "pos": [573, 599]}], "task": "NER"}
{"text": "Dynamic light scattering ( DLS ) and transmission electron microscopy ( TEM ) studies showed that diblock copolymers P ( MAGP - co - DMAEMA ) - b - PPDSMA can self - assemble into micelles .", "entity": [{"entity": "P ( MAGP - co - DMAEMA ) - b - PPDSMA", "entity_type": "Chemical", "pos": [117, 154]}], "task": "NER"}
{"text": "Doxorubicin ( DOX ) could be encapsulated by P ( MAGP - co - DMAEMA ) - b - PPDSMA upon micellization and released upon adding glutathione ( GSH ) into the micelle solution .", "entity": [{"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "P ( MAGP - co - DMAEMA ) - b - PPDSMA", "entity_type": "Chemical", "pos": [45, 82]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [127, 138]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [141, 144]}], "task": "NER"}
{"text": "The galactose functional groups in the PMAGP block had specific interaction with HepG2 cells , and P ( MAGP - co - DMAEMA ) - b - PPDSMA can act as gene delivery vehicle .", "entity": [{"entity": "galactose", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "PMAGP", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "P ( MAGP - co - DMAEMA ) - b - PPDSMA", "entity_type": "Chemical", "pos": [99, 136]}], "task": "NER"}
{"text": "So , this kind of polymer has potential applications in hepatoma - targeting drug and gene delivery and biodetection .", "entity": [], "task": "NER"}
{"text": "Effects of prediabetes and diabetes on left ventricular and coronary microvascular functions .", "entity": [], "task": "NER"}
{"text": "BACKGROUND : Coronary flow reserve ( CFR ) provides independent prognostic information in diabetic patients with known or suspected coronary artery disease .", "entity": [], "task": "NER"}
{"text": "However , there have been no substantial data to evaluate CFR in prediabetics .", "entity": [], "task": "NER"}
{"text": "Accordingly , we aimed to evaluate CFR in subjects with prediabetes using second harmonic transthoracic Doppler echocardiography .", "entity": [], "task": "NER"}
{"text": "METHODS AND RESULTS : We measured CFR of 65 subjects with prediabetes , 45 patients with overt type 2 diabetes , and 43 sex and age matched normoglycemic healthy subjects with normal glucose tolerance .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [183, 190]}], "task": "NER"}
{"text": "Ages , gender , existence of hypertension or hypercholesterolemia , smoking status were similar among the groups .", "entity": [], "task": "NER"}
{"text": "CFR was significantly lower in diabetics ( 2 . 15 +/- 0 . 39 ) than in prediabetics ( 2 . 39 +/- 0 . 45 ) and controls ( 2 . 75 +/- 0 . 35 ) ; in addition , it was significantly lower in prediabetics than controls .", "entity": [], "task": "NER"}
{"text": "Only 2 ( 5 % ) of control subjects had abnormal CFR ( < 2 ) but 11 ( 17 % ) prediabetic subjects and 19 ( 42 % ) diabetic patients had abnormal CFR .", "entity": [], "task": "NER"}
{"text": "We found that only age ( beta = - 0 . 31 , P < 0 . 01 ) and presence of the diabetes ( beta = - 0 . 57 , P < 0 . 01 ) were significant predictors of lower CFR in a multivariable model that adjusted for other variables .", "entity": [], "task": "NER"}
{"text": "CFR was significantly and inversely correlated with age ( r = - 0 . 15 , P = 0 . 04 ) , fasting glucose level ( r = - 0 . 27 , P = 0 . 001 ) , postprandial glucose level ( r = 0 . 43 , P < 0 . 001 ) , hemoglobin A1C level ( r = - 0 . 34 , P < 0 . 001 ) , LDL cholesterol level ( r = 0 . 22 , P = 0 . 009 ) , mitral A velocity ( r = - 0 . 27 , P = 0 . 001 ) and Tei index ( r = - 0 . 19 , P = 0 . 02 ) , whereas mitral E / A ratio , mitral Em ( r = 0 . 18 , P = 0 . 02 ) , mitral Em / Am ratio ( r = 0 . 23 , P = 0 . 004 ) were significantly and positively correlated with CFR .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [96, 103]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [156, 163]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [259, 270]}], "task": "NER"}
{"text": "CONCLUSION : CFR is impaired in subjects with prediabetics , but this impairment is not as severe as that in diabetics .", "entity": [], "task": "NER"}
{"text": "Does 4 - tert - octylphenol affect estrogen signaling pathways in bank vole Leydig cells and tumor mouse Leydig cells in vitro ?", "entity": [{"entity": "4 - tert - octylphenol", "entity_type": "Chemical", "pos": [5, 27]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "Primary Leydig cells obtained from bank vole testes and the established tumor Leydig cell line ( MA - 10 ) have been used to explore the effects of 4 - tert - octylphenol ( OP ) .", "entity": [{"entity": "4 - tert - octylphenol", "entity_type": "Chemical", "pos": [148, 170]}], "task": "NER"}
{"text": "Leydig cells were treated with two concentrations of OP ( 10 ( - 4 ) M , 10 ( - 8 ) M ) alone or concomitantly with anti - estrogen ICI 182 , 780 ( 1 mu M ) .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [123, 131]}, {"entity": "ICI 182 , 780", "entity_type": "Chemical", "pos": [132, 145]}], "task": "NER"}
{"text": "In OP - treated bank vole Leydig cells , inhomogeneous staining of estrogen receptor alpha ( ER alpha ) within cell nuclei was found , whereas it was of various intensity among MA - 10 Leydig cells .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "The expression of ER alpha mRNA and protein decreased in both primary and immortalized Leydig cells independently of OP dose .", "entity": [], "task": "NER"}
{"text": "ICI partially reversed these effects at mRNA level while at protein level abrogation was found only in vole cells .", "entity": [], "task": "NER"}
{"text": "Dissimilar action of OP on cAMP and androgen production was also observed .", "entity": [{"entity": "cAMP", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "This study provides further evidence that OP shows estrogenic properties acting on Leydig cells .", "entity": [], "task": "NER"}
{"text": "However , its effect is diverse depending on the cellular origin .", "entity": [], "task": "NER"}
{"text": "mTOR Regulates Nox4 - Mediated Podocyte Depletion in Diabetic Renal Injury .", "entity": [], "task": "NER"}
{"text": "Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis .", "entity": [], "task": "NER"}
{"text": "Pharmacological doses of the mTOR inhibitor rapamycin reduce albuminura in diabetes .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [44, 53]}], "task": "NER"}
{"text": "We explored the hypothesis that mTOR mediates podocyte injury in diabetes .", "entity": [], "task": "NER"}
{"text": "High glucose ( HG ) induces apoptosis of podocytes , inhibits AMPK activation , inactivates tuberin and activates mTOR .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [5, 12]}], "task": "NER"}
{"text": "HG also increases the levels of Nox4 and Nox1 and NADPH oxidase activity .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [50, 55]}], "task": "NER"}
{"text": "Inhibition of mTOR by low dose rapamycin decreases HG - induced Nox4 and Nox1 , NADPH oxidase activity and podocyte apoptosis .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [80, 85]}], "task": "NER"}
{"text": "Inhibition of mTOR had no effect on AMPK or tuberin phosphorylation indicating that mTOR is downstream of these signaling molecules .", "entity": [], "task": "NER"}
{"text": "In isolated glomeruli of OVE26 mice , there is similar decrease in the activation of AMPK and tuberin and activation of mTOR with increase in Nox4 and NADPH oxidase activity .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [151, 156]}], "task": "NER"}
{"text": "Inhibition of mTOR by small dose of rapamycin reduces podocyte apoptosis , attenuates glomerular injury and albuminuria .", "entity": [{"entity": "rapamycin", "entity_type": "Chemical", "pos": [36, 45]}], "task": "NER"}
{"text": "Our data provide evidence for a novel function of mTOR in Nox4 - derived ROS generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "Thus mTOR and or NADPH oxidase inhibition may represent a therapeutic modality of diabetic kidney disease .", "entity": [{"entity": "NADPH", "entity_type": "Chemical", "pos": [17, 22]}], "task": "NER"}
{"text": "Application of Target - Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors .", "entity": [], "task": "NER"}
{"text": "Replacement of hydrogen with fluorine within three pairs of structurally similar small molecule inhibitors of heat shock protein 90 ( HSP90 ) resulted in differences in inhibition constants ( Ki ) in vitro as well as marked differences in rat intravenous pharmacokinetic profiles .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "fluorine", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "The difference in pharmacokinetic profiles between lower and higher affinity inhibitors ( LAIs and HAIs , respectively ) was characterized by remarkably different estimates for steady - state volumes of distribution ( Vss : 1 . 8 to 2 . 0 versus 10 to 13 L / kg ) with comparable clearance estimates ( 3 . 2 to 3 . 5 L / h / kg ) .", "entity": [], "task": "NER"}
{"text": "When the observed Vss estimates were compared to the values predicted with the tissue - composition - based model , the observed Vss estimates for HAIs were 4 to 8 - fold larger than the predicted values whereas the Vss values for LAIs were comparable each other .", "entity": [], "task": "NER"}
{"text": "Accordingly , a negative relationship between in vitro HSP90 Ki versus in vivo Vss estimates was observed among these inhibitors .", "entity": [], "task": "NER"}
{"text": "We therefore hypothesized that pharmacokinetic profiles of these inhibitors could be characterized by target - mediated drug disposition ( TMDD ) model .", "entity": [], "task": "NER"}
{"text": "In vivo equilibrium dissociation constant ( KD ) estimates for HAIs due to target binding by TMDD model with rapid binding approximation were 1 to 6 nM ( equivalent to 0 . 3 to 2 nM free drug ) , which appeared comparable to the in vitro Ki estimates ( 2 to 3 nM ) .", "entity": [], "task": "NER"}
{"text": "In vivo KD values of LAIs were not accurately determined by the TMDD model , likely due to non - specific binding dependent - tissue distribution obscuring TMDD profiles .", "entity": [], "task": "NER"}
{"text": "Overall , these results suggest that the observed large Vss estimates for potent HSP90 inhibitors are likely due to pharmacological target binding .", "entity": [], "task": "NER"}
{"text": "1 , 3 , 4 - Oxadiazol - 2 - ones as fatty - acid amide hydrolase and monoacylglycerol lipase inhibitors : Synthesis , in vitro evaluation and insight into potency and selectivity determinants by molecular modelling .", "entity": [{"entity": "1 , 3 , 4 - Oxadiazol - 2 - ones", "entity_type": "Chemical", "pos": [0, 32]}, {"entity": "fatty - acid amide", "entity_type": "Chemical", "pos": [36, 54]}, {"entity": "monoacylglycerol", "entity_type": "Chemical", "pos": [69, 85]}], "task": "NER"}
{"text": "Inhibition of the key hydrolytic enzymes of the endocannabinoid system , fatty acid amide hydrolase ( FAAH ) and monoacylglycerol lipase ( MAGL ) , has been proposed as potential mode of action for various therapeutic applications .", "entity": [{"entity": "fatty acid amide", "entity_type": "Chemical", "pos": [73, 89]}, {"entity": "monoacylglycerol", "entity_type": "Chemical", "pos": [113, 129]}], "task": "NER"}
{"text": "Continuing our previous work , we take the first steps of structure - activity relationship exploration and show that 1 , 3 , 4 - oxadiazol - 2 - ones can serve as scaffold for both selective FAAH and MAGL inhibitors , and also function as a dual FAAH / MAGL inhibitor at sub - micromolar IC50 values .", "entity": [{"entity": "1 , 3 , 4 - oxadiazol - 2 - ones", "entity_type": "Chemical", "pos": [118, 150]}], "task": "NER"}
{"text": "Moreover , 10 - fold selectivity against MAGL over FAAH was achieved with compound 3d ( FAAH and MAGL IC50 ; 2 . 0 and 0 . 22 mu M ) .", "entity": [], "task": "NER"}
{"text": "Lastly , enzyme and ligand features contributing to the potency and selectivity differences are analysed by molecular docking .", "entity": [], "task": "NER"}
{"text": "Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride .", "entity": [{"entity": "terbinafine hydrochloride", "entity_type": "Chemical", "pos": [97, 122]}], "task": "NER"}
{"text": "The study describes the development and evaluation of solid lipid nanoparticles ( SLNs ) of terbinafine hydrochloride ( TH ) for sustained release and skin targeting .", "entity": [{"entity": "terbinafine hydrochloride", "entity_type": "Chemical", "pos": [92, 117]}], "task": "NER"}
{"text": "TH - loaded SLNs were prepared by solvent - injection technique and optimized using 3 ( 3 ) full - factorial design .", "entity": [], "task": "NER"}
{"text": "Effect of drug : lipid ratio , surfactant concentration and volume of organic solvent were studied on % entrapment efficiency ( % EE ) and particle size ( PS ) .", "entity": [], "task": "NER"}
{"text": "The optimum formulation based on desirability ( 0 . 945 ) exhibited % EE of 73 . 74 % and PS of 300nm .", "entity": [], "task": "NER"}
{"text": "Optimized SLNs were incorporated into Carbopol gel and evaluated for drug content , pH , in vitro release , ex vivo retention , in vivo pharmacodynamic and stability studies .", "entity": [{"entity": "Carbopol", "entity_type": "Chemical", "pos": [38, 46]}], "task": "NER"}
{"text": "Drug release from SLNs dispersion followed Korsmeyer - Peppas model , indicating Fickian drug release , while that from the gel followed Higuchi model .", "entity": [], "task": "NER"}
{"text": "The ex vivo studies through rat abdominal skin indicated skin retention ability of SLNs as compared to commercial product .", "entity": [], "task": "NER"}
{"text": "In vivo pharmacodynamic studies showed that the SLNs based gel reduced fungal burden of Candida albicans in rats as compared to commercial product in shorter duration of time .", "entity": [], "task": "NER"}
{"text": "The SLNs dispersion and gel exhibited physicochemical stability under refrigeration upto 3months .", "entity": [], "task": "NER"}
{"text": "It was concluded that SLNs incorporated Carbopol gel had skin targeting ability and may serve as a promising carrier in treatment of fungal skin infections .", "entity": [{"entity": "Carbopol", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "Antitumor effect of 5 - fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [20, 36]}], "task": "NER"}
{"text": "5 - Fluorouracil ( 5 - FU ) is the most used chemotherapeutic agent in colorectal cancer .", "entity": [{"entity": "5 - Fluorouracil", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [19, 25]}], "task": "NER"}
{"text": "However , resistance to this drug is relatively frequent , and new strategies to overcome it are urgently needed .", "entity": [], "task": "NER"}
{"text": "The aim of this work was to determine the antitumor properties of a supercritical fluid rosemary extract ( SFRE ) , alone and in combination with 5 - FU , as a potential adjuvant therapy useful for colon cancer patients .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [146, 152]}], "task": "NER"}
{"text": "This extract has been recognized as a healthy component by the European Food Safety Authority ( EFSA ) .", "entity": [], "task": "NER"}
{"text": "The effects of SFRE both alone and in combination with 5 - FU were evaluated in different human colon cancer cells in terms of cell viability , cytotoxicity , and cell transformation .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [55, 61]}], "task": "NER"}
{"text": "Additionally , colon cancer cells resistant to 5 - FU were used to assay the effects of SFRE on drug resistance .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "Finally , qRT - PCR was performed to ascertain the mechanism by which SFRE potentiates the effect of 5 - FU .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [101, 107]}], "task": "NER"}
{"text": "Our results show that SFRE displays dose - dependent antitumor activities and exerts a synergistic effect in combination with 5 - FU on colon cancer cells .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [126, 132]}], "task": "NER"}
{"text": "Furthermore , SFRE sensitizes 5 - FU - resistant cells to the therapeutic activity of this drug , constituting a beneficial agent against both 5 - FU sensitive and resistant tumor cells .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [30, 36]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [143, 149]}], "task": "NER"}
{"text": "Gene expression analysis indicates that the enhancement of the effect of 5 - FU by SFRE might be explained by the downregulation of TYMS and TK1 , enzymes related to 5 - FU resistance .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [73, 79]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "A new method for stranded whole transcriptome RNA - seq .", "entity": [], "task": "NER"}
{"text": "This report describes an improved protocol to generate stranded , barcoded RNA - seq libraries to capture the whole transcriptome .", "entity": [], "task": "NER"}
{"text": "By optimizing the use of duplex specific nuclease ( DSN ) to remove ribosomal RNA reads from stranded barcoded libraries , we demonstrate improved efficiency of multiplexed next generation sequencing ( NGS ) .", "entity": [], "task": "NER"}
{"text": "This approach detects expression profiles of all RNA types , including miRNA ( microRNA ) , piRNA ( Piwi - interacting RNA ) , snoRNA ( small nucleolar RNA ) , lincRNA ( long non - coding RNA ) , mtRNA ( mitochondrial RNA ) and mRNA ( messenger RNA ) without the use of gel electrophoresis .", "entity": [], "task": "NER"}
{"text": "The improved protocol generates high quality data that can be used to identify differential expression in known and novel coding and non - coding transcripts , splice variants , mitochondrial genes and SNPs ( single nucleotide polymorphisms ) .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [216, 226]}], "task": "NER"}
{"text": "A diarylheptanoid phytoestrogen from Curcuma comosa , 1 , 7 - diphenyl - 4 , 6 - heptadien - 3 - ol , accelerates human osteoblast proliferation and differentiation .", "entity": [{"entity": "diarylheptanoid", "entity_type": "Chemical", "pos": [2, 17]}, {"entity": "1 , 7 - diphenyl - 4 , 6 - heptadien - 3 - ol", "entity_type": "Chemical", "pos": [54, 99]}], "task": "NER"}
{"text": "Curcuma comosa Roxb .", "entity": [], "task": "NER"}
{"text": "is ginger - family plant used to relieve menopausal symptoms .", "entity": [], "task": "NER"}
{"text": "Previous work showed that C . comosa extracts protect mice from ovariectomy - induced osteopenia with minimal effects on reproductive organs , and identified the diarylheptanoid ( 3R ) - 1 , 7 - diphenyl - ( 4E , 6E ) - 4 , 6 - heptadien - 3 - ol ( DPHD ) as the major active component of C . comosa rhizomes .", "entity": [{"entity": "diarylheptanoid", "entity_type": "Chemical", "pos": [162, 177]}, {"entity": "( 3R ) - 1 , 7 - diphenyl - ( 4E , 6E ) - 4 , 6 - heptadien - 3 - ol", "entity_type": "Chemical", "pos": [178, 246]}, {"entity": "DPHD", "entity_type": "Chemical", "pos": [249, 253]}], "task": "NER"}
{"text": "At 1 - 10 mu M , DPHD increased differentiation in transformed mouse osteoblasts , but the effect of DPHD on normal bone cells was unknown .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [17, 21]}, {"entity": "DPHD", "entity_type": "Chemical", "pos": [101, 105]}], "task": "NER"}
{"text": "We examined the concentration dependency and mechanism of action of DPHD relative to 17 beta - estradiol in nontransformed human osteoblasts ( h - OB ) .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [68, 72]}, {"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [85, 104]}], "task": "NER"}
{"text": "The h - OB were 10 - 100 fold more sensitive to DPHD than transformed osteoblasts : DPHD increased h - OB proliferation at 10nM and , at 100nM , activated MAP kinase signaling within 30min .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [48, 52]}, {"entity": "DPHD", "entity_type": "Chemical", "pos": [84, 88]}], "task": "NER"}
{"text": "In long - term differentiation assays , responses of h - OB to DPHD were significant at 10nM , and optimal response in most cases was at 100nM .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [63, 67]}], "task": "NER"}
{"text": "At 7 - 21 days , DPHD accelerated osteoblast differentiation , indicated by alkaline phosphatase activity and osteoblast - specific mRNA production .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [17, 21]}], "task": "NER"}
{"text": "Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780 .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [11, 15]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [39, 47]}, {"entity": "ICI182780", "entity_type": "Chemical", "pos": [68, 77]}], "task": "NER"}
{"text": "During differentiation , DPHD promoted early expression of osteoblast transcription factors , RUNX2 and osterix .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [25, 29]}], "task": "NER"}
{"text": "Subsequently , DPHD accelerated production of bone structural genes , including COL1A1 and osteocalcin comparably to 17 beta - estradiol .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [117, 136]}], "task": "NER"}
{"text": "In h - OB , DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10nM 17 beta - estradiol .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "17 beta - estradiol", "entity_type": "Chemical", "pos": [118, 137]}], "task": "NER"}
{"text": "We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations , making it a promising compound to protect bone in menopausal women .", "entity": [{"entity": "DPHD", "entity_type": "Chemical", "pos": [17, 21]}], "task": "NER"}
{"text": "Cyclohexanone derivatives with cytotoxicity from the fungus Penicillium commune .", "entity": [{"entity": "Cyclohexanone", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Four new cyclohexanone derivatives ( 2 - 5 ) and one known analog , ( - ) - Palitantin ( 1 ) were isolated from the EtOAc extract of Penicillium commune , a fungal strain of low - temperature habitats .", "entity": [{"entity": "cyclohexanone", "entity_type": "Chemical", "pos": [9, 22]}, {"entity": "( - ) - Palitantin", "entity_type": "Chemical", "pos": [68, 86]}, {"entity": "EtOAc", "entity_type": "Chemical", "pos": [116, 121]}], "task": "NER"}
{"text": "The structures of 2 - 5 were determined on the basis of extensive spectroscopic analysis .", "entity": [], "task": "NER"}
{"text": "Furthermore , the absolute configuration of 2 was assigned by electronic circular dichroism ( ECD ) calculations , whereas that 3 - 5 were deduced via the CD data .", "entity": [], "task": "NER"}
{"text": "Cytotoxicities of 2 - 5 against five human carcinoma cell lines ( Hela , A549 , MCF7 , HCT116 , T24 ) were evaluated .", "entity": [], "task": "NER"}
{"text": "Biological Therapies for Rheumatoid Arthritis : Progress to Date .", "entity": [], "task": "NER"}
{"text": "Biologic drugs for the management of rheumatoid arthritis ( RA ) have revolutionized the therapeutic armamentarium with the development of several novel monoclonal antibodies , which include murine , chimeric , humanized , fully human antibodies and fusion proteins .", "entity": [], "task": "NER"}
{"text": "These biologics bind to their targets with high affinity and specificity .", "entity": [], "task": "NER"}
{"text": "Since 1998 , nine different biologics have been approved by the US Food and Drug Administration ( FDA ) and European Medicines Agency ( EMA ) for the treatment of RA , and several others are in different stages of clinical trials .", "entity": [], "task": "NER"}
{"text": "This field is in continuous evolution and new biologics are tested every year .", "entity": [], "task": "NER"}
{"text": "Therefore a precise analysis is required in order to have a detailed and updated state of the art of this field .", "entity": [], "task": "NER"}
{"text": "In this review , our main aim is to analyse all available biological therapies that are FDA and EMA approved for the treatment of RA and also those that are in clinical trials for the management of RA patients .", "entity": [], "task": "NER"}
{"text": "Lixisenatide : first global approval .", "entity": [], "task": "NER"}
{"text": "The selective once - daily prandial glucagon - like peptide - 1 ( GLP - 1 ) receptor agonist lixisenatide ( Lyxumia ( (R) ) ) is under development with Sanofi for the treatment of type 2 diabetes mellitus .", "entity": [], "task": "NER"}
{"text": "Lixisenatide belongs to a class of GLP - 1 compounds designed to mimic the endogenous hormone GLP - 1 .", "entity": [], "task": "NER"}
{"text": "Native GLP - 1 stimulates insulin secretion in a glucose - dependent manner , as well as suppressing glucagon production and slowing gastric emptying .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [49, 56]}], "task": "NER"}
{"text": "A once - daily subcutaneous formulation of lixisenatide has been approved in the EU , Iceland , Liechtenstein , Norway and Mexico for the treatment of type 2 diabetes , and is under regulatory review in the USA , Switzerland , Brazil , Canada , Ukraine , South Africa , Japan and Australia .", "entity": [], "task": "NER"}
{"text": "This article summarizes the milestones in the development of lixisenatide , leading to this first approval for use in adults with type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Annexin A2 regulates beta 1 integrin internalization and intestinal epithelial cell migration .", "entity": [], "task": "NER"}
{"text": "The gastrointestinal epithelium functions as an important barrier that separates luminal contents from the underlying tissue compartment and is vital in maintaining mucosal homeostasis .", "entity": [{"entity": "luminal", "entity_type": "Chemical", "pos": [81, 88]}], "task": "NER"}
{"text": "Mucosal wounds in inflammatory disorders compromise the critical epithelial barrier .", "entity": [], "task": "NER"}
{"text": "In response to injury , intestinal epithelial cells ( IECs ) rapidly migrate to reseal wounds .", "entity": [], "task": "NER"}
{"text": "We have previously observed that a membrane associated , Actin binding protein , Annexin A2 ( AnxA2 ) , is up - regulated in migrating IECs and plays an important role in promoting wound closure .", "entity": [], "task": "NER"}
{"text": "To identify the mechanisms by which AnxA2 promotes IEC movement and wound closure we used a loss of function approach .", "entity": [], "task": "NER"}
{"text": "AnxA2 specific shRNA was utilized to generate IECs with stable down - regulation of AnxA2 .", "entity": [], "task": "NER"}
{"text": "Loss of AnxA2 inhibited IEC migration while promoting enhanced cell - matrix adhesion .", "entity": [], "task": "NER"}
{"text": "These functional effects were associated with increased levels of beta 1 integrin protein , which is reported to play an important role in mediating the cell - matrix adhesive properties of epithelial cells .", "entity": [], "task": "NER"}
{"text": "Since cell migration requires dynamic turnover of integrin based adhesions , we tested if AnxA2 modulates internalization of cell surface beta 1 integrin required for forward cell movement .", "entity": [], "task": "NER"}
{"text": "Indeed , pulse - chase biotinylation experiments in IECs lacking AnxA2 demonstrated a significant increase in cell surface beta 1 integrin that was accompanied by decreased beta 1 integrin internalization and degradation .", "entity": [], "task": "NER"}
{"text": "These findings support an important role of AnxA2 in controlling dynamics of beta 1 integrin at the cell surface that in turn is required for the active turnover of cell - matrix associations , cell migration and wound closure .", "entity": [], "task": "NER"}
{"text": "Human polymerase kappa uses a template - slippage deletion mechanism , but can realign the slipped strands to favour base substitution mutations over deletions .", "entity": [], "task": "NER"}
{"text": "Polymerases belonging to the DinB class of the Y - family translesion synthesis DNA polymerases have a preference for accurately and efficiently bypassing damaged guanosines .", "entity": [{"entity": "guanosines", "entity_type": "Chemical", "pos": [163, 173]}], "task": "NER"}
{"text": "These DinB polymerases also generate single - base ( - 1 ) deletions at high frequencies with most occurring on repetitive ' deletion hotspot ' sequences .", "entity": [], "task": "NER"}
{"text": "Human DNA polymerase kappa ( hPol kappa ) , the eukaryotic DinB homologue , displays an unusual efficiency for to extend from mispaired primer termini , either by extending directly from the mispair or by primer - template misalignment .", "entity": [], "task": "NER"}
{"text": "This latter property explains how hPol kappa creates single - base deletions in non - repetitive sequences , but does not address how deletions occur in repetitive deletion hotspots .", "entity": [], "task": "NER"}
{"text": "Here , we show that hPol kappa uses a classical Streisinger template - slippage mechanism to generate - 1 deletions in repetitive sequences , as do the bacterial and archaeal homologues .", "entity": [], "task": "NER"}
{"text": "After the first nucleotide is added by template slippage , however , hPol kappa can efficiently realign the primer - template duplex before continuing DNA synthesis .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [16, 26]}], "task": "NER"}
{"text": "Strand realignment results in a base - substitution mutation , minimizing generation of more deleterious frameshift mutations .", "entity": [], "task": "NER"}
{"text": "On non - repetitive sequences , we find that nucleotide misincorporation is slower if the incoming nucleotide can correctly basepair with the nucleotide immediately 5 ' to the templating base , thereby competing against the mispairing with the templating base .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [45, 55]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [99, 109]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [142, 152]}], "task": "NER"}
{"text": "Exploring the zebrafish embryo as an alternative model for the evaluation of liver toxicity by histopathology and expression profiling .", "entity": [], "task": "NER"}
{"text": "The whole zebrafish embryo model ( ZFE ) has proven its applicability in developmental toxicity testing .", "entity": [], "task": "NER"}
{"text": "Since functional hepatocytes are already present from 36 h post fertilization onwards , whole ZFE have been proposed as an attractive alternative to mammalian in vivo models in hepatotoxicity testing .", "entity": [], "task": "NER"}
{"text": "The goal of the present study is to further underpin the applicability of whole ZFE for hepatotoxicity testing by combining histopathology and next - generation sequencing - based gene expression profiling .", "entity": [], "task": "NER"}
{"text": "To this aim , whole ZFE and adult zebrafish were exposed to a set of hepatotoxic reference compounds .", "entity": [], "task": "NER"}
{"text": "Histopathology revealed compound and life - stage - specific effects indicative of toxic injury in livers of whole ZFE and adult zebrafish .", "entity": [], "task": "NER"}
{"text": "Next - generation sequencing ( NGS ) was used to compare transcript profiles in pooled individual RNA samples of whole ZFE and livers of adult zebrafish .", "entity": [], "task": "NER"}
{"text": "This revealed that hepatotoxicity - associated expression can be detected beyond the overall transcription noise in the whole embryo .", "entity": [], "task": "NER"}
{"text": "In situ hybridization verified liver specificity of selected highly expressed markers in whole ZFE .", "entity": [], "task": "NER"}
{"text": "Finally , cyclosporine A ( CsA ) was used as an illustrative case to support applicability of ZFE in hepatotoxicity testing by comparing CsA - induced gene expression between ZFE , in vivo mouse liver and HepaRG cells on the levels of single genes , pathways and transcription factors .", "entity": [{"entity": "cyclosporine A", "entity_type": "Chemical", "pos": [10, 24]}, {"entity": "CsA", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "CsA", "entity_type": "Chemical", "pos": [137, 140]}], "task": "NER"}
{"text": "While there was no clear overlap on single gene level between the whole ZFE and in vivo mouse liver , strong similarities were observed between whole ZFE and in vivo mouse liver in regulated pathways related to hepatotoxicity , as well as in relevant overrepresented transcription factors .", "entity": [], "task": "NER"}
{"text": "In conclusion , both the use of NGS of pooled RNA extracts analysis combined with histopathology and traditional microarray in single case showed the potential to detect liver - related genes and processes within the transcriptome of a whole zebrafish embryo .", "entity": [], "task": "NER"}
{"text": "This supports the applicability of the whole ZFE model for compound - induced hepatotoxicity screening .", "entity": [], "task": "NER"}
{"text": "Synthesis and Cytostatic and Antiviral Activities of 2 ' - Deoxy - 2 ' , 2 ' - difluororibo - and 2 ' - Deoxy - 2 ' - fluororibonucleosides Derived from 7 - ( Het ) aryl - 7 - deazaadenines .", "entity": [{"entity": "2 ' - Deoxy - 2 ' , 2 ' - difluororibo - and 2 ' - Deoxy - 2 ' - fluororibonucleosides", "entity_type": "Chemical", "pos": [53, 139]}, {"entity": "7 - ( Het ) aryl - 7 - deazaadenines", "entity_type": "Chemical", "pos": [153, 189]}], "task": "NER"}
{"text": "A series of sugar - modified derivatives of cytostatic 7 - heteroaryl - 7 - deazaadenosines ( 2 ' - deoxy - 2 ' - fluororibo - and 2 ' - deoxy - 2 ' , 2 ' - difluororibonucleosides ) bearing an aryl or heteroaryl group at position 7 was prepared and screened for biological activity .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [12, 17]}, {"entity": "7 - heteroaryl - 7 - deazaadenosines", "entity_type": "Chemical", "pos": [55, 91]}, {"entity": "2 ' - deoxy - 2 ' - fluororibo - and 2 ' - deoxy - 2 ' , 2 ' - difluororibonucleosides", "entity_type": "Chemical", "pos": [94, 180]}, {"entity": "aryl", "entity_type": "Chemical", "pos": [194, 198]}, {"entity": "heteroaryl", "entity_type": "Chemical", "pos": [202, 212]}], "task": "NER"}
{"text": "The difluororibonucleosides were prepared by non - stereoselective glycosidation of 6 - chloro - 7 - deazapurine with benzoyl - protected 2 - deoxy - 2 , 2 - difluoro - D - erythro - pentofuranosyl - 1 - mesylate , followed by amination and aqueous Suzuki cross - couplings with ( het ) arylboronic acids .", "entity": [{"entity": "difluororibonucleosides", "entity_type": "Chemical", "pos": [4, 27]}, {"entity": "6 - chloro - 7 - deazapurine", "entity_type": "Chemical", "pos": [84, 112]}, {"entity": "benzoyl - protected 2 - deoxy - 2 , 2 - difluoro - D - erythro - pentofuranosyl - 1 - mesylate", "entity_type": "Chemical", "pos": [118, 212]}, {"entity": "( het ) arylboronic acids", "entity_type": "Chemical", "pos": [279, 304]}], "task": "NER"}
{"text": "The fluororibo derivatives were prepared by aqueous palladium - catalyzed cross - coupling reactions of the corresponding 7 - iodo - 7 - deazaadenine 2 ' - deoxy - 2 ' - fluororibonucleoside 20 with ( het ) arylboronic acids .", "entity": [{"entity": "fluororibo", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "palladium", "entity_type": "Chemical", "pos": [52, 61]}, {"entity": "7 - iodo - 7 - deazaadenine 2 ' - deoxy - 2 ' - fluororibonucleoside", "entity_type": "Chemical", "pos": [122, 190]}, {"entity": "( het ) arylboronic acids", "entity_type": "Chemical", "pos": [199, 224]}], "task": "NER"}
{"text": "The key intermediate 20 was prepared by a six - step sequence from the corresponding arabinonucleoside by selective protection of 3 ' - and 5 ' - hydroxy groups with acid - labile groups , followed by stereoselective SN 2 fluorination and deprotection .", "entity": [{"entity": "arabinonucleoside", "entity_type": "Chemical", "pos": [85, 102]}, {"entity": "3 ' - and 5 ' - hydroxy", "entity_type": "Chemical", "pos": [130, 153]}], "task": "NER"}
{"text": "Some of the title nucleosides and 7 - iodo - 7 - deazaadenine intermediates showed micromolar cytostatic or anti - HCV activity .", "entity": [{"entity": "nucleosides", "entity_type": "Chemical", "pos": [18, 29]}, {"entity": "7 - iodo - 7 - deazaadenine", "entity_type": "Chemical", "pos": [34, 61]}], "task": "NER"}
{"text": "The most active were 7 - iodo and 7 - ethynyl derivatives .", "entity": [{"entity": "7 - iodo", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "7 - ethynyl", "entity_type": "Chemical", "pos": [34, 45]}], "task": "NER"}
{"text": "The corresponding 2 ' - deoxy - 2 ' , 2 ' - difluororibonucleoside 5 ' - O - triphosphates were found to be good substrates for bacterial DNA polymerases , but are inhibitors of human polymerase alpha .", "entity": [{"entity": "2 ' - deoxy - 2 ' , 2 ' - difluororibonucleoside 5 ' - O - triphosphates", "entity_type": "Chemical", "pos": [18, 90]}], "task": "NER"}
{"text": "Tissue Factor Activity and ECM - Related Gene Expression in Human Aortic Endothelial Cells Grown on Electrospun Biohybrid Scaffolds .", "entity": [], "task": "NER"}
{"text": "All blood vessels are lined with a quiescent endothelium , which aids in regulating regular blood flow and avoiding thrombus formation .", "entity": [], "task": "NER"}
{"text": "Current attempts at replacing diseased blood vessels frequently fail due to the intrinsic thrombogenicity of the materials used as vascular grafts .", "entity": [], "task": "NER"}
{"text": "In extending our previous work where we introduced a new candidate scaffolds for vascular grafts electrospun from a blend solution of PLGA , gelatin , and elastin ( PGE ) , this study aimed to evaluate the potential of PGE scaffolds to support nonthrombogenic monolayers of primary isolates of human aortic endothelial cells ( HAECs ) , as assessed by a combination of biochemical , molecular , and bioinformatics - based analyses .", "entity": [], "task": "NER"}
{"text": "After 24 h of culture on 3 - D fibrous PGE scaffolds , HAECs formed a confluent , nonthrombogenic , and physiologically competent monolayer , as assessed by tissue factor ( TF ) gene expression and protein activity assays .", "entity": [], "task": "NER"}
{"text": "The levels of TF mRNA / protein activity in HAECs grown on PGE scaffolds were similar to those on gelatin or collagen IV - coated 2 - D surfaces .", "entity": [], "task": "NER"}
{"text": "In addition , bioinformatics - based analysis of a focused microarray containing 84 ECM - related cDNA probes demonstrated that HAECs essentially expressed a histotypic ECM - related \" transcriptome \" on PGE scaffolds , where cells were more quiescent than cells cultured on 2 - D coverslips coated with gelatin ( a well - known \" inert \" substrate for conventional EC culture ) , but less so than on 2 - D PGE films .", "entity": [], "task": "NER"}
{"text": "These data suggest an important role for nanorough substrates ( PGE films ) in passivating endothelial cells and confirm the crucial effect of substrate composition in this process .", "entity": [], "task": "NER"}
{"text": "Principal component analysis of microarray data on the above substrates ( including collagen IV ) implied that substrate composition plays a greater role than surface topography in affecting the endothelial ECM - related \" transcriptome \" .", "entity": [], "task": "NER"}
{"text": "Taken together , our findings suggest that electrospun PGE scaffolds are potentially suitable for application in small diameter vascular tissue engineering .", "entity": [], "task": "NER"}
{"text": "Pressure modulation of ras - membrane interactions and intervesicle transfer .", "entity": [], "task": "NER"}
{"text": "Proteins attached to the plasma membrane frequently encounter mechanical stresses , including high hydrostatic pressure ( HHP ) stress .", "entity": [], "task": "NER"}
{"text": "Signaling pathways involving membrane - associated small GTPases ( e . g . , Ras ) have been identified as critical loci for pressure perturbation .", "entity": [], "task": "NER"}
{"text": "However , the impact of mechanical stimuli on biological outputs is still largely terra incognita .", "entity": [], "task": "NER"}
{"text": "The present study explores the effect of HHP on the membrane association , dissociation , and intervesicle transfer process of N - Ras by using a FRET - based assay to obtain the kinetic parameters and volumetric properties along the reaction path of these processes .", "entity": [], "task": "NER"}
{"text": "Notably , membrane association is fostered upon pressurization .", "entity": [], "task": "NER"}
{"text": "Conversely , depending on the nature and lateral organization of the lipid membrane , acceleration or retardation is observed for the dissociation step .", "entity": [], "task": "NER"}
{"text": "In addition , HHP can be inferred as a positive regulator of N - Ras clustering , in particular in heterogeneous membranes .", "entity": [], "task": "NER"}
{"text": "The susceptibility of membrane interaction to pressure raises the idea of a role of lipidated signaling molecules as mechanosensors , transducing mechanical stimuli to chemical signals by regulating their membrane binding and dissociation .", "entity": [], "task": "NER"}
{"text": "Finally , our results provide first insights into the influence of pressure on membrane - associated Ras - controlled signaling events in organisms living under extreme environmental conditions such as those that are encountered in the deep sea and sub - seafloor environments , where pressures reach the kilobar ( 100 MPa ) range .", "entity": [], "task": "NER"}
{"text": "Modeling the Conformational Preference of the Carbon - Bonded Covalent Adduct Formed upon Exposure of 2 ' - Deoxyguanosine to Ochratoxin A .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "2 ' - Deoxyguanosine", "entity_type": "Chemical", "pos": [102, 122]}, {"entity": "Ochratoxin A", "entity_type": "Chemical", "pos": [126, 138]}], "task": "NER"}
{"text": "The conformational flexibility of the C8 - linked guanine adduct formed from attachment of ochratoxin A ( OTA ) was analyzed using a systematic computational approach and models ranging from the nucleobase to the adducted DNA helix .", "entity": [{"entity": "guanine", "entity_type": "Chemical", "pos": [50, 57]}, {"entity": "ochratoxin A", "entity_type": "Chemical", "pos": [91, 103]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [106, 109]}, {"entity": "nucleobase", "entity_type": "Chemical", "pos": [195, 205]}], "task": "NER"}
{"text": "A focus was placed on the influence of the C8 - modification of 2 ' - deoxyguanosine ( dG ) on the preferred relative arrangement of the nucleobase and the C8 - substituent and , more importantly , the anti / syn conformational preference with respect to the glycosidic bond .", "entity": [{"entity": "2 ' - deoxyguanosine", "entity_type": "Chemical", "pos": [64, 84]}, {"entity": "nucleobase", "entity_type": "Chemical", "pos": [137, 147]}], "task": "NER"}
{"text": "Although OTA is twisted with respect to the base in the nucleobase model , addition of the deoxyribose sugar induces a further twist and restricts rotation about the C - C linkage due to close contacts between OTA and the sugar .", "entity": [{"entity": "OTA", "entity_type": "Chemical", "pos": [9, 12]}, {"entity": "nucleobase", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "deoxyribose sugar", "entity_type": "Chemical", "pos": [91, 108]}, {"entity": "C - C", "entity_type": "Chemical", "pos": [166, 171]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [210, 213]}], "task": "NER"}
{"text": "The nucleoside model preferentially adpots a syn orientation ( by 10 - 20 kJ mol ( - 1 ) depending on the OTA conformation ) due to the presence of an O5 ' - H . . . N3 interaction .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "OTA", "entity_type": "Chemical", "pos": [106, 109]}, {"entity": "H", "entity_type": "Chemical", "pos": [158, 159]}], "task": "NER"}
{"text": "However , when this hydrogen bond is eliminated , which better mimics the DNA environment , a small ( < 5 kJ mol ( - 1 ) ) anti / syn energy difference is predicted .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "Inclusion of the 5 ' - monophosphate group leads to an up to 20 kJ mol ( - 1 ) preference for the syn ( nucleotide ) conformation due to stabilizing base - phosphate interactions involving the amino group of guanine .", "entity": [{"entity": "5 ' - monophosphate", "entity_type": "Chemical", "pos": [17, 36]}, {"entity": "syn ( nucleotide )", "entity_type": "Chemical", "pos": [98, 116]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [156, 165]}, {"entity": "amino", "entity_type": "Chemical", "pos": [193, 198]}, {"entity": "guanine", "entity_type": "Chemical", "pos": [208, 215]}], "task": "NER"}
{"text": "Nevertheless , MD simulations and free energy analysis predict that both syn - and anti - conformations of OTB - dG are equally stable in helices when paired opposite cytosine .", "entity": [{"entity": "OTB - dG", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "cytosine", "entity_type": "Chemical", "pos": [167, 175]}], "task": "NER"}
{"text": "These results indicate that the adduct will likely adopt a syn conformation in an isolated nucleoside and nucleotide , while a mixture of syn and anti conformations will be observed in DNA duplexes .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [91, 101]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [106, 116]}], "task": "NER"}
{"text": "Since the syn conformation could stabilize base mismatches upon DNA replication or Z - DNA structures with varied biological outcomes , future computational and experimental work should elucidate the consequences of the conformational preference of this potentially harmful DNA lesion .", "entity": [], "task": "NER"}
{"text": "Synthesis and Biological Evaluation of a New Series of Hexahydro - 2H - pyrano [ 3 , 2 - c ] quinolines as Novel Selective sigma 1 Receptor Ligands .", "entity": [{"entity": "Hexahydro - 2H - pyrano [ 3 , 2 - c ] quinolines", "entity_type": "Chemical", "pos": [55, 103]}], "task": "NER"}
{"text": "The synthesis and pharmacological activity of a new series of hexahydro - 2H - pyrano [ 3 , 2 - c ] quinoline derivatives as potent sigma 1 receptor ( sigma 1R ) ligands are reported .", "entity": [{"entity": "hexahydro - 2H - pyrano [ 3 , 2 - c ] quinoline", "entity_type": "Chemical", "pos": [62, 109]}], "task": "NER"}
{"text": "This family , which does not contain the highly basic amino group usually present in other sigma 1R ligands , showed high selectivity over the sigma 2 receptor ( sigma 2R ) .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [54, 59]}], "task": "NER"}
{"text": "The activity was shown to reside in only one of the four possible diastereoisomers , which exhibited a perfect match with known sigma 1R pharmacophores .", "entity": [], "task": "NER"}
{"text": "A hit to lead program based on a high - throughput screening hit ( 8a ) led to the identification of compound 32c , with substantially improved activity and physicochemical properties .", "entity": [], "task": "NER"}
{"text": "Compound 32c also exhibited a good ADMET ( absorption , distribution , metabolism , excretion , toxicity ) profile and was identified as a sigma 1R antagonist on the basis of its analgesic activity in the mouse capsaicin and formalin models of neurogenic pain .", "entity": [{"entity": "capsaicin", "entity_type": "Chemical", "pos": [211, 220]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [225, 233]}], "task": "NER"}
{"text": "Mycoleptodiscins A and B , Cytotoxic Alkaloids from the Endophytic Fungus Mycoleptodiscus sp .", "entity": [{"entity": "Mycoleptodiscins A and B", "entity_type": "Chemical", "pos": [0, 24]}], "task": "NER"}
{"text": "F0194 .", "entity": [], "task": "NER"}
{"text": "Two novel reddish - orange alkaloids , mycoleptodiscin A ( 1 ) and mycoleptodiscin B ( 2 ) , were isolated from liquid cultures of the endophytic fungus Mycoleptodiscus sp . that had been isolated from Desmotes incomparabilis in Panama .", "entity": [{"entity": "mycoleptodiscin A", "entity_type": "Chemical", "pos": [39, 56]}, {"entity": "mycoleptodiscin B", "entity_type": "Chemical", "pos": [67, 84]}], "task": "NER"}
{"text": "Elucidation of their structures was accomplished using 1D and 2D NMR spectroscopy in combination with IR spectroscopic and MS data .", "entity": [], "task": "NER"}
{"text": "These compounds are indole - terpenes with a new skeleton uncommon in nature .", "entity": [{"entity": "indole", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "terpenes", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Mycoleptodiscin B ( 2 ) was active in inhibiting the growth of cancer cell lines with IC50 values in the range 0 . 60 - 0 . 78 mu M .", "entity": [{"entity": "Mycoleptodiscin B", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Altering colloidal surface functionalization using DNA encapsulated inside monodisperse gelatin microsphere templates .", "entity": [], "task": "NER"}
{"text": "Soluble oligonucleotides are typically introduced to bulk solution to promote hybridization activity on DNA - functionalized surfaces .", "entity": [], "task": "NER"}
{"text": "Here , an alternative approach is explored by encapsulating secondary target strands inside semipermeable colloidal satellite assemblies , then triggering their release at 37 degrees C for subsequent surface hybridization activity .", "entity": [], "task": "NER"}
{"text": "To prepare DNA - loaded satellite assemblies , uniform gelatin microspheres are fabricated using microfluidics , loaded with 15 base - long secondary DNA targets , capped with a polyelectrolyte bilayer , and finally coated with a monolayer of polystyrene microspheres functionalized with duplexes comprised of immobilized probes and soluble , 13 base - long hybridization partner strands .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [243, 254]}], "task": "NER"}
{"text": "Once warmed to 37 degrees C , secondary DNA targets are released from the gelatin template and then competitively displace the shorter , original hybridization partners on the polystyrene microspheres .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [176, 187]}], "task": "NER"}
{"text": "Quantitating the Lattice Strain Dependence of Monolayer Pt Shell Activity toward Oxygen Reduction .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [56, 58]}, {"entity": "Oxygen", "entity_type": "Chemical", "pos": [81, 87]}], "task": "NER"}
{"text": "Lattice strain of Pt - based catalysts reflecting d - band status is the decisive factor of their catalytic activity toward oxygen reduction reaction ( ORR ) .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [124, 130]}], "task": "NER"}
{"text": "For the newly arisen monolayer Pt system , however , no general strategy to isolate the lattice strain has been achieved due to the short - range ordering structure of monolayer Pt shells on different facets of core nanoparticles .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [31, 33]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [178, 180]}], "task": "NER"}
{"text": "Herein , based on the extended X - ray absorption fine structure of monolayer Pt atoms on various single crystal facets , we propose an effective methodology for evaluating the lattice strain of monolayer Pt shells on core nanoparticles .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [78, 80]}, {"entity": "Pt", "entity_type": "Chemical", "pos": [205, 207]}], "task": "NER"}
{"text": "The quantitative lattice strain establishes a direct correlation to monolayer Pt shell ORR activity .", "entity": [{"entity": "Pt", "entity_type": "Chemical", "pos": [78, 80]}], "task": "NER"}
{"text": "Antioxidant capacity of anthocyanins from Rhodomyrtus tomentosa ( Ait . ) and identification of the major anthocyanins .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [106, 118]}], "task": "NER"}
{"text": "The anthocyanins in the fruits of Rhodomyrtus tomentosa ( ACN ) were extracted by 1 % TFA in methanol , and then purified by X - 5 resin column and C18 ( SPE ) cartridges .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "TFA", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "The purified anthocyanin extract ( ART ) from the fruits of R . tomentosa showed strong antioxidant activities , including DPPH radical - scavenging capacity , ABTS radical scavenging capacity , reducing power and oxygen radical absorbance capacity ( ORAC ) .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [13, 24]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [123, 127]}, {"entity": "ABTS", "entity_type": "Chemical", "pos": [160, 164]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [214, 220]}], "task": "NER"}
{"text": "The purified anthocyanin extract was analyzed by high performance liquid chromatography ( HPLC ) .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [13, 24]}], "task": "NER"}
{"text": "The major anthocyanins were purified by semi - preparative HPLC and Sephadex LH - 20 column chromatography , and were identified as cyanidin - 3 - O - glucoside , peonidin - 3 - O - glucoside , malvidin - 3 - O - glucoside , petunidin - 3 - O - glucoside , delphinidin - 3 - O - glucoside and pelargonidin - 3 - glucoside by HPLC - ESI / MS and nuclear magnetic resonance spectroscopy ( NMR ) .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [10, 22]}, {"entity": "cyanidin - 3 - O - glucoside", "entity_type": "Chemical", "pos": [132, 160]}, {"entity": "peonidin - 3 - O - glucoside", "entity_type": "Chemical", "pos": [163, 191]}, {"entity": "malvidin - 3 - O - glucoside", "entity_type": "Chemical", "pos": [194, 222]}, {"entity": "petunidin - 3 - O - glucoside", "entity_type": "Chemical", "pos": [225, 254]}, {"entity": "delphinidin - 3 - O - glucoside", "entity_type": "Chemical", "pos": [257, 288]}, {"entity": "pelargonidin - 3 - glucoside", "entity_type": "Chemical", "pos": [293, 321]}], "task": "NER"}
{"text": "Cyanidin - 3 - O - glucoside was considered as the most abundant anthocyanin , which was 29 . 4mg / 100g dry weight of R . tomentosa fruits .", "entity": [{"entity": "Cyanidin - 3 - O - glucoside", "entity_type": "Chemical", "pos": [0, 28]}, {"entity": "anthocyanin", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "Additionally , all the major anthocyanins were identified from R . tomentosa fruit for the first time .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [29, 41]}], "task": "NER"}
{"text": "Dummy - template molecularly imprinted solid phase extraction for selective analysis of ractopamine in pork .", "entity": [{"entity": "ractopamine", "entity_type": "Chemical", "pos": [88, 99]}], "task": "NER"}
{"text": "Molecularly imprinted polymers ( MIPs ) for selective adsorption of ractopamine hydrochloride ( RAC ) were synthesised by an in situ method , in which salbutamol ( SAL ) was used as the dummy - template to avoid the template leakage .", "entity": [{"entity": "ractopamine hydrochloride", "entity_type": "Chemical", "pos": [68, 93]}, {"entity": "RAC", "entity_type": "Chemical", "pos": [96, 99]}, {"entity": "salbutamol", "entity_type": "Chemical", "pos": [151, 161]}, {"entity": "SAL", "entity_type": "Chemical", "pos": [164, 167]}], "task": "NER"}
{"text": "Scanning electron microscopy ( SEM ) , mercury porosimerty and Fourier transform infrared spectroscopy ( FTIR ) were used to investigate the physical and morphological characteristics of the dummy - template MIPs .", "entity": [], "task": "NER"}
{"text": "The test of adsorption selectivity indicated that the dummy - template MIPs exhibited high selectivity to RAC .", "entity": [{"entity": "RAC", "entity_type": "Chemical", "pos": [106, 109]}], "task": "NER"}
{"text": "The saturated adsorption capacity for RAC on dummy - template MIPs was 90 . 9 mu gg ( - 1 ) .", "entity": [{"entity": "RAC", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Based on the dummy - template polymers , a liquid chromatography - mass spectrometry ( LC - MS ) method was developed for the selective analysis of RAC in real pork samples .", "entity": [{"entity": "RAC", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "The averages of intra - and inter - day accuracy ranged from 78 . 9 % to 92 . 2 % and from 90 . 7 % to 93 . 1 % , respectively .", "entity": [], "task": "NER"}
{"text": "The RSD % of repeatability ranged from 1 . 9 % to 6 . 3 % , and the RSD % of intermediate precision ranged from 3 . 5 % to 9 . 2 % , while the limit of detection ( LOD ) was 0 . 02 mu gkg ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "Plums ( Prunus domestica L . ) are a good source of yeasts producing organic acids of industrial interest from glycerol .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "The production of organic acids from several yeasts isolated from mature plums on media containing glycerol as carbon source was analysed by HPLC - UV .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [99, 107]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [111, 117]}], "task": "NER"}
{"text": "The yeasts isolated were identified by sequencing the 5 . 8S internal transcribed spacer as Pichia fermentans , Wickerhamomyces anomalus and Candida oleophila .", "entity": [], "task": "NER"}
{"text": "The organic acid profiles of these strains comprise acetic , citric , succinic and malic acids that qualitatively and quantitatively vary between different species as well as among strains from the same species .", "entity": [{"entity": "acetic , citric , succinic and malic acids", "entity_type": "Chemical", "pos": [52, 94]}], "task": "NER"}
{"text": "The production from glycerol of succinic , acetic , citric , malic and oxalic acids from C . oleophila and W . anomalus , and that of succinic , oxalic and acetic acids by P . fermentans is reported for the first time in this work , as is the production of oxalic acid from glycerol in yeasts .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "succinic , acetic , citric , malic and oxalic acids", "entity_type": "Chemical", "pos": [32, 83]}, {"entity": "succinic , oxalic and acetic acids", "entity_type": "Chemical", "pos": [134, 168]}, {"entity": "oxalic acid", "entity_type": "Chemical", "pos": [257, 268]}, {"entity": "glycerol", "entity_type": "Chemical", "pos": [274, 282]}], "task": "NER"}
{"text": "Our results also showed that mature fruits can be a good source of new yeasts able to metabolise glycerol , producing different organic acids with industrial and biotechnological interest .", "entity": [{"entity": "glycerol", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "Active films based on cocoa extract with antioxidant , antimicrobial and biological applications .", "entity": [], "task": "NER"}
{"text": "Novel films of ethylene - vinyl alcohol copolymer ( EVOH ) containing flavonoid - rich cocoa were developed .", "entity": [{"entity": "ethylene - vinyl alcohol", "entity_type": "Chemical", "pos": [15, 39]}, {"entity": "EVOH", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "To understand their potential application as active packaging material , antioxidant and antimicrobial properties of the films were determined as well as the antioxidant activity of the release compounds in Caco - 2 human epithelial colorectal adenocarcinoma cells .", "entity": [], "task": "NER"}
{"text": "Exposure of the films to aqueous food simulant showed antioxidant capacity .", "entity": [], "task": "NER"}
{"text": "The release of cocoa extract components was dependent on the antioxidant concentration incorporated in the film and on temperature .", "entity": [], "task": "NER"}
{"text": "Cocoa extract and the fraction obtained after in vitro gastrointestinal digestion presented antioxidant activity against oxidative stress induced by hydrogen peroxide in Caco - 2 cells .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [149, 166]}], "task": "NER"}
{"text": "Films with 10 % , 15 % , and 20 % cocoa extract produced bactericidal effect against Staphylococcus aureus , Listeria monocytogenes , Escherichia coli and Salmonella enterica .", "entity": [], "task": "NER"}
{"text": "The application of films to an infant milk formula , previously inoculated with L . monocytogenes , inhibited the growth of bacteria 1 . 5log units the first day and showed sustained release , inhibiting 0 . 52 and 0 . 76log units , respectively , by the sixth day , while cocoa powder added directly did not produce any effect .", "entity": [], "task": "NER"}
{"text": "In vivo and in vitro antioxidant activity and alpha - glucosidase , alpha - amylase inhibitory effects of flavonoids from Cichorium glandulosum seeds .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [106, 116]}], "task": "NER"}
{"text": "The aim of this study was to investigate the antioxidant , anti - glucosidase and anti - amylase activities of total flavonoids ( TFs ) from Cichorium glandulosum seeds , and to analyse its chemical composition by HPLC - ESI / MS .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [117, 127]}], "task": "NER"}
{"text": "In vitro study , radical scavenging IC50 values of TFs were 7 . 33 +/- 0 . 093 , 9 . 24 +/- 0 . 100 , 154 . 33 +/- 11 . 38 and 256 . 7 +/- 4 . 86 mu g / ml for DPPH , ABTS , hydroxyl radicals , and superoxide anion , respectively .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [160, 164]}, {"entity": "ABTS", "entity_type": "Chemical", "pos": [167, 171]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [174, 182]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [198, 208]}], "task": "NER"}
{"text": "In the 8 - 64mg / ml range , alpha - glucosidase and alpha - amylase were inhibited by TFs to a certain extent .", "entity": [], "task": "NER"}
{"text": "In vivo , the treatment groups with TFs ( 100 , 200 , 400mg / kg ) showed a significant decrease in the malondialdehyde level , the superoxide dismutase and glutathione levels were restored to almost normal levels , and the catalase and glutathione peroxidase levels significantly increased compared to the CCl4 - intoxicated group in rats .", "entity": [{"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [104, 119]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [132, 142]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [157, 168]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [237, 248]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [307, 311]}], "task": "NER"}
{"text": "The present study suggests that C . glandulosum seeds should be given special attention because of their antioxidant and anti - glucosidase , anti - amylase activity .", "entity": [], "task": "NER"}
{"text": "Distribution , antioxidant and characterisation of phenolic compounds in soybeans , flaxseed and olives .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [51, 59]}], "task": "NER"}
{"text": "The distribution of free and bound phenolic compounds present in soybean , flaxseed and olive were investigated .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [35, 43]}], "task": "NER"}
{"text": "The phenolic compounds were fractionated on the basis on their solubility characteristics in water , alcohol , dilute base and dilute acid .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "alcohol", "entity_type": "Chemical", "pos": [101, 108]}], "task": "NER"}
{"text": "Reversed phase high pressure liquid chromatography ( RP - HPLC ) and mass spectrometry ( MS ) were used for identification of individual components of phenolic compounds .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "Antioxidant activity ( AA % ) of free and bound phenolic compounds was measured using the linoleic acid / beta - carotene assay .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "linoleic acid", "entity_type": "Chemical", "pos": [90, 103]}, {"entity": "beta - carotene", "entity_type": "Chemical", "pos": [106, 121]}], "task": "NER"}
{"text": "The water - soluble phenolic compound fractions represented 68 - 81 % , 50 - 72 % and 46 - 56 % of the total phenolic compounds measured in full - fat soybean , olive and flaxseed , respectively .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [109, 117]}], "task": "NER"}
{"text": "Methanolic extraction of free phenolic compounds without heat , solubilised 21 - 56 % , 42 - 62 % and 34 - 51 % of the total phenolic compounds measured in soybean , olive and flaxseed , respectively ; methanol extraction of free phenolic compounds with heat solubilised a further 24 - 34 % , 31 - 37 % and 36 - 37 % of phenolic compounds from soybean , olive and flaxseed , respectively .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [125, 133]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [202, 210]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [230, 238]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [320, 328]}], "task": "NER"}
{"text": "Further dilute alkali and dilute acid solubilised the remaining 10 - 40 % , 1 - 21 % and 12 - 29 % of the total phenolic compounds from soybean , olive and flaxseed , respectively .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [112, 120]}], "task": "NER"}
{"text": "Results indicated that the full - fat meals of soybean , flaxseed and olive showed higher antioxidant activity compared to defatted meals .", "entity": [], "task": "NER"}
{"text": "RP - HPLC and LC - MS / MS profil1 for soybean , flaxseed and olive indicate two classes of phenolic compounds designated as free and bound phenolic compounds .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [92, 100]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [140, 148]}], "task": "NER"}
{"text": "Maqui berry ( Aristotelia chilensis ) and the constituent delphinidin glycoside inhibit photoreceptor cell death induced by visible light .", "entity": [{"entity": "delphinidin glycoside", "entity_type": "Chemical", "pos": [58, 79]}], "task": "NER"}
{"text": "The protective effects of maqui berry ( Aristotelia chilensis ) extract ( MBE ) and its major anthocyanins [ delphinidin 3 , 5 - O - diglucoside ( D3G5G ) and delphinidin 3 - O - sambubioside - 5 - O - glucoside ( D3S5G ) ] against light - induced murine photoreceptor cells ( 661W ) death were evaluated .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [94, 106]}, {"entity": "delphinidin 3 , 5 - O - diglucoside", "entity_type": "Chemical", "pos": [109, 144]}, {"entity": "D3G5G", "entity_type": "Chemical", "pos": [147, 152]}, {"entity": "delphinidin 3 - O - sambubioside - 5 - O - glucoside", "entity_type": "Chemical", "pos": [159, 211]}, {"entity": "D3S5G", "entity_type": "Chemical", "pos": [214, 219]}], "task": "NER"}
{"text": "Viability of 661W after light treatment for 24h , assessed by the tetrazolium salt ( WST - 8 ) assay and Hoechst 33342 nuclear staining , was improved by addition of MBE , D3G5G , and D3S5G .", "entity": [{"entity": "tetrazolium", "entity_type": "Chemical", "pos": [66, 77]}, {"entity": "Hoechst 33342", "entity_type": "Chemical", "pos": [105, 118]}, {"entity": "D3G5G", "entity_type": "Chemical", "pos": [172, 177]}, {"entity": "D3S5G", "entity_type": "Chemical", "pos": [184, 189]}], "task": "NER"}
{"text": "Intracellular radical activation in 661W , evaluated using the reactive oxygen species ( ROS ) - sensitive probe 5 - ( and - 6 ) - chloromethyl - 2 , 7 - dichlorodihydro fluorescein diacetate acetyl ester ( CM - H2DCFDA ) , was reduced by MBE and its anthocyanins .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [72, 78]}, {"entity": "5 - ( and - 6 ) - chloromethyl - 2 , 7 - dichlorodihydro fluorescein diacetate acetyl ester", "entity_type": "Chemical", "pos": [113, 204]}, {"entity": "CM - H2DCFDA", "entity_type": "Chemical", "pos": [207, 219]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [251, 263]}], "task": "NER"}
{"text": "The anti - apoptosis mechanism of MBE was evaluated by light - induced phosphorylation of p38 .", "entity": [], "task": "NER"}
{"text": "MBE significantly suppressed the light - induced phosphorylation of p38 .", "entity": [], "task": "NER"}
{"text": "These findings indicate that MBE and its anthocyanidins suppress the light - induced photoreceptor cell death by inhibiting ROS production , suggesting that the inhibition of phosphorylated - p38 may be involved in the underlying mechanism .", "entity": [{"entity": "anthocyanidins", "entity_type": "Chemical", "pos": [41, 55]}], "task": "NER"}
{"text": "Encapsulation of indole - 3 - carbinol and 3 , 3 ' - diindolylmethane in zein / carboxymethyl chitosan nanoparticles with controlled release property and improved stability .", "entity": [{"entity": "indole - 3 - carbinol", "entity_type": "Chemical", "pos": [17, 38]}, {"entity": "3 , 3 ' - diindolylmethane", "entity_type": "Chemical", "pos": [43, 69]}, {"entity": "carboxymethyl", "entity_type": "Chemical", "pos": [80, 93]}], "task": "NER"}
{"text": "Indole - 3 - carbinol ( I3C ) and 3 , 3 ' - diindolylmethane ( DIM ) are two bioactive compounds from Cruciferous vegetables .", "entity": [{"entity": "Indole - 3 - carbinol", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "I3C", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "3 , 3 ' - diindolylmethane", "entity_type": "Chemical", "pos": [34, 60]}, {"entity": "DIM", "entity_type": "Chemical", "pos": [63, 66]}], "task": "NER"}
{"text": "The stability of these compounds is a major challenge for their pharmaceutical applications .", "entity": [], "task": "NER"}
{"text": "In this study , zein and zein / carboxymethyl chitosan ( CMCS ) nanoparticles were prepared to encapsulate I3C and DIM by a combined liquid - liquid phase separation and ionic gelation method .", "entity": [{"entity": "carboxymethyl", "entity_type": "Chemical", "pos": [32, 45]}, {"entity": "I3C", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "DIM", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "After zein nanoparticles were coated with CMCS , the zeta potential was decreased from around - 10 to - 20mV , and encapsulation efficiency was greatly improved .", "entity": [], "task": "NER"}
{"text": "Both nanoparticle formulations provided controlled release of I3C and DIM in PBS medium .", "entity": [{"entity": "I3C", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "DIM", "entity_type": "Chemical", "pos": [70, 73]}], "task": "NER"}
{"text": "Zein and zein / CMCS nanoparticles demonstrated similar protection for both I3C and DIM against ultraviolet ( UV ) light , attributed mainly to the contribution of the zein protein .", "entity": [{"entity": "I3C", "entity_type": "Chemical", "pos": [76, 79]}, {"entity": "DIM", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Compared with zein nanoparticles , zein / CMCS nanoparticles exhibited better protection of I3C against degradation and better inhibition against its oligomerization to DIM under thermal condition ( 37 degrees C ) .", "entity": [{"entity": "I3C", "entity_type": "Chemical", "pos": [92, 95]}, {"entity": "DIM", "entity_type": "Chemical", "pos": [169, 172]}], "task": "NER"}
{"text": "Based on our results , the encapsulation of hydrophobic bioactives in zein / CMCS nanoparticles is a promising approach to improve their stability against harsh conditions and provide controlled release for food / pharmaceutical applications .", "entity": [], "task": "NER"}
{"text": "Sonicated pineapple juice as substrate for L . casei cultivation for probiotic beverage development : Process optimisation and product stability .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to evaluate the use of sonicated pineapple juice as substrate for producing a probiotic beverage by Lactobacillus casei NRRL B442 .", "entity": [], "task": "NER"}
{"text": "Maximal microbial viability was found by cultivating L . casei at 31 degrees C and pH 5 . 8 ( optimised conditions ) .", "entity": [], "task": "NER"}
{"text": "After fermentation , samples of sweetened and non - sweetened juice were stored .", "entity": [], "task": "NER"}
{"text": "After 42days of storage under refrigeration ( 4 degrees C ) , the microbial viability was 6 . 03LogCFU / mL in the non - sweetened sample and 4 . 77LogCFU / mL in the sweetened sample .", "entity": [], "task": "NER"}
{"text": "The pH of both samples decreased during storage due to lactic acid production ( post acidification ) .", "entity": [{"entity": "lactic acid", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "The characteristic colour of the juice was maintained throughout the shelf life and no browning was observed .", "entity": [], "task": "NER"}
{"text": "Sonicated pineapple juice was shown to be a suitable substrate for L . casei cultivation and for the development of an alternative non - dairy probiotic beverage .", "entity": [], "task": "NER"}
{"text": "Ligands affecting silver antimicrobial efficacy on Listeria monocytogenes and Salmonella enterica .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [18, 24]}], "task": "NER"}
{"text": "Although silver is being extensively used in food or other applications as the key component to control microbial proliferation , many factors affecting its real potential are still unknown .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [9, 15]}], "task": "NER"}
{"text": "In the present work , the presence of specific ligands or the contents in organic matter was correlated with silver speciation and its antibacterial performance .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [109, 115]}], "task": "NER"}
{"text": "Silver was found to be only active in form of free silver ions ( FSI ) .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "silver", "entity_type": "Chemical", "pos": [51, 57]}], "task": "NER"}
{"text": "The presence of chloride ions produced an equilibrium of stable silver chloride complexes which were void of antimicrobial efficacy .", "entity": [{"entity": "chloride", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "silver chloride", "entity_type": "Chemical", "pos": [64, 79]}], "task": "NER"}
{"text": "However , even at relatively high concentrations of chlorides , a small fraction of FSI may still be present , producing a bactericidal effect with concentrations at the nanomolar level under optimum conditions .", "entity": [{"entity": "chlorides", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "Low concentrations of thiol groups completely inactivated silver , while methylsulphur groups only affected its efficacy at very high concentrations .", "entity": [{"entity": "thiol", "entity_type": "Chemical", "pos": [22, 27]}, {"entity": "silver", "entity_type": "Chemical", "pos": [58, 64]}, {"entity": "methylsulphur", "entity_type": "Chemical", "pos": [73, 86]}], "task": "NER"}
{"text": "Antibacterial performance revealed differences of about 1000 - fold between results for environments with high organic matter content and results for aqueous salt buffers .", "entity": [], "task": "NER"}
{"text": "Thiol groups were nonetheless not found directly associated with the decrease in antimicrobial performance in a nutrient rich environment .", "entity": [{"entity": "Thiol", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "These results point out the complexity of the antimicrobial systems based on silver and can have relevance in food or other applications of silver as an antimicrobial .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [77, 83]}, {"entity": "silver", "entity_type": "Chemical", "pos": [140, 146]}], "task": "NER"}
{"text": "Antioxidant capacity , polyphenolic content and tandem HPLC - DAD - ESI / MS profiling of phenolic compounds from the South American berries Luma apiculata and L . chequ e n .", "entity": [{"entity": "polyphenolic", "entity_type": "Chemical", "pos": [23, 35]}, {"entity": "phenolic", "entity_type": "Chemical", "pos": [90, 98]}], "task": "NER"}
{"text": "Native Myrtaceae fruits were gathered by South American Amerindians as a food source .", "entity": [], "task": "NER"}
{"text": "At present , there is still some regional consume of the small berries from trees belonging to genus Luma that occurs in southern Chile and Argentina .", "entity": [], "task": "NER"}
{"text": "The aerial parts and berries from Luma apiculata and Luma chequen were investigated for phenolic constituents and antioxidant capacity .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "A high performance electrospray ionisation mass spectrometry method was developed for the rapid identification of phenolics in polar extracts from both species .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [114, 123]}], "task": "NER"}
{"text": "Thirty - one phenolic compounds were detected and 27 were identified or tentatively characterised based on photodiode array UV - vis spectra ( DAD ) , ESI - MS - MS spectrometric data and spiking experiments with authentic standards .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [13, 21]}], "task": "NER"}
{"text": "Twelve phenolic compounds were detected in L . apiculata fruits and 12 in the aerial parts while L . chequen yielded 10 compounds in fruits and 16 in aerial parts , respectively .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [7, 15]}], "task": "NER"}
{"text": "From the compounds occurring in both Luma species , seven were identified as tannins or their monomers , 15 were flavonol derivatives and five were anthocyanins .", "entity": [{"entity": "tannins", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "flavonol", "entity_type": "Chemical", "pos": [113, 121]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [148, 160]}], "task": "NER"}
{"text": "The whole berry and aerial parts extracts presented high antioxidant capacity in the DPPH assay ( IC50 of 10 . 41 +/- 0 . 02 and 2 . 44 +/- 0 . 03 mu g / mL for L . apiculata , 12 . 89 +/- 0 . 05 and 3 . 22 +/- 0 . 05 for L . chequen , respectively ) , which can be related to the diverse range of phenolics detected .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [85, 89]}, {"entity": "phenolics", "entity_type": "Chemical", "pos": [298, 307]}], "task": "NER"}
{"text": "The antioxidant capacity together with the high polyphenolic contents and compounds identified can support at least in part , their use as botanical drugs .", "entity": [{"entity": "polyphenolic", "entity_type": "Chemical", "pos": [48, 60]}], "task": "NER"}
{"text": "From the compounds identified in both species , 3 - O - ( 6 '' - O - galloyl ) - hexose derivatives of myricetin , quercetin , laricitrin and isorhamnetin are reported for the first time for the genus Luma .", "entity": [{"entity": "3 - O - ( 6 '' - O - galloyl ) - hexose", "entity_type": "Chemical", "pos": [48, 87]}, {"entity": "myricetin", "entity_type": "Chemical", "pos": [103, 112]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [115, 124]}, {"entity": "laricitrin", "entity_type": "Chemical", "pos": [127, 137]}, {"entity": "isorhamnetin", "entity_type": "Chemical", "pos": [142, 154]}], "task": "NER"}
{"text": "Structural characterisation of partially glycosylated whey protein as influenced by pH and heat using surface - enhanced Raman spectroscopy .", "entity": [], "task": "NER"}
{"text": "Maillard - induced glycosylation of whey protein improves solubility and thermal stability over a wide pH range .", "entity": [], "task": "NER"}
{"text": "However , the relationship between structural changes and functional enhancement upon glycosylation is not well - characterized .", "entity": [], "task": "NER"}
{"text": "Therefore , our objective was to characterise these structural changes and determine the protein conformation at various pH and thermal treatments , using surface - enhanced Raman - spectroscopy .", "entity": [], "task": "NER"}
{"text": "The spectra of glycosylated protein revealed a new peak at 983cm ( - 1 ) that can be used as a Raman marker for the early stage glycosylation .", "entity": [], "task": "NER"}
{"text": "Upon glycosylation , structural variations were significant at the disulfide , hydrophobic , amide III , amide II , and amide I regions .", "entity": [{"entity": "disulfide", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "amide", "entity_type": "Chemical", "pos": [93, 98]}, {"entity": "amide", "entity_type": "Chemical", "pos": [105, 110]}, {"entity": "amide", "entity_type": "Chemical", "pos": [120, 125]}], "task": "NER"}
{"text": "Ionisation of carboxyl groups at all tested pH values , and increased beta - sheet configuration were also observed .", "entity": [{"entity": "carboxyl", "entity_type": "Chemical", "pos": [14, 22]}], "task": "NER"}
{"text": "The noted structural modifications imparted molecular rigidity and a consequent resistance to denaturation upon thermal treatment over a wide pH range .", "entity": [], "task": "NER"}
{"text": "These findings can be used to explain various functional enhancements of whey protein upon glycosylation .", "entity": [], "task": "NER"}
{"text": "Changes in urocanic acid , histamine , putrescine and cadaverine levels in Indian mackerel ( Rastrelliger kanagurta ) during storage at different temperatures .", "entity": [{"entity": "urocanic acid", "entity_type": "Chemical", "pos": [11, 24]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "putrescine", "entity_type": "Chemical", "pos": [39, 49]}, {"entity": "cadaverine", "entity_type": "Chemical", "pos": [54, 64]}], "task": "NER"}
{"text": "Histamine , putrescine cadaverine and cis - urocanic acid ( UCA ) have all been implicated or suggested in scombroid fish poisoning .", "entity": [{"entity": "Histamine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "putrescine", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "cadaverine", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "cis - urocanic acid", "entity_type": "Chemical", "pos": [38, 57]}, {"entity": "UCA", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "However , there is little information on UCA especially during storage .", "entity": [{"entity": "UCA", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "Changes in their contents during storage of whole Indian mackerel at 0 , 3 +/- 1 , 10 +/- 1 for up to 15days and 23 +/- 2 degrees C for up to 2days were monitored .", "entity": [], "task": "NER"}
{"text": "Fresh muscles contained 14 . 83mg / kg trans - UCA , 2 . 23mg / kg cis - UCA and 1 . 86mg / kg cadaverine .", "entity": [{"entity": "trans - UCA", "entity_type": "Chemical", "pos": [39, 50]}, {"entity": "cis - UCA", "entity_type": "Chemical", "pos": [67, 76]}, {"entity": "cadaverine", "entity_type": "Chemical", "pos": [95, 105]}], "task": "NER"}
{"text": "Histamine and putrescine were not detected .", "entity": [{"entity": "Histamine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "putrescine", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "After 15days at 0 and 3 degrees C , trans - UCA content increased to 52 . 83 and 189 . 51mg / kg , respectively , and decreased to < 2mg / kg at the other two temperatures .", "entity": [{"entity": "trans - UCA", "entity_type": "Chemical", "pos": [36, 47]}], "task": "NER"}
{"text": "Storage at 10 degrees C also resulted in an increase in trans - UCA after 3days , only to decrease after 6days .", "entity": [{"entity": "trans - UCA", "entity_type": "Chemical", "pos": [56, 67]}], "task": "NER"}
{"text": "The concentration of cis - UCA increased nearly 13 - fold after 15days at 0 and 3 degrees C , decreased at 10 degrees C and remained unchanged at 23 degrees C .", "entity": [{"entity": "cis - UCA", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Histamine , putrescine and cadaverine levels increased significantly ( P value < 0 . 05 ) at all temperatures especially at 23 degrees C .", "entity": [{"entity": "Histamine", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "putrescine", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "cadaverine", "entity_type": "Chemical", "pos": [27, 37]}], "task": "NER"}
{"text": "Fundamental studies on the structural functionality of whey protein isolate in the presence of small polyhydroxyl compounds as co - solute .", "entity": [{"entity": "polyhydroxyl", "entity_type": "Chemical", "pos": [101, 113]}], "task": "NER"}
{"text": "The present work deals with the changing network morphology of whey protein isolate ( 15 % , w / w ) in the presence of glucose syrup ( co - solute ) with concentrations ranging from 0 % to 65 % ( w / w ) in 10mM CaCl2 solution , thus producing formulations with a total level of solids of up to 80 % ( w / w ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [120, 127]}, {"entity": "CaCl2", "entity_type": "Chemical", "pos": [213, 218]}], "task": "NER"}
{"text": "Denaturation behaviour and aggregation of whey protein systems were investigated using small deformation dynamic oscillation on shear , micro and modulated differential scanning calorimetry , and confocal laser scanning microscopy .", "entity": [], "task": "NER"}
{"text": "A progression in the mechanical strength of protein aggregates was observed resulting from enhanced protein - protein interactions in the presence of glucose syrup .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [150, 157]}], "task": "NER"}
{"text": "Addition of the co - solute resulted in better thermal stability of protein molecules by shifting the process of denaturation to higher temperature , as observed by calorimetry .", "entity": [], "task": "NER"}
{"text": "Observations are supported by micrographs showing coherent networks with reduced size of whey protein aggregates in the presence of high levels of glucose syrup , as opposed to thick and random clusters for systems of whey protein by itself .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [147, 154]}], "task": "NER"}
{"text": "Glass transition phenomenon was observed for condensed protein / co - solute systems , which were treated with theoretical concepts adapted from synthetic polymer research to pinpoint the mechanical glass transition temperature .", "entity": [], "task": "NER"}
{"text": "Croton lechleri M u ll .", "entity": [], "task": "NER"}
{"text": "( Euphorbiaceae ) stem bark essential oil as possible mutagen - protective food ingredient against heterocyclic amines from cooked food .", "entity": [{"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [99, 118]}], "task": "NER"}
{"text": "The Amazonian Croton lechleri stem bark essential oil was tested for its anti - mutagenic potential by performing the Ames test against heterocyclic amines ( HCAs ) , in continuing research on applicative functional profile of this phytocomplex as food ingredient ( Rossi et al . , 2011 ) .", "entity": [{"entity": "heterocyclic amines", "entity_type": "Chemical", "pos": [136, 155]}, {"entity": "HCAs", "entity_type": "Chemical", "pos": [158, 162]}], "task": "NER"}
{"text": "Salmonella typhimurium strain TA98 was used with and without metabolic activation ( S9 mix ) .", "entity": [], "task": "NER"}
{"text": "The anti - mutagenic properties was assayed with the following HCAs : 2 - amino - 3 - methylimidazo - [ 4 , 5 - f ] quinoline ( IQ ) , 2 - amino - 3 , 4 - dimethylimidazo - [ 4 , 5 - f ] quinoline ( MeIQ ) , 2 - amino - 3 , 8 - dimethylimidazo - [ 4 , 5 - f ] quinoxaline ( MeIQx ) , the imidazoles 2 - amino - 6 - methyldipyrido - [ 1 , 2 - a : 3 ' , 2 ' - d ] imidazole ( Glu - P - 1 ) and 2 - aminodipirydo - [ 1 , 2 - a : 3 ' , 2 ' - d ] imidazole ( Glu - P - 2 ) .", "entity": [{"entity": "HCAs", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "2 - amino - 3 - methylimidazo - [ 4 , 5 - f ] quinoline", "entity_type": "Chemical", "pos": [70, 125]}, {"entity": "2 - amino - 3 , 4 - dimethylimidazo - [ 4 , 5 - f ] quinoline", "entity_type": "Chemical", "pos": [135, 196]}, {"entity": "MeIQ", "entity_type": "Chemical", "pos": [199, 203]}, {"entity": "2 - amino - 3 , 8 - dimethylimidazo - [ 4 , 5 - f ] quinoxaline", "entity_type": "Chemical", "pos": [208, 271]}, {"entity": "MeIQx", "entity_type": "Chemical", "pos": [274, 279]}, {"entity": "imidazoles", "entity_type": "Chemical", "pos": [288, 298]}, {"entity": "2 - amino - 6 - methyldipyrido - [ 1 , 2 - a : 3 ' , 2 ' - d ] imidazole", "entity_type": "Chemical", "pos": [299, 371]}, {"entity": "Glu - P - 1", "entity_type": "Chemical", "pos": [374, 385]}, {"entity": "2 - aminodipirydo - [ 1 , 2 - a : 3 ' , 2 ' - d ] imidazole", "entity_type": "Chemical", "pos": [392, 451]}, {"entity": "Glu - P - 2", "entity_type": "Chemical", "pos": [454, 465]}], "task": "NER"}
{"text": "All HCAs with S9 induced mutagenicity at 10 ( - 10 ) mol / plate .", "entity": [{"entity": "HCAs", "entity_type": "Chemical", "pos": [4, 8]}], "task": "NER"}
{"text": "Without S9 , IQ and MeIQ showed mutagenicity at 10 ( - 8 ) mol / plate , MeIQx and Glu - P - 1 at 10 ( - 5 ) mol / plate , while Glu - P - 2 was inactive .", "entity": [{"entity": "MeIQ", "entity_type": "Chemical", "pos": [20, 24]}, {"entity": "MeIQx", "entity_type": "Chemical", "pos": [73, 78]}, {"entity": "Glu - P - 1", "entity_type": "Chemical", "pos": [83, 94]}, {"entity": "Glu - P - 2", "entity_type": "Chemical", "pos": [129, 140]}], "task": "NER"}
{"text": "In presence of HACs ( 10 ( - 9 ) mol / plate ) , C . lechleri essential oil was tested for mutagen - protective properties ( concentration range : 0 . 01 - 0 . 10mg / plate ) taking the Highest Uneffective Dose ( HUD ) as threshold reference .", "entity": [{"entity": "HACs", "entity_type": "Chemical", "pos": [15, 19]}], "task": "NER"}
{"text": "With S9 mix , C . lechleri essential oil displayed a significant reduction of revertants at 0 . 05mg / plate , from 21 % to 34 % .", "entity": [], "task": "NER"}
{"text": "The essential oil showed mutagen - protective efficacy against IQ and MeIQ tested as direct mutagens ( 10 ( - 7 ) mol / plate ) , with a revertants percentage reduction of 39 % and 40 % , respectively .", "entity": [{"entity": "MeIQ", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "No anti - mutagen capacity was noted for MeIQx and Glu - P - 1 ( 10 ( - 5 ) mol / plate ) .", "entity": [{"entity": "MeIQx", "entity_type": "Chemical", "pos": [41, 46]}, {"entity": "Glu - P - 1", "entity_type": "Chemical", "pos": [51, 62]}], "task": "NER"}
{"text": "Since HACs are known as possible colon and liver cancer inducers , C . lechleri essential oil was tested for its cytotoxicity and anti - proliferative capacity against LoVo and HepG2 cancer cell lines showing IC50 of 74 . 95 +/- 0 . 05 mu g / ml ( LoVo ) and 82 . 28 +/- 0 . 03 mu g / ml ( HepG2 ) , displaying a promising role of this essential oil as a functional food ingredient with interesting mutagen preventing properties .", "entity": [{"entity": "HACs", "entity_type": "Chemical", "pos": [6, 10]}], "task": "NER"}
{"text": "Characterisation of non - polar dimers formed during thermo - oxidative degradation of beta - sitosterol .", "entity": [{"entity": "beta - sitosterol", "entity_type": "Chemical", "pos": [87, 104]}], "task": "NER"}
{"text": "Thermo - oxidative degradation of sterols at temperature typical for frying leads to the formation of oxidised derivatives , fragmented sterols and oligomers .", "entity": [{"entity": "sterols", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "sterols", "entity_type": "Chemical", "pos": [136, 143]}], "task": "NER"}
{"text": "Recent research on sterol oxidation focuses mainly on the oxysterol derivatives formation to the exclusion of compounds with high molecular mass .", "entity": [{"entity": "sterol", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "oxysterol", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "The aim of this work was to decipher the chemical structure of non - polar dimers formed during beta - sitosterol oxidation at 180 degrees C in the presence of oxygen .", "entity": [{"entity": "beta - sitosterol", "entity_type": "Chemical", "pos": [96, 113]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [160, 166]}], "task": "NER"}
{"text": "The dimer fraction was separated by size - exclusion chromatography ( SEC ) after pre - fractionation on silica gel .", "entity": [{"entity": "silica gel", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "The chemical structure of the dimers was assessed by 1D and 2D NMR , IR , Raman and MS spectroscopies .", "entity": [], "task": "NER"}
{"text": "NMR data confirmed that the predominant non - polar dimer formed during beta - sitosterol oxidative degradation has a configuration of 3 beta , 3 beta ' - disitosteryl ether .", "entity": [{"entity": "beta - sitosterol", "entity_type": "Chemical", "pos": [72, 89]}, {"entity": "3 beta , 3 beta ' - disitosteryl ether", "entity_type": "Chemical", "pos": [135, 173]}], "task": "NER"}
{"text": "Data from IR and Raman spectroscopies further proved it chemical structure .", "entity": [], "task": "NER"}
{"text": "Applied analytical techniques also confirmed presence of dimers with different configuration than disteryl ethers .", "entity": [{"entity": "disteryl ethers", "entity_type": "Chemical", "pos": [98, 113]}], "task": "NER"}
{"text": "Proportions of A1 , A2 , B and C beta - casein protein variants in retail milk in the UK .", "entity": [], "task": "NER"}
{"text": "The A1 variant protein of the beta - casein family has been implicated in various disease states although much evidence is weak or contradictory .", "entity": [], "task": "NER"}
{"text": "The primary objective was to measure , for the first time , the proportions of the key beta - casein variant proteins in UK retail milk over the course of one year .", "entity": [], "task": "NER"}
{"text": "In total , 55 samples of semi - skimmed milk were purchased from five supermarkets over the course of a year and the proportions of the A1 , A2 , B and C casein variant proteins were measured , using high resolution HPLC - MS .", "entity": [], "task": "NER"}
{"text": "The results showed that beta - casein in UK retail milk comprises approximately 0 . 58 , 0 . 31 , 0 . 07 and 0 . 03 A2 , A1 , B and C protein variants , respectively .", "entity": [], "task": "NER"}
{"text": "The proportion of A2 is higher than some early studies would predict although the reasons for this and any implications for health are unclear .", "entity": [], "task": "NER"}
{"text": "RP - HPLC and chemometrics for wheat flour protein characterisation in an industrial bread - making process monitoring context .", "entity": [], "task": "NER"}
{"text": "In the baking industry , a difficult task is to keep the quality perceived by the consumer as constant as possible , given the inner variability of flour , e . g . due to different wheat mixtures , harvesting time , etc .", "entity": [], "task": "NER"}
{"text": "Here , we evaluated the influence of flour batches properties on bread quality , considering an industrial bread making process .", "entity": [], "task": "NER"}
{"text": "In particular , flour composition in terms of protein fractions ( gliadins , glutenins ) has been determined by means of RP - HPLC , to assess the inter - and intra - batch variability of flour mixtures deliveries at a baking plant .", "entity": [], "task": "NER"}
{"text": "Multivariate data analysis allowed evaluation of correlation between flour protein composition and technological properties .", "entity": [], "task": "NER"}
{"text": "A great variability within different deliveries of a same flour batch emerged , as well as a considerable seasonal variability .", "entity": [], "task": "NER"}
{"text": "Correlation models among protein sub - fractions , technological properties and bread quality are difficult to establish ; however , the role of the protein profile on flour behaviour in bread making could be highlighted .", "entity": [], "task": "NER"}
{"text": "Anthocyanins in the ripe fruits of Rubus coreanus Miquel and their protective effect on neuronal PC - 12 cells .", "entity": [{"entity": "Anthocyanins", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Phenolics of the fresh ripe fruits of Rubus coreanus Miquel were extracted and separated into anthocyanin and the non - anthocyanin fractions , which were used for the evaluation for antioxidant capacity and neuroprotective effects .", "entity": [{"entity": "Phenolics", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "anthocyanin", "entity_type": "Chemical", "pos": [94, 105]}, {"entity": "anthocyanin", "entity_type": "Chemical", "pos": [120, 131]}], "task": "NER"}
{"text": "The anthocyanin fraction accounted for approximately 47 - 55 % of the total antioxidant capacity of the whole extract and had significantly higher free radical - scavenging capacity than the non - anthocyanin fraction .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [4, 15]}, {"entity": "anthocyanin", "entity_type": "Chemical", "pos": [197, 208]}], "task": "NER"}
{"text": "Furthermore , the anthocyanins alleviated intracellular oxidative stress , as assayed by in vitro fluorescent measurements .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [18, 30]}], "task": "NER"}
{"text": "The anthocyanins showed neuroprotective effects on PC - 12 cells in vitro against oxidative stress in a dose - dependent manner .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [4, 16]}], "task": "NER"}
{"text": "Triple quadrupole LC / MS and Q - TOF LC / MS analyses revealed four major anthocyanins ; cyanidin 3 - O - sambubioside , cyanidin 3 - O - glucoside , cyanidin 3 - O - xylosylrutinoside , and cyanidin 3 - O - rutinoside in increasing order of amounts .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [75, 87]}, {"entity": "cyanidin 3 - O - sambubioside", "entity_type": "Chemical", "pos": [90, 119]}, {"entity": "cyanidin 3 - O - glucoside", "entity_type": "Chemical", "pos": [122, 148]}, {"entity": "cyanidin 3 - O - xylosylrutinoside", "entity_type": "Chemical", "pos": [151, 185]}, {"entity": "cyanidin 3 - O - rutinoside", "entity_type": "Chemical", "pos": [192, 219]}], "task": "NER"}
{"text": "These results demonstrated that anthocyanins are the major components and contributors to the antioxidant capacity of ripe R . coreanus Miquel fruits .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [32, 44]}], "task": "NER"}
{"text": "Further studies are warranted to determine whether consumption of the fruits reduces oxidative stress in the brain and promotes health .", "entity": [], "task": "NER"}
{"text": "Extraction and structural characterisation of rhamnogalacturonan I - type pectic polysaccharides from potato cell wall .", "entity": [], "task": "NER"}
{"text": "Cell wall material from potato pulp by - product was used for the extraction of galactan - rich rhamnogalacturonan I ( RG - I ) type pectic polysaccharides using alkaline ( NaOH and KOH ) and enzymatic ( endopolygalacturonase from Aspergillus niger ) methods .", "entity": [{"entity": "NaOH", "entity_type": "Chemical", "pos": [173, 177]}, {"entity": "KOH", "entity_type": "Chemical", "pos": [182, 185]}], "task": "NER"}
{"text": "The extraction yield increased as the concentration of alkaline solution was increased from 0 . 5M ( 22 - 24 % ) to 2M ( 53 - 56 % ) .", "entity": [], "task": "NER"}
{"text": "The yield of 38 % obtained upon the enzymatic treatment was similar to those observed with 1M alkaline solutions .", "entity": [], "task": "NER"}
{"text": "The results reveal the high debranching of arabinan side chains of RG I as compared to the galactan ones under harsh alkaline conditions .", "entity": [], "task": "NER"}
{"text": "The molecular weight distribution shows that the enzymatic extraction led to the highest proportion of high - molecular weight polysaccharides ( > 500kDa ; 62 . 2 % ) .", "entity": [], "task": "NER"}
{"text": "According to monosaccharide pattern , the weak acidic fractions of high alkaline ( 1 - 2M ) - based polysaccharide extracts was the most enriched with galactan - rich RG I .", "entity": [], "task": "NER"}
{"text": "Using milder conditions ( enzyme and weak alkaline ) , two RG I populations with low and high linked homogalacturonan fragments were recovered in the weak and strong acidic fractions , respectively .", "entity": [], "task": "NER"}
{"text": "The structure of galactan - rich RG I was confirmed by H ( 1 ) NMR spectroscopy analysis .", "entity": [{"entity": "H ( 1 )", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "Distribution of carotenoids in endosperm , germ , and aleurone fractions of cereal grain kernels .", "entity": [], "task": "NER"}
{"text": "To compare the distribution of carotenoids across the grain , non - corn and corn cereals were hand dissected into endosperm , germ and aleurone fractions .", "entity": [], "task": "NER"}
{"text": "Total carotenoid content ( TCC ) and carotenoid composition were analysed using spectrophotometry and HPLC .", "entity": [], "task": "NER"}
{"text": "Cereal carotenoid composition was similar ; however , concentrations varied significantly ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "Endosperm fractions had TCC ranging from 0 . 88 to 2 . 27 and 14 . 17 to 31 . 35mg / kg in non - corn cereals and corn , respectively .", "entity": [], "task": "NER"}
{"text": "TCC , lutein and zeaxanthin in germ fractions were higher in non - corn cereals than in corn .", "entity": [{"entity": "lutein", "entity_type": "Chemical", "pos": [6, 12]}, {"entity": "zeaxanthin", "entity_type": "Chemical", "pos": [17, 27]}], "task": "NER"}
{"text": "Lutein and zeaxanthin contents were lower in non - corn cereal endosperms .", "entity": [{"entity": "Lutein", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "zeaxanthin", "entity_type": "Chemical", "pos": [11, 21]}], "task": "NER"}
{"text": "The aleurone layer had zeaxanthin levels 2 - to 5 - fold higher than lutein among the cereals .", "entity": [{"entity": "zeaxanthin", "entity_type": "Chemical", "pos": [23, 33]}, {"entity": "lutein", "entity_type": "Chemical", "pos": [69, 75]}], "task": "NER"}
{"text": "Positive significant correlations ( p < 0 . 05 ) were found between TCC , carotenoids analysed by HPLC and DPPH results .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [107, 111]}], "task": "NER"}
{"text": "This study is the first to report on carotenoid composition of the aleurone layer .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that the aleurone of wheat , oat , corn and germ of barley have significantly enhanced carotenoid levels .", "entity": [], "task": "NER"}
{"text": "Aluminium and other elements in selected herbal tea plant species and their infusions .", "entity": [{"entity": "Aluminium", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The determination of Al , B , Cu , Fe , Mn , Ni , P , Zn and Ca , K , Mg by inductively coupled plasma optical emission spectrometry ( ICP - OES ) and flame atomic absorption spectroscopy ( FAAS ) , respectively , in digests and infusions of Hibiscus sabdariffa ( petals ) , Rosa canina ( receptacles ) , Ginkgo biloba ( leaves ) , Cymbopogon citratus ( leaves ) , Aloe vera ( leaves ) and Panax ginseng ( roots ) was carried out in this study .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [21, 23]}, {"entity": "B", "entity_type": "Chemical", "pos": [26, 27]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [30, 32]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [35, 37]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [45, 47]}, {"entity": "P", "entity_type": "Chemical", "pos": [50, 51]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [61, 63]}, {"entity": "K", "entity_type": "Chemical", "pos": [66, 67]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [70, 72]}], "task": "NER"}
{"text": "Particular attention has been given to Al and heavy metals for the identification of possible raw material contaminants , their transformation into the infusion and for predicting their eventual role in the human diet during daily consumption .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [39, 41]}], "task": "NER"}
{"text": "Additionally , Ion Chromatography ( IC ) speciation of Al in the leachates was carried out .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [55, 57]}], "task": "NER"}
{"text": "In dry herbs , hibiscus and ginkgo appeared to contain the greatest contents of Al , Fe , K , Mn , Ni , Zn and B , Mg , P , respectively .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [80, 82]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [85, 87]}, {"entity": "K", "entity_type": "Chemical", "pos": [90, 91]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [94, 96]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [99, 101]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [104, 106]}, {"entity": "B", "entity_type": "Chemical", "pos": [111, 112]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [115, 117]}, {"entity": "P", "entity_type": "Chemical", "pos": [120, 121]}], "task": "NER"}
{"text": "A . vera contained the highest amount of Ca and highest values of Cu and P were observed in ginseng .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [66, 68]}, {"entity": "P", "entity_type": "Chemical", "pos": [73, 74]}], "task": "NER"}
{"text": "In infusions , the topmost concentrations of Al , B , Cu , Fe , P , K , Mn , Ni , Zn were detected in those prepared from hibiscus petals , Ca from aloe leaves and Mg from leaves of ginkgo .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [45, 47]}, {"entity": "B", "entity_type": "Chemical", "pos": [50, 51]}, {"entity": "Cu", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "Fe", "entity_type": "Chemical", "pos": [59, 61]}, {"entity": "P", "entity_type": "Chemical", "pos": [64, 65]}, {"entity": "K", "entity_type": "Chemical", "pos": [68, 69]}, {"entity": "Mn", "entity_type": "Chemical", "pos": [72, 74]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [77, 79]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [82, 84]}, {"entity": "Ca", "entity_type": "Chemical", "pos": [140, 142]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [164, 166]}], "task": "NER"}
{"text": "According to a possible daily consumption exceeding 1L , hibiscus decoction was identified as potentially dietetically significant in the content of certain elements .", "entity": [], "task": "NER"}
{"text": "It seems to be possibly one of the top contributors of B from food ( up to 5 . 5 +/- 0 . 2mg / L ) .", "entity": [{"entity": "B", "entity_type": "Chemical", "pos": [55, 56]}], "task": "NER"}
{"text": "The Mg contained in the infusion ( up to 106 +/- 5mg / L ) may be a contributor in the attenuation of blood pressure .", "entity": [{"entity": "Mg", "entity_type": "Chemical", "pos": [4, 6]}], "task": "NER"}
{"text": "A high amount of accessible Mn ( up to 17 . 4 +/- 1 . 1mg / L ) can probably have an adverse effect in humans .", "entity": [{"entity": "Mn", "entity_type": "Chemical", "pos": [28, 30]}], "task": "NER"}
{"text": "The total Al allowance ( up to 1 . 2 +/- 0 . 1mg / L ) suggests that no more than 1L of the hibiscus infusion should be consumed per day by sensitive individuals including pregnant women and should be completely excluded from the diet of children under 6months of age and children with chronic renal failure .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [10, 12]}], "task": "NER"}
{"text": "Cultivar variations in antioxidant and antihyperlipidemic properties of pomelo pulp ( Citrus grandis [ L . ] Osbeck ) in Thailand .", "entity": [], "task": "NER"}
{"text": "Pomelo ( Citrus grandis L . Osbeck ) is a native fruit of great economic importance in Southeast Asia .", "entity": [], "task": "NER"}
{"text": "To provide experimental evidence for the antioxidant and antihyperlipidemic properties of pomelo , 6 cultivars , including Kao - Yai ( KY ) , Thong - dee ( TD ) , Kao - Tangkwa ( KT ) , Kao - Numpueng ( KN ) , Ta - Koi ( TK ) , and Tubtim Siam ( TS ) were evaluated .", "entity": [], "task": "NER"}
{"text": "KY had the highest phenolic content , and the strongest 1 , 1 - diphenyl - 2 - pireyhydrazyl radical scavenging capacity and hydroxyl radical scavenging activity .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "1 , 1 - diphenyl - 2 - pireyhydrazyl", "entity_type": "Chemical", "pos": [56, 92]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [125, 133]}], "task": "NER"}
{"text": "From the high - performance liquid chromatography analysis , naringin and naringenin were the major flavonoids in the KT and TK cultivars .", "entity": [{"entity": "naringin", "entity_type": "Chemical", "pos": [61, 69]}, {"entity": "naringenin", "entity_type": "Chemical", "pos": [74, 84]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [100, 110]}], "task": "NER"}
{"text": "Six pomelo cultivars had antihyperlipidemic activities including the inhibition of pancreatic lipase and cholesterol esterase , as well as cholesterol micelle formation and bile acid binding .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [105, 116]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [139, 150]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [173, 182]}], "task": "NER"}
{"text": "Hierarchical clustering analysis showed that the 6 cultivars were separated into 2 classifications .", "entity": [], "task": "NER"}
{"text": "In addition , the total phenolics of the pomelo cultivars were significantly correlated with ferric reducing antioxidant power and Trolox equivalent antioxidant capacity .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "ferric", "entity_type": "Chemical", "pos": [93, 99]}, {"entity": "Trolox", "entity_type": "Chemical", "pos": [131, 137]}], "task": "NER"}
{"text": "The results suggest that pomelo provides significant health benefits and may be used for developing functional foods .", "entity": [], "task": "NER"}
{"text": "Identification and quantification of active alkaloids in Catharanthus roseus by liquid chromatography - ion trap mass spectrometry .", "entity": [], "task": "NER"}
{"text": "Catharanthus roseus is an important dicotyledonous medicinal plant that produces anticancer compounds .", "entity": [], "task": "NER"}
{"text": "The active alkaloids vinblastine , vindoline , ajmalicine , catharanthine , and vinleurosine were identified by direct - injection ion trap - mass spectrometry ( IT - MS ) for collecting MS ( 1 - 2 ) spectra .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [21, 32]}, {"entity": "vindoline", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "ajmalicine", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "catharanthine", "entity_type": "Chemical", "pos": [60, 73]}, {"entity": "vinleurosine", "entity_type": "Chemical", "pos": [80, 92]}], "task": "NER"}
{"text": "The determinations of five alkaloids were accomplished by liquid chromatography ( LC ) with UV and MS detections .", "entity": [], "task": "NER"}
{"text": "The analytes provided good signals corresponding to the protonated molecular ions [ M + H ] ( + ) and product ions .", "entity": [], "task": "NER"}
{"text": "The precursor ions and product ions for quantification of vinblastine , vindoline , ajmalicine , catharanthine , and vinleurosine were m / z 825 --> 807 , 457 --> 397 , 353 --> 144 , 337 --> 144 and 809 --> 748 by LC - IT - MS , respectively .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [58, 69]}, {"entity": "vindoline", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "ajmalicine", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "catharanthine", "entity_type": "Chemical", "pos": [97, 110]}, {"entity": "vinleurosine", "entity_type": "Chemical", "pos": [117, 129]}], "task": "NER"}
{"text": "Two methods were used to evaluate a number of validation characteristics ( repeatability , LOD , calibration range , and recovery ) .", "entity": [], "task": "NER"}
{"text": "MS provided a high selectivity and sensitivity for determination of five alkaloids in positive mode .", "entity": [], "task": "NER"}
{"text": "After optimisation of the methods , separation , identification and quantification of the five components in C . roseus were comprehensively accomplished by HPLC with UV and MS detection .", "entity": [], "task": "NER"}
{"text": "Structures and reactions of compounds involved in pink discolouration of onion .", "entity": [], "task": "NER"}
{"text": "In \" pinking \" of onion , E - ( + ) - S - ( 1 - propenyl ) - l - cysteine sulfoxide is first cleaved by alliinase to yield colour developers ( CDs ) , which react with amino acids , such as valine , to form pigment precursors ( PPs ) .", "entity": [{"entity": "E - ( + ) - S - ( 1 - propenyl ) - l - cysteine sulfoxide", "entity_type": "Chemical", "pos": [26, 83]}, {"entity": "amino acids", "entity_type": "Chemical", "pos": [168, 179]}, {"entity": "valine", "entity_type": "Chemical", "pos": [190, 196]}], "task": "NER"}
{"text": "The PPs react with naturally occurring carbonyls ( NOCs ) to form pigments .", "entity": [{"entity": "carbonyls", "entity_type": "Chemical", "pos": [39, 48]}], "task": "NER"}
{"text": "By inducing a PP from previously isolated cepathiolanes and l - valine , it was confirmed that cepathiolanes constitute at least a part of the CDs .", "entity": [{"entity": "cepathiolanes", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "l - valine", "entity_type": "Chemical", "pos": [60, 70]}, {"entity": "cepathiolanes", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "From the PP and formaldehyde as a NOC , two colourless and two pink compounds were derived .", "entity": [{"entity": "formaldehyde", "entity_type": "Chemical", "pos": [16, 28]}], "task": "NER"}
{"text": "The structure of one of the colourless compounds was established as 2 - ( 2 - ( 1 - ( 1 - carboxy - 2 - methylpropyl ) - 3 , 4 - dimethyl - 1H - pyrrol - 2 - yl ) methyl - 3 , 4 - dimethyl - 1H - pyrrol - 1 - yl ) - 3 - methylbutanoic acid .", "entity": [{"entity": "2 - ( 2 - ( 1 - ( 1 - carboxy - 2 - methylpropyl ) - 3 , 4 - dimethyl - 1H - pyrrol - 2 - yl ) methyl - 3 , 4 - dimethyl - 1H - pyrrol - 1 - yl ) - 3 - methylbutanoic acid", "entity_type": "Chemical", "pos": [68, 239]}], "task": "NER"}
{"text": "The structures of the other colourless compound and the pink pigments were predicted based on their molecular formula and the MS ( n ) spectral data .", "entity": [], "task": "NER"}
{"text": "A trimeric pigment structure was predicted for one of the pink pigments , which was believed to be the first to be reported in the literature .", "entity": [], "task": "NER"}
{"text": "With these , a new reaction scheme for \" pinking \" of onion is proposed .", "entity": [], "task": "NER"}
{"text": "Effect of floral sources on the antioxidant , antimicrobial , and anti - inflammatory activities of honeys in Taiwan .", "entity": [], "task": "NER"}
{"text": "We evaluated the antioxidant , antibacterial , and anti - inflammatory activities of honey made from different floral sources , including the medicinal herb Bidens pilosa , fruit trees , Dimocarpus longan , Litchi chinensis , and Citrus maxima , the Taiwanese endemic plant Aglaia formosana , and a multifloral forest .", "entity": [], "task": "NER"}
{"text": "The total phenolic and flavonoid contents of the honey made from B . pilosa were significantly higher than those of the other honeys .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [23, 32]}], "task": "NER"}
{"text": "The honey from B . pilosa also had significantly greater scavenging activities for 1 , 1 - diphenyl - 2 - picrylhydrazyl ( DPPH . ) and hydroxyl radical , and substantially more reducing power .", "entity": [{"entity": "1 , 1 - diphenyl - 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [83, 120]}, {"entity": "DPPH .", "entity_type": "Chemical", "pos": [123, 129]}, {"entity": "hydroxyl", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "In addition , the honey from B . pilosa showed greater antibacterial activity against Gram - positive and Gram - negative bacteria .", "entity": [], "task": "NER"}
{"text": "However , B . pilosa honey showed little inhibitory activity against IL - 8 secretion , whereas the other honeys did .", "entity": [], "task": "NER"}
{"text": "These findings suggest that the levels of antioxidant and antibacterial activities are attributable to the total phenolic and flavonoid contents of honeys , while the IL - 8 inhibition is attributable to components other than phenols .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [113, 121]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [126, 135]}, {"entity": "phenols", "entity_type": "Chemical", "pos": [226, 233]}], "task": "NER"}
{"text": "Fatty acid profiling of the seed oils of some varieties of field peas ( Pisum sativum ) by RP - LC / ESI - MS / MS : Towards the development of an oilseed pea .", "entity": [{"entity": "Fatty acid", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Reversed - phase liquid chromatography coupled to negative - ion electrospray tandem mass spectrometry ( RP - LC / ESI - MS / MS ) was used to study the fatty acid profile from the oil of harvested field pea ( Pisum sativum ) varieties as part of a research project to develop this legume as a commercial oilseed for Canada .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [153, 163]}], "task": "NER"}
{"text": "The seed oils from pea samples contained palmitic and stearic acids as major saturated fatty acids .", "entity": [{"entity": "palmitic and stearic acids", "entity_type": "Chemical", "pos": [41, 67]}, {"entity": "saturated fatty acids", "entity_type": "Chemical", "pos": [77, 98]}], "task": "NER"}
{"text": "Oleic , linoleic and linolenic acids were the major unsaturated fatty acids found .", "entity": [{"entity": "Oleic , linoleic and linolenic acids", "entity_type": "Chemical", "pos": [0, 36]}, {"entity": "unsaturated fatty acids", "entity_type": "Chemical", "pos": [52, 75]}], "task": "NER"}
{"text": "Small percentages of other long chain fatty acids were also detected .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [38, 49]}], "task": "NER"}
{"text": "This profile suggests that the species of field pea investigated might have the potential to be used as raw materials to develop a future new oilseed crop for the food industry .", "entity": [], "task": "NER"}
{"text": "Fatty acid extracts did not require further manipulation before final analysis by RP - LC / ESI - MS / MS , indicating the utility and relative simplicity of this technique for future screening studies .", "entity": [{"entity": "Fatty acid", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Tert - butylhydroquinone recognition of molecular imprinting electrochemical sensor based on core - shell nanoparticles .", "entity": [{"entity": "Tert - butylhydroquinone", "entity_type": "Chemical", "pos": [0, 24]}], "task": "NER"}
{"text": "One novel electrochemistry - molecular imprinting sensor for determining tert - butylhydroquinone ( TBHQ ) in foodstuff was developed .", "entity": [{"entity": "tert - butylhydroquinone", "entity_type": "Chemical", "pos": [73, 97]}, {"entity": "TBHQ", "entity_type": "Chemical", "pos": [100, 104]}], "task": "NER"}
{"text": "TBHQ - imprinted core - shell nanoparticles ( TICSNs ) were fabricated using silica nanoparticles as core material .", "entity": [{"entity": "TBHQ", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "silica", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "The silica nanoparticles were modified with ( 3 - chloropropyl ) trimethoxysilan and polyethylenimine , respectively , and polymerised to form the TICSNs with ethylene glycol dimethacrylate as cross - linker .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [4, 10]}, {"entity": "( 3 - chloropropyl ) trimethoxysilan", "entity_type": "Chemical", "pos": [44, 80]}, {"entity": "polyethylenimine", "entity_type": "Chemical", "pos": [85, 101]}, {"entity": "ethylene glycol dimethacrylate", "entity_type": "Chemical", "pos": [159, 189]}], "task": "NER"}
{"text": "The specific core - shell structure demonstrates extremely high specific surface area which greatly increases the effective binding sites and improves the recognition capability for model molecules .", "entity": [], "task": "NER"}
{"text": "Under the optimal conditions , the linear range of the calibration curve was 0 . 1 - 50 . 0mgkg ( - 1 ) with the detection limit of 0 . 27mgkg ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "The sensor has been successfully applied to the determination of TBHQ in food samples and achieved high sensitivity and selectivity .", "entity": [{"entity": "TBHQ", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "Curcumin inhibits invasion and metastasis in K1 papillary thyroid cancer cells .", "entity": [{"entity": "Curcumin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Curcumin , the active constituent of dietary spice turmeric , possesses a strong potential for cancer prevention and treatment .", "entity": [{"entity": "Curcumin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "However , there is no study to address the effects of curcumin on invasion and metastasis of thyroid cancers .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "Thyroid cancer is the most common malignancy of endocrine organs , and its incidence rates have steadily increased over recent decades .", "entity": [], "task": "NER"}
{"text": "Although most indolent tumours can be effectively managed , metastatic tumours at distant secondary sites behave aggressively and currently there is no effective form of treatment .", "entity": [], "task": "NER"}
{"text": "Here , for the first time it has been reported that curcumin inhibit multiple metastasis steps of K1 papillary thyroid cancer cells .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [52, 60]}], "task": "NER"}
{"text": "Curcumin dose - dependently suppressed viability of K1 cells as well as its cell attachment , spreading , migration and invasion abilities .", "entity": [{"entity": "Curcumin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Moreover , curcumin could also down - regulate the expression and activity of matrix metalloproteinase - 9 ( MMP - 9 ) .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "The findings showed that curcumin might be an effective tumouristatic agent for the treatment of aggressive papillary thyroid carcinomas .", "entity": [{"entity": "curcumin", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "The potential of solvent - minimized extraction methods in the determination of polycyclic aromatic hydrocarbons in fish oils .", "entity": [{"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [80, 112]}], "task": "NER"}
{"text": "Fish oil has been identified as one of the most important contributors to the level of Persistent Organic Pollutants ( POPs ) in feed products .", "entity": [], "task": "NER"}
{"text": "The determination of polycyclic aromatic hydrocarbons ( PAHs ) in fish oils is complicated due to the fat matrix , which affects both extraction efficiency and analytical quality .", "entity": [{"entity": "polycyclic aromatic hydrocarbons", "entity_type": "Chemical", "pos": [21, 53]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "This article reviews and addresses two of the most relevant analytical methods for determining 11 mutagenic and carcinogenic PAHs , as well as two EPA indicator PAHs in fish oils .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [125, 129]}, {"entity": "PAHs", "entity_type": "Chemical", "pos": [161, 165]}], "task": "NER"}
{"text": "We discuss and critically evaluate two different extraction procedures , such as ultrasound - assisted solvent extraction ( USAE ) and ultrasound - assisted emulsification - microextraction ( USAEME ) .", "entity": [], "task": "NER"}
{"text": "Clean - up of extracts was performed by solid - phase extraction using C18 and glass columns containing silica gel and florisil for USAE or only C18 for USAEME .", "entity": [{"entity": "silica gel", "entity_type": "Chemical", "pos": [104, 114]}, {"entity": "florisil", "entity_type": "Chemical", "pos": [119, 127]}], "task": "NER"}
{"text": "Detection of the selected PAHs was carried out by high - performance liquid chromatography coupled with fluorescence detection for determination .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [26, 30]}], "task": "NER"}
{"text": "Optimization of the variables affecting extraction by the selected extraction techniques was conducted and recoveries ranged from 70 % to 100 % by USAE and from 70 % to 108 % by USAEME with estimated quantification limits between 0 . 020 and 2 . 6 mu g / kg were achieved .", "entity": [], "task": "NER"}
{"text": "Moreover , the applicability of the selected methods was evaluated by the analysis of real samples .", "entity": [], "task": "NER"}
{"text": "To our knowledge , this is the first time that USAEME has been applied to the determination of PAHs in food matrices , such as oil fish samples .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "The methods proposed were applied to the determination of the target PAHs in fish samples from different countries , and it was found that the low PAH contamination of the selected fish oils could mainly occur by atmospheric sources .", "entity": [{"entity": "PAHs", "entity_type": "Chemical", "pos": [69, 73]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [147, 150]}], "task": "NER"}
{"text": "Non - enzymatic glycation of natural actomyosin ( NAM ) with glucosamine in a liquid system at moderate temperatures .", "entity": [{"entity": "glucosamine", "entity_type": "Chemical", "pos": [61, 72]}], "task": "NER"}
{"text": "Muscle protein functionality plays an important role in routine applications in the food industry .", "entity": [], "task": "NER"}
{"text": "Glycation by the Maillard reaction is a naturally occurring process , which can be used to develop new ingredients with improved functionality using a food grade approach .", "entity": [], "task": "NER"}
{"text": "Actomyosin was conjugated with glucose or glucosamine in a liquid system at moderate temperatures ( 40 degrees C ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "glucosamine", "entity_type": "Chemical", "pos": [42, 53]}], "task": "NER"}
{"text": "Sugar to protein conjugation was evident by UV - Vis spectral changes , with the glycation level determined by matrix assisted laser desorption / ionisation mass spectrometry .", "entity": [{"entity": "Sugar", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Parameters for glycation of muscle protein were optimised using the bidimensional hierarchical clustering analyses .", "entity": [], "task": "NER"}
{"text": "The best glycation conditions were 40 degrees C for 8h at 1 : 3 protein : sugar ratio .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [74, 79]}], "task": "NER"}
{"text": "Solubility and emulsifying properties of glycoconjugates were significantly improved as compared to non - glycated proteins .", "entity": [], "task": "NER"}
{"text": "At pH 7 glycated actomyosin was on average 31 % more soluble compared to non - treated protein .", "entity": [], "task": "NER"}
{"text": "Glucosamine was found to be more effective for glycation and provided higher protein functionality as compared to glucose .", "entity": [{"entity": "Glucosamine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [114, 121]}], "task": "NER"}
{"text": "Mechanisms of saccharide protection against epigallocatechin - 3 - gallate deterioration in aqueous solutions .", "entity": [{"entity": "saccharide", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [44, 74]}], "task": "NER"}
{"text": "We investigated the mechanisms of the protection conferred by sugars to epigallocatechin - 3 - gallate ( EGCG ) against deterioration .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "epigallocatechin - 3 - gallate", "entity_type": "Chemical", "pos": [72, 102]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [105, 109]}], "task": "NER"}
{"text": "Additionally , we present a rapid method for evaluating the deterioration rate of EGCG using absorbance spectroscopy .", "entity": [{"entity": "EGCG", "entity_type": "Chemical", "pos": [82, 86]}], "task": "NER"}
{"text": "We found that various sugars provided different levels of protection at identical weight percentage , and the combination of sugars and beta - lactoglobulin nanocomplexes provided greater protection for EGCG than each protective component alone .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "sugars", "entity_type": "Chemical", "pos": [125, 131]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [203, 207]}], "task": "NER"}
{"text": "We suggest that the concentration - dependent protection by sugars resulted from a combination of mechanisms , including : ( 1 ) reduced aqueous O2 solubility , ( 2 ) scavenging of reactive oxygen species , and ( 3 ) chelation of traces of transition metal ions , which is suggested to be the main reason for the differences among the sugars .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "O2", "entity_type": "Chemical", "pos": [145, 147]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [190, 196]}, {"entity": "transition metal", "entity_type": "Chemical", "pos": [240, 256]}, {"entity": "sugars", "entity_type": "Chemical", "pos": [335, 341]}], "task": "NER"}
{"text": "The observed protective effect of sugars can be easily applied by the industry in proper selection of sugars for enrichment of syrups or concentrates with EGCG and for the preparation of enriched beverages and foods for health promotion .", "entity": [{"entity": "sugars", "entity_type": "Chemical", "pos": [34, 40]}, {"entity": "sugars", "entity_type": "Chemical", "pos": [102, 108]}, {"entity": "EGCG", "entity_type": "Chemical", "pos": [155, 159]}], "task": "NER"}
{"text": "Combined impact of Bacillus stearothermophilus maltogenic alpha - amylase and surfactants on starch pasting and gelation properties .", "entity": [], "task": "NER"}
{"text": "In baking applications involving starch gelatinisation , surfactants such as sodium stearoyl lactylate ( SSL ) and monoacylglycerols ( MAG ) and Bacillus stearothermophilus maltogenic alpha - amylase ( BStA ) can be used jointly .", "entity": [{"entity": "sodium stearoyl lactylate", "entity_type": "Chemical", "pos": [77, 102]}, {"entity": "SSL", "entity_type": "Chemical", "pos": [105, 108]}, {"entity": "monoacylglycerols", "entity_type": "Chemical", "pos": [115, 132]}, {"entity": "MAG", "entity_type": "Chemical", "pos": [135, 138]}], "task": "NER"}
{"text": "We here showed that SSL but not MAG delays wheat starch hydrolysis by BStA .", "entity": [{"entity": "SSL", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "MAG", "entity_type": "Chemical", "pos": [32, 35]}], "task": "NER"}
{"text": "The effects were explained in terms of different degrees of adsorption of the surfactants on the starch granule surface , retarded and / or decreased water uptake and delayed availability of gelatinised starch for hydrolysis by BStA .", "entity": [], "task": "NER"}
{"text": "Additional experiments with waxy maize starch led to the conclusion that SSL impacts swelling power and carbohydrate leaching more by covering the starch granule surface than by forming amylose - lipid complexes .", "entity": [{"entity": "SSL", "entity_type": "Chemical", "pos": [73, 76]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [104, 116]}], "task": "NER"}
{"text": "SSL postponed starch hydrolysis by BStA , but this did not influence subsequent starch gelation .", "entity": [{"entity": "SSL", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Finally , when adding SSL or MAG on top of BStA to starch suspensions , the effect of the surfactants on gel strength predominated over that of BStA .", "entity": [{"entity": "SSL", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "MAG", "entity_type": "Chemical", "pos": [29, 32]}], "task": "NER"}
{"text": "Polyphasic approach to the identification of Aspergillus section Flavi isolated from Brazil nuts .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to use a polyphasic approach to identify Aspergillus section Flavi isolated from Brazil nuts collected in the Amazon forest : investigation of macro - and microscopic morphology , production of extrolites , heat - resistance fungi , and sequencing of DNA regions .", "entity": [], "task": "NER"}
{"text": "The following Aspergillus section Flavi species were identified : Aspergillus flavus ( 75 . 5 % ) , Aspergillus nomius ( 22 . 3 % ) , and Aspergillus parasiticus ( 2 . 2 % ) .", "entity": [], "task": "NER"}
{"text": "All A . nomius and A . parasiticus isolates produced aflatoxins B and G , but not cyclopiazonic acid ( CPA ) .", "entity": [{"entity": "aflatoxins B and G", "entity_type": "Chemical", "pos": [53, 71]}, {"entity": "cyclopiazonic acid", "entity_type": "Chemical", "pos": [82, 100]}, {"entity": "CPA", "entity_type": "Chemical", "pos": [103, 106]}], "task": "NER"}
{"text": "A . flavus isolates were more diversified and a high frequency of mycotoxigenic strains was observed .", "entity": [], "task": "NER"}
{"text": "The polyphasic approach permitted the reliable identification of section Flavi species .", "entity": [], "task": "NER"}
{"text": "The rate of mycotoxigenic strains was high ( 92 . 7 % ) and mainly included A . flavus strains producing elevated levels of aflatoxins and CPA .", "entity": [{"entity": "aflatoxins", "entity_type": "Chemical", "pos": [124, 134]}, {"entity": "CPA", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "These results highlight the possibility of co - occurrence of both toxins , increasing their potential toxic effect in this commodity .", "entity": [], "task": "NER"}
{"text": "Flavour profiles of three novel acidic varieties of muskmelon ( Cucumis melo L . ) .", "entity": [], "task": "NER"}
{"text": "Novel acidic varieties of muskmelon ( Cucumis melo L . ) are emerging onto the UK market .", "entity": [], "task": "NER"}
{"text": "These melons contain almost twice the amount of citric acid compared to standard melons and are described as ' zesty and fresh ' .", "entity": [{"entity": "citric acid", "entity_type": "Chemical", "pos": [48, 59]}], "task": "NER"}
{"text": "This study compared the flavour components of three acidic varieties with a standard Galia - type melon .", "entity": [], "task": "NER"}
{"text": "The volatile and semivolatile compounds were extracted , using dynamic headspace extraction ( DHE ) or solid - phase microextraction ( SPME ) and solid phase extraction ( SPE ) , respectively , followed by gas chromatography - mass spectrometry ( GC - MS ) and gas chromatography - olfactometry ( GC - O ) .", "entity": [], "task": "NER"}
{"text": "More than 50 volatile and 50 semivolatile compounds were identified in the headspace and the SPE extracts , respectively .", "entity": [], "task": "NER"}
{"text": "GC - O revealed 15 odour - active components in the headspace , with esters being consistently higher in the acidic variety .", "entity": [{"entity": "esters", "entity_type": "Chemical", "pos": [69, 75]}], "task": "NER"}
{"text": "This study showed quantitative and qualitative differences among all four varieties and key differences between acidic varieties and standard melons .", "entity": [], "task": "NER"}
{"text": "Ostreol A : A new cytotoxic compound isolated from the epiphytic dinoflagellate Ostreopsis cf . ovata from the coastal waters of Jeju Island , Korea .", "entity": [{"entity": "Ostreol A", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Ostreol A was isolated from cultures of the epiphytic dinoflagellate Ostreopsis cf . ovata from the coastal waters of Jeju Island , Korea .", "entity": [{"entity": "Ostreol A", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The compound , a non - palytoxin derivative , has a polyhydroxy chain ending with the primary amino group and contains an amide bond , along with two tetrahydropyran rings in the chain .", "entity": [{"entity": "polyhydroxy", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "primary amino", "entity_type": "Chemical", "pos": [86, 99]}, {"entity": "amide", "entity_type": "Chemical", "pos": [122, 127]}, {"entity": "tetrahydropyran", "entity_type": "Chemical", "pos": [150, 165]}], "task": "NER"}
{"text": "Its chemical structure was elucidated by nuclear magnetic resonance ( NMR ) spectroscopy methods and confirmed by mass analysis .", "entity": [], "task": "NER"}
{"text": "The compound exhibited significant cytotoxicity in the brine shrimp lethality test at a concentration of 0 . 9 mu g / mL .", "entity": [], "task": "NER"}
{"text": "Arylsulfonamide pyrimidines as VLA - 4 antagonists .", "entity": [{"entity": "Arylsulfonamide pyrimidines", "entity_type": "Chemical", "pos": [0, 27]}], "task": "NER"}
{"text": "A series of ( S ) - 2 - ( 2 - ( diethylamino ) - 5 - ( N - alkyl - N - sulfonamido ) pyrimidin - 4 - ylamino ) - 3 - ( 4 - ( carbamoyloxy ) phenyl ) propanoic acid is discovered as orally available VLA - 4 antagonists .", "entity": [{"entity": "( S ) - 2 - ( 2 - ( diethylamino ) - 5 - ( N - alkyl - N - sulfonamido ) pyrimidin - 4 - ylamino ) - 3 - ( 4 - ( carbamoyloxy ) phenyl ) propanoic acid", "entity_type": "Chemical", "pos": [12, 163]}], "task": "NER"}
{"text": "Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models .", "entity": [], "task": "NER"}
{"text": "The in vitro selectivity of 11p is also described .", "entity": [], "task": "NER"}
{"text": "The fibroblast as a therapeutic target in rheumatoid arthritis .", "entity": [], "task": "NER"}
{"text": "Significant advances have been made in the last 5 years that have finally allowed investigators to start targeting stromal cells such as fibroblasts in inflammatory disease .", "entity": [], "task": "NER"}
{"text": "Rheumatoid arthritis is a prototype inflammatory disease , in which fibroblasts maintain the persistence of inflammation in the joint underpinned by a unique pathological phenotype driven by multiple epigenetic modifications .", "entity": [], "task": "NER"}
{"text": "The step changes that are enabling the development of such therapies are an improved understanding of the mechanisms by which fibroblasts mediate persistence and the discovery of new markers that identify discrete functional subsets of fibroblast cells that have potential as disease - specific therapeutic targets .", "entity": [], "task": "NER"}
{"text": "Melittin peptide kills Trypanosoma cruzi parasites by inducing different cell death pathways .", "entity": [], "task": "NER"}
{"text": "Antimicrobial peptides ( AMPs ) are components of the innate immune response that represent desirable alternatives to conventional pharmaceuticals , as they have a fast mode of action , a low likelihood of resistance development and can act in conjunction with existing drug regimens .", "entity": [], "task": "NER"}
{"text": "AMPs exhibit strong inhibitory activity against both Gram - positive and Gram - negative bacteria , fungi , viruses , metazoans and other parasites , such as the protozoan Leishmania .", "entity": [], "task": "NER"}
{"text": "Melittin is a naturally occurring AMP , which comprises 40 - 50 % of the dry weight of Apis mellifera venom .", "entity": [], "task": "NER"}
{"text": "Our group has recently shown that crude A . mellifera venom is lethal to Trypanosoma cruzi , the Chagas disease etiologic agent , and generates a variety of cell death phenotypes among treated parasites .", "entity": [], "task": "NER"}
{"text": "Here , we demonstrate that the melittin affected all of T . cruzi developmental forms , including the intracellular amastigotes .", "entity": [], "task": "NER"}
{"text": "The ultrastructural changes induced by melittin suggested the occurrence of different programmed cell death pathways , as was observed in A . mellifera - treated parasites .", "entity": [], "task": "NER"}
{"text": "Autophagic cell death appeared to be the main death mechanism in epimastigotes .", "entity": [], "task": "NER"}
{"text": "In contrast , melittin - treated trypomastigotes appeared to be dying via an apoptotic mechanism .", "entity": [], "task": "NER"}
{"text": "Our findings confirm the great potential of AMPs , including melittin , as a potential source of new drugs for the treatment of neglected diseases , such as Chagas disease .", "entity": [], "task": "NER"}
{"text": "TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate .", "entity": [{"entity": "citronellyl acetate", "entity_type": "Chemical", "pos": [60, 79]}], "task": "NER"}
{"text": "Background Citronellyl acetate ( CAT ) , a monoterpene product of the secondary metabolism of plants , has been shown in the literature to possess several different biological activities .", "entity": [{"entity": "Citronellyl acetate", "entity_type": "Chemical", "pos": [11, 30]}, {"entity": "CAT", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "monoterpene", "entity_type": "Chemical", "pos": [43, 54]}], "task": "NER"}
{"text": "However , no antinociceptive abilities have yet been discussed .", "entity": [], "task": "NER"}
{"text": "Here , we used acute pain animal models to describe the antinociceptive action of CAT .", "entity": [{"entity": "CAT", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "Methods The acetic acid - induced writhing test and the paw - licking test , in which paw licking was induced by glutamate and formalin , were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC , PKA , TRPV1 , TRPA1 , TRPM8 and ASIC in its antinociceptive mechanism .", "entity": [{"entity": "acetic acid", "entity_type": "Chemical", "pos": [12, 23]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [113, 122]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [127, 135]}, {"entity": "CAT", "entity_type": "Chemical", "pos": [195, 198]}], "task": "NER"}
{"text": "To do so , we induced paw - linking using agonists .", "entity": [], "task": "NER"}
{"text": "Results CAT was administered intragastrically ( 25 , 50 , 75 , 100 and 200mg / kg ) , and the two higher doses caused antinociceptive effects in the acetic acid model ; the highest dose reduced pain for 4h after it was administered ( 200mg / kg ) .", "entity": [{"entity": "CAT", "entity_type": "Chemical", "pos": [8, 11]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [149, 160]}], "task": "NER"}
{"text": "In the formalin test , two doses of CAT promoted antinociception in both the early and later phases of the test .", "entity": [{"entity": "formalin", "entity_type": "Chemical", "pos": [7, 15]}, {"entity": "CAT", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "CAT", "entity_type": "Chemical", "pos": [94, 97]}], "task": "NER"}
{"text": "Pretreatment with CAT did not alter locomotor activity or motor coordination .", "entity": [{"entity": "CAT", "entity_type": "Chemical", "pos": [18, 21]}], "task": "NER"}
{"text": "In an investigation into the participation of TRP channels and ASICs in CAT ' s antinociceptive mechanism , we used capsaicin ( 2 . 2 mu g / paw ) , cinnamaldehyde ( 10mmol / paw ) , menthol ( 1 . 2mmol / paw ) and acidified saline ( 2 % acetic acid , pH 1 . 98 ) .", "entity": [{"entity": "CAT", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "capsaicin", "entity_type": "Chemical", "pos": [116, 125]}, {"entity": "cinnamaldehyde", "entity_type": "Chemical", "pos": [149, 163]}, {"entity": "menthol", "entity_type": "Chemical", "pos": [183, 190]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [238, 249]}], "task": "NER"}
{"text": "The results showed that TRPV1 , TRPM8 and ASIC , but not TRPA1 , are involved in the antinociceptive mechanism .", "entity": [], "task": "NER"}
{"text": "Finally , the involvement of PKC and PKA was also studied , and we showed that both play a role in the antinociceptive mechanism of CAT .", "entity": [{"entity": "CAT", "entity_type": "Chemical", "pos": [132, 135]}], "task": "NER"}
{"text": "Conclusion The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that , at least in part , TRPV1 , TRPM8 , ASIC , glutamate receptors , PKC and PKA participate in CAT ' s antinociceptive mechanism .", "entity": [{"entity": "CAT", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [179, 188]}, {"entity": "CAT", "entity_type": "Chemical", "pos": [228, 231]}], "task": "NER"}
{"text": "Discovering and targeting the basic mechanism of neurodegeneration : The role of peptides from the C - terminus of acetylcholinesterase : Non - hydrolytic effects of ache : The actions of peptides derived from the C - terminal and their relevance to neurodegeneration .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [99, 100]}, {"entity": "C", "entity_type": "Chemical", "pos": [214, 215]}], "task": "NER"}
{"text": "Acetylcholinesterase ( AChE ) is now well - established widely as a signalling molecule with non - hydrolytic functions including trophic activity in a diverse variety of situations in both neural and non - neural tissues .", "entity": [], "task": "NER"}
{"text": "We have focussed on the observation that AChE , operating as a trophic agent independent of its enzymatic action , does indeed trigger calcium entry into neurons .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [135, 142]}], "task": "NER"}
{"text": "It is possible that AChE has a dual non - classical action that ranges along a trophic - toxic axis , depending on amount , duration of availability and , most significantly , age .", "entity": [], "task": "NER"}
{"text": "The neurodegenerative diseases could therefore be viewed as aberrant activation of developmental mechanisms with ' non - cholinergic ' AChE as a , perhaps the , pivotal molecule .", "entity": [], "task": "NER"}
{"text": "We have identified two peptides that could be cleaved from the C - terminus of T - AChE , one ( T14 ) , within the other ( T30 ) , and which have a strong sequence homology to the comparable region of beta - amyloid whilst the inert residue within the T30 sequence ( ' T15 ' ) acts as a control , and is without effect .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [63, 64]}], "task": "NER"}
{"text": "We have subsequently been able to ascribe the trophic - toxic actions of the both T14 and T30 peptides to the modulation of calcium influx via an allosteric site on the alpha - 7 nicotinic acetylcholine receptor ( alpha 7 - nAChR ) .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [124, 131]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [189, 202]}], "task": "NER"}
{"text": "If the scenario described here is indeed the primary mechanism of neurodegeneration , then interception of the actions of the ' non - cholinergic ' AChE - peptides T14 and T30 at the alpha 7 - nAChR , would be a promising novel therapy for arresting and stabilising cell loss in Alzheimer ' s disease , whereas detection of the peptides ideally in the blood , could provide a sensitive surrogate marker .", "entity": [], "task": "NER"}
{"text": "If the marker was sensitive enough to be detected pre - symptomatically in a routine blood test , then the medication for arresting further cell loss could be initiated at that time , and the symptoms would never appear .", "entity": [], "task": "NER"}
{"text": "This dual approach of identifying the marker and then intercepting its further action , could thus amount to an effective treatment for Alzheimer ' s and other neurodegenerative diseases .", "entity": [], "task": "NER"}
{"text": "Poly ( N - isopropylacrylamide - co - hydroxyethylacrylamide ) thermosensitive microspheres : The size of microgels dictates the pulsatile release mechanism .", "entity": [{"entity": "Poly ( N - isopropylacrylamide - co - hydroxyethylacrylamide )", "entity_type": "Chemical", "pos": [0, 62]}], "task": "NER"}
{"text": "Poly ( N - isopropylacrylamide - co - N - hydroxyethylacrylamide ) ( poly ( NIPAAm - co - HEAAm ) ) was prepared as a new thermosensitive copolymer possessing a sharp phase transition around the human body temperature .", "entity": [{"entity": "Poly ( N - isopropylacrylamide - co - N - hydroxyethylacrylamide )", "entity_type": "Chemical", "pos": [0, 66]}, {"entity": "poly ( NIPAAm - co - HEAAm )", "entity_type": "Chemical", "pos": [69, 97]}], "task": "NER"}
{"text": "The effect of the copolymer concentration on the lower critical solution temperature ( LCST ) was determined under physiological conditions by cloud point ( CP ) and differential scanning calorimetric ( DSC ) methods .", "entity": [], "task": "NER"}
{"text": "Then , thermosensitive microspheres were prepared from preformed copolymers by chemical cross - linking of hydroxyl groups with glutaraldehyde at a temperature situated slightly below LCST of the copolymer solution .", "entity": [{"entity": "hydroxyl", "entity_type": "Chemical", "pos": [107, 115]}, {"entity": "glutaraldehyde", "entity_type": "Chemical", "pos": [128, 142]}], "task": "NER"}
{"text": "The volume phase transition temperature ( VPTT ) of corresponding cross - linked microspheres was determined from swelling degree - temperature curve .", "entity": [], "task": "NER"}
{"text": "The microspheres were loaded with model drug indomethacin by the solvent evaporation method .", "entity": [{"entity": "indomethacin", "entity_type": "Chemical", "pos": [45, 57]}], "task": "NER"}
{"text": "The DSC analysis proved that the drug is molecularly dispersed in the polymer network .", "entity": [], "task": "NER"}
{"text": "Finally , the influence of the microsphere size on drug release was investigated .", "entity": [], "task": "NER"}
{"text": "It was established that microspheres with the diameter ranging between 5 and 60 mu m release the drug with almost the same rate below ( in the swollen state ) and above the VPTT ( in the collapsed state ) .", "entity": [], "task": "NER"}
{"text": "On the contrary , microspheres with the diameter ranging between 125 and 220 mu m release a significantly higher amount of indomethacin below than above the VPTT .", "entity": [{"entity": "indomethacin", "entity_type": "Chemical", "pos": [123, 135]}], "task": "NER"}
{"text": "This different behavior is enough to assure a pulsatile release mechanism when the temperature changes cyclically below and above the VPTT .", "entity": [], "task": "NER"}
{"text": "However , both small and large microspheres release a large amount of the drug during the collapsing process .", "entity": [], "task": "NER"}
{"text": "Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery : I .", "entity": [{"entity": "Carboxymethyl", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Monolithic Mesalamine forms for colon delivery .", "entity": [{"entity": "Mesalamine", "entity_type": "Chemical", "pos": [11, 21]}], "task": "NER"}
{"text": "For drugs expected to act locally in the colon , and for successful treatment , a delivery device is necessary , in order to limit the systemic absorption which decreases effectiveness and causes important side effects .", "entity": [], "task": "NER"}
{"text": "Various delayed release systems are currently commercialized ; most of them based on pH - dependent release which is sensitive to gastrointestinal pH variation .", "entity": [], "task": "NER"}
{"text": "This study proposes a novel excipient for colon delivery .", "entity": [], "task": "NER"}
{"text": "This new preparation consists in the complexation between carboxymethyl starch ( CMS ) and Lecithin ( L ) .", "entity": [{"entity": "carboxymethyl", "entity_type": "Chemical", "pos": [58, 71]}], "task": "NER"}
{"text": "As opposed to existing excipients , the new complex is pH - independent , inexpensive , and easy to manufacture and allows a high drug loading .", "entity": [], "task": "NER"}
{"text": "FTIR , X - ray , and SEM structural analysis all support the hypothesis of the formation of a complex .", "entity": [], "task": "NER"}
{"text": "By minor variation of the excipient content within the tablet , it is possible to modulate the release time and delivery at specific sites of the gastrointestinal tract .", "entity": [], "task": "NER"}
{"text": "This study opens the door to a new pH - independent delivery system for mesalamine targeted administration .", "entity": [{"entity": "mesalamine", "entity_type": "Chemical", "pos": [72, 82]}], "task": "NER"}
{"text": "Our novel formulation fits well with the posology of mesalamine , used in the treatment of Inflammatory Bowel Disease ( IBD ) , which requires repeated administrations ( 1g orally four times a day ) to maintain a good quality of life .", "entity": [{"entity": "mesalamine", "entity_type": "Chemical", "pos": [53, 63]}], "task": "NER"}
{"text": "Crystallization of poly ( ethylene oxide ) with acetaminophen - A study on solubility , spherulitic growth , and morphology .", "entity": [{"entity": "poly ( ethylene oxide )", "entity_type": "Chemical", "pos": [19, 42]}, {"entity": "acetaminophen", "entity_type": "Chemical", "pos": [48, 61]}], "task": "NER"}
{"text": "A simple , sensitive , efficient , and novel method analyzing the number of spherulitic nuclei was proposed to estimate the solubility of a model drug acetaminophen ( APAP ) in poly ( ethylene oxide ) ( PEO ) .", "entity": [{"entity": "acetaminophen", "entity_type": "Chemical", "pos": [151, 164]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [167, 171]}, {"entity": "poly ( ethylene oxide )", "entity_type": "Chemical", "pos": [177, 200]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [203, 206]}], "task": "NER"}
{"text": "At high crystallization temperature ( 323K ) , 10 % APAP - PEO had the same low number of spherulitic nuclei as pure PEO , indicating that APAP and PEO were fully miscible .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [117, 120]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [139, 143]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [148, 151]}], "task": "NER"}
{"text": "At low crystallization temperature ( 303K ) , the number of nuclei for 10 % APAP - PEO was significantly higher , suggesting that APAP was oversaturated and therefore recrystallized and acted as a nucleating agent .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [76, 80]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [130, 134]}], "task": "NER"}
{"text": "Based on the results obtained , the solubility of APAP in PEO is possibly between the concentration of 0 . 1 % and 1 % at 303K .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [58, 61]}], "task": "NER"}
{"text": "The spherulitic growth rate G of PEO was found to decrease with increasing APAP concentration , suggesting that APAP is most likely functioning as a chemical defect and is either rejected from or included in the PEO crystals during chain folding .", "entity": [{"entity": "PEO", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [75, 79]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [112, 116]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [212, 215]}], "task": "NER"}
{"text": "APAP could possibly locate in the inter - spherulitic , inter - fibrillar , inter - lamellar , or intra - lamellar regions of PEO .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [126, 129]}], "task": "NER"}
{"text": "At 323K , the morphology of 10 % APAP - PEO is more dendritic than spherulitic with large unfilled space in between dendrites and spherulites , which is a sign of one or the combination of the four modes of segregation .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [33, 37]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [40, 43]}], "task": "NER"}
{"text": "An extensive spherulitic nucleation and growth kinetics study using the classical theoretical relationships , for example , the Hoffman - Lauritzen ( HL ) and Avrami theories , was conducted .", "entity": [], "task": "NER"}
{"text": "Both microscopic and differential scanning calorimetric ( DSC ) analysis yielded similar values for the nucleation constant Kg as well as the fold surface free energy sigma e and work of chain folding q .", "entity": [], "task": "NER"}
{"text": "The values of sigma e and q increased with APAP concentration , indicating that the chain folding of PEO was hindered by APAP .", "entity": [{"entity": "APAP", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "PEO", "entity_type": "Chemical", "pos": [101, 104]}, {"entity": "APAP", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "Hyaluronic acid / chitosan multilayer coatings on neuronal implants for localized delivery of siRNA nanoplexes .", "entity": [], "task": "NER"}
{"text": "Binding , stabilizing and promoting cellular uptake of siRNA are all critical efforts in creating matrices for the localized delivery of siRNA molecules to target cells .", "entity": [], "task": "NER"}
{"text": "In this study , we describe the generation of chitosan imidazole / siRNA nanoplexes ( NPs ) embedded in nano scope polyelectrolyte multilayers ( PEMs ) composed of hyaluronic acid and chitosan for sustained and localized drug delivery .", "entity": [{"entity": "imidazole", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "Regular PEM build - up , successful integration of NPs and controlled release under physiological conditions were shown .", "entity": [], "task": "NER"}
{"text": "Biological efficacy was evaluated in neuronal cell culture concerning cell adhesion , viability , NPs uptake and gene silencing .", "entity": [], "task": "NER"}
{"text": "The additionally shown biological functionalization of neuronal implants possesses potential for future applications in the field of regenerative medicine and treatment of spinal cord injuries .", "entity": [], "task": "NER"}
{"text": "Medicinal plants of genus Curculigo : Traditional uses and a phytochemical and ethnopharmacological review .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : In the genus Curculigo , Curculigo orchioides Gaertn , Curculigo capitulata ( Lour ) O .", "entity": [], "task": "NER"}
{"text": "Ktze and Curculigo pilosa ( Schumach . & Thonn . ) Engl are often used in traditional medicine .", "entity": [], "task": "NER"}
{"text": "Curculigo orchioides is used for the treatment of impotence , limb limpness , arthritis of the lumbar and knee joints , and watery diarrhea in traditional Chinese medicine , and also used as a potent immunomodulator and aphrodisiac in the Ayurvedic medical system .", "entity": [], "task": "NER"}
{"text": "Curculigo capitulata is used for the treatment of consumptive cough , kidney asthenia , impotence and spermatorrhea , hemorrhoids , asthma , jaundice , diarrhea , colic and gonorrhea in traditional Chinese and India medicine , and to treat urinary tract infection , acute renal pelvis and nephritis , nephritis - edema , cystitis , nephrolithiasis , hypertension and rheumatic arthritis in traditional Dai medicine .", "entity": [], "task": "NER"}
{"text": "Curculigo pilosa are applied to treat gastrointestinal and heart diseases in Africa .", "entity": [], "task": "NER"}
{"text": "AIM OF THE REVIEW : This review aims to exhibit up - to - date and comprehensive information about traditional uses , phytochemistry , pharmacology and toxicology of medicinal plants in the genus Curculigo , and has an insight into the opportunities for the future research and development of Curculigo plant .", "entity": [], "task": "NER"}
{"text": "METHODS : A bibliographic investigation was performed by analyzing the information available on Curculigo plant from worldwide accepted scientific databases ( Pubmed , Scopus and Web of Science , SciFinder , Google Scholar , Yahoo ) .", "entity": [], "task": "NER"}
{"text": "Furthermore , information also was obtained from some local and foreign books on ethnobotany and ethnomedicines .", "entity": [], "task": "NER"}
{"text": "RESULTS : Curculigo orchioides , Curculigo capitulata and Curculigo pilosa have been used as traditional medicine to treat kinds of diseases such as impotence , limb limpness , gastrointestinal and heart diseases , etc .", "entity": [], "task": "NER"}
{"text": "Phytochemical investigation of eight species of the genus Curculigo has resulted in identification of more than 110 compounds .", "entity": [], "task": "NER"}
{"text": "The content of curculigoside is used as an indicator to evaluate the quality of rhizome of Curculigo orchioides .", "entity": [{"entity": "curculigoside", "entity_type": "Chemical", "pos": [15, 28]}], "task": "NER"}
{"text": "The medicinal plants have showed a wide spectrum pharmacological activities , including adaptive , immunostimulatory , taste - modifying and sweet - tasting , antioxidant , mast cell stabilization , antihistaminic and antiasthmatic , hepatoprotective and neuroprotective activity .", "entity": [], "task": "NER"}
{"text": "Toxicological test indicated that Curculigo orchioides at the dose of 120g / kg after administrating rats for 180 days may cause injury of liver and kidney .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : The medicinal plants of genus Curculigo have emerged as a good source of the traditional medicines .", "entity": [], "task": "NER"}
{"text": "Some uses of these plants in the traditional medicines have been validated by pharmacological investigation .", "entity": [], "task": "NER"}
{"text": "However , the mechanism of their actions should be further elucidated ; the particular constituent responsible for toxicity should be isolated and identified , and the target tissue and mechanism of toxic ingredients also deserve to be further investigated ; more reference substances should be prepared , and sophisticated analytical technologies should be developed to comprehensively assess the quality of Curculigo herbs .", "entity": [], "task": "NER"}
{"text": "These investigations will be helpful for further utilization of the plants of genus Curculigo .", "entity": [], "task": "NER"}
{"text": "Anti - inflammatory activity of hexane extracts from bones and internal organs of Anguilla japonica suppresses cyclooxygenase - 2 - dependent prostaglandin D2 generation in mast cells and anaphylaxis in mice .", "entity": [{"entity": "hexane", "entity_type": "Chemical", "pos": [32, 38]}, {"entity": "prostaglandin D2", "entity_type": "Chemical", "pos": [142, 158]}], "task": "NER"}
{"text": "The purpose of this study is to investigate the effects of n - hexane extracts from bones and internal organs of Japanese eel , Anguilla japonica ( HEE ) , on cyclooxygenase - 2 ( COX - 2 ) - dependent prostaglandin D2 ( PGD2 ) generation in stem cell factor ( SCF ) , IL - 10 , plus LPS - induced mouse bone marrow - derived mast cells ( BMMCs ) and on passive cutaneous anaphylaxis ( PCA ) in mice .", "entity": [{"entity": "n - hexane", "entity_type": "Chemical", "pos": [59, 69]}, {"entity": "prostaglandin D2", "entity_type": "Chemical", "pos": [202, 218]}, {"entity": "PGD2", "entity_type": "Chemical", "pos": [221, 225]}], "task": "NER"}
{"text": "HEE suppressed SCF / IL - 10 / LPS - induced PGD2 generation , and concomitantly reduced COX - 2 protein expression dose - dependently .", "entity": [{"entity": "PGD2", "entity_type": "Chemical", "pos": [45, 49]}], "task": "NER"}
{"text": "To understand the mechanistic basis for the inhibition of PGD2 generation by HEE , we examined the effects of HEE on upstream signaling pathways essential for COX - 2 induction .", "entity": [{"entity": "PGD2", "entity_type": "Chemical", "pos": [58, 62]}], "task": "NER"}
{"text": "HEE was found to inhibit the translocation of nuclear factor - kappa B ( NF - kappa B ) p65 subunit to the nucleus and its DNA - binding ability through the inhibition of TAK1 , IKK and I kappa B phosphorylation .", "entity": [], "task": "NER"}
{"text": "Furthermore , HEE also attenuated mitogen - activated protein kinase ( MAPK ) - mediated regulation of DNA binding of activator protein - 1 ( AP - 1 ) .", "entity": [], "task": "NER"}
{"text": "Moreover , oral administration of HEE inhibited anti - dinitrophenyl ( DNP ) IgE - induced PCA in a dose dependent manner .", "entity": [{"entity": "dinitrophenyl", "entity_type": "Chemical", "pos": [55, 68]}, {"entity": "DNP", "entity_type": "Chemical", "pos": [71, 74]}], "task": "NER"}
{"text": "Taken together , the present study provides new insights into the anti - inflammatory activity of HEE , which could be a promising candidate to be used for an inflammatory therapy .", "entity": [], "task": "NER"}
{"text": "Vinblastine - induced apoptosis of melanoma cells is mediated by Ras homologous A protein ( Rho A ) via mitochondrial and non - mitochondrial - dependent mechanisms .", "entity": [{"entity": "Vinblastine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Despite the availability of melanoma treatment at the primary site , the recurrence of local melanoma can metastasize to any distant organ .", "entity": [], "task": "NER"}
{"text": "Currently , the available therapies for the treatment of metastatic melanoma are of limited benefit .", "entity": [], "task": "NER"}
{"text": "Thus , the functional analysis of conventional therapies may help to improve their efficiency in the treatment of metastatic melanoma .", "entity": [], "task": "NER"}
{"text": "In the present study , the exposure of melanoma cells to vinblastine was found to trigger apoptosis as evidenced by the loss of mitochondrial membrane potential , the release of both cytochrome c and apoptosis inducing factor , activation of caspase - 9 and 3 , and cleavage of Poly ( ADP - ribose ) - Polymerase .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [57, 68]}, {"entity": "Poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [278, 299]}], "task": "NER"}
{"text": "Also , vinblastine enhances the phosphorylation of Ras homologous protein A , the accumulation of reactive oxygen species , the release of intracellular Ca ( 2 + ) , as well as the activation of apoptosis signal - regulating kinase 1 , c - jun - N - terminal kinase , p38 , inhibitor of kappaB alpha ( I kappa B alpha ) kinase , and inositol requiring enzyme 1 alpha .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [7, 18]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [107, 113]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [153, 163]}, {"entity": "N", "entity_type": "Chemical", "pos": [246, 247]}, {"entity": "inositol", "entity_type": "Chemical", "pos": [333, 341]}], "task": "NER"}
{"text": "In addition , vinblastine induces the DNA - binding activities of the transcription factor NF - kappa B , HSF1 , AP - 1 , and ATF - 2 , together with the expression of HSP70 and Bax proteins .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [14, 25]}], "task": "NER"}
{"text": "Moreover , inhibitory experiments addressed a central role for Rho A in the regulation of vinblastine - induced apoptosis of melanoma cells via mitochondrial and non - mitochondrial - dependent mechanisms .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [90, 101]}], "task": "NER"}
{"text": "In conclusion , the present study addresses for the first time a central role for Rho A in the modulation of vinblastine - induced apoptosis of melanoma cells and thereby provides an insight into the molecular action of vinblastine in melanoma treatment .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "vinblastine", "entity_type": "Chemical", "pos": [220, 231]}], "task": "NER"}
{"text": "Gene expression profiling of three different stressors in the water flea Daphnia magna .", "entity": [], "task": "NER"}
{"text": "Microarrays are an ideal tool to screen for differences in gene expression of thousands of genes simultaneously .", "entity": [], "task": "NER"}
{"text": "However , often commercial arrays are not available .", "entity": [], "task": "NER"}
{"text": "In this study , we performed microarray analyses to evaluate patterns of gene transcription following exposure to two natural and one anthropogenic stressor .", "entity": [], "task": "NER"}
{"text": "cDNA microarrays compiled of three life stage specific and three stressor - specific EST libraries , yielding 1734 different EST sequences , were used .", "entity": [], "task": "NER"}
{"text": "We exposed juveniles of the water flea Daphnia magna for 48 , 96 and 144 h to three stressors known to exert strong selection in natural populations of this species i . e . a sublethal concentration of the pesticide carbaryl , infective spores of the endoparasite Pasteuria ramosa , and fish predation risk mimicked by exposure to fish kairomones .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [216, 224]}], "task": "NER"}
{"text": "A total of 148 gene fragments were differentially expressed compared to the control .", "entity": [], "task": "NER"}
{"text": "Based on a PCA , the exposure treatments were separated into two main groups based on the extent of the transcriptional response : a low and a high ( 144 h of fish or carbaryl exposure and 96 h of parasite exposure ) stress group .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [167, 175]}], "task": "NER"}
{"text": "Firstly , we observed a general stress - related transcriptional expression profile independent of the treatment characterized by repression of transcripts involved in transcription , translation , signal transduction and energy metabolism .", "entity": [], "task": "NER"}
{"text": "Secondly , we observed treatment - specific responses including signs of migration to deeper water layers in response to fish predation , structural challenge of the cuticle in response to carbaryl exposure , and disturbance of the ATP production in parasite exposure .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [189, 197]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [232, 235]}], "task": "NER"}
{"text": "A third important conclusion is that transcription expression patterns exhibit stress - specific changes over time .", "entity": [], "task": "NER"}
{"text": "Parasite exposure shows the most differentially expressed gene fragments after 96 h .", "entity": [], "task": "NER"}
{"text": "The peak of differentially expressed transcripts came only after 144 h of fish exposure , while carbaryl exposure induced a more stable number of differently expressed gene fragments over time .", "entity": [{"entity": "carbaryl", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "Structure - Property Investigations of Substituted Triarylamines and Their Applications as Fluorescent pH Sensors .", "entity": [{"entity": "Triarylamines", "entity_type": "Chemical", "pos": [51, 64]}], "task": "NER"}
{"text": "Fourteen triphenylamine derivatives functionalized with fluorophenyl , methoxyphenyl , and pyridinyl groups as respective donors and acceptors were synthesized and characterized .", "entity": [{"entity": "triphenylamine", "entity_type": "Chemical", "pos": [9, 23]}, {"entity": "fluorophenyl", "entity_type": "Chemical", "pos": [56, 68]}, {"entity": "methoxyphenyl", "entity_type": "Chemical", "pos": [71, 84]}, {"entity": "pyridinyl", "entity_type": "Chemical", "pos": [91, 100]}], "task": "NER"}
{"text": "Their photophysical properties were systematically investigated in various solvents with different polarities .", "entity": [], "task": "NER"}
{"text": "The solvent - dependent Stokes shifts of these compounds were observed and analyzed by the Lippert - Mataga equation .", "entity": [], "task": "NER"}
{"text": "The synthesized compounds , especially tris ( 4 - ( pyridin - 4 - yl ) phenyl ) amine , presented pH - dependent absorptions and emissions , indicating that these compounds might be used as pH sensors .", "entity": [{"entity": "tris ( 4 - ( pyridin - 4 - yl ) phenyl ) amine", "entity_type": "Chemical", "pos": [39, 85]}], "task": "NER"}
{"text": "Twisted Signatures of GC - Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype .", "entity": [], "task": "NER"}
{"text": "The genomes of many vertebrates show a characteristic heterogeneous distribution of GC content , the so - called GC isochore structure .", "entity": [], "task": "NER"}
{"text": "The origin of isochores has been explained via the mechanism of GC - biased gene conversion ( gBGC ) .", "entity": [], "task": "NER"}
{"text": "However , although the isochore structure is declining in many mammalian genomes , the heterogeneity in GC content is being reinforced in the avian genome .", "entity": [], "task": "NER"}
{"text": "Despite this discrepancy , which remains unexplained , examinations of individual substitution frequencies in mammals and birds are both consistent with the gBGC model of isochore evolution .", "entity": [], "task": "NER"}
{"text": "On the other hand , a negative correlation between substitution and recombination rate found in the chicken genome is inconsistent with the gBGC model .", "entity": [], "task": "NER"}
{"text": "It should therefore be important to consider along with gBGC other consequences of recombination on the origin and fate of mutations , as well as to account for relationships between recombination rate and other genomic features .", "entity": [], "task": "NER"}
{"text": "We therefore developed an analytical model to describe the substitution patterns found in the chicken genome , and further investigated the relationships between substitution patterns and several genomic features in a rigorous statistical framework .", "entity": [], "task": "NER"}
{"text": "Our analysis indicates that GC content itself , either directly or indirectly via interrelations to other genomic features , has an impact on the substitution pattern .", "entity": [], "task": "NER"}
{"text": "Further , we suggest that this phenomenon is particularly visible in avian genomes due to their unusually low rate of chromosomal evolution .", "entity": [], "task": "NER"}
{"text": "Because of this , interrelations between GC content and other genomic features are being reinforced , and are as such more pronounced in avian genomes as compared with other vertebrate genomes with a less stable karyotype .", "entity": [], "task": "NER"}
{"text": "Combinatorial Treatment of Tart Cherry Extract and Essential Fatty Acids Reduces Cognitive Impairments and Inflammation in the mu - p75 Saporin - Induced Mouse Model of Alzheimer ' s Disease .", "entity": [{"entity": "Fatty Acids", "entity_type": "Chemical", "pos": [61, 72]}], "task": "NER"}
{"text": "Abstract Alzheimer ' s disease ( AD ) is a progressive neurodegenerative disorder that affects more than five million Americans and is characterized by a progressive loss of memory , loss of cholinergic neurons in the basal forebrain , formation of amyloid plaques and neurofibrillary tangles , and an increase in oxidative stress .", "entity": [], "task": "NER"}
{"text": "Recent studies indicate that dietary supplements of antioxidants and omega - 3 and omega - 6 fatty acids may reduce the cognitive deficits in AD patients .", "entity": [{"entity": "omega - 3 and omega - 6 fatty acids", "entity_type": "Chemical", "pos": [69, 104]}], "task": "NER"}
{"text": "The current study tested a combinatorial treatment of antioxidants from tart cherry extract and essential fatty acids from Nordic fish and emu oils for reducing cognitive deficits in the mu - p75 saporin ( SAP ) - induced mouse model of AD .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [106, 117]}], "task": "NER"}
{"text": "Mice were given daily gavage treatments of Cerise ( (R) ) Total - Body - Rhythm (TM) ( TBR ; containing tart cherry extract , Nordic fish oil , and refined emu oil ) or vehicle ( methylcellulose ) for 2 weeks before intracerebroventricular injections of the cholinergic toxin , mu - p75 SAP , or phosphate - buffered saline .", "entity": [{"entity": "phosphate", "entity_type": "Chemical", "pos": [296, 305]}], "task": "NER"}
{"text": "The TBR treatments continued for an additional 17 days , when the mice were tested on a battery of cognitive and motor tasks .", "entity": [], "task": "NER"}
{"text": "Results indicate that TBR decreased the SAP - induced cognitive deficits assessed by the object - recognition , place - recognition , and Morris - water - maze tasks .", "entity": [], "task": "NER"}
{"text": "Histological examination of the brain tissue indicated that TBR protected against SAP - induced inflammatory response and loss of cholinergic neurons in the area around the medial septum .", "entity": [], "task": "NER"}
{"text": "These findings indicate that TBR has the potential to serve as an adjunctive treatment which may help reduce the severity of cognitive deficits in disorders involving cholinergic deficits , such as AD .", "entity": [], "task": "NER"}
{"text": "Zhizhu decoction promotes gastric emptying and protects the gastric mucosa .", "entity": [], "task": "NER"}
{"text": "Abstract The aim of this study was to evaluate the effects of the Zhizhu decoction on gastric emptying and gastric mucosal protection .", "entity": [], "task": "NER"}
{"text": "The Zhizhu decoction is composed of Aurantii fructus and Atractylodes macrocephala Rhizoma .", "entity": [], "task": "NER"}
{"text": "Results showed that oral administration of the Zhizhu decoction accelerated gastric emptying in mouse and protected gastric mucosa from ethanol - induced ulcers in rat .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [136, 143]}], "task": "NER"}
{"text": "Our investigations demonstrated that the Zhizhu decoction accelerated gastric emptying , at least in part , by activating the muscarinic and 5 - HT3 receptors .", "entity": [], "task": "NER"}
{"text": "The gastroprotective effect is involved in its antioxidant effects and increased vascular endothelial growth factor expression .", "entity": [], "task": "NER"}
{"text": "The immunomodulation effect of aronia extract lacks association with its antioxidant anthocyanins .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [85, 97]}], "task": "NER"}
{"text": "Abstract Polyphenols comprise a diverse group of molecules with antioxidative and anti - inflammatory activities .", "entity": [{"entity": "Polyphenols", "entity_type": "Chemical", "pos": [9, 20]}], "task": "NER"}
{"text": "To compare the antioxidative and anti - inflammatory capacity of Aronia melanocarpa berries ( chokeberries ) , recognized for their high content of anthocyanins , a noncytotoxic isolation method was developed to obtain high - purity anthocyanins in the extract .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [148, 160]}, {"entity": "anthocyanins", "entity_type": "Chemical", "pos": [233, 245]}], "task": "NER"}
{"text": "The antioxidative activity of the extract , the anthocyanin - rich fraction ( AF ) was determined by 1 , 1 - diphenyl - 2 - picrylhydrazyl radical and ferric - reducing ability of plasma along with resveratrol as a reference .", "entity": [{"entity": "anthocyanin", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "1 , 1 - diphenyl - 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [101, 138]}, {"entity": "ferric", "entity_type": "Chemical", "pos": [151, 157]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [198, 209]}], "task": "NER"}
{"text": "The immunomodulation properties were assessed in lipopolysaccharide ( LPS ) - stimulated human monocytes mono mac 6 .", "entity": [], "task": "NER"}
{"text": "The isolated AF , containing six different anthocyanins , exhibited a stronger antioxidative capacity compared to resveratrol .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [43, 55]}, {"entity": "resveratrol", "entity_type": "Chemical", "pos": [114, 125]}], "task": "NER"}
{"text": "Resveratrol enhanced tumor necrosis factor - alpha and reduced interleukin - 10 ( IL - 10 ) production by LPS , whereas AF only had a slight effect in reducing IL - 10 .", "entity": [{"entity": "Resveratrol", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "These results demonstrated that there was no major relationship between the antioxidative effect and immunomodulation capacities of AF and resveratrol .", "entity": [{"entity": "resveratrol", "entity_type": "Chemical", "pos": [139, 150]}], "task": "NER"}
{"text": "The immunomodulatory activity of the extract is associated with bioactive compounds in Aronia other than its anthocyanins .", "entity": [{"entity": "anthocyanins", "entity_type": "Chemical", "pos": [109, 121]}], "task": "NER"}
{"text": "Novel sulfonamide compounds for inhibition of metastatic tumor growth ( WO2012021963 ) .", "entity": [{"entity": "sulfonamide", "entity_type": "Chemical", "pos": [6, 17]}], "task": "NER"}
{"text": "A series of novel ureido - sulfonamides was prepared by reaction of aminobenzenesulfonamide with alkyl / aryl isocyanate .", "entity": [{"entity": "ureido - sulfonamides", "entity_type": "Chemical", "pos": [18, 39]}, {"entity": "aminobenzenesulfonamide", "entity_type": "Chemical", "pos": [68, 91]}, {"entity": "alkyl / aryl isocyanate", "entity_type": "Chemical", "pos": [97, 120]}], "task": "NER"}
{"text": "These compounds are claimed for use as therapeutic agents of metastatic tumors , which are poorly responsive to classical chemotherapies and constitute a conceptually novel approach for cancer treatment .", "entity": [], "task": "NER"}
{"text": "High glucose , insulin and free fatty acid concentrations synergistically enhance perilipin 3 expression and lipid accumulation in macrophages .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [5, 12]}, {"entity": "free fatty acid", "entity_type": "Chemical", "pos": [27, 42]}], "task": "NER"}
{"text": "OBJECTIVE : Perilipin ( PLIN ) 3 , an intracellular lipid droplet ( LD ) - associated protein , is implicated in foam cell formation .", "entity": [], "task": "NER"}
{"text": "Since metabolic derangements found in metabolic syndrome , such as high serum levels of glucose , insulin and free fatty acids ( FFAs ) , are major risk factors promoting atherosclerosis , we investigated whether PLIN3 expression is affected by glucose , insulin and oleic acid ( OA ) using RAW264 . 7 cells .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [88, 95]}, {"entity": "free fatty acids", "entity_type": "Chemical", "pos": [110, 126]}, {"entity": "FFAs", "entity_type": "Chemical", "pos": [129, 133]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [245, 252]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [267, 277]}], "task": "NER"}
{"text": "METHODS : Real - time PCR and Western blotting were performed to detect PLIN3 or PLIN2 expression .", "entity": [], "task": "NER"}
{"text": "Oil - red O staining and Lipid Analysis were employed to measure cellular content of triacylglycerides ( TAG ) and cholesterol .", "entity": [{"entity": "Oil - red O", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "triacylglycerides", "entity_type": "Chemical", "pos": [85, 102]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [105, 108]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [115, 126]}], "task": "NER"}
{"text": "RESULTS : PLIN3 mRNA was stimulated by high glucose or insulin concentrations individually , but not by OA .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "A combination of any two factors did not enhance PLIN3 expression any more than that evoked by glucose alone at 24h .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "Interestingly , however , simultaneous addition of all three factors synergistically enhanced the PLIN3 expression .", "entity": [], "task": "NER"}
{"text": "This synergistic effect was not apparent for PLIN2 mRNA expression .", "entity": [], "task": "NER"}
{"text": "Inhibitors of Src family tyrosine kinase and / or phosphatidylinositol 3 - kinase , both of which are activated by insulin and FFA signaling , partially suppressed PLIN3 expression induced by the combination of the three factors .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [25, 33]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [50, 70]}, {"entity": "FFA", "entity_type": "Chemical", "pos": [127, 130]}], "task": "NER"}
{"text": "While simultaneous addition of glucose , insulin and OA remarkably increased the cellular content of TAG and cholesterol , knocking - down of PLIN3 predominantly reduced TAG content .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [31, 38]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [101, 104]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [170, 173]}], "task": "NER"}
{"text": "CONCLUSIONS : These results indicate that PLIN3 expression is synergistically stimulated by high glucose , insulin and FFA concentrations , in parallel with TAG accumulation in macrophages .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [97, 104]}, {"entity": "FFA", "entity_type": "Chemical", "pos": [119, 122]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [157, 160]}], "task": "NER"}
{"text": "This finding raises new evidence of PLIN3 involvement in conversion of macrophages into foam cells .", "entity": [], "task": "NER"}
{"text": "( 1 ) H NMR - based metabonomic analysis of the serum and urine of rats following subchronic exposure to dichlorvos , deltamethrin , or a combination of these two pesticides .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [105, 115]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [118, 130]}], "task": "NER"}
{"text": "Metabonomic analysis , clinical chemical analysis and histopathology were used to investigate the toxic effects of subchronic exposure to dichlorvos , deltamethrin , and a combination of these two pesticides , in rats .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [138, 148]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [151, 163]}], "task": "NER"}
{"text": "Weight loss , hind limb weakness and histopathological changes in kidney tissue were only observed in rats exposed to high doses of deltamethrin , or a combination of deltamethrin and dichlorvos .", "entity": [{"entity": "deltamethrin", "entity_type": "Chemical", "pos": [132, 144]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [167, 179]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [184, 194]}], "task": "NER"}
{"text": "Urinary metabonomic analysis indicated that exposure to a mixture of dichlorvos and deltamethrin was followed by increases in urinary lactate , dimethylamine , N - glycoprotein ( NAC ) and glycine similar to those observed in rats treated with either dichlorvos or deltamethrin alone .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [69, 79]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [84, 96]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [134, 141]}, {"entity": "dimethylamine", "entity_type": "Chemical", "pos": [144, 157]}, {"entity": "N", "entity_type": "Chemical", "pos": [160, 161]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [189, 196]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [251, 261]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [265, 277]}], "task": "NER"}
{"text": "Serum metabonomic analysis suggests that dichlorvos induced an increase in lactate and alanine and a decrease in dimethylglycine ( DMG ) , NAC and very low - and low - density lipoprotein ( VLDL / LDL ) .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [41, 51]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [75, 82]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "dimethylglycine", "entity_type": "Chemical", "pos": [113, 128]}, {"entity": "DMG", "entity_type": "Chemical", "pos": [131, 134]}], "task": "NER"}
{"text": "High levels of lactate and low levels of NAC and VLDL / LDL were observed in the deltamethrin treatment group .", "entity": [{"entity": "lactate", "entity_type": "Chemical", "pos": [15, 22]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [81, 93]}], "task": "NER"}
{"text": "Treating rats with a mixture of dichlorvos and deltamethrin caused an increase in serum lactate , trimethylamine - N - oxide ( TMAO ) , choline and alanine , with the highest levels of these metabolites observed in those that received the highest dose .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [32, 42]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [47, 59]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [88, 95]}, {"entity": "trimethylamine - N - oxide", "entity_type": "Chemical", "pos": [98, 124]}, {"entity": "TMAO", "entity_type": "Chemical", "pos": [127, 131]}, {"entity": "choline", "entity_type": "Chemical", "pos": [136, 143]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "Exposure to a mixture of dichlorvos and deltamethrin also resulted in a decrease in serum acetone , DMG , NAC , and VLDL / LDL .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [25, 35]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [40, 52]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [90, 97]}, {"entity": "DMG", "entity_type": "Chemical", "pos": [100, 103]}], "task": "NER"}
{"text": "Changes in serum TMAO , alanine , choline and acetone in this treatment group were higher than in rats treated with either dichlorvos or deltamethrin .", "entity": [{"entity": "TMAO", "entity_type": "Chemical", "pos": [17, 21]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [24, 31]}, {"entity": "choline", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "dichlorvos", "entity_type": "Chemical", "pos": [123, 133]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [137, 149]}], "task": "NER"}
{"text": "These results suggest that exposing rats to subchronic doses of dichlorvos , deltamethrin , or a combination of these pesticides , disrupted the energy metabolism of the liver and reduced kidney function .", "entity": [{"entity": "dichlorvos", "entity_type": "Chemical", "pos": [64, 74]}, {"entity": "deltamethrin", "entity_type": "Chemical", "pos": [77, 89]}], "task": "NER"}
{"text": "Identification of active compounds from Caesalpinia sappan L . extracts suppressing IL - 6 production in RAW 264 . 7 cells by PLS .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Caesalpinia sappan L .", "entity": [], "task": "NER"}
{"text": "is distributed in Southeast Asia and also used as herbal medicine for the treatment of various diseases such as burning sensations , leprosy , dysentery , osteoarthritis and rheumatoid arthritis ( RA ) .", "entity": [], "task": "NER"}
{"text": "The overproduction of IL - 6 plays an important role in the prognosis of RA , but the active compounds from the extracts of Caesalpinia sappan L . suppressing IL - 6 production remain unknown .", "entity": [], "task": "NER"}
{"text": "AIMS OF THE STUDY : Identifying the main active compounds of Caesalpinia sappan L . extracts inhibiting the IL - 6 production in LPS - stimulated RAW 264 . 7 cells by partial least squares ( PLS ) .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : Sixty - four samples with different proportions of compounds were prepared from Caesalpinia sappan L . by supercritical CO2 fluid extraction ( SCFE ) and refluxing .", "entity": [{"entity": "CO2", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "Each of 64 samples was applied to RAW 264 . 7 cells with LPS to evaluate whether IL - 6 production by LPS is affected by addition of each sample .", "entity": [], "task": "NER"}
{"text": "The IL - 6 production in medium was determined by ELISA and the inhibitory activity of each sample was analyzed .", "entity": [], "task": "NER"}
{"text": "In addition , the fingerprints of these 64 samples were also established by ultra - performance liquid chromatography electrospray ionization tandem mass spectrometry ( UPLC - MS ) .", "entity": [], "task": "NER"}
{"text": "We used the PLS , a simplified method , to evaluate the results from IL - 6 production and fingerprints .", "entity": [], "task": "NER"}
{"text": "RESULTS : Each of 64 samples markedly suppressed LPS - induced IL - 6 production in RAW cells .", "entity": [], "task": "NER"}
{"text": "The fingerprints by UPLC - MS clearly revealed variations among 64 samples produced in different extract conditions .", "entity": [], "task": "NER"}
{"text": "The PLS analysis with IL - 6 production and fingerprints by UPLC - MS suggested that the peaks 71 , 93 , 150 , 157 , 168 have more influence on the inhibitory activity of Caesalpinia sappan L . extracts .", "entity": [], "task": "NER"}
{"text": "The peaks 71 , 93 , 150 are likely representing sappanone A , protosappanin E and neoprotosappanin , respectively .", "entity": [{"entity": "sappanone A", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "protosappanin E", "entity_type": "Chemical", "pos": [62, 77]}, {"entity": "neoprotosappanin", "entity_type": "Chemical", "pos": [82, 98]}], "task": "NER"}
{"text": "The peaks 157 and 168 are still at large .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : This is the first report that sappanone A , protosappanin E , neoprotosappanin and two unidentified compounds can be considered as possible active compounds that might inhibit IL - 6 production .", "entity": [{"entity": "sappanone A", "entity_type": "Chemical", "pos": [43, 54]}, {"entity": "protosappanin E", "entity_type": "Chemical", "pos": [57, 72]}, {"entity": "neoprotosappanin", "entity_type": "Chemical", "pos": [75, 91]}], "task": "NER"}
{"text": "Further studies are needed to confirm the effectiveness of these five compounds on IL - 6 production and possible mechanism .", "entity": [], "task": "NER"}
{"text": "Commonly used metal and crystalline salts in South African traditional medicine .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Traditional medicines in the form of plants , animals and / or minerals are used by millions of South Africans .", "entity": [], "task": "NER"}
{"text": "There is currently no data regarding the commonly used mineral elements thus the potential benefits or hazards of such products remain unclear .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : Metal and crystalline salts were purchased from a rural market ( Nongoma , Zululand , South Africa ) .", "entity": [], "task": "NER"}
{"text": "Information regarding the colloquial name , price and weight was recorded .", "entity": [], "task": "NER"}
{"text": "Energy dispersive X - ray spectroscopy ( EDX ) was used to quantatively determine the unknown salts .", "entity": [], "task": "NER"}
{"text": "RESULTS : Six widely available salts were analyzed .", "entity": [], "task": "NER"}
{"text": "Ndonya , as it is colloquially known , refers to two products which look identical to the untrained eye - one is dyed table salt and the other is hexavalent chromium .", "entity": [{"entity": "salt", "entity_type": "Chemical", "pos": [124, 128]}, {"entity": "hexavalent chromium", "entity_type": "Chemical", "pos": [146, 165]}], "task": "NER"}
{"text": "A further product used medicinally , although not widely available , was identified as iron chromite ore .", "entity": [{"entity": "iron chromite", "entity_type": "Chemical", "pos": [87, 100]}], "task": "NER"}
{"text": "CONCLUSIONS : The array of substances documented , ranging from benign to carcinogenic , stresses the importance of documenting components used in traditional medicine and confirms the necessity to regulate South Africa traditional medicine .", "entity": [], "task": "NER"}
{"text": "Healthcare workers should be aware of the complexities of using such metal salt .", "entity": [], "task": "NER"}
{"text": "Real - time imaging and kinetics measurements of focused ultrasound - induced extravasation in skeletal muscle using SPECT / CT .", "entity": [], "task": "NER"}
{"text": "Drugs need to overcome several biological barriers such as the endothelium and cellular membranes in order to reach their target .", "entity": [], "task": "NER"}
{"text": "Promising new therapeutics , many of which are charged and macromolecular , are not able to passively extravasate , let alone cross cell membranes , and stay mainly in the blood pool upon intravenous injection until clearance .", "entity": [], "task": "NER"}
{"text": "Using focused ultrasound ( fUS ) in combination with circulating microbubbles ( MBs ) leads to temporary localized tissue permeabilization allowing extravasation of ( macro ) molecules from the vascular system .", "entity": [], "task": "NER"}
{"text": "Thus , fUS is a promising approach for localized drug delivery .", "entity": [], "task": "NER"}
{"text": "However , little is known about the permeabilization kinetics in skeletal muscle .", "entity": [], "task": "NER"}
{"text": "In this study , we used single photon emission computed tomography ( SPECT ) to characterize the kinetics of extravasation of ( 111 ) In - labeled bovine serum albumin ( BSA ) , a model macromolecular drug , in muscle treated with fUS and MBs .", "entity": [{"entity": "( 111 ) In", "entity_type": "Chemical", "pos": [126, 136]}], "task": "NER"}
{"text": "The same fUS protocol was applied to 6 groups of mice with different times , increment t , between fUS application and BSA injection ( increment t = - 10 , 2 . 5 , 10 , 30 , 60 , 90min ) followed by SPECT imaging .", "entity": [], "task": "NER"}
{"text": "For increment t <= 30min we observed an exponential accumulation of activity in an area of the treated muscle which extended to a volume larger than the fUS pattern with highest accumulation for short waiting times increment t .", "entity": [], "task": "NER"}
{"text": "The extent of extravasation decreased exponentially with increasing increment t , with a calculated half - life of ca .", "entity": [], "task": "NER"}
{"text": "21min , defining the time window of extravasation .", "entity": [], "task": "NER"}
{"text": "The same treatment without MBs did not induce extravasation of BSA thus supporting MBs and drug co - injection strategies .", "entity": [], "task": "NER"}
{"text": "These results provide essential information for the development of fUS based strategies for localized drug delivery .", "entity": [], "task": "NER"}
{"text": "Comparative study on transcriptional activity of 17 parabens mediated by estrogen receptor alpha and beta and androgen receptor .", "entity": [{"entity": "parabens", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [73, 81]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [110, 118]}], "task": "NER"}
{"text": "The structure - activity relationships of parabens which are widely used as preservatives for transcriptional activities mediated by human estrogen receptor alpha ( hER alpha ) , hER beta and androgen receptor ( hAR ) were investigated .", "entity": [{"entity": "parabens", "entity_type": "Chemical", "pos": [42, 50]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [139, 147]}, {"entity": "androgen", "entity_type": "Chemical", "pos": [192, 200]}], "task": "NER"}
{"text": "Fourteen of 17 parabens exhibited hER alpha and / or hER beta agonistic activity at concentrations of >= 1 x 10 ( - 5 ) M , whereas none of the 17 parabens showed AR agonistic or antagonistic activity .", "entity": [{"entity": "parabens", "entity_type": "Chemical", "pos": [15, 23]}, {"entity": "parabens", "entity_type": "Chemical", "pos": [147, 155]}], "task": "NER"}
{"text": "Among 12 parabens with linear alkyl chains ranging in length from C1 to C12 , heptylparaben ( C7 ) and pentylparaben ( C5 ) showed the most potent ER alpha and ER beta agonistic activity in the order of 10 ( - 7 ) M and 10 ( - 8 ) M , respectively , and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12 .", "entity": [{"entity": "parabens", "entity_type": "Chemical", "pos": [9, 17]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [30, 35]}, {"entity": "heptylparaben", "entity_type": "Chemical", "pos": [78, 91]}, {"entity": "pentylparaben", "entity_type": "Chemical", "pos": [103, 116]}], "task": "NER"}
{"text": "Most parabens showing estrogenic activity exhibited ER beta - agonistic activity at lower concentrations than those inducing ER alpha - agonistic activity .", "entity": [{"entity": "parabens", "entity_type": "Chemical", "pos": [5, 13]}], "task": "NER"}
{"text": "The estrogenic activity of butylparaben was markedly decreased by incubation with rat liver microsomes , and the decrease of activity was blocked by a carboxylesterase inhibitor .", "entity": [{"entity": "butylparaben", "entity_type": "Chemical", "pos": [27, 39]}], "task": "NER"}
{"text": "These results indicate that parabens are selective agonists for ER beta over ER alpha ; their interactions with ER alpha / beta are dependent on the size and bulkiness of the alkyl groups ; and they are metabolized by carboxylesterases , leading to attenuation of their estrogenic activity .", "entity": [{"entity": "parabens", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [175, 180]}], "task": "NER"}
{"text": "DICO , a novel nonaromatic B - ring flavonoid , induces G2 / M cell cycle arrest and apoptosis in human hepatoma cells .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [36, 45]}], "task": "NER"}
{"text": "DICO was a novel nonaromatic B - ring flavonoid obtained from Macrothelypteris torresiana .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "In the present work , we investigated the antitumor activity and the antineoplastic mechanism of DICO .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [97, 101]}], "task": "NER"}
{"text": "Our study showed that DICO inhibited the growth of HepG2 cells in dose and time - dependent manners .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [22, 26]}], "task": "NER"}
{"text": "As well as DICO induced G2 / M cell cycle arrest and apoptosis via a ROS - mediated mitochondrial pathway .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [11, 15]}], "task": "NER"}
{"text": "Western blot assay demonstrated that DICO decreased Bcl - 2 level and induced Bax translocation to cause cytochrome c release .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [37, 41]}], "task": "NER"}
{"text": "Subsequently , caspase - 9 and caspase - 3 were activated .", "entity": [], "task": "NER"}
{"text": "Meanwhile , the alterations of cyclin A and B1 , p - CDK1 and p - cdc25c levels were also observed in response to DICO treatment .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [114, 118]}], "task": "NER"}
{"text": "Taken together , DICO displayed a significant antitumor effect through G2 / M cell cycle arrest and apoptosis induction , which suggested DICO might have therapeutic potential against tumors .", "entity": [{"entity": "DICO", "entity_type": "Chemical", "pos": [17, 21]}, {"entity": "DICO", "entity_type": "Chemical", "pos": [138, 142]}], "task": "NER"}
{"text": "Chloroquine causes similar electroretinogram modifications , neuronal phospholipidosis and marked impairment of synaptic vesicle transport in Albino and Pigmented Rats .", "entity": [{"entity": "Chloroquine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Retinal toxicity of chloroquine has been known for several years , but the mechanism ( s ) of toxicity remain controversial ; some author support the idea that the binding of chloroquine to melanin pigments in the retinal pigmented epithelium ( RPE ) play a major toxic role by concentrating the drug in the eye .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [20, 31]}, {"entity": "chloroquine", "entity_type": "Chemical", "pos": [175, 186]}], "task": "NER"}
{"text": "In our study , 12 albinos Sprague - Dawley ( SD ) and 12 pigmented Brown Norway ( BN ) rats were treated orally for 3 months with chloroquine to compare functional and pathological findings .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [130, 141]}], "task": "NER"}
{"text": "On Flash electroretinograms ( ERG ) performed in scotopic conditions , similar and progressive ( time - dependent ) delayed onset and decreased amplitudes of oscillatory potentials ( from Day 71 ) and b - waves ( on Day 92 ) were identified in both BN and SD rats .", "entity": [], "task": "NER"}
{"text": "In both strains , identical morphological changes consisted of neuronal phospholipidosis associated with UV auto - fluorescence without evidence of retinal degeneration and gliosis ; the RPE did not show any morphological lesions or autofluorescence .", "entity": [], "task": "NER"}
{"text": "IHC analyses demonstrated a decrease in GABA expression in the inner nuclear layer .", "entity": [{"entity": "GABA", "entity_type": "Chemical", "pos": [40, 44]}], "task": "NER"}
{"text": "In addition , a marked accumulation of synaptic vesicles coupled with a marked disruption of neurofilaments in the optic nerve fibers was identified .", "entity": [], "task": "NER"}
{"text": "In conclusion , ERG observations were very similar to those described in humans .", "entity": [], "task": "NER"}
{"text": "Comparable ERG modifications , histopathology and immunohistochemistry findings were observed in the retina of both rat strains suggesting that melanin pigment is unlikely involved . chloroquine - induced impairment of synaptic vesicle transport , likely related to disruption of neurofilaments was identified and non - previously reported .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [183, 194]}], "task": "NER"}
{"text": "This new mechanism of toxicity may also be responsible for the burry vision described in humans chronically treated with chloroquine .", "entity": [{"entity": "chloroquine", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "Thiazolidin - 4 - one and thiazinan - 4 - one derivatives analogous to rosiglitazone as potential antihyperglycemic and antidyslipidemic agents .", "entity": [{"entity": "Thiazolidin - 4 - one", "entity_type": "Chemical", "pos": [0, 21]}, {"entity": "thiazinan - 4 - one", "entity_type": "Chemical", "pos": [26, 45]}, {"entity": "rosiglitazone", "entity_type": "Chemical", "pos": [71, 84]}], "task": "NER"}
{"text": "A number of thiazolidin - 4 - one and thiazinan - 4 - one derivatives were prepared by three component condensation in one pot reaction method .", "entity": [{"entity": "thiazolidin - 4 - one", "entity_type": "Chemical", "pos": [12, 33]}, {"entity": "thiazinan - 4 - one", "entity_type": "Chemical", "pos": [38, 57]}], "task": "NER"}
{"text": "These compounds were evaluated for anti - hyperglycemic activity by in vitro and in vivo assay systems .", "entity": [], "task": "NER"}
{"text": "The compounds with thiazolidin - 4 - one and thiazinan - 4 - one moieties exhibited significant anti - hyperglycemic activity .", "entity": [{"entity": "thiazolidin - 4 - one", "entity_type": "Chemical", "pos": [19, 40]}, {"entity": "thiazinan - 4 - one", "entity_type": "Chemical", "pos": [45, 64]}], "task": "NER"}
{"text": "A few compounds ( 3a , 3b , 4a and 4b ) have exhibited both anti - hyperglycemic and anti - dyslipidemic activities .", "entity": [], "task": "NER"}
{"text": "Among them the thiazinan - 4 - one derivative 4a showed maximal ( 45 % ) improvement in oral glucose tolerance test in db / db mice at 30 mg / kg oral dose .", "entity": [{"entity": "thiazinan - 4 - one", "entity_type": "Chemical", "pos": [15, 34]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [93, 100]}], "task": "NER"}
{"text": "Synthesis and biological evaluation of novel aliphatic amido - quaternary ammonium salts for anticancer chemotherapy : Part II .", "entity": [{"entity": "aliphatic amido - quaternary ammonium salts", "entity_type": "Chemical", "pos": [45, 88]}], "task": "NER"}
{"text": "A series of novel aliphatic amido - quaternary ammonium salts were synthesized and evaluated for their anticancer effects involving induction of RhoB .", "entity": [{"entity": "aliphatic amido - quaternary ammonium salts", "entity_type": "Chemical", "pos": [18, 61]}], "task": "NER"}
{"text": "Most of these compounds , featuring open - ring forms of aliphatic amido - quaternary ammonium salts , exhibited potent anti - proliferative activities in human cancer cell lines , including PC - 3 , NUGC - 3 , MDA - MB - 231 , ACHN , HCT - 15 , and NCI - H23 .", "entity": [{"entity": "aliphatic amido - quaternary ammonium salts", "entity_type": "Chemical", "pos": [57, 100]}], "task": "NER"}
{"text": "In further evaluation , the representative compound N , N - diethyl - N - ( 2 - ( N - methyltetradecanamido ) ethyl ) prop - 2 - en - 1 - aminium bromide ( 3b ) exhibited potent pro - apoptotic activity , through RhoB activation , in HeLa cells .", "entity": [{"entity": "N , N - diethyl - N - ( 2 - ( N - methyltetradecanamido ) ethyl ) prop - 2 - en - 1 - aminium bromide", "entity_type": "Chemical", "pos": [52, 153]}], "task": "NER"}
{"text": "Identification of novel FLT3 kinase inhibitors .", "entity": [], "task": "NER"}
{"text": "FLT3 and PDGFR tyrosine kinases are important targets for therapy of different types of leukemia .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "Several FLT3 / PDGFR inhibitors are currently under clinical investigation for combination with standard therapy for treatment of acute myeloid leukemia ( AML ) , however these agents only induce partial remission and development of resistance has been reported .", "entity": [], "task": "NER"}
{"text": "In this work we describe the identification of potent and novel dual FLT3 / PDGFR inhibitors that resulted from our efforts to screen a library of 25 , 607 small molecules against the FLT3 dependent cell line MOLM - 13 and the PDGFR dependent cell line EOL - 1 .", "entity": [], "task": "NER"}
{"text": "This effort led to the identification of five compounds that were confirmed to be active on additional FLT3 dependent cell lines ( cellular EC50 values between 35 and 700 nM ) , while having no significant effect on 24 other tyrosine kinases .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [225, 233]}], "task": "NER"}
{"text": "Preparation and antimalarial activity of semisynthetic lycorenine derivatives .", "entity": [{"entity": "lycorenine", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "A set of twenty one lycorenine derivatives has been prepared from the alkaloid hippeastrine ( 1 ) .", "entity": [{"entity": "lycorenine", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "hippeastrine", "entity_type": "Chemical", "pos": [79, 91]}], "task": "NER"}
{"text": "The modifications performed on hippeastrine included some functional group transformations , structural simplification and preparation of dimers .", "entity": [{"entity": "hippeastrine", "entity_type": "Chemical", "pos": [31, 43]}], "task": "NER"}
{"text": "All alkaloids were tested as potential antimalarial agents , being the hippeastrine dimers the most active compounds .", "entity": [{"entity": "hippeastrine", "entity_type": "Chemical", "pos": [71, 83]}], "task": "NER"}
{"text": "Transport of gabapentin by LAT1 ( SLC7A5 ) .", "entity": [{"entity": "gabapentin", "entity_type": "Chemical", "pos": [13, 23]}], "task": "NER"}
{"text": "Gabapentin is used in the treatment of epilepsy and neuropathic pain .", "entity": [{"entity": "Gabapentin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Gabapentin has high and saturable permeability across the BBB , but no mechanistic studies underpinning this process have been reported .", "entity": [{"entity": "Gabapentin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The aim of the current study was to investigate the transport of gabapentin in a model of the BBB , identify the important drug transporter ( s ) and to use mathematical modelling to quantify the processes involved .", "entity": [{"entity": "gabapentin", "entity_type": "Chemical", "pos": [65, 75]}], "task": "NER"}
{"text": "A human brain endothelial cell line ( hCMEC / D3 ) was utilised as an in - vitro model of the BBB .", "entity": [], "task": "NER"}
{"text": "Uptake of radiolabeled gabapentin into cells in the presence of chemical inhibitors , siRNA or overexpressed drug transporters of interest was investigated .", "entity": [{"entity": "radiolabeled gabapentin", "entity_type": "Chemical", "pos": [10, 33]}], "task": "NER"}
{"text": "Gabapentin was demonstrated to be a LAT1 substrate in brain endothelial cells ( LAT1 - process ; Km = 530 mu M and Vmax = 7039pmoles / million cells / min versus other - processes ; Km = 923 mu M and Vmax = 3656pmoles / million cells / min ) and in transfected HEK 293 LAT1 cells ( LAT1 - process ; Km = 217 mu M and Vmax = 5192pmoles / million cells / min versus otherprocesses ; Km = 1546 mu M and Vmax = 3375pmoles / million cells / min ) .", "entity": [{"entity": "Gabapentin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "At physiological concentrations of gabapentin , LAT1 mediated transport was 3 or ~ 10 - fold higher than the other transport processes in the two systems , respectively , demonstrating clear selectivity for gabapentin .", "entity": [{"entity": "gabapentin", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "gabapentin", "entity_type": "Chemical", "pos": [207, 217]}], "task": "NER"}
{"text": "In - silico structural homology modelling confirmed that LAT1 could have the LeuT conserved fold and functions by the alternative access mechanism .", "entity": [], "task": "NER"}
{"text": "Mathematical modelling of this mechanism revealed revised significance of Vmax and Km so that a low Km may not necessarily imply a high affinity transport process .", "entity": [], "task": "NER"}
{"text": "Gabapentin was negative for OCT like transport and LAT2 activity in the hCMEC / D3 and OCT1 transfected cells .", "entity": [{"entity": "Gabapentin", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Our data shows that gabapentin is a substrate for the influx transporter LAT1 at therapeutic concentrations .", "entity": [{"entity": "gabapentin", "entity_type": "Chemical", "pos": [20, 30]}], "task": "NER"}
{"text": "Single - photon sources : non - blinking single - photon generation with anisotropic colloidal nanocrystals : towards room - temperature , efficient , colloidal quantum sources ( adv . Mater . 14 / 2013 ) .", "entity": [], "task": "NER"}
{"text": "High - quality core / shell CdSe / CdS colloidal nanocrystals are demonstrated to be efficient sources of non - classical light .", "entity": [{"entity": "CdSe", "entity_type": "Chemical", "pos": [28, 32]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [35, 38]}], "task": "NER"}
{"text": "As shown by Ferruccio Pisanello and co - workers on page 1974 , the intrinsic anisotropy of these nanoparticles allows an independent tuning of shell length and thickness , resulting in a full control of photon statistics .", "entity": [], "task": "NER"}
{"text": "This can be exploited to obtain non - blinking , room - temperature single - photon generation , thus bringing colloidal nanocrystals one step closer to non - classical light sources for quantum applications .", "entity": [], "task": "NER"}
{"text": "Light - Emitting Field - Effect Transistors Having Combined Organic Semiconductor and Metal Oxide Layers .", "entity": [{"entity": "Metal Oxide", "entity_type": "Chemical", "pos": [86, 97]}], "task": "NER"}
{"text": "A new organic light - emitting field - effect transistor characterized by a metal oxide layer inserted between the organic layer and the gate insulator is proposed .", "entity": [{"entity": "metal oxide", "entity_type": "Chemical", "pos": [76, 87]}], "task": "NER"}
{"text": "The metal oxide is indirectly connected with source and drain electrodes through the organic layer .", "entity": [{"entity": "metal oxide", "entity_type": "Chemical", "pos": [4, 15]}], "task": "NER"}
{"text": "Upon increasing the potential difference between the source and drain electrodes , the emission becomes exceedingly strong and the emission region encompasses the whole channel zone .", "entity": [], "task": "NER"}
{"text": "Patterned Growth of Crystalline Organic Heterostructures .", "entity": [], "task": "NER"}
{"text": "Organic droplet epitaxy is presented as a method for growing nanopatterned crystalline heterostructures , thanks to the transport of molecules of an amorphous first - layer on top of a crystalline second - layer , where they form an epitaxial interface .", "entity": [], "task": "NER"}
{"text": "Such heterostructures may be transferred to any substrates , raising particular interest for applications ( e . g . , for organic photovoltaics ) , where crystallinity and nanopatterning constitute well recognized advantages .", "entity": [], "task": "NER"}
{"text": "Decreased consumption of sweet fluids in mu opioid receptor knockout mice : a microstructural analysis of licking behavior .", "entity": [], "task": "NER"}
{"text": "RATIONALE : Evidence suggests that the palatability of food ( i . e . , the hedonic impact produced by its sensory features ) can promote feeding and may underlie compulsive eating , leading to obesity .", "entity": [], "task": "NER"}
{"text": "Pharmacological studies implicate opioid transmission in the hedonic control of feeding , though these studies often rely on agents lacking specificity for particular opioid receptors .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : Here , we investigated the role of mu opioid receptors ( MORs ) specifically in determining hedonic responses to palatable sweet stimuli .", "entity": [], "task": "NER"}
{"text": "METHODS : In Experiment 1 , licking microstructure when consuming sucrose solution ( 2 to 20 % ) was compared in MOR knockout and wildtype mice as a function of sucrose concentration and level of food deprivation .", "entity": [{"entity": "sucrose", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "sucrose", "entity_type": "Chemical", "pos": [161, 168]}], "task": "NER"}
{"text": "In Experiment 2 , a similar examination was conducted using the palatable but calorie - free stimulus sucralose ( 0 . 001 to 1 % ) , allowing study of licking behavior independent of homeostatic variables .", "entity": [{"entity": "sucralose", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "RESULTS : In Experiment 1 , MOR knockout mice exhibited several alterations in sucrose licking .", "entity": [{"entity": "sucrose", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "Although wildtype mice exhibited a twofold increase in the burst length when food deprived , relative to the nondeprived test , this aspect of sucrose licking was generally insensitive to manipulations of food deprivation for MOR knockout mice .", "entity": [{"entity": "sucrose", "entity_type": "Chemical", "pos": [143, 150]}], "task": "NER"}
{"text": "Furthermore , during concentration testing , their rate of sucrose licking was less than half that of wildtype mice .", "entity": [{"entity": "sucrose", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "During sucralose testing ( Experiment 2 ) , MOR knockout mice licked at approximately half the wildtype rate , providing more direct evidence that MOR knockout mice were impaired in processing stimulus palatability .", "entity": [{"entity": "sucralose", "entity_type": "Chemical", "pos": [7, 16]}], "task": "NER"}
{"text": "CONCLUSIONS : These results suggest that transmission through MORs mediates hedonic responses to palatable stimuli , and therefore likely contributes to normal and pathological eating .", "entity": [], "task": "NER"}
{"text": "Non - classical Pharmacology of the Dopamine Transporter : Atypical Inhibitors , Allosteric Modulators and Partial Substrates .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "The dopamine transporter ( DAT ) is a sodium - coupled symporter protein responsible for modulating the concentration of extraneuronal dopamine in the brain .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [4, 12]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [38, 44]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [135, 143]}], "task": "NER"}
{"text": "The DAT is a principle target of various psychostimulant , nootropic and antidepressant drugs , as well as certain drugs used recreationally , including the notoriously addictive stimulant cocaine .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [189, 196]}], "task": "NER"}
{"text": "DAT ligands have traditionally been divided into two categories : cocaine - like inhibitors and amphetamine - like substrates .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [96, 107]}], "task": "NER"}
{"text": "Whereas inhibitors block monoamine uptake by the DAT , but are not translocated across the membrane , substrates are actively translocated and trigger DAT - mediated release of dopamine by reversal of the translocation cycle .", "entity": [{"entity": "monoamine", "entity_type": "Chemical", "pos": [25, 34]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "As both inhibitors and substrates increase extraneuronal dopamine levels , it is often assumed that all DAT ligands posses an addictive liability equivalent to cocaine .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [57, 65]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [160, 167]}], "task": "NER"}
{"text": "However , the recent development of novel ' atypical ' inhibitors and ' partial substrate ' ligands with reduced or even a complete lack of cocaine - like rewarding effects suggests that addictiveness is not a constant property of DAT - affecting compounds .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [140, 147]}], "task": "NER"}
{"text": "These atypical ligands do not conform to the classical preconception that all DAT inhibitors ( or substrates ) are functionally and mechanistically alike .", "entity": [], "task": "NER"}
{"text": "Instead , they suggest the possibility that the DAT exhibits some of the ligand - specific ' pleiotropic ' functional qualities inherent to G - protein - coupled receptors .", "entity": [], "task": "NER"}
{"text": "That is , ligands with different chemical structures induce specific conformational changes in the transporter protein , which can be differentially transduced by the cell , ultimately eliciting unique behavioral and psychical effects .", "entity": [], "task": "NER"}
{"text": "The present overview discusses compounds with conformation - specific activity , useful not only as tools for studying the mechanics of dopamine transport , but also as leads for medication development in addictive disorders .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Molecular Identification and Characterization of an Essential Pyruvate Transporter from Trypanosoma brucei .", "entity": [{"entity": "Pyruvate", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "Pyruvate export is an essential physiological process for the bloodstream form of T . brucei as the parasite would otherwise accumulate this end product of glucose metabolism to toxic levels .", "entity": [{"entity": "Pyruvate", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [156, 163]}], "task": "NER"}
{"text": "In the studies reported here genetic complementation in Saccharomyces cerevisiae has been employed to identify a gene ( TbPT0 ) that encodes this vital pyruvate transporter from T . brucei .", "entity": [{"entity": "pyruvate", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "Expression of TbPT0 in S . cerevisiae reveals that TbPT0 is a high affinity pyruvate transporter .", "entity": [{"entity": "pyruvate", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "TbPT0 belongs to a clustered multigene family consisting of five members , whose expression is up - regulated in the bloodstream form .", "entity": [], "task": "NER"}
{"text": "Interestingly , TbPT family permeases are related to polytopic proteins from plants but not to characterized monocarboxylate transporters from mammals .", "entity": [{"entity": "monocarboxylate", "entity_type": "Chemical", "pos": [109, 124]}], "task": "NER"}
{"text": "Remarkably , inhibition of the TbPT gene family expression in bloodstream parasites by RNAi is lethal , confirming the physiological relevance of these transporters .", "entity": [], "task": "NER"}
{"text": "The discovery of TbPT0 reveals for the first time the identity of the essential pyruvate transporter and provides a potential drug target against the mammalian life cycle stage of T . brucei .", "entity": [{"entity": "pyruvate", "entity_type": "Chemical", "pos": [80, 88]}], "task": "NER"}
{"text": "DNA repair and cytotoxic drugs : the potential role of RAD51 in clinical outcome of non - small - cell lung cancer patients .", "entity": [], "task": "NER"}
{"text": "Many of the cytotoxic drugs used in the treatment of non - small - cell lung carcinoma patients can interfere with DNA activity and the definition of an individual DNA repair profile could be a key strategy to achieve better response to chemotherapeutic treatment .", "entity": [], "task": "NER"}
{"text": "Although DNA repair mechanisms are important factors in the prevention of carcinogenesis , these molecular pathways are also involved in therapy response .", "entity": [], "task": "NER"}
{"text": "RAD51 is a crucial element in DNA repair by homologous recombination and has been shown to interfere with the prognosis of patients treated with chemoradiotherapy .", "entity": [], "task": "NER"}
{"text": "There is increasing evidence that genetic polymorphisms in repair enzymes can influence DNA repair capacity and , consequently , affect chemotherapy efficacy .", "entity": [], "task": "NER"}
{"text": "We conducted this review to show the possible influence of the RAD51 genetic variants in damage repair capacity and treatment response in non - small - cell lung carcinoma patients .", "entity": [], "task": "NER"}
{"text": "Extracellular Signal - Regulated Kinases ( ERK ) Inhibitors from Aristolochia yunnanensis .", "entity": [], "task": "NER"}
{"text": "Six new sesquiterpenoids , aristoyunnolins A - F ( 1 - 6 ) , an artifact of isolation [ 7 - O - ethyl madolin W ( 7 ) ] , and 12 known analogues were isolated from stems of Aristolochia yunnanensis .", "entity": [{"entity": "sesquiterpenoids", "entity_type": "Chemical", "pos": [8, 24]}, {"entity": "aristoyunnolins A - F", "entity_type": "Chemical", "pos": [27, 48]}, {"entity": "7 - O - ethyl madolin W", "entity_type": "Chemical", "pos": [88, 111]}], "task": "NER"}
{"text": "The structures were determined by combined chemical and spectral methods , and the absolute configurations of compounds 2 , 3 , 5 - 7 , 9 , 14 , and 17 were determined by the modified Mosher ' s method and CD analysis .", "entity": [], "task": "NER"}
{"text": "Compounds 1 - 19 were screened using a bioassay system designed to evaluate the effect on mitogen - activated protein kinases ( MAPKs ) signaling pathways .", "entity": [], "task": "NER"}
{"text": "Among three MAPKs ( ERK1 / 2 , JNK , and p38 ) , compounds 1 , 4 , 10 - 13 , 16 , 18 , and 19 exhibited selective inhibition of the phosphorylation of ERK1 / 2 .", "entity": [], "task": "NER"}
{"text": "Compounds 16 and 19 were more active than the positive control PD98059 , a known inhibitor of the ERK1 / 2 signaling pathway .", "entity": [{"entity": "PD98059", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "Different levels of prenatal zinc and selenium had different effects on neonatal neurobehavioral development .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [29, 33]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [38, 46]}], "task": "NER"}
{"text": "Either deficient or excessive of essential nutrients had adverse effects .", "entity": [], "task": "NER"}
{"text": "Effects of different levels of prenatal zinc ( Zn ) and selenium ( Se ) on fetal neurobehavioral development remain unclear .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [40, 44]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [47, 49]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "Se", "entity_type": "Chemical", "pos": [67, 69]}], "task": "NER"}
{"text": "To determine the effects of different cord serum levels of Zn and Se on neurobehavioral development in neonates and to explore possible threshold level of Zn and Se based on fetal neurodevelopment , we conducted this epidemiological research .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [59, 61]}, {"entity": "Se", "entity_type": "Chemical", "pos": [66, 68]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [155, 157]}, {"entity": "Se", "entity_type": "Chemical", "pos": [162, 164]}], "task": "NER"}
{"text": "In the multi - center study , we investigated these questions in 927 mother - newborn pairs in Shanghai , China , from 2008 through 2009 .", "entity": [], "task": "NER"}
{"text": "Umbilical cord serum concentrations of Zn and Se were measured and Neonatal Behavioral Neurological Assessment ( NBNA ) tests were conducted .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "Se", "entity_type": "Chemical", "pos": [46, 48]}], "task": "NER"}
{"text": "The median cord serum Zn and Se concentrations were 794 . 3 mu g / L and 63 . 1 mu g / L , respectively .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "Se", "entity_type": "Chemical", "pos": [29, 31]}], "task": "NER"}
{"text": "A nonlinear relationship was observed between cord serum Zn and NBNA after adjusting for potential confounders .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [57, 59]}], "task": "NER"}
{"text": "NBNA score decreased with increasing Zn levels after 794 . 3 mu g / L ( adjusted beta = - 3 . 0 , 95 % CI : - 3 . 6 to - 2 . 4 , p < 0 . 001 ) .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [37, 39]}], "task": "NER"}
{"text": "Additionally , an invert U - shape with a threshold Se of 100 mu g / L was observed between cord serum Se and NBNA .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "Se", "entity_type": "Chemical", "pos": [103, 105]}], "task": "NER"}
{"text": "The adjusted regression coefficient was 4 . 4 ( 95 % CI : 3 . 6 - 5 . 2 , p < 0 . 001 ) for Se < 100 mu g / L while - 3 . 6 ( 95 % CI : - 6 . 1 to - 1 . 1 , p < 0 . 01 ) for Se >= 100 mu g / L .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [92, 94]}, {"entity": "Se", "entity_type": "Chemical", "pos": [174, 176]}], "task": "NER"}
{"text": "Of the 927 infants , 50 % had a high level Zn ( >= 794 . 3 mu g / L ) and 8 . 6 % had a high level Se ( >= 100 mu g / L ) .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [43, 45]}, {"entity": "Se", "entity_type": "Chemical", "pos": [99, 101]}], "task": "NER"}
{"text": "High levels of both Zn and Se mainly had adverse effects on behavior and passive tone ( p < 0 . 001 ) .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [20, 22]}, {"entity": "Se", "entity_type": "Chemical", "pos": [27, 29]}], "task": "NER"}
{"text": "Taken together , our study suggested that a threshold of cord blood Zn and Se was existed for fetal neurodevelopment and the prevalence of excessive Zn was high .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [68, 70]}, {"entity": "Se", "entity_type": "Chemical", "pos": [75, 77]}, {"entity": "Zn", "entity_type": "Chemical", "pos": [149, 151]}], "task": "NER"}
{"text": "Thus , the supplementation of Zn during pregnancy should be considered with caution in Shanghai , China .", "entity": [{"entity": "Zn", "entity_type": "Chemical", "pos": [30, 32]}], "task": "NER"}
{"text": "Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium - dependent protein kinase 1 ( PfCDPK1 ) .", "entity": [{"entity": "imidazopyridazines", "entity_type": "Chemical", "pos": [12, 30]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "A series of imidazopyridazines which are potent inhibitors of Plasmodium falciparum calcium - dependent protein kinase 1 ( PfCDPK1 ) was identified from a high - throughput screen against the isolated enzyme .", "entity": [{"entity": "imidazopyridazines", "entity_type": "Chemical", "pos": [12, 30]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "Subsequent exploration of the SAR and optimisation has yielded leading members which show promising in vitro anti - parasite activity along with good in vitro ADME and selectivity against human kinases .", "entity": [], "task": "NER"}
{"text": "Initial in vivo testing has revealed good oral bioavailability in a mouse PK study and modest in vivo efficacy in a Plasmodium berghei mouse model of malaria .", "entity": [], "task": "NER"}
{"text": "Development and evaluation of novel solid nanodispersion system for oral delivery of poorly water - soluble drugs .", "entity": [], "task": "NER"}
{"text": "The aim of the present study was to develop and evaluate a novel drug solubilization platform ( so - called solid nanodispersion ) prepared by a simple co - grinding and solvent - free process .", "entity": [], "task": "NER"}
{"text": "Using structurally diverse model compounds from the Pfizer drug library , including ingliforib , furosemide and celecoxib , we successfully prepared stable solid nanodispersions ( SNDs ) without the use of solvent or heat .", "entity": [{"entity": "ingliforib", "entity_type": "Chemical", "pos": [84, 94]}, {"entity": "furosemide", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "celecoxib", "entity_type": "Chemical", "pos": [112, 121]}], "task": "NER"}
{"text": "Stable colloidal particles ( < 350nm ) containing drug , polyvinylpyrrolidone ( PVP ) K12 and sodium dodecyl sulfate ( SDS ) in 1 : 2 . 75 : 0 . 25 ratio were produced after 2h of co - grinding .", "entity": [{"entity": "polyvinylpyrrolidone", "entity_type": "Chemical", "pos": [57, 77]}, {"entity": "( PVP ) K12", "entity_type": "Chemical", "pos": [78, 89]}, {"entity": "sodium dodecyl sulfate", "entity_type": "Chemical", "pos": [94, 116]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [119, 122]}], "task": "NER"}
{"text": "The composition and particle size of SNDs were optimized by varying the grinding media size , powder - to - grinding media ratio , milling speed and milling time .", "entity": [], "task": "NER"}
{"text": "The resulting formulations contained crystalline drug and were stable at room temperature for over one month .", "entity": [], "task": "NER"}
{"text": "Greater than 80 % of the drug was released from the SND in less than 30min , with sustained supersaturation over 4h .", "entity": [], "task": "NER"}
{"text": "Using furosemide ( BCS class IV compound ) as a model compound , we conducted transport studies with Madin - Darby canine kidney cells transfected with human MDR1 gene ( MDCK / MDR1 ) , followed by pharmacokinetics studies in rats .", "entity": [{"entity": "furosemide", "entity_type": "Chemical", "pos": [6, 16]}], "task": "NER"}
{"text": "Results showed that the SND formulation enhanced the absorptive flux of furosemide by more than 3 - fold .", "entity": [{"entity": "furosemide", "entity_type": "Chemical", "pos": [72, 82]}], "task": "NER"}
{"text": "In the pharmacokinetics studies , the SND formulation increased Cmax and AUC of furosemide by 36 . 6 and 43 . 2 fold respectively , relative to Methocel formulation .", "entity": [{"entity": "furosemide", "entity_type": "Chemical", "pos": [80, 90]}], "task": "NER"}
{"text": "Interestingly , physical mixture containing furosemide , PVP K12 and SDS produced a similar level of oral exposure as the SNDs , albeit with a longer Tmax than the SND formulation .", "entity": [{"entity": "furosemide", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "PVP K12", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "The results suggest that PVP K12 and SDS were able to increase the furosemide free fraction available for oral absorption .", "entity": [{"entity": "PVP K12", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "furosemide", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Low solubility , poor permeability , and high first - pass effect of furosemide may also have produced the effect that small improvements in solubilization resulted in significant potentiation of the oral exposure of the physical mixture .", "entity": [{"entity": "furosemide", "entity_type": "Chemical", "pos": [69, 79]}], "task": "NER"}
{"text": "However the use of a physical mixture of drug , polymer and surfactant , to increase drug bioavailability cannot be generalized to all drugs .", "entity": [], "task": "NER"}
{"text": "There are only a few reported cases of such phenomenon .", "entity": [], "task": "NER"}
{"text": "While SNDs may not be the only option to solubilize compounds in every case , SNDs are expected to be applicable to a broader chemical space of pharmaceutical compounds compared to a physical mixture .", "entity": [], "task": "NER"}
{"text": "Ultimately , formulation scientists have to exercise judgment in choosing the appropriate formulation strategy for the compound of interest .", "entity": [], "task": "NER"}
{"text": "SNDs represent a significant improvement over current enabling technologies such as nanocrystal and spray - dried dispersion technologies , in that SNDs are simple , do not require solvent or heat , are applicable to a structurally diverse chemical space , and are amenable to the development of solid dosage forms .", "entity": [], "task": "NER"}
{"text": "In vivo and in vitro anti - inflammatory potential of pentahydroxy - pregn - 14 - ol , 20 - one - beta - d - thevetopyranoside in rats .", "entity": [{"entity": "pentahydroxy - pregn - 14 - ol , 20 - one - beta - d - thevetopyranoside", "entity_type": "Chemical", "pos": [54, 126]}], "task": "NER"}
{"text": "Polyhydroxy pregnane glycoside ( PPG ) , a steroidal glycoside was isolated from Wattakaka volubilis Linn .", "entity": [{"entity": "Polyhydroxy pregnane glycoside", "entity_type": "Chemical", "pos": [0, 30]}, {"entity": "PPG", "entity_type": "Chemical", "pos": [33, 36]}, {"entity": "steroidal glycoside", "entity_type": "Chemical", "pos": [43, 62]}], "task": "NER"}
{"text": "( Stap . f . ) .", "entity": [], "task": "NER"}
{"text": "PPG was evaluated for in vivo and in vitro anti - inflammatory activity using acute inflammation and chronic model of inflammation in rats and LPS - induced RAW 264 . 7 macrophage cells .", "entity": [{"entity": "PPG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "PPG seemed to be responsible for the anti - inflammatory activity in the studied models .", "entity": [{"entity": "PPG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "PPG at dose level of both 5 and 10mg / kg significantly reduced the edema induced by the carrageenan in acute model of inflammation .", "entity": [{"entity": "PPG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "It also showed significant anti - proliferative effect ( dry pellet weight basis ) in chronic model of inflammation .", "entity": [], "task": "NER"}
{"text": "Cellular content of granuloma was measured by assaying activity of N - acetyl glucosaminidase ( NAG ) and total nucleic acid content .", "entity": [{"entity": "N - acetyl", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "PPG at 5 and 10mg / kg significantly suppressed the cellular infiltration measured by total nucleic acid content .", "entity": [{"entity": "PPG", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "In contrast , NAG activity decreased over a period of 10 days resulting in inhibition of granuloma weight gain .", "entity": [], "task": "NER"}
{"text": "PPG had a more effective response than the reference drug diclofenac sodium in both the models of inflammation .", "entity": [{"entity": "PPG", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "diclofenac sodium", "entity_type": "Chemical", "pos": [58, 75]}], "task": "NER"}
{"text": "Wattakaka volubilis steroidal glycoside mixture ( WVSM ) and PPG ( 1 - 50 mu M ) significantly inhibited the COX - 2 and iNOS enzymes resulting in low levels of PGE2 and NO in LPS - induced RAW 264 . 7 macrophage cells .", "entity": [{"entity": "steroidal glycoside", "entity_type": "Chemical", "pos": [20, 39]}, {"entity": "PPG", "entity_type": "Chemical", "pos": [61, 64]}], "task": "NER"}
{"text": "Hence the study supports the traditional use of Wattakaka volubilis and its constituent PPG in treatment of inflammatory disorders .", "entity": [{"entity": "PPG", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "DNA repair activity in fish and interest in ecotoxicology : A review .", "entity": [], "task": "NER"}
{"text": "The knowledge of DNA repair in a target species is of first importance as it is the primary line of defense against genotoxicants , and a better knowledge of DNA repair capacity in fish could help to interpret genotoxicity data and / or assist in the choice of target species , developmental stage and tissues to focus on , both for environmental biomonitoring studies and DNA repair testing .", "entity": [], "task": "NER"}
{"text": "This review focuses in a first part on what is presently known on a mechanistic basis , about the various DNA repair systems in fish , in vivo and in established cell lines .", "entity": [], "task": "NER"}
{"text": "Data on base excision repair ( BER ) , direct reversal with O ( 6 ) - alkylguanine transferase and double strand breaks repair , although rather scarce , are being reviewed , as well as nucleotide excision repair ( NER ) and photoreactivation repair ( PER ) , which are by far the most studied repair mechanisms in fish .", "entity": [{"entity": "O ( 6 ) - alkylguanine", "entity_type": "Chemical", "pos": [60, 82]}, {"entity": "nucleotide", "entity_type": "Chemical", "pos": [186, 196]}], "task": "NER"}
{"text": "Most of these repair mechanisms seem to be strongly species and tissue dependent ; they also depend on the developmental stage of the organisms .", "entity": [], "task": "NER"}
{"text": "BER is efficient in vivo , although no data has been found on in vitro models .", "entity": [], "task": "NER"}
{"text": "NER activity is quite low or even inexistent depending on the studies ; however this lack is partly compensated by a strong PER activity , especially in early developmental stage .", "entity": [], "task": "NER"}
{"text": "In a second part , a survey of the ecotoxicological studies integrating DNA repair as a parameter responding to single or mixture of contaminant is realized .", "entity": [], "task": "NER"}
{"text": "Three main approaches are being used : the measurement of DNA repair gene expression after exposure , although it has not yet been clearly established whether gene expression is indicative of repair capacity ; the monitoring of DNA damage removal by following DNA repair kinetics ; and the modulation of DNA repair activity following exposure in situ , in order to assess the impact of exposure history on DNA repair capacity .", "entity": [], "task": "NER"}
{"text": "Since all DNA repair processes are possible targets for environmental pollutants , we can also wonder at which extent such a modulation of repair capacities in fish could be the base for the development of new biomarkers of genotoxicity .", "entity": [], "task": "NER"}
{"text": "Knowing the importance of the germ cell DNA integrity in the reproductive success of aquatic organisms , the DNA repair capacity of such cells deserve to be more studied , as well as DNA repair capacities of established fish cell lines .", "entity": [], "task": "NER"}
{"text": "The limited amount of available data , which shows low / slow DNA repair capacities of fish cell lines compared with mammalian cell lines , concerned mainly the NER system ; thus this point merits to be explored more deeply .", "entity": [], "task": "NER"}
{"text": "Additionally , since some of the DNA repair systems appear more efficient in embryo larval stages , it would be of interest to consider embryonic cell lineages more closely .", "entity": [], "task": "NER"}
{"text": "The Ras - GTPase activity of neurofibromin restrains ERK - dependent FGFR signaling during endochondral bone formation .", "entity": [], "task": "NER"}
{"text": "The severe defects in growth plate development caused by chondrocyte extracellular signal - regulated protein kinases 1 and 2 ( ERK1 / 2 ) gain or loss - of - function suggest that tight spatial and temporal regulation of mitogen - activated protein kinase signaling is necessary to achieve harmonious growth plate elongation and structure .", "entity": [], "task": "NER"}
{"text": "We provide here evidence that neurofibromin , via its Ras guanosine triphosphatase - activating activity , controls ERK1 / 2 - dependent fibroblast growth factor receptor ( FGFR ) signaling in chondrocytes .", "entity": [{"entity": "guanosine", "entity_type": "Chemical", "pos": [58, 67]}], "task": "NER"}
{"text": "We show first that neurofibromin is expressed in FGFR - positive prehypertrophic and hypertrophic chondrocytes during growth plate endochondral ossification .", "entity": [], "task": "NER"}
{"text": "Using mice lacking neurofibromin 1 ( Nf1 ) in type II collagen - expressing cells , ( Nf1col2 ( - / - ) mutant mice ) , we then show that lack of neurofibromin in post - mitotic chondrocytes triggers a number of phenotypes reminiscent of the ones observed in mice characterized by FGFR gain - of - function mutations .", "entity": [], "task": "NER"}
{"text": "Those include dwarfism , constitutive ERK1 / 2 activation , strongly reduced Ihh expression and decreased chondrocyte proliferation and maturation , increased chondrocytic expression of Rankl , matrix metalloproteinase 9 ( Mmp9 ) and Mmp13 and enhanced growth plate osteoclastogenesis , as well as increased sensitivity to caspase - 9 mediated apoptosis .", "entity": [], "task": "NER"}
{"text": "Using wildtype ( WT ) and Nf1 ( - / - ) chondrocyte cultures in vitro , we show that FGF2 pulse - stimulation triggers rapid ERK1 / 2 phosphorylation in both genotypes , but that return to the basal level is delayed in Nf1 ( - / - ) chondrocytes .", "entity": [], "task": "NER"}
{"text": "Importantly , in vivo ERK1 / 2 inhibition by daily injection of a recombinant form of C - type natriuretic peptide to post - natal pups for 18 days was able to correct the short stature of Nf1col2 ( - / - ) mice .", "entity": [], "task": "NER"}
{"text": "Together , these results underscore the requirement of neurofibromin and ERK1 / 2 for normal endochondral bone formation and support the notion that neurofibromin , by restraining RAS - ERK1 / 2 signaling , is a negative regulator of FGFR signaling in differentiating chondrocytes .", "entity": [], "task": "NER"}
{"text": "Stereoselective Glucuronidation of Ornidazole in Humans : Predominant Contribution of UDP - Glucuronosyltransferases 1A9 and 2B7 .", "entity": [{"entity": "Ornidazole", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "UDP", "entity_type": "Chemical", "pos": [86, 89]}], "task": "NER"}
{"text": "Ornidazole [ R , S - 1 - chloro - 3 - ( 2 - methyl - 5 - nitro - 1H - imidazol - 1 - yl ) propan - 2 - ol ] is a chiral 5 - nitroimidazole class antimicrobial agent .", "entity": [{"entity": "Ornidazole", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "R , S - 1 - chloro - 3 - ( 2 - methyl - 5 - nitro - 1H - imidazol - 1 - yl ) propan - 2 - ol", "entity_type": "Chemical", "pos": [13, 105]}, {"entity": "5 - nitroimidazole", "entity_type": "Chemical", "pos": [120, 138]}], "task": "NER"}
{"text": "This study aimed to investigate the principal metabolic pathway of ornidazole in humans and identify the major enzymes involved .", "entity": [{"entity": "ornidazole", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "A total of 19 metabolites were identified in human urine collected from patients with hepatobiliary diseases after an intravenous drip infusion of 500 mg of racemic ornidazole .", "entity": [{"entity": "racemic ornidazole", "entity_type": "Chemical", "pos": [157, 175]}], "task": "NER"}
{"text": "Stereoselective glucuronidation , followed by renal excretion , was the principal metabolic pathway of ornidazole in humans , accounting for 37 . 3 % of the administered dose .", "entity": [{"entity": "ornidazole", "entity_type": "Chemical", "pos": [103, 113]}], "task": "NER"}
{"text": "Screening assays with 12 available human recombinant UDP - glucuronosyltransferases ( UGTs ) demonstrated that UGT1A9 was the predominant UGT isoform involved in R - ornidazole glucuronidation , whereas S - ornidazole glucuronidation was almost exclusively catalyzed by UGT2B7 .", "entity": [{"entity": "UDP", "entity_type": "Chemical", "pos": [53, 56]}, {"entity": "R - ornidazole", "entity_type": "Chemical", "pos": [162, 176]}, {"entity": "S - ornidazole", "entity_type": "Chemical", "pos": [203, 217]}], "task": "NER"}
{"text": "Chemical inhibition study with niflumic acid and flurbiprofen supported these findings .", "entity": [{"entity": "niflumic acid", "entity_type": "Chemical", "pos": [31, 44]}, {"entity": "flurbiprofen", "entity_type": "Chemical", "pos": [49, 61]}], "task": "NER"}
{"text": "Enzyme kinetic parameters were then determined in human liver microsomes ( HLMs ) , human kidney microsomes ( HKMs ) , UGT1A9 and 2B7 .", "entity": [], "task": "NER"}
{"text": "The Km values for UGT1A9 ( 15 . 6 +/- 1 . 6 mM for R - ornidazole ) and 2B7 ( 3 . 8 +/- 0 . 9 mM for S - ornidazole ) were quite similar to those determined in HLMs and HKMs ( 20 . 1 +/- 1 . 4 and 17 . 7 +/- 4 . 0 mM for R - ornidazole ; 6 . 6 +/- 1 . 3 and 3 . 2 +/- 0 . 4 mM for S - ornidazole ) .", "entity": [{"entity": "R - ornidazole", "entity_type": "Chemical", "pos": [51, 65]}, {"entity": "S - ornidazole", "entity_type": "Chemical", "pos": [101, 115]}, {"entity": "R - ornidazole", "entity_type": "Chemical", "pos": [221, 235]}, {"entity": "S - ornidazole", "entity_type": "Chemical", "pos": [281, 295]}], "task": "NER"}
{"text": "The in vitro intrinsic clearance ( CLint ) ratios of S - and R - ornidazole were approximately 4 . 3 in HLMs and 6 . 5 in HKMs , respectively .", "entity": [{"entity": "S - and R - ornidazole", "entity_type": "Chemical", "pos": [53, 75]}], "task": "NER"}
{"text": "The hepatic and renal clearances were estimated based on the well - stirred model .", "entity": [], "task": "NER"}
{"text": "Overall , stereoselective glucuronidation was the principal metabolic pathway of ornidazole in humans .", "entity": [{"entity": "ornidazole", "entity_type": "Chemical", "pos": [81, 91]}], "task": "NER"}
{"text": "Furthermore , UGT1A9 and 2B7 were the predominant UGT isoforms responsible for R - and S - ornidazole glucuronidation in humans , respectively .", "entity": [{"entity": "R - and S - ornidazole", "entity_type": "Chemical", "pos": [79, 101]}], "task": "NER"}
{"text": "Ion Mobility Spectrometry - Mass Spectrometry Analysis for the Site of Aromatic Hydroxylation .", "entity": [], "task": "NER"}
{"text": "Hydroxylated metabolites often retain the pharmacological activity of parent compound , and the position of hydroxylation determines the formation of chemically reactive intermediates such as quinones and analogues from para - and / or ortho - hydroxylation of phenols or arylamines .", "entity": [{"entity": "quinones", "entity_type": "Chemical", "pos": [192, 200]}, {"entity": "phenols", "entity_type": "Chemical", "pos": [261, 268]}, {"entity": "arylamines", "entity_type": "Chemical", "pos": [272, 282]}], "task": "NER"}
{"text": "Therefore , the identification of exact position of hydroxylation is often required at the early development stage of new drug candidates .", "entity": [], "task": "NER"}
{"text": "In many cases , liquid chromatography - tandem mass spectrometry ( LC - MS / MS ) provides identical MS / MS spectra among isomeric hydroxylated metabolites , and therefore , it alone cannot unequivocally identify the exact position ( s ) of hydroxylation .", "entity": [], "task": "NER"}
{"text": "Ion mobility spectrometry ( IMS ) , integrated with LC - MS / MS , recently demonstrates the capability of separating isomeric species based on differences in their drift times from IMS , which are linearly proportional to the collision cross - section ( CCS ) reflecting physical size and shape .", "entity": [], "task": "NER"}
{"text": "In the present study , a chemical derivatization of isomeric hydroxylated metabolites with 2 - fluoro - N - methyl pyridinium p - toluenesulfonate was found to confer distinct theoretical CCS value on each isomer by forming corresponding N - methyl pyridine ( NMP ) derivative .", "entity": [{"entity": "2 - fluoro - N - methyl pyridinium p - toluenesulfonate", "entity_type": "Chemical", "pos": [91, 146]}, {"entity": "N - methyl pyridine", "entity_type": "Chemical", "pos": [238, 257]}, {"entity": "NMP", "entity_type": "Chemical", "pos": [260, 263]}], "task": "NER"}
{"text": "The regression lines established by the comparison between theoretical CCS values and observed drift times from IMS for each set of parent compound ( labetalol , ezetimibe , atorvastatin and warfarin ) and its MS / MS product ions accurately and selectively projected the actual drift times of NMP derivatives of corresponding aromatic or isomeric hydroxylated metabolites .", "entity": [{"entity": "labetalol", "entity_type": "Chemical", "pos": [150, 159]}, {"entity": "ezetimibe", "entity_type": "Chemical", "pos": [162, 171]}, {"entity": "atorvastatin", "entity_type": "Chemical", "pos": [174, 186]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [191, 199]}, {"entity": "NMP", "entity_type": "Chemical", "pos": [294, 297]}], "task": "NER"}
{"text": "The established method was used for the accurate assignment of predominant formation of 2 - hydroxylated metabolite from imipramine in NADPH - fortified human liver microsomes .", "entity": [{"entity": "imipramine", "entity_type": "Chemical", "pos": [121, 131]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [135, 140]}], "task": "NER"}
{"text": "The present application expands the versatility of LC - IMS - MS technique to the structure identification of isomeric hydroxylated metabolites at the early stage for drug development .", "entity": [], "task": "NER"}
{"text": "Pharmacovigilance Using Clinical Notes .", "entity": [], "task": "NER"}
{"text": "With increasing adoption of electronic health records ( EHRs ) , there is an opportunity to use the free - text portion of EHRs for pharmacovigilance .", "entity": [], "task": "NER"}
{"text": "We present novel methods that annotate the unstructured clinical notes and transform them into a deidentified patient - feature matrix encoded using medical terminologies .", "entity": [], "task": "NER"}
{"text": "We demonstrate the use of the resulting high - throughput data for detecting drug - adverse event associations and adverse events associated with drug - drug interactions .", "entity": [], "task": "NER"}
{"text": "We show that these methods flag adverse events early ( in most cases before an official alert ) , allow filtering of spurious signals by adjusting for potential confounding , and compile prevalence information .", "entity": [], "task": "NER"}
{"text": "We argue that analyzing large volumes of free - text clinical notes enables drug safety surveillance using a yet untapped data source .", "entity": [], "task": "NER"}
{"text": "Such data mining can be used for hypothesis generation and for rapid analysis of suspected adverse event risk . Clinical Pharmacology & Therapeutics ( 2013 ) ; advance online publication 10 April 2013 . doi : 10 . 1038 / clpt . 2013 . 47 .", "entity": [], "task": "NER"}
{"text": "Attenuation of erythrocytic actylcholinesterase by antidepressants : Evidence in an in vitro experiment .", "entity": [], "task": "NER"}
{"text": "The current study was aimed to scrutinize acetylcholinesterase ( AchE ) inhibitory profile of two antidepressants , diazepam and phenobarbitone .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [116, 124]}, {"entity": "phenobarbitone", "entity_type": "Chemical", "pos": [129, 143]}], "task": "NER"}
{"text": "The experimental designed was based on Michaelis - Menten parameters ( apparent Michaelis constant ( aKm ) and apparent maximum velocity ( aVm ) ) that estimate inhibition ( % ) as well as the type of inhibition ( mechanism ) .", "entity": [], "task": "NER"}
{"text": "The results showed marked inhibition of AchE by diazepam and the values of aKm and aVm were 65 . 5 % and 52 . 63 % , respectively .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "These values suggested a competitive type of antagonism for diazepam .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "Similar trend of antagonism was shown by phenobarbitone when it was subjected to the challenge of AchE with aKm and aVm values of 51 . 99 % and 71 . 80 % , respectively .", "entity": [{"entity": "phenobarbitone", "entity_type": "Chemical", "pos": [41, 55]}], "task": "NER"}
{"text": "It is concluded that diazepam and phenobarbitone exhibited prominent AchE attenuation apart from their well - established antidepressant activity , which could be more useful in related diseased conditions .", "entity": [{"entity": "diazepam", "entity_type": "Chemical", "pos": [21, 29]}, {"entity": "phenobarbitone", "entity_type": "Chemical", "pos": [34, 48]}], "task": "NER"}
{"text": "A Role for Cargo in the Activation of ADP - Ribosylation Factors ( Arf ) and Adaptor Recruitment .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [38, 41]}], "task": "NER"}
{"text": "Membrane traffic requires the specific concentration of protein cargos and exclusion of other proteins into nascent carriers .", "entity": [], "task": "NER"}
{"text": "Critical components of this selectivity are the protein adaptors that bind to short , linear motifs in the cytoplasmic tails of transmembrane protein cargos and sequester them into nascent carriers .", "entity": [], "task": "NER"}
{"text": "The recruitment of the adaptors is mediated by activated Arf GTPases and the Arf - adaptor complexes mark sites of carrier formation .", "entity": [], "task": "NER"}
{"text": "However , the nature of the signal ( s ) that initiate carrier biogenesis remains unknown .", "entity": [], "task": "NER"}
{"text": "We examined the specificity and initial sites of recruitment of Arf - dependent adaptors ( AP - 1 and GGAs ) in response to the Golgi or endosomal localization of specific cargo proteins ( furin , mannose - 6 - phosphate receptor ( M6PR ) and M6PR lacking a C - terminal domain M6PR Delta C ) .", "entity": [{"entity": "mannose - 6 - phosphate", "entity_type": "Chemical", "pos": [197, 220]}, {"entity": "C", "entity_type": "Chemical", "pos": [258, 259]}], "task": "NER"}
{"text": "We find that cargo promotes the recruitment of specific adaptors , suggesting that it is part of an upstream signaling event .", "entity": [], "task": "NER"}
{"text": "Cargos do not promote adaptor recruitment to all compartments in which they reside and thus additional factors regulate the cargo ' s ability to promote Arf activation and adaptor recruitment .", "entity": [], "task": "NER"}
{"text": "We document that within a given compartment different cargos recruit different adaptors suggesting that there is little or no free , activated Arf at the membrane and that Arf activation is spatially and temporally coupled to the cargo and the adaptor .", "entity": [], "task": "NER"}
{"text": "Using temperature block , Brefeldin A , and recovery from each , we found that the cytoplasmic tail of M6PR causes the recruitment of AP - 1 and GGAs to recycling endosomes and not at the Golgi , as predicted by steady state staining profiles .", "entity": [{"entity": "Brefeldin A", "entity_type": "Chemical", "pos": [26, 37]}], "task": "NER"}
{"text": "These results are discussed with respect to the generation of novel models for cargo - dependent regulation of membrane traffic .", "entity": [], "task": "NER"}
{"text": "Gelation - induced visible supramolecular chiral recognition by fluorescent metal complexes of quinolinol - glutamide .", "entity": [{"entity": "quinolinol", "entity_type": "Chemical", "pos": [95, 105]}, {"entity": "glutamide", "entity_type": "Chemical", "pos": [108, 117]}], "task": "NER"}
{"text": "Three metal complexes consisting of Li ( + ) , Zn ( 2 + ) , and Al ( 3 + ) and quinolinol - functionalized l - glutamides ( HQLG ) , ( abbreviated as LiHQLG , Zn ( HQLG ) 2 , and Al ( HQLG ) 3 ) were found to form fluorescent metallogels in several organic solvents .", "entity": [{"entity": "Li ( + )", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "Zn ( 2 + )", "entity_type": "Chemical", "pos": [47, 57]}, {"entity": "Al ( 3 + )", "entity_type": "Chemical", "pos": [64, 74]}, {"entity": "quinolinol - functionalized l - glutamides", "entity_type": "Chemical", "pos": [79, 121]}, {"entity": "HQLG", "entity_type": "Chemical", "pos": [124, 128]}, {"entity": "LiHQLG", "entity_type": "Chemical", "pos": [150, 156]}, {"entity": "Zn ( HQLG ) 2", "entity_type": "Chemical", "pos": [159, 172]}, {"entity": "Al ( HQLG ) 3", "entity_type": "Chemical", "pos": [179, 192]}], "task": "NER"}
{"text": "In solution , these chiral complexes showed neither any CD signal in the chromophore region nor chiral recognition of the chiral species .", "entity": [], "task": "NER"}
{"text": "However , upon gel formation , the supramolecular chirality emerged because of the self - assembled nanostructures , which provided an opportunity for the chiral recognition of enantiomeric ligands .", "entity": [], "task": "NER"}
{"text": "The metallogels showed different fluorescence changes when they met with enantiomeric ( R , R ) - or ( S , S ) - 1 , 2 - diaminocyclohexane .", "entity": [{"entity": "( R , R ) - or ( S , S ) - 1 , 2 - diaminocyclohexane", "entity_type": "Chemical", "pos": [86, 139]}], "task": "NER"}
{"text": "Among them , the Al ( HQLG ) 3 metallogels did not show any change whereas the LiHQLG gels exhibited the same decrease in fluorescence .", "entity": [{"entity": "Al ( HQLG ) 3", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "LiHQLG", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "Interestingly , the Zn ( HQLG ) 2 gels showed obviously different fluorescent color with respect to ( R , R ) - and ( S , S ) - 1 , 2 - diaminocyclohexane , thus providing visible chiral recognition via the naked eye .", "entity": [{"entity": "Zn ( HQLG ) 2", "entity_type": "Chemical", "pos": [20, 33]}, {"entity": "( R , R ) - and ( S , S ) - 1 , 2 - diaminocyclohexane", "entity_type": "Chemical", "pos": [100, 154]}], "task": "NER"}
{"text": "Such different recognition ability was discussed on the basis of the assembled chiral nanostructures and the primary molecular structures of the metal complexes .", "entity": [], "task": "NER"}
{"text": "It was shown that both of them played important roles in chiral recognition .", "entity": [], "task": "NER"}
{"text": "JNK inhibitors as anti - inflammatory and neuroprotective agents .", "entity": [], "task": "NER"}
{"text": "JNK is involved in a broad range of physiological processes .", "entity": [], "task": "NER"}
{"text": "Several inflammatory and neurodegenerative diseases , such as multiple sclerosis , Alzheimer ' s and Parkinson ' s disease have been linked with the dysregulated JNK pathway .", "entity": [], "task": "NER"}
{"text": "Research on disease models using the relevant knockout mice has highlighted the importance of specific JNK isoformsin - particular disorders and has stimulated further efforts in the drug - discovery area .", "entity": [], "task": "NER"}
{"text": "However , most of the experimental evidence for the efficacy of JNK inhibition in animal models is from studies using JNK inhibitors , which are not isoform selective .", "entity": [], "task": "NER"}
{"text": "Some of the more recent compounds exhibit good oral bioavailability , CNS penetration and selectivity against the rest of the kinome .", "entity": [], "task": "NER"}
{"text": "Efforts to design isoform - selective inhibitors have produced a number of examples with various selectivity profiles .", "entity": [], "task": "NER"}
{"text": "This article presents recent progress in this area and comment on the role of isoform selectivity for efficacy .", "entity": [], "task": "NER"}
{"text": "Effects of 17 alpha - ethynylestradiol - induced cholestasis on the pharmacokinetics of doxorubicin in rats : reduced biliary excretion and hepatic metabolism of doxorubicin .", "entity": [{"entity": "17 alpha - ethynylestradiol", "entity_type": "Chemical", "pos": [11, 38]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "Since the prevalent hormonal combination therapy with estrogen analogues in cancer patients has frequency and possibility to induce the cholestasis , the frequent combination therapy with 17 alpha - ethynylestradiol ( EE , an oral contraceptive ) and doxorubicin ( an anticancer drug ) might be monitored in aspect of efficacy and safety .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "17 alpha - ethynylestradiol", "entity_type": "Chemical", "pos": [188, 215]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [251, 262]}], "task": "NER"}
{"text": "Doxorubicin is mainly excreted into the bile via P - glycoprotein ( P - gp ) and multidrug resistance - associated protein 2 ( Mrp2 ) in hepatobiliary route and metabolized via cytochrome P450 ( CYP ) 3A subfamily .", "entity": [{"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Also the hepatic Mrp2 ( not P - gp ) and CYP3A subfamily levels were reduced in EE - induced cholestatic ( EEC ) rats .", "entity": [], "task": "NER"}
{"text": "Thus , we herein report the pharmacokinetic changes of doxorubicin with respect to the changes in its biliary excretion and hepatic metabolism in EEC rats .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "The pharmacokinetic study of doxorubicin after intravenous administration of its hydrochloride was conducted along with the investigation of bile flow rate and hepatobiliary excretion of doxorubicin in control and EEC rats .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [29, 40]}, {"entity": "hydrochloride", "entity_type": "Chemical", "pos": [81, 94]}, {"entity": "doxorubicin", "entity_type": "Chemical", "pos": [187, 198]}], "task": "NER"}
{"text": "The significantly greater AUC ( 58 . 7 % increase ) of doxorubicin in EEC rats was due to the slower CL ( 32 . 9 % decrease ) .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "The slower CL was due to the reduction of hepatic biliary excretion ( 67 . 0 % decrease ) and hepatic CYP3A subfamily - mediated metabolism ( 21 . 9 % decrease ) of doxorubicin .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [165, 176]}], "task": "NER"}
{"text": "These results might have broader implications to understand the altered pharmacokinetics and / or pharmacologic effects of doxorubicin via biliary excretion and hepatic metabolism in experimental and clinical estrogen - induced cholestasis .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [123, 134]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [209, 217]}], "task": "NER"}
{"text": "Oxidation of CO by Nickel Oxide Clusters Revealed by Post Heating .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [13, 15]}, {"entity": "Nickel Oxide", "entity_type": "Chemical", "pos": [19, 31]}], "task": "NER"}
{"text": "Reactions of nickel oxide cluster ions , NinOn + x ( + ) ( n = 4 - 10 , x = - 1 ~ + 3 ) , with CO in a He buffer gas were investigated using mass spectrometry .", "entity": [{"entity": "nickel oxide", "entity_type": "Chemical", "pos": [13, 25]}, {"entity": "NinOn + x ( + )", "entity_type": "Chemical", "pos": [41, 56]}, {"entity": "CO", "entity_type": "Chemical", "pos": [95, 97]}, {"entity": "He", "entity_type": "Chemical", "pos": [103, 105]}], "task": "NER"}
{"text": "When the cluster ions react at room temperature , a CO molecule tends to attach readily to NinOn + x ( + ) for all of the cluster ions with different stoichiometry , although rate constants of the CO attachment reaction are more or less stoichiometry - dependent .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "NinOn + x ( + )", "entity_type": "Chemical", "pos": [91, 106]}, {"entity": "CO", "entity_type": "Chemical", "pos": [197, 199]}], "task": "NER"}
{"text": "However , CO was found to be released from the cluster ions when the cluster ions were heated up to 523 K after the reaction .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [10, 12]}], "task": "NER"}
{"text": "This finding is interpreted such that the CO molecule that physisorbs weakly to NinOn + x ( + ) at room temperature desorbs into the gas phase by the post heating .", "entity": [{"entity": "CO", "entity_type": "Chemical", "pos": [42, 44]}, {"entity": "NinOn + x ( + )", "entity_type": "Chemical", "pos": [80, 95]}], "task": "NER"}
{"text": "In addition , we found that an oxygen extraction reaction by a CO molecule actually occurs for oxygen - rich clusters such as Ni6O7 ( + ) and Ni8O9 ( + ) .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "CO", "entity_type": "Chemical", "pos": [63, 65]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [95, 101]}, {"entity": "Ni6O7 ( + )", "entity_type": "Chemical", "pos": [126, 137]}, {"entity": "Ni8O9 ( + )", "entity_type": "Chemical", "pos": [142, 153]}], "task": "NER"}
{"text": "As the oxygen extraction reaction is one order of magnitude slower than physisorption , it lies hidden underneath of the faster physisorption processes in the mass spectrum but is revealed by the elimination of physisorption through the post heating .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [7, 13]}], "task": "NER"}
{"text": "Antigen presentation by dendritic cells in rheumatoid arthritis .", "entity": [], "task": "NER"}
{"text": "Rheumatoid Arthritis ( RA ) is a chronic autoimmune inflammatory disease that affects largely synovial joints .", "entity": [], "task": "NER"}
{"text": "It has been postulated that activated autoreactive CD4 T cells play a key role in triggering and / or maintaining the chronic inflammatory process in RA .", "entity": [], "task": "NER"}
{"text": "Dendritic cells ( DCs ) are antigen - presenting cells that activate cognate clonal CD4 T cells in the lymph nodes .", "entity": [], "task": "NER"}
{"text": "The activation process involves the formation of a molecular structure at the DC - CD4 T cell contact zone called immunological synapse ( IS ) .", "entity": [], "task": "NER"}
{"text": "In RA , the synovium , a thin layer of tissue below the capsule in the joints , shows a massive infiltration of DCs and CD4 T cells .", "entity": [], "task": "NER"}
{"text": "Subjects bearing HLA - DRB1 alleles of the Major Histocompatibility Complex II gene displaying a motif called RA \" shared epitope ( SE ) \" , have an enhanced susceptibility to suffer RA .", "entity": [], "task": "NER"}
{"text": "Interestingly , the SE - containing HLA - DRB1 molecules display a pocket with a high affinity for citrullinated antigens , which are found at higher levels in subjects prone to develop RA .", "entity": [], "task": "NER"}
{"text": "Thus , it is possible that the DCs of susceptible individuals may form IS with particular features that may present citrullinated peptides to autorreactive na i ve CD4 T clones that , after being activated , contribute to the initiation or development of the disease .", "entity": [], "task": "NER"}
{"text": "Herein I put forward a model of RA initiation based on current information on the immune response and RA .", "entity": [], "task": "NER"}
{"text": "Citrullinated peptides in the diagnosis of rheumatoid arthritis .", "entity": [], "task": "NER"}
{"text": "Antibodies directed against citrullinated proteins and peptides ( ACPAs ) are the most specific serological markers available for diagnosing rheumatoid arthritis ( RA ) .", "entity": [], "task": "NER"}
{"text": "ACPAs may be detected several years before symptoms of RA appear , and their presence at disease onset is a good predictor of the development of erosive joint lesions .", "entity": [], "task": "NER"}
{"text": "RA patients can be classified into two major groups : those who have ACPAs and those who do not .", "entity": [], "task": "NER"}
{"text": "The presence of ACPAs at early stages of RA predicts the development of earlier and more widespread joint erosions , and low remission rates . Synthetic peptides can replace cognate proteins in solid - phase assays for specific autoantibody recognition in RA patients .", "entity": [], "task": "NER"}
{"text": "The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays .", "entity": [], "task": "NER"}
{"text": "Proteins also contain non - citrullinated epitopes that are recognized by non - RA sera and this could reduce the specificity of the test .", "entity": [], "task": "NER"}
{"text": "The use of synthetic citrullinated peptides gives absolute control over the exact epitopes presented .", "entity": [], "task": "NER"}
{"text": "Furthermore , it is difficult to prepare sufficient amounts of high - quality antigenic proteins with a well - defined degree of citrullination .", "entity": [], "task": "NER"}
{"text": "Synthetic citrullinated peptides , in contrast , are easily obtained in a pure form with a well - defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides . Chimeric peptides bearing different citrullinated protein domains have recently been used in the design of RA diagnosis systems .", "entity": [], "task": "NER"}
{"text": "The results of the application of those systems indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs .", "entity": [], "task": "NER"}
{"text": "Each of the target molecules reported ( fibrin , vimentin and filaggrin ) helps to identify a particular subset of RA patients .", "entity": [], "task": "NER"}
{"text": "Benchmark quantum - chemical calculations on a complete set of rotameric families of the DNA sugar - phosphate backbone and their comparison with modern density functional theory .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [93, 98]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [101, 110]}], "task": "NER"}
{"text": "The DNA sugar - phosphate backbone has a substantial influence on the DNA structural dynamics .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [8, 13]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [16, 25]}], "task": "NER"}
{"text": "Structural biology and bioinformatics studies revealed that the DNA backbone in experimental structures samples a wide range of distinct conformational substates , known as rotameric DNA backbone conformational families .", "entity": [], "task": "NER"}
{"text": "Their correct description is essential for methods used to model nucleic acids and is known to be the Achilles heel of force field computations .", "entity": [], "task": "NER"}
{"text": "In this study we report the benchmark database of MP2 calculations extrapolated to the complete basis set of atomic orbitals with aug - cc - pVTZ and aug - cc - pVQZ basis sets , MP2 ( T , Q ) , augmented by Delta CCSD ( T ) / aug - cc - pVDZ corrections .", "entity": [], "task": "NER"}
{"text": "The calculations are performed in the gas phase as well as using a COSMO solvent model .", "entity": [], "task": "NER"}
{"text": "This study includes a complete set of 18 established and biochemically most important families of DNA backbone conformations and several other salient conformations that we identified in experimental structures .", "entity": [], "task": "NER"}
{"text": "We utilize an electronically sufficiently complete DNA sugar - phosphate - sugar ( ) backbone model system truncated to prevent undesired intramolecular interactions .", "entity": [{"entity": "sugar", "entity_type": "Chemical", "pos": [55, 60]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [63, 72]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [75, 80]}], "task": "NER"}
{"text": "The calculations are then compared with other QM methods .", "entity": [], "task": "NER"}
{"text": "The BLYP and TPSS functionals supplemented with Grimme ' s D3 ( BJ ) dispersion term provide the best tradeoff between computational demands and accuracy and can be recommended for preliminary conformational searches as well as calculations on large model systems .", "entity": [], "task": "NER"}
{"text": "Among the tested methods , the best agreement with the benchmark database has been obtained for the double - hybrid DSD - BLYP functional in combination with a quadruple - zeta basis set , which is , however , computationally very demanding .", "entity": [], "task": "NER"}
{"text": "The new hybrid density functionals PW6B95 - D3 and MPW1B95 - D3 yield outstanding results and even slightly outperform the computationally more demanding PWPB95 double - hybrid functional .", "entity": [], "task": "NER"}
{"text": "B3LYP - D3 is somewhat less accurate compared to the other hybrids .", "entity": [], "task": "NER"}
{"text": "Extrapolated MP2 ( D , T ) calculations are not as accurate as the less demanding DFT - D3 methods .", "entity": [], "task": "NER"}
{"text": "Preliminary force field tests using several charge sets reveal an almost order of magnitude larger deviations from the reference QM data compared to modern DFT - D3 , underlining the challenges facing force field simulations of nucleic acids .", "entity": [], "task": "NER"}
{"text": "As expected , inclusion of the solvent environment approximated by a continuum approach has a large impact on the relative stabilities of different backbone substates and is important when comparing the QM data with structural bioinformatics and other experimental data .", "entity": [], "task": "NER"}
{"text": "Golimumab for the Treatment of Rheumatoid Arthritis After the Failure of Previous Disease - Modifying Antirheumatic Drugs : A NICE Single Technology Appraisal .", "entity": [], "task": "NER"}
{"text": "As part of the National Institute for Health and Clinical Excellence ( NICE ) single technology appraisal ( STA ) process , the manufacturer of golimumab ( Simponi ( (R) ) ; Merck Sharp & Dohme , USA ) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis ( RA ) after the failure of previous disease - modifying antirheumatic drugs ( DMARDs ) .", "entity": [], "task": "NER"}
{"text": "The School of Health and Related Research Technology Appraisal Group ( ScHARR - TAG ) at The University of Sheffield was commissioned to act as the independent Evidence Review Group ( ERG ) .", "entity": [], "task": "NER"}
{"text": "This article provides details of the manufacturer ' s initial submission , the ERG ' s clarification questions and the ERG report submitted to NICE .", "entity": [], "task": "NER"}
{"text": "The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee .", "entity": [], "task": "NER"}
{"text": "The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer ' s submission to NICE .", "entity": [], "task": "NER"}
{"text": "The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA : GO - FORWARD and Kay et al .", "entity": [], "task": "NER"}
{"text": "( DMARD - experienced population ) and GO - AFTER ( tumour necrosis factor [ TNF ] - alpha inhibitor - experienced population ) .", "entity": [], "task": "NER"}
{"text": "The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes .", "entity": [], "task": "NER"}
{"text": "The trials for golimumab , as well as comparator treatments , were synthesized using mixed - treatment comparison methods for the DMARD - experienced population and an indirect comparison using the Bucher method for the TNF - alpha inhibitor - experienced population .", "entity": [], "task": "NER"}
{"text": "The trials used were appropriate , although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible .", "entity": [], "task": "NER"}
{"text": "The manufacturer provided a DMARD - experienced population model and a TNF - alpha inhibitor - experienced population model .", "entity": [], "task": "NER"}
{"text": "The models allowed sequences of treatments to be evaluated for each population , although a fully incremental analysis between the use of golimumab following DMARD failure and the use of golimumab following TNF - alpha inhibitor failure was not possible .", "entity": [], "task": "NER"}
{"text": "Several limitations with the model were identified , and after a request from NICE and suspension of the appraisal , the manufacturer submitted sensitivity analyses with an additional American College of Rheumatology 70 % improvement criteria ( ACR70 ) health state included , using SF - 36 data directly from the GO - FORWARD study .", "entity": [], "task": "NER"}
{"text": "The annual rate of the Health Assessment Questionnaire ( HAQ ) score increase for patients receiving palliative treatment was also changed from 0 . 09 to 0 . 06 .", "entity": [], "task": "NER"}
{"text": "The further analyses provided highlighted the particular sensitivity of the results to HAQ progression rates and the re - administration frequency for rituximab in the TNF - alpha inhibitor - experienced population .", "entity": [], "task": "NER"}
{"text": "The Appraisal Committee concluded that golimumab should be recommended in combination with methotrexate as an option for patients with severe active RA who have failed on conventional DMARDs , or who have failed on a TNF - alpha inhibitor and are contraindicated to or withdrawn from rituximab .", "entity": [{"entity": "methotrexate", "entity_type": "Chemical", "pos": [91, 103]}], "task": "NER"}
{"text": "Evolutionary concepts in ecotoxicology : tracing the genetic background of differential cadmium sensitivities in invertebrate lineages .", "entity": [{"entity": "cadmium", "entity_type": "Chemical", "pos": [88, 95]}], "task": "NER"}
{"text": "In many toxicological and ecotoxicological studies and experimental setups , the investigator is mainly interested in traditional parameters such as toxicity data and effects of toxicants on molecular , cellular or physiological functions of individuals , species or statistical populations .", "entity": [], "task": "NER"}
{"text": "It is clear , however , that such approaches focus on the phenotype level of animal species , whilst the genetic and evolutionary background of reactions to environmental toxicants may remain untold .", "entity": [], "task": "NER"}
{"text": "In ecotoxicological risk assessment , moreover , species sensitivities towards pollutants are often regarded as random variables in a statistical approach .", "entity": [], "task": "NER"}
{"text": "Beyond statistics , however , toxicant sensitivity of every species assumes a biological significance , especially if we consider that sensitivity traits have developed in lineages of species with common evolutionary roots .", "entity": [], "task": "NER"}
{"text": "In this article , the genetic and evolutionary background of differential Cd sensitivities among invertebrate populations and species and their potential of adaptation to environmental Cd exposure will be highlighted .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [74, 76]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [185, 187]}], "task": "NER"}
{"text": "Important evolutionary and population genetic concepts such as genome structure and their importance for evolutionary adaptation , population structure of affected individuals , as well as micro and macroevolutionary mechanisms of Cd resistance in invertebrate lineages will be stressed by discussing examples of work from our own laboratory along with a review of relevant literature data and a brief discussion of open questions along with some perspectives for further research .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [231, 233]}], "task": "NER"}
{"text": "Both , differences and similarities in Cd sensitivity traits of related invertebrate species can only be understood if we consider the underlying evolutionary processes and genetic ( or epigenetic ) mechanisms .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [39, 41]}], "task": "NER"}
{"text": "Keeping in mind this perception can help us to better understand and interpret more precisely why the sensitivity of some species or species groups towards a certain toxicant ( or metal ) may be ranked in the lower or higher range of species sensitivity distributions .", "entity": [], "task": "NER"}
{"text": "Hence , such a perspective will transcend a purely statistical view of the sensitivity distributions concept , and will enhance ecotoxicology in many respects .", "entity": [], "task": "NER"}
{"text": "A Platform for Large - Scale Graphene Electronics - CVD Growth of Single - Layer Graphene on CVD - Grown Hexagonal Boron Nitride .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "Graphene", "entity_type": "Chemical", "pos": [81, 89]}, {"entity": "Boron Nitride", "entity_type": "Chemical", "pos": [115, 128]}], "task": "NER"}
{"text": "Direct chemical vapor deposition ( CVD ) growth of single - layer graphene on CVD - grown hexagonal boron nitride ( h - BN ) film can suggest a large - scale and high - quality graphene / h - BN film hybrid structure with a defect - free interface .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "boron nitride", "entity_type": "Chemical", "pos": [100, 113]}, {"entity": "BN", "entity_type": "Chemical", "pos": [120, 122]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [177, 185]}, {"entity": "BN", "entity_type": "Chemical", "pos": [192, 194]}], "task": "NER"}
{"text": "This sequentially grown graphene / h - BN film shows better electronic properties than that of graphene / SiO2 or graphene transferred on h - BN film , and suggests a new promising template for graphene device fabrication .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [24, 32]}, {"entity": "BN", "entity_type": "Chemical", "pos": [39, 41]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [106, 110]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [114, 122]}, {"entity": "BN", "entity_type": "Chemical", "pos": [142, 144]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [194, 202]}], "task": "NER"}
{"text": "The cation - pi box is a specific phosphatidylcholine membrane targeting motif .", "entity": [{"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [34, 53]}], "task": "NER"}
{"text": "PPeripheral membrane proteins can be targeted to specific organelles or the plasma membrane by differential recognition of phospholipid headgroups .", "entity": [], "task": "NER"}
{"text": "While molecular determinants of specificity for several headgroups , including phosphatidylserine and phosphoinositides are well defined , specific recognition of the headgroup of the zwitterionic phosphatidylcholine ( PC ) is less well understood .", "entity": [{"entity": "phosphatidylserine", "entity_type": "Chemical", "pos": [79, 97]}, {"entity": "phosphoinositides", "entity_type": "Chemical", "pos": [102, 119]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [197, 216]}], "task": "NER"}
{"text": "In cytosolic proteins the cation - pi box provides a suitable receptor for choline recognition and binding through the trimethylammonium moiety .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [75, 82]}, {"entity": "trimethylammonium", "entity_type": "Chemical", "pos": [119, 136]}], "task": "NER"}
{"text": "In PC , this moiety might provide a sufficient handle to bind to peripheral proteins via a cation - pi cage , where the pi systems of two or more aromatic residues are within 4 - 5 A of the quaternary amine .", "entity": [{"entity": "quaternary amine", "entity_type": "Chemical", "pos": [190, 206]}], "task": "NER"}
{"text": "We prove this hypothesis by engineering the cation - pi box into secreted phosphatidylinositol - specific phospholipase C from Staphylococcus aureus , which lacks specific PC recognition .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [74, 94]}], "task": "NER"}
{"text": "The N254Y / H258Y variant selectively binds PC - enriched vesicles , and X - ray crystallography reveals N254Y / H258Y binds choline and dibutyroylphosphatidylcholine within the cation - pi motif .", "entity": [{"entity": "choline", "entity_type": "Chemical", "pos": [125, 132]}, {"entity": "dibutyroylphosphatidylcholine", "entity_type": "Chemical", "pos": [137, 166]}], "task": "NER"}
{"text": "Such simple PC recognition motifs could be engineered into a wide variety of secondary structures providing a generally applicable method for specific recognition of PC .", "entity": [], "task": "NER"}
{"text": "Theoretical Investigation of Generator - Collector Microwell Arrays for Improving Electroanalytical Selectivity : Application to Selective Dopamine Detection in the Presence of Ascorbic Acid .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [139, 147]}, {"entity": "Ascorbic Acid", "entity_type": "Chemical", "pos": [177, 190]}], "task": "NER"}
{"text": "Recessed generator - collector assemblies consisting of an array of recessed disks ( generator electrodes ) with a gold layer ( collector electrode ) deposited over the top - plane insulator reportedly allow increased selectivity and sensitivity during electrochemical detection of dopamine ( DA ) in the presence of ascorbic acid ( AA ) , a situation which is frequently encountered .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [282, 290]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [317, 330]}], "task": "NER"}
{"text": "In sensor design , the potential of the disk electrodes is set to the wave plateau of DA , whereas the plane electrode is biased at the irreversible wave plateau of AA before the onset of the DA oxidation wave .", "entity": [], "task": "NER"}
{"text": "Thus , AA is scavenged but DA is allowed to enter the nanocavities to be oxidized at the disk electrodes , and its signal is further amplified by redox cycling between disk and plane electrodes .", "entity": [], "task": "NER"}
{"text": "Several different theoretical approaches are elaborated herein to analyze the behavior of the system , and their conclusions are successfully tested by experiments .", "entity": [], "task": "NER"}
{"text": "This reveals the crucial role of the plane - electrode area which screens access to the recessed disks ( i . e . acts as a diffusional Faraday cage ) and simultaneously contributes to amplification of the analyte signal through positive feedback , as occurs in interdigitated arrays and scanning electrochemical microscopy .", "entity": [], "task": "NER"}
{"text": "Simulations also allow for the evaluation of the benefits of different geometries inspired by the above design and different operating modes for increasing the sensor performance .", "entity": [], "task": "NER"}
{"text": "Tuning the Electrical and Optical Properties of Graphene by Ozone Treatment for Patterning Monolithic Transparent Electrodes .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "Ozone", "entity_type": "Chemical", "pos": [60, 65]}], "task": "NER"}
{"text": "Tunable electrical and optical properties of graphene are vital to promote its use as film electrodes in a variety of devices .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [45, 53]}], "task": "NER"}
{"text": "We developed an etching - free ozone treatment method to continuously tune the electrical resistance and optical transmittance of graphene films by simply varying the time and temperature of graphene exposure to ozone .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [31, 36]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [191, 199]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [212, 217]}], "task": "NER"}
{"text": "Initially , ozone exposure dramatically decreases the electrical resistance of graphene films by p - doping , but this is followed by increases in the resistance and optical transmittance as a result of surface oxidation .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [12, 17]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "The rate of resistance increase can be significantly increased by raising the treatment temperature .", "entity": [], "task": "NER"}
{"text": "The ozone - oxidized graphene is not removed but is gradually transformed to graphene oxide ( GO ) .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [4, 9]}, {"entity": "oxidized graphene", "entity_type": "Chemical", "pos": [12, 29]}, {"entity": "graphene oxide", "entity_type": "Chemical", "pos": [77, 91]}], "task": "NER"}
{"text": "On the basis of such effects of ozone treatment , we demonstrate a well - defined graphene pattern by using ozone photolithography , in which the ozone - treated graphene electrodes are monolithic but separated by insulating GO regions .", "entity": [{"entity": "ozone", "entity_type": "Chemical", "pos": [32, 37]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [82, 90]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [108, 113]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [146, 151]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [162, 170]}], "task": "NER"}
{"text": "Such a monolithic graphene pattern shows low optical contrast , a clean and more hydrophilic surface , indicating the promising use of ozone treatment to achieve high - performance graphene - based optoelectronic devices .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [18, 26]}, {"entity": "ozone", "entity_type": "Chemical", "pos": [135, 140]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [181, 189]}], "task": "NER"}
{"text": "Asymmetric dimethylarginine predicts decline of glucose tolerance in men with stable coronary artery disease : a 4 . 5 - year follow - up study .", "entity": [{"entity": "Asymmetric dimethylarginine", "entity_type": "Chemical", "pos": [0, 27]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [48, 55]}], "task": "NER"}
{"text": "BACKGROUND : Endothelial dysfunction , largely dependent on impaired nitric oxide bioavailability , has been reportedly associated with incident type 2 diabetes .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [69, 81]}], "task": "NER"}
{"text": "Our aim was to test the hypothesis that asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of nitric oxide formation , might be linked to future deterioration in glucose tolerance in stable coronary artery disease ( CAD ) .", "entity": [{"entity": "asymmetric dimethylarginine", "entity_type": "Chemical", "pos": [40, 67]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [70, 74]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [106, 118]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [174, 181]}], "task": "NER"}
{"text": "METHODS : We studied 80 non - diabetic men ( mean age 55 + / - 11 years ) with stable angina who underwent successful elective complex coronary angioplasty and were receiving a standard medical according to practice guidelines .", "entity": [], "task": "NER"}
{"text": "Plasma ADMA and its structural isomer symmetric dimethylarginine ( SDMA ) were measured prior to coronary angiography .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [7, 11]}, {"entity": "symmetric dimethylarginine", "entity_type": "Chemical", "pos": [38, 64]}, {"entity": "SDMA", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "An estimate of insulin resistance by homeostasis model assessment ( HOMA - IR index ) was calculated from fasting insulin and glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Deterioration in glucose tolerance was defined as development of type 2 diabetes or progression from a normal glucose tolerance to impaired fasting glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [17, 24]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [110, 117]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "RESULTS : Over a median follow - up of 55 months 11 subjects developed type 2 diabetes and 13 progressed to impaired fasting glucose .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "Incident deterioration of glucose tolerance was associated with ADMA ( hazard ratio [ HR ] per 1 - SD increment 1 . 64 [ 95 % CI : 1 . 14 - - 2 . 35 ] ; P = 0 . 007 ) , log ( HOMA - IR index ) ( HR = 1 . 60 [ 1 . 16 - - 2 . 20 ] ; P = 0 . 004 ) and body - mass index ( HR = 1 . 44 [ 0 . 95 - - 2 . 17 ] ; P = 0 . 08 ) by univariate Cox regression .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [26, 33]}, {"entity": "ADMA", "entity_type": "Chemical", "pos": [64, 68]}], "task": "NER"}
{"text": "ADMA ( HR = 1 . 65 [ 1 . 14 - - 2 . 38 ] ; p = 0 . 008 ) and log ( HOMA - IR index ) ( HR = 1 . 55 [ 1 . 10 - - 2 . 17 ] ; P = 0 . 01 ) were multivariate predictors of a decline in glucose tolerance .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "ADMA and SDMA were unrelated to body - mass index , HOMA - IR index , insulin or glucose .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "SDMA", "entity_type": "Chemical", "pos": [9, 13]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [81, 88]}], "task": "NER"}
{"text": "CONCLUSIONS : ADMA predicts future deterioration of glucose tolerance independently of baseline insulin resistance in men with stable CAD .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [14, 18]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [52, 59]}], "task": "NER"}
{"text": "Whether this association reflects a contribution of endothelial dysfunction to accelerated decline of insulin sensitivity , or represents only an epiphenomenon accompanying pre - diabetes , remains to be elucidated .", "entity": [], "task": "NER"}
{"text": "The observed relationship might contribute to the well - recognized ability of ADMA to predict cardiovascular outcome .", "entity": [{"entity": "ADMA", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "Sodium fluoride induces apoptosis in odontoblasts via a JNK - dependent mechanism .", "entity": [{"entity": "Sodium fluoride", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Sodium fluoride ( NaF ) is widely used for the treatment of dental caries and dentin hypersensitivity .", "entity": [{"entity": "Sodium fluoride", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "NaF", "entity_type": "Chemical", "pos": [18, 21]}], "task": "NER"}
{"text": "However , its pro - apoptotic effect on odontoblasts may lead to harmful side - effects .", "entity": [], "task": "NER"}
{"text": "The purpose of this study was to evaluate the pro - apoptotic effects of NaF in odontoblasts and elucidate the possible underlying molecular mechanisms .", "entity": [{"entity": "NaF", "entity_type": "Chemical", "pos": [73, 76]}], "task": "NER"}
{"text": "NaF generated cytotoxic effects in odontoblast - lineage cell ( OLC ) in a dose - and time - dependent manner .", "entity": [{"entity": "NaF", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Exposure of cells to 4mM NaF for 24h induced caspase - 3 activation , ultrastructural alterations , and resulted in the translocation of Bax to the mitochondria and the release of cytochrome c from the mitochondrial inter - membrane space into the cytosol , indicating that fluoride - mediated apoptosis is mitochondria - dependent .", "entity": [{"entity": "NaF", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [274, 282]}], "task": "NER"}
{"text": "Fluoride treatment also increased phosphorylation of JNK and ERK , but not p38 , and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors , respectively .", "entity": [{"entity": "Fluoride", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "fluoride", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "Taken together , these findings suggest that NaF induces apoptosis in OLC odontoblasts through a JNK - dependent mitochondrial pathway .", "entity": [{"entity": "NaF", "entity_type": "Chemical", "pos": [45, 48]}], "task": "NER"}
{"text": "Perinatal exposure to BDE - 99 causes learning disorders and decreases serum thyroid hormone levels and BDNF gene expression in hippocampus in rat offspring .", "entity": [{"entity": "BDE - 99", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [77, 92]}], "task": "NER"}
{"text": "Exposure of pregnant women to polybrominated diphenyl ethers ( PBDEs ) may mean serious health risks .", "entity": [{"entity": "polybrominated diphenyl ethers", "entity_type": "Chemical", "pos": [30, 60]}, {"entity": "PBDEs", "entity_type": "Chemical", "pos": [63, 68]}], "task": "NER"}
{"text": "The main goal of the present study was to examine the neurobehavioral changes in rat offspring that were perinatally exposed to one of the most prevalent PBDEs congeners found in humans , 2 , 2 ' , 4 , 4 ' , 5 - pentaBDE ( BDE - 99 ) .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [154, 159]}, {"entity": "2 , 2 ' , 4 , 4 ' , 5 - pentaBDE", "entity_type": "Chemical", "pos": [188, 220]}, {"entity": "BDE - 99", "entity_type": "Chemical", "pos": [223, 231]}], "task": "NER"}
{"text": "Rat dams were exposed to 0 , 1 and 2mg / kg / day of BDE - 99 from gestation day 6 to post - natal day 21 .", "entity": [{"entity": "BDE - 99", "entity_type": "Chemical", "pos": [53, 61]}], "task": "NER"}
{"text": "When pups were weaning , cortex and hippocampal gene expressions of brain - derived neurotrophic factor ( BDNF ) of the different isoforms of the thyroid hormone ( TH ) receptors ( TRs ) were evaluated .", "entity": [{"entity": "thyroid hormone", "entity_type": "Chemical", "pos": [146, 161]}], "task": "NER"}
{"text": "Serum TH levels were also determined .", "entity": [], "task": "NER"}
{"text": "The remaining pups were assessed by neurobehavioral testing for learning and memory function .", "entity": [], "task": "NER"}
{"text": "The results showed that maternal transference of BDE - 99 produced a delay in the spatial learning task in the water maze test .", "entity": [{"entity": "BDE - 99", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "Moreover , the open - field test revealed a significant dose - response anxiolytic effect .", "entity": [], "task": "NER"}
{"text": "It was also found that the serum levels of triiodothyronine ( T3 ) , tetraiiodothyronine ( T4 ) and free - T4 ( FT4 ) decreased .", "entity": [{"entity": "triiodothyronine", "entity_type": "Chemical", "pos": [43, 59]}, {"entity": "tetraiiodothyronine", "entity_type": "Chemical", "pos": [69, 88]}], "task": "NER"}
{"text": "Although no effect on the gene expression of the different isoforms of TRs was observed , the expression of the TH - mediated gene BDNF was down - regulated in the hippocampus .", "entity": [], "task": "NER"}
{"text": "These results indicate a clear signal disruption of TH and reinforce previous studies in which neurotoxic effects of PBDEs in animal research were observed at levels comparable to those found in humans .", "entity": [{"entity": "PBDEs", "entity_type": "Chemical", "pos": [117, 122]}], "task": "NER"}
{"text": "Reward and aversion in a heterogeneous midbrain dopamine system .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "The ventral tegmental area ( VTA ) is a heterogeneous brain structure that serves a central role in motivation and reward processing .", "entity": [], "task": "NER"}
{"text": "Abnormalities in the function of VTA dopamine ( DA ) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections .", "entity": [], "task": "NER"}
{"text": "These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events .", "entity": [], "task": "NER"}
{"text": "Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse , in particular cocaine , alter circuit function within a heterogeneous midbrain DA system .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [173, 180]}], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' NIDA 40th Anniversary Issue ' .", "entity": [], "task": "NER"}
{"text": "Phytotoxic effects of the cyanobacterial neurotoxin anatoxin - a : Morphological , physiological and biochemical responses in aquatic macrophyte , Ceratophyllum demersum .", "entity": [{"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [52, 64]}], "task": "NER"}
{"text": "Anatoxin - a is one of the common and major cyanobacterial neurotoxins acting as a powerful agonist at nicotinic acetylcholine receptors ( nAChR ) .", "entity": [{"entity": "Anatoxin - a", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [113, 126]}], "task": "NER"}
{"text": "In recent years , the toxin has become the focus of public attention , due to the mass development of cyanobacteria ( cyanobacterial blooms ) in freshwater bodies triggered by eutrophication and climate change .", "entity": [], "task": "NER"}
{"text": "Anatoxin - a is suspected to have a distinct toxic mechanism depending on physiological and nervous systems in exposed organisms .", "entity": [{"entity": "Anatoxin - a", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "The numerous researches have been actively conducted with respect to the toxic effects of anatoxin - a on mammals ; however , little research has aimed at its possible effects on aquatic plants , wherein well - structured nervous system is absent with the lack of various components of the acetylcholine mechanism .", "entity": [{"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [90, 102]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [290, 303]}], "task": "NER"}
{"text": "In this study , submerged macrophyte Ceratophyllum demersum ( C . demersum ) was adopted to examine the effects of anatoxin - a on morphological ( growth ) , physiological ( photosynthetic pigment contents ) and biochemical ( hydrogen peroxide level , biotransformation and antioxidative enzymes ) responses in the aquatic plant at environmentally relevant concentrations ( 0 . 005 , 0 . 05 , 0 . 5 , 5 and 50 mu g / L ) .", "entity": [{"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [115, 127]}, {"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [226, 243]}], "task": "NER"}
{"text": "The significant elevation of antioxidative enzymes in parallel with increased formation of hydrogen peroxide appeared from 0 . 5 mu g / L of anatoxin - a .", "entity": [{"entity": "hydrogen peroxide", "entity_type": "Chemical", "pos": [91, 108]}, {"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [141, 153]}], "task": "NER"}
{"text": "In the measurement of photosynthetic pigments , the decrease in chlorophyll a content was detected at 5 and 50 mu g / L , whereas the increase in carotenoids / total chlorophyll was observed from 0 . 05 mu g / L .", "entity": [{"entity": "chlorophyll a", "entity_type": "Chemical", "pos": [64, 77]}, {"entity": "chlorophyll", "entity_type": "Chemical", "pos": [166, 177]}], "task": "NER"}
{"text": "Accordingly , the alteration in growth was manifested in the presence of 5 and 50 mu g / L of anatoxin - a .", "entity": [{"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [94, 106]}], "task": "NER"}
{"text": "The results clearly indicate that anatoxin - a can disrupt homeostasis of C . demersum through induction of oxidative stress ; furthermore this aquatic plant possesses effective defense mechanisms to cope with low concentrations of anatoxin - a .", "entity": [{"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [34, 46]}, {"entity": "anatoxin - a", "entity_type": "Chemical", "pos": [232, 244]}], "task": "NER"}
{"text": "The next generation of novel low - density lipoprotein cholesterol - lowering agents : Proprotein convertase subtilisin / kexin 9 inhibitors .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [55, 66]}], "task": "NER"}
{"text": "Proprotein convertase subtilisin / kexin 9 ( PCSK9 ) has been shown to degrade hepatic low - density lipoprotein receptors ( LDLR ) .", "entity": [], "task": "NER"}
{"text": "Gain - of - function mutations promote the development of familial hypercholesterolemia , whereas loss - of - function mutations are associated with lower levels of circulating low - density lipoprotein cholesterol ( LDL - C ) and significant protection against coronary heart disease .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "The major classes of commonly prescribed lipid - lowering medications , such as statins , increase serum PCSK9 levels , thus PCSK9 inhibition would increase the efficacy of statins on LDL - C lowering .", "entity": [], "task": "NER"}
{"text": "Therefore , PCSK9 is an attractive therapeutic target for the new generation of cholesterol - lowering drugs .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "Here , we present a brief overview of the development of PCSK9 inhibitors and highlight the effect of currently prescribed LDL - C - lowering drugs on PCSK9 , and the strategies that are being explored for its therapeutic inhibition .", "entity": [], "task": "NER"}
{"text": "Current research and clinical trial results indicate that a PCSK9 inhibitor may be an exciting new therapeutic drug for the treatment of dyslipidemia and relevant cardiovascular diseases .", "entity": [], "task": "NER"}
{"text": "Role of plant stanol derivatives in the modulation of cholesterol metabolism and liver gene expression in mice .", "entity": [{"entity": "stanol", "entity_type": "Chemical", "pos": [14, 20]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [54, 65]}], "task": "NER"}
{"text": "The present study was to evaluate the cholesterol - lowering effect of two novel plant stanol derivatives and its potential molecular mechanism in hyper - cholesterol mice induced by a high - cholesterol diet .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [38, 49]}, {"entity": "stanol", "entity_type": "Chemical", "pos": [87, 93]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [155, 166]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [192, 203]}], "task": "NER"}
{"text": "Results showed that oral administration of plant stanyl hemisuccinate ( 2 x , 5 x ) and plant stanyl sorbitol succinate ( 2 x , 5 x ) effectively attenuated the serum total cholesterol and low density lipoprotein cholesterol levels , while had no effect on the serum triacylglycerol and high density lipoprotein cholesterol .", "entity": [{"entity": "stanyl hemisuccinate", "entity_type": "Chemical", "pos": [49, 69]}, {"entity": "stanyl sorbitol succinate", "entity_type": "Chemical", "pos": [94, 119]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [173, 184]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [213, 224]}, {"entity": "triacylglycerol", "entity_type": "Chemical", "pos": [267, 282]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [312, 323]}], "task": "NER"}
{"text": "And plant stanol derivatives decreased liver cholesterol concentration and increased faecal cholesterol output .", "entity": [{"entity": "stanol", "entity_type": "Chemical", "pos": [10, 16]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [92, 103]}], "task": "NER"}
{"text": "Meanwhile , both plant stanyl hemisuccinate and plant stanyl sorbitol succinate could remarkably promote liver X receptor alpha ( LXR alpha ) expression , and increased cholesterol 7 alpha - hydroxylase ( CYP7A1 ) expression and faecal total bile acid output to varying degrees .", "entity": [{"entity": "stanyl hemisuccinate", "entity_type": "Chemical", "pos": [23, 43]}, {"entity": "stanyl sorbitol succinate", "entity_type": "Chemical", "pos": [54, 79]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [169, 180]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [242, 251]}], "task": "NER"}
{"text": "These results suggested two novel plant stanol derivatives possessed hypocholesterolemic effect , and the cholesterol - lowering action of plant stanol derivatives may be through activating the potential LXR alpha - CYP7A1 - bile acid excretion pathway .", "entity": [{"entity": "stanol", "entity_type": "Chemical", "pos": [40, 46]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "stanol", "entity_type": "Chemical", "pos": [145, 151]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [225, 234]}], "task": "NER"}
{"text": "An optimised method for the accurate determination of zeranol and diethylstilbestrol in animal tissues using isotope dilution - liquid chromatography / mass spectrometry .", "entity": [{"entity": "zeranol", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "diethylstilbestrol", "entity_type": "Chemical", "pos": [66, 84]}], "task": "NER"}
{"text": "Isotope dilution - liquid chromatography / mass spectrometry ( ID - LC / MS ) has been established as a candidate reference method for the accurate determination of growth promoters ( zeranol , taleranol , and diethylstilbesterol ) in raw meat samples .", "entity": [{"entity": "zeranol", "entity_type": "Chemical", "pos": [184, 191]}, {"entity": "taleranol", "entity_type": "Chemical", "pos": [194, 203]}, {"entity": "diethylstilbesterol", "entity_type": "Chemical", "pos": [210, 229]}], "task": "NER"}
{"text": "Sample preparation processes including an enzymatic hydrolysis , extraction , and SPE clean - up were optimised .", "entity": [], "task": "NER"}
{"text": "The sensitivity difference of trans - and cis - diethylstilbestrol ( isomerizing in sample preparation processes ) by the LC / MS was measured by running a trans / cis mixture ( ratio measured by a quantitative NMR ) with and without sample matrices , and applied for the determination of total diethylstilbestrol .", "entity": [{"entity": "trans - and cis - diethylstilbestrol", "entity_type": "Chemical", "pos": [30, 66]}, {"entity": "diethylstilbestrol", "entity_type": "Chemical", "pos": [295, 313]}], "task": "NER"}
{"text": "Validity , repeatability , and reproducibility of the analytical method were tested by measuring gravimetrically fortified samples ( chicken breast , bovine muscles , and porcine muscle ) in a number of different time periods .", "entity": [], "task": "NER"}
{"text": "Measurement results agreed with the fortified values within their uncertainties .", "entity": [], "task": "NER"}
{"text": "The method provided accurate results of the target analytes in the range of 0 . 05 - 15 mu g / kg with the relative expanded uncertainty of 2 - 15 % .", "entity": [], "task": "NER"}
{"text": "Characterization of Muscat wines aroma evolution using comprehensive gas chromatography followed by a post - analytic approach to 2D contour plots comparison .", "entity": [], "task": "NER"}
{"text": "This study presents the application of a headspace solid - phase microextraction ( HS - SPME ) method on the analysis of Muscat - based wines volatiles by comprehensive two - dimensional gas chromatography ( GC x GC ) and Time - Of - Flight mass spectrometry ( TOF - MS ) .", "entity": [], "task": "NER"}
{"text": "The aroma patterns were established for different samples of Asti Spumante and Moscato d ' Asti wines , stored in bottles for 6months at different temperatures .", "entity": [], "task": "NER"}
{"text": "Wines stored at 5 degrees C for 6months did not show significant changes in flavor ; otherwise , the samples stored at 15 and 25 degrees C , showed a significant decrease in linalool , beta - damascenone , ethyl hexanoate , and ethyl octanoate levels .", "entity": [{"entity": "linalool", "entity_type": "Chemical", "pos": [174, 182]}, {"entity": "beta - damascenone", "entity_type": "Chemical", "pos": [185, 203]}, {"entity": "ethyl hexanoate", "entity_type": "Chemical", "pos": [206, 221]}, {"entity": "ethyl octanoate", "entity_type": "Chemical", "pos": [228, 243]}], "task": "NER"}
{"text": "In these last samples , alpha - terpineol , hotrienol , nerol oxide , furanic linalool oxides A / B and rose oxide concentrations significantly increased .", "entity": [{"entity": "alpha - terpineol", "entity_type": "Chemical", "pos": [24, 41]}, {"entity": "hotrienol", "entity_type": "Chemical", "pos": [44, 53]}, {"entity": "nerol oxide", "entity_type": "Chemical", "pos": [56, 67]}, {"entity": "furanic linalool oxides A / B", "entity_type": "Chemical", "pos": [70, 99]}, {"entity": "rose oxide", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "A mathematical approach was developed and applied to raw data exported after the chromatographic course , in order ( i ) to normalise different 2D chromatograms , permitting their direct comparison and ( ii ) to automatically identify and calculate from pixel - to - pixel re - designed 2D chromatograms any differences among key volatile compounds .", "entity": [], "task": "NER"}
{"text": "Evolution of quality parameters during red wine dealcoholization by osmotic distillation .", "entity": [], "task": "NER"}
{"text": "Osmotic distillation technique was used for the total dealcoholization of a red wine ( Aglianico grape variety ) up to 0 . 19vol . % .", "entity": [], "task": "NER"}
{"text": "The dealcoholization process was performed in subsequent cycles which gave rise wine samples at different alcoholic degrees .", "entity": [], "task": "NER"}
{"text": "The effect of processing on the main chemical and physical properties of Aglianico wine was evaluated .", "entity": [], "task": "NER"}
{"text": "Among wine samples , no significant differences ( p < 0 . 05 ) of oenological parameters such as pH , total acidity were found .", "entity": [], "task": "NER"}
{"text": "Similarly , the total phenolic , flavonoids and tartaric esters content and the composition of organic acids did not show significant differences ( p < 0 . 05 ) during the process .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "tartaric esters", "entity_type": "Chemical", "pos": [48, 63]}], "task": "NER"}
{"text": "On the contrary , colour intensity and tonality of wine samples changed significantly when the alcohol reduction was over the 6 . 5vol . % .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "Finally , the total dealcoholized wine showed properties similar to Aglianico wine except for the volatile compounds , which decreased over 98 % .", "entity": [], "task": "NER"}
{"text": "Hence , flavour enrichment may be required to produce a pleasurable and delicious non alcoholic beverage from wine .", "entity": [], "task": "NER"}
{"text": "The impact of catechin and epicatechin , total phenols and PPO activity on the Mal d 1 content in apple fruit .", "entity": [{"entity": "catechin", "entity_type": "Chemical", "pos": [14, 22]}, {"entity": "epicatechin", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "phenols", "entity_type": "Chemical", "pos": [47, 54]}], "task": "NER"}
{"text": "The most important apple allergen in Central Europe and North America is Mal d 1 .", "entity": [], "task": "NER"}
{"text": "Apples are a very important source of secondary plant metabolites like polyphenols in human nutrition .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [71, 82]}], "task": "NER"}
{"text": "It is known that oxidised phenols can bind proteins .", "entity": [{"entity": "oxidised phenols", "entity_type": "Chemical", "pos": [17, 33]}], "task": "NER"}
{"text": "These irreversible bindings can lead to a reduced allergenicity .", "entity": [], "task": "NER"}
{"text": "The most important phenols in apple are epicatechin , catechin and their polymeric structures , which have been identified as substrates of the polyphenoloxidase ( PPO ) .", "entity": [{"entity": "phenols", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "epicatechin", "entity_type": "Chemical", "pos": [40, 51]}, {"entity": "catechin", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "The aim of this study was to analyse the influence of naturally occurring catechin and epicatechin contents in apple on the allergenicity of apple fruits .", "entity": [{"entity": "catechin", "entity_type": "Chemical", "pos": [74, 82]}, {"entity": "epicatechin", "entity_type": "Chemical", "pos": [87, 98]}], "task": "NER"}
{"text": "Fruits of the cultivars ' Elstar ' , ' Diwa ' and ' Boskoop ' were harvested and stored for 8 and 12weeks in a cold - chamber at 2 degrees C .", "entity": [], "task": "NER"}
{"text": "Mal d 1 - , catechin - , epicatechin - and total phenol content as well as the activity of PPO were determined .", "entity": [{"entity": "catechin", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "epicatechin", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "phenol", "entity_type": "Chemical", "pos": [49, 55]}], "task": "NER"}
{"text": "Correlation analysis showed that naturally occurring catechin as well as epicatechin has no impact on the Mal d 1 content of the tested cultivars : correlation coefficient ranged from - 0 . 203 to 0 . 501 for the correlation between Mal d 1 and catechin .", "entity": [{"entity": "catechin", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "epicatechin", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "catechin", "entity_type": "Chemical", "pos": [245, 253]}], "task": "NER"}
{"text": "The results further indicated that the activity of PPO is more important than the content of total phenols to reduce the Mal d 1 level .", "entity": [{"entity": "phenols", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "If there is a high PPO activity , Mal d 1 could be reduced even if the total phenol concentration is low .", "entity": [{"entity": "phenol", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "Modeling and prediction of extraction profile for microwave - assisted extraction based on absorbed microwave energy .", "entity": [], "task": "NER"}
{"text": "A modeling technique based on absorbed microwave energy was proposed to model microwave - assisted extraction ( MAE ) of antioxidant compounds from cocoa ( Theobroma cacao L . ) leaves .", "entity": [], "task": "NER"}
{"text": "By adapting suitable extraction model at the basis of microwave energy absorbed during extraction , the model can be developed to predict extraction profile of MAE at various microwave irradiation power ( 100 - 600W ) and solvent loading ( 100 - 300ml ) .", "entity": [], "task": "NER"}
{"text": "Verification with experimental data confirmed that the prediction was accurate in capturing the extraction profile of MAE ( R - square value greater than 0 . 87 ) .", "entity": [], "task": "NER"}
{"text": "Besides , the predicted yields from the model showed good agreement with the experimental results with less than 10 % deviation observed .", "entity": [], "task": "NER"}
{"text": "Furthermore , suitable extraction times to ensure high extraction yield at various MAE conditions can be estimated based on absorbed microwave energy .", "entity": [], "task": "NER"}
{"text": "The estimation is feasible as more than 85 % of active compounds can be extracted when compared with the conventional extraction technique .", "entity": [], "task": "NER"}
{"text": "A new method for detection of five alternaria toxins in food matrices based on LC - APCI - MS .", "entity": [], "task": "NER"}
{"text": "A new method for the detection of alternariol ( AOH ) , alternariol monomethyl ether ( AME ) , altenuene ( ALT ) , tentoxin ( TEN ) , and tenuazonic acid ( TeA ) , five alternaria toxins ( ATs ) was developed by liquid chromatography - triple quadrupole mass spectrometry equipped with atmospheric pressure chemical ionisation ( APCI ) .", "entity": [{"entity": "alternariol", "entity_type": "Chemical", "pos": [34, 45]}, {"entity": "AOH", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "alternariol monomethyl ether", "entity_type": "Chemical", "pos": [56, 84]}, {"entity": "AME", "entity_type": "Chemical", "pos": [87, 90]}, {"entity": "altenuene", "entity_type": "Chemical", "pos": [95, 104]}, {"entity": "ALT", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "tentoxin", "entity_type": "Chemical", "pos": [115, 123]}, {"entity": "TEN", "entity_type": "Chemical", "pos": [126, 129]}, {"entity": "tenuazonic acid", "entity_type": "Chemical", "pos": [138, 153]}, {"entity": "TeA", "entity_type": "Chemical", "pos": [156, 159]}], "task": "NER"}
{"text": "A single extraction was used to recover the five ATs by apple juices , beers , tomato sauces , olives and dried basil .", "entity": [], "task": "NER"}
{"text": "Different Solid Phase Extractions ( SPE ) and clean - up were selected to optimise the purification step for each food matrix .", "entity": [], "task": "NER"}
{"text": "Limits of detection and quantification were , respectively , in the range 0 . 16 - 12 . 31 and 0 . 54 - 41 . 04ngg ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "Recovery rates were generally above 70 % , except for dried basil and olives .", "entity": [], "task": "NER"}
{"text": "Thirty out of 70 samples analysed ( 7 apple juices , 14 beers and 9 tomato sauces ) resulted positive to at least one alternaria toxin investigated .", "entity": [], "task": "NER"}
{"text": "AOH was the most common AT ( 14 samples ) , followed by ALT ( 10 samples ) .", "entity": [{"entity": "AOH", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "ALT", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "The highest concentration of ATs was found in commercial apple juices ( 35 . 33ngg ( - 1 ) ) .", "entity": [], "task": "NER"}
{"text": "Extraction of oak volatiles and ellagitannins compounds and sensory profile of wine aged with French winewoods subjected to different toasting methods : Behaviour during storage .", "entity": [], "task": "NER"}
{"text": "In Merlot wines the evolution of volatile and non - volatile ( ellagitannins ) compounds extracted from winewoods while being macerated for 12months was studied .", "entity": [], "task": "NER"}
{"text": "Seven types of winewoods subjected to different toasting methods were used .", "entity": [], "task": "NER"}
{"text": "Different rates of extraction , depending mainly on wood compounds origin ( toasting or naturally present in wood ) and on the watering process during toasting , were observed , which were reflected in sensory differences .", "entity": [], "task": "NER"}
{"text": "Globally , volatile phenols together with aldehydes , phenols and lactones showed an increase with increasing maceration time .", "entity": [{"entity": "phenols", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [42, 51]}, {"entity": "phenols", "entity_type": "Chemical", "pos": [54, 61]}, {"entity": "lactones", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "Ellagitannins were extracted faster during the first 3months ; after 6months an important decrease was observed .", "entity": [], "task": "NER"}
{"text": "Wines with winewoods subjected to watering during toasting were lower in ellagitannins concentrations and demonstrated the greatest decrease of these compounds during maceration .", "entity": [], "task": "NER"}
{"text": "Astringency and bitterness intensified with increasing ellagitannins .", "entity": [], "task": "NER"}
{"text": "Lactones induced positive sweetness sensations , whereas furanic and guaiacol compounds influenced bitterness and astringency .", "entity": [{"entity": "Lactones", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "furanic", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "guaiacol", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "Spicy and vanilla descriptors were related to eugenol , vanillin and other odorous chemicals .", "entity": [{"entity": "eugenol", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "vanillin", "entity_type": "Chemical", "pos": [56, 64]}], "task": "NER"}
{"text": "Selenium bioaccessibility and speciation in biofortified Pleurotus mushrooms grown on selenium - rich agricultural residues .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [86, 94]}], "task": "NER"}
{"text": "Cultivation of saprophytic fungi on selenium - rich substrates can be an effective means to produce selenium - fortified food .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [36, 44]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "Pleurotus florida , an edible species of oyster mushrooms , was grown on wheat straw from the seleniferous belt of Punjab ( India ) and its potential to mobilize and accumulate selenium from the growth substrate was studied .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [177, 185]}], "task": "NER"}
{"text": "Selenium concentration in biofortified mushrooms was 800 times higher compared with control samples grown on wheat straw from non selenium - rich areas ( 141 vs 0 . 17 mu gSeg ( - 1 ) dry weight ) .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "gSeg", "entity_type": "Chemical", "pos": [171, 175]}], "task": "NER"}
{"text": "Seventy - five percent of the selenium was extracted after in vitro simulated gastrointestinal digestion and investigation of the selenium molecular fractions by size exclusion HPLC - ICP - MS revealed that proteins and any other high molecular weight selenium - containing molecule were hydrolyzed to peptides and low molecular weight selenocompounds .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [130, 138]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [252, 260]}], "task": "NER"}
{"text": "Analysis of the gastrointestinal hydrolysates by anion exchange HPLC - ICP - MS showed that the bioaccessible selenium was mainly present as selenomethionine , a good bioavailable source of selenium , which accounted for 73 % of the sum of the detected species .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [110, 118]}, {"entity": "selenomethionine", "entity_type": "Chemical", "pos": [141, 157]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [190, 198]}], "task": "NER"}
{"text": "This study demonstrates the feasibility of producing selenium - biofortified edible mushrooms using selenium - rich agricultural by - products as growth substrates .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [100, 108]}], "task": "NER"}
{"text": "The proposed approach can be used to evaluate whether selenium - contaminated plant waste materials harvested from high - selenium areas may be used to produce selenium - biofortified edible mushrooms based on the concentration , bioaccessibility and speciation of selenium in the mushrooms .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [54, 62]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [122, 130]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [160, 168]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [265, 273]}], "task": "NER"}
{"text": "Characterization of Hatay honeys according to their multi - element analysis using ICP - OES combined with chemometrics .", "entity": [], "task": "NER"}
{"text": "Chemical characterisation has been carried out on 45 honey samples collected from Hatay region of Turkey .", "entity": [], "task": "NER"}
{"text": "The concentrations of 17 elements were determined by inductively coupled plasma optical emission spectrometry ( ICP - OES ) .", "entity": [], "task": "NER"}
{"text": "Ca , K , Mg and Na were the most abundant elements , with mean contents of 219 . 38 , 446 . 93 , 49 . 06 and 95 . 91mgkg ( - 1 ) respectively .", "entity": [{"entity": "Ca", "entity_type": "Chemical", "pos": [0, 2]}, {"entity": "K", "entity_type": "Chemical", "pos": [5, 6]}, {"entity": "Mg", "entity_type": "Chemical", "pos": [9, 11]}, {"entity": "Na", "entity_type": "Chemical", "pos": [16, 18]}], "task": "NER"}
{"text": "The trace element mean contents ranged between 0 . 03 and 15 . 07mgkg ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "Chemometric methods such as principal component analysis ( PCA ) and cluster analysis ( CA ) techniques were applied to classify honey according to mineral content .", "entity": [], "task": "NER"}
{"text": "The first most important principal component ( PC ) was strongly associated with the value of Al , B , Cd and Co .", "entity": [{"entity": "Al", "entity_type": "Chemical", "pos": [94, 96]}, {"entity": "B", "entity_type": "Chemical", "pos": [99, 100]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [103, 105]}, {"entity": "Co", "entity_type": "Chemical", "pos": [110, 112]}], "task": "NER"}
{"text": "CA showed eight clusters corresponding to the eight botanical origins of honey .", "entity": [], "task": "NER"}
{"text": "PCA explained 75 . 69 % of the variance with the first six PC variables .", "entity": [], "task": "NER"}
{"text": "Chemometric analysis of the analytical data allowed the accurate classification of the honey samples according to origin .", "entity": [], "task": "NER"}
{"text": "Proteolytic activities in fillets of selected underutilized Australian fish species .", "entity": [], "task": "NER"}
{"text": "The hydrolytic activity of major endogenous proteases , responsible for proteolysis of myofibrillar proteins during post - mortem storage , may be an indicator of the textural quality of fish which influences consumer purchasing behaviour and thus market value of the final product .", "entity": [], "task": "NER"}
{"text": "Furthermore , it may also influence the type and bioactive properties of the peptides released during post - mortem proteolysis of myofibrillar proteins .", "entity": [], "task": "NER"}
{"text": "This study compared the activities of cathepsins B , B + L , D , H and calpain - like enzymes in crude muscle extracted from 16 Australian underutilized fish species .", "entity": [], "task": "NER"}
{"text": "Fish species had a significant effect on the activity of these enzymes with barracouta showing the highest cathepsins B , B + L , D and H activities .", "entity": [], "task": "NER"}
{"text": "Activities of cathepsins B and B + L were higher than cathepsin H for all studied species .", "entity": [], "task": "NER"}
{"text": "The more commercially important rock ling and tiger flathead demonstrated higher cathepsin B + L activity , whereas gemfish and eastern school whiting showed higher activity towards cathepsin B .", "entity": [], "task": "NER"}
{"text": "Underutilized fish species showing higher endogenous protease activities may be suitable for fish sauce production , whereas those with lower protease activities for surimi processing .", "entity": [], "task": "NER"}
{"text": "Flavonol glycosides with lipid accumulation inhibitory activity and simultaneous quantitative analysis of 15 polyphenols and caffeine in the flower buds of Camellia sinensis from different regions by LCMS .", "entity": [{"entity": "Flavonol glycosides", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "polyphenols", "entity_type": "Chemical", "pos": [109, 120]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [125, 133]}], "task": "NER"}
{"text": "A simultaneous quantitative analytical method for 15 major polyphenols , e . g . five catechins ( 1 - 5 ) and 10 flavonols ( 6 - 15 ) , as functional constituents in the extracts of \" tea flowers \" , the flower buds of Camellia sinensis ( Theaceae ) , has been developed .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [59, 70]}, {"entity": "catechins", "entity_type": "Chemical", "pos": [86, 95]}, {"entity": "flavonols", "entity_type": "Chemical", "pos": [113, 122]}], "task": "NER"}
{"text": "The content of caffeine ( 16 ) , which showed similar chromatographic behaviour under the analytical conditions , was also determined .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "To approve the validity of the newly developed protocol , thirteen extracts of the plant ' s flower buds collected from different regions , i . e . China , Taiwan , Japan and India , were evaluated .", "entity": [], "task": "NER"}
{"text": "The results indicated that the assay was reproducible and precise , and could be readily underutilised for the quality evaluation of tea flowers on the basis of polyphenols ' contents .", "entity": [{"entity": "polyphenols", "entity_type": "Chemical", "pos": [161, 172]}], "task": "NER"}
{"text": "It was noteworthy that the contents of two major constituents , kaempferol 3 - O - beta - d - glucopyranosyl - ( 1 --> 3 ) - alpha - l - rhamnopyranosyl - ( 1 --> 6 ) - beta - d - glucopyranoside ( 10 ) and kaempferol 3 - O - beta - d - glucopyranosyl - ( 1 --> 3 ) - alpha - l - rhamnopyranosyl - ( 1 --> 6 ) - beta - d - galactopyranoside ( 11 ) , varied by region where the flower buds were produced .", "entity": [{"entity": "kaempferol 3 - O - beta - d - glucopyranosyl - ( 1 --> 3 ) - alpha - l - rhamnopyranosyl - ( 1 --> 6 ) - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [64, 195]}, {"entity": "kaempferol 3 - O - beta - d - glucopyranosyl - ( 1 --> 3 ) - alpha - l - rhamnopyranosyl - ( 1 --> 6 ) - beta - d - galactopyranoside", "entity_type": "Chemical", "pos": [207, 340]}], "task": "NER"}
{"text": "A new flavonol glycoside , chakaflavonoside B ( 17 ) , which was isolated in the course of this analytical study , was found to show oleic acid - albumin - induced lipid accumulation inhibitory activity .", "entity": [{"entity": "flavonol glycoside", "entity_type": "Chemical", "pos": [6, 24]}, {"entity": "chakaflavonoside B", "entity_type": "Chemical", "pos": [27, 45]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [133, 143]}], "task": "NER"}
{"text": "Hemocyanin - derived phenoloxidase activity : A contributing factor to hyperpigmentation in Nephrops norvegicus .", "entity": [], "task": "NER"}
{"text": "The phenomenon of hyperpigmentation ( melanosis ) in shellfish has long been attributed to phenoloxidase enzymes .", "entity": [], "task": "NER"}
{"text": "Over the last number of years , the oxygen carrier hemocyanin , has demonstrated several immune - and physiological functionalities , most notably , inducible phenoloxidase activity .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [36, 42]}], "task": "NER"}
{"text": "In this study , hemocyanin purified from the hemolymph of Nephrops norvegicus displays diphenoloxidase activity in the presence of a number of elicitors and retains structural and functional integrity throughout the process of freeze - thawing ( at - 25 degrees C ) .", "entity": [], "task": "NER"}
{"text": "Conversely , cellular phenoloxidase activity ( present in cell - lysates ) , demonstrates > 98 % reduction in activity after freeze - thawing .", "entity": [], "task": "NER"}
{"text": "We present evidence that hemocyanin may act as a causative agent of hyperpigmentation in N . norvegicus .", "entity": [], "task": "NER"}
{"text": "The inhibition of hemocyanin - derived phenoloxidase activity is discussed , and for the first time , the biophysical interactions of shellfish hemocyanin with known phenoloxidase inhibitors are presented .", "entity": [], "task": "NER"}
{"text": "Residues and dissipation of kresoxim methyl in apple under field condition .", "entity": [{"entity": "kresoxim methyl", "entity_type": "Chemical", "pos": [28, 43]}], "task": "NER"}
{"text": "The dissipation and residual levels of kresoxim methyl in apple under field condition were determined by using HPLC - DAD with QuEChERS method .", "entity": [{"entity": "kresoxim methyl", "entity_type": "Chemical", "pos": [39, 54]}], "task": "NER"}
{"text": "At fortification levels of 0 . 05 , 0 . 1 , 0 . 5 and 1 . 0mgkg ( - 1 ) in apple , it was shown that recoveries were ranged from 91 . 1 % to 96 . 9 % with coefficient variation of the method ( CV % ) for repeatability ranged from 1 . 27 % to 4 . 77 % .", "entity": [], "task": "NER"}
{"text": "The limit of quantification ( LOQ ) of the method was 0 . 05mgkg ( - 1 ) .", "entity": [], "task": "NER"}
{"text": "The dissipation rates of kresoxim methyl were described by using first - order kinetics and its half - life , as they are ranged from 4 . 58 to 4 . 77days in apple .", "entity": [{"entity": "kresoxim methyl", "entity_type": "Chemical", "pos": [25, 40]}], "task": "NER"}
{"text": "The terminal residues of kresoxim methyl were below the FAO / WHO maximum residue limit ( MRL , 0 . 2mgkg ( - 1 ) ) in apple when measured 14days after the final application , which suggested that the use of this fungicide was safe for humans .", "entity": [{"entity": "kresoxim methyl", "entity_type": "Chemical", "pos": [25, 40]}], "task": "NER"}
{"text": "This study would help in providing the basic information for developing regulation to guard a safe use of kresoxim methyl in apple orchard and to prevent health problem from consumers .", "entity": [{"entity": "kresoxim methyl", "entity_type": "Chemical", "pos": [106, 121]}], "task": "NER"}
{"text": "Impact of the Mediterranean fruit fly ( Medfly ) Ceratitis capitata on different peach cultivars : The possible role of peach volatile compounds .", "entity": [], "task": "NER"}
{"text": "The relationship between susceptibility of different peach cultivars ( cvs ) to the Mediterranean fruit fly ( medfly ) , Ceratitis capitata , and the volatile composition of ripe fruit of each cv has been investigated , since understanding the fruit - insect interaction mechanism is crucial for developing control strategies for such a pest .", "entity": [], "task": "NER"}
{"text": "Volatile compounds were analyzed by SPME - GC - MS in three cvs highly susceptible to medfly attack ( Fair Time , Flaminia , Sicilia Piatta ) , and in two less susceptible cvs ( Percoca Romagnola 7 and Doctor Davis ) .", "entity": [], "task": "NER"}
{"text": "Among the volatile compounds detected , 88 could be identified .", "entity": [], "task": "NER"}
{"text": "The main differences found in the volatile composition of the cvs , concerned the relative abundance of esters .", "entity": [{"entity": "esters", "entity_type": "Chemical", "pos": [104, 110]}], "task": "NER"}
{"text": "The least susceptible cvs , above all Percoca Romagnola 7 , contained the higher amounts of hexenyl , hexyl , 3 - methylbutyl , butyl and 2 - methylpropyl esters ; among these , some C6 derivatives detected , such as ( Z ) - 3 - hexenyl acetate , are known to act as priming agents , enhancing plant defence response to insects .", "entity": [{"entity": "hexenyl , hexyl , 3 - methylbutyl , butyl and 2 - methylpropyl esters", "entity_type": "Chemical", "pos": [92, 161]}, {"entity": "( Z ) - 3 - hexenyl acetate", "entity_type": "Chemical", "pos": [217, 244]}], "task": "NER"}
{"text": "Instead , a lower relative content of methyl esters , such as methyl hexanoate and methyl octanoate , known to act as medfly pheromone and attractant respectively , was found in the least susceptible cvs .", "entity": [{"entity": "methyl esters", "entity_type": "Chemical", "pos": [38, 51]}, {"entity": "methyl hexanoate", "entity_type": "Chemical", "pos": [62, 78]}, {"entity": "methyl octanoate", "entity_type": "Chemical", "pos": [83, 99]}], "task": "NER"}
{"text": "Comparison of spectrophotometric and HPLC methods for determination of carotenoids in foods .", "entity": [], "task": "NER"}
{"text": "This report is aimed at intra - laboratory and inter - laboratory comparison of the results obtained during spectrophotometric and HPLC analyses of lycopene , beta - carotene and total carotenoids in tomato products and yellow maize flours / grits .", "entity": [{"entity": "lycopene", "entity_type": "Chemical", "pos": [148, 156]}, {"entity": "beta - carotene", "entity_type": "Chemical", "pos": [159, 174]}], "task": "NER"}
{"text": "Extensive statistical analyses are performed in order to identify the main sources of uncertainties which may occur when using : ( i ) different techniques / methods / approaches in the same / different laboratories , in various food samples , and ( ii ) to indicate the facts / conditions under which the biases between results may remain unidentified after applying statistical testing .", "entity": [], "task": "NER"}
{"text": "Our data points to the inertness of t - test to detect significance of differences , particularly at low R values : in general , the higher correlation coefficient , the higher is sensitivity of statistical testing , especially of the paired t - test .", "entity": [], "task": "NER"}
{"text": "Therefore , simple deviation of relationship line slope from unity could be used as additional evaluation parameter .", "entity": [], "task": "NER"}
{"text": "This adds to reliable and objective quality assurance of foods in regard to carotenoids .", "entity": [], "task": "NER"}
{"text": "Animal communication : sniffing is about more than just smell .", "entity": [], "task": "NER"}
{"text": "A recent study shows that subordinate rats reduce their rate of sniffing while dominants explore their faces thus delaying dominants ' subsequent aggression .", "entity": [], "task": "NER"}
{"text": "Sniffing not only facilitates acquisition of olfactory information , but unexpectedly , also serves as a medium for communication .", "entity": [], "task": "NER"}
{"text": "Irisin levels correlate with energy expenditure in a subgroup of humans with energy expenditure greater than predicted by fat free mass .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : Obesity is a result of chronic overconsumption of calories relative to the amount of energy expended .", "entity": [], "task": "NER"}
{"text": "While fat free mass can account for ~ 80 % of the variance in energy expenditure , there is still considerable variability in energy requirements between individuals that cannot be explained .", "entity": [], "task": "NER"}
{"text": "We hypothesized that responsiveness to the recently discovered myokine , irisin , which has been touted to increase energy expenditure via activation of brown adipocytes in rodents and possibly humans , may explain some of the variability in energy expenditure .", "entity": [], "task": "NER"}
{"text": "MATERIALS / METHODS : Post - menopausal women ( n = 17 ) spent 24 - h in a whole room indirect calorimeter .", "entity": [], "task": "NER"}
{"text": "During the study day , subjects remained sedentary and consumed meals tailored to their energy requirements .", "entity": [], "task": "NER"}
{"text": "Plasma irisin , leptin and adiponectin were measured in samples taken from each subject .", "entity": [], "task": "NER"}
{"text": "RESULTS : Our results suggest that in general , irisin levels do not correlate with 24 - h energy expenditure , however , for a subpopulation irisin levels and energy expenditure are highly correlative .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : Irisin may help explain some of the observed variability in individual energy requirements that cannot be accounted for by fat free mass .", "entity": [], "task": "NER"}
{"text": "Therefore , interventions designed to increase irisin action may prove to be promising avenues for the treatment of obesity .", "entity": [], "task": "NER"}
{"text": "In vitro toxicological assessment of clays for their use in food packaging applications .", "entity": [], "task": "NER"}
{"text": "Montmorillonite based clays have a wide range of applications that are going to contribute to increase human exposure to these materials .", "entity": [{"entity": "Montmorillonite", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "One of the most promising uses of clays is the development of reinforced food contact materials that results in nanocomposites with improved barrier properties .", "entity": [], "task": "NER"}
{"text": "Different organoclays have been developed introducing modifiers in the natural clay which is commercially available .", "entity": [], "task": "NER"}
{"text": "However , the toxicological aspects of these materials have been scarcely studied so far .", "entity": [], "task": "NER"}
{"text": "In the present study , the cytotoxic effects of a non - modified clay ( Cloisite (R) Na + ) and an organoclay ( Cloisite (R) 30B ) have been investigated in the hepatic cell line HepG2 .", "entity": [{"entity": "Cloisite", "entity_type": "Chemical", "pos": [72, 80]}, {"entity": "Na +", "entity_type": "Chemical", "pos": [85, 89]}, {"entity": "Cloisite", "entity_type": "Chemical", "pos": [112, 120]}], "task": "NER"}
{"text": "Only Cloisite (R) 30B showed cytotoxicity .", "entity": [{"entity": "Cloisite", "entity_type": "Chemical", "pos": [5, 13]}], "task": "NER"}
{"text": "In order to elucidate the toxic mechanisms underlying these effects , apoptosis , inflammation , oxidative stress and genotoxicity biomarkers were assayed .", "entity": [], "task": "NER"}
{"text": "Moreover , a morphology study with light and electron microscopy was performed .", "entity": [], "task": "NER"}
{"text": "Results showed genotoxic effects and glutathione decrease .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [37, 48]}], "task": "NER"}
{"text": "The most relevant ultraestructural alterations observed were mitochondrial degeneration , dilated endomembrane systems , heterophagosomes formation , fat droplets appearance and presence of nuclear lipid inclusions .", "entity": [], "task": "NER"}
{"text": "Cloisite (R) 30B , therefore , induces toxic effects in HepG2 cells .", "entity": [{"entity": "Cloisite", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Further research is needed to assess the risk of this clay on the human health .", "entity": [], "task": "NER"}
{"text": "Sclerostin : how human mutations have helped reveal a new target for the treatment of osteoporosis .", "entity": [], "task": "NER"}
{"text": "In the 1990s there was a tremendous mood of optimism among pharmaceutical scientists that identification of disease - associated variations in the human genome would result in a surge of new drug targets ( the ' gene - to - drug ' mantra ) .", "entity": [], "task": "NER"}
{"text": "To date the expected deluge of new drugs has not arrived .", "entity": [], "task": "NER"}
{"text": "However , a small number of drugs arising directly from the study of rare human disorders showing Mendelian inheritance are now entering late stage clinical trials .", "entity": [], "task": "NER"}
{"text": "Here we describe the advantages of this approach and discuss the background and early clinical trial findings with antibodies directed at a target identified in this way .", "entity": [], "task": "NER"}
{"text": "Mechanisms of Glucose Lowering of Dipeptidyl Peptidase - 4 Inhibitor Sitagliptin When Used Alone or With Metformin in Type 2 Diabetes : A double - tracer study .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "Sitagliptin", "entity_type": "Chemical", "pos": [69, 80]}, {"entity": "Metformin", "entity_type": "Chemical", "pos": [105, 114]}], "task": "NER"}
{"text": "OBJECTIVETo assess glucose - lowering mechanisms of sitagliptin ( S ) , metformin ( M ) , and the two combined ( M + S ) . RESEARCH DESIGN AND METHODSWe randomized 16 patients with type 2 diabetes mellitus ( T2DM ) to four 6 - week treatments with placebo ( P ) , M , S , and M + S .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "sitagliptin", "entity_type": "Chemical", "pos": [52, 63]}, {"entity": "metformin", "entity_type": "Chemical", "pos": [72, 81]}], "task": "NER"}
{"text": "After each period , subjects received a 6 - h meal tolerance test ( MTT ) with [ ( 14 ) C ] glucose to calculate glucose kinetics .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [68, 71]}, {"entity": "[ ( 14 ) C ] glucose", "entity_type": "Chemical", "pos": [79, 99]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [113, 120]}], "task": "NER"}
{"text": "Fasting plasma glucose ( FPG ) , fasting plasma insulin , C - peptide ( insulin secretory rate [ ISR ] ) , fasting plasma glucagon , and bioactive glucagon - like peptide ( GLP - 1 ) and gastrointestinal insulinotropic peptide ( GIP ) was measured . RESULTSFPG decreased from P , 160 +/- 4 to M , 150 +/- 4 ; S , 154 +/- 4 ; and M + S , 125 +/- 3 mg / dL .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [15, 22]}, {"entity": "C", "entity_type": "Chemical", "pos": [58, 59]}], "task": "NER"}
{"text": "Mean post - MTT PG decreased from P , 207 +/- 5 to M , 191 +/- 4 ; S , 195 +/- 4 ; and M + S , 161 +/- 3 mg / dL ( P < 0 . 01 ] .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [12, 15]}], "task": "NER"}
{"text": "The increase in mean post - MTT plasma insulin and in ISR was similar in P , M , and S and slightly greater in M + S .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "Fasting plasma glucagon was equal ( ~ 65 - 75 pg / mL ) with all treatments , but there was a significant drop during the initial 120 min with S 24 % and M + S 34 % ( both P < 0 . 05 ) vs . P 17 % and M 16 % .", "entity": [], "task": "NER"}
{"text": "Fasting and mean post - MTT plasma bioactive GLP - 1 were higher ( P < 0 . 01 ) after S and M + S vs . M and P .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [24, 27]}], "task": "NER"}
{"text": "Basal endogenous glucose production ( EGP ) fell from P 2 . 0 +/- 0 . 1 to S 1 . 8 +/- 0 . 1 mg / kg . min , M 1 . 8 +/- 0 . 2 mg / kg . min [ both P < 0 . 05 vs . P ) , and M + S 1 . 5 +/- 0 . 1 mg / kg . min ( P < 0 . 01 vs . P ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [17, 24]}], "task": "NER"}
{"text": "Although the EGP slope of decline was faster in M and M + S vs . S , all had comparable greater post - MTT EGP inhibition vs . P ( P < 0 . 05 ) . CONCLUSIONSM + S combined produce additive effects to 1 ) reduce FPG and postmeal PG , 2 ) augment GLP - 1 secretion and beta - cell function , 3 ) decrease plasma glucagon , and 4 ) inhibit fasting and postmeal EGP compared with M or S monotherapy .", "entity": [], "task": "NER"}
{"text": "Involvement of nNOS / NO / sGC / cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations : does phosphodiesterase 5 inhibition help to drug vulnerability ?", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [59, 66]}], "task": "NER"}
{"text": "RATIONALE : Repeated cocaine administration induces behavioral sensitization in about 50 % of treated animals .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [21, 28]}], "task": "NER"}
{"text": "Nitric oxide could be involved in the acquisition and maintenance of behavioral cocaine effects , probably by activation of neuronal nitric oxide synthase ( nNOS ) / NO / soluble guanylyl cyclase ( sGC ) / cyclic guanosine monophosphate ( cGMP ) signaling pathway , since inhibition of the nNOS enzyme attenuates development of sensitization in rats .", "entity": [{"entity": "Nitric oxide", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [80, 87]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [133, 145]}, {"entity": "NO", "entity_type": "Chemical", "pos": [158, 160]}, {"entity": "guanylyl", "entity_type": "Chemical", "pos": [179, 187]}, {"entity": "cyclic guanosine monophosphate", "entity_type": "Chemical", "pos": [206, 236]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [239, 243]}], "task": "NER"}
{"text": "On the other hand , increased cGMP availability by phosphodiesterase 5 inhibitors has been correlated to the misuse and recreational use of these agents and also to the concomitant use with illicit drugs in humans .", "entity": [{"entity": "cGMP", "entity_type": "Chemical", "pos": [30, 34]}], "task": "NER"}
{"text": "Hippocampus is an important brain region for conditioning to general context previously associated to drug availability , influencing drug - seeking behavior and sensitization .", "entity": [], "task": "NER"}
{"text": "Moreover , cocaine and other drugs of abuse can affect the strength of glutamate synapses in this structure , lastly modifying neuronal activity in main regions of the reward circuitry .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [11, 18]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "OBJECTIVE : The objective of this study is to determine whether the pharmacological manipulation of nNOS / NO / sGC / cGMP signaling pathway altered changes induced by repeated cocaine exposure .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [101, 103]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [118, 122]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [177, 184]}], "task": "NER"}
{"text": "RESULTS : The present investigation showed a relationship between behavioral cocaine sensitization , reduced threshold to generate long - term potentiation ( LTP ) in hippocampal dentate gyrus , and increased nNOS activity in this structure .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "However , when nNOS or sGC were inhibited , the number of sensitized animals was reduced , and the threshold to generate LTP was increased .", "entity": [], "task": "NER"}
{"text": "The opposite occurred when cGMP availability was increased .", "entity": [{"entity": "cGMP", "entity_type": "Chemical", "pos": [27, 31]}], "task": "NER"}
{"text": "CONCLUSION : We demonstrate a key role of the nNOS activity and NO / sGC / cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic transmission .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [47, 49]}, {"entity": "cGMP", "entity_type": "Chemical", "pos": [75, 79]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [120, 127]}], "task": "NER"}
{"text": "Plasmonic fluorescence enhancement by metal nanostructures : shaping the future of bionanotechnology .", "entity": [], "task": "NER"}
{"text": "This review focuses on metal enhanced fluorescence ( MEF ) and its current and future applications in biotechnology .", "entity": [], "task": "NER"}
{"text": "The mechanisms of MEF are discussed in terms of the additional radiative and nonradiative decay rates caused by the close proximity of the metal .", "entity": [], "task": "NER"}
{"text": "We then review the current MEF materials and structures that show promise in bioapplications .", "entity": [], "task": "NER"}
{"text": "The use of electromagnetic modelling to predict fluorescent rate enhancement is then considered .", "entity": [], "task": "NER"}
{"text": "We then give particular focus to the recent work carried out in the homogeneous fabrication of metal nanoparticles using colloidal lithography .", "entity": [], "task": "NER"}
{"text": "It is concluded that the use of computational electromagnetic modelling alongside homogeneous fabrication techniques will lead to predictable and controllable MEF , paving the way for increased applications in biotechnology .", "entity": [], "task": "NER"}
{"text": "A statistical approach for analyzing the development of ( 1 ) H multiple - quantum coherence in solids .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "A novel statistical approach for analyzing ( 1 ) H multiple - quantum ( MQ ) spin dynamics in so - called spin - counting solid - state NMR experiments is presented .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [43, 50]}], "task": "NER"}
{"text": "The statistical approach is based on the percolation theory with Monte Carlo methods and is examined by applying it to the experimental results of three solid samples having unique hydrogen arrangement for 1 - 3 dimensions : the n - alkane / d - urea inclusion complex as a one - dimensional ( 1D ) system , whose ( 1 ) H nuclei align approximately in 1D , and magnesium hydroxide and adamantane as a two - dimensional ( 2D ) and a three - dimensional ( 3D ) system , respectively .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [181, 189]}, {"entity": "n - alkane", "entity_type": "Chemical", "pos": [229, 239]}, {"entity": "d - urea", "entity_type": "Chemical", "pos": [242, 250]}, {"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [314, 321]}, {"entity": "magnesium hydroxide", "entity_type": "Chemical", "pos": [361, 380]}, {"entity": "adamantane", "entity_type": "Chemical", "pos": [385, 395]}], "task": "NER"}
{"text": "Four lattice models , linear , honeycomb , square and cubic , are used to represent the ( 1 ) H arrangement of the three samples .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [88, 95]}], "task": "NER"}
{"text": "It is shown that the MQ dynamics in adamantane is consistent with that calculated using the cubic lattice and that in Mg ( OH ) 2 with that calculated using the honeycomb and the square lattices .", "entity": [{"entity": "adamantane", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "Mg ( OH ) 2", "entity_type": "Chemical", "pos": [118, 129]}], "task": "NER"}
{"text": "For n - C20H42 / d - urea , these 4 lattice models fail to express its result .", "entity": [{"entity": "n - C20H42", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "d - urea", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "It is shown that a more realistic model representing the ( 1 ) H arrangement of n - C20H42 / d - urea can describe the result .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [57, 64]}, {"entity": "n - C20H42", "entity_type": "Chemical", "pos": [80, 90]}, {"entity": "d - urea", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "The present approach can thus be used to determine ( 1 ) H arrangement in solids .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "Graphene sheets : gram - scale synthesis of graphene sheets by a catalytic arc - discharge method ( small 8 / 2013 ) .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "Gram - scale amounts of high - quality graphene sheets are synthesized on page 1330 through an arc - discharge method .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "An arc , which is generated between two graphite rods when a high voltage is applied by Y .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "Liu and co - workers , can cause the graphite layers to separate into graphene sheets via a high - temperature exfoliation , or even broken into small clusters / atoms , which then form graphene sheets by catalytic growth , demonstrating that two mechanisms exist in an arc discharge process simultaneously .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [37, 45]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [70, 78]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [186, 194]}], "task": "NER"}
{"text": "Free radicals : free radical reactions in two dimensions : a case study on photochlorination of graphene ( small 8 / 2013 ) .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [96, 104]}], "task": "NER"}
{"text": "Graphene is a 2D giant polycyclic aromatic molecule that provides opportunities for studying chemical reactions in two dimensions .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "H .", "entity": [], "task": "NER"}
{"text": "Peng , Z .", "entity": [], "task": "NER"}
{"text": "Liu , and co - workers have systematically investigated the influence of specific features of 2D molecules , such as their thickness , stacking order , single - and double - side upon graphene ' s radical reactivity by utilizing a free radical photochlorination as a probe .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [184, 192]}], "task": "NER"}
{"text": "The result , described on page 1388 , can contribute to a deeper understanding of dimensionality effects for the chemistry of 2D graphene .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [129, 137]}], "task": "NER"}
{"text": "Optoelectronic Processes in Squaraine Dye - Doped OLEDs for Emission in the Near - Infrared .", "entity": [{"entity": "Squaraine Dye", "entity_type": "Chemical", "pos": [28, 41]}], "task": "NER"}
{"text": "A novel all - organic host - guest system for emission in the NIR is introduced and investigated with respect to its opto - electronic processes .", "entity": [], "task": "NER"}
{"text": "The good agreement between theoretical and experimental results highlights the model character of this system and its potential for electroluminescent application .", "entity": [], "task": "NER"}
{"text": "Comparative measurements provide access to the recombination mechanisms on molecular length scale and show that the emission behavior of the device under operation is controlled by charge carrier dynamics .", "entity": [], "task": "NER"}
{"text": "Small Molecule Inhibitors of ERCC1 - XPF Protein - Protein Interaction Synergize Alkylating Agents in Cancer Cells .", "entity": [], "task": "NER"}
{"text": "The benefit of cancer chemotherapy based on alkylating agents is limited due to the action of DNA repair enzymes which mitigate the damage induced by these agents .", "entity": [], "task": "NER"}
{"text": "The interaction between the proteins ERCC1 and XPF , involves two major components of the nucleotide excision repair pathway .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [90, 100]}], "task": "NER"}
{"text": "Here , novel inhibitors of this interaction were identified by virtual screening based on available structures using the National Cancer Institute ( NCI ) diversity set and a panel of DrugBank - small - molecules .", "entity": [], "task": "NER"}
{"text": "Subsequently , experimental validation of the in silico screening was undertaken .", "entity": [], "task": "NER"}
{"text": "Top hits were evaluated on A549 and HCT116 cancer cells .", "entity": [], "task": "NER"}
{"text": "In particular , the compound labeled NSC130813 was shown to act synergistically with cisplatin and mitomycin C , to increase UVC mediated cytotoxicity , to modify DNA repair as indicated by the staining of phosphorylated H2AX and to disrupt interaction between ERCC1 and XPF in cells .", "entity": [{"entity": "NSC130813", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "cisplatin", "entity_type": "Chemical", "pos": [85, 94]}, {"entity": "mitomycin C", "entity_type": "Chemical", "pos": [99, 110]}], "task": "NER"}
{"text": "In addition , using the Biacore technique , we showed that this compound interacts with the domain of XPF responsible for interaction with ERCC1 .", "entity": [], "task": "NER"}
{"text": "This study shows that small molecules targeting the protein - protein interaction of ERCC1 and XPF can be developed in order to enhance the effects of alkylating agents on cancer cells .", "entity": [], "task": "NER"}
{"text": "Magnetic Cooling at a Single Molecule Level : a Spectroscopic Investigation of Isolated Molecules on a Surface .", "entity": [], "task": "NER"}
{"text": "A sub - monolayer distribution of isolated molecular Fe14 ( bta ) 6 nanomagnets is deposited intact on a Au ( 111 ) surface and investigated by X - ray magnetic circular dichroism spectroscopy .", "entity": [{"entity": "Fe14 ( bta ) 6", "entity_type": "Chemical", "pos": [53, 67]}, {"entity": "Au ( 111 )", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "The entropy variation with respect to the applied magnetic field is extracted from the magnetization curves and evidences high magnetocaloric values at the single molecule level .", "entity": [], "task": "NER"}
{"text": "Transgenic Mouse alpha - and beta - Cardiac Myosins Containing the R403Q Mutation Show Isoform Dependent Transient Kinetic Differences .", "entity": [], "task": "NER"}
{"text": "Familial hypertrophic cardiomyopathy ( FHC ) is a major cause of sudden cardiac death in young athletes .", "entity": [], "task": "NER"}
{"text": "The discovery in 1990 that a point mutation at residue 403 ( R403Q ) in the beta - myosin heavy chain ( MHC ) caused a severe form of FHC was the first of many demonstrations linking FHC to mutations in muscle proteins .", "entity": [], "task": "NER"}
{"text": "A mouse model for FHC has been widely used to study the mechanochemical properties of mutated cardiac myosin , but mouse hearts express alpha - MHC , whereas the ventricles of larger mammals express predominantly beta - MHC .", "entity": [], "task": "NER"}
{"text": "To address the role of the isoform backbone on function , we generated a transgenic mouse in which the endogenous alpha - MHC was partially replaced with transgenically encoded beta - MHC or alpha - MHC .", "entity": [], "task": "NER"}
{"text": "A His - tag was cloned at the N - terminus , along with R403Q , to facilitate isolation of myosin subfragment - 1 ( S1 ) .", "entity": [{"entity": "His", "entity_type": "Chemical", "pos": [2, 5]}, {"entity": "N", "entity_type": "Chemical", "pos": [30, 31]}], "task": "NER"}
{"text": "Stopped - flow kinetics were used to measure the equilibrium constants and rates of nucleotide binding and release for the mouse S1 isoforms bound to actin .", "entity": [{"entity": "nucleotide", "entity_type": "Chemical", "pos": [84, 94]}], "task": "NER"}
{"text": "For the wildtype isoforms , we found that the affinity of MgADP for alpha - S1 ( 100 mu M ) is ~ 4 - fold weaker than for beta - S1 ( 25 mu M ) .", "entity": [{"entity": "MgADP", "entity_type": "Chemical", "pos": [58, 63]}], "task": "NER"}
{"text": "Correspondingly , the MgADP release rate for alpha - S1 ( 350 s - 1 ) is ~ 3 - fold greater than for beta - S1 ( 120 s - 1 ) .", "entity": [{"entity": "MgADP", "entity_type": "Chemical", "pos": [22, 27]}], "task": "NER"}
{"text": "Introducing the R403Q mutation caused only a minor reduction in kinetics for beta - S1 , but R403Q in alpha - S1 caused the ADP release rate to increase by 20 % ( 430 s - 1 ) .", "entity": [{"entity": "ADP", "entity_type": "Chemical", "pos": [124, 127]}], "task": "NER"}
{"text": "These transient kinetic studies on mouse cardiac myosins provide strong evidence that the functional impact of an FHC mutation on myosin depends on the isoform backbone .", "entity": [], "task": "NER"}
{"text": "A new isobenzofuranone from the mangrove endophytic fungus Penicillium sp .", "entity": [{"entity": "isobenzofuranone", "entity_type": "Chemical", "pos": [6, 22]}], "task": "NER"}
{"text": "( ZH58 ) .", "entity": [], "task": "NER"}
{"text": "A new isobenzofuranone , 4 - ( methoxymethyl ) - 7 - methoxy - 6 - methyl - 1 ( 3H ) - isobenzofuranone ( 1 ) , together with seven known compounds , dilation ( 2 ) , lumichrome ( 3 ) , curvulari ( 4 ) , 5 , 5 ' - oxy - dimethylene - bis ( 2 - furaldehyde ) ( 5 ) , chromone ( 6 ) , harman ( 1 - methyl - beta - carboline ) ( 7 ) , N9 - methyl - 1methyl - beta - carboline ( 8 ) , was isolated from the mangrove endophytic fungus , Penicillium sp .", "entity": [{"entity": "isobenzofuranone", "entity_type": "Chemical", "pos": [6, 22]}, {"entity": "4 - ( methoxymethyl ) - 7 - methoxy - 6 - methyl - 1 ( 3H ) - isobenzofuranone", "entity_type": "Chemical", "pos": [25, 103]}, {"entity": "dilation", "entity_type": "Chemical", "pos": [150, 158]}, {"entity": "lumichrome", "entity_type": "Chemical", "pos": [167, 177]}, {"entity": "curvulari", "entity_type": "Chemical", "pos": [186, 195]}, {"entity": "5 , 5 ' - oxy - dimethylene - bis ( 2 - furaldehyde )", "entity_type": "Chemical", "pos": [204, 257]}, {"entity": "chromone", "entity_type": "Chemical", "pos": [266, 274]}, {"entity": "harman ( 1 - methyl - beta - carboline )", "entity_type": "Chemical", "pos": [283, 323]}, {"entity": "N9 - methyl - 1methyl - beta - carboline", "entity_type": "Chemical", "pos": [332, 372]}], "task": "NER"}
{"text": "ZH58 obtained from the South China Sea coast .", "entity": [], "task": "NER"}
{"text": "Their structures were determined by analysis of spectroscopic data .", "entity": [], "task": "NER"}
{"text": "Compound 1 exhibited cytotoxicity against KB and KBV200 cells with IC50 values of 6 and 10 mu g / mL , respectively .", "entity": [], "task": "NER"}
{"text": "Design , Synthesis , and Structure - Activity Relationship Studies of Novel 3 - Alkylindole Derivatives as Selective and Highly Potent Myeloperoxidase Inhibitors .", "entity": [{"entity": "3 - Alkylindole", "entity_type": "Chemical", "pos": [76, 91]}], "task": "NER"}
{"text": "Due to its production of potent antimicrobial oxidants including hypochlorous acid , human myeloperoxidase ( MPO ) plays a critical role in innate immunity and inflammatory diseases .", "entity": [{"entity": "hypochlorous acid", "entity_type": "Chemical", "pos": [65, 82]}], "task": "NER"}
{"text": "Thus MPO is an attractive target in drug design .", "entity": [], "task": "NER"}
{"text": "( Aminoalkyl ) fluoroindole derivatives were detected to be very potent MPO inhibitors ; however , they also promote inhibition of the serotonin reuptake transporter ( SERT ) at the same concentration range .", "entity": [{"entity": "( Aminoalkyl ) fluoroindole", "entity_type": "Chemical", "pos": [0, 27]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [135, 144]}], "task": "NER"}
{"text": "Via structure - based drug design , a new series of MPO inhibitors derived from 3 - alkylindole were synthesized and their effects were assessed on MPO - mediated taurine chlorination and low - density lipoprotein oxidation as well as on inhibition of SERT .", "entity": [{"entity": "3 - alkylindole", "entity_type": "Chemical", "pos": [80, 95]}, {"entity": "taurine", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "The fluoroindole compound with three carbons in the side chain and one amide group exhibited a selectivity index of 35 ( Ki / IC50 ) with high inhibition of MPO activity ( IC50 = 18 nM ) , whereas its effect on SERT was in the micromolar range .", "entity": [{"entity": "fluoroindole", "entity_type": "Chemical", "pos": [4, 16]}, {"entity": "carbons", "entity_type": "Chemical", "pos": [37, 44]}, {"entity": "amide", "entity_type": "Chemical", "pos": [71, 76]}], "task": "NER"}
{"text": "Structure - function relationships , mechanism of action , and safety of the molecule are discussed .", "entity": [], "task": "NER"}
{"text": "Sacchathridine A , a Prostaglandin Release Inhibitor from Saccharothrix sp .", "entity": [{"entity": "Sacchathridine A", "entity_type": "Chemical", "pos": [0, 16]}, {"entity": "Prostaglandin", "entity_type": "Chemical", "pos": [21, 34]}], "task": "NER"}
{"text": "Sacchathridine A ( 1 ) was isolated from the fermentation broth of strain Saccharothrix sp .", "entity": [{"entity": "Sacchathridine A", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "MI559 - 46F5 .", "entity": [], "task": "NER"}
{"text": "The structure was determined as a new naphthoquinone derivative with an acetylhydrazino moiety by a combination of NMR , MS spectral analyses , and chemical degradation .", "entity": [{"entity": "naphthoquinone", "entity_type": "Chemical", "pos": [38, 52]}, {"entity": "acetylhydrazino", "entity_type": "Chemical", "pos": [72, 87]}], "task": "NER"}
{"text": "Compound 1 showed inhibitory activity of prostaglandin E2 release in a concentration - dependent manner from human synovial sarcoma cells , SW982 , with an IC50 value of 1 . 0 mu M , but had no effect on cell growth up to 30 mu M .", "entity": [{"entity": "prostaglandin E2", "entity_type": "Chemical", "pos": [41, 57]}], "task": "NER"}
{"text": "Design and synthesis of a tetrahydroisoquinoline - based hydroxamate derivative ( ZYJ - 34v ) , an oral active histone deacetylase inhibitor with potent antitumor activity .", "entity": [{"entity": "tetrahydroisoquinoline", "entity_type": "Chemical", "pos": [26, 48]}, {"entity": "hydroxamate", "entity_type": "Chemical", "pos": [57, 68]}, {"entity": "ZYJ - 34v", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "In our previous study we developed a novel series of tetrahydroisoquinoline - based hydroxamic acid derivatives as histone deacetylase ( HDAC ) inhibitors ( Bioorg . Med . Chem . , 2010 , 18 , 1761 - 1772 . , J . Med . Chem . , 2011 , 54 , 2823 - 2838 . ) , among which compound ZYJ - 34c ( 1 ) was identified and validated as the most potent one with marked in vitro and in vivo antitumor potency ( J . Med . Chem . , 2011 , 54 , 5532 - 5539 . ) .", "entity": [{"entity": "tetrahydroisoquinoline", "entity_type": "Chemical", "pos": [53, 75]}, {"entity": "hydroxamic acid", "entity_type": "Chemical", "pos": [84, 99]}, {"entity": "ZYJ - 34c", "entity_type": "Chemical", "pos": [279, 288]}], "task": "NER"}
{"text": "Herein further modification of 1 afforded another oral active analogue ZYJ - 34v ( 2 ) with simplified structure and lower molecular weight .", "entity": [{"entity": "ZYJ - 34v", "entity_type": "Chemical", "pos": [71, 80]}], "task": "NER"}
{"text": "Biological evaluation of compound 2 showed efficacious inhibition against HDAC1 , 2 , 3 and 6 , which was confirmed by western blot analysis results .", "entity": [], "task": "NER"}
{"text": "Most importantly , compound 2 exhibited similar even more potent in vitro and in vivo antitumor activities relative to the approved HDAC inhibitor SAHA This article is protected by copyright .", "entity": [{"entity": "SAHA", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "All rights reserved .", "entity": [], "task": "NER"}
{"text": "Metabolism of 2 , 2 ' , 3 , 3 ' , 6 , 6 ' - hexachlorobiphenyl ( PCB 136 ) atropisomers in tissue slices from phenobarbital or dexamethasone - induced rats is sex - dependent .", "entity": [{"entity": "2 , 2 ' , 3 , 3 ' , 6 , 6 ' - hexachlorobiphenyl", "entity_type": "Chemical", "pos": [14, 62]}, {"entity": "PCB 136", "entity_type": "Chemical", "pos": [65, 72]}, {"entity": "phenobarbital", "entity_type": "Chemical", "pos": [110, 123]}, {"entity": "dexamethasone", "entity_type": "Chemical", "pos": [127, 140]}], "task": "NER"}
{"text": "Chiral polychlorinated biphenyls ( PCBs ) such as PCB 136 enantioselectively sensitize the ryanodine receptor ( RyR ) .", "entity": [{"entity": "polychlorinated biphenyls", "entity_type": "Chemical", "pos": [7, 32]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [35, 39]}, {"entity": "PCB 136", "entity_type": "Chemical", "pos": [50, 57]}, {"entity": "ryanodine", "entity_type": "Chemical", "pos": [91, 100]}], "task": "NER"}
{"text": "In light of recent evidence that PCBs cause developmental neurotoxicity via RyR - dependent mechanisms , this suggests that enantioselective PCB metabolism may influence the developmental neurotoxicity of chiral PCBs .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [33, 37]}, {"entity": "PCB", "entity_type": "Chemical", "pos": [141, 144]}, {"entity": "PCBs", "entity_type": "Chemical", "pos": [212, 216]}], "task": "NER"}
{"text": "However , enantioselective disposition of PCBs has not been fully characterized .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [42, 46]}], "task": "NER"}
{"text": "The effect of sex and cytochrome P450 ( P450 ) enzyme induction on the enantioselective metabolism of PCB 136 was studied using liver tissue slices prepared from na i ve control ( CTL ) , phenobarbital ( PB ; CYP2B inducer ) or dexamethasone ( DEX ; CYP3A inducer ) pretreated adult Sprague - Dawley rats .", "entity": [{"entity": "PCB 136", "entity_type": "Chemical", "pos": [102, 109]}, {"entity": "phenobarbital", "entity_type": "Chemical", "pos": [188, 201]}, {"entity": "dexamethasone", "entity_type": "Chemical", "pos": [228, 241]}, {"entity": "DEX", "entity_type": "Chemical", "pos": [244, 247]}], "task": "NER"}
{"text": "PCB 136 metabolism was also examined in hippocampal slices derived from untreated rat pups .", "entity": [{"entity": "PCB 136", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In liver tissue slices , hydroxylated PCB ( OH - PCB ) profiles depended on sex and inducer pretreatment , and OH - PCB levels followed the rank orders male > female and PB > DEX > CTL .", "entity": [{"entity": "hydroxylated PCB", "entity_type": "Chemical", "pos": [25, 41]}, {"entity": "OH - PCB", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "OH - PCB", "entity_type": "Chemical", "pos": [111, 119]}, {"entity": "DEX", "entity_type": "Chemical", "pos": [175, 178]}], "task": "NER"}
{"text": "In contrast , the enantiomeric enrichment of PCB 136 and its metabolites was independent of sex and inducer pretreatment .", "entity": [{"entity": "PCB 136", "entity_type": "Chemical", "pos": [45, 52]}], "task": "NER"}
{"text": "Only small amounts of PCB 136 partitioned into hippocampal tissue slices and no OH - PCB metabolites were detected .", "entity": [{"entity": "PCB 136", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "OH - PCB", "entity_type": "Chemical", "pos": [80, 88]}], "task": "NER"}
{"text": "Our results suggest that enantioselective metabolism , sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs .", "entity": [{"entity": "PCBs", "entity_type": "Chemical", "pos": [182, 186]}], "task": "NER"}
{"text": "Self - Sorting Click Reactions That Generate Spatially Controlled Chemical Functionality on Surfaces .", "entity": [], "task": "NER"}
{"text": "This Article describes the generation of a patterned surface that can be postpolymerization modified to incorporate fragile macromolecules or delicate biomolecules without the need for special equipment .", "entity": [], "task": "NER"}
{"text": "Two monomers that undergo different click reactions , pentafluorophenyl acrylate ( PFPA ) and 4 - ( trimethylsilyl ) ethynylstyrene ( TMSES ) , were sequentially polymerized from a silicon surface in the presence of a shadowmask with UV light , generating 12 . 5 and 62 mu m pitch patterns .", "entity": [{"entity": "pentafluorophenyl acrylate", "entity_type": "Chemical", "pos": [54, 80]}, {"entity": "PFPA", "entity_type": "Chemical", "pos": [83, 87]}, {"entity": "4 - ( trimethylsilyl ) ethynylstyrene", "entity_type": "Chemical", "pos": [94, 131]}, {"entity": "TMSES", "entity_type": "Chemical", "pos": [134, 139]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "Two different dyes , 1 - aminomethylpyrene ( AMP ) and 5 - azidofluorescein ( AF ) , were covalently attached to the polymer brushes through aminolysis and dual desilylation / copper ( I ) - catalyzed alkyne / azide cycloaddition ( CuAAC ) in one pot .", "entity": [{"entity": "1 - aminomethylpyrene", "entity_type": "Chemical", "pos": [21, 42]}, {"entity": "AMP", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "5 - azidofluorescein", "entity_type": "Chemical", "pos": [55, 75]}, {"entity": "copper ( I )", "entity_type": "Chemical", "pos": [176, 188]}, {"entity": "alkyne", "entity_type": "Chemical", "pos": [201, 207]}, {"entity": "azide", "entity_type": "Chemical", "pos": [210, 215]}], "task": "NER"}
{"text": "Unlike most CuAAC reactions , the terminal alkyne of TMSES was not deprotected prior to functionalization .", "entity": [{"entity": "TMSES", "entity_type": "Chemical", "pos": [53, 58]}], "task": "NER"}
{"text": "Although a 2 nm thickness increase was observed for poly ( PFPA ) brushes after polymerization of TMSES , cross - contamination was not visible through fluorescence microscopy after functionalization .", "entity": [{"entity": "poly ( PFPA )", "entity_type": "Chemical", "pos": [52, 65]}, {"entity": "TMSES", "entity_type": "Chemical", "pos": [98, 103]}], "task": "NER"}
{"text": "Agonism of human pregnane X receptor by rilpivirine and etravirine : Comparison with first generation non - nucleoside reverse transcriptase inhibitors .", "entity": [{"entity": "pregnane", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "rilpivirine", "entity_type": "Chemical", "pos": [40, 51]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "nucleoside", "entity_type": "Chemical", "pos": [108, 118]}], "task": "NER"}
{"text": "Rilpivirine and etravirine are second generation non - nucleoside reverse transcriptase inhibitors approved recently by the United States Food and Drug Administration for the treatment of human immunodeficiency virus - 1 infection .", "entity": [{"entity": "Rilpivirine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [16, 26]}, {"entity": "nucleoside", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "Pregnane X receptor ( PXR ) is a member of the superfamily of nuclear receptors that regulate the expression of various genes controlling diverse biological functions .", "entity": [{"entity": "Pregnane", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The present study investigated the effects of rilpivirine and etravirine on the activity of human PXR ( hPXR ) , including the mode of activation , and compared them to those of efavirenz , nevirapine , and delavirdine , which are first generation non - nucleoside reverse transcriptase inhibitors .", "entity": [{"entity": "rilpivirine", "entity_type": "Chemical", "pos": [46, 57]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [62, 72]}, {"entity": "efavirenz", "entity_type": "Chemical", "pos": [178, 187]}, {"entity": "nevirapine", "entity_type": "Chemical", "pos": [190, 200]}, {"entity": "delavirdine", "entity_type": "Chemical", "pos": [207, 218]}, {"entity": "nucleoside", "entity_type": "Chemical", "pos": [254, 264]}], "task": "NER"}
{"text": "In transiently transfected HepG2 cells , rilpivirine , etravirine , and efavirenz , but not nevirapine or delavirdine , activated human , mouse , and rat PXR .", "entity": [{"entity": "rilpivirine", "entity_type": "Chemical", "pos": [41, 52]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [55, 65]}, {"entity": "efavirenz", "entity_type": "Chemical", "pos": [72, 81]}, {"entity": "nevirapine", "entity_type": "Chemical", "pos": [92, 102]}, {"entity": "delavirdine", "entity_type": "Chemical", "pos": [106, 117]}], "task": "NER"}
{"text": "Results from mechanistic studies indicated that rilpivirine , etravirine , and efavirenz , but not nevirapine or delavirdine , bound to the ligand - binding domain of hPXR , as assessed by a transactivation assay and by a competitive ligand - binding assay using time - resolved fluorescence resonance energy transfer ; triggered nuclear translocation of a green fluorescence protein - tagged hPXR , as visualized by confocal imaging ; and recruited steroid receptor coactivator - 1 ( SRC - 1 ) , SRC - 2 , and SRC - 3 to hPXR , as demonstrated by mammalian two - hybrid assays .", "entity": [{"entity": "rilpivirine", "entity_type": "Chemical", "pos": [48, 59]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [62, 72]}, {"entity": "efavirenz", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "nevirapine", "entity_type": "Chemical", "pos": [99, 109]}, {"entity": "delavirdine", "entity_type": "Chemical", "pos": [113, 124]}, {"entity": "steroid", "entity_type": "Chemical", "pos": [450, 457]}], "task": "NER"}
{"text": "Rilpivirine , etravirine , and efavirenz , but not nevirapine or delavirdine , increased hPXR target gene ( CYP3A4 ) expression in primary cultures of human hepatocytes .", "entity": [{"entity": "Rilpivirine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "efavirenz", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "nevirapine", "entity_type": "Chemical", "pos": [51, 61]}, {"entity": "delavirdine", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "In summary , select non - nucleoside reverse transcriptase inhibitors activated human and rodent PXR .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [26, 36]}], "task": "NER"}
{"text": "Rilpivirine , etravirine , and efavirenz , but not nevirapine or delavirdine , were identified as agonists of hPXR , as assessed in mechanistic experiments , and inducers of CYP3A4 , as determined in primary cultures of human hepatocytes .", "entity": [{"entity": "Rilpivirine", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "etravirine", "entity_type": "Chemical", "pos": [14, 24]}, {"entity": "efavirenz", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "nevirapine", "entity_type": "Chemical", "pos": [51, 61]}, {"entity": "delavirdine", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "Inhibitory effects of gypenosides on seven human cytochrome P450 enzymes in vitro .", "entity": [{"entity": "gypenosides", "entity_type": "Chemical", "pos": [22, 33]}], "task": "NER"}
{"text": "Among the various possible causes for drug interactions , pharmacokinetic factors such as inhibition of drug - metabolizing enzymes , especially cytochrome P450 ( CYP ) enzymes , are regarded as the most frequent and clinically important .", "entity": [], "task": "NER"}
{"text": "Gypenosides is widely used as functional food and over - the - counter drug in East Asia .", "entity": [{"entity": "Gypenosides", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In this study , the in vitro inhibitory effects of gypenosides on the major human CYP enzymes ( CYP1A2 , CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP2D6 , and CYP3A4 ) activities in human liver microsomes were examined using liquid chromatography - tandem mass spectrometry .", "entity": [{"entity": "gypenosides", "entity_type": "Chemical", "pos": [51, 62]}], "task": "NER"}
{"text": "Gypenosides showed the strongest inhibition of CYP2D6 , followed by CYP2C8 , CYP3A4 and CYP2C9 .", "entity": [{"entity": "Gypenosides", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "The IC50 values were 1 . 61 mu g / mL , 20 . 06 mu g / mL , 34 . 76 mu g / mL ( CYP3A4 / midazolam ) , 46 . 73 mu g / mL ( CYP3A4 / testosterone ) , and 54 . 52 mu g / mL , respectively .", "entity": [{"entity": "midazolam", "entity_type": "Chemical", "pos": [89, 98]}, {"entity": "testosterone", "entity_type": "Chemical", "pos": [132, 144]}], "task": "NER"}
{"text": "Gypenosides exhibited competitive inhibition of CYP2D6 ( Ki = 1 . 18 ) .", "entity": [{"entity": "Gypenosides", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "In conclusion , Gypenosides might cause herb - drug interactions via inhibition of CYP2D6 .", "entity": [{"entity": "Gypenosides", "entity_type": "Chemical", "pos": [16, 27]}], "task": "NER"}
{"text": "An in vivo study is needed to examine this further .", "entity": [], "task": "NER"}
{"text": "Novel racemic tetrahydrocurcuminoid dihydropyrimidinone analogues as potent acetylcholinesterase inhibitors .", "entity": [{"entity": "tetrahydrocurcuminoid dihydropyrimidinone", "entity_type": "Chemical", "pos": [14, 55]}], "task": "NER"}
{"text": "The synthesis of racemic tetrahydrocurcumin - ( THC - ) , tetrahydrodemethoxycurcumin - ( THDC - ) and tetrahydrobisdemethoxycurcumin - ( THBDC - ) dihydropyrimidinone ( DHPM ) analogues was achieved by utilizing the multi - component Biginelli reaction in the presence of copper sulphate as a catalyst .", "entity": [{"entity": "tetrahydrocurcumin", "entity_type": "Chemical", "pos": [25, 43]}, {"entity": "THC", "entity_type": "Chemical", "pos": [48, 51]}, {"entity": "tetrahydrodemethoxycurcumin", "entity_type": "Chemical", "pos": [58, 85]}, {"entity": "THDC", "entity_type": "Chemical", "pos": [90, 94]}, {"entity": "tetrahydrobisdemethoxycurcumin", "entity_type": "Chemical", "pos": [103, 133]}, {"entity": "THBDC", "entity_type": "Chemical", "pos": [138, 143]}, {"entity": "dihydropyrimidinone", "entity_type": "Chemical", "pos": [148, 167]}, {"entity": "DHPM", "entity_type": "Chemical", "pos": [170, 174]}, {"entity": "copper sulphate", "entity_type": "Chemical", "pos": [273, 288]}], "task": "NER"}
{"text": "The evaluation of acetylcholinesterase inhibitors for Alzheimer ' s disease of these compounds showed that they exhibited higher inhibitory activity than their parent analogues .", "entity": [], "task": "NER"}
{"text": "THBDC - DHPM demonstrated the most potent inhibitory activity with an IC50 value of 1 . 34 +/- 0 . 03 mu M which was more active than the approved drug galanthamine ( IC50 = 1 . 45 +/- 0 . 04 mu M ) .", "entity": [{"entity": "THBDC - DHPM", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "galanthamine", "entity_type": "Chemical", "pos": [152, 164]}], "task": "NER"}
{"text": "Design considerations for PAMAM dendrimer therapeutics .", "entity": [{"entity": "PAMAM", "entity_type": "Chemical", "pos": [26, 31]}], "task": "NER"}
{"text": "We have previously shown that methotrexate ( MTX ) conjugated to a cancer - specific poly amido amine ( PAMAM ) dendrimer has a higher therapeutic index than MTX alone .", "entity": [{"entity": "methotrexate", "entity_type": "Chemical", "pos": [30, 42]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [45, 48]}, {"entity": "poly amido amine", "entity_type": "Chemical", "pos": [85, 101]}, {"entity": "PAMAM", "entity_type": "Chemical", "pos": [104, 109]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [158, 161]}], "task": "NER"}
{"text": "Unfortunately , these therapeutics have been difficult to advance because of the complicated syntheses and an incomplete understanding of the dendrimer properties .", "entity": [], "task": "NER"}
{"text": "We wished to address these obstacles by using copper - free click chemistry to functionalize the dendrimer scaffolds and to exploring the effects of two dendrimer properties ( the targeting ligand and drug linkage ) on cytotoxicity .", "entity": [{"entity": "copper", "entity_type": "Chemical", "pos": [46, 52]}], "task": "NER"}
{"text": "We conjugated either ester or amide - linker modified MTX to dendrimer scaffolds with or without folic acid ( FA ) .", "entity": [{"entity": "ester", "entity_type": "Chemical", "pos": [21, 26]}, {"entity": "amide", "entity_type": "Chemical", "pos": [30, 35]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [54, 57]}, {"entity": "folic acid", "entity_type": "Chemical", "pos": [97, 107]}], "task": "NER"}
{"text": "Because of multivalency , the FA and MTX functionalized dendrimers had similar capacities to target the folate receptor on cancer cells .", "entity": [{"entity": "MTX", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "folate", "entity_type": "Chemical", "pos": [104, 110]}], "task": "NER"}
{"text": "Additionally , we found that the ester - and amide - linker modified MTX compounds had similar cytotoxicity but the dendrimer - ester MTX conjugates were much more cytotoxic than the dendrimer - amide MTX conjugates .", "entity": [{"entity": "ester", "entity_type": "Chemical", "pos": [33, 38]}, {"entity": "amide", "entity_type": "Chemical", "pos": [45, 50]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "ester", "entity_type": "Chemical", "pos": [128, 133]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [134, 137]}, {"entity": "amide", "entity_type": "Chemical", "pos": [195, 200]}, {"entity": "MTX", "entity_type": "Chemical", "pos": [201, 204]}], "task": "NER"}
{"text": "These results clarify the impact of these properties on therapeutic efficacy and will allow us to design more effective polymer therapeutics .", "entity": [], "task": "NER"}
{"text": "A urinary metabonomics study on biochemical changes in yeast - induced pyrexia rats : a new approach to elucidating the biochemical basis of the febrile response .", "entity": [], "task": "NER"}
{"text": "Fever is a prominent feature of many diseases , such as infection , inflammation and trauma .", "entity": [], "task": "NER"}
{"text": "In the clinic , fever can be easily judged by measuring the body temperature ; however , the pathogenesis of fever is still not fully understood .", "entity": [], "task": "NER"}
{"text": "A febrile response is a systemic pathological process that can cause metabolic disorders .", "entity": [], "task": "NER"}
{"text": "Metabonomics can provide powerful tools to reveal the pathological mechanisms for such a systemic disease .", "entity": [], "task": "NER"}
{"text": "Thus , to reveal subtle metabolic changes under the condition of fever and to explore its mechanism , an ultra performance liquid chromatography coupled with a quadrupole time - of - flight mass spectrometry metabonomics approach was employed to investigate the urine biochemical characteristics of yeast - induced pyrexia rats .", "entity": [], "task": "NER"}
{"text": "The acquired data were subjected to principal component analysis for differentiating the pyrexia rats from the control rats .", "entity": [], "task": "NER"}
{"text": "Potential biomarkers were screened by using orthogonal partial least - squares - discriminant analysis and were identified by accurate mass , database , and MS / MS fragment information obtained from the MS ( E ) technique .", "entity": [], "task": "NER"}
{"text": "Sixteen metabolites in rat urine were identified as potential biomarkers .", "entity": [], "task": "NER"}
{"text": "The relative intensities of the 15 potential biomarkers were calculated .", "entity": [], "task": "NER"}
{"text": "The thermoregulatory circuitry of \" endogenous pyrogen ( EP ) ^ - hypothalamus Na ( + ) / Ca ( 2 + ) - cAMP ^ \" was partially confirmed in this study .", "entity": [{"entity": "Na ( + ) / Ca ( 2 + ) - cAMP", "entity_type": "Chemical", "pos": [79, 107]}], "task": "NER"}
{"text": "The results suggested that UPLC / MS - based metabolic profiling of rat urine identifies impaired tryptophan metabolism as the mechanism of yeast - induced fever .", "entity": [{"entity": "tryptophan", "entity_type": "Chemical", "pos": [98, 108]}], "task": "NER"}
{"text": "This research provided informative data that the impaired tryptophan metabolism might be one of the important reasons in elucidating the biochemical basis of the febrile response .", "entity": [{"entity": "tryptophan", "entity_type": "Chemical", "pos": [58, 68]}], "task": "NER"}
{"text": "Xiaoxuming decoction for acute ischemic stroke : A systematic review and meta - analysis .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Xiaoxuming decoction ( XXMD ) is a well - known traditional Chinese herbal prescription in treatment of patients with stroke .", "entity": [], "task": "NER"}
{"text": "The objective of this study is to assess the efficacy and safety of XXMD for acute ischemic stroke .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : A systematic literature search was conducted in 6 databases until June 2012 to identify randomized controlled trials ( RCTs ) of XXMD for acute ischemic stroke compared with western conventional medicine ( WCM ) .", "entity": [], "task": "NER"}
{"text": "The primary outcome measures were National Institutes of Health Stroke Scale ( NIHSS ) scores and modified Rankin Scale ( mRS ) scores .", "entity": [], "task": "NER"}
{"text": "The secondary outcome measures were the clinical effective rate and adverse events at the end of treatment course .", "entity": [], "task": "NER"}
{"text": "The methodological quality of RCTs was assessed independently using 12 - item criteria according to the Cochrane Back Review Group .", "entity": [], "task": "NER"}
{"text": "All data were analyzed using Review Manager 5 . 0 software .", "entity": [], "task": "NER"}
{"text": "RESULTS : Eight RCTs with 601 individuals published from 1992 to 2012 were identified .", "entity": [], "task": "NER"}
{"text": "The studies were deemed to have a high risk of bias .", "entity": [], "task": "NER"}
{"text": "Compared with WCM , 1 RCT showed significant effects of XXMD for improving mRS after stroke ( p < 0 . 05 ) ; 3 RCTs for improving NIHSS scores [ n = 186 , weighted mean difference ( WMD ) : - 1 . 86 , 95 % CI : - 3 . 25 to - 0 . 48 , z = 2 . 63 , p < 0 . 01 ] ; 7 RCTs for improving the clinical effective rate [ n = 531 , risk ratio ( RR ) = 1 . 17 , 95 % CI , 1 . 09 to 1 . 26 , z = 4 . 38 , p < 0 . 01 ] .", "entity": [], "task": "NER"}
{"text": "Five trials contained safety assessments and stated that no adverse event was found , whereas the other 3 trials did not provide the information about adverse events .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : This systematic review showed positive but weak evidence of XXMD for acute ischemic stroke because of the poor methodological quality and the small quantity of the included trials .", "entity": [], "task": "NER"}
{"text": "The difficulties of fitting Chinese herbal medicine ( CHM ) into the double blinded RCTs have raised as follows : ( A ) traditional Chinese medicine ( TCM ) as whole systems of healthcare offers unique methodological and theoretical challenges for RCTs ; ( B ) suspicions against the placebo and unwillingness to stop taking other CHMs make recruitment more difficulty , time - consumption , and cost ; ( C ) the shortcomings of the TCM diagnostic process includes the lack of standardization in terminology , disagreement of pattern differentiation ( Bianzheng ) , and neglect of formula corresponding to syndrome ( TCM Zheng ) ; ( D ) It is difficult to design credible herbal placebos with similar appearance , smells and tastes to the experimental CHM and at the same time is absent of any pharmacological activity ; ( E ) the achieving efficacy of CHM complex interventions is often nonspecific and the outcome measures is subjective using Chinese quantitative instrument .", "entity": [], "task": "NER"}
{"text": "Insights into mast cell functions in asthma using mouse models .", "entity": [], "task": "NER"}
{"text": "Therapeutics targeting specific mechanisms of asthma have shown promising results in mouse models of asthma .", "entity": [], "task": "NER"}
{"text": "However , these successes have not transferred well to the clinic or to the treatment of asthma sufferers .", "entity": [], "task": "NER"}
{"text": "We suggest a reason for this incongruity is that mast cell - dependent responses , which may play an important role in the pathogenesis of both atopic and non - atopic asthma , are not a key component in most of the current asthma mouse models .", "entity": [], "task": "NER"}
{"text": "Two reasons for this are that wild type mice have , in contrast to humans , a negligible number of mast cells localized in the smaller airways and in the parenchyma , and that only specific protocols show mast cell - dependent reactions .", "entity": [], "task": "NER"}
{"text": "The development of mast cell - deficient mice and the reconstitution of mast cells within these mice have opened up the possibility to generate mouse models of asthma with a marked role of mast cells .", "entity": [], "task": "NER"}
{"text": "In addition , mast cell - deficient mice engrafted with mast cells have a distribution of mast cells more similar to humans .", "entity": [], "task": "NER"}
{"text": "In this article we review and highlight the mast cell - dependent and - independent responses with respect to airway hyperresponsiveness and inflammation in asthma models using mast cell - deficient and mast cell - engrafted mice .", "entity": [], "task": "NER"}
{"text": "Melanoidins isolated from heated potato fiber ( Potex ) affect human colon cancer cells growth via modulation of cell cycle and proliferation regulatory proteins .", "entity": [], "task": "NER"}
{"text": "Melanoidins are brown , nitrogen containing , high molecular weight end products of Maillard reaction with poorly established activity towards tumor cells .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [24, 32]}], "task": "NER"}
{"text": "The goal of present study was to verify whether both heated potato fiber Potex extract ( 180 degrees C for 2h ) and melanoidins isolated from the extract exerts growth - inhibiting activity in human colon cancer cells in vitro .", "entity": [], "task": "NER"}
{"text": "The cells of LS180 colon cancer cell line were tested upon treatment with roasted potato fiber extract ( AM4 ) as well as with high ( HMW ) and low ( LMW ) molecular weight fractions isolated from the extract , since both may be regarded as / or contain melanoidins .", "entity": [], "task": "NER"}
{"text": "The tested compounds at concentration of 1000 mu g / ml reduced cell growth down to 45 % , 69 % and 54 % , respectively .", "entity": [], "task": "NER"}
{"text": "Furthermore , deregulated ERK1 / 2 signaling was revealed upon treatment .", "entity": [], "task": "NER"}
{"text": "Moreover , multiple alternations in cell cycle regulators activity were found ( i . e . cyclinD1 , cyclin - dependent kinase 4 and 6 , p21 , p27 , p53 , pRb ) leading to cell cycle cessation in G0 phase .", "entity": [], "task": "NER"}
{"text": "Importantly , LMW compounds revealed markedly stronger potential to alter specific molecular targets comparing to HMW compounds .", "entity": [], "task": "NER"}
{"text": "Summarizing , the results emphasize that both high and low molecular weight melanoidins contribute to antiproliferative activity of heated potato fiber in LS180 colon cancer cells in vitro .", "entity": [], "task": "NER"}
{"text": "Short - term heating reduces the anti - inflammatory effects of fresh raw garlic extracts on the LPS - induced production of NO and pro - inflammatory cytokines by downregulating allicin activity in RAW 264 . 7 macrophages .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [125, 127]}, {"entity": "allicin", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "Garlic has a variety of biologic activities , including anti - inflammatory properties .", "entity": [], "task": "NER"}
{"text": "Although garlic has several biologic activities , some people dislike eating fresh raw garlic because of its strong taste and smell .", "entity": [], "task": "NER"}
{"text": "Therefore , garlic formulations involving heating procedures have been developed .", "entity": [], "task": "NER"}
{"text": "In this study , we investigated whether short - term heating affects the anti - inflammatory properties of garlic .", "entity": [], "task": "NER"}
{"text": "Fresh and heated raw garlic extracts ( FRGE and HRGE ) were prepared with incubation at 25 degrees C and 95 degrees C , respectively , for 2h .", "entity": [], "task": "NER"}
{"text": "Treatment with FRGE and HRGE significantly reduced the LPS - induced increase in the pro - inflammatory cytokine concentration ( TNF - alpha , IL - 1 beta , and IL - 6 ) and NO through HO - 1 upregulation in RAW 264 . 7 macrophages .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [174, 176]}], "task": "NER"}
{"text": "The anti - inflammatory effect was greater in FRGE than in HRGE .", "entity": [], "task": "NER"}
{"text": "The allicin concentration was higher in FRGE than in HRGE .", "entity": [{"entity": "allicin", "entity_type": "Chemical", "pos": [4, 11]}], "task": "NER"}
{"text": "Allicin treatment showed reduced production of pro - inflammatory cytokines and NO and increased HO - 1 activity .", "entity": [{"entity": "Allicin", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "NO", "entity_type": "Chemical", "pos": [80, 82]}], "task": "NER"}
{"text": "The results show that the decrease in LPS - induced NO and pro - inflammatory cytokines in RAW 264 . 7 macrophages through HO - 1 induction was greater for FRGE compared with HRGE .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [52, 54]}], "task": "NER"}
{"text": "Additionally , the results indicate that allicin is responsible for the anti - inflammatory effect of FRGE .", "entity": [{"entity": "allicin", "entity_type": "Chemical", "pos": [41, 48]}], "task": "NER"}
{"text": "Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease .", "entity": [{"entity": "allicin", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "Motor neuron dysfunction in a mouse model of ALS : Gender - dependent effect of P2X7 antagonism .", "entity": [], "task": "NER"}
{"text": "Amyotrophic lateral sclerosis ( ALS ) is a neurodegenerative progressive currently untreatable disease , characterized by selective motor neuron degeneration ; the incidence and prevalence of ALS are greater in men than in women .", "entity": [], "task": "NER"}
{"text": "Although some important mechanisms that might contribute to the death of motor neurons have been identified , the mechanisms underlying disease pathophysiology are still uncertain .", "entity": [], "task": "NER"}
{"text": "In particular , the mechanisms underlying the role of gender in ALS and whether treatments should take into account sexual dimorphism remain only partially understood .", "entity": [], "task": "NER"}
{"text": "Recently , the P2X7 receptor for ATP was reported to display neurotoxic potential in motor neuron disorders , and antagonism of the receptor has been suggested to be helpful in these disorders .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [33, 36]}], "task": "NER"}
{"text": "Studying transgenic mice with superoxide dismutase 1 gene mutations , widely used as model for ALS , may provide a better understanding of pathogenic mechanisms and of toxicity towards motor neurons , also possibly helping to understand whether treatments for ALS should take into account sexual dimorphism .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [30, 40]}], "task": "NER"}
{"text": "The aim of the work was ( 1 ) investigating on gender - dependence of disease progression in the standard model for ALS - the transgenic mouse bearing superoxide dismutase 1 gene mutations - and ( 2 ) assessing if a P2X7 receptor antagonist treatment should take into account sexual dimorphism .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [151, 161]}], "task": "NER"}
{"text": "We evaluated if gender affect the disease course , the motor performance , the weight loss and the lifespan in mice overexpressing mutant superoxide dismutase 1 .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [138, 148]}], "task": "NER"}
{"text": "We measured motor impairment , motor strength and coordination by rotarod and grip strength testing .", "entity": [], "task": "NER"}
{"text": "Further , we assessed if a treatment with the P2X7 receptor antagonist Brilliant Blue G - a dye that can cross the blood - brain barrier , has low toxicity , and has exhibited therapeutic effects in animal models of neurodegenerative diseases - impact on the disease progression , in male and female ALS mice .", "entity": [{"entity": "Brilliant Blue G", "entity_type": "Chemical", "pos": [71, 87]}], "task": "NER"}
{"text": "We found that ( 1 ) the onset and the disease progression , and the survival were dependent on gender : male performed worst than female , lost body weight and died before ; ( 2 ) treatment with the P2X7 receptor antagonist Brilliant Blue G ameliorated the disease progression .", "entity": [{"entity": "Brilliant Blue G", "entity_type": "Chemical", "pos": [224, 240]}], "task": "NER"}
{"text": "The treatment effect was gender - dependent : amelioration was greater in male than in female .", "entity": [], "task": "NER"}
{"text": "In conclusions , we suggest that not only pathogenetic mechanism of motor neuron toxicity but also the drug treatment effectiveness may depend on gender ; sexual dimorphism should be considered when investigating on ALS treatment efficacy in the ALS animal model .", "entity": [], "task": "NER"}
{"text": "Our findings also point on the potential relevance of P2X7 receptor antagonism for ALS treatment , and highlight the importance of adopting a sex - specific approach to searching for treatment of ALS .", "entity": [], "task": "NER"}
{"text": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin - induced inflammatory activation is mediated by intracellular free calcium in microglial cells .", "entity": [{"entity": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [0, 47]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [116, 123]}], "task": "NER"}
{"text": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin ( TCDD ) has been known to induce inflammatory signaling in a number of cell types and tissues .", "entity": [{"entity": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [0, 47]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [50, 54]}], "task": "NER"}
{"text": "However , the adverse effects of TCDD on the central nervous system ( CNS ) have not been entirely elucidated .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [33, 37]}], "task": "NER"}
{"text": "In this study , using reverse transcriptase PCR ( RT - PCR ) and ELISA , we showed that TCDD up - regulated the expression and secretion of tumor necrosis factor - alpha ( TNF - alpha ) in a time - dependent manner in cultured HAPI microglial cells .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [88, 92]}], "task": "NER"}
{"text": "TCDD also caused a fast ( within 30min as judged by the increase in its mRNA level ) activation of cytosolic phospholipase A2 ( cPLA2 ) .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "This initial action was accompanied by up - regulation of cyclooxygenase - 2 ( COX - 2 ) , an important inflammation marker within 1h after TCDD treatment .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [140, 144]}], "task": "NER"}
{"text": "These pro - inflammatory responses were inhibited by two types of Ca ( 2 + ) blockers , bis - ( o - aminophenoxy ) ethane - N , N , N ' , N ' - tetra - acetic acid acetoxymethyl ester ( BAPTA - AM ) and nifedipine , thus , indicating that the effects are triggered by initial increase in the intracellular concentration of free Ca ( 2 + ) ( [ Ca ( 2 + ) ] i ) .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [66, 76]}, {"entity": "bis - ( o - aminophenoxy ) ethane - N , N , N ' , N ' - tetra - acetic acid acetoxymethyl ester", "entity_type": "Chemical", "pos": [88, 183]}, {"entity": "BAPTA - AM", "entity_type": "Chemical", "pos": [186, 196]}, {"entity": "nifedipine", "entity_type": "Chemical", "pos": [203, 213]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [328, 338]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [343, 353]}], "task": "NER"}
{"text": "Further , TCDD exposure could induce phosphorylation - and ubiquitination - dependent degradation of I k B alpha , and the translocation of NF - kappa B p65 from the cytosol to the nucleus in this microglial cell line .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [10, 14]}], "task": "NER"}
{"text": "Thus , the NF - kappa B signaling pathway can be activated after TCDD treatment .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [65, 69]}], "task": "NER"}
{"text": "However , Ca ( 2 + ) blockers also obviously attenuated NF - kappa B activation and transnuclear transport induced by TCDD .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [10, 20]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [118, 122]}], "task": "NER"}
{"text": "In concert with these results , we highlighted that the secretion of pro - inflammatory cytokine and NF - kappa B activation induced by TCDD can be mediated by elevation of [ Ca ( 2 + ) ] i in HAPI microglial cells .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [136, 140]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [175, 185]}], "task": "NER"}
{"text": "Extract from Mimosa pigra attenuates chronic experimental pulmonary hypertension .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Different parts of Mimosa pigra ( MPG ) are used in traditional medicine in Madagascar , tropical Africa , South America and Indonesia for various troubles including cardiovascular disorders .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : To investigate the mechanisms underlying the vascular effects of MPG by assessing in vitro its antioxidant and anti - inflammatory properties , and its vascular relaxing effects , and in vivo , its action on hypoxic pulmonary hypertension ( PAH ) in rats .", "entity": [], "task": "NER"}
{"text": "MATERIAL AND METHODS : The antioxidant activity of MPG leaf hydromethanolic extract was determined by using both the 1 , 1 - diphenyl - 2 - picrylhydrazyl radical scavenging and the oxygen radical absorbance capacity in vitro assays .", "entity": [{"entity": "1 , 1 - diphenyl - 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [117, 154]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [182, 188]}], "task": "NER"}
{"text": "Anti - inflammatory properties were assayed on TNF alpha - induced VCAM - 1 expression in endothelial cells .", "entity": [], "task": "NER"}
{"text": "The vasorelaxant effect of MPG extract was studied on rat arterial rings pre - contracted with phenylephrine ( 1 mu M ) in the presence or absence of the endothelium .", "entity": [{"entity": "phenylephrine", "entity_type": "Chemical", "pos": [95, 108]}], "task": "NER"}
{"text": "In vivo MPG extract effects were analyzed in chronic hypoxic PAH , obtained by housing male Wistar rats , orally treated or not with MPG extract ( 400mg / kg / d ) , in a hypobaric chamber for 21 days .", "entity": [], "task": "NER"}
{"text": "RESULTS : MPG leaf extract had antioxidant and anti - inflammatory properties .", "entity": [], "task": "NER"}
{"text": "It induced endothelium - dependent , NO - mediated relaxation of rat aorta and pulmonary artery .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [37, 39]}], "task": "NER"}
{"text": "In vivo , chronic MPG treatment reduced hypoxic PAH in rat by decreasing by 22 . 3 % the pulmonary arterial pressure and by 20 . 0 % and 23 . 9 % the pulmonary artery and cardiac remodelling , respectively .", "entity": [], "task": "NER"}
{"text": "This effect was associated with a restoration of endothelium function and a 2 . 3 - fold increase in endothelial NO synthase phosphorylation .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [113, 115]}], "task": "NER"}
{"text": "MPG leaf hydromethanolic extract contained tryptophan and flavonoids , including quercetin glycosides .", "entity": [{"entity": "tryptophan", "entity_type": "Chemical", "pos": [43, 53]}, {"entity": "flavonoids", "entity_type": "Chemical", "pos": [58, 68]}, {"entity": "quercetin glycosides", "entity_type": "Chemical", "pos": [81, 101]}], "task": "NER"}
{"text": "Both compounds also efficiently limit hypoxia - induced PAH .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Our results show endothelial protective action of MPG leaf hydromethanolic extract which is likely to be due to its antioxidant action .", "entity": [], "task": "NER"}
{"text": "MPG successfully attenuated the development of PAH , thus demonstrating the protective effect of MPG on cardiovascular diseases .", "entity": [], "task": "NER"}
{"text": "The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [4, 7]}], "task": "NER"}
{"text": "During repetitive stimulation of skeletal muscle , extracellular ATP levels raise , activating purinergic receptors , increasing Ca ( 2 + ) influx , and enhancing contractile force , a response called potentiation .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [65, 68]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [129, 139]}], "task": "NER"}
{"text": "We found that ATP appears to be released through pannexin1 hemichannels ( Panx1 HCs ) .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [14, 17]}], "task": "NER"}
{"text": "Immunocytochemical analyses and function were consistent with pannexin1 localization to T - tubules intercalated with dihydropyridine and ryanodine receptors in slow ( soleus ) and fast ( extensor digitorum longus , EDL ) muscles .", "entity": [{"entity": "dihydropyridine", "entity_type": "Chemical", "pos": [118, 133]}, {"entity": "ryanodine", "entity_type": "Chemical", "pos": [138, 147]}], "task": "NER"}
{"text": "Isolated myofibers took up ethidium ( Etd ( + ) ) and released small molecules ( as ATP ) during electrical stimulation .", "entity": [{"entity": "ethidium", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "Etd ( + )", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Consistent with two glucose uptake pathways , induced uptake of 2 - NBDG , a fluorescent glucose derivative , was decreased by inhibition of HCs or glucose transporter ( GLUT4 ) , and blocked by dual blockade .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [20, 27]}, {"entity": "2 - NBDG", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "Adult skeletal muscles apparently do not express connexins , making it unlikely that connexin hemichannels contribute to the uptake and release of small molecules .", "entity": [], "task": "NER"}
{"text": "ATP release , Etd ( + ) uptake , and potentiation induced by repetitive electrical stimulation were blocked by HC blockers and did not occur in muscles of pannexin1 knockout mice .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "Etd ( + )", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "MRS2179 , a P2Y1R blocker , prevented potentiation in EDL , but not soleus muscles , suggesting that in fast muscles ATP activates P2Y1 but not P2X receptors .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [117, 120]}], "task": "NER"}
{"text": "Phosphorylation on Ser and Thr residues of pannexin1 was increased during potentiation , possibly mediating HC opening .", "entity": [{"entity": "Ser", "entity_type": "Chemical", "pos": [19, 22]}, {"entity": "Thr", "entity_type": "Chemical", "pos": [27, 30]}], "task": "NER"}
{"text": "Opening of Panx1 HCs during repetitive activation allows efflux of ATP , influx of glucose and possibly Ca ( 2 + ) too , which are required for potentiation of contraction .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [67, 70]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [83, 90]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [104, 114]}], "task": "NER"}
{"text": "Genetic deletion of the adenosine A2A receptor prevents nicotine - induced upregulation of alpha 7 , but not alpha 4 beta 2 * nicotinic acetylcholine receptor binding in the brain .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [136, 149]}], "task": "NER"}
{"text": "Considerable evidence indicates that adenosine A2A receptors ( A2ARs ) modulate cholinergic neurotransmission , nicotinic acetylcholine receptor ( nAChR ) function , and nicotine - induced behavioural effects .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [37, 46]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [122, 135]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [170, 178]}], "task": "NER"}
{"text": "To explore the interaction between A2A and nAChRs , we examined if the complete genetic deletion of adenosine A2ARs in mice induces compensatory alterations in the binding of different nAChR subtypes , and whether the long - term effects of nicotine on nAChR regulation are altered in the absence of the A2AR gene .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [100, 109]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [241, 249]}], "task": "NER"}
{"text": "Quantitative autoradiography was used to measure cytisine - sensitive [ ( 125 ) I ] epibatidine and [ ( 125 ) I ] alpha - bungarotoxin binding to alpha 4 beta 2 * and alpha 7 nAChRs , respectively , in brain sections of drug - na i ve ( n = 6 ) or nicotine treated ( n = 5 - 7 ) , wild - type and adenosine A2AR knockout mice .", "entity": [{"entity": "cytisine", "entity_type": "Chemical", "pos": [49, 57]}, {"entity": "[ ( 125 ) I ] epibatidine", "entity_type": "Chemical", "pos": [70, 95]}, {"entity": "( 125 ) I", "entity_type": "Chemical", "pos": [102, 111]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [248, 256]}, {"entity": "adenosine", "entity_type": "Chemical", "pos": [297, 306]}], "task": "NER"}
{"text": "Saline or nicotine ( 7 . 8 mg / kg / day ; free - base weight ) were administered to male CD1 mice via subcutaneous osmotic minipumps for a period of 14 days .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "Blood plasma levels of nicotine and cotinine were measured at the end of treatment .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [23, 31]}, {"entity": "cotinine", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "There were no compensatory developmental alterations in nAChR subtype distribution or density in drug - na i ve A2AR knockout mice .", "entity": [], "task": "NER"}
{"text": "In nicotine treated wild - type mice , both alpha 4 beta 2 * and alpha 7 nAChR binding sites were increased compared with saline treated controls .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [3, 11]}], "task": "NER"}
{"text": "The genetic ablation of adenosine A2ARs prevented nicotine - induced upregulation of alpha 7 nAChRs , without affecting alpha 4 beta 2 * receptor upregulation .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [24, 33]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "This selective effect was observed at plasma levels of nicotine that were within the range reported for smokers ( 10 - 50 ng ml ( - 1 ) ) .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [55, 63]}], "task": "NER"}
{"text": "Our data highlight the involvement of adenosine A2ARs in the mechanisms of nicotine - induced alpha 7 nAChR upregulation , and identify A2ARs as novel pharmacological targets for modulating the long - term effects of nicotine on alpha 7 receptors .", "entity": [{"entity": "adenosine", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [75, 83]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [217, 225]}], "task": "NER"}
{"text": "Profiling the venom gland transcriptome of Tetramorium bicarinatum ( Hymenoptera : Formicidae ) : The first transcriptome analysis of an ant species .", "entity": [], "task": "NER"}
{"text": "Animal venoms are complex mixtures containing a range of bioactive elements with potential pharmacological and therapeutic use .", "entity": [], "task": "NER"}
{"text": "Even though ants account among the most diverse zoological group , little information is available regarding their venom composition .", "entity": [], "task": "NER"}
{"text": "To initiate the characterization of the transcriptomic venom gland expression of the ant species Tetramorium bicarinatum , 400 randomly selected clones from cDNA library were sequenced and a total of 364 high quality expressed sequence tags ( ESTs ) were generated .", "entity": [], "task": "NER"}
{"text": "Based on the results of BLAST searches , these sequences were clustered and assembled into 83 contigs ( 22 multiple sequences ) and 61 singletons .", "entity": [], "task": "NER"}
{"text": "About 74 % ( 267 ) of the contigs matched BLASTx hits with an interesting diversity together with an unusual abundance of cellular transcripts related to gene expression regulation ( 29 % of the total library ) reflecting the specialization of this tissue .", "entity": [], "task": "NER"}
{"text": "About eighteen per cent of the ESTs were categorized as Hymenoptera venom compounds , the major part represented by allergens ( 62 % of the total venom compounds ) .", "entity": [], "task": "NER"}
{"text": "In addition , a high number of sequences ( 26 % ) had no similarity to any known sequences .", "entity": [], "task": "NER"}
{"text": "This study provides a first insight of the gene expression scenario of the venom gland of T . bicarinatum which might contribute to acquiring a more comprehensive view on the origin and functional diversity of venom proteins among ants and more broadly among Hymenopteran insects .", "entity": [], "task": "NER"}
{"text": "Simultaneous determination of methanol , acetaldehyde , acetone , and ethanol in human blood by gas chromatography with flame ionization detection .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [30, 38]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [70, 77]}], "task": "NER"}
{"text": "Background : Methanol , acetaldehyde , acetone , and ethanol , which are commonly used as biomarkers of several diseases , in acute intoxications , and forensic settings , can be detected and quantified in biological fluids .", "entity": [{"entity": "Methanol", "entity_type": "Chemical", "pos": [13, 21]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [39, 46]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [53, 60]}], "task": "NER"}
{"text": "Gas chromatography ( GC ) - mass spectrometry techniques are complex , require highly trained personnel and expensive materials .", "entity": [], "task": "NER"}
{"text": "Gas chromatographic determinations of ethanol , methanol , and acetone have been reported in one study with suboptimal accuracy .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [38, 45]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [48, 56]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [63, 70]}], "task": "NER"}
{"text": "Our objective was to improve the assessment of these compounds in human blood using GC with flame ionization detection . Methods : An amount of 50 micro l of blood was diluted with 300 micro l of sterile water , 40 micro l of 10 % sodium tungstate , and 20 micro l of 1 % sulphuric acid .", "entity": [{"entity": "sodium tungstate", "entity_type": "Chemical", "pos": [231, 247]}, {"entity": "sulphuric acid", "entity_type": "Chemical", "pos": [272, 286]}], "task": "NER"}
{"text": "After centrifugation , 1 micro l of the supernatant was inje - cted into the gas chromatograph .", "entity": [], "task": "NER"}
{"text": "We used a dimethylpolysiloxane capillary column of 30 m 0 . 25 mm 0 . 25 micro m . Results : We observed linear correlations from 7 . 5 to 240 mg / l for methanol , acetaldehyde , and acetone and from 75 to 2400 mg / l for ethanol .", "entity": [{"entity": "dimethylpolysiloxane", "entity_type": "Chemical", "pos": [10, 30]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [154, 162]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [165, 177]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [184, 191]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [223, 230]}], "task": "NER"}
{"text": "Precision at concentrations 15 , 60 , and 120 mg / l for methanol , acetaldehyde , and acetone and 150 , 600 , and 1200 mg / ml for ethanol were 0 . 8 - 6 . 9 % .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [57, 65]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [68, 80]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [87, 94]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "Ranges of accuracy were 94 . 7 - 98 . 9 % for methanol , 91 . 2 - 97 . 4 % for acetaldehyde , 96 . 1 - 98 . 7 % for acetone , and 105 . 5 - 111 . 6 % for ethanol .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [79, 91]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [116, 123]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [154, 161]}], "task": "NER"}
{"text": "Limits of detection were 0 . 80 mg / l for methanol , 0 . 61 mg / l for acetaldehyde , 0 . 58 mg / l for acetone , and 0 . 53 mg / l for ethanol . Conclusion : This method is suitable for routine clinical and forensic practices .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [43, 51]}, {"entity": "acetaldehyde", "entity_type": "Chemical", "pos": [72, 84]}, {"entity": "acetone", "entity_type": "Chemical", "pos": [105, 112]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [137, 144]}], "task": "NER"}
{"text": "Progression rates from HbA1c 6 . 0 - 6 . 4 % and other prediabetes definitions to type 2 diabetes : a meta - analysis .", "entity": [], "task": "NER"}
{"text": "AIMS / HYPOTHESIS : Precise estimates of progression rates from ' prediabetes ' to type 2 diabetes are needed to optimise prevention strategies for high - risk individuals .", "entity": [], "task": "NER"}
{"text": "There is acceptance of prediabetes defined by impaired fasting glucose ( IFG ) and impaired glucose tolerance ( IGT ) , but there is some controversy surrounding HbA1c - defined prediabetes ranges , with some favouring 6 . 0 - 6 . 4 % ( 42 - 46 mmol / mol ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [63, 70]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "Comparing progression rates between groups might aid this issue , thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories .", "entity": [], "task": "NER"}
{"text": "METHODS : Meta - analysis of prospective observational studies in which participants had prediabetes at baseline ( ADA - defined IFG [ 5 . 6 - 6 . 9 mmol / l ] , WHO - defined IFG [ 6 . 1 - 6 . 9 mmol / l ] , IGT ( 7 . 8 - 11 . 0 mmol / l ) or raised HbA1c [ 6 . 0 - 6 . 4 % / 42 - 46 mmol / mol ] ) and were followed up for incident diabetes .", "entity": [], "task": "NER"}
{"text": "Incidence rates were combined using Bayesian random effects models .", "entity": [], "task": "NER"}
{"text": "RESULTS : Overall , 70 studies met the inclusion criteria .", "entity": [], "task": "NER"}
{"text": "In the six studies that used raised HbA1c , the pooled incidence rate ( 95 % credible interval ) of diabetes was 35 . 6 ( 15 . 1 , 83 . 0 ) per 1 , 000 person - years .", "entity": [], "task": "NER"}
{"text": "This rate was most similar to that for ADA - defined IFG ( 11 studies ; 35 . 5 [ 26 . 6 , 48 . 0 ] ) and was non - significantly lower than WHO - defined IFG ( 34 studies ; 47 . 4 [ 37 . 4 , 59 . 8 ] ) , IGT ( 46 studies , 45 . 5 [ 37 . 8 , 54 . 5 ] ) and IFG plus IGT ( 15 studies , 70 . 4 [ 53 . 8 , 89 . 7 ] ) .", "entity": [], "task": "NER"}
{"text": "Similar results were seen when the data were analysed by the criteria used to diagnose diabetes .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS / INTERPRETATION : This study provides evidence that progression rates differ by prediabetes definition , which has implications for the planning and implementation of diabetes prevention programmes .", "entity": [], "task": "NER"}
{"text": "HbA1c 6 . 0 - 6 . 4 % might identify people at a lower diabetes risk than other prediabetes definitions , but further research is needed .", "entity": [], "task": "NER"}
{"text": "Antibacterial oxazolidinone analogues having a N - hydroxyacetyl - substituted seven - membered [ 1 , 2 , 5 ] triazepane or [ 1 , 2 , 5 ] oxadiazepane C - ring unit .", "entity": [{"entity": "oxazolidinone", "entity_type": "Chemical", "pos": [14, 27]}, {"entity": "N - hydroxyacetyl", "entity_type": "Chemical", "pos": [47, 64]}, {"entity": "[ 1 , 2 , 5 ] triazepane", "entity_type": "Chemical", "pos": [96, 120]}, {"entity": "[ 1 , 2 , 5 ] oxadiazepane", "entity_type": "Chemical", "pos": [124, 150]}, {"entity": "C", "entity_type": "Chemical", "pos": [151, 152]}], "task": "NER"}
{"text": "We synthesized a series of oxazolidinone analogues bearing a N - hydroxyacetyl - substituted [ 1 , 2 , 5 ] triazepane or [ 1 , 2 , 5 ] oxadiazepane C - ring unit as homologues of an earlier drug candidate , eperezolid .", "entity": [{"entity": "oxazolidinone", "entity_type": "Chemical", "pos": [27, 40]}, {"entity": "N - hydroxyacetyl - substituted [ 1 , 2 , 5 ] triazepane or [ 1 , 2 , 5 ] oxadiazepane", "entity_type": "Chemical", "pos": [61, 147]}, {"entity": "C", "entity_type": "Chemical", "pos": [148, 149]}, {"entity": "eperezolid", "entity_type": "Chemical", "pos": [207, 217]}], "task": "NER"}
{"text": "Several of these compounds exhibited potent in vitro antibacterial activities towards not only Gram - positive , but also Gram - negative and linezolid - resistant pathogens .", "entity": [{"entity": "linezolid", "entity_type": "Chemical", "pos": [142, 151]}], "task": "NER"}
{"text": "Compounds 21a and 21b , bearing a thiocarbamate side chain , showed high in vivo activity against methicillin - resistant Staphylococcus aureus SR3637 , together with a promising safety profile in terms of weak inhibition of monoamine oxidase and cytochrome P450 isozymes .", "entity": [{"entity": "thiocarbamate", "entity_type": "Chemical", "pos": [34, 47]}, {"entity": "methicillin", "entity_type": "Chemical", "pos": [98, 109]}, {"entity": "monoamine", "entity_type": "Chemical", "pos": [225, 234]}], "task": "NER"}
{"text": "Proteasomal cleavage site prediction of protein antigen using BP neural network based on a new set of amino acid descriptor .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "The accurate identification of cytotoxic T lymphocyte epitopes is becoming increasingly important in peptide vaccine design .", "entity": [], "task": "NER"}
{"text": "The ubiquitin - proteasome system plays a key role in processing and presenting major histocompatibility complex class I restricted epitopes by degrading the antigenic protein .", "entity": [], "task": "NER"}
{"text": "To enhance the specificity and efficiency of epitope prediction and identification , the recognition mode between the ubiquitin - proteasome complex and the protein antigen must be considered .", "entity": [], "task": "NER"}
{"text": "Hence , a model that accurately predicts proteasomal cleavage must be established .", "entity": [], "task": "NER"}
{"text": "This study proposes a new set of parameters to characterize the cleavage window and uses a backpropagation neural network algorithm to build a model that accurately predicts proteasomal cleavage .", "entity": [], "task": "NER"}
{"text": "The accuracy of the prediction model , which depends on the window sizes of the cleavage , reaches 95 . 454 % for the N - terminus and 95 . 011 % for the C - terminus .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [118, 119]}, {"entity": "C", "entity_type": "Chemical", "pos": [154, 155]}], "task": "NER"}
{"text": "The results show that the identification of proteasomal cleavage sites depends on the sequence next to it and that the prediction performance of the C - terminus is better than that of the N - terminus on average .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [149, 150]}, {"entity": "N", "entity_type": "Chemical", "pos": [189, 190]}], "task": "NER"}
{"text": "Thus , models based on the properties of amino acids can be highly reliable and reflect the structural features of interactions between proteasomes and peptide sequences .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [41, 52]}], "task": "NER"}
{"text": "Effects of Dietary Factors on the Pharmacokinetics of ( 58 ) Fe - labeled Hemin After Oral Administration in Normal Rats and the Iron - deficient Rats .", "entity": [{"entity": "( 58 ) Fe", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "Hemin", "entity_type": "Chemical", "pos": [74, 79]}, {"entity": "Iron", "entity_type": "Chemical", "pos": [129, 133]}], "task": "NER"}
{"text": "Hemin , iron ( III ) protoporphyrin chloride ( IX ) , as a stable form of heme iron , has been used in iron absorption studies .", "entity": [{"entity": "Hemin", "entity_type": "Chemical", "pos": [0, 5]}, {"entity": "iron ( III ) protoporphyrin chloride ( IX )", "entity_type": "Chemical", "pos": [8, 51]}, {"entity": "heme", "entity_type": "Chemical", "pos": [74, 78]}, {"entity": "iron", "entity_type": "Chemical", "pos": [79, 83]}, {"entity": "iron", "entity_type": "Chemical", "pos": [103, 107]}], "task": "NER"}
{"text": "The aim of the present study was to elucidate the influences of body iron status and three dietary factors ( green tea extract , ascorbic acid , and calcium ) on the pharmacokinetics of hemin using stable isotope labeling methods followed by ICP - MS measurement .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [69, 73]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [129, 142]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [149, 156]}, {"entity": "hemin", "entity_type": "Chemical", "pos": [186, 191]}], "task": "NER"}
{"text": "In this study , a rapid , sensitive , and specific ICP - MS method for the determination of ( 58 ) Fe originating from hemin in rat plasma was developed and a rat model of iron deficiency anemia was established .", "entity": [{"entity": "( 58 ) Fe", "entity_type": "Chemical", "pos": [92, 101]}, {"entity": "hemin", "entity_type": "Chemical", "pos": [119, 124]}, {"entity": "iron", "entity_type": "Chemical", "pos": [172, 176]}], "task": "NER"}
{"text": "It was found that hemin iron absorption increased significantly under iron deficiency anemia status , with AUC0 - t and AUC0 - infinity showing significant increase in anemic rats compared to normal ones .", "entity": [{"entity": "hemin", "entity_type": "Chemical", "pos": [18, 23]}, {"entity": "iron", "entity_type": "Chemical", "pos": [24, 28]}, {"entity": "iron", "entity_type": "Chemical", "pos": [70, 74]}], "task": "NER"}
{"text": "Green tea extract strongly inhibited hemin iron absorption in both normal rats and iron - deficient rats .", "entity": [{"entity": "hemin", "entity_type": "Chemical", "pos": [37, 42]}, {"entity": "iron", "entity_type": "Chemical", "pos": [43, 47]}, {"entity": "iron", "entity_type": "Chemical", "pos": [83, 87]}], "task": "NER"}
{"text": "In normal rats administered with green tea extract , C max resulted significantly reduced , whereas in anemic rats administered with green tea extract both AUC0 - t and AUC0 - infinity were reduced .", "entity": [], "task": "NER"}
{"text": "On the other hand , ascorbic acid significantly affected hemin iron absorption only in iron - deficient rats , in which C max showed a significant increase .", "entity": [{"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [20, 33]}, {"entity": "hemin", "entity_type": "Chemical", "pos": [57, 62]}, {"entity": "iron", "entity_type": "Chemical", "pos": [63, 67]}, {"entity": "iron", "entity_type": "Chemical", "pos": [87, 91]}], "task": "NER"}
{"text": "Interestingly , calcium slowed down the hemin iron absorption rate in normal rats , MRT0 - t being significantly different in calcium - treated animals compared to untreated ones .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [16, 23]}, {"entity": "hemin", "entity_type": "Chemical", "pos": [40, 45]}, {"entity": "iron", "entity_type": "Chemical", "pos": [46, 50]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "This trend also appeared in the iron - deficient group but it did not reach statistical significance .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "Our data suggest that the mechanism of hemin iron absorption is regulated by body iron status and dietary factors can influence hemin iron absorption to varying degrees .", "entity": [{"entity": "hemin", "entity_type": "Chemical", "pos": [39, 44]}, {"entity": "iron", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "iron", "entity_type": "Chemical", "pos": [82, 86]}, {"entity": "hemin", "entity_type": "Chemical", "pos": [128, 133]}, {"entity": "iron", "entity_type": "Chemical", "pos": [134, 138]}], "task": "NER"}
{"text": "Moreover , these results may also have general implication in the iron deficiency treatment with iron supplements and fortification of foods .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [66, 70]}, {"entity": "iron", "entity_type": "Chemical", "pos": [97, 101]}], "task": "NER"}
{"text": "Biocatalytic and structural properties of a highly engineered halohydrin dehalogenase .", "entity": [{"entity": "halohydrin", "entity_type": "Chemical", "pos": [62, 72]}], "task": "NER"}
{"text": "Two highly engineered halohydrin dehalogenase variants were characterized in terms of their performance in dehalogenation and epoxide cyanolysis reactions .", "entity": [{"entity": "halohydrin", "entity_type": "Chemical", "pos": [22, 32]}, {"entity": "epoxide", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Both enzyme variants outperformed the wild - type enzyme in the cyanolysis of ethyl ( S ) - 3 , 4 - epoxybutyrate , a conversion yielding ethyl ( R ) - 4 - cyano - 3 - hydroxybutyrate , an important chiral building block for statin synthesis .", "entity": [{"entity": "ethyl ( S ) - 3 , 4 - epoxybutyrate", "entity_type": "Chemical", "pos": [78, 113]}, {"entity": "ethyl ( R ) - 4 - cyano - 3 - hydroxybutyrate", "entity_type": "Chemical", "pos": [138, 183]}], "task": "NER"}
{"text": "One of the enzyme variants , HheC2360 , displayed catalytic rates for this cyanolysis reaction enhanced up to tenfold .", "entity": [], "task": "NER"}
{"text": "Furthermore , the enantioselectivity of this variant was the opposite of that of the wild - type enzyme , both for dehalogenation and for cyanolysis reactions .", "entity": [], "task": "NER"}
{"text": "The 37 - fold mutant HheC2360 showed an increase in thermal stability of 8 degrees C relative to the wild - type enzyme .", "entity": [], "task": "NER"}
{"text": "Crystal structures of this enzyme were elucidated with chloride and ethyl ( S ) - 3 , 4 - epoxybutyrate or with ethyl ( R ) - 4 - cyano - 3 - hydroxybutyrate bound in the active site .", "entity": [{"entity": "chloride", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "ethyl ( S ) - 3 , 4 - epoxybutyrate", "entity_type": "Chemical", "pos": [68, 103]}, {"entity": "ethyl ( R ) - 4 - cyano - 3 - hydroxybutyrate", "entity_type": "Chemical", "pos": [112, 157]}], "task": "NER"}
{"text": "The observed increase in temperature stability was explained in terms of a substantial increase in buried surface area relative to the wild - type HheC , together with enhanced interfacial interactions between the subunits that form the tetramer .", "entity": [], "task": "NER"}
{"text": "The structures also revealed that the substrate binding pocket was modified both by substitutions and by backbone movements in loops surrounding the active site .", "entity": [], "task": "NER"}
{"text": "The observed changes in the mutant structures are partly governed by coupled mutations , some of which are necessary to remove steric clashes or to allow backbone movements to occur .", "entity": [], "task": "NER"}
{"text": "The importance of interactions between substitutions suggests that efficient directed evolution strategies should allow for compensating and synergistic mutations during library design .", "entity": [], "task": "NER"}
{"text": "RNA global alignment in the joint sequence - structure space using elastic shape analysis .", "entity": [], "task": "NER"}
{"text": "The functions of RNAs , like proteins , are determined by their structures , which , in turn , are determined by their sequences .", "entity": [], "task": "NER"}
{"text": "Comparison / alignment of RNA molecules provides an effective means to predict their functions and understand their evolutionary relationships .", "entity": [], "task": "NER"}
{"text": "For RNA sequence alignment , most methods developed for protein and DNA sequence alignment can be directly applied .", "entity": [], "task": "NER"}
{"text": "RNA 3 - dimensional structure alignment , on the other hand , tends to be more difficult than protein structure alignment due to the lack of regular secondary structures as observed in proteins .", "entity": [], "task": "NER"}
{"text": "Most of the existing RNA 3D structure alignment methods use only the backbone geometry and ignore the sequence information .", "entity": [], "task": "NER"}
{"text": "Using both the sequence and backbone geometry information in RNA alignment may not only produce more accurate classification , but also deepen our understanding of the sequence - structure - function relationship of RNA molecules .", "entity": [], "task": "NER"}
{"text": "In this study , we developed a new RNA alignment method based on elastic shape analysis ( ESA ) .", "entity": [], "task": "NER"}
{"text": "ESA treats RNA structures as three dimensional curves with sequence information encoded on additional dimensions so that the alignment can be performed in the joint sequence - structure space .", "entity": [], "task": "NER"}
{"text": "The similarity between two RNA molecules is quantified by a formal distance , geodesic distance .", "entity": [], "task": "NER"}
{"text": "Based on ESA , a rigorous mathematical framework can be built for RNA structure comparison .", "entity": [], "task": "NER"}
{"text": "Means and covariances of full structures can be defined and computed , and probability distributions on spaces of such structures can be constructed for a group of RNAs .", "entity": [], "task": "NER"}
{"text": "Our method was further applied to predict functions of RNA molecules and showed superior performance compared with previous methods when tested on benchmark datasets .", "entity": [], "task": "NER"}
{"text": "The programs are available at http : / / stat . fsu . edu / ~ jinfeng / ESA . html .", "entity": [], "task": "NER"}
{"text": "Fine Tuning of the Structure of Pt - Cu Alloy Nanocrystals by Glycine - Mediated Sequential Reduction Kinetics .", "entity": [{"entity": "Pt - Cu", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "Glycine", "entity_type": "Chemical", "pos": [62, 69]}], "task": "NER"}
{"text": "Uniform Pt - Cu alloy nanocrystals in the shape of dendrite , , yolk - cage , and box structures are prepared via a facile wet - chemical reduction route in which glycine is demonstrated to alter the reduction kinetics of metal cations , critical to the morphology of the obtained product .", "entity": [{"entity": "Pt - Cu", "entity_type": "Chemical", "pos": [8, 15]}, {"entity": "glycine", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "These alloy nanocrystals exhibit superior specific activity and stability in the electro - oxidation of methanol .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Relationship between serum thyrotropin levels and intrarenal hemodynamic parameters in euthyroid subjects .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : Low thyroid function may be associated with a reduced glomerular filtration rate ( GFR ) calculated on the basis of creatinine metabolism .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [128, 138]}], "task": "NER"}
{"text": "Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney .", "entity": [{"entity": "Thyroid hormone", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [39, 49]}], "task": "NER"}
{"text": "The goal of the study was to evaluate this possibility by assessment of the inulin - based GFR and to examine the mechanism underlying the reduction of GFR .", "entity": [], "task": "NER"}
{"text": "PATIENTS AND METHODS : Renal and glomerular hemodynamics were assessed by simultaneous measurements of plasma clearance of para - aminohippurate ( CPAH ) and inulin ( Cin ) in 26 patients with serum creatinine < 1 . 00 mg / dl and without thyroid disease .", "entity": [{"entity": "para - aminohippurate", "entity_type": "Chemical", "pos": [123, 144]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [199, 209]}], "task": "NER"}
{"text": "All subjects were normotensive with or without antihypertensive treatment and were kept in a sodium - replete state .", "entity": [{"entity": "sodium", "entity_type": "Chemical", "pos": [93, 99]}], "task": "NER"}
{"text": "Renal and glomerular hemodynamics were calculated using Gomez ` s formulae .", "entity": [], "task": "NER"}
{"text": "RESULTS : Serum thyroid stimulating hormone ( TSH ) , including within the normal range ( 0 . 69 - 4 . 30 mu IU / ml ) , was positively correlated with vascular resistance at the afferent arteriole ( Ra ) ( r = 0 . 609 , p = 0 . 0010 ) , but not at the efferent arteriole ( Re ) .", "entity": [], "task": "NER"}
{"text": "Serum TSH was significantly and negatively correlated with renal plasma flow ( RPF ) , renal blood flow ( RBF ) , and glomerular filtration rate ( GFR ) ( r = - 0 . 456 , p = 0 . 0192 ; r = - 0 . 438 , p = 0 . 0252 ; r = - 0 . 505 , p = 0 . 0086 , respectively ) .", "entity": [], "task": "NER"}
{"text": "In multiple regression analysis , serum TSH was significantly positively associated with Ra after adjustment for age and mean blood pressure .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : These findings suggest that low thyroid function , even within the normal range , is associated with reduced RPF , RBF and GFR , which might be caused by a preferential increase of Ra .", "entity": [], "task": "NER"}
{"text": "Deformation of an elastic capsule in a rectangular microfluidic channel .", "entity": [], "task": "NER"}
{"text": "In the present study we investigate computationally the deformation of an elastic capsule in a rectangular microfluidic channel and compare it with that of a droplet .", "entity": [], "task": "NER"}
{"text": "In contrast to the bullet or parachute shape in a square or cylindrical channel where the capsule extends along the flow direction , in a rectangular channel the capsule extends mainly along the less - confined lateral direction of the channel cross - section ( i . e . the channel width ) , obtaining a pebble - like shape .", "entity": [], "task": "NER"}
{"text": "The different shape evolution in these two types of solid channels results from the different tension development on the capsule membrane required for interfacial stability .", "entity": [], "task": "NER"}
{"text": "Furthermore , in asymmetric channel flows , capsules show a different deformation compared to droplets with constant surface tension ( which extend mainly along the flow direction ) and to vesicles which extend along the more - confined channel height .", "entity": [], "task": "NER"}
{"text": "Therefore , our study highlights the different stability dynamics associated with these three types of interfaces .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that the erythrocyte deformation in asymmetric vessels ( which is similar to that of capsules ) results from the erythrocyte ' s inner spectrin skeleton rather than from its outer lipid bilayer .", "entity": [], "task": "NER"}
{"text": "Molecular - Beam Optical Stark and Zeeman Study of the [ 17 . 8 ] 0 ( + ) - X ( 1 ) Sigma ( + ) ( 0 , 0 ) Band System of AuF .", "entity": [{"entity": "AuF", "entity_type": "Chemical", "pos": [121, 124]}], "task": "NER"}
{"text": "The [ 17 . 8 ] 0 ( + ) - X ( 1 ) Sigma ( + ) ( 0 , 0 ) band of gold monofluoride , AuF , has been recorded at a resolution of 40 MHz both field free and in the presence of a static electric and magnetic field .", "entity": [{"entity": "gold monofluoride", "entity_type": "Chemical", "pos": [63, 80]}, {"entity": "AuF", "entity_type": "Chemical", "pos": [83, 86]}], "task": "NER"}
{"text": "The observed Stark shifts were analyzed to determine the permanent electric dipole moment , mu el , of 2 . 03 +/- 0 . 05 D and 4 . 13 +/- 0 . 02 D , for the [ 17 . 8 ] 0 ( + ) ( v = 0 ) and X ( 1 ) Sigma ( + ) ( v = 0 ) states , respectively .", "entity": [], "task": "NER"}
{"text": "The small magnetic tuning observed for the [ 17 . 8 ] 0 ( + ) ( v = 0 ) state is attributed to rotational and magnetic field mixing with the [ 17 . 7 ] 1 state and has been successfully modeled using an effective Hamiltonian for the ( 3 ) Pi state .", "entity": [], "task": "NER"}
{"text": "A comparison with the numerous published theoretical predictions is made .", "entity": [], "task": "NER"}
{"text": "Dynamic and Electronic Transport Properties of DNA Translocation through Graphene Nanopores .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [73, 81]}], "task": "NER"}
{"text": "Graphene layers have been targeted in the last years as excellent host materials for sensing a remarkable variety of gases and molecules .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Such sensing abilities can also benefit other important scientific fields such as medicine and biology .", "entity": [], "task": "NER"}
{"text": "This has automatically led scientists to probe graphene as a potential platform for sequencing DNA strands .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [47, 55]}], "task": "NER"}
{"text": "In this work , we use robust numerical tools to model the dynamic and electronic properties of molecular sensor devices composed of a graphene nanopore through which DNA molecules are driven by external electric fields .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "We performed molecular dynamic simulations to determine the relation between the intensity of the electric field and the translocation time spent by the DNA to pass through the pore .", "entity": [], "task": "NER"}
{"text": "Our results reveal that one can have extra control on the DNA passage when four additional graphene layers are deposited on the top of the main graphene platform containing the pore in a 2 x 2 grid arrangement .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [91, 99]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [144, 152]}], "task": "NER"}
{"text": "In addition to the dynamic analysis , we carried electronic transport calculations on realistic pore structures with diameters reaching nanometer scales .", "entity": [], "task": "NER"}
{"text": "The transmission obtained along the graphene sensor at the Fermi level is affected by the presence of the DNA .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "However , it is rather hard to distinguish the respective nucleobases .", "entity": [{"entity": "nucleobases", "entity_type": "Chemical", "pos": [58, 69]}], "task": "NER"}
{"text": "This scenario can be significantly altered when the transport is conducted away from the Fermi level of the graphene platform .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "Under an energy shift , we observed that the graphene pore manifests selectiveness toward DNA nucleobases .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [45, 53]}, {"entity": "nucleobases", "entity_type": "Chemical", "pos": [94, 105]}], "task": "NER"}
{"text": "The tail wagging the dog - regulation of lipid metabolism by protein kinase C .", "entity": [], "task": "NER"}
{"text": "Upon their discovery almost 40 years ago , isoforms of the lipid - activated protein kinase C ( PKC ) family were initially regarded only as downstream effectors of the second messengers calcium and diacylglycerol , undergoing activation upon phospholipid hydrolysis in response to acute stimuli .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [187, 194]}, {"entity": "diacylglycerol", "entity_type": "Chemical", "pos": [199, 213]}], "task": "NER"}
{"text": "Subsequently , several isoforms were found to be associated with the inhibitory effects of lipid over - supply on glucose homeostasis , especially the negative cross - talk with insulin signal transduction , observed upon accumulation of diacylglycerol in insulin target tissues .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [114, 121]}, {"entity": "diacylglycerol", "entity_type": "Chemical", "pos": [238, 252]}], "task": "NER"}
{"text": "The PKC family has therefore attracted much attention in diabetes and obesity research , because intracellular lipid accumulation is strongly correlated with defective insulin action and the development of type 2 diabetes .", "entity": [], "task": "NER"}
{"text": "Causal roles for various isoforms in the generation of insulin resistance have more recently been confirmed using PKC - deficient mice .", "entity": [], "task": "NER"}
{"text": "However , during characterization of these animals , it became increasingly evident that the enzymes play key roles in the modulation of lipid metabolism itself , and may control the supply of lipids between tissues such as adipose and liver .", "entity": [], "task": "NER"}
{"text": "Molecular studies have also demonstrated roles for PKC isoforms in several aspects of lipid metabolism , such as adipocyte differentiation and hepatic lipogenesis .", "entity": [], "task": "NER"}
{"text": "While the precise mechanisms involved , especially the identities of protein substrates , are still unclear , the emerging picture suggests that the currently held view of the contribution of PKC isoforms to metabolism is an over - simplification .", "entity": [], "task": "NER"}
{"text": "Although PKCs may inhibit insulin signal transduction , these enzymes are not merely downstream effectors of lipid accumulation , but in fact control the fate of fatty acids , thus the tail wags the dog .", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [162, 173]}], "task": "NER"}
{"text": "Kappa - opioid receptor - selective dicarboxylic ester - derived salvinorin A ligands .", "entity": [{"entity": "dicarboxylic ester", "entity_type": "Chemical", "pos": [36, 54]}, {"entity": "salvinorin A", "entity_type": "Chemical", "pos": [65, 77]}], "task": "NER"}
{"text": "Salvinorin A , the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective kappa - opioid receptor agonist .", "entity": [{"entity": "Salvinorin A", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "To better understand the ligand - receptor interactions , a series of dicarboxylic ester - type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at kappa - , delta - and mu - opioid receptors .", "entity": [{"entity": "dicarboxylic ester", "entity_type": "Chemical", "pos": [70, 88]}, {"entity": "salvinorin A", "entity_type": "Chemical", "pos": [99, 111]}], "task": "NER"}
{"text": "Most of the analogues show high affinity to the kappa - opioid receptor .", "entity": [], "task": "NER"}
{"text": "Methyl malonyl derivative 4 shows the highest binding affinity ( Ki = 2nM ) , analogues 5 , 7 , and 14 exhibit significant affinity for the kappa - receptor ( Ki = 21 , 36 and 39nM ) .", "entity": [{"entity": "Methyl malonyl", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Acute and chronic interference with BDNF / TrkB - signaling impair LTP selectively at mossy fiber synapses in the CA3 region of mouse hippocampus .", "entity": [], "task": "NER"}
{"text": "Brain - derived neurotrophic factor ( BDNF ) signaling via TrkB crucially regulates synaptic plasticity in the brain .", "entity": [], "task": "NER"}
{"text": "Although BDNF is abundant at hippocampal mossy fiber ( MF ) synapses , which critically contribute to hippocampus dependent memory , its role in MF synaptic plasticity ( long - term potentiation , LTP ) remained largely unclear .", "entity": [], "task": "NER"}
{"text": "Using field potential recordings in CA3 of adult heterozygous BDNF knockout ( ko , BDNF + / - ) mice we observed impaired ( ~ 50 % ) NMDAR - independent MF - LTP .", "entity": [], "task": "NER"}
{"text": "In contrast to MF synapses , LTP at neighboring associative / commissural ( A / C ) fiber synapses remained unaffected .", "entity": [], "task": "NER"}
{"text": "To exclude that impaired MF - LTP in BDNF + / - mice was due to developmental changes in response to chronically reduced BDNF levels , and to prove the importance of acute availability of BDNF in MF - LTP , we also tested effects of acute interference with BDNF / TrkB signaling .", "entity": [], "task": "NER"}
{"text": "Inhibition of TrkB tyrosine kinase signaling with k252a , or with the selective BDNF scavenger TrkB - Fc , both inhibited MF - LTP to the same extent as observed in BDNF + / - mice .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [19, 27]}], "task": "NER"}
{"text": "Basal synaptic transmission , short - term plasticity , and synaptic fatigue during LTP induction were not significantly altered by treatment with k252a or TrkB - Fc , or by chronic BDNF reduction in BDNF + / - mice .", "entity": [], "task": "NER"}
{"text": "Since the acute interference with BDNF - signaling did not completely block MF - LTP , our results provide evidence that an additional mechanism besides BDNF induced TrkB signaling contributes to this type of LTP .", "entity": [], "task": "NER"}
{"text": "Our results prove for the first time a mechanistic action of acute BDNF / TrkB signaling in presynaptic expression of MF - LTP in adult hippocampus .", "entity": [], "task": "NER"}
{"text": "Genetics of diabetes - Are we missing the genes or the disease ?", "entity": [], "task": "NER"}
{"text": "Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion , insulin action , or both .", "entity": [], "task": "NER"}
{"text": "The chronic hyperglycemia of diabetes is associated with long - term damage , dysfunction , and failure of different organs , especially the eyes , kidneys , nerves , heart , and blood vessels .", "entity": [], "task": "NER"}
{"text": "Several pathogenic processes are involved in the development of diabetes .", "entity": [], "task": "NER"}
{"text": "These range from autoimmune destruction of the beta - cells of the pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action ( American Diabetes Association , 2011 ) .", "entity": [], "task": "NER"}
{"text": "The vast majority of cases of diabetes fall into two broad categories .", "entity": [], "task": "NER"}
{"text": "In type 1 diabetes ( T1D ) , the cause is an absolute deficiency of insulin secretion , whereas in type 2 diabetes ( T2D ) , the cause is a combination of resistance to insulin action and an inadequate compensatory insulin secretory response .", "entity": [], "task": "NER"}
{"text": "However , the subdivision into two main categories represents a simplification of the real situation , and research during the recent years has shown that the disease is much more heterogeneous than a simple subdivision into two major subtypes assumes .", "entity": [], "task": "NER"}
{"text": "Worldwide prevalence figures estimate that there are 280 million diabetic patients in 2011 and more than 500 million in 2030 ( http : / / www . diabetesatlas . org / ) .", "entity": [], "task": "NER"}
{"text": "In Europe , about 6 - 8 % of the population suffer from diabetes , of them about 90 % has T2D and 10 % T1D , thereby making T2D to the fastest increasing disease in Europe and worldwide .", "entity": [], "task": "NER"}
{"text": "This epidemic has been ascribed to a collision between the genes and the environment .", "entity": [], "task": "NER"}
{"text": "While our knowledge about the genes is clearly better for T1D than for T2D given the strong contribution of variation in the HLA region to the risk of T1D , the opposite is the case for T2D , where our knowledge about the environmental triggers ( obesity , lack of exercise ) is much better than the understanding of the underlying genetic causes .", "entity": [], "task": "NER"}
{"text": "This lack of knowledge about the underlying genetic causes of diabetes is often referred to as missing heritability ( Manolio et al . , 2009 ) which exceeds 80 % for T2D but less than 25 % for T1D .", "entity": [], "task": "NER"}
{"text": "In the following review , we will discuss potential sources of this missing heritability which also includes the possibility that our definition of diabetes and its subgroups is imprecise and thereby making the identification of genetic causes difficult .", "entity": [], "task": "NER"}
{"text": "Structure - activity relationships of hybrid annonaceous acetogenins : Powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines .", "entity": [{"entity": "annonaceous acetogenins", "entity_type": "Chemical", "pos": [45, 68]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [169, 175]}, {"entity": "THF", "entity_type": "Chemical", "pos": [190, 193]}], "task": "NER"}
{"text": "Five novel hybrid molecules of annonaceous acetogenins and insecticides targeting mitochondrial complex I were synthesized and their growth inhibitory activities against 39 human cancer cell lines were investigated .", "entity": [{"entity": "annonaceous acetogenins", "entity_type": "Chemical", "pos": [31, 54]}], "task": "NER"}
{"text": "It was revealed that the connecting group between the N - methylpyrazole part and the hydrophobic alkyl chain bearing the THF ring influenced their biological activities significantly .", "entity": [{"entity": "N - methylpyrazole", "entity_type": "Chemical", "pos": [54, 72]}, {"entity": "alkyl", "entity_type": "Chemical", "pos": [98, 103]}, {"entity": "THF", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "Amide - connected analog 2 , in particular , showed selective and very potent activity ( < 10 nM ) against some cancer cell lines .", "entity": [{"entity": "Amide", "entity_type": "Chemical", "pos": [0, 5]}], "task": "NER"}
{"text": "Prevalence and natural history of Graves ' orbitopathy in the XXI century .", "entity": [], "task": "NER"}
{"text": "Graves ' orbitopathy ( GO ) is an autoimmune disorder and the main extrathyroidal expression of Graves ' disease .", "entity": [], "task": "NER"}
{"text": "There is a spectrum of ocular involvement in Graves ' disease , from complete absence of symptoms and signs to sight - threatening conditions .", "entity": [], "task": "NER"}
{"text": "The prevalence of GO varies in different published series of Graves ' patients , due to confounding factors ( new diagnosis vs . long - lasting disease , way of defining and assessing ocular involvement , treatment of hyperthyroidism with potentially GO - modifying treatments , such as radioiodine ) .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [287, 298]}], "task": "NER"}
{"text": "Recent studies , however , suggest that most Graves ' patients have mild or no GO at presentation , while moderate - to - severe GO is rare , and sight - threatening GO ( mostly due to dysthyroid optic neuropathy ) is exceptional in non - tertiary referral centers .", "entity": [], "task": "NER"}
{"text": "The natural course of GO is incompletely defined , particularly in patients with moderate - to12 severe GO , because these patients require prompt and disease - modifying therapies for orbital disease .", "entity": [], "task": "NER"}
{"text": "In patients with mild GO at presentation , progression to severe forms is rare , while partial or complete remission is frequent .", "entity": [], "task": "NER"}
{"text": "Progression of preexisting GO or de novo occurrence of GO is more likely in smokers .", "entity": [], "task": "NER"}
{"text": "There seems to be a trend towards a decline in progression of GO , possibly due to a better control of risk factors ( cigarette smoking , thyroid dysfunction , etc . ) and a closer interaction between endocrinologists and ophthalmologists allowing an improved integrated management of thyroid and orbital disease .", "entity": [], "task": "NER"}
{"text": "Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq . in rats .", "entity": [{"entity": "dichloromethane", "entity_type": "Chemical", "pos": [47, 62]}, {"entity": "piplartine", "entity_type": "Chemical", "pos": [76, 86]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Piper tuberculatum Jacq .", "entity": [], "task": "NER"}
{"text": "( Piperaceae ) is medicinally used as an analgesic and as a treatment for gastric complaints .", "entity": [], "task": "NER"}
{"text": "Thus , the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum ( DFPT ) and piplartine , a compound isolated from the DFPT , in rats .", "entity": [{"entity": "dichloromethane", "entity_type": "Chemical", "pos": [103, 118]}, {"entity": "piplartine", "entity_type": "Chemical", "pos": [176, 186]}], "task": "NER"}
{"text": "MATERIALS AND METHODS : Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione ( GSH ) levels were measured .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [102, 109]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [137, 148]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [151, 154]}], "task": "NER"}
{"text": "Mechanisms underlying the antisecretory action were studied through gastric H ( + ) , K ( + ) - ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats .", "entity": [{"entity": "H ( + )", "entity_type": "Chemical", "pos": [76, 83]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [86, 93]}], "task": "NER"}
{"text": "RESULTS : In the acute toxicity test the values of estimated LD50 for oral and intraperitoneal administration of DFPT were 1 . 6266 and 0 . 2684g / kg , respectively .", "entity": [], "task": "NER"}
{"text": "The DFPT ( ED50 = 29mg / kg , p . o . ) and piplartine ( 4 . 5mg / kg , p . o . ) promoted gastroprotection against acute lesions induced by ethanol , effect that could be related with the maintenance of GSH levels in the gastric mucosa .", "entity": [{"entity": "piplartine", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [141, 148]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [204, 207]}], "task": "NER"}
{"text": "However , only DFPT stimulated gastric mucus secretion .", "entity": [], "task": "NER"}
{"text": "In vitro , the DFPT and piplartine inhibited the H ( + ) , K ( + ) - ATPase activity and , in vivo DFPT and piplartine also reduced basal gastric acid secretion , as well as that stimulated by pentagastrin .", "entity": [{"entity": "piplartine", "entity_type": "Chemical", "pos": [24, 34]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [49, 56]}, {"entity": "K ( + )", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "piplartine", "entity_type": "Chemical", "pos": [108, 118]}, {"entity": "pentagastrin", "entity_type": "Chemical", "pos": [193, 205]}], "task": "NER"}
{"text": "CONCLUSIONS : These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels , as well as a reduction in gastric acid secretion through the gastrinergic pathway .", "entity": [{"entity": "piplatine", "entity_type": "Chemical", "pos": [54, 63]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "Emerging Transporters of Clinical Importance : An Update from the International Transporter Consortium .", "entity": [], "task": "NER"}
{"text": "The International Transporter Consortium ( ITC ) has described recently seven transporters of particular relevance for drug development ( Giacomini et al . , Nat . Rev . Drug Discov . 9 : 215 - 236 , 2010 ) .", "entity": [], "task": "NER"}
{"text": "Based on the second ITC transporter workshop in 2012 , we have identified additional transporters of emerging importance in pharmacokinetics , interference of drugs with transport of endogenous compounds and drug - drug interactions in humans .", "entity": [], "task": "NER"}
{"text": "The multidrug and toxin extrusion proteins ( MATEs , gene symbol SLC47A ) mediate excretion of organic cations into bile and urine .", "entity": [], "task": "NER"}
{"text": "MATEs are important in renal drug - drug interactions .", "entity": [], "task": "NER"}
{"text": "Multidrug resistance proteins ( MRPs or ABCCs ) are drug and conjugate efflux pumps , and impaired activity of MRP2 results in conjugated hyperbilirubinemia .", "entity": [], "task": "NER"}
{"text": "The bile salt export pump ( BSEP or ABCB11 ) prevents accumulation of toxic bile salt concentrations in hepatocytes , and BSEP inhibition or deficiency may cause cholestasis and liver injury .", "entity": [{"entity": "bile salt", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "bile salt", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Additionally , examples are presented on the roles of nucleoside and peptide transporters in drug targeting and disposition . Clinical Pharmacology & Therapeutics ( 2013 ) ; accepted article preview online 8 April 2013 doi : 10 . 1038 / clpt . 2013 . 74 .", "entity": [{"entity": "nucleoside", "entity_type": "Chemical", "pos": [54, 64]}], "task": "NER"}
{"text": "Biomarkers for Smoking Cessation .", "entity": [], "task": "NER"}
{"text": "One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers .", "entity": [], "task": "NER"}
{"text": "This review focuses on putative diagnostic , pharmacodynamic , and predictive biomarkers for smoking cessation .", "entity": [], "task": "NER"}
{"text": "These types of biomarkers may be used to more accurately diagnose a disease , personalize treatment , identify novel targets for drug discovery , and enhance the efficiency of drug development .", "entity": [], "task": "NER"}
{"text": "Promising biomarkers are presented across a range of approaches including metabolism , genetics , and neuroimaging .", "entity": [], "task": "NER"}
{"text": "A preclinical viewpoint is also offered , as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification . Clinical Pharmacology & Therapeutics ( 2013 ) ; advance online publication 8 May 2013 . doi : 10 . 1038 / clpt . 2013 . 57 .", "entity": [], "task": "NER"}
{"text": "The effects of water molecules on the electronic and structural properties of peptide nanotubes .", "entity": [], "task": "NER"}
{"text": "The self - assembly of short amino acid chains appears to be one of the most promising strategies for the fabrication of nanostructures .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "Their solubility in water and the possibility of chemical modification by targeting the amino or carboxyl terminus give peptide - based nanostructures several advantages over carbon nanotube nanostructures .", "entity": [{"entity": "amino", "entity_type": "Chemical", "pos": [88, 93]}, {"entity": "carboxyl", "entity_type": "Chemical", "pos": [97, 105]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [175, 181]}], "task": "NER"}
{"text": "However , because these systems are synthesized in aqueous solution , a deeper understanding is needed on the effects of water especially with respect to the electronic , structural and transport properties .", "entity": [], "task": "NER"}
{"text": "In this work , the electronic properties of l - diphenylalanine nanotubes ( FF - NTs ) have been studied using the Self - Consistent Charge Density - Functional - based Tight - Binding method augmented with dispersion interaction .", "entity": [{"entity": "l - diphenylalanine", "entity_type": "Chemical", "pos": [44, 63]}], "task": "NER"}
{"text": "The presence of water molecules in the central hydrophilic channel and their interaction with the nanostructures are addressed .", "entity": [], "task": "NER"}
{"text": "We demonstrate that the presence of water leads to significant changes in the electronic properties of these systems decreasing the band gap which can lead to an increase in the hopping probability and the conductivity .", "entity": [], "task": "NER"}
{"text": "Low allopurinol doses are sufficient to optimize azathioprine therapy in inflammatory bowel disease patients with inadequate thiopurine metabolite concentrations .", "entity": [{"entity": "allopurinol", "entity_type": "Chemical", "pos": [4, 15]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [49, 61]}, {"entity": "thiopurine", "entity_type": "Chemical", "pos": [125, 135]}], "task": "NER"}
{"text": "PURPOSE : Recent studies in patients with inflammatory bowel diseases ( IBD ) on thiopurine therapy suggest that too low 6 - thioguanine nucleotide concentrations ( 6 - TGN ) and too high methylmercaptopurine nucleotide concentrations ( MMPN ) can be reversed by a combination therapy of allopurinol and low - dose thiopurines .", "entity": [{"entity": "thiopurine", "entity_type": "Chemical", "pos": [81, 91]}, {"entity": "6 - thioguanine nucleotide", "entity_type": "Chemical", "pos": [121, 147]}, {"entity": "6 - TGN", "entity_type": "Chemical", "pos": [165, 172]}, {"entity": "methylmercaptopurine nucleotide", "entity_type": "Chemical", "pos": [188, 219]}, {"entity": "MMPN", "entity_type": "Chemical", "pos": [237, 241]}, {"entity": "allopurinol", "entity_type": "Chemical", "pos": [288, 299]}, {"entity": "thiopurines", "entity_type": "Chemical", "pos": [315, 326]}], "task": "NER"}
{"text": "To date , however , optimal dosing has not been established .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to evaluate the minimal allopurinol doses necessary to achieve adequate 6 - TGN concentrations in combination with low - dose azathioprine .", "entity": [{"entity": "allopurinol", "entity_type": "Chemical", "pos": [50, 61]}, {"entity": "6 - TGN", "entity_type": "Chemical", "pos": [98, 105]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [152, 164]}], "task": "NER"}
{"text": "METHODS : A stepwise dose - escalation of allopurinol was performed in 11 azathioprine - pretreated IBD patients with inadequately low 6 - TGN concentrations ( < 235 pmol / 8 x 10 ( 8 ) erythrocytes ) and / or elevated MMPN concentrations ( > 5 , 000 pmol / 8 x 10 ( 8 ) erythrocytes ) and / or elevated liver enzymes ( alanine aminotransferase and / or aspartate aminotransferase levels one - to threefold the upper limit of normal ) .", "entity": [{"entity": "allopurinol", "entity_type": "Chemical", "pos": [42, 53]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [74, 86]}, {"entity": "6 - TGN", "entity_type": "Chemical", "pos": [135, 142]}, {"entity": "MMPN", "entity_type": "Chemical", "pos": [219, 223]}, {"entity": "alanine", "entity_type": "Chemical", "pos": [320, 327]}, {"entity": "aspartate", "entity_type": "Chemical", "pos": [354, 363]}], "task": "NER"}
{"text": "Six patients were recruited into an open study , and five were treated in the context of an individualized therapeutic approach .", "entity": [], "task": "NER"}
{"text": "Adverse effects , azathioprine metabolites , liver enzymes and whole blood counts were monitored two to three times per month .", "entity": [{"entity": "azathioprine", "entity_type": "Chemical", "pos": [18, 30]}], "task": "NER"}
{"text": "RESULTS : Adequate 6 - TGN concentrations were achieved with a combination of 25 mg allopurinol and 50 mg azathioprine in one patient and with 50 mg allopurinol and 50 mg azathioprine in nine patients .", "entity": [{"entity": "6 - TGN", "entity_type": "Chemical", "pos": [19, 26]}, {"entity": "allopurinol", "entity_type": "Chemical", "pos": [84, 95]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [106, 118]}, {"entity": "allopurinol", "entity_type": "Chemical", "pos": [149, 160]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [171, 183]}], "task": "NER"}
{"text": "Median 6 - TGN concentrations ( range ) were 336 ( 290 - 488 ) pmol / 8 x 10 ( 8 ) erythrocytes after an 8 - week - long intake of the final dose combination .", "entity": [{"entity": "6 - TGN", "entity_type": "Chemical", "pos": [7, 14]}], "task": "NER"}
{"text": "One patient dropped out due to nausea after the first intake .", "entity": [], "task": "NER"}
{"text": "MMPN concentrations and liver enzymes normalized immediately in all affected patients .", "entity": [{"entity": "MMPN", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "All patients finishing the dose - escalation regimen tolerated the treatment without toxicity .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Combination therapy with only 50 mg allopurinol and 50 mg azathioprine daily is sufficient , efficacious and safe in most IBD patients with inadequate thiopurine metabolite concentrations to optimize azathioprine - based IBD therapy .", "entity": [{"entity": "allopurinol", "entity_type": "Chemical", "pos": [50, 61]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [72, 84]}, {"entity": "thiopurine", "entity_type": "Chemical", "pos": [165, 175]}, {"entity": "azathioprine", "entity_type": "Chemical", "pos": [214, 226]}], "task": "NER"}
{"text": "Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation .", "entity": [{"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [40, 56]}], "task": "NER"}
{"text": "PURPOSE : To build a population pharmacokinetic ( PK ) model of cyclophosphamide ( CY ) and its metabolite , 4 - hydroxycyclophosphamide ( HCY ) , in patients undergoing allogeneic haematopoietic stem cell transplantation ( HSCT ) and to identify covariates , including genetic polymorphisms , which affect CY and HCY PK parameters .", "entity": [{"entity": "cyclophosphamide", "entity_type": "Chemical", "pos": [64, 80]}, {"entity": "4 - hydroxycyclophosphamide", "entity_type": "Chemical", "pos": [109, 136]}, {"entity": "HCY", "entity_type": "Chemical", "pos": [139, 142]}, {"entity": "HCY", "entity_type": "Chemical", "pos": [314, 317]}], "task": "NER"}
{"text": "METHOD : The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011 .", "entity": [], "task": "NER"}
{"text": "Clinical characteristics and CY and HCY concentration data were collected for all patients , and ABCB1 , ABCC2 , GSTA1 , GSTM1 , GSTP1 , GSTT1 , CYP2B6 , CYP2C19 , and CYP3A5 genotyping was performed .", "entity": [{"entity": "HCY", "entity_type": "Chemical", "pos": [36, 39]}], "task": "NER"}
{"text": "A hypothetical enzyme compartment was conducted using the NONMEM program .", "entity": [], "task": "NER"}
{"text": "RESULTS : A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non - induced clearance ( CL UI ) and induced clearance ( CL I ) of CY , respectively .", "entity": [{"entity": "aspartate", "entity_type": "Chemical", "pos": [75, 84]}], "task": "NER"}
{"text": "The final estimate of the mean CL UI and CL I of CY was 15 . 5 and 0 . 683 L / h , respectively , and the mean volume of distribution ( V 1 ) of CY was 88 . 0 L .", "entity": [], "task": "NER"}
{"text": "The inter - individual variability for CL UI , CL I , and V 1 of CY was 52 . 8 , 200 , and 18 . 0 % , respectively .", "entity": [], "task": "NER"}
{"text": "Additionally , the CL UI of CY was significantly decreased to approximately 51 % in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild - type genotype ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "There were only three heterozygous GA variants of ABCC2 1249 in the study patients .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : The population PK model developed in this study implies an influence of genetic factors on the clearance of CY .", "entity": [], "task": "NER"}
{"text": "Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype .", "entity": [], "task": "NER"}
{"text": "Synthesis , characterization and organic field effect transistor performance of a diketopyrrolopyrrole - fluorenone copolymer .", "entity": [{"entity": "diketopyrrolopyrrole", "entity_type": "Chemical", "pos": [82, 102]}, {"entity": "fluorenone", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "A diketopyrrolopyrrole ( DPP ) with fluorenone ( FN ) based low band gap alternating copolymer ( PDPPT - alt - FN ) has been synthesized via Suzuki coupling .", "entity": [{"entity": "diketopyrrolopyrrole", "entity_type": "Chemical", "pos": [2, 22]}, {"entity": "DPP", "entity_type": "Chemical", "pos": [25, 28]}, {"entity": "fluorenone", "entity_type": "Chemical", "pos": [36, 46]}, {"entity": "PDPPT - alt - FN", "entity_type": "Chemical", "pos": [97, 113]}], "task": "NER"}
{"text": "PDPPT - alt - FN exhibits a deep HOMO level with a lower band gap .", "entity": [{"entity": "PDPPT - alt - FN", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Fabricated organic thin film transistors using PDPPT - alt - FN as a channel semiconductor show p - channel behaviour with the highest hole mobility of 0 . 083 cm ( 2 ) V ( - 1 ) s ( - 1 ) measured in air .", "entity": [{"entity": "PDPPT - alt - FN", "entity_type": "Chemical", "pos": [47, 63]}], "task": "NER"}
{"text": "Dermatoprotective effects of some plant extracts ( genus Ficus ) against experimentally induced toxicological insults in rabbits .", "entity": [], "task": "NER"}
{"text": "Aim : Present study was conducted to evaluate the dermatoprotective effects of plant extracts ( Ficus religiosa , Ficus benghalensis , and Ficus racemosa ) against known irritants such as sodium dodecyl sulfate ( SDS ) , atrazine , and petrol .", "entity": [{"entity": "sodium dodecyl sulfate", "entity_type": "Chemical", "pos": [188, 210]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [213, 216]}, {"entity": "atrazine", "entity_type": "Chemical", "pos": [221, 229]}], "task": "NER"}
{"text": "METHODS : The study was conducted in adult male rabbits .", "entity": [], "task": "NER"}
{"text": "Ethanol extracts of plants were obtained through Soxhlet .", "entity": [{"entity": "Ethanol", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "All irritants and Ficus extracts were topically applied to the backs of rabbits daily for 4 days , while pure ethanol served as control .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [110, 117]}], "task": "NER"}
{"text": "Skin was examined after 24 , 48 , and 96 h for erythema .", "entity": [], "task": "NER"}
{"text": "Skin biopsies were taken on 5th day for microscopic examination .", "entity": [], "task": "NER"}
{"text": "RESULTS : Erythema produced by irritants reduced significantly with the simultaneous application of Ficus extracts .", "entity": [], "task": "NER"}
{"text": "The mean +/- SEM epidermal thickness ( micrometer ) with SDS was 45 . 40 +/- 1 . 89 , F . religiosa + SDS was 18 . 60 +/- 0 . 51 , F . benghalensis + SDS was 18 . 40 +/- 0 . 25 , F . racemosa + SDS was 18 . 80 +/- 0 . 37 , and mixture of three Ficus species + SDS was 16 . 80 +/- 0 . 37 .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [57, 60]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [150, 153]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [194, 197]}, {"entity": "SDS", "entity_type": "Chemical", "pos": [260, 263]}], "task": "NER"}
{"text": "Similar findings were revealed after using plant extracts with atrazine and petrol .", "entity": [{"entity": "atrazine", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "The mean +/- SEM epidermal layer count for SDS was 3 . 60 +/- 0 . 25 , atrazine was 3 . 40 +/- 0 . 25 , petrol was 3 . 40 +/- 0 . 25 , and ethanol ( control ) was 1 . 00 +/- 0 . 20 .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [43, 46]}, {"entity": "atrazine", "entity_type": "Chemical", "pos": [71, 79]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [139, 146]}], "task": "NER"}
{"text": "This count reduced to 1 . 20 +/- 0 . 20 for three Ficus species + SDS , 1 . 40 +/- 0 . 25 for Ficus species + atrazine , and 1 . 40 +/- 0 . 25 for Ficus species + petrol .", "entity": [{"entity": "SDS", "entity_type": "Chemical", "pos": [66, 69]}, {"entity": "atrazine", "entity_type": "Chemical", "pos": [110, 118]}], "task": "NER"}
{"text": "CONCLUSION : Ficus species demonstrated the potential to block the dermatotoxic effects of topical irritants and could be used successfully to prevent skin toxicity .", "entity": [], "task": "NER"}
{"text": "Protective effects of caffeic acid phenethyl ester on dose - dependent intoxication of rats with paraquat .", "entity": [{"entity": "caffeic acid phenethyl ester", "entity_type": "Chemical", "pos": [22, 50]}, {"entity": "paraquat", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "PURPOSE : Paraquat ( PQ ; 1 , 1 ' dimethyl - bipyridilium 4 , 4 ' - dichloride ) , which is used extensively throughout the world , is highly toxic to humans .", "entity": [{"entity": "Paraquat", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "1 , 1 ' dimethyl - bipyridilium 4 , 4 ' - dichloride", "entity_type": "Chemical", "pos": [26, 78]}], "task": "NER"}
{"text": "We aimed to investigate the protective effects of different doses of caffeic acid phenethyl ester ( CAPE ) on PQ - intoxicated rats . Materials and methods : A total of 80 rats were divided into the following eight groups , comprising 10 rats in each group : group 1 : control ; group 2 : administered with CAPE ( 10 micro mol / kg ) ; group 3 : administered with 15 mg / kg PQ ( PQ15 group ) ; group 4 : administered with 30 mg / kg PQ ( PQ30 group ) ; group 5 : administered with 45 mg / kg PQ ( PQ45 group ) ; group 6 : administered with 15 mg / kg PQ + CAPE ; group 7 : administered with 30 mg / kg PQ + CAPE and group 8 : administered with 45 mg / kg PQ + CAPE .", "entity": [{"entity": "caffeic acid phenethyl ester", "entity_type": "Chemical", "pos": [69, 97]}, {"entity": "CAPE", "entity_type": "Chemical", "pos": [100, 104]}, {"entity": "CAPE", "entity_type": "Chemical", "pos": [307, 311]}, {"entity": "CAPE", "entity_type": "Chemical", "pos": [557, 561]}, {"entity": "CAPE", "entity_type": "Chemical", "pos": [608, 612]}, {"entity": "CAPE", "entity_type": "Chemical", "pos": [661, 665]}], "task": "NER"}
{"text": "Both PQ and CAPE were injected intraperitoneally .", "entity": [{"entity": "CAPE", "entity_type": "Chemical", "pos": [12, 16]}], "task": "NER"}
{"text": "Pancreatic tissue was examined with both haematoxylin and eosin and immunochemical staining .", "entity": [{"entity": "haematoxylin", "entity_type": "Chemical", "pos": [41, 53]}, {"entity": "eosin", "entity_type": "Chemical", "pos": [58, 63]}], "task": "NER"}
{"text": "RESULTS : The ratio of the immunohistochemical staining area to the total pancreatic area of the beta cells revealed that statistically significant differences were observed only between the PQ and PQ + CAPE groups ( p < 0 . 05 ) .", "entity": [{"entity": "CAPE", "entity_type": "Chemical", "pos": [203, 207]}], "task": "NER"}
{"text": "Discussion : The evaluation of the data suggests that CAPE can be used to prevent acute effects of PQ intoxication .", "entity": [{"entity": "CAPE", "entity_type": "Chemical", "pos": [54, 58]}], "task": "NER"}
{"text": "Modulation of carbon tetrachloride - induced nephrotoxicity in rats by n - hexane extract of Sonchus asper .", "entity": [{"entity": "carbon tetrachloride", "entity_type": "Chemical", "pos": [14, 34]}, {"entity": "n - hexane", "entity_type": "Chemical", "pos": [71, 81]}], "task": "NER"}
{"text": "Sonchus asper is traditionally used in the treatment of renal dysfunction .", "entity": [], "task": "NER"}
{"text": "In the present study , protective effects of S . asper against carbon tetrachloride ( CCl4 ) - induced nephrotoxicity of rats were determined .", "entity": [{"entity": "carbon tetrachloride", "entity_type": "Chemical", "pos": [63, 83]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [86, 90]}], "task": "NER"}
{"text": "In this study , 24 male albino rats ( 190 - 200 g ) were equally divided into four groups .", "entity": [], "task": "NER"}
{"text": "Group I ( control group ) was given saline ( 1 ml / kg body weight ( b . w . ) , 0 . 85 % NaCl ) and dimethyl sulfoxide ( 1 ml / kg b . w . ) ; group II was treated with CCl4 ( 1 ml / kg b . w . intraperitoneally ) ; groups III and IV were administered with CCl4 and after 48 h with S . asper n - hexane extract ( SHE ; 100 and 200 mg / kg b . w . ) .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [90, 94]}, {"entity": "dimethyl sulfoxide", "entity_type": "Chemical", "pos": [101, 119]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [170, 174]}, {"entity": "CCl4", "entity_type": "Chemical", "pos": [258, 262]}, {"entity": "n - hexane", "entity_type": "Chemical", "pos": [293, 303]}], "task": "NER"}
{"text": "All the treatments were given twice a week for 4 weeks .", "entity": [], "task": "NER"}
{"text": "The results revealed that CCl4 - induced oxidative stress as evidenced by the significant depletion of antioxidant enzymes , namely , superoxide dismutase , catalase , peroxidase , glutathione - S - transferase , glutathione peroxidase , glutathione reductase , and glutathione contents , while increased lipid peroxidation ( thiobarbituric acid - reactive substances contents ) .", "entity": [{"entity": "CCl4", "entity_type": "Chemical", "pos": [26, 30]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [134, 144]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [181, 192]}, {"entity": "S", "entity_type": "Chemical", "pos": [195, 196]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [213, 224]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [238, 249]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [266, 277]}, {"entity": "thiobarbituric acid", "entity_type": "Chemical", "pos": [326, 345]}], "task": "NER"}
{"text": "Administration of SHE significantly ameliorated ( p < 0 . 01 ) the activity of antioxidant enzymes and reduced lipid peroxides .", "entity": [], "task": "NER"}
{"text": "Coadministration revealed that S . asper extract can protect the kidney against CCl4 - mediated oxidative damage by restoring the activity of antioxidant enzyme , due to the presence of plant bioactive constituents .", "entity": [{"entity": "CCl4", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "Ecosystem services and the protection , restoration , and management of ecosystems exposed to chemical stressors .", "entity": [], "task": "NER"}
{"text": "Ecosystem services - the benefits people obtain from ecosystem structures and processes - are essential for human survival and well - being .", "entity": [], "task": "NER"}
{"text": "Chemicals are also an essential component of modern life ; however , they may cause adverse ecological effects and reduce ecosystem service provision .", "entity": [], "task": "NER"}
{"text": "Environmental policy makers are increasingly adopting the ecosystem services concept , but applying this approach to the protection , restoration , and management of ecosystems requires the development of new understanding , tools , and frameworks .", "entity": [], "task": "NER"}
{"text": "There is an urgent need to understand and predict the effect of single and multiple stressors on ecosystem service delivery across different spatial scales ( local to global ) , to develop indicators that can be used to quantify and map services and identify synergies and trade - offs between them , to establish protection goals and restoration targets defined in terms of the types and levels of service delivery required , and to develop approaches for the assessment and management of chemical risk to ecosystem services that consider the whole life cycle of products and processes .", "entity": [], "task": "NER"}
{"text": "These are major research challenges for the environmental science community in general and for ecotoxicologists and risk assessors in particular .", "entity": [], "task": "NER"}
{"text": "2013 ; 32 : 974 - 983 .", "entity": [], "task": "NER"}
{"text": "Hypoglycemia and diabetes : a report of a workgroup of the american diabetes association and the endocrine society .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice .", "entity": [], "task": "NER"}
{"text": "PARTICIPANTS Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair , who is a member of both , to participate in a planning conference call and a 2 - day meeting that was also attended by staff from both organizations .", "entity": [], "task": "NER"}
{"text": "Subsequent communications took place via e - mail and phone calls .", "entity": [], "task": "NER"}
{"text": "The writing group consisted of those invitees who participated in the writing of the manuscript .", "entity": [], "task": "NER"}
{"text": "The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA , LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi .", "entity": [], "task": "NER"}
{"text": "The sponsors had no input into the development of or content of the report .", "entity": [], "task": "NER"}
{"text": "EVIDENCE The writing group considered data from recent clinical trials and other studies to update the prior workgroup report .", "entity": [], "task": "NER"}
{"text": "Unpublished data were not used .", "entity": [], "task": "NER"}
{"text": "Expert opinion was used to develop some conclusions .", "entity": [], "task": "NER"}
{"text": "CONSENSUS PROCESS Consensus was achieved by group discussion during conference calls and face - to - face meetings , as well as by iterative revisions of the written document .", "entity": [], "task": "NER"}
{"text": "The document was reviewed and approved by the American Diabetes Association ' s Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society ' s Clinical Affairs Core Committee in October 2012 and by Council in November 2012 .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes , reviewed the implications of hypoglycemia on both short - and long - term outcomes , considered the implications of hypoglycemia on treatment outcomes , presented strategies to prevent hypoglycemia , and identified knowledge gaps that should be addressed by future research .", "entity": [], "task": "NER"}
{"text": "In addition , tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided .", "entity": [], "task": "NER"}
{"text": "Free - Standing Polyelectrolyte Membranes Made of Chitosan and Alginate .", "entity": [], "task": "NER"}
{"text": "Free - standing films have increasing applications in the biomedical field as drug delivery systems for wound healing and tissue engineering .", "entity": [], "task": "NER"}
{"text": "Here , we prepared free - standing membranes by the layer - by - layer assembly of chitosan and alginate , two widely used biomaterials .", "entity": [], "task": "NER"}
{"text": "Our aim was to produce a thick membrane and to study the permeation of model drugs and the adhesion of muscle cells .", "entity": [], "task": "NER"}
{"text": "We first defined the optimal growth conditions in terms of pH and alginate concentration .", "entity": [], "task": "NER"}
{"text": "The membranes could be easily detached from polystyrene or polypropylene substrate without any postprocessing step .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [44, 55]}, {"entity": "polypropylene", "entity_type": "Chemical", "pos": [59, 72]}], "task": "NER"}
{"text": "The dry thickness was varied over a large range from 4 to 35 mu m .", "entity": [], "task": "NER"}
{"text": "A 2 - fold swelling was observed by confocal microscopy when they were immersed in PBS .", "entity": [], "task": "NER"}
{"text": "In addition , we quantified the permeation of model drugs ( fluorescent dextrans ) through the free - standing membrane , which depended on the dextran molecular weight .", "entity": [], "task": "NER"}
{"text": "Finally , we showed that myoblast cells exhibited a preferential adhesion on the alginate - ending membrane as compared to the chitosan - ending membrane or to the substrate side .", "entity": [], "task": "NER"}
{"text": "Concentration - Dependent Supramolecular Engineering of Hydrogen - Bonded Nanostructures at Surfaces : Predicting Self - Assembly in 2D .", "entity": [{"entity": "Hydrogen", "entity_type": "Chemical", "pos": [56, 64]}], "task": "NER"}
{"text": "We report a joint computational and experimental study on the concentration - dependent self - assembly of a flat C3 - symmetric molecule at surfaces .", "entity": [], "task": "NER"}
{"text": "As a model system we have chosen a rigid molecular module , 1 , 3 , 5 - tris ( pyridine - 4 - ylethynyl ) benzene , which can undergo self - association via hydrogen bonding ( H - bonding ) to form ordered 2D nanostructures .", "entity": [{"entity": "1 , 3 , 5 - tris ( pyridine - 4 - ylethynyl ) benzene", "entity_type": "Chemical", "pos": [60, 113]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [157, 165]}, {"entity": "H", "entity_type": "Chemical", "pos": [176, 177]}], "task": "NER"}
{"text": "In particular , the lattice Monte Carlo method , combined with density functional calculations , was employed to explore the spontaneous supramolecular organization of this tripod - shaped molecule under surface confinement .", "entity": [], "task": "NER"}
{"text": "We analyzed the stability of different weak H - bonded patterns and the influence of the concentration of the starting molecule on the 2D supramolecular packing .", "entity": [{"entity": "H", "entity_type": "Chemical", "pos": [44, 45]}], "task": "NER"}
{"text": "We found that ordered , densely packed monolayers and 2D porous networks are obtained at high and low concentrations , respectively .", "entity": [], "task": "NER"}
{"text": "A concentration - dependent scanning tunneling microscopy investigation of the molecular self - assembly at a graphite - solution interface revealed supramolecular motifs , which are in perfect agreement with those obtained by simulations .", "entity": [{"entity": "graphite", "entity_type": "Chemical", "pos": [110, 118]}], "task": "NER"}
{"text": "Therefore , our computational approach represents a step forward toward the deterministic prediction of molecular self - assembly at surfaces and interfaces .", "entity": [], "task": "NER"}
{"text": "Emergence of whole - cell MALDI - MS biotyping for high - throughput bioanalysis of mammalian cells ?", "entity": [], "task": "NER"}
{"text": "Since their inception in the 1970s , methods for classification of microorganisms based on mass spectral fingerprints obtained by MALDI - TOF MS have become a mainstay in environmental as well as in clinical microbiology .", "entity": [], "task": "NER"}
{"text": "Recently , related whole - cell MALDI - TOF fingerprinting workflows have been adopted for the classification of mammalian cells .", "entity": [], "task": "NER"}
{"text": "In this report we summarize this work and discuss the challenges of adapting whole - cell MS fingerprinting methods for the successful classification of mammalian cells .", "entity": [], "task": "NER"}
{"text": "We highlight current limitations as well as opportunities and emerging applications of this technology in industrial and clinical settings , such as cell - line authentication , clinical diagnostics , and quality and productivity control in bioprocesses .", "entity": [], "task": "NER"}
{"text": "Theoretical and Kinetic Study of the Reaction of Ethyl Methyl Ketone with HO2 for T = 600 - 1 , 600 K .", "entity": [{"entity": "Ethyl Methyl Ketone", "entity_type": "Chemical", "pos": [49, 68]}, {"entity": "HO2", "entity_type": "Chemical", "pos": [74, 77]}], "task": "NER"}
{"text": "Part II : Addition Reaction Channels .", "entity": [], "task": "NER"}
{"text": "The temperature and pressure dependence of the addition reaction of ethyl methyl ketone ( EMK ) with HO2 radical has been calculated with the master equation method employing conventional transition state theory estimates for the microcanonical rate coefficients in the temperature range of 600 - 1600 K .", "entity": [{"entity": "ethyl methyl ketone", "entity_type": "Chemical", "pos": [68, 87]}, {"entity": "EMK", "entity_type": "Chemical", "pos": [90, 93]}, {"entity": "HO2", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Geometries , frequencies , and hindrance potentials were obtained at the B3LYP / 6 - 311G ( d , p ) level of theory .", "entity": [], "task": "NER"}
{"text": "A modified G3 ( MP2 , CC ) method has been used to calculate accurate electronic energies for all of the species involved in the reactions .", "entity": [], "task": "NER"}
{"text": "The rigid - rotor harmonic oscillator approximation has been used for all of the vibrations except for the torsional degrees of freedom which are being treated as 1D hindered rotor .", "entity": [], "task": "NER"}
{"text": "Asymmetric Eckart barriers were used to model tunneling effect in a one - dimensional reaction coordinate through saddle points .", "entity": [], "task": "NER"}
{"text": "Our calculated results show that the four reaction channels forming 1 - buten - 2 - ol + H y O2 radical ( R5 ) , 2 - buten - 2 - ol + H y O2 radical ( R10 ) , acetic acid + ethylene + y O H radical ( R13 ) , 2 - methyl - 2 - oxetanol + y OH radical ( R15 ) are the dominant channels .", "entity": [{"entity": "1 - buten - 2 - ol", "entity_type": "Chemical", "pos": [68, 86]}, {"entity": "H y O2", "entity_type": "Chemical", "pos": [89, 95]}, {"entity": "2 - buten - 2 - ol", "entity_type": "Chemical", "pos": [113, 131]}, {"entity": "H y O2", "entity_type": "Chemical", "pos": [134, 140]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [159, 170]}, {"entity": "ethylene", "entity_type": "Chemical", "pos": [173, 181]}, {"entity": "O H", "entity_type": "Chemical", "pos": [186, 189]}, {"entity": "2 - methyl - 2 - oxetanol", "entity_type": "Chemical", "pos": [208, 233]}, {"entity": "OH", "entity_type": "Chemical", "pos": [238, 240]}], "task": "NER"}
{"text": "When the temperature is below 1000 K , the reaction R15 forming the cyclic ether , 2 - methyl - 2 - oxetanol , is dominant ; while the reaction R13 forming acetic acid + ethylene + y OH radical becomes increasingly dominant at temperatures above 1000 K .", "entity": [{"entity": "cyclic ether", "entity_type": "Chemical", "pos": [68, 80]}, {"entity": "2 - methyl - 2 - oxetanol", "entity_type": "Chemical", "pos": [83, 108]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [156, 167]}, {"entity": "ethylene", "entity_type": "Chemical", "pos": [170, 178]}, {"entity": "OH", "entity_type": "Chemical", "pos": [183, 185]}], "task": "NER"}
{"text": "The other two channels forming 1 - buten - 2 - ol , 2 - buten - 2 - ol and HO2 radical are not dominant but are still important product channels over the whole temperature range investigated here .", "entity": [{"entity": "1 - buten - 2 - ol", "entity_type": "Chemical", "pos": [31, 49]}, {"entity": "2 - buten - 2 - ol", "entity_type": "Chemical", "pos": [52, 70]}, {"entity": "HO2", "entity_type": "Chemical", "pos": [75, 78]}], "task": "NER"}
{"text": "No pressure dependence has been found for the reaction channels forming 2 - methyl - 2 - oxetanol + OH radical and acetic acid + ethylene + OH radical .", "entity": [{"entity": "2 - methyl - 2 - oxetanol", "entity_type": "Chemical", "pos": [72, 97]}, {"entity": "OH", "entity_type": "Chemical", "pos": [100, 102]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [115, 126]}, {"entity": "ethylene", "entity_type": "Chemical", "pos": [129, 137]}, {"entity": "OH", "entity_type": "Chemical", "pos": [140, 142]}], "task": "NER"}
{"text": "A slightly negative pressure dependence has been found for the reaction channels producing the two butenols .", "entity": [{"entity": "butenols", "entity_type": "Chemical", "pos": [99, 107]}], "task": "NER"}
{"text": "Rate constants for the four important reaction channels at 1 atm ( in cm3mol - 1s - 1 ) are : kR5 = 2 . 67 x 1015 x T - 1 . 32 exp ( - 16637 / T ) kR10 = 1 . 62 x 108 x T 0 . 57 exp ( - 13142 / T ) kR13 = 2 . 29 x 1017 x T - 1 . 66 exp ( - 18169 / T ) kR15 = 6 . 17 x 10 - 2 x T 3 . 35 exp ( - 10136 / T ) A comparison of the total rate constants for the addition of HO2 radical to EMK and that for H - atom abstraction by HO2 radical from EMK has also been carried out .", "entity": [{"entity": "HO2", "entity_type": "Chemical", "pos": [367, 370]}, {"entity": "EMK", "entity_type": "Chemical", "pos": [382, 385]}, {"entity": "H", "entity_type": "Chemical", "pos": [399, 400]}, {"entity": "HO2", "entity_type": "Chemical", "pos": [423, 426]}, {"entity": "EMK", "entity_type": "Chemical", "pos": [440, 443]}], "task": "NER"}
{"text": "We find that the abstraction reaction channels are dominant over the entire temperature range of 600 - 1600 K .", "entity": [], "task": "NER"}
{"text": "Phase - selective sorbent xerogels as reclamation agents for oil spills .", "entity": [], "task": "NER"}
{"text": "12 - Hydroxystearic acid ( 12 - HSA ) xerogels derived from 12 - HSA - acetronitrile organogels are highly effective sorbent materials capable of adsorbing apolar , spilled materials in aqueous environments .", "entity": [{"entity": "12 - Hydroxystearic acid", "entity_type": "Chemical", "pos": [0, 24]}, {"entity": "12 - HSA", "entity_type": "Chemical", "pos": [27, 35]}, {"entity": "12 - HSA", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "acetronitrile", "entity_type": "Chemical", "pos": [71, 84]}], "task": "NER"}
{"text": "12 - HSA xerogels made from 12 - HSA - acetronitrile organogels are more effective than 12 - HSA xerogels made from 12 - HSA - pentane organogels because of the highly branched fibrillar networks established in acetonitrile molecular gels .", "entity": [{"entity": "12 - HSA", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "12 - HSA", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "acetronitrile", "entity_type": "Chemical", "pos": [39, 52]}, {"entity": "12 - HSA", "entity_type": "Chemical", "pos": [88, 96]}, {"entity": "12 - HSA", "entity_type": "Chemical", "pos": [116, 124]}, {"entity": "pentane", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [211, 223]}], "task": "NER"}
{"text": "This difference arises because of dissimilarities in the network structure between 12 - HSA in various solvents .", "entity": [{"entity": "12 - HSA", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "These xerogels , being thermoreversible , allow for both the spilled oil to be reclaimed but also the gelator may be reused to engineer new xerogels for oil spill containment and cleanup .", "entity": [], "task": "NER"}
{"text": "Pregnancy outcome in women exposed to antiepileptic drugs : teratogenic role of maternal epilepsy and its pharmacologic treatment .", "entity": [], "task": "NER"}
{"text": "Infants born to epileptic women treated with Antiepileptic Drugs ( AEDs ) have an increased risk of major congenital malformations ( MCMs ) .", "entity": [], "task": "NER"}
{"text": "In order to determine the role of maternal epilepsy we conducted a prospective cohort study on three cohorts of pregnant women : i ) 385 epileptic women treated with AEDs , ii ) 310 non - epileptic women treated with AEDs , iii ) 867 healthy women not exposed to AEDs ( control group ) .", "entity": [], "task": "NER"}
{"text": "The rate of MCMs in the epileptic group ( 7 . 7 % ) was not statistically higher than in the non - epileptic one ( 3 . 9 % ) ( p = 0 . 068 ) .", "entity": [], "task": "NER"}
{"text": "The rate in the first group was higher compared to the control group ( p = 0 . 001 ) , while the rate in the second one was not ( p = 0 . 534 ) .", "entity": [], "task": "NER"}
{"text": "Our data confirm that AEDs therapy is the main cause of the increased risk of malformations in the offspring of epileptic women ; however a teratogenic role of the maternal epilepsy itself cannot be excluded .", "entity": [], "task": "NER"}
{"text": "Electrophysiological evidence for 4 - isobutyl - 3 - isopropylbicyclophosphorothionate as a selective blocker of insect GABA - gated chloride channels .", "entity": [{"entity": "4 - isobutyl - 3 - isopropylbicyclophosphorothionate", "entity_type": "Chemical", "pos": [34, 86]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [120, 124]}, {"entity": "chloride", "entity_type": "Chemical", "pos": [133, 141]}], "task": "NER"}
{"text": "Invertebrate gamma - aminobutyric acid ( GABA ) - gated chloride channels ( GABACls ) and glutamate - gated chloride channels ( GluCls ) , which function as inhibitory neurotransmitter receptors , are important targets of insecticides and antiparasitic agents .", "entity": [{"entity": "gamma - aminobutyric acid", "entity_type": "Chemical", "pos": [13, 38]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [41, 45]}, {"entity": "chloride", "entity_type": "Chemical", "pos": [56, 64]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [90, 99]}, {"entity": "chloride", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "The antagonism of GABACls and GluCls by 4 - isobutyl - 3 - isopropylbicyclophosphorothionate ( PS - 14 ) was examined in cultured cockroach and rat neurons using a whole - cell patch - clamp method .", "entity": [{"entity": "4 - isobutyl - 3 - isopropylbicyclophosphorothionate", "entity_type": "Chemical", "pos": [40, 92]}, {"entity": "PS - 14", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "The results indicated that PS - 14 selectively blocks cockroach GABACls relative to cockroach GluCls and rat GABACls .", "entity": [{"entity": "PS - 14", "entity_type": "Chemical", "pos": [27, 34]}], "task": "NER"}
{"text": "PS - 14 represents a useful probe for the study of insect GABA receptors .", "entity": [{"entity": "PS - 14", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "GABA", "entity_type": "Chemical", "pos": [58, 62]}], "task": "NER"}
{"text": "Synthesis and antibacterial evaluation of a novel series of 10 - hydroxyl ketolide derivatives .", "entity": [{"entity": "10 - hydroxyl ketolide", "entity_type": "Chemical", "pos": [60, 82]}], "task": "NER"}
{"text": "A novel series of 10 - hydroxyl ketolide derivatives were synthesized , during which a distinctive intermediate , 3 - O - descladinosyl - 3 - oxo - 11 - deoxy - 10 , 11 - epoxy - 6 - O - methylerythromycin A , was obtained from 6 - O - methylerythromycin A .", "entity": [{"entity": "10 - hydroxyl ketolide", "entity_type": "Chemical", "pos": [18, 40]}, {"entity": "3 - O - descladinosyl - 3 - oxo - 11 - deoxy - 10 , 11 - epoxy - 6 - O - methylerythromycin A", "entity_type": "Chemical", "pos": [114, 207]}, {"entity": "6 - O - methylerythromycin A", "entity_type": "Chemical", "pos": [228, 256]}], "task": "NER"}
{"text": "The structure and stereochemistry of this novel structure were confirmed via NMR and X - ray crystallography .", "entity": [], "task": "NER"}
{"text": "Moreover , antibacterial evaluations were established in order to assess our modifications and acquire a deep understanding of the ketolides ' structure - activity relationship ( SAR ) .", "entity": [{"entity": "ketolides", "entity_type": "Chemical", "pos": [131, 140]}], "task": "NER"}
{"text": "Synthesis and cytotoxic evaluation of novel pyrimidine deoxyapiothionucleosides .", "entity": [{"entity": "pyrimidine deoxyapiothionucleosides", "entity_type": "Chemical", "pos": [44, 79]}], "task": "NER"}
{"text": "The synthesis of novel pyrimidine deoxyapiothionucleosides of d - and l - series was realized following application of a versatile and high - yielding scheme , which utilized inexpensive l - and d - arabinose as starting materials , respectively , and which makes use of a regio - and stereo - selective Pummerer rearrangement reaction for the coupling of the nucleobase with the thiosugar moiety .", "entity": [{"entity": "pyrimidine deoxyapiothionucleosides", "entity_type": "Chemical", "pos": [23, 58]}, {"entity": "l - and d - arabinose", "entity_type": "Chemical", "pos": [187, 208]}, {"entity": "nucleobase", "entity_type": "Chemical", "pos": [360, 370]}, {"entity": "thiosugar", "entity_type": "Chemical", "pos": [380, 389]}], "task": "NER"}
{"text": "Some of the targeted compounds have shown selective cytotoxic effects ( with IC50 < 10 mu M ) against specific cancer cell lines .", "entity": [], "task": "NER"}
{"text": "All of the tested compounds had no cytotoxic effect on the normal cell line tested .", "entity": [], "task": "NER"}
{"text": "Oxidative stress and MAPK involved into ATF2 expression in immortalized human urothelial cells treated by arsenic .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [106, 113]}], "task": "NER"}
{"text": "ATF2 is a subfamily member of AP - 1 and has an important role in cellular stress responses .", "entity": [], "task": "NER"}
{"text": "ATF2 has been implicated in a transcriptional response leading to cell migration and malignant tumor progression .", "entity": [], "task": "NER"}
{"text": "However , little is known about the effect of arsenic on expression of ATF2 and regulatory pathways in human urothelial cells .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "In this study , ATF2 expression was measured in NaAsO2 - treated human uroepithelial cell line ( SV - HUC - 1 ) with 1 , 2 , 4 , 8 and 10 mu M concentrations in order to provide some basis data for the study on mechanism of bladder cancer induced by arsenic .", "entity": [{"entity": "NaAsO2", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [250, 257]}], "task": "NER"}
{"text": "We found that ATF2 expression levels at 2 , 4 , 8 and 10 mu M arsenic - treated cells were significantly higher than those of control cells , and the strongest expression occurred in 4 mu M NaAsO2 - treated cells .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [62, 69]}, {"entity": "NaAsO2", "entity_type": "Chemical", "pos": [190, 196]}], "task": "NER"}
{"text": "Antioxidants ( melatonin ) and JNK or p38 inhibitors decreased significantly arsenic - induced ATF2 expression .", "entity": [{"entity": "melatonin", "entity_type": "Chemical", "pos": [15, 24]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "Taken together , these data indicated that the increasing of ATF2 expression is mediated via oxidative stress induced by arsenic in SV - HUC - 1 cells , and JNK or p38 rather than ERK is responsible for arsenic - induced ATF2 expression .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [121, 128]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [203, 210]}], "task": "NER"}
{"text": "ROS were also involved in arsenic induced the activation of JNK and p38 MAPK signaling pathway .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [26, 33]}], "task": "NER"}
{"text": "Two Common Bean Genotypes with Contrasting Response to Phosphorus Deficiency Show Variations in the microRNA 399 - Mediated PvPHO2 Regulation within the PvPHR1 Signaling Pathway .", "entity": [{"entity": "Phosphorus", "entity_type": "Chemical", "pos": [55, 65]}], "task": "NER"}
{"text": "Crop production of the important legume , the common bean ( Phaseolus vulgaris ) , is often limited by low phosphorus ( P ) in the soil .", "entity": [{"entity": "phosphorus", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "P", "entity_type": "Chemical", "pos": [120, 121]}], "task": "NER"}
{"text": "The genotypes , BAT477 and DOR364 , of the common bean have contrasting responses to P starvation .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [85, 86]}], "task": "NER"}
{"text": "Plants from the BAT477 P deficiency tolerant genotype showed higher phosphate content and root biomass as compared to the DOR364 plants under P starvation .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [0, 1]}, {"entity": "phosphate", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "P", "entity_type": "Chemical", "pos": [142, 143]}], "task": "NER"}
{"text": "The PvPHR1 transcription factor - signaling pathway plays an essential role in the response to P starvation .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [4, 5]}], "task": "NER"}
{"text": "PvPHO2 , a negative regulator of this pathway , encodes an ubiquitin E2 conjugase that promotes degradation of P - responsive proteins and is the target gene of PvmiR399 .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "PvPHO2 is downregulated in BAT477 plants under P deficiency , while such a response is not observed in P - starved DOR364 plants .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [0, 1]}, {"entity": "P", "entity_type": "Chemical", "pos": [2, 3]}], "task": "NER"}
{"text": "Five putative PvmiR399 binding sites were identified in the 5 ' UTR region in both genotypes .", "entity": [], "task": "NER"}
{"text": "While four sites showed an identical DNA sequence , the fifth ( binding site of PvPHO2 one ) showed three base changes and higher complementarity scores in DOR364 as compared to BAT477 .", "entity": [], "task": "NER"}
{"text": "Modified 5 ' RACE experiments indicated that PvmiR399 binding and / or processing was affected in DOR364 P - starved plants .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [45, 46]}], "task": "NER"}
{"text": "We propose that a less efficient cleavage of the PvPHO2 mRNA directed by PvmiR399 would result in a higher PvPHO2 - mediated degradation of P - responsive proteins in the DOR364 genotype with decreased P deficiency tolerance .", "entity": [{"entity": "P", "entity_type": "Chemical", "pos": [49, 50]}], "task": "NER"}
{"text": "Widening the pH Activity Profile of a Fungal Laccase by Directed Evolution .", "entity": [], "task": "NER"}
{"text": "Unnatural selection : A fungal laccase was tailored by directed evolution to be active at neutral / alkaline pH .", "entity": [], "task": "NER"}
{"text": "After five generations , the final mutant showed a broader pH profile while retaining 50 to 80 % of its activity at neutral pH .", "entity": [], "task": "NER"}
{"text": "An in Vivo Tagging Method Reveals that Ras Undergoes Sustained Activation upon Transglutaminase - Mediated Protein Serotonylation .", "entity": [], "task": "NER"}
{"text": "Don ' t interrupt !", "entity": [], "task": "NER"}
{"text": "Protein serotonylation has been implicated in living cells , yet its role remains poorly defined because of the lack of characterization tools .", "entity": [], "task": "NER"}
{"text": "We synthesized a serotonin derivative to enable selective tagging of serotonylation and to investigate its effect on Ras ; the latter displayed undisrupted interaction with Raf - 1 at the Ras binding domain .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [17, 26]}], "task": "NER"}
{"text": "A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post - Bariatric Surgery .", "entity": [{"entity": "Bile Acids", "entity_type": "Chemical", "pos": [67, 77]}], "task": "NER"}
{"text": "Bariatric surgery elevates serum bile acids .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "Conjugated bile acid administration , such as tauroursodeoxycholic acid ( TUDCA ) , improves insulin sensitivity , while short - circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [11, 20]}, {"entity": "tauroursodeoxycholic acid", "entity_type": "Chemical", "pos": [46, 71]}, {"entity": "TUDCA", "entity_type": "Chemical", "pos": [74, 79]}, {"entity": "bile acid", "entity_type": "Chemical", "pos": [140, 149]}, {"entity": "TUDCA", "entity_type": "Chemical", "pos": [213, 218]}], "task": "NER"}
{"text": "We hypothesized that bariatric surgery outcomes could be recapitulated by short - circuiting the normal entero - hepatic bile circulation .", "entity": [], "task": "NER"}
{"text": "We established a model wherein male obese rats underwent either bile diversion ( BD ) or Sham ( SH ) surgery .", "entity": [], "task": "NER"}
{"text": "The BD group had a catheter inserted into the common bile duct and its distal end anchored into the mid - distal jejunum for 4 - 5 weeks .", "entity": [], "task": "NER"}
{"text": "Glucose tolerance , insulin and glucagon - like peptide - 1 ( GLP - 1 ) response , hepatic steatosis and endoplasmic reticulum ( ER ) stress were measured .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Rats ' post - BD lost significantly more weight than the SH - rats .", "entity": [], "task": "NER"}
{"text": "BD rats gained less fat mass post - surgery .", "entity": [], "task": "NER"}
{"text": "BD rats had improved glucose tolerance , increased higher post - prandial GLP - 1 response and serum bile acids but less liver steatosis .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [21, 28]}, {"entity": "bile acids", "entity_type": "Chemical", "pos": [101, 111]}], "task": "NER"}
{"text": "Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair - fed rats .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [6, 15]}, {"entity": "TUDCA", "entity_type": "Chemical", "pos": [33, 38]}], "task": "NER"}
{"text": "Fecal bile acid levels were not different .", "entity": [{"entity": "bile acid", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "Liver ER stress ( CHOP mRNA and pJNK protein ) was decreased in BD rats .", "entity": [], "task": "NER"}
{"text": "Bile acid gavage ( TUDCA / UDCA ) in diet - induced obese rats , elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress ( CHOP mRNA ) .", "entity": [{"entity": "Bile acid", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "TUDCA", "entity_type": "Chemical", "pos": [19, 24]}, {"entity": "UDCA", "entity_type": "Chemical", "pos": [27, 31]}, {"entity": "TUDCA", "entity_type": "Chemical", "pos": [80, 85]}], "task": "NER"}
{"text": "These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [53, 63]}], "task": "NER"}
{"text": "Further , our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease .", "entity": [{"entity": "bile acids", "entity_type": "Chemical", "pos": [60, 70]}], "task": "NER"}
{"text": "Silver nanoparticles enhance Pseudomonas aeruginosa PAO1 biofilm detachment .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [0, 6]}], "task": "NER"}
{"text": "Abstract Objectives : Silver nanoparticles ( AgNPs ) with a size ranging from 7 to 70 nm were synthesized using the ascorbic acid - citrate seed - mediated growth approach at room temperature .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [116, 129]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "Methods : The 8 nm silver particles were prepared using gallic acid in alkaline conditions and used as seed to prepare AgNPs .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "gallic acid", "entity_type": "Chemical", "pos": [56, 67]}], "task": "NER"}
{"text": "Results : The presence of ascorbic acid and citrate allows the regulation of size and size distribution of the nanoparticles .", "entity": [{"entity": "ascorbic acid", "entity_type": "Chemical", "pos": [26, 39]}, {"entity": "citrate", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "The increase in free silver ion - to - seed ratio ( Ag ( + ) / Ag ( 0 ) ) resulted in changes of particle shape from spherical to pseudo - spherical and minor cylindrical shape .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [21, 27]}, {"entity": "Ag ( + )", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "Ag ( 0 )", "entity_type": "Chemical", "pos": [63, 71]}], "task": "NER"}
{"text": "Further , a repetitive seeding approach resulted in the formation of pseudo - spherical particles with higher polydispersity index and minor distributions of tetrahedral particles .", "entity": [], "task": "NER"}
{"text": "Citrate - capped AgNPs were stable and did not agglomerate upon centrifugation .", "entity": [{"entity": "Citrate", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "The effect of AgNPs on biofilm reduction was evaluated using static culture on 96 - well microtiter plates .", "entity": [], "task": "NER"}
{"text": "Results showed that AgNPs with the smallest average diameter were most effective in the reduction of Pseudomonas aeruginosa biofilm colonies , which accounted for 90 % of removal .", "entity": [], "task": "NER"}
{"text": "Conclusion : The biofilm removal activities of the nanoparticles were found to be concentration - independent particularly for the concentration within the range of 80 - 200 micro g / mL .", "entity": [], "task": "NER"}
{"text": "Bacteriolysis by vancomycin - conjugated acryl nanoparticles and morphological component analysis .", "entity": [{"entity": "vancomycin", "entity_type": "Chemical", "pos": [17, 27]}, {"entity": "acryl", "entity_type": "Chemical", "pos": [41, 46]}], "task": "NER"}
{"text": "Abstract Nanoparticles are currently attracting considerable attention because of their ability to conjugate to various substances .", "entity": [], "task": "NER"}
{"text": "As such , these nanoparticles can assist the transfer of the conjugated substance to target tissues where they are gradually released .", "entity": [], "task": "NER"}
{"text": "In this study , vancomycin - conjugated nanoparticles ( VCM NPs ) were prepared .", "entity": [{"entity": "vancomycin", "entity_type": "Chemical", "pos": [16, 26]}, {"entity": "VCM", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "The antibacterial activity of VCM NPs was compared with that of VCM alone by exposure to vancomycin - resistant enterococci ( VRE ) .", "entity": [{"entity": "VCM", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "VCM", "entity_type": "Chemical", "pos": [64, 67]}, {"entity": "vancomycin", "entity_type": "Chemical", "pos": [89, 99]}], "task": "NER"}
{"text": "The morphology of the cells was then analyzed by electron microscopy .", "entity": [], "task": "NER"}
{"text": "VCM NPs were found to have more potent antibacterial activity against VRE compared to VCM alone , but the activity against vancomycin - sensitive enterococci ( VSE ) remained the same .", "entity": [{"entity": "VCM", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "VCM", "entity_type": "Chemical", "pos": [86, 89]}, {"entity": "vancomycin", "entity_type": "Chemical", "pos": [123, 133]}], "task": "NER"}
{"text": "The antibacterial activity of nanoparticles alone was the same against VSE and VRE .", "entity": [], "task": "NER"}
{"text": "The nanoparticles were found to induce characteristic morphological changes in the bacteria based on scanning and transmission electron microscopy .", "entity": [], "task": "NER"}
{"text": "The results suggest that the strong antibacterial activity of VCM NPs against VRE may be attributable not only to the well - known control release carrier property of the nanoparticles but to an additional mechanism that involves VCM NPs avoiding the drug resistant mechanism of VRE .", "entity": [{"entity": "VCM", "entity_type": "Chemical", "pos": [62, 65]}, {"entity": "VCM", "entity_type": "Chemical", "pos": [230, 233]}], "task": "NER"}
{"text": "Ingestion toxicity of three Lamiaceae essential oils incorporated in protein baits against the olive fruit fly , Bactrocera oleae ( Rossi ) ( Diptera Tephritidae ) .", "entity": [], "task": "NER"}
{"text": "The ingestion toxicity of three Lamiaceae essential oils ( EOs ) - Hyptis suaveolens , Rosmarinus officinalis and Lavandula angustifolia - incorporated in protein baits was evaluated against Bactrocera oleae , a worldwide pest of olive fruits .", "entity": [], "task": "NER"}
{"text": "In laboratory conditions , all the tested EOs showed dose - dependent toxicity on B . oleae , with mortality rates ranging from 12 % ( EO concentration : 0 . 01 % w : v ) to 100 % ( EO concentration : 1 . 75 % w : v ) .", "entity": [], "task": "NER"}
{"text": "Semi - field results highlighted the toxicity of L . angustifolia and H . suaveolens EOs , which exerted more than 60 % of flies mortality at a concentration of 1 . 75 % ( w : v ) .", "entity": [], "task": "NER"}
{"text": "Gas Chromatography - Electron Impact Mass Spectrometry analyses of the three EOs showed that H . suaveolens EO was dominated by monoterpene and sesquiterpene hydrocarbons .", "entity": [{"entity": "monoterpene", "entity_type": "Chemical", "pos": [128, 139]}, {"entity": "sesquiterpene hydrocarbons", "entity_type": "Chemical", "pos": [144, 170]}], "task": "NER"}
{"text": "Oxygenated monoterpenes were the main chemical class in R . officinalis and L . angustifolia EOs .", "entity": [{"entity": "Oxygenated monoterpenes", "entity_type": "Chemical", "pos": [0, 23]}], "task": "NER"}
{"text": "Further research is needed to evaluate the efficacy of these EOs plus food bait against the olive fruit fly in the open field .", "entity": [], "task": "NER"}
{"text": "Aberrant free radical biology is a unifying theme in the etiology and pathogenesis of major human diseases .", "entity": [], "task": "NER"}
{"text": "The seemingly disparate areas of oxygen toxicity , radiation exposure , and aging are now recognized to share a common feature - the aberrant production and / or removal of biologically derived free radicals and other reactive oxygen and nitrogen species ( ROS / RNS ) .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [33, 39]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [227, 233]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [238, 246]}], "task": "NER"}
{"text": "Advances in our understanding of the effects of free radicals in biology and medicine have been , and continue to be , actively translated into clinically tractable diagnostic and therapeutic applications .", "entity": [], "task": "NER"}
{"text": "This issue is dedicated to recent advances , both basic discoveries and clinical applications , in the field of free radicals in biology and medicine .", "entity": [], "task": "NER"}
{"text": "As more is understood about the proximal biological targets of aberrantly produced or removed reactive species , their sensors , and effectors of compensatory response , a great deal more will be learned about the commonalities in mechanisms underlying seemingly disparate disease states .", "entity": [], "task": "NER"}
{"text": "Together with this deeper understanding , opportunities will arise to devise rational therapeutic interventions to decrease the incidence and severity of these diseases and positively impact the human healthspan .", "entity": [], "task": "NER"}
{"text": "Structural and Immunochemical Studies of the Lipopolysaccharide from the Fish Pathogen , Aeromonas bestiarum Strain K296 , Serotype O18 .", "entity": [], "task": "NER"}
{"text": "Chemical analyses and mass spectrometry were used to study the structure of the lipopolysaccharide ( LPS ) isolated from Aeromonas bestiarum strain K296 , serotype O18 .", "entity": [], "task": "NER"}
{"text": "ESI - MS revealed that the most abundant A . bestiarum LPS glycoforms have a hexa - acylated or tetra - acylated lipid A with conserved architecture of the backbone , consisting of a 1 , 4 ' - bisphosphorylated beta - ( 1 --> 6 ) - linked d - GlcN disaccharide with an AraN residue as a non - stoichiometric substituent and a core oligosaccharide composed of Kdo1Hep6Hex1HexN1P1 .", "entity": [{"entity": "1 , 4 ' - bisphosphorylated beta - ( 1 --> 6 ) - linked d - GlcN disaccharide", "entity_type": "Chemical", "pos": [183, 260]}, {"entity": "AraN", "entity_type": "Chemical", "pos": [269, 273]}], "task": "NER"}
{"text": "1D and 2D NMR spectroscopy revealed that the O - specific polysaccharide ( OPS ) of A . bestiarum K296 consists of a branched tetrasaccharide repeating unit containing two 6 - deoxy - l - talose ( 6dTalp ) , one Manp and one GalpNAc residues ; thus , it is similar to that of the OPS of A . hydrophila AH - 3 ( serotype O34 ) in both the sugar composition and the glycosylation pattern .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [45, 46]}, {"entity": "tetrasaccharide", "entity_type": "Chemical", "pos": [126, 141]}, {"entity": "6 - deoxy - l - talose", "entity_type": "Chemical", "pos": [172, 194]}, {"entity": "6dTalp", "entity_type": "Chemical", "pos": [197, 203]}, {"entity": "GalpNAc", "entity_type": "Chemical", "pos": [225, 232]}, {"entity": "sugar", "entity_type": "Chemical", "pos": [338, 343]}], "task": "NER"}
{"text": "Moreover , 3 - substituted 6dTalp was 2 - O - acetylated and additional O - acetyl groups were identified at O - 2 and O - 4 ( or O - 3 ) positions of the terminal 6dTalp .", "entity": [{"entity": "6dTalp", "entity_type": "Chemical", "pos": [27, 33]}, {"entity": "O - acetyl", "entity_type": "Chemical", "pos": [42, 52]}, {"entity": "6dTalp", "entity_type": "Chemical", "pos": [164, 170]}], "task": "NER"}
{"text": "Western blots with polyclonal rabbit sera showed that serotypes O18 and O34 share some epitopes in the LPS .", "entity": [], "task": "NER"}
{"text": "The very weak reaction of the anti - O34 serum with the O - deacylated LPS of A . bestiarum K296 might have been due to the different O - acetylation pattern of the terminal 6dTalp .", "entity": [{"entity": "O", "entity_type": "Chemical", "pos": [37, 38]}, {"entity": "O", "entity_type": "Chemical", "pos": [56, 57]}, {"entity": "6dTalp", "entity_type": "Chemical", "pos": [174, 180]}], "task": "NER"}
{"text": "The latter suggestion was further confirmed by NMR .", "entity": [], "task": "NER"}
{"text": "Protective Effects of HemoHIM on Immune and Hematopoietic Systems Against gamma - Irradiation .", "entity": [], "task": "NER"}
{"text": "We examined the effect of HemoHIM on the protective efficacy of hematopoietic stem cells and on the recovery of immune cells against sublethal doses of ionizing radiation .", "entity": [], "task": "NER"}
{"text": "Two - month - old mice were exposed to gamma - rays at a dose of 8 , 6 . 5 , or 5 Gy for a30 - day survival study , endogenous spleen colony formation , or other experiments , respectively .", "entity": [], "task": "NER"}
{"text": "HemoHIM was injected intraperitoneally before and after irradiation .", "entity": [], "task": "NER"}
{"text": "Our results showed that HemoHIM significantly decreased the mortality of sublethally irradiated mice .", "entity": [], "task": "NER"}
{"text": "The HemoHIM administration decreased the apoptosis of bone marrow cells in irradiated mice .", "entity": [], "task": "NER"}
{"text": "On the other hand , HemoHIM increased the formation of endogenous spleen colony in irradiated mice .", "entity": [], "task": "NER"}
{"text": "In irradiated mice , the recovery of total leukocytes in the peripheral blood and lymphocytes in the spleen were enhanced significantly by HemoHIM .", "entity": [], "task": "NER"}
{"text": "Moreover , the function of B cells , T cells , and NK cells regenerated in irradiated mice were significantly improved by the administration of HemoHIM .", "entity": [], "task": "NER"}
{"text": "HemoHIM showed an ideal radioprotector for protecting hematopoietic stem cells and for accelerating the recovery of immune cells .", "entity": [], "task": "NER"}
{"text": "We propose HemoHIM as a beneficial supplement drug during radiotherapy to alleviate adverse radiation - induced effects for cancer patients .", "entity": [], "task": "NER"}
{"text": "Palbinone from Paeonia suffruticosa Protects Hepatic Cells via Up - regulation of Heme Oxygenase - 1 .", "entity": [{"entity": "Palbinone", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Heme", "entity_type": "Chemical", "pos": [82, 86]}], "task": "NER"}
{"text": "Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases .", "entity": [], "task": "NER"}
{"text": "The pathways by which palbinone ( PB ) isolated from P . suffruticosa mediates heme oxygenase - 1 ( HO - 1 ) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways .", "entity": [{"entity": "palbinone", "entity_type": "Chemical", "pos": [22, 31]}, {"entity": "heme", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "The effect of PB - treatment on Nrf2 translocalization and HO - 1 - antioxidant response element ( ARE ) regulation was examined employing Western blot and luciferase assays .", "entity": [], "task": "NER"}
{"text": "PB induced HO - 1 expression via the activation of Nrf2 in the hepatic cells , and ARE - dependent genes were stimulated via the PB - mediated Nrf2 activation .", "entity": [], "task": "NER"}
{"text": "PB - mediated HO - 1 expression could be involved with PI3K / Akt and ERK1 / 2 pathways .", "entity": [], "task": "NER"}
{"text": "Our study suggests the mechanism by which PB induces HO - 1 expression in the hepatic cells .", "entity": [], "task": "NER"}
{"text": "This might substantiate the traditional applications of P . suffruticosa for the treatment of oxidative stress - related diseases including oxidant and inflammatory - mediated vascular and liver diseases .", "entity": [], "task": "NER"}
{"text": "Identification of candidate genes encoding an LDL - C QTL in baboons .", "entity": [], "task": "NER"}
{"text": "Cardiovascular disease ( CVD ) , the leading cause of death in developed countries and dyslipidemia , is a major risk factor for CVD .", "entity": [], "task": "NER"}
{"text": "We previously identified a cluster of quantitative trait loci ( QTL ) on baboon chromosome 11 for multiple related quantitative traits for serum low - density lipoprotein cholesterol ( LDL - C ) .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [171, 182]}], "task": "NER"}
{"text": "Here we report differentially regulated hepatic genes that appear to encode an LDL - C QTL that influences LDL - C levels in baboons .", "entity": [], "task": "NER"}
{"text": "We performed hepatic whole genome expression profiling for LDL - C discordant baboons fed a high - cholesterol , high - fat ( HCHF ) diet for 7 weeks .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [99, 110]}], "task": "NER"}
{"text": "We detected expression of 117 genes within the QTL 2 - LOD - support interval .", "entity": [], "task": "NER"}
{"text": "Three genes were differentially expressed in low LDL - C responders and 8 in high LDL - C responders in response to a HCHF diet .", "entity": [], "task": "NER"}
{"text": "Seven genes ( ACVR1B , CALCOCO1 , DGKA , ERBB3 , KRT73 , MYL6B , TENC1 ) showed discordant expression between low and high LDL - C responders .", "entity": [], "task": "NER"}
{"text": "To prioritize candidate genes , we integrated miRNA and mRNA expression profiles using network tools and found that four candidates ( ACVR1B , DGKA , ERBB3 , TENC1 ) were miRNA targets and the miRNAs were inversely expressed to the target genes .", "entity": [], "task": "NER"}
{"text": "Candidate gene expression was validated using QRT - PCR and Westerns .", "entity": [], "task": "NER"}
{"text": "This study reveals candidate genes that influence variation in LDL - C in baboons and potential genetic mechanisms for further investigation .", "entity": [], "task": "NER"}
{"text": "Macromolecular amplification of binding response in superaptamer hydrogels .", "entity": [], "task": "NER"}
{"text": "It is becoming more important to detect ultralow concentrations of analytes for biomedical , environmental , and national security applications .", "entity": [], "task": "NER"}
{"text": "Equally important is that new methods should be easy to use , inexpensive , portable , and if possible allow detection by the naked eye .", "entity": [], "task": "NER"}
{"text": "By and large , detection of low concentrations of analytes cannot be achieved directly but requires signal amplification by catalysts , macromolecules , metal surfaces , or supramolecular aggregates .", "entity": [], "task": "NER"}
{"text": "The rapidly progressing field of macromolecular signal amplification has been advanced using conjugated polymers , chirality in polymers , solvating polymers , and polymerization / depolymerization strategies .", "entity": [], "task": "NER"}
{"text": "A new type of aptamer - based hydrogel with specific response to target proteins presented in this report demonstrates an additional category of macromolecular signal amplification .", "entity": [], "task": "NER"}
{"text": "This superaptamer assembly provides the first example of using protein - specific aptamers to create volume - changing hydrogels with amplified response to the target protein .", "entity": [], "task": "NER"}
{"text": "A remarkable aspect of these superaptamer hydrogels is that volume shrinking is visible to the naked eye down to femtomolar concentrations of protein .", "entity": [], "task": "NER"}
{"text": "This extraordinary macromolecular amplification is attributed to a complex interplay between protein - aptamer supramolecular cross - links and the consequential reduction of excluded volume in the hydrogel .", "entity": [], "task": "NER"}
{"text": "Specific recognition is even maintained in biological matrices such as urine and tears .", "entity": [], "task": "NER"}
{"text": "Furthermore , the gels can be dried for long - term storage and regenerated for use without loss of activity .", "entity": [], "task": "NER"}
{"text": "In practice , the ease of this biomarker detection method offers an alternative to traditional analytical techniques that require sophisticated instrumentation and highly trained personnel .", "entity": [], "task": "NER"}
{"text": "Polyelectrolyte Multilayers Promote Stent - Mediated Delivery of DNA to Vascular Tissue .", "entity": [], "task": "NER"}
{"text": "We report an approach to deliver DNA to vascular tissue in vivo using intravascular stents coated with degradable , DNA - containing polyelectrolyte multilayers ( PEMs ) .", "entity": [], "task": "NER"}
{"text": "Ionically cross - linked multilayers ~ 120 nm thick were fabricated layer - by - layer on the surfaces of balloon - mounted stainless steel stents using plasmid DNA and a hydrolytically degradable poly ( beta - amino ester ) ( polymer 1 ) .", "entity": [{"entity": "poly ( beta - amino ester )", "entity_type": "Chemical", "pos": [197, 224]}], "task": "NER"}
{"text": "Characterization of stents coated using a fluorescently end - labeled analog of polymer 1 revealed film erosion to be uniform across the surfaces of the stents ; differential stresses experienced upon balloon expansion did not lead to faster film erosion or dose dumping of DNA in areas near stent joints when stents were incubated in physiologically relevant media .", "entity": [], "task": "NER"}
{"text": "The ability of film - coated stents to transfer DNA and transfect arterial tissue in vivo was then investigated in pigs and rabbits .", "entity": [], "task": "NER"}
{"text": "Stents coated with films fabricated using fluorescently labeled DNA resulted in uniform transfer of DNA to sub - endothelial tissue in the arteries of pigs in patterns corresponding to the locations and geometries of stent struts .", "entity": [], "task": "NER"}
{"text": "Stents coated with films fabricated using polymer 1 and plasmid DNA encoding EGFP resulted in expression of EGFP in the medial layers of stented tissue in both pigs and rabbits two days after implantation .", "entity": [], "task": "NER"}
{"text": "The results of this study , combined with the modular and versatile nature of layer - by - layer assembly , provide a polymer - based platform that is well suited for fundamental studies of stent - mediated gene transfer .", "entity": [], "task": "NER"}
{"text": "With further development , this approach could also prove useful for the design of nonviral , gene - based approaches for prevention of complications that arise from the implantation of stents and other implantable interventional devices .", "entity": [], "task": "NER"}
{"text": "Kinase Scaffold Repurposing for Neglected Disease Drug Discovery : Discovery of an Efficacious , Lapatanib - Derived Lead Compound for Trypanosomiasis .", "entity": [{"entity": "Lapatanib", "entity_type": "Chemical", "pos": [97, 106]}], "task": "NER"}
{"text": "Human African trypanosomiasis ( HAT ) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei .", "entity": [], "task": "NER"}
{"text": "Because drugs in use against HAT are toxic and require intravenous dosing , new drugs are needed .", "entity": [], "task": "NER"}
{"text": "Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases .", "entity": [], "task": "NER"}
{"text": "We demonstrated recently that the 4 - anilinoquinazolines lapatinib ( GW572016 , 1 ) and canertinib ( CI - 1033 ) kill T . brucei with low micromolar EC50 values .", "entity": [{"entity": "4 - anilinoquinazolines", "entity_type": "Chemical", "pos": [34, 57]}, {"entity": "lapatinib", "entity_type": "Chemical", "pos": [58, 67]}, {"entity": "GW572016", "entity_type": "Chemical", "pos": [70, 78]}, {"entity": "canertinib", "entity_type": "Chemical", "pos": [89, 99]}, {"entity": "CI - 1033", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "We now report promising activity of analogues of 1 , which provided an excellent starting point for optimization of the chemotype .", "entity": [], "task": "NER"}
{"text": "Our compound optimization that has led to synthesis of several potent 4 - anilinoquinazolines , including NEU617 , 23a , a highly potent , orally bioavailable inhibitor of trypanosome replication .", "entity": [{"entity": "4 - anilinoquinazolines", "entity_type": "Chemical", "pos": [70, 93]}, {"entity": "NEU617", "entity_type": "Chemical", "pos": [106, 112]}], "task": "NER"}
{"text": "At the cellular level , 23a blocks duplication of the kinetoplast and arrests cytokinesis , making it a new chemical tool for studying regulation of the trypanosome cell cycle .", "entity": [], "task": "NER"}
{"text": "Molecular Mechanisms in the Pyrolysis of Unsaturated Chlorinated Hydrocarbons : Formation of Benzene Rings Part II - Experimental and Kinetic Modeling Studies .", "entity": [{"entity": "Unsaturated Chlorinated Hydrocarbons", "entity_type": "Chemical", "pos": [41, 77]}, {"entity": "Benzene", "entity_type": "Chemical", "pos": [93, 100]}], "task": "NER"}
{"text": "The mechanism of formation of benzene rings during the pyrolysis of dichloro - and trichloroethylene has been investigated by the method of Laser Powered Homogeneous Pyrolysis coupled with product analysis by gas chromatography .", "entity": [{"entity": "benzene", "entity_type": "Chemical", "pos": [30, 37]}, {"entity": "dichloro - and trichloroethylene", "entity_type": "Chemical", "pos": [68, 100]}], "task": "NER"}
{"text": "Additionally , selected ( co ) - pyrolyses between the chlorinated ethylenes , CH2Cl2 , C4Cl4 , C4Cl6 , and C2H2 have been performed to explicitly probe the roles of 2C3 and C4 / C2 reaction pairs in aromatic growth .", "entity": [{"entity": "chlorinated ethylenes", "entity_type": "Chemical", "pos": [55, 76]}, {"entity": "CH2Cl2", "entity_type": "Chemical", "pos": [79, 85]}, {"entity": "C4Cl4", "entity_type": "Chemical", "pos": [88, 93]}, {"entity": "C4Cl6", "entity_type": "Chemical", "pos": [96, 101]}, {"entity": "C2H2", "entity_type": "Chemical", "pos": [108, 112]}, {"entity": "2C3", "entity_type": "Chemical", "pos": [166, 169]}, {"entity": "C4", "entity_type": "Chemical", "pos": [174, 176]}, {"entity": "C2", "entity_type": "Chemical", "pos": [179, 181]}], "task": "NER"}
{"text": "The presence of odd - carbon products in neat C4Cl6 pyrolyses indicates 2C3 processes are operative in these systems ; however , comparison with product yields from C2HCl3 suggests C4 / C2 processes dominate most other systems .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [22, 28]}, {"entity": "C4Cl6", "entity_type": "Chemical", "pos": [46, 51]}, {"entity": "2C3", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "C2HCl3", "entity_type": "Chemical", "pos": [165, 171]}, {"entity": "C4", "entity_type": "Chemical", "pos": [181, 183]}, {"entity": "C2", "entity_type": "Chemical", "pos": [186, 188]}], "task": "NER"}
{"text": "This is further evidenced by an absence of C3 and other odd - carbon species in ( co ) - pyrolyses with dichloromethane which should seed C3 - based growth .", "entity": [{"entity": "C3", "entity_type": "Chemical", "pos": [43, 45]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "dichloromethane", "entity_type": "Chemical", "pos": [104, 119]}, {"entity": "C3", "entity_type": "Chemical", "pos": [138, 140]}], "task": "NER"}
{"text": "The reactions of perchlorinated C4 species C4Cl5 , C4Cl3 , and C4Cl4 with C2Cl2 were subsequently explored through extensive kinetic simulations of the possible reaction pathways based on previous kinetic models and the exhaustive quantum chemical investigations of our preceding work .", "entity": [{"entity": "perchlorinated C4", "entity_type": "Chemical", "pos": [17, 34]}, {"entity": "C4Cl5", "entity_type": "Chemical", "pos": [43, 48]}, {"entity": "C4Cl3", "entity_type": "Chemical", "pos": [51, 56]}, {"entity": "C4Cl4", "entity_type": "Chemical", "pos": [63, 68]}, {"entity": "C2Cl2", "entity_type": "Chemical", "pos": [74, 79]}], "task": "NER"}
{"text": "The experimental and theoretical results strongly suggest that , at moderate temperatures , aromatic ring formation from chlorinated ethylenes normally follows a Diels - Alder coupling of C4 and C2 molecular units followed by internal shifts ; the one exception is the C4Cl4 + C2Cl2 system , where steric factors lead to the formation of non - aromatic products .", "entity": [{"entity": "chlorinated ethylenes", "entity_type": "Chemical", "pos": [121, 142]}, {"entity": "C4", "entity_type": "Chemical", "pos": [188, 190]}, {"entity": "C2", "entity_type": "Chemical", "pos": [195, 197]}, {"entity": "C4Cl4", "entity_type": "Chemical", "pos": [269, 274]}, {"entity": "C2Cl2", "entity_type": "Chemical", "pos": [277, 282]}], "task": "NER"}
{"text": "There is little evidence for radical - based routes in these systems .", "entity": [], "task": "NER"}
{"text": "CH - 01 is a hypoxia - activated prodrug that sensitizes cells to hypoxia / reoxygenation through inhibition of Chk1 and Aurora A .", "entity": [{"entity": "CH - 01", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "The increased resistance of hypoxic cells to all forms of cancer therapy presents a major barrier to the successful treatment of most solid tumors .", "entity": [], "task": "NER"}
{"text": "Inhibition of the essential kinase , Checkpoint kinase 1 ( Chk1 ) has been described as a promising cancer therapy for tumors with high levels of hypoxia - induced replication stress .", "entity": [], "task": "NER"}
{"text": "However , as inhibition of Chk1 affects normal replication and induces DNA damage , these agents also have the potential to induce genomic instability and contribute to tumorigenesis .", "entity": [], "task": "NER"}
{"text": "To overcome this problem , we have developed a bioreductive prodrug , which functions as a Chk1 / Aurora A inhibitor specifically in hypoxic conditions .", "entity": [], "task": "NER"}
{"text": "To achieve this activity , a key functionality on the Chk1 inhibitor ( CH - 01 ) is masked by a bioreductive group , rendering the compound inactive as a Chk1 / Aurora A inhibitor .", "entity": [{"entity": "CH - 01", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "Reduction of the bioreductive group nitro moiety , under hypoxic conditions , reveals an electron - donating substituent that leads to fragmentation of the molecule , affording the active inhibitor .", "entity": [{"entity": "nitro", "entity_type": "Chemical", "pos": [36, 41]}], "task": "NER"}
{"text": "Most importantly , we show a significant loss of viability in cancer cell lines exposed to hypoxia in the presence of CH - 01 .", "entity": [{"entity": "CH - 01", "entity_type": "Chemical", "pos": [118, 125]}], "task": "NER"}
{"text": "This novel approach targets the most aggressive and therapy - resistant tumor fraction while protecting normal tissue from therapy - induced genomic instability .", "entity": [], "task": "NER"}
{"text": "Toxicity study of isolated polypeptide from wool hydrolysate .", "entity": [], "task": "NER"}
{"text": "The cytotoxicity of wool polypeptide has been evaluated by both cell and animal models .", "entity": [], "task": "NER"}
{"text": "Wool was dissolved in sodium hydroxide solution , the pH value of the solution was adjusted to 5 . 55 and the precipitate was harvested as wool polypeptide .", "entity": [{"entity": "sodium hydroxide", "entity_type": "Chemical", "pos": [22, 38]}], "task": "NER"}
{"text": "The spray - dried polypeptide was collected as powders and characterized by SEM , FTIR and TG - DSC .", "entity": [], "task": "NER"}
{"text": "The cell culturing results showed that wool polypeptide had no obvious negative effect on cell viability in vitro .", "entity": [], "task": "NER"}
{"text": "Both acute oral toxicity and subacute 30 - day oral toxicology studies showed that wool polypeptide had no influence on body weight , feed consumption , blood chemistry , and hematology at any dose levels .", "entity": [], "task": "NER"}
{"text": "There were no treatment related findings on gross or detailed necroscopy , organ weights , organ / body weight ratios and histology .", "entity": [], "task": "NER"}
{"text": "Our study indicated the absence of toxicity in wool polypeptide and supported its safe use as a food ingredient or drug carrier .", "entity": [], "task": "NER"}
{"text": "A c ai ( Euterpe oleracea Mart . ) feeding attenuates dimethylhydrazine - induced rat colon carcinogenesis .", "entity": [{"entity": "dimethylhydrazine", "entity_type": "Chemical", "pos": [54, 71]}], "task": "NER"}
{"text": "This study investigated the protective effect of spray - dried a c a i powder ( AP ) intake on colon carcinogenesis induced by 1 , 2 - dimethylhydrazine ( DMH ) in male Wistar rats .", "entity": [{"entity": "1 , 2 - dimethylhydrazine", "entity_type": "Chemical", "pos": [127, 152]}, {"entity": "DMH", "entity_type": "Chemical", "pos": [155, 158]}], "task": "NER"}
{"text": "After 4weeks of DMH administrations , the groups were fed with standard diet , a diet containing 2 . 5 % or 5 . 0 % AP or a diet containing 0 . 2 % N - acetylcysteine ( NAC ) for 10weeks , using aberrant crypt foci ( ACF ) as the endpoint .", "entity": [{"entity": "DMH", "entity_type": "Chemical", "pos": [16, 19]}, {"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [148, 166]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [169, 172]}], "task": "NER"}
{"text": "Additionally , two groups were fed with standard diet or a diet containing 5 . 0 % AP for 20weeks , using colon tumors as the endpoint .", "entity": [], "task": "NER"}
{"text": "In ACF assay , a reduction in the number of aberrant crypts ( ACs ) and ACF ( 1 - 3 AC ) were observed in the groups fed with 5 . 0 % AP ( 37 % AC and 47 % ACF inhibition , p = 0 . 036 ) and 0 . 2 % NAC ( 39 % AC and 41 % ACF inhibition , p = 0 . 042 ) .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [199, 202]}], "task": "NER"}
{"text": "In tumor assay , a reduction in the number of invasive tumors ( p < 0 . 005 ) and tumor multiplicity ( p = 0 . 001 ) was observed in the group fed with 5 . 0 % AP .", "entity": [], "task": "NER"}
{"text": "Also , a reduction in tumor Ki - 67 cell proliferation ( p = 0 . 003 ) and net growth index ( p = 0 . 001 ) was observed in the group fed with 5 . 0 % AP .", "entity": [], "task": "NER"}
{"text": "Therefore the findings of this study indicate that AP feeding may reduce the development of chemically - induced rat colon carcinogenesis .", "entity": [], "task": "NER"}
{"text": "Connexin channel modulators and their mechanisms of action .", "entity": [], "task": "NER"}
{"text": "Gap junction channels and hemichannels formed by the connexin family of proteins play important roles in many aspects of tissue homeostasis in the brain and in other organs .", "entity": [], "task": "NER"}
{"text": "In addition , connexin channels have been proposed as pharmacological targets in the treatment of a number of human disorders .", "entity": [], "task": "NER"}
{"text": "In this review , we describe the connexin - subtype selectivity and specificity of pharmacological agents that are commonly used to modulate connexin channels .", "entity": [], "task": "NER"}
{"text": "We also highlight recent progress made towardtoward identifying new agents for connexin channels that act in a selective and specific manner .", "entity": [], "task": "NER"}
{"text": "Finally , we discuss developing insights into possible mechanisms by which these agents modulate connexin channel function .", "entity": [], "task": "NER"}
{"text": "1 , 1 - Difluoroethyl - substituted triazolothienopyrimidines as inhibitors of a human urea transport protein ( UT - B ) : New analogs and binding model .", "entity": [{"entity": "1 , 1 - Difluoroethyl - substituted triazolothienopyrimidines", "entity_type": "Chemical", "pos": [0, 61]}, {"entity": "urea", "entity_type": "Chemical", "pos": [87, 91]}], "task": "NER"}
{"text": "The kidney urea transport protein UT - B is an attractive target for the development of small - molecule inhibitors with a novel diuretic ( ' urearetic ' ) action .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [11, 15]}], "task": "NER"}
{"text": "Previously , two compounds in the triazolothienopyrimidine scaffold ( 1a and 1c ) were reported as UT - B inhibitors .", "entity": [{"entity": "triazolothienopyrimidine", "entity_type": "Chemical", "pos": [34, 58]}], "task": "NER"}
{"text": "Compound 1c incorporates a 1 , 1 - difluoroethyl group , which affords improved microsomal stability when compared to the corresponding ethyl - substituted compound 1a .", "entity": [{"entity": "1 , 1 - difluoroethyl", "entity_type": "Chemical", "pos": [27, 48]}, {"entity": "ethyl", "entity_type": "Chemical", "pos": [136, 141]}], "task": "NER"}
{"text": "Here , a small focused library ( 4a - 4f ) was developed around lead inhibitor 1c to investigate the requirement of an amidine - linked thiophene in the inhibitor scaffold .", "entity": [{"entity": "amidine", "entity_type": "Chemical", "pos": [119, 126]}, {"entity": "thiophene", "entity_type": "Chemical", "pos": [136, 145]}], "task": "NER"}
{"text": "Two compounds ( 4a and 4b ) with nanomolar inhibitory potency ( IC50 =~ 40nM ) were synthesized .", "entity": [], "task": "NER"}
{"text": "Computational docking of lead structure 1c and 4a - 4f into a homology model of the UT - B cytoplasmic surface suggested binding with the core heterocycle buried deep into the hydrophobic pore region of the protein .", "entity": [], "task": "NER"}
{"text": "Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia .", "entity": [{"entity": "triacylglycerol", "entity_type": "Chemical", "pos": [35, 50]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [56, 63]}], "task": "NER"}
{"text": "OBJECTIVE : Studies have started to question whether a specific component or combinations of metabolic syndrome ( MetS ) components may be more important in relation to cardiovascular disease risk .", "entity": [], "task": "NER"}
{"text": "Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [68, 75]}], "task": "NER"}
{"text": "METHODS : Men classified with the MetS underwent a sequential test meal investigation , in which blood samples were taken at regular intervals after a test breakfast ( t = 0 min ) and lunch ( t = 330 min ) .", "entity": [], "task": "NER"}
{"text": "Lipids , glucose and insulin were measured in the fasting and postprandial samples .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [9, 16]}], "task": "NER"}
{"text": "RESULTS : MetS subjects with 3 or 4 components were subdivided into those without ( n = 34 ) and with ( n = 23 ) fasting hyperglycaemia ( >= 5 . 6mmol / l ) , irrespective of the combination of components .", "entity": [], "task": "NER"}
{"text": "Fasting lipids and insulin were similar in the two groups , with glucose significantly higher in the men with glucose as a MetS component ( P < 0 . 001 ) .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [65, 72]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [110, 117]}], "task": "NER"}
{"text": "Following the test meals , there were higher maximum concentration ( maxC ) , area under the curve ( AUC ) and incremental AUC ( P <= 0 . 016 ) for the postprandial triacylglycerol ( TAG ) response in men with fasting hyperglycaemia .", "entity": [{"entity": "triacylglycerol", "entity_type": "Chemical", "pos": [165, 180]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [183, 186]}], "task": "NER"}
{"text": "Greater glucose AUC ( P < 0 . 001 ) and insulin maxC ( P = 0 . 010 ) were also observed in these individuals after the test meals .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [8, 15]}], "task": "NER"}
{"text": "Multiple regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "TAG", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [111, 118]}], "task": "NER"}
{"text": "CONCLUSION : Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose .", "entity": [{"entity": "TAG", "entity_type": "Chemical", "pos": [81, 84]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [90, 97]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [144, 151]}], "task": "NER"}
{"text": "The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia .", "entity": [], "task": "NER"}
{"text": "HIV Cure : Knocking on the Door .", "entity": [], "task": "NER"}
{"text": "Although major advances in drug development and public health are helping to control the HIV / AIDS epidemic , there is a strong rationale for pursuing a more definitive cure .", "entity": [], "task": "NER"}
{"text": "Several bold but unproven strategies for HIV eradication are reviewed in this issue of CPT , including novel drugs , gene therapy , and bone marrow transplantation ( BMT ) .", "entity": [], "task": "NER"}
{"text": "Early results , including one probable case of HIV eradication in a leukemia patient , are intriguing but raise many questions .", "entity": [], "task": "NER"}
{"text": "New Diterpenes from a Godavari Mangrove , Ceriops decandra .", "entity": [{"entity": "Diterpenes", "entity_type": "Chemical", "pos": [4, 14]}], "task": "NER"}
{"text": "Eleven new diterpenes , named decandrins A - K ( 1 - 11 ) , including nine abietanes ( 1 - 9 ) and two podocarpanes ( 10 - 11 ) , were isolated from the barks of an Indian mangrove , Ceriops decandra , collected in the mangrove swamp of Godavari estuary , Andhra Pradesh , together with four known abietanes .", "entity": [{"entity": "diterpenes", "entity_type": "Chemical", "pos": [11, 21]}, {"entity": "decandrins A - K", "entity_type": "Chemical", "pos": [30, 46]}, {"entity": "abietanes", "entity_type": "Chemical", "pos": [75, 84]}, {"entity": "podocarpanes", "entity_type": "Chemical", "pos": [103, 115]}, {"entity": "abietanes", "entity_type": "Chemical", "pos": [298, 307]}], "task": "NER"}
{"text": "The structures of these compounds were established on the basis of spectroscopic data ( new compounds ) or comparison with data in the literature ( known compounds ) .", "entity": [], "task": "NER"}
{"text": "This is the first report of abietane and podocarpane diterpenoids from C . decandra .", "entity": [{"entity": "abietane", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "podocarpane", "entity_type": "Chemical", "pos": [41, 52]}, {"entity": "diterpenoids", "entity_type": "Chemical", "pos": [53, 65]}], "task": "NER"}
{"text": "Spin - polarized transport through single - molecule magnet Mn6 complexes .", "entity": [{"entity": "Mn6", "entity_type": "Chemical", "pos": [60, 63]}], "task": "NER"}
{"text": "The coherent transport properties of a device , constructed by sandwiching a Mn6 single - molecule magnet between two gold surfaces , are studied theoretically by using the non - equilibrium Green ' s function approach combined with density functional theory .", "entity": [{"entity": "Mn6", "entity_type": "Chemical", "pos": [77, 80]}], "task": "NER"}
{"text": "Two spin states of such Mn6 complexes are explored , namely the ferromagnetically coupled configuration of the six Mn ( III ) cations , leading to the S = 12 ground state , and the low S = 4 spin state .", "entity": [{"entity": "Mn6", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "Mn ( III )", "entity_type": "Chemical", "pos": [115, 125]}], "task": "NER"}
{"text": "For voltages up to 1 volt the S = 12 ground state shows a current one order of magnitude larger than that of the S = 4 state .", "entity": [], "task": "NER"}
{"text": "Furthermore this is almost completely spin - polarized , since the Mn6 frontier molecular orbitals for S = 12 belong to the same spin manifold .", "entity": [{"entity": "Mn6", "entity_type": "Chemical", "pos": [67, 70]}], "task": "NER"}
{"text": "As such the high - anisotropy Mn6 molecule appears as a promising candidate for implementing , at the single molecular level , both spin - switches and low - temperature spin - valves .", "entity": [{"entity": "Mn6", "entity_type": "Chemical", "pos": [30, 33]}], "task": "NER"}
{"text": "Concentration and Strain Fields inside a Ag / Au Core - Shell Nanowire Studied by Coherent X - ray Diffraction .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [41, 43]}, {"entity": "Au", "entity_type": "Chemical", "pos": [46, 48]}], "task": "NER"}
{"text": "Three - dimensional coherent diffraction patterns of an isolated , single - crystalline Ag / Au core - shell nanowire were recorded at different X - ray beam energies close to the Au LIII absorption edge .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [88, 90]}, {"entity": "Au", "entity_type": "Chemical", "pos": [93, 95]}, {"entity": "Au", "entity_type": "Chemical", "pos": [180, 182]}], "task": "NER"}
{"text": "Two - dimensional slices of the three - dimensional diffraction pattern , with the diffraction vector oriented perpendicular to the wire axis , were investigated in detail .", "entity": [], "task": "NER"}
{"text": "In reciprocal space , facet streaks with thickness fringes were clearly observed in the two - dimensional diffraction patterns , from which the shape and size of the corresponding cross sections of the nanowire could be revealed .", "entity": [], "task": "NER"}
{"text": "Comparison with simulated diffraction patterns exhibited the coherency strain field in the nanowire .", "entity": [], "task": "NER"}
{"text": "During in situ annealing at temperatures which would lead to significant intermixing by volume diffusion in bulk material , according to literature data , a core - shell morphology was preserved ; that is , intermixing in the nanowire was pronouncedly decelerated compared to bulk diffusion .", "entity": [], "task": "NER"}
{"text": "Assessing the Accuracy and Performance of Implicit Solvent Models for Drug Molecules : Conformational Ensemble Approaches .", "entity": [], "task": "NER"}
{"text": "The accuracy and performance of implicit solvent methods for solvation free energy calculations were assessed on a set of 20 neutral drug molecules .", "entity": [], "task": "NER"}
{"text": "Molecular dynamics ( MD ) provided ensembles of conformations in water and water - saturated octanol .", "entity": [{"entity": "octanol", "entity_type": "Chemical", "pos": [93, 100]}], "task": "NER"}
{"text": "The solvation free energies were calculated by popular implicit solvent models based on quantum mechanical ( QM ) electronic densities ( COSMO - RS , MST , SMD ) as well as on molecular mechanical ( MM ) point - charge models ( GB , PB ) .", "entity": [], "task": "NER"}
{"text": "The performance of the implicit models was tested by a comparison with experimental water - octanol transfer free energies ( Delta Gow ) by using single - and multiconformation approaches .", "entity": [{"entity": "octanol", "entity_type": "Chemical", "pos": [92, 99]}], "task": "NER"}
{"text": "MD simulations revealed difficulties in a priori estimation of the flexibility features of the solutes from simple structural descriptors , such as the number of rotatable bonds .", "entity": [], "task": "NER"}
{"text": "An increasing accuracy of the calculated Delta Gow was observed in the following order : GB1 ~ PB < GB7 << MST < SMD ~ COSMO - RS with a clear distinction identified between MM - and QM - based models , although for the set excluding three largest molecules , the differences among COSMO - RS , MST , and SMD were negligible .", "entity": [], "task": "NER"}
{"text": "It was shown that the single - conformation approach applied to crystal geometries provides a rather accurate estimate of Delta Gow for rigid molecules yet fails completely for the flexible ones .", "entity": [], "task": "NER"}
{"text": "The multiconformation approaches improved the performance , but only when the deformation contribution was ignored .", "entity": [], "task": "NER"}
{"text": "It was revealed that for large - scale calculations on small molecules a recent GB model , GB7 , provided a reasonable accuracy / speed ratio .", "entity": [], "task": "NER"}
{"text": "In conclusion , the study contributes to the understanding of solvation free energy calculations for physical and medicinal chemistry applications .", "entity": [], "task": "NER"}
{"text": "Three - dimensional plasmonic chiral tetramers assembled by DNA origami .", "entity": [], "task": "NER"}
{"text": "Molecular chemistry offers a unique toolkit to draw inspiration for the design of artificial metamolecules .", "entity": [], "task": "NER"}
{"text": "For a long time , optical circular dichroism has been exclusively the terrain of natural chiral molecules , which exhibit optical activity mainly in the UV spectral range , thus greatly hindering their significance for a broad range of applications .", "entity": [], "task": "NER"}
{"text": "Here we demonstrate that circular dichroism can be generated with artificial plasmonic chiral nanostructures composed of the minimum number of spherical gold nanoparticles required for three - dimensional ( 3D ) chirality .", "entity": [], "task": "NER"}
{"text": "We utilize a rigid addressable DNA origami template to precisely organize four nominally identical gold nanoparticles into a three - dimensional asymmetric tetramer .", "entity": [], "task": "NER"}
{"text": "Because of the chiral structural symmetry and the strong plasmonic resonant coupling between the gold nanoparticles , the 3D plasmonic assemblies undergo different interactions with left and right circularly polarized light , leading to pronounced circular dichroism .", "entity": [], "task": "NER"}
{"text": "Our experimental results agree well with theoretical predictions .", "entity": [], "task": "NER"}
{"text": "The simplicity of our structure geometry and , most importantly , the concept of resorting on biology to produce artificial photonic functionalities open a new pathway to designing smart artificial plasmonic nanostructures for large - scale production of optically active metamaterials .", "entity": [], "task": "NER"}
{"text": "Demonstration of Efficient On - Chip Photon Transfer in Self - Assembled Optoplasmonic Networks .", "entity": [], "task": "NER"}
{"text": "Plasmonic nanoantennas facilitate the manipulation of light fields on deeply sub - diffraction - limited length scales , but high dissipative losses in metals make new approaches for an efficient energy transfer in extended on - chip integrated plasmonic circuits mandatory .", "entity": [], "task": "NER"}
{"text": "We demonstrate in this article efficient photon transfer in discrete optoplasmonic molecules comprising gold nanoparticle ( NP ) dimer antennas located in the evanescent field of a 2 mu m diameter polystyrene bead , which served as an optical microcavity ( OM ) .", "entity": [{"entity": "polystyrene", "entity_type": "Chemical", "pos": [197, 208]}], "task": "NER"}
{"text": "The optoplasmonic molecules were generated through a guided self - assembly strategy in which the OMs were immobilized in binding sites generated by quartz ( SiO2 ) or silicon posts that contained plasmonic nanoantennas on their tips .", "entity": [{"entity": "quartz", "entity_type": "Chemical", "pos": [149, 155]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [158, 162]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [168, 175]}], "task": "NER"}
{"text": "Control of the post height facilitated an accurate positioning of the plasmonic antennas into the evanescent field of the whispering gallery modes located in the equatorial plane of the OM .", "entity": [], "task": "NER"}
{"text": "Cy3 and Cy5 . 5 dyes were tethered to the plasmonic antennas through oligonucleotide spacers to act as on - chip light sources .", "entity": [{"entity": "Cy3", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "Cy5 . 5", "entity_type": "Chemical", "pos": [8, 15]}], "task": "NER"}
{"text": "The intensity of Cy3 was found to be increased relative to that of Cy5 . 5 in the vicinity of the plasmonic antennas where strongly enhanced electric field intensity and optical density of states selectively increase the excitation and emission rates of Cy3 due to spectral overlap with the plasmon .", "entity": [{"entity": "Cy3", "entity_type": "Chemical", "pos": [17, 20]}, {"entity": "Cy5 . 5", "entity_type": "Chemical", "pos": [67, 74]}, {"entity": "Cy3", "entity_type": "Chemical", "pos": [254, 257]}], "task": "NER"}
{"text": "The fluorescent dyes preferentially emitted into the OM , which efficiently trapped and recirculated the photons .", "entity": [], "task": "NER"}
{"text": "We experimentally determined a relative photon transfer efficiency of 44 % in non - optimized self - assembled optoplasmonic molecules in this proof - of - principle study .", "entity": [], "task": "NER"}
{"text": "The effect of inorganic salt type and concentration on hydrophilic drug loading into microspheres using the emulsion / solvent diffusion method .", "entity": [], "task": "NER"}
{"text": "Abstract Aim : In order to avoid gastric irritation caused by tolmetin sodium ( TS ) , gastro resistant Eudragit (R) S 100 microsphere formulations were prepared with the emulsion / solvent diffusion method .", "entity": [{"entity": "tolmetin sodium", "entity_type": "Chemical", "pos": [62, 77]}, {"entity": "Eudragit", "entity_type": "Chemical", "pos": [104, 112]}], "task": "NER"}
{"text": "Materials : Considering the high water solubility of the TS molecule , the effects of the presence of inorganic salt ( NaCl , NaBr and KH2PO4 ; 0 . 1 M and 1 . 0 M ) in external phase and external phase pH on the encapsulation efficiency were evaluated .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [119, 123]}, {"entity": "NaBr", "entity_type": "Chemical", "pos": [126, 130]}, {"entity": "KH2PO4", "entity_type": "Chemical", "pos": [135, 141]}], "task": "NER"}
{"text": "Results : Percentage yield value was found to vary between 55 . 8 % and 72 . 1 % .", "entity": [], "task": "NER"}
{"text": "Improvement in encapsulation efficiency was determined by increasing concentrations of NaCl , NaBr and KH2PO4 .", "entity": [{"entity": "NaCl", "entity_type": "Chemical", "pos": [87, 91]}, {"entity": "NaBr", "entity_type": "Chemical", "pos": [94, 98]}, {"entity": "KH2PO4", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "The microspheres were observed to have a spherical shape and the measured particle size values varied between 52 . 1 and 81 . 5 micro m .", "entity": [], "task": "NER"}
{"text": "The released amounts of the drug were found to be low as the inorganic salt concentrations increased .", "entity": [], "task": "NER"}
{"text": "Conclusion : Conclusively , drug release in stomach pH was significantly prevented by the microspheres prepared using Eudragit (R) S 100 polymer , and these formulations are considered to be a model for other orally administered drugs with similar problems .", "entity": [{"entity": "Eudragit", "entity_type": "Chemical", "pos": [118, 126]}], "task": "NER"}
{"text": "Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery .", "entity": [], "task": "NER"}
{"text": "Abstract Objective : The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system .", "entity": [], "task": "NER"}
{"text": "Materials and methods : With bovine albumin - fluorescein isothiocyanate conjugate ( FITC - BSA ) as a vaccine model , formulations were selected with the construction of pseudo - ternary phase diagrams and a short - term stability study .", "entity": [{"entity": "fluorescein isothiocyanate", "entity_type": "Chemical", "pos": [46, 72]}, {"entity": "FITC", "entity_type": "Chemical", "pos": [85, 89]}], "task": "NER"}
{"text": "The size of the emulsion droplets was furthered optimized with high - pressure homogenization .", "entity": [], "task": "NER"}
{"text": "The optimized formulation was evaluated for its skin permeation efficiency .", "entity": [], "task": "NER"}
{"text": "In vitro skin permeation studies were conducted with shaved BALB / c mice skin samples with a Franz diffusion cell system .", "entity": [], "task": "NER"}
{"text": "Different drug concentrations were compared , and the effect of the nanoemulsion excipients on the permeation of the FITC - BSA was also studied .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [117, 121]}], "task": "NER"}
{"text": "Results : The optimum homogenization regime was determined to be five passes at 20 000 psi , with no evidence of protein degradation during processing .", "entity": [], "task": "NER"}
{"text": "With these conditions , the particle diameter was 85 . 2 nm +/- 15 . 5 nm with a polydispersity index of 0 . 186 +/- 0 . 026 and viscosity of 14 . 6 cP +/- 1 . 2 cP .", "entity": [], "task": "NER"}
{"text": "The optimized formulation proved stable for 1 year at 4 degrees C .", "entity": [], "task": "NER"}
{"text": "In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC - BSA through skin with an enhancement ratio of 4 . 2 compared to a neat control solution .", "entity": [{"entity": "FITC", "entity_type": "Chemical", "pos": [95, 99]}], "task": "NER"}
{"text": "Finally , a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23 . 44 mu g / cm ( 2 ) / h for the nanoemulsion as opposed to 6 . 10 mu g / cm ( 2 ) / h for the emulsifiers .", "entity": [], "task": "NER"}
{"text": "Conclusion : A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured .", "entity": [], "task": "NER"}
{"text": "The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle .", "entity": [], "task": "NER"}
{"text": "Polymer - based protein engineering can rationally tune enzyme activity , pH - dependence , and stability .", "entity": [], "task": "NER"}
{"text": "The attachment of inert polymers , such as polyethyleneglycol , to proteins has driven the emergence of a multibillion dollar biotechnology industry .", "entity": [{"entity": "polyethyleneglycol", "entity_type": "Chemical", "pos": [43, 61]}], "task": "NER"}
{"text": "In all cases , proteins have been stabilized or altered by covalently coupling the pre - existing polymer to the surface of the protein .", "entity": [], "task": "NER"}
{"text": "This approach is inherently limited by a lack of exquisite control of polymer architecture , chain length , site and density of attachment .", "entity": [], "task": "NER"}
{"text": "Using a novel water - soluble atom transfer radical polymerization initiator , we have grown temperature - and pH - responsive polymers from the surface of a model protein , the enzyme chymotrypsin .", "entity": [], "task": "NER"}
{"text": "Poly ( 2 - ( dimethylamino ) ethyl methacrylate ) changes in conformation with altered temperature and pH .", "entity": [{"entity": "Poly ( 2 - ( dimethylamino ) ethyl methacrylate )", "entity_type": "Chemical", "pos": [0, 49]}], "task": "NER"}
{"text": "Growing the polymer from the surface of chymotrypsin we were able to demonstrate that changes in temperature or pH can change predictably the conformation of the polymer surrounding the enzyme , which in turn enabled the rational tailoring of enzyme activity and stability .", "entity": [], "task": "NER"}
{"text": "Using what we now term \" Polymer - Based Protein Engineering \" we have increased the activity and stability of chymotrypsin by an order of magnitude at pH ' s where the enzyme is usually inactive or unstable .", "entity": [], "task": "NER"}
{"text": "The Chemical constituents of the twigs of Ammopiptanthus nanus .", "entity": [], "task": "NER"}
{"text": "Two new isoflavone glycosides , ammopiptanosides A and B , have been isolated from the 95 % EtOH extract of the twigs of Ammopiptanthus nanus ( M . Pop . ) Cheng f . , together with six known compounds , and their structures were characterized by spectroscopic methods and compared with the data in the literature .", "entity": [{"entity": "isoflavone glycosides", "entity_type": "Chemical", "pos": [8, 29]}, {"entity": "ammopiptanosides A and B", "entity_type": "Chemical", "pos": [32, 56]}, {"entity": "EtOH", "entity_type": "Chemical", "pos": [92, 96]}], "task": "NER"}
{"text": "Sulfonated Polyaniline - Based Organic Electrodes for Controlled Electrical Stimulation of Human Osteosarcoma Cells .", "entity": [{"entity": "Sulfonated Polyaniline", "entity_type": "Chemical", "pos": [0, 22]}], "task": "NER"}
{"text": "Electrically conducting polymers ( CPs ) were found to stimulate various cell types such as neurons , osteoblasts , and fibroblasts in both in vitro and in vivo studies .", "entity": [], "task": "NER"}
{"text": "However , to our knowledge , no studies have been reported on the utility of CPs in stimulation of cancer or tumor cells in the literature .", "entity": [], "task": "NER"}
{"text": "Here we report a facile fabrication method of self - doped sulfonated polyaniline ( SPAN ) - based interdigitated electrodes ( IDEs ) for controlled electrical stimulation of human osteosarcoma ( HOS ) cells .", "entity": [{"entity": "sulfonated polyaniline", "entity_type": "Chemical", "pos": [59, 81]}, {"entity": "SPAN", "entity_type": "Chemical", "pos": [84, 88]}], "task": "NER"}
{"text": "Increased degree of sulfonation was found to increase the SPAN conductivity , which in turn improved the cell attachment and cell growth without electrical stimulation .", "entity": [{"entity": "SPAN", "entity_type": "Chemical", "pos": [58, 62]}], "task": "NER"}
{"text": "However , an enhanced cell growth was observed under controlled electrical ( AC ) stimulation at low applied voltage and frequency ( <= 800 mV and <= 1 kHz ) .", "entity": [], "task": "NER"}
{"text": "The cell growth reached a maximum threshold at an applied voltage or frequency and beyond which pronounced cell death was observed .", "entity": [], "task": "NER"}
{"text": "We believe that these organic electrodes may find utility in electrical stimulation of cancer or tumor cells for therapy and research and may also provide an alternative to the conventional metal - based electrodes .", "entity": [], "task": "NER"}
{"text": "Three new triterpene glycosides from Ilex asprella .", "entity": [{"entity": "triterpene glycosides", "entity_type": "Chemical", "pos": [10, 31]}], "task": "NER"}
{"text": "Three new sulfated triterpene glycosides , asprellanosides C - E ( 1 - 3 ) , were isolated from the roots of Ilex asprella .", "entity": [{"entity": "sulfated triterpene glycosides", "entity_type": "Chemical", "pos": [10, 40]}, {"entity": "asprellanosides C - E", "entity_type": "Chemical", "pos": [43, 64]}], "task": "NER"}
{"text": "Their structures were elucidated as 3 beta - [ ( 2 - O - sulfo - beta - d - xylopyranosyl ) oxy ] urs - 12 , 19 ( 29 ) - diene - 28 - oic acid 28 - beta - d - glucopyranoside ( 1 ) , 3 beta - [ ( 2 - O - sulfo - beta - d - xylopyranosyl ) oxy ] urs - 12 , 19 - diene - 28 - oic acid 28 - beta - d - glucopyranoside ( 2 ) , and 3 beta - [ ( 2 - O - sulfo - beta - d - xylopyranosyl ) oxy ] urs - 12 , 19 - diene - 28 - oic acid ( 3 ) on the basis of the spectral and chemical methods .", "entity": [{"entity": "3 beta - [ ( 2 - O - sulfo - beta - d - xylopyranosyl ) oxy ] urs - 12 , 19 ( 29 ) - diene - 28 - oic acid 28 - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [36, 174]}, {"entity": "3 beta - [ ( 2 - O - sulfo - beta - d - xylopyranosyl ) oxy ] urs - 12 , 19 - diene - 28 - oic acid 28 - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [183, 314]}, {"entity": "3 beta - [ ( 2 - O - sulfo - beta - d - xylopyranosyl ) oxy ] urs - 12 , 19 - diene - 28 - oic acid", "entity_type": "Chemical", "pos": [327, 426]}], "task": "NER"}
{"text": "The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy .", "entity": [], "task": "NER"}
{"text": "Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton : the dystrophin - and utrophin - glycoprotein complexes and alpha 7 beta 1 integrin .", "entity": [], "task": "NER"}
{"text": "Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy .", "entity": [], "task": "NER"}
{"text": "Muscular dystrophy is a progressive , lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration .", "entity": [], "task": "NER"}
{"text": "Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy .", "entity": [], "task": "NER"}
{"text": "Recently , we demonstrated that sarcospan facilitates protein - protein interactions amongst the adhesion complexes and is an important therapeutic target .", "entity": [], "task": "NER"}
{"text": "Here , we review current protein replacement strategies , discuss the potential benefits of sarcospan expression , and identify important experiments that must be addressed for sarcospan to move to the clinic .", "entity": [], "task": "NER"}
{"text": "This article is protected by copyright .", "entity": [], "task": "NER"}
{"text": "Design , Synthesis and biological evaluation of catecholamine vehicle for studying dopaminergic system .", "entity": [{"entity": "catecholamine", "entity_type": "Chemical", "pos": [48, 61]}], "task": "NER"}
{"text": "Catecholamine mimetic EDTA - bis ( tyramide ) was synthesized and characterized by various spectroscopic techniques ( NMR , Mass spectroscopy ) and lambda em 310 nm for the excitation at 270 nm .", "entity": [{"entity": "Catecholamine", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "EDTA - bis ( tyramide )", "entity_type": "Chemical", "pos": [22, 45]}], "task": "NER"}
{"text": "Molecular docking studies were performed with Human Serum Albumin ( HSA : PDB 1E78 ) , showing binding pattern with amino acid residues Arg218 , Arg222 and Lys444 , identifies the ligand - HSA interaction for the transportation affinity of the ligand at the specific site of the target .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [116, 126]}, {"entity": "Arg218", "entity_type": "Chemical", "pos": [136, 142]}, {"entity": "Arg222", "entity_type": "Chemical", "pos": [145, 151]}, {"entity": "Lys444", "entity_type": "Chemical", "pos": [156, 162]}], "task": "NER"}
{"text": "Subsequently binding study with HSA at lambda ex = 350 nm found to be 5 . 847x10 ( 4 ) M ( - 1 ) shows effective quenching effect .", "entity": [], "task": "NER"}
{"text": "Additionally to go more insight AChE binding affinity was investigated , which shows 90 % binding affinity for the 10 mM concentration .", "entity": [], "task": "NER"}
{"text": "IC50 value was was found 18 . 60 mu M for MAO - B inhibition .", "entity": [], "task": "NER"}
{"text": "Finally , EDTA - bis ( tyramide ) labeled with ( 99m ) Tc to investigate its in - vivo radiopharmaceutical efficiency , having 97 % binding affinity with 98 % radiochemical purity .", "entity": [{"entity": "EDTA - bis ( tyramide )", "entity_type": "Chemical", "pos": [10, 33]}, {"entity": "( 99m ) Tc", "entity_type": "Chemical", "pos": [47, 57]}], "task": "NER"}
{"text": "In - vivo studies were carried out for ( 99m ) Tc - EDTA - bis ( tyramide ) included blood kinetics showed a quick wash out from the circulation via renal route and biodistribution revealed that maximum % ID / g was found in kidney at 1h and its scintigraphy image shows 3 . 96 % brain uptake with respect to whole body .", "entity": [{"entity": "( 99m ) Tc - EDTA - bis ( tyramide )", "entity_type": "Chemical", "pos": [39, 75]}], "task": "NER"}
{"text": "Discovery of a new bioactive molecule for neuroblastoma .", "entity": [], "task": "NER"}
{"text": "Neuroblastoma , a common pediatric malignancy of neural crest origin , is unique in its wide spectrum of clinical and biological behavior , ranging from spontaneous regression or differentiation to rapid progression and metastasis .", "entity": [], "task": "NER"}
{"text": "Overexpression of neurotrophin receptors of the tyrosine kinase ( Trk ) family has been identified as a major prognostic and biological factor for this disease .", "entity": [{"entity": "tyrosine", "entity_type": "Chemical", "pos": [48, 56]}], "task": "NER"}
{"text": "Novel molecules were selected using cheminformatics tools ( SBVS & LBVS ) and screened in cell - based assays to modulate Trk receptor activity .", "entity": [], "task": "NER"}
{"text": "One compound ( C390 - 0031 ) had a potent anti - proliferative activity in dose - response studies using neuroblastoma cell lines .", "entity": [], "task": "NER"}
{"text": "The molecular effects of this molecule were further characterized by using cell - cycle and western blot analysis .", "entity": [], "task": "NER"}
{"text": "Interestingly , despite the presence of the anchoring fragment to the Trk kinase domain composing its structure , this molecule does not inhibit TrkA like lestaurtinib , constituting a new chemical with a yet unknown mechanism of action .", "entity": [{"entity": "lestaurtinib", "entity_type": "Chemical", "pos": [155, 167]}], "task": "NER"}
{"text": "Health benefits of seafood ; Is it just the fatty acids ?", "entity": [{"entity": "fatty acids", "entity_type": "Chemical", "pos": [44, 55]}], "task": "NER"}
{"text": "There is a considerable body of literature suggesting a wide range of health benefits associated with diets high in seafood .", "entity": [], "task": "NER"}
{"text": "However , the demand for seafood across the world now exceeds that available from capture fisheries .", "entity": [], "task": "NER"}
{"text": "This has created a rapidly increasing market for aquaculture products , the nutrient composition of which is dependent on feed composition .", "entity": [], "task": "NER"}
{"text": "The use of fishmeal in this food chain does little to counteract the environmental impact of fisheries and so the on - going development of alternative sources is to be welcomed .", "entity": [], "task": "NER"}
{"text": "Nevertheless , an in - depth understanding as to which nutrients in seafood provide benefit is required to permit the production of foods of maximal health benefit to humans .", "entity": [], "task": "NER"}
{"text": "This paper reviews our current knowledge of the beneficial nutrient composition of seafood , in particular omega - 3 fatty acids , selenium , taurine , vitamins D and B12 , in the context of the development of environmentally sustainable aquaculture .", "entity": [{"entity": "omega - 3 fatty acids", "entity_type": "Chemical", "pos": [107, 128]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [131, 139]}, {"entity": "taurine", "entity_type": "Chemical", "pos": [142, 149]}, {"entity": "vitamins D and B12", "entity_type": "Chemical", "pos": [152, 170]}], "task": "NER"}
{"text": "Assessing caffeine intake in the United Kingdom diet .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "Caffeine occurs naturally in the leaves and seeds of many plants and is artificially added to some beverages .", "entity": [{"entity": "Caffeine", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Consumption of caffeine has been linked to both positive and adverse health outcomes .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [15, 23]}], "task": "NER"}
{"text": "We incorporated estimates of caffeine content ( mg / 100g or ml ) of foods and drinks , taken from the published literature , to provide a preliminary estimate of caffeine intake for the UK population , based on data collected in the National Diet and Nutrition Survey 2008 - 10 .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [29, 37]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [163, 171]}], "task": "NER"}
{"text": "Among consumers mean total caffeine intakes of adult men 19 + y were significantly greater than intakes by boys 4 - 10y and 11 - 18y ( p < 0 . 05 ) , with the same age - related differences seen for females .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [27, 35]}], "task": "NER"}
{"text": "4 . 1 % of men 19 + y and 3 . 8 % of women 19 + y had caffeine intakes in excess of 300mg / d .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [54, 62]}], "task": "NER"}
{"text": "The addition of caffeine to UK food composition databases will allow more detailed study of the health effects of caffeine consumption .", "entity": [{"entity": "caffeine", "entity_type": "Chemical", "pos": [16, 24]}, {"entity": "caffeine", "entity_type": "Chemical", "pos": [114, 122]}], "task": "NER"}
{"text": "Nutrients and bioactive compounds of Thai indigenous fruits .", "entity": [], "task": "NER"}
{"text": "This study determined the nutritional potential of Thai indigenous fruits in terms of nutrients , bioactive compounds , and antioxidant activities .", "entity": [], "task": "NER"}
{"text": "Three indigenous fruits were collected at two conservation areas in Kanchanaburi province , Thailand .", "entity": [], "task": "NER"}
{"text": "The results showed that Phyllanthus emblica L . exhibited the highest levels of vitamin C ( 575 +/- 452mg / 100g ) , total phenolics ( TP ) ( 3703 +/- 1244mGAE / 100g ) , and antioxidant activities , as measured by DPPH , FRAP and ORAC assays .", "entity": [{"entity": "vitamin C", "entity_type": "Chemical", "pos": [80, 89]}, {"entity": "phenolics", "entity_type": "Chemical", "pos": [123, 132]}, {"entity": "DPPH", "entity_type": "Chemical", "pos": [215, 219]}], "task": "NER"}
{"text": "Compared to the other two fruits , Antidesma velutinosum Blume contained higher levels of most nutrients and dietary fibre ( 15 . 6 +/- 5 . 9g / 100g ) , as well as carotenoids ( 335 +/- 98 mu g / 100g ) and phytosterols ( 22 . 1 +/- 3 . 9mg / 100g ) .", "entity": [{"entity": "phytosterols", "entity_type": "Chemical", "pos": [208, 220]}], "task": "NER"}
{"text": "Spondias pinnata ( L . f . ) Kurz was high in total phenolics ( 3178 +/- 887mGAE / 100g ) and antioxidant activity .", "entity": [{"entity": "phenolics", "entity_type": "Chemical", "pos": [52, 61]}], "task": "NER"}
{"text": "Moreover , high correlations were found between TP and antioxidant activities ( r > 0 . 9 ) .", "entity": [], "task": "NER"}
{"text": "These Thai indigenous fruits are potentially good sources of nutrients , bioactive compounds , and antioxidant activities .", "entity": [], "task": "NER"}
{"text": "Conservation and utilisation should be promoted for food security and consumption as part of a healthy diet .", "entity": [], "task": "NER"}
{"text": "Effect of different maize meal diets on growth and vitamin A : Case - study on chickens .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [51, 60]}], "task": "NER"}
{"text": "South Africa embarked on mandatory vitamin and mineral fortification of wheat flour and maize meal in 2003 as part of a multi - faceted approach to alleviate malnutrition .", "entity": [], "task": "NER"}
{"text": "However , it was reported , in 2008 , that vitamin A deficiency increased despite the mandatory fortification programme .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [43, 52]}], "task": "NER"}
{"text": "This motivates an investigation into the absorption of vitamin A as fortificant in the maize meal .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [55, 64]}], "task": "NER"}
{"text": "Relative absorption , in chickens as the biological model , was determined by evaluating growth and vitamin A status .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [100, 109]}], "task": "NER"}
{"text": "The weight , cumulative feed intake and liver retinol stores of chickens on different diets were measured over a 6week period .", "entity": [{"entity": "retinol", "entity_type": "Chemical", "pos": [46, 53]}], "task": "NER"}
{"text": "The fortified white maize meal diet was able to maintain the vitamin A status of the chickens .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [61, 70]}], "task": "NER"}
{"text": "Poor absorption of the fortificant vitamin A is therefore not a constraint in combating vitamin A deficiency .", "entity": [{"entity": "vitamin A", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "vitamin A", "entity_type": "Chemical", "pos": [88, 97]}], "task": "NER"}
{"text": "It is in therefore also important to focus on the level of fortification delivered when consumed as a traditional prepared dish .", "entity": [], "task": "NER"}
{"text": "In the traditional diet , maize porridge is often consumed with only a relish .", "entity": [], "task": "NER"}
{"text": "The total fat content of the traditional meal is very low , lacking absorption enhancers .", "entity": [], "task": "NER"}
{"text": "Voluntary food fortification with folic acid in Spain : Predicted contribution to children ' s dietary intakes as assessed with new food folate composition data .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [34, 44]}, {"entity": "folate", "entity_type": "Chemical", "pos": [137, 143]}], "task": "NER"}
{"text": "The Spanish market offers a significant number of folic acid ( FA ) voluntarily fortified foods .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [50, 60]}], "task": "NER"}
{"text": "We analysed FA and ( 6S ) - 5 - methyltetrahydrofolic acid ( ( 6S ) - 5 - CH3 - H4PteGlu ) content in ready - to - eat cereals ( RTEC ) ( n = 68 ) and cow ' s milk ( n = 25 ) by a previously validated affinity chromatography - HPLC method .", "entity": [{"entity": "( 6S ) - 5 - methyltetrahydrofolic acid", "entity_type": "Chemical", "pos": [19, 58]}, {"entity": "( 6S ) - 5 - CH3 - H4PteGlu", "entity_type": "Chemical", "pos": [61, 88]}], "task": "NER"}
{"text": "Contribution to potential FA intakes for children aged 2 - 13years , was assessed using food consumption data from a representative nationwide study , folate Recommended Dietary Intakes ( RDI ) , and Upper Levels ( UL ) .", "entity": [{"entity": "folate", "entity_type": "Chemical", "pos": [151, 157]}], "task": "NER"}
{"text": "Results showed that at all food fortification levels obtained , fortified products provided more than tenfold FA than ( 6S ) - 5 - CH3 - H4PteGlu .", "entity": [{"entity": "( 6S ) - 5 - CH3 - H4PteGlu", "entity_type": "Chemical", "pos": [118, 145]}], "task": "NER"}
{"text": "For RTEC , the high fortification level provided 6 - 21 % , per serving , of RDI and >= 32 % of ULs at 90th percentile of RTEC consumption ( P90 ) .", "entity": [], "task": "NER"}
{"text": "Milk products fortified at the higher level reached on average 54 - 136 % of RDI per serving and only exceeded UL at P90 of milk consumption in children aged 2 - 5years .", "entity": [], "task": "NER"}
{"text": "Data collection and assessment of commonly consumed foods and recipes in six geo - political zones in Nigeria : Important for the development of a National Food Composition Database and Dietary Assessment .", "entity": [], "task": "NER"}
{"text": "A cross - sectional study was undertaken to collect and assess commonly consumed foods / recipes from the six geopolitical zones in Nigeria for the production of food composition database ( FCDB ) for dietary assessment .", "entity": [], "task": "NER"}
{"text": "Communities used were selected using a multi - stage sampling plan .", "entity": [], "task": "NER"}
{"text": "Focus group discussions , interviews , recipe documentation , food preparations and literature reviews were employed .", "entity": [], "task": "NER"}
{"text": "Qualitative methods were used to analyse and present data .", "entity": [], "task": "NER"}
{"text": "SWOT ( strengths , weaknesses , opportunities , and threats ) analysis was used to evaluate the project .", "entity": [], "task": "NER"}
{"text": "A total of 322 recipes were collected out of which 110 were soups .", "entity": [], "task": "NER"}
{"text": "Food consumption patterns across the geographical zones were found to be changing .", "entity": [], "task": "NER"}
{"text": "Variations in recipes and methods of preparation of similar foods were observed .", "entity": [], "task": "NER"}
{"text": "Factors to be considered in the development of a country - specific FCDB were identified .", "entity": [], "task": "NER"}
{"text": "There were challenges with the use of values reported in literature for Nigerian foods .", "entity": [], "task": "NER"}
{"text": "The study justifies the need for a country - specific FCDB that will include traditional recipes .", "entity": [], "task": "NER"}
{"text": "Dietary fibre fractions in cereal foods measured by a new integrated AOAC method .", "entity": [], "task": "NER"}
{"text": "The reliable determination of soluble , insoluble and total dietary fibre in baked goods and cereal flours is an important issue for research , nutritional labelling and marketing .", "entity": [], "task": "NER"}
{"text": "We compared total dietary fibre ( TDF ) contents of selected cereal based foods determined by AOAC Method 991 . 43 and the new AOAC Method 2009 . 01 .", "entity": [], "task": "NER"}
{"text": "Fifteen bread and bakery products were included in the study .", "entity": [], "task": "NER"}
{"text": "Our results showed that TDF values of cereal products determined by AOAC Method 2009 . 01 were always significantly higher than those determined by AOAC Method 991 . 43 .", "entity": [], "task": "NER"}
{"text": "This was explained by the inclusion of low molecular weight soluble fibre fractions and resistant starch fractions in the TDF measurement by AOAC 2009 . 01 .", "entity": [], "task": "NER"}
{"text": "This documents that nutritional labelling of cereal products poses the challenge how to update TDF data in nutrient databases in a reasonable time with an acceptable expenditure .", "entity": [], "task": "NER"}
{"text": "Total nitrogen vs . amino - acid profile as indicator of protein content of beef .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [6, 14]}, {"entity": "amino - acid", "entity_type": "Chemical", "pos": [20, 32]}], "task": "NER"}
{"text": "In most cited food composition studies and tables , the proximate system measures protein as total nitrogen ( N ) ( determined by Kjeldahl or Dumas method ) multiplied by a specific factor .", "entity": [{"entity": "nitrogen", "entity_type": "Chemical", "pos": [99, 107]}, {"entity": "N", "entity_type": "Chemical", "pos": [110, 111]}], "task": "NER"}
{"text": "A factor of 6 . 25 is used for determining total protein from total N ( Jones , Munsey , & Walker , 1942 ) .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [68, 69]}], "task": "NER"}
{"text": "Although more expensive , it is considered more accurate to base protein content of foods on amino acid data ( Greenfield & Southgate , 2003 ) .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [93, 103]}], "task": "NER"}
{"text": "A study on the nutrient composition of beef analysed the full amino - acid profile of fifteen retail cuts from three age groups and six fat codes , as well as determined total nitrogen content to determine proximate protein composition .", "entity": [{"entity": "amino - acid", "entity_type": "Chemical", "pos": [62, 74]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [176, 184]}], "task": "NER"}
{"text": "For all cuts , the correlation coefficient of total amino acids to protein ( N x 6 . 25 ) was 0 . 635 .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [52, 63]}], "task": "NER"}
{"text": "This indicates a poor correlation for predicting actual protein content ( as determined by total amino acid count ) , based on the nitrogen factor of 6 . 25 .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [97, 107]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "On average , the sum of amino acids per cut amounted to 91 % of total determined protein ( N x 6 . 25 ) for the same cut .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [24, 35]}], "task": "NER"}
{"text": "Biosynthetic conclusions from the functional dissection of oxygenases for biosynthesis of actinorhodin and related streptomyces antibiotics .", "entity": [{"entity": "actinorhodin", "entity_type": "Chemical", "pos": [90, 102]}], "task": "NER"}
{"text": "Actinorhodin ( ACT ) produced by Streptomyces coelicolor A3 ( 2 ) belongs to the benzoisochromanequinone ( BIQ ) class of antibiotics .", "entity": [{"entity": "Actinorhodin", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "ACT", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "benzoisochromanequinone", "entity_type": "Chemical", "pos": [81, 104]}, {"entity": "BIQ", "entity_type": "Chemical", "pos": [107, 110]}], "task": "NER"}
{"text": "ActVA - ORF5 , a flavin - dependent monooxygenase ( FMO ) essential for ACT biosynthesis , forms a two - component enzyme system in combination with a flavin : NADH oxidoreductase , ActVB .", "entity": [{"entity": "flavin", "entity_type": "Chemical", "pos": [17, 23]}, {"entity": "ACT", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "flavin", "entity_type": "Chemical", "pos": [151, 157]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [160, 164]}], "task": "NER"}
{"text": "The genes for homologous two - component FMOs are found in the biosynthetic gene clusters for two other BIQs , granaticin ( GRA ) and medermycin ( MED ) , and a closely related antibiotic , alnumycin ( ALN ) .", "entity": [{"entity": "BIQs", "entity_type": "Chemical", "pos": [104, 108]}, {"entity": "granaticin", "entity_type": "Chemical", "pos": [111, 121]}, {"entity": "GRA", "entity_type": "Chemical", "pos": [124, 127]}, {"entity": "medermycin", "entity_type": "Chemical", "pos": [134, 144]}, {"entity": "MED", "entity_type": "Chemical", "pos": [147, 150]}, {"entity": "alnumycin", "entity_type": "Chemical", "pos": [190, 199]}, {"entity": "ALN", "entity_type": "Chemical", "pos": [202, 205]}], "task": "NER"}
{"text": "Our functional analysis of these FMOs ( ActVA - ORF5 , Gra - ORF21 , Med - ORF7 , and AlnT ) in S . coelicolor unambiguously demonstrated that ActVA - ORF5 and Gra - ORF21 are bifunctional and capable of both p - quinone formation at C - 6 in the central ring and C - 8 hydroxylation in the lateral ring , whereas Med - ORF7 catalyzes only p - quinone formation .", "entity": [{"entity": "Gra", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "Med", "entity_type": "Chemical", "pos": [69, 72]}, {"entity": "Gra", "entity_type": "Chemical", "pos": [160, 163]}, {"entity": "p - quinone", "entity_type": "Chemical", "pos": [209, 220]}, {"entity": "Med", "entity_type": "Chemical", "pos": [314, 317]}, {"entity": "p - quinone", "entity_type": "Chemical", "pos": [340, 351]}], "task": "NER"}
{"text": "No p - quinone formation on a BIQ substrate was observed for AlnT , which is involved in lateral p - quinone formation in ALN .", "entity": [{"entity": "p - quinone", "entity_type": "Chemical", "pos": [3, 14]}, {"entity": "BIQ", "entity_type": "Chemical", "pos": [30, 33]}, {"entity": "p - quinone", "entity_type": "Chemical", "pos": [97, 108]}, {"entity": "ALN", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "2 - ( 1H - Pyrazol - 4 - yl ) acetic acids as CRTh2 antagonists .", "entity": [{"entity": "2 - ( 1H - Pyrazol - 4 - yl ) acetic acids", "entity_type": "Chemical", "pos": [0, 42]}], "task": "NER"}
{"text": "High throughput screening identified the pyrazole - 4 - acetic acid substructure as CRTh2 receptor antagonists .", "entity": [{"entity": "pyrazole - 4 - acetic acid", "entity_type": "Chemical", "pos": [41, 67]}], "task": "NER"}
{"text": "Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors .", "entity": [], "task": "NER"}
{"text": "Genome - wide Analysis Reveals TET - and TDG - Dependent 5 - Methylcytosine Oxidation Dynamics .", "entity": [{"entity": "5 - Methylcytosine", "entity_type": "Chemical", "pos": [57, 75]}], "task": "NER"}
{"text": "TET dioxygenases successively oxidize 5 - methylcytosine ( 5mC ) in mammalian genomes to 5 - hydroxymethylcytosine ( 5hmC ) , 5 - formylcytosine ( 5fC ) , and 5 - carboxylcytosine ( 5caC ) .", "entity": [{"entity": "5 - methylcytosine", "entity_type": "Chemical", "pos": [38, 56]}, {"entity": "5mC", "entity_type": "Chemical", "pos": [59, 62]}, {"entity": "5 - hydroxymethylcytosine", "entity_type": "Chemical", "pos": [89, 114]}, {"entity": "5hmC", "entity_type": "Chemical", "pos": [117, 121]}, {"entity": "5 - formylcytosine", "entity_type": "Chemical", "pos": [126, 144]}, {"entity": "5fC", "entity_type": "Chemical", "pos": [147, 150]}, {"entity": "5 - carboxylcytosine", "entity_type": "Chemical", "pos": [159, 179]}, {"entity": "5caC", "entity_type": "Chemical", "pos": [182, 186]}], "task": "NER"}
{"text": "5fC / 5caC can be excised and repaired to regenerate unmodified cytosines by thymine - DNA glycosylase ( TDG ) and base excision repair ( BER ) pathway , but it is unclear to what extent and at which part of the genome this active demethylation process takes place .", "entity": [{"entity": "5fC", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "5caC", "entity_type": "Chemical", "pos": [6, 10]}, {"entity": "cytosines", "entity_type": "Chemical", "pos": [64, 73]}, {"entity": "thymine", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "Here , we have generated genome - wide distribution maps of 5hmC / 5fC / 5caC using modification - specific antibodies in wild - type and Tdg - deficient mouse embryonic stem cells ( ESCs ) .", "entity": [{"entity": "5hmC", "entity_type": "Chemical", "pos": [60, 64]}, {"entity": "5fC", "entity_type": "Chemical", "pos": [67, 70]}, {"entity": "5caC", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "In wild - type mouse ESCs , 5fC / 5caC accumulates to detectable levels at major satellite repeats but not at nonrepetitive loci .", "entity": [{"entity": "5fC", "entity_type": "Chemical", "pos": [28, 31]}, {"entity": "5caC", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "In contrast , Tdg depletion in mouse ESCs causes marked accumulation of 5fC and 5caC at a large number of proximal and distal gene regulatory elements .", "entity": [{"entity": "5fC", "entity_type": "Chemical", "pos": [72, 75]}, {"entity": "5caC", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "Thus , these results reveal the genome - wide view of iterative 5mC oxidation dynamics and indicate that TET / TDG - dependent active DNA demethylation process occurs extensively in the mammalian genome .", "entity": [{"entity": "5mC", "entity_type": "Chemical", "pos": [64, 67]}], "task": "NER"}
{"text": "Synthesis and antiproliferative evaluation of piperazine - 1 - carbothiohydrazide derivatives of indolin - 2 - one .", "entity": [{"entity": "piperazine - 1 - carbothiohydrazide", "entity_type": "Chemical", "pos": [46, 81]}, {"entity": "indolin - 2 - one", "entity_type": "Chemical", "pos": [97, 114]}], "task": "NER"}
{"text": "By varying the substituents ( R ( 1 ) ) at the indolin - 2 - one scaffold , a series of indolin - 2 - one derivatives bearing 4 - phenylpiperazine - 1 - carbothiohydrazide moiety at the C3 - position were synthesized and evaluated for their antiproliferative activity against three human cancer cell lines .", "entity": [{"entity": "indolin - 2 - one", "entity_type": "Chemical", "pos": [47, 64]}, {"entity": "indolin - 2 - one", "entity_type": "Chemical", "pos": [88, 105]}, {"entity": "4 - phenylpiperazine - 1 - carbothiohydrazide", "entity_type": "Chemical", "pos": [126, 171]}], "task": "NER"}
{"text": "We further selected the 5 - chloroindolin - 2 - one moiety for the extension to another series of compounds by varying the substituents ( R ( 2 ) ) at the phenyl group connected with the piperazine ring .", "entity": [{"entity": "5 - chloroindolin - 2 - one", "entity_type": "Chemical", "pos": [24, 51]}, {"entity": "phenyl", "entity_type": "Chemical", "pos": [155, 161]}, {"entity": "piperazine", "entity_type": "Chemical", "pos": [187, 197]}], "task": "NER"}
{"text": "Among all the compounds synthesized , 6d and 6l were most potent with IC50 values of 3 . 59 and 5 . 58 mu M , respectively against A549 lung cancer cells , while 5f and 6l possessed IC50 values of 3 . 49 and 4 . 57 mu M , respectively against HCT - 116 colon cancer cells which were comparable to that of Sunitinib , an indolin - 2 - one derivative in cancer therapy .", "entity": [{"entity": "Sunitinib", "entity_type": "Chemical", "pos": [305, 314]}, {"entity": "indolin - 2 - one", "entity_type": "Chemical", "pos": [320, 337]}], "task": "NER"}
{"text": "BDNF - induced local protein synthesis and synaptic plasticity .", "entity": [], "task": "NER"}
{"text": "Brain - derived neurotrophic factor ( BDNF ) is an important regulator of synaptic transmission and long - term potentiation ( LTP ) in the hippocampus and in other brain regions , playing a role in the formation of certain forms of memory .", "entity": [], "task": "NER"}
{"text": "The effects of BDNF in LTP are mediated by TrkB ( tropomyosin - related kinase B ) receptors , which are known to be coupled to the activation of the Ras / ERK , phosphatidylinositol 3 - kinase / Akt and phospholipase C - gamma ( PLC - gamma ) pathways .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [162, 182]}], "task": "NER"}
{"text": "The role of BDNF in LTP is best studied in the hippocampus , where the neurotrophin is thought to act at pre - and post - synaptic levels .", "entity": [], "task": "NER"}
{"text": "Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse , by modulating the initiation and elongation phases of protein synthesis , and by acting on specific miRNAs .", "entity": [], "task": "NER"}
{"text": "Furthermore , the effect of BDNF on transcription regulation may further contribute to long - term changes in the synaptic proteome .", "entity": [], "task": "NER"}
{"text": "In this review we discuss the recent progress in understanding the mechanisms contributing to the short - and long - term regulation of the synaptic proteome by BDNF , and the role in synaptic plasticity , which is likely to influence learning and memory formation .", "entity": [], "task": "NER"}
{"text": "This article is part of a Special Issue entitled ' BDNF ' .", "entity": [], "task": "NER"}
{"text": "Protective effects of naringin against paraquat - induced acute lung injury and pulmonary fibrosis in mice .", "entity": [{"entity": "naringin", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "paraquat", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "The present study evaluates protective effects of naringin against paraquat ( PQ ) - induced acute lung injury ( ALI ) and pulmonary fibrosis in mice .", "entity": [{"entity": "naringin", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "paraquat", "entity_type": "Chemical", "pos": [67, 75]}], "task": "NER"}
{"text": "Survival probability against PQ intoxication was tested by a single intraperitoneal injection of PQ .", "entity": [], "task": "NER"}
{"text": "Results showed that survival rates of mice exposed to PQ only ( 50mg / kg within 7days ) were much lower than that in mice daily treatment with NAC or naringin .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [144, 147]}, {"entity": "naringin", "entity_type": "Chemical", "pos": [151, 159]}], "task": "NER"}
{"text": "Moreover , protection against PQ - induced ALI was tested by daily pretreatment mice with saline , NAC or naringin for 3days before PQ ( 30mg / kg , i . p . ) .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "naringin", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "Results showed that increase in leukocytes infiltration and overexpressions of TNF - alpha and TGF - beta 1 caused by 8h of PQ exposure were dose - dependently ameliorated by naringin .", "entity": [{"entity": "naringin", "entity_type": "Chemical", "pos": [175, 183]}], "task": "NER"}
{"text": "Furthermore , protection against PQ - induced pulmonary fibrosis was tested by pretreatment mice with PQ ( 20mg / kg , i . p . ) , and then daily administration with saline , NAC or naringin for prolonged 21days .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [175, 178]}, {"entity": "naringin", "entity_type": "Chemical", "pos": [182, 190]}], "task": "NER"}
{"text": "Results showed that naringin of 60 and 120mg / kg significantly reduced PQ - induced upregulations of TNF - alpha , TGF - beta 1 , MMP - 9 and TIMP - 1 , levels of pulmonary malonaldehyde and hydroxyproline , as well as pulmonary fibrosis deposition , while increased activities of SOD , GSH - Px and HO - 1 .", "entity": [{"entity": "naringin", "entity_type": "Chemical", "pos": [20, 28]}, {"entity": "malonaldehyde", "entity_type": "Chemical", "pos": [174, 187]}, {"entity": "hydroxyproline", "entity_type": "Chemical", "pos": [192, 206]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [288, 291]}], "task": "NER"}
{"text": "These results indicated that naringin had effective protection against PQ - induced ALI and pulmonary fibrosis .", "entity": [{"entity": "naringin", "entity_type": "Chemical", "pos": [29, 37]}], "task": "NER"}
{"text": "Immunotoxicological effects of inorganic arsenic on gilthead seabream ( Sparus aurata L . ) .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [41, 48]}], "task": "NER"}
{"text": "Arsenic ( As ) has been associated with multitude of animal and human health problems ; however , its impact on host immune system has not been extensively investigated .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "As", "entity_type": "Chemical", "pos": [10, 12]}], "task": "NER"}
{"text": "In fish , there are very few works on the potential risks or problems associated to the presence of arsenic .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "In the present study we have evaluated the effects of exposure ( 30 days ) to sub - lethal concentrations of arsenic ( 5 mu M As2O3 ) in the teleost fish gilthead seabream ( Sparus aurata ) , with special emphasis in the innate immune response .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [109, 116]}, {"entity": "As2O3", "entity_type": "Chemical", "pos": [126, 131]}], "task": "NER"}
{"text": "The arsenic concentration was determined using atomic fluorescence spectrometry ( AFS ) in liver and muscle of exposed fish showing As accumulation in the liver after 30 days of exposure .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [4, 11]}, {"entity": "As", "entity_type": "Chemical", "pos": [132, 134]}], "task": "NER"}
{"text": "The hepatosomatic index was increased at significant extent after 10 days but returned to control values after 30 days of exposure .", "entity": [], "task": "NER"}
{"text": "Histological alterations in the liver were observed including hypertrophy , vacuolization and cell - death processes .", "entity": [], "task": "NER"}
{"text": "Focusing on the immunological response , the humoral immune parameters ( seric IgM , complement and peroxidase activities ) were no affected to a statistically significant extent .", "entity": [], "task": "NER"}
{"text": "Regarding the cellular innate parameters , head - kidney leucocyte peroxidase , respiratory burst and phagocytic activities were significantly increased after 10 days of exposition compared to the control fish .", "entity": [], "task": "NER"}
{"text": "Overall , As - exposure in the seabream affects the immune system .", "entity": [{"entity": "As", "entity_type": "Chemical", "pos": [10, 12]}], "task": "NER"}
{"text": "How this might interfere with fish biology , aquaculture management or human consumers warrants further investigations .", "entity": [], "task": "NER"}
{"text": "This paper describes , for the first time , the immunotoxicological effects of arsenic exposure in the gilthead seabream , which is a species with the largest production in Mediterranean aquaculture .", "entity": [{"entity": "arsenic", "entity_type": "Chemical", "pos": [79, 86]}], "task": "NER"}
{"text": "Evaluation of mechanisms involved in the antinociception of the ethanol extract from the inner bark of Caesalpinia pyramidalis in mice .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [64, 71]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Caesalpinia pyramidalis Tul .", "entity": [], "task": "NER"}
{"text": "( Fabaceae ) is an endemic tree of the Northeast region of Brazil , mainly in the Caatinga region .", "entity": [], "task": "NER"}
{"text": "More commonly , inner bark or flowers are traditionally used to treat many painful and inflammatory processes .", "entity": [], "task": "NER"}
{"text": "A common use of this plant is made by macerating a handful of its stem bark in a liter of wine or sugarcane brandy .", "entity": [], "task": "NER"}
{"text": "It is drunk against stomachache , dysenteries , and diarrheas .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : The ethanol extract of Caesalpinia pyramidalis inner bark was used in mice via oral route , at the doses of 10 , 30 , and 100mg / kg , in behavioral models of nociception and investigates some of the mechanisms underlying this effect .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [28, 35]}], "task": "NER"}
{"text": "RESULTS : The ethanol extract ( 30 and 100mg / kg , P < 0 . 001 ) , given orally , produced dose dependent inhibition of acetic acid - induced visceral pain .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [14, 21]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "The ethanol extract also caused significant and dose - dependent inhibition of capsaicin - ( 100mg / kg , P < 0 . 001 ) and glutamate - ( 10 , 30 , and 100mg / kg , P < 0 . 01 ) induced pain .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [4, 11]}, {"entity": "capsaicin", "entity_type": "Chemical", "pos": [79, 88]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [124, 133]}], "task": "NER"}
{"text": "The antinociception caused by the ethanol extract ( 30mg / kg ) in the abdominal constriction test was significantly attenuated ( P < 0 . 001 ) by intraperitoneal treatment of mice with l - arginine ( 600mg / kg ) .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [34, 41]}, {"entity": "l - arginine", "entity_type": "Chemical", "pos": [186, 198]}], "task": "NER"}
{"text": "CONCLUSIONS : Collectively , the present results suggest that the ethanol extract of Caesalpinia pyramidalis produced dose - related antinociception in several models of pain through mechanisms that involved both glutamatergic system and / or the l - arginine - nitric oxide pathway , supporting the folkloric usage of the plant to treat various painful processes .", "entity": [{"entity": "ethanol", "entity_type": "Chemical", "pos": [66, 73]}, {"entity": "l - arginine - nitric oxide", "entity_type": "Chemical", "pos": [247, 274]}], "task": "NER"}
{"text": "The PERICLES research program : An integrated approach to characterize the combined effects of mixtures of pesticide residues to which the French population is exposed .", "entity": [], "task": "NER"}
{"text": "Due to the broad spectrum of pesticide usages , consumers are exposed to mixtures of residues , which may have combined effects on human health .", "entity": [], "task": "NER"}
{"text": "The PERICLES research program aims to test the potential combined effects of pesticide mixtures , which are likely to occur through dietary exposure .", "entity": [], "task": "NER"}
{"text": "The co - exposure of the French general population to 79 pesticide residues present in the diet was first assessed .", "entity": [], "task": "NER"}
{"text": "A Bayesian non - parametric model was then applied to define the main mixtures to which the French general population is simultaneously and most heavily exposed .", "entity": [], "task": "NER"}
{"text": "Seven mixtures made of two to six pesticides were identified from the exposure assessment .", "entity": [], "task": "NER"}
{"text": "An in vitro approach was used for investigating the toxicological effects of these mixtures and their corresponding individual compounds , using a panel of cellular models , i . e . primary rat and human hepatocytes , liver , intestine , kidney , colon and brain human cell lines .", "entity": [], "task": "NER"}
{"text": "A set of cell functions and corresponding end - points were monitored such as cytotoxicity , real - time cell impedance , genotoxicity , oxidative stress , apoptosis and PXR nuclear receptor transactivation .", "entity": [], "task": "NER"}
{"text": "The mixtures were tested in equimolar concentrations .", "entity": [], "task": "NER"}
{"text": "Among the seven mixtures , two appeared highly cytotoxic , five activated PXR and depending on the assay one or two were genotoxic .", "entity": [], "task": "NER"}
{"text": "In some experiments , the mixture effect was quantitatively different from the effect expected from the addition concept .", "entity": [], "task": "NER"}
{"text": "The PERICLES program shows that , for the most pesticides mixtures to which the French general population is exposed , the toxic effects observed on human cells cannot be easily predicted based on the toxic potential of each compound .", "entity": [], "task": "NER"}
{"text": "Consequently , additional studies should be carried on in order to more accurately define the mixtures of chemicals to which the consumers are exposed , as well as to improve the investigation , prediction and monitoring of their potential human health effects .", "entity": [], "task": "NER"}
{"text": "Adult siRNA - induced knockdown of mGlu7 receptors reduces anxiety in the mouse .", "entity": [], "task": "NER"}
{"text": "Our knowledge regarding the molecular pathophysiology underlying anxiety disorders remains incomplete .", "entity": [], "task": "NER"}
{"text": "Increasing evidence points to a role of glutamate in anxiety .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [40, 49]}], "task": "NER"}
{"text": "The group III metabotropic glutamate receptors ( mGlu4 , mGlu6 , mGlu7 and mGlu8 receptors ) remain the least investigated glutamate receptor subtypes partially due to a delay in the development of specific pharmacological tools .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [27, 36]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [123, 132]}], "task": "NER"}
{"text": "Early work using knockout animals and pharmacological tools aimed at investigating the role of mGlu7 receptor in the pathophysiology of anxiety disorders has yielded exciting yet not always consistent results .", "entity": [], "task": "NER"}
{"text": "To further investigate the role this receptor plays in anxiety - like behaviour , we knocked down mGlu7 receptor mRNA levels in the adult mouse brain using siRNA delivered via an osmotic minipump .", "entity": [], "task": "NER"}
{"text": "This reduced anxiety - like behaviour in the light - dark box coupled with an attenuation of stress - induced hyperthermia ( SIH ) and a reduction of the acoustic startle response ( ASRs ) in the fear - potentiated startle paradigm ( FPS ) .", "entity": [], "task": "NER"}
{"text": "These effects on anxiety - like behaviour were independent of any impairment of locomotor activity and surprisingly , no behavioural changes were observed in the forced swim test ( FST ) , which is in contrast to mGlu7 receptor knockout animals .", "entity": [], "task": "NER"}
{"text": "Furthermore , the previously reported epilepsy - prone phenotype seen in mGlu7 receptor knockout animals was not observed following siRNA - induced knockdown of the receptor .", "entity": [], "task": "NER"}
{"text": "These data suggest targeting mGlu7 receptors with selective antagonist drugs may be an effective and safe strategy for the treatment of anxiety disorders .", "entity": [], "task": "NER"}
{"text": "Infliximab counteracts tumor necrosis factor - alpha - enhanced induction of matrix metalloproteinases that degrade claudin and occludin in non - pigmented ciliary epithelium .", "entity": [], "task": "NER"}
{"text": "Infliximab , a monoclonal antibody directed against human tumor necrosis factor - alpha ( TNF - alpha ) , effectively treats anterior uveitis , which can accompany Beh c et ' s disease .", "entity": [], "task": "NER"}
{"text": "Here , we investigated the underlying mechanism of this action .", "entity": [], "task": "NER"}
{"text": "We examined human , non - pigmented ciliary epithelial cells ( HNPCECs ) , which make up the blood - aqueous barrier ( BAB ) in the uvea .", "entity": [], "task": "NER"}
{"text": "We measured the expression levels of matrix metalloproteinases ( MMPs ) and tissue inhibitors of MMPs in the presence or absence of TNF - alpha using quantitative , real - time polymerase chain reaction and enzyme - linked immunosorbent assays .", "entity": [], "task": "NER"}
{"text": "The expression of MMP - 1 , MMP - 3 , and MMP - 9 increased in the presence of TNF - alpha , and the addition of infliximab reversed the increase .", "entity": [], "task": "NER"}
{"text": "The TNF - alpha effects were more attenuated when infliximab was added before than when it was added after TNF - alpha exposure .", "entity": [], "task": "NER"}
{"text": "Gelatin zymography demonstrated that the protease activity of these MMPs was also increased in the presence of TNF - alpha and attenuated with infliximab .", "entity": [], "task": "NER"}
{"text": "Immunostaining showed that MMP - 1 , MMP - 3 , and MMP - 9 degraded claudin - 1 and occludin in HNPCECs and in non - pigmented ciliary epithelial cells of the swine ciliary body .", "entity": [], "task": "NER"}
{"text": "In a monolayer of HNPCECs , we found that permeability was significantly increased with MMP treatment .", "entity": [], "task": "NER"}
{"text": "Thus , TNF - alpha increased levels of MMPs in cells that form the BAB , and MMPs degraded components of the tight junctions in the BAB , which increased permeability through the cellular barrier .", "entity": [], "task": "NER"}
{"text": "Furthermore , infliximab effectively attenuated the TNF - alpha - induced increases in MMP expression in cells that make up the BAB .", "entity": [], "task": "NER"}
{"text": "These findings might suggest a basis for the clinical prevention of anterior uveitis .", "entity": [], "task": "NER"}
{"text": "Protective effects of selenium on oxidative damage and oxidative stress related gene expression in rat liver under chronic poisoning of arsenic .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [22, 30]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [136, 143]}], "task": "NER"}
{"text": "Arsenic ( As ) is a toxic metalloid existing widely in the environment , and chronic exposure to it through contaminated drinking water has become a global problem of public health .", "entity": [{"entity": "Arsenic", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "As", "entity_type": "Chemical", "pos": [10, 12]}], "task": "NER"}
{"text": "The present study focused on the protective effects of selenium on oxidative damage of chronic arsenic poisoning in rat liver .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [55, 63]}, {"entity": "arsenic", "entity_type": "Chemical", "pos": [95, 102]}], "task": "NER"}
{"text": "Rats were divided into four groups at random and given designed treatments for 20weeks .", "entity": [], "task": "NER"}
{"text": "The oxidative damage of liver tissue was evaluated by lipid peroxidation and antioxidant enzymes .", "entity": [], "task": "NER"}
{"text": "Oxidative stress related genes were detected to reflect the liver stress state at the molecular level .", "entity": [], "task": "NER"}
{"text": "Compared to the control and Na2SeO3 groups , the MDA content in liver tissue was decreased and the activities of antioxidant enzymes were increased in the Na2SeO3 intervention group .", "entity": [{"entity": "Na2SeO3", "entity_type": "Chemical", "pos": [28, 35]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [49, 52]}, {"entity": "Na2SeO3", "entity_type": "Chemical", "pos": [155, 162]}], "task": "NER"}
{"text": "The mRNA levels of SOD1 , CAT , GPx and Txnrd1 were increased significantly ( P < 0 . 05 ) in the combined Na2SeO3 + NaAsO2 treatment group .", "entity": [{"entity": "Na2SeO3", "entity_type": "Chemical", "pos": [107, 114]}, {"entity": "NaAsO2", "entity_type": "Chemical", "pos": [117, 123]}], "task": "NER"}
{"text": "The expressions of HSP70 and HO - 1 were significantly ( P < 0 . 05 ) increased in the NaAsO2 group and reduced in the combined treatment group .", "entity": [{"entity": "NaAsO2", "entity_type": "Chemical", "pos": [87, 93]}], "task": "NER"}
{"text": "The results indicate that long - term intake of NaAsO2 causes oxidative damage in the rat liver , and Na2SeO3 protects liver cells by adjusting the expression of oxidative stress related genes to improve the activities of antioxidant enzymes .", "entity": [{"entity": "NaAsO2", "entity_type": "Chemical", "pos": [48, 54]}, {"entity": "Na2SeO3", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "Juniperus oxycedrus L . subsp .", "entity": [], "task": "NER"}
{"text": "oxycedrus and Juniperus oxycedrus L . subsp .", "entity": [], "task": "NER"}
{"text": "macrocarpa ( Sibth . & Sm . ) Ball .", "entity": [], "task": "NER"}
{"text": "\" berries \" from Turkey : Comparative evaluation of phenolic profile , antioxidant , cytotoxic and antimicrobial activities .", "entity": [], "task": "NER"}
{"text": "This work aimed to evaluate and compare the phenolic profile and some biological properties of the ripe \" berries \" methanol extracts of Juniperus oxycedrus L . subsp .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [116, 124]}], "task": "NER"}
{"text": "oxycedrus ( Joo ) and Juniperus oxycedrus L . subsp .", "entity": [], "task": "NER"}
{"text": "( Jom ) from Turkey .", "entity": [], "task": "NER"}
{"text": "The total phenolic content resulted about 3 - fold higher in Jom ( 17 . 89 +/- 0 . 23mg GAE / g extract ) than in Joo ( 5 . 14 +/- 0 . 06mg GAE / g extract ) .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [10, 18]}], "task": "NER"}
{"text": "The HPLC - DAD - ESI - MS analysis revealed a similar flavonoid fingerprint in Joo and Jom , whereas a difference in their quantitative content was found ( 4632 mu g / g extract and 12 , 644 mu g / g extract ) .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "In addition , three phenolic acids were detected in Jom only ( 5765 mu g / g extract ) , and protocatechuic acid was the most abundant one .", "entity": [{"entity": "phenolic acids", "entity_type": "Chemical", "pos": [20, 34]}, {"entity": "protocatechuic acid", "entity_type": "Chemical", "pos": [93, 112]}], "task": "NER"}
{"text": "The antioxidant capacity of the extracts was evaluated by different in vitro assays : in the DPPH and in the TBA tests a stronger activity in Jom was highlighted , while Joo exhibited higher reducing power and metal chelating activity .", "entity": [{"entity": "DPPH", "entity_type": "Chemical", "pos": [93, 97]}, {"entity": "TBA", "entity_type": "Chemical", "pos": [109, 112]}], "task": "NER"}
{"text": "Joo and Jom did not affect HepG2 cell viability and both extracts resulted virtually non - toxic against Artemia salina .", "entity": [], "task": "NER"}
{"text": "The extracts were also studied for their antimicrobial potential , displaying efficacy against Gram - positive bacteria .", "entity": [], "task": "NER"}
{"text": "The molecular basis of simple relationships between exposure concentration and toxic effects with time .", "entity": [], "task": "NER"}
{"text": "Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time .", "entity": [], "task": "NER"}
{"text": "Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective .", "entity": [], "task": "NER"}
{"text": "This paper re - introduces an old approach that takes into account the biochemical mode of action and their resulting biological effects over time of exposure .", "entity": [], "task": "NER"}
{"text": "Empirical evidence demonstrates that the Druckrey - K u pfm u ller toxicity model , which was validated for chemical carcinogens in the early 1960s , is also applicable to a wide range of toxic compounds in ecotoxicology .", "entity": [], "task": "NER"}
{"text": "According to this model , the character of a poison is primarily determined by the reversibility of critical receptor binding .", "entity": [], "task": "NER"}
{"text": "Chemicals showing irreversible or slowly reversible binding to specific receptors will produce cumulative effects with time of exposure , and whenever the effects are also irreversible ( e . g . death ) they are reinforced over time ; these chemical have time - cumulative toxicity .", "entity": [], "task": "NER"}
{"text": "Compounds having non - specific receptor binding , or involving slowly reversible binding to some receptors that do not contribute to toxicity , may also be time - dependent ; however , their effects depend primarily on the exposure concentration , with time playing a minor role .", "entity": [], "task": "NER"}
{"text": "Consequently , the mechanism of toxic action has important implications for risk assessment .", "entity": [], "task": "NER"}
{"text": "Traditional risk approaches cannot predict the impacts of toxicants with time - cumulative toxicity in the environment .", "entity": [], "task": "NER"}
{"text": "New assessment procedures are needed to evaluate the risk that the latter chemicals pose on humans and the environment .", "entity": [], "task": "NER"}
{"text": "An example is shown to explain how the risk of time - dependent toxicants is underestimated when using current risk assessment protocols .", "entity": [], "task": "NER"}
{"text": "Cognitive effects of variations in pubertal timing : Is puberty a period of brain organization for human sex - typed cognition ?", "entity": [], "task": "NER"}
{"text": "There is considerable interest in the organizational effects of pubertal sex hormones on human sex - related characteristics .", "entity": [], "task": "NER"}
{"text": "Recent evidence from rodents suggests that there is a decreasing window of sensitivity to sex hormones throughout adolescence .", "entity": [], "task": "NER"}
{"text": "If adolescence also represents a period of brain organization in human beings , then the timing of exposure to sex - typical hormones at puberty should have long - term effects on sex - typed characteristics : individuals with early timing should be more sex - typed than individuals with late timing .", "entity": [], "task": "NER"}
{"text": "We tested this hypothesis in 320 young adults by relating their pubertal timing ( retrospective comparison to peers ) to cognitive abilities that show sex differences .", "entity": [], "task": "NER"}
{"text": "Results provide partial support for the hypothesis .", "entity": [], "task": "NER"}
{"text": "For men , pubertal timing was inversely related to scores on a test of three - dimensional mental rotations .", "entity": [], "task": "NER"}
{"text": "Effects do not appear to be due to duration of hormone exposure ( time since puberty ) , but other potential influences need further study .", "entity": [], "task": "NER"}
{"text": "New anticancer active and selective phenylene - bisbenzothiazoles : Synthesis , antiproliferative evaluation and DNA binding .", "entity": [{"entity": "phenylene - bisbenzothiazoles", "entity_type": "Chemical", "pos": [36, 65]}], "task": "NER"}
{"text": "Novel amidino - derivatives of phenylene - bisbenzothiazoles were synthesized and tested for their antiproliferative activity against several human cancer cell lines , as well as DNA - binding properties .", "entity": [{"entity": "amidino", "entity_type": "Chemical", "pos": [6, 13]}, {"entity": "phenylene - bisbenzothiazoles", "entity_type": "Chemical", "pos": [31, 60]}], "task": "NER"}
{"text": "The synthetic approach used for preparation of isomeric amidino substituted - phenylene - bis - benzothyazoles 3a - 3f was achieved by condensation reaction of isophthaloyl dichloride 1a and terephthaloyl dichloride 1b or with phthalic acid 1c with 5 - amidinium - 2 - aminobenzothiolate 2a and 5 - ( imidazolinium - 2 - yl ) - 2 - aminobenzothiolate 2b in good yields .", "entity": [{"entity": "amidino substituted - phenylene - bis - benzothyazoles", "entity_type": "Chemical", "pos": [56, 110]}, {"entity": "isophthaloyl dichloride", "entity_type": "Chemical", "pos": [160, 183]}, {"entity": "terephthaloyl dichloride", "entity_type": "Chemical", "pos": [191, 215]}, {"entity": "phthalic acid", "entity_type": "Chemical", "pos": [227, 240]}, {"entity": "5 - amidinium - 2 - aminobenzothiolate", "entity_type": "Chemical", "pos": [249, 287]}, {"entity": "5 - ( imidazolinium - 2 - yl ) - 2 - aminobenzothiolate", "entity_type": "Chemical", "pos": [295, 350]}], "task": "NER"}
{"text": "The targeted compounds were converted in the desired water soluble dihydrochloride salts by reaction of appropriate free base with concd HCl in ethanol or acetic acid .", "entity": [{"entity": "dihydrochloride", "entity_type": "Chemical", "pos": [67, 82]}, {"entity": "HCl", "entity_type": "Chemical", "pos": [137, 140]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [144, 151]}, {"entity": "acetic acid", "entity_type": "Chemical", "pos": [155, 166]}], "task": "NER"}
{"text": "All tested compounds ( 3a - 3f ) showed antiproliferative effects on tumour cells in a concentration - dependant manner .", "entity": [], "task": "NER"}
{"text": "The strongest activity and cytotoxicity was observed for diimidazolinyl substituted phenylene - bisbenzothiazole compound 3b .", "entity": [{"entity": "diimidazolinyl substituted phenylene - bisbenzothiazole", "entity_type": "Chemical", "pos": [57, 112]}], "task": "NER"}
{"text": "These effects were shown to be related to DNA - binding properties , topoisomerase I and II poisoning effects and apoptosis induction .", "entity": [], "task": "NER"}
{"text": "The highest tested selectivity towards tumour cells was observed for the imidazolyl substituted phenylene - benzothiazole 3d that showed no cytotoxic effects on normal fibroblasts making it an excellent candidate for further chemical optimization and preclinical evaluation .", "entity": [{"entity": "imidazolyl substituted phenylene - benzothiazole", "entity_type": "Chemical", "pos": [73, 121]}], "task": "NER"}
{"text": "A Bioluminescent Assay System for Whole - Cell Determination of Hormones .", "entity": [], "task": "NER"}
{"text": "A bioluminescent - assay system was fabricated for an efficient determination of bioactive small molecules in physiological samples .", "entity": [], "task": "NER"}
{"text": "The following three components were newly created for this assay system : ( i ) a single - chain probe exerting a 7 . 2 - times stronger optical intensity than conventional ones , ( ii ) a high throughput assay device uniquely designed for the assay system with ca . one - fourth smaller standard deviation ( SD ) to samples than without the device , ( iii ) a buffer cocktail optimized for the assay system .", "entity": [], "task": "NER"}
{"text": "The advantages of the assay system were evaluated by determining ( i ) the stress hormone levels in human saliva and ( ii ) multicolor imaging of genomic and nongenomic effects of woman sex hormones .", "entity": [], "task": "NER"}
{"text": "This study guides on how to fabricate an efficient assay system for bioactive small molecules with convenience and high precision .", "entity": [], "task": "NER"}
{"text": "Large networks of vertical multi - layer graphenes with morphology - tunable magnetoresistance .", "entity": [{"entity": "graphenes", "entity_type": "Chemical", "pos": [41, 50]}], "task": "NER"}
{"text": "We report on the comparative study of magnetotransport properties of large - area vertical few - layer graphene networks with different morphologies , measured in a strong ( up to 10 T ) magnetic field over a wide temperature range .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [103, 111]}], "task": "NER"}
{"text": "The petal - like and tree - like graphene networks grown by a plasma enhanced CVD process on a thin ( 500 nm ) silicon oxide layer supported by a silicon wafer demonstrate a significant difference in the resistance - magnetic field dependencies at temperatures ranging from 2 to 200 K .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [33, 41]}, {"entity": "silicon oxide", "entity_type": "Chemical", "pos": [111, 124]}, {"entity": "silicon", "entity_type": "Chemical", "pos": [146, 153]}], "task": "NER"}
{"text": "This behaviour is explained in terms of the effect of electron scattering at ultra - long reactive edges and ultra - dense boundaries of the graphene nanowalls .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "Our results pave a way towards three - dimensional vertical graphene - based magnetoelectronic nanodevices with morphology - tuneable anisotropic magnetic properties .", "entity": [{"entity": "graphene", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "The structure of the biliverdin cofactor in the Pfr state of bathy and prototypical phytochromes .", "entity": [{"entity": "biliverdin", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "The structures of the chromophore binding pockets in the Pfr states of various bathy and prototypical biliverdin - binding phytochromes were analysed by using a combined spectroscopic - theoretical approach .", "entity": [{"entity": "biliverdin", "entity_type": "Chemical", "pos": [102, 112]}], "task": "NER"}
{"text": "For the Pfr state of the bathy phytochrome from Pseudomonas aeruginosa ( PaBphP ) the very good agreement between calculated Raman spectra of the tetrapyrrole cofactor , obtained by quantum - mechanical / molecular - mechanical hybrid methods , and the experimental resonance Raman ( RR ) spectra confirms important conclusions derived from the previous crystallographic analyses , particularly the ZZEssa configuration of the chromophore and its attachment to the thiol side chain of Cys12 via the exocyclic vinyl group of ring A .", "entity": [{"entity": "tetrapyrrole", "entity_type": "Chemical", "pos": [146, 158]}, {"entity": "thiol", "entity_type": "Chemical", "pos": [465, 470]}, {"entity": "Cys12", "entity_type": "Chemical", "pos": [485, 490]}, {"entity": "vinyl", "entity_type": "Chemical", "pos": [509, 514]}], "task": "NER"}
{"text": "The match between the RR spectra of the Pfr states of PaBphP and the bathy phytochrome Agp2 from Agrobacterium tumefaciens indicates very similar structures of the chromophore binding pockets .", "entity": [], "task": "NER"}
{"text": "The homogeneous chromophore conformation in bathy phytochromes is in sharp contrast to the Pfr states of prototypical phytochromes as demonstrated by comparative RR spectroscopic analyses .", "entity": [], "task": "NER"}
{"text": "The Pfr states of prototypical phytochromes , thoroughly studied for Agp1 ( A . tumefaciens ) , display conformational equilibria between two sub - states differing with respect to the CD methine bridge torsional angle and the AB methine bridge geometry .", "entity": [{"entity": "methine", "entity_type": "Chemical", "pos": [188, 195]}, {"entity": "methine", "entity_type": "Chemical", "pos": [230, 237]}], "task": "NER"}
{"text": "These differences may mainly root in the interactions of the cofactor with the highly conserved Asp194 ( PaBphP ) that occur via its carboxylate function in bathy phytochromes .", "entity": [{"entity": "Asp194", "entity_type": "Chemical", "pos": [96, 102]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [133, 144]}], "task": "NER"}
{"text": "The weaker interactions via the carbonyl function in prototypical phytochromes may lead to a higher structural flexibility of the chromophore binding pocket that opens the reaction channel for the thermal ( ZZE --> ZZZ ) Pfr - to - Pr back - conversion .", "entity": [{"entity": "carbonyl", "entity_type": "Chemical", "pos": [32, 40]}], "task": "NER"}
{"text": "Genetic Information and the Prediction of Incident Type 2 Diabetes in a High - Risk Multi - Ethnic Population : The EpiDREAM Genetic Study .", "entity": [], "task": "NER"}
{"text": "OBJECTIVESTo determine if 16 single nucleotide polymorphisms ( SNPs ) associated with type 2 diabetes ( T2DM ) in Europeans are also associated with T2DM in South Asians and Latinos , and if they can add to the prediction of incident T2DM in a high - risk population . RESEARCH DESIGN AND METHODSIn the EpiDREAM prospective cohort study , physical measures , questionnaires , and blood samples were collected from 25 , 063 individuals at risk for dysglycemia .", "entity": [], "task": "NER"}
{"text": "Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped .", "entity": [], "task": "NER"}
{"text": "Among 15 , 466 European , South Asian , and Latino subjects , we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM ( n = 1 , 016 ) that developed during 3 . 3 years of follow - up . RESULTSNine of the 16 SNPs were significantly associated with T2DM , and their direction of effect was consistent across the three ethnic groups .", "entity": [], "task": "NER"}
{"text": "The gene score was significantly higher among subjects who developed incident T2DM ( cases vs . noncases : 16 . 47 [ 2 . 50 ] vs . 15 . 99 [ 2 . 56 ] ; P = 0 . 00001 ) .", "entity": [], "task": "NER"}
{"text": "The gene score remained an independent predictor of incident T2DM with an odds ratio of 1 . 08 ( 95 % CI , 1 . 05 - 1 . 11 ) per additional risk allele after adjustment for T2DM risk factors .", "entity": [], "task": "NER"}
{"text": "The gene score in those with no family history of T2DM was 16 . 02 , whereas it was 16 . 19 in those with one parent with T2DM and it was 16 . 32 in those with two parents with T2DM ( P trend = 0 . 0004 ) .", "entity": [], "task": "NER"}
{"text": "The C statistic of T2DM risk factors was 0 . 708 ( 0 . 691 - 0 . 725 ) and increased only marginally to 0 . 714 ( 0 . 698 - 0 . 731 ) with the addition of the gene score ( P for C statistic change = 0 . 0052 ) . CONCLUSIONT2DM genetic associations are generally consistent across ethnic groups , and a gene score only adds marginal information to clinical factors for T2DM prediction .", "entity": [], "task": "NER"}
{"text": "Strain - induced Dirac cone - like electronic structures and semiconductor - semimetal transition in graphdiyne .", "entity": [{"entity": "graphdiyne", "entity_type": "Chemical", "pos": [101, 111]}], "task": "NER"}
{"text": "By means of first - principles calculations combined with the tight - binding approximation , the strain - induced semiconductor - semimetal transition in graphdiyne is discovered .", "entity": [{"entity": "graphdiyne", "entity_type": "Chemical", "pos": [155, 165]}], "task": "NER"}
{"text": "It is shown that the band gap of graphdiyne increases from 0 . 47 eV to 1 . 39 eV with increasing the biaxial tensile strain , while the band gap decreases from 0 . 47 eV to nearly zero with increasing the uniaxial tensile strain , and Dirac cone - like electronic structures are observed .", "entity": [{"entity": "graphdiyne", "entity_type": "Chemical", "pos": [33, 43]}], "task": "NER"}
{"text": "The uniaxial strain - induced changes of the electronic structures of graphdiyne come from the breaking of geometrical symmetry that lifts the degeneracy of energy bands .", "entity": [{"entity": "graphdiyne", "entity_type": "Chemical", "pos": [70, 80]}], "task": "NER"}
{"text": "The properties of graphdiyne under strains are found to differ remarkably from that of graphene .", "entity": [{"entity": "graphdiyne", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "The nascent polypeptide - associated complex is a key regulator of proteostasis .", "entity": [], "task": "NER"}
{"text": "The adaptation of protein synthesis to environmental and physiological challenges is essential for cell viability .", "entity": [], "task": "NER"}
{"text": "Here , we show that translation is tightly linked to the protein - folding environment of the cell through the functional properties of the ribosome bound chaperone NAC ( nascent polypeptide - associated complex ) .", "entity": [], "task": "NER"}
{"text": "Under non - stress conditions , NAC associates with ribosomes to promote translation and protein folding .", "entity": [], "task": "NER"}
{"text": "When proteostasis is imbalanced , NAC relocalizes from a ribosome - associated state to protein aggregates in its role as a chaperone .", "entity": [], "task": "NER"}
{"text": "This results in a functional depletion of NAC from the ribosome that diminishes translational capacity and the flux of nascent proteins .", "entity": [], "task": "NER"}
{"text": "Depletion of NAC from polysomes and re - localisation to protein aggregates is observed during ageing , in response to heat shock and upon expression of the highly aggregation - prone polyglutamine - expansion proteins and A beta - peptide .", "entity": [{"entity": "polyglutamine", "entity_type": "Chemical", "pos": [184, 197]}], "task": "NER"}
{"text": "These results demonstrate that NAC has a central role as a proteostasis sensor to provide the cell with a regulatory feedback mechanism in which translational activity is also controlled by the folding state of the cellular proteome and the cellular response to stress .", "entity": [], "task": "NER"}
{"text": "Antifungal Azoles : Structural Insights into Undesired Tight Binding to Cholesterol - Metabolizing CYP46A1 .", "entity": [{"entity": "Azoles", "entity_type": "Chemical", "pos": [11, 17]}, {"entity": "Cholesterol", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "Although there are currently three generations of antifungal azoles on the market , even the third generation agents show undesired interactions with human cytochrome P450 enzymes .", "entity": [{"entity": "azoles", "entity_type": "Chemical", "pos": [61, 67]}], "task": "NER"}
{"text": "CYP46A1 is a cholesterol - metabolizing P450 in the brain tightly binding a number of structurally distinct azoles .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [13, 24]}, {"entity": "azoles", "entity_type": "Chemical", "pos": [108, 114]}], "task": "NER"}
{"text": "Previously , we determined the crystal structures of CYP46A1 in complex with voriconazole and clotrimazole , and in the present work we co - crystallized the P450 with posaconazole at 2 . 5 A resolution .", "entity": [{"entity": "voriconazole", "entity_type": "Chemical", "pos": [77, 89]}, {"entity": "clotrimazole", "entity_type": "Chemical", "pos": [94, 106]}, {"entity": "posaconazole", "entity_type": "Chemical", "pos": [168, 180]}], "task": "NER"}
{"text": "This long antifungal drug coordinates the P450 heme iron with the nitrogen atom of its terminal azole ring and adopts a linear configuration occupying the whole length of the substrate access channel and extending beyond the protein surface .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [47, 51]}, {"entity": "iron", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [66, 74]}, {"entity": "azole", "entity_type": "Chemical", "pos": [96, 101]}], "task": "NER"}
{"text": "Numerous drug - protein interactions determine the submicromolar Kd of posaconazole for CYP46A1 .", "entity": [{"entity": "posaconazole", "entity_type": "Chemical", "pos": [71, 83]}], "task": "NER"}
{"text": "We compared the crystal structure of posaconazole - bound CYP46A1 with those of the P450 in complex with other drugs including the antifungal voriconazole and clotrimazole .", "entity": [{"entity": "posaconazole", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "voriconazole", "entity_type": "Chemical", "pos": [142, 154]}, {"entity": "clotrimazole", "entity_type": "Chemical", "pos": [159, 171]}], "task": "NER"}
{"text": "We also analyzed the accommodation of posaconazole in the active site of the target enzymes , CYPs 51 , from several pathogenic species .", "entity": [{"entity": "posaconazole", "entity_type": "Chemical", "pos": [38, 50]}], "task": "NER"}
{"text": "These and the solution studies with different marketed azoles , collectively , allowed us to identify the determinants of tight azole binding to CYP46A1 and generate an overall picture of azole binding to this important P450 .", "entity": [{"entity": "azoles", "entity_type": "Chemical", "pos": [55, 61]}, {"entity": "azole", "entity_type": "Chemical", "pos": [128, 133]}, {"entity": "azole", "entity_type": "Chemical", "pos": [188, 193]}], "task": "NER"}
{"text": "The data obtained suggest that development of CYP51 - specific antifungal agents will continue to be a challenge .", "entity": [], "task": "NER"}
{"text": "Therefore , structural understanding of the azole binding not only to CYPs 51 from the pathogenic species but also to different human P450s is required to deal efficiently with this challenge .", "entity": [{"entity": "azole", "entity_type": "Chemical", "pos": [44, 49]}], "task": "NER"}
{"text": "Pharmacological activation of kappa opioid receptors : aversive effects in adolescent and adult male rats .", "entity": [], "task": "NER"}
{"text": "RATIONALE : The dynorphin ( DYN ) / kappa opioid receptor ( KOR ) system is involved in the dysphoric properties of drugs of abuse .", "entity": [], "task": "NER"}
{"text": "Given that adolescents show reduced sensitivity to aversive effects of many drugs , alterations in the DYN / KOR system may contribute to the prevalence of drug use during adolescence .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The present study was designed to assess dysphoric properties of a selective kappa agonist , U62 , 066 , in adolescent and adult rats using both conditioned taste aversion ( CTA ) and conditioned place aversion ( CPA ) paradigms .", "entity": [{"entity": "U62 , 066", "entity_type": "Chemical", "pos": [106, 115]}], "task": "NER"}
{"text": "METHODS : For CTA , water - restricted rats were administered U62 , 066 following 30 min access to a saccharin solution , with subsequent saccharin consumption used to index aversion .", "entity": [{"entity": "U62 , 066", "entity_type": "Chemical", "pos": [62, 71]}, {"entity": "saccharin", "entity_type": "Chemical", "pos": [101, 110]}, {"entity": "saccharin", "entity_type": "Chemical", "pos": [138, 147]}], "task": "NER"}
{"text": "For CPA , animals were allowed access to both compartments of a two - compartment chamber for a 15 - min pre - and post - conditioning test .", "entity": [], "task": "NER"}
{"text": "For conditioning , subjects were administered U62 , 066 prior to confinement to one side of the chamber and saline prior to confinement to the other side for a total of four pairings .", "entity": [{"entity": "U62 , 066", "entity_type": "Chemical", "pos": [46, 55]}], "task": "NER"}
{"text": "RESULTS : Overall , adolescents displayed reduced sensitivity to the kappa agonist relative to adults .", "entity": [], "task": "NER"}
{"text": "Adults demonstrated taste aversions to the 0 . 2 and 0 . 3 mg / kg doses of U62 , 066 , whereas adolescents did not display aversions to any tested doses .", "entity": [{"entity": "U62 , 066", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Adults demonstrated a place aversion to the 0 . 1 and 0 . 2 mg / kg dose of U62 , 066 when paired with the preferred side of the conditioning chamber .", "entity": [{"entity": "U62 , 066", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "Adolescents did not display aversions to any of the doses tested .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Reduced sensitivity to DYN / KOR system activation during adolescence may be a contributing factor to the age - typical insensitivity to aversive properties of drugs commonly abused by adolescents .", "entity": [], "task": "NER"}
{"text": "Automatic approach bias towards smoking cues is present in smokers but not in ex - smokers .", "entity": [], "task": "NER"}
{"text": "RATIONALE : Drug - addicted individuals show automatic approach tendencies towards drug - related cues , i . e . , an approach bias ( ApB ) .", "entity": [], "task": "NER"}
{"text": "Nevertheless , little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : We investigated ApB to smoking cues in heavy tobacco smokers versus never - smokers and studied its relation to smoking characteristics and craving .", "entity": [], "task": "NER"}
{"text": "Second , we compared ApBs of heavy smokers with biases of abstinent heavy smokers .", "entity": [], "task": "NER"}
{"text": "METHOD : A group of current heavy smokers ( n = 24 ) , ex - smokers who were abstinent for at least 5 years ( n = 20 ) , and never - smokers ( n = 20 ) took part in the experiment .", "entity": [], "task": "NER"}
{"text": "An indirect smoking approach avoidance task was performed , in which participants were required to respond to pictures of smoking and neutral cues by pulling ( approach ) or pushing ( avoid ) on a joystick , according to the content - irrelevant format of the picture ( landscape or portrait ) .", "entity": [], "task": "NER"}
{"text": "Craving scores were examined using the Questionnaire of Smoking Urges .", "entity": [], "task": "NER"}
{"text": "RESULTS : Heavy smokers showed an ApB for smoking cues compared to ex - smokers and never - smokers , which correlated positively to craving scores .", "entity": [], "task": "NER"}
{"text": "There were no group differences in ApB scores for ex - smokers and never - smokers .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long - term successful smoking cessation .", "entity": [], "task": "NER"}
{"text": "Methylphenidate reduces functional connectivity of nucleus accumbens in brain reward circuit .", "entity": [{"entity": "Methylphenidate", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Release of dopamine in the nucleus accumbens ( NAcc ) is essential for acute drug reward .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "The present study was designed to trace the reinforcing effect of dopamine release by measuring the functional connectivity ( FC ) between the NAcc and brain regions involved in a limbic cortical - subcortical circuit during a dopaminergic challenge .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [66, 74]}], "task": "NER"}
{"text": "Twenty healthy volunteers received single doses of methylphenidate ( 40 mg ) and placebo on separate test days according to a double - blind , cross - over study design .", "entity": [{"entity": "methylphenidate", "entity_type": "Chemical", "pos": [51, 66]}], "task": "NER"}
{"text": "Resting state functional magnetic resonance imaging ( fMRI ) was measured between 1 . 5 and 2 h postdosing .", "entity": [], "task": "NER"}
{"text": "FC between regions of interest ( ROI ) in the NAcc , the medial dorsal nucleus ( MDN ) of the thalamus and remote areas within the limbic circuit was explored .", "entity": [], "task": "NER"}
{"text": "Methylphenidate significantly reduced FC between the NAcc and the basal ganglia ( i . e . , subthalamic nucleus and ventral pallidum ( VP ) ) , relative to placebo .", "entity": [{"entity": "Methylphenidate", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "pallidum", "entity_type": "Chemical", "pos": [124, 132]}], "task": "NER"}
{"text": "Methylphenidate also decreased FC between the NAcc and the medial prefrontal cortex ( mPFC ) as well as the temporal cortex .", "entity": [{"entity": "Methylphenidate", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Methylphenidate did not affect FC between MDN and the limbic circuit .", "entity": [{"entity": "Methylphenidate", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "It is concluded that methylphenidate directly affects the limbic reward circuit .", "entity": [{"entity": "methylphenidate", "entity_type": "Chemical", "pos": [21, 36]}], "task": "NER"}
{"text": "Drug - induced changes in FC of the NAcc may serve as a useful marker of drug activity in in the brain reward circuit .", "entity": [], "task": "NER"}
{"text": "Balancing power density based quantum yield characterization of upconverting nanoparticles for arbitrary excitation intensities .", "entity": [], "task": "NER"}
{"text": "Upconverting nanoparticles ( UCNPs ) have recently shown great potential as contrast agents in biological applications .", "entity": [], "task": "NER"}
{"text": "In developing different UCNPs , the characterization of their quantum yield ( QY ) is a crucial issue , as the typically drastic decrease in QY for low excitation power densities can either impose a severe limitation or provide an opportunity in many applications .", "entity": [], "task": "NER"}
{"text": "The power density dependence of the QY is governed by the competition between the energy transfer upconversion ( ETU ) rate and the linear decay rate in the depopulation of the intermediate state of the involved activator in the upconversion process .", "entity": [], "task": "NER"}
{"text": "Here we show that the QYs of Yb ( 3 + ) sensitized two - photon upconversion emissions can be well characterized by the balancing power density , at which the ETU rate and the linear decay rate have equal contributions , and its corresponding QY .", "entity": [{"entity": "Yb ( 3 + )", "entity_type": "Chemical", "pos": [29, 39]}], "task": "NER"}
{"text": "The results in this paper provide a method to fully describe the QY of upconverting nanoparticles for arbitrary excitation power densities , and is a fast and simple approach for assessing the applicability of UCNPs from the perspective of energy conversion .", "entity": [], "task": "NER"}
{"text": "Sparstolonin B suppresses lipopolysaccharide - induced inflammation in human umbilical vein endothelial cells .", "entity": [{"entity": "Sparstolonin B", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "Sparstolonin B ( SsnB ) is an isocoumarin compound isolated from the tubers of both Sparganium stoloniferum and Scirpus yagara .", "entity": [{"entity": "Sparstolonin B", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "SsnB", "entity_type": "Chemical", "pos": [17, 21]}, {"entity": "isocoumarin", "entity_type": "Chemical", "pos": [30, 41]}], "task": "NER"}
{"text": "We previously demonstrated that SsnB blocked the Toll - like receptor ( TLR ) 2 - and TLR4 - triggered inflammatory signaling in macrophages by inhibiting the recruitment of MyD88 to the TIR domains of TLR2 and TLR4 .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [32, 36]}], "task": "NER"}
{"text": "The present study was designed to examine the effects of SsnB on vascular inflammatory responses in human umbilical vein endothelial cells ( HUVECs ) challenged by lipopolysaccharide ( LPS , a TLR4 ligand ) .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [57, 61]}], "task": "NER"}
{"text": "We found that SsnB dose - dependently attenuated the LPS - induced expression of interleukin ( IL ) - 1 beta and monocyte chemoattractant protein 1 both at the transcription and translation levels in HUVEC .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "LPS - induced endothelial cell adhesion molecules , intercellular adhesion molecular - 1 and vascular cell adhesion molecule - 1 expressions were also reduced by treatment with SsnB .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [177, 181]}], "task": "NER"}
{"text": "In addition , co - incubation with SsnB attenuated THP - 1 monocyte adhesion to LPS - activated HUVECs .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [35, 39]}], "task": "NER"}
{"text": "Furthermore , SsnB efficiently suppressed LPS - induced phosphorylation of extracellular - signal - regulated kinase ( Erk1 / 2 ) and Akt in HUVECs .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "These findings show that SsnB can suppress endothelial cell inflammation , suggesting that SsnB might be suitable for development as a therapeutic agent for inflammatory cardiovascular disease .", "entity": [{"entity": "SsnB", "entity_type": "Chemical", "pos": [25, 29]}, {"entity": "SsnB", "entity_type": "Chemical", "pos": [91, 95]}], "task": "NER"}
{"text": "Cytochrome p450 - mediated changes in oxycodone pharmacokinetics / pharmacodynamics and their clinical implications .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [38, 47]}], "task": "NER"}
{"text": "In recent years the use of the opioid oxycodone has increased markedly and replacing morphine as the first - line choice of opioid in several countries .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [85, 93]}], "task": "NER"}
{"text": "There are formulations for oral immediate , oral extended release and intravenous use .", "entity": [], "task": "NER"}
{"text": "The bioavailability is higher than for morphine and less variable .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "Oxycodone is primarily metabolized in the liver by the cytochrome P450 ( CYP ) enzymes with CYP3A as the major metabolic pathway and CYP2D6 as the minor metabolic pathway to noroxycodone , oxymorphone and noroxymorphone .", "entity": [{"entity": "Oxycodone", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "noroxycodone", "entity_type": "Chemical", "pos": [174, 186]}, {"entity": "oxymorphone", "entity_type": "Chemical", "pos": [189, 200]}, {"entity": "noroxymorphone", "entity_type": "Chemical", "pos": [205, 219]}], "task": "NER"}
{"text": "Oxycodone exerts its analgesic effect via the micro - opioid receptor .", "entity": [{"entity": "Oxycodone", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The metabolism of CYP2D6 substrates varies to a large degree between individuals as a result of allele functionality .", "entity": [], "task": "NER"}
{"text": "Poor metabolizers ( PM ) have two non - functional alleles , extensive metabolizers ( EM ) are homozygous with two functional alleles or heterozygous with one functional allele and ultrarapid metabolizers ( UM ) have more than two functional alleles .", "entity": [], "task": "NER"}
{"text": "There are pronounced interethnic differences in the allele distribution .", "entity": [], "task": "NER"}
{"text": "On the basis of studies performed thus far , oxycodone concentrations in comparison with EM are similar in PM and reduced in UM .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [45, 54]}], "task": "NER"}
{"text": "The pharmacokinetics in UM are insufficiently investigated .", "entity": [], "task": "NER"}
{"text": "Simultaneous inhibition of both CYP3A and CYP2D6 results in increased oxycodone concentrations and such a combination should be avoided .", "entity": [{"entity": "oxycodone", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "A similar effect is to be expected with use of a CYP3A inhibitor in CYP2D6 PM .", "entity": [], "task": "NER"}
{"text": "Concomitant use of enzyme inducers such as rifampicin , St John ' s wort and carbamazepine should be avoided because of the risk of subtherapeutic concentrations of oxycodone .", "entity": [{"entity": "rifampicin", "entity_type": "Chemical", "pos": [43, 53]}, {"entity": "carbamazepine", "entity_type": "Chemical", "pos": [77, 90]}, {"entity": "oxycodone", "entity_type": "Chemical", "pos": [165, 174]}], "task": "NER"}
{"text": "When the dosage of morphine may result in unpredictable bioavailability , like in patients with severe hepatic cirrhosis , oxycodone might be beneficial because it has higher and less variability in bioavailability between patients than morphine .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [19, 27]}, {"entity": "oxycodone", "entity_type": "Chemical", "pos": [123, 132]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [237, 245]}], "task": "NER"}
{"text": "Using multiple targeted therapies in oncology : considerations for use , and progress to date in breast cancer .", "entity": [], "task": "NER"}
{"text": "There has been significant progress in our basic understanding of drugs and targets in the management of breast cancer .", "entity": [], "task": "NER"}
{"text": "Recent breast cancer clinical trials have examined whether combinations of drugs targeting transmembrane receptors or their downstream effectors involved in cell signal transduction can increase response rates and overcome acquired and / or de novo drug resistance compared to a single targeted agent with or without systemic chemotherapy .", "entity": [], "task": "NER"}
{"text": "We reviewed published clinical trials and conference proceedings examining combinations of targeted therapies across different breast cancer subtypes .", "entity": [], "task": "NER"}
{"text": "Improvements in pathological complete response ( pCR ) rates and progression free survival ( PFS ) in preoperatively treated and metastatic human epidermal growth factor 2 ( HER2 ) - positive breast cancer , respectively , have been observed with combinations of anti - HER2 therapies given concomitantly .", "entity": [], "task": "NER"}
{"text": "Promising results were also observed in estrogen receptor ( ER ) - positive , HER2 - negative breast cancer using a mammalian target of rapamycin inhibitor with tamoxifen or an aromatase inhibitor ( AI ) in the preoperative setting and for patients with metastatic breast cancer that had previously progressed on endocrine therapy alone .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [40, 48]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [136, 145]}, {"entity": "tamoxifen", "entity_type": "Chemical", "pos": [161, 170]}], "task": "NER"}
{"text": "A recent phase II trial reported a statistically significant improvement in PFS with the addition of an oral inhibitor of cyclin - dependent kinase 4 / 6 to letrozole compared to letrozole alone ( 26 . 1 versus 7 . 5 months ) .", "entity": [{"entity": "letrozole", "entity_type": "Chemical", "pos": [157, 166]}, {"entity": "letrozole", "entity_type": "Chemical", "pos": [179, 188]}], "task": "NER"}
{"text": "A phase III study is planned for early 2013 .", "entity": [], "task": "NER"}
{"text": "On the basis of preclinical data , clinical trials have examined combinations of hormonal agents such as fulvestrant with an AI .", "entity": [{"entity": "fulvestrant", "entity_type": "Chemical", "pos": [105, 116]}], "task": "NER"}
{"text": "However , the results are conflicting .", "entity": [], "task": "NER"}
{"text": "Early data indicated that poly ( ADP - ribose ) polymerase ( PARP ) inhibitors exploiting the concept of synthetic lethality would offer improved outcomes for patients with ER - negative , progesterone receptor ( PR ) - negative , HER2 - negative breast cancer often referred to as triple negative breast cancer ( TNBC ) ; however , data in the phase III setting failed to confirm these findings but this may be because the drug was not a true PARP inhibitor .", "entity": [{"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [26, 47]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [189, 201]}], "task": "NER"}
{"text": "Chemotherapy continues to be the mainstay of treatment for TNBC until specific drugs and their associated targets are identified .", "entity": [], "task": "NER"}
{"text": "As advances in medical technologies continue to identify multiple molecularly distinct breast cancer subgroups that are predicted to respond to combinations of targeted agents new challenges have arisen .", "entity": [], "task": "NER"}
{"text": "In particular , how do we evaluate the safety and efficacy of these new drug combinations in relatively small subgroups of patients ?", "entity": [], "task": "NER"}
{"text": "Novel clinical trial designs will be required and increasingly regulatory agencies will require companion diagnostic tests that can identify the subgroups likely to respond to these therapies .", "entity": [], "task": "NER"}
{"text": "The US Food and Drug Administration is assessing the role of pCR in breast cancer studies as a surrogate endpoint to predict clinical benefit in the accelerated drug approval process .", "entity": [], "task": "NER"}
{"text": "Hedgehog Signaling Pathway and Cancer Therapeutics : Progress to Date .", "entity": [], "task": "NER"}
{"text": "The Hedgehog ( Hh ) pathway is a developmental signaling pathway involved in numerous developmental processes , including determination of cell fate , patterning , proliferation , survival , and differentiation .", "entity": [], "task": "NER"}
{"text": "While this pathway is silenced in most adult tissues , aberrant activation of it has been documented in a variety of malignancies .", "entity": [], "task": "NER"}
{"text": "In cancers such as basal cell carcinoma ( BCC ) , ligand - independent mechanisms lead to constitutive Hh pathway activation through mutations in components of the pathway , including patched - 1 ( PTCH1 ) or smoothened ( SMO ) .", "entity": [], "task": "NER"}
{"text": "On the contrary , numerous other solid and hematologic tumors have been shown to harbor ligand - dependent activation of the Hh pathway by autocrine or paracrine mechanisms .", "entity": [], "task": "NER"}
{"text": "Given that aberrant Hh pathway signaling has been seen in a number of malignancies , this pathway has been an attractive target for drug development .", "entity": [], "task": "NER"}
{"text": "While the best - characterized approach is to target the SMO receptor , other rational approaches for inhibiting the Hh pathway include inhibiting downstream components or directly binding Hh ligands .", "entity": [], "task": "NER"}
{"text": "In January of 2012 , vismodegib , a SMO antagonist , became the first agent to target the Hh pathway to receive approval by the United States Food and Drug Administration ( FDA ) after this agent showed remarkable activity in phase I and II trials for the treatment of BCC .", "entity": [{"entity": "vismodegib", "entity_type": "Chemical", "pos": [21, 31]}], "task": "NER"}
{"text": "Despite promising preclinical studies with Hh pathway inhibitors in other malignancies that have suggested a potential role for these agents , attempts to translate this potential to clinical benefit has been disappointing .", "entity": [], "task": "NER"}
{"text": "Future efforts will require further careful interpretation and analysis to determine the potential determinants and predictors of efficacy .", "entity": [], "task": "NER"}
{"text": "Currently , several phase I and II trials evaluating Hh inhibitors in a variety of tumor settings are underway .", "entity": [], "task": "NER"}
{"text": "Morphological Change and Mobility Enhancement in PEDOT : PSS by Adding Co - solvents .", "entity": [{"entity": "PEDOT", "entity_type": "Chemical", "pos": [49, 54]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [57, 60]}], "task": "NER"}
{"text": "Adding ethylene glycol ( EG ) to poly ( 3 , 4 - ethylenedioxythiophene ) : poly ( styrenesulfonate ) ( PEDOT : PSS ) solution improves the crystallinity of the PEDOT and the ordering of the PEDOT nanocrystals in solid films .", "entity": [{"entity": "ethylene glycol", "entity_type": "Chemical", "pos": [7, 22]}, {"entity": "poly ( 3 , 4 - ethylenedioxythiophene )", "entity_type": "Chemical", "pos": [33, 72]}, {"entity": "poly ( styrenesulfonate )", "entity_type": "Chemical", "pos": [75, 100]}, {"entity": "PEDOT", "entity_type": "Chemical", "pos": [103, 108]}, {"entity": "PSS", "entity_type": "Chemical", "pos": [111, 114]}, {"entity": "PEDOT", "entity_type": "Chemical", "pos": [160, 165]}, {"entity": "PEDOT", "entity_type": "Chemical", "pos": [190, 195]}], "task": "NER"}
{"text": "The carrier - mobility enhancement is confirmed by using ion - gel transistors combined with in situ UV - vis - NIR spectroscopy .", "entity": [], "task": "NER"}
{"text": "A Generic Micropatterning Platform to Direct Human Mesenchymal Stem Cells from Different Origins Towards Myogenic Differentiation .", "entity": [], "task": "NER"}
{"text": "Human mesenchymal stem cells ( MSCs ) derived from various origins show varied differentiation capability .", "entity": [], "task": "NER"}
{"text": "Recent work shows that cell shape manipulation via micropatterning can modulate the differentiation of bone - marrow - derived MSCs .", "entity": [], "task": "NER"}
{"text": "Herein , the effect of micropatterning on the myogenesis of MSCs isolated from three different sources ( bone marrow , fetal tissue , and adipose ) is reported .", "entity": [], "task": "NER"}
{"text": "All the well - aligned cells , regardless of source , predominantly commit to myogenic lineage , as shown by the significant upregulation of myogenic gene markers and positive myosin heavy chain staining .", "entity": [], "task": "NER"}
{"text": "It is demonstrated that our novel micropattern can be used as a generic platform for inducing myogenesis of MSCs from different sources and may also have the potential to be extended to induce other lineage commitment .", "entity": [], "task": "NER"}
{"text": "3D Graphene Foams Cross - linked with Pre - encapsulated Fe3 O4 Nanospheres for Enhanced Lithium Storage .", "entity": [{"entity": "Graphene", "entity_type": "Chemical", "pos": [3, 11]}, {"entity": "Fe3 O4", "entity_type": "Chemical", "pos": [57, 63]}, {"entity": "Lithium", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "Electrostatic assembly between Fe3 O4 nanospheres and graphene oxide , and subsequent hydrothermal assembly with additional graphene sheets , leads to Fe3 O4 nanospheres encapsulated in the graphene shells and interconnected by the graphene networks .", "entity": [{"entity": "Fe3 O4", "entity_type": "Chemical", "pos": [31, 37]}, {"entity": "graphene oxide", "entity_type": "Chemical", "pos": [54, 68]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [124, 132]}, {"entity": "Fe3 O4", "entity_type": "Chemical", "pos": [151, 157]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [190, 198]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [232, 240]}], "task": "NER"}
{"text": "Such 3D Fe3 O4 / graphene foams exhibit enhanced lithium storage with excellent cycling performance and rate capability .", "entity": [{"entity": "Fe3 O4", "entity_type": "Chemical", "pos": [8, 14]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [49, 56]}], "task": "NER"}
{"text": "Morphometric and Functional Changes of Salivary Gland Dysfunction after Radioiodine Ablation in a Murine Model .", "entity": [{"entity": "Radioiodine", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "Background : Ablation of the thyroid tissue using radioiodine ( RI ) after the surgical removal of well - differentiated thyroid cancer ( WDTC ) can induce radiation - related salivary gland ( SG ) dysfunction .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "However , in vivo changes of SGs following RI administration in appropriate animal models are not well described in the literature .", "entity": [], "task": "NER"}
{"text": "This study was undertaken to document morphometric and functional changes during the 12 months following RI administration in a murine model of RI - induced SG dysfunction .", "entity": [], "task": "NER"}
{"text": "Methods : Female C57BL / 6 , 4 - week - old mice ( n = 60 ) were divided into a RI - treated group ( n = 30 ) that received RI orally ( 0 . 01 mCi / g body weight ) or an unexposed control group ( n = 30 ) .", "entity": [], "task": "NER"}
{"text": "Mice in both groups were divided into five subgroups ( n = 6 per subgroup ) and sacrificed at 1 , 2 , 3 , 6 , and 12 months post - RI administration .", "entity": [], "task": "NER"}
{"text": "Salivary flow rates ( SFR ) and salivary lag times were measured at 1 , 2 , 3 , 6 , and 12 months after RI administration .", "entity": [], "task": "NER"}
{"text": "Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) assays were performed .", "entity": [{"entity": "deoxynucleotidyl", "entity_type": "Chemical", "pos": [57, 73]}, {"entity": "dUTP", "entity_type": "Chemical", "pos": [86, 90]}], "task": "NER"}
{"text": "In addition , changes in salivary 99m Tc pertechnetate uptake and excretion were observed by single - photon emission computed tomography ( SPECT ) .", "entity": [{"entity": "99m Tc pertechnetate", "entity_type": "Chemical", "pos": [34, 54]}], "task": "NER"}
{"text": "Results : In RI - treated mice , the SGs were significantly lighter compared to unexposed controls at all study time points .", "entity": [], "task": "NER"}
{"text": "Lag times to salivation in the RI - treated group were greater than in the unexposed controls , but mean SFR were lower .", "entity": [], "task": "NER"}
{"text": "Histologic examinations of SGs in the RI - group showed pale cytoplasm , atypical ductal configuration , septal widening , cytoplasmic vacuolization with pleomorphism , lymphocyte infiltration , and increased fibrosis .", "entity": [], "task": "NER"}
{"text": "Furthermore , more apoptotic cells were observed in acini and ducts in the RI group .", "entity": [], "task": "NER"}
{"text": "In addition , patterns of 99m Tc pertechnetate uptake and excretion in the RI - group were quite different from those observed in controls at 1 and 12 months post - RI .", "entity": [{"entity": "99m Tc pertechnetate", "entity_type": "Chemical", "pos": [26, 46]}], "task": "NER"}
{"text": "Conclusion : Various histological alterations were observed in mice exposed to radioiodine , that is , an increase in apoptotic acini and ductal cells and functional SG deterioration .", "entity": [{"entity": "radioiodine", "entity_type": "Chemical", "pos": [79, 90]}], "task": "NER"}
{"text": "The murine model of RI - induced SG dysfunction used in the present study appears to be applicable to preclinical research on RI - induced sialadenitis in patients with WDTC .", "entity": [], "task": "NER"}
{"text": "Recommendations for the Use of Prolonged - Release Fampridine in Patients with Multiple Sclerosis ( MS ) .", "entity": [{"entity": "Fampridine", "entity_type": "Chemical", "pos": [51, 61]}], "task": "NER"}
{"text": "Prolonged - release fampridine ( fampridine PR ) is a potassium channel blocker that improves conductivity of signal on demyelinated axons in central nervous system .", "entity": [{"entity": "fampridine", "entity_type": "Chemical", "pos": [20, 30]}, {"entity": "fampridine PR", "entity_type": "Chemical", "pos": [33, 46]}, {"entity": "potassium", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "Fampridine PR has been approved to improve speed of walking in patients with multiple sclerosis .", "entity": [{"entity": "Fampridine PR", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "This statement provides a brief summary of data on fampridine PR and recommendations on practical use of the medication in clinical practice , prediction , and evaluation of response to treatment and patient management .", "entity": [{"entity": "fampridine PR", "entity_type": "Chemical", "pos": [51, 64]}], "task": "NER"}
{"text": "Synaptotagmin 1 is required for vesicular Ca ( 2 + ) / H ( + ) - antiport activity .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [42, 52]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "A low - affinity Ca ( 2 + ) / H ( + ) - antiport was described in the membrane of mammalian brain synaptic vesicles .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [17, 27]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Electrophysiological studies showed that this antiport contributes to the extreme brevity of excitation - release coupling in rapid synapses .", "entity": [], "task": "NER"}
{"text": "Synaptotagmin - 1 , a vesicular protein interacting with membranes upon low - affinity Ca ( 2 + ) - binding , plays a major role in excitation - release coupling , by synchronizing calcium entry with fast neurotransmitter release .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [87, 97]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "Here , we report that synaptotagmin - 1 is necessary for expression of the vesicular Ca ( 2 + ) / H ( + ) - antiport .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [85, 95]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [98, 105]}], "task": "NER"}
{"text": "We measured Ca ( 2 + ) / H ( + ) - antiport activity in vesicles and granules of pheochromocytoma PC12 cells by three methods : ( 1 ) Ca ( 2 + ) - induced dissipation of the vesicular H ( + ) - gradient ; ( 2 ) bafilomycin - sensitive calcium accumulation and ( 3 ) pH - jump - induced calcium accumulation .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [12, 22]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [25, 32]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [134, 144]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [184, 191]}, {"entity": "bafilomycin", "entity_type": "Chemical", "pos": [211, 222]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [235, 242]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [286, 293]}], "task": "NER"}
{"text": "The results were congruent and highly significant : Ca ( 2 + ) / H ( + ) - antiport activity is detectable only in acidic organelles expressing functional synaptotagmin - 1 .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [52, 62]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [65, 72]}], "task": "NER"}
{"text": "In contrast , synaptotagmin - 1 - deficient cells - and cells where transgenically encoded synaptotagmin - 1 was acutely photo - inactivated - were devoid of any Ca ( 2 + ) / H ( + ) - antiport activity .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [162, 172]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [175, 182]}], "task": "NER"}
{"text": "Therefore , in addition to its previously described functions , synaptotagmin - 1 is involved in a rapid vesicular Ca ( 2 + ) sequestration through a Ca ( 2 + ) / H ( + ) antiport .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [115, 125]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [150, 160]}, {"entity": "H ( + )", "entity_type": "Chemical", "pos": [163, 170]}], "task": "NER"}
{"text": "Cell - Cycle Changes and Oxidative Stress Response to Magnetite in A549 Human Lung Cells .", "entity": [{"entity": "Magnetite", "entity_type": "Chemical", "pos": [54, 63]}], "task": "NER"}
{"text": "In a recent study , magnetite was investigated for its potential to induce toxic effects and influence signaling pathways .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [20, 29]}], "task": "NER"}
{"text": "It was clearly demonstrated that ROS formation leads to mitochondrial damage and genotoxic effects in A549 cells .", "entity": [], "task": "NER"}
{"text": "On the basis of these findings , we wanted to elucidate the origin of magnetite - mediated ROS formation and its influence on the cell cycle of A549 and H1299 human lung epithelial cells .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [70, 79]}], "task": "NER"}
{"text": "Concentration - and size - dependent superoxide formation , measured by electron paramagnetic resonance ( EPR ) , was observed .", "entity": [{"entity": "superoxide", "entity_type": "Chemical", "pos": [37, 47]}], "task": "NER"}
{"text": "Furthermore , we could show that the GSH level decreased significantly after exposure to magnetite particles , while catalase ( CAT ) activity was increased .", "entity": [{"entity": "GSH", "entity_type": "Chemical", "pos": [37, 40]}, {"entity": "magnetite", "entity_type": "Chemical", "pos": [89, 98]}], "task": "NER"}
{"text": "These effects were also dependent on particle size , albeit less pronounced than those observed with EPR .", "entity": [], "task": "NER"}
{"text": "We were able to show that incubation of A549 cells prior to particle treatment with diphenyleneiodonium ( DPI ) , a NADPH - oxidase ( NOX ) inhibitor , leads to decreased ROS formation , but this effect was not observed for the NOX inhibitor apocynin .", "entity": [{"entity": "diphenyleneiodonium", "entity_type": "Chemical", "pos": [84, 103]}, {"entity": "DPI", "entity_type": "Chemical", "pos": [106, 109]}, {"entity": "NADPH", "entity_type": "Chemical", "pos": [116, 121]}, {"entity": "apocynin", "entity_type": "Chemical", "pos": [242, 250]}], "task": "NER"}
{"text": "Soluble iron does not contribute considerably to ROS production .", "entity": [{"entity": "iron", "entity_type": "Chemical", "pos": [8, 12]}], "task": "NER"}
{"text": "Analysis of cell - cycle distribution revealed a pronounced sub - G1 peak , which cannot be linked to increased cell death .", "entity": [], "task": "NER"}
{"text": "Western blot analysis did not show activation of p53 but upregulation of p21 in A549 .", "entity": [], "task": "NER"}
{"text": "Here , we were unexpectedly able to demonstrate that exposure to magnetite leads to p21 - mediated G1 - like arrest .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [65, 74]}], "task": "NER"}
{"text": "This has been reported previously only for low concentrations of microtubule stabilization drugs .", "entity": [], "task": "NER"}
{"text": "Importantly , the arrested sub - G1 cells were viable and showed no caspase 3 / 7 activation .", "entity": [], "task": "NER"}
{"text": "Antimicrobial and demelanizing activity of Ganoderma lucidum extract , p - hydroxybenzoic and cinnamic acids and their synthetic acetylated glucuronide methyl esters .", "entity": [{"entity": "p - hydroxybenzoic and cinnamic acids", "entity_type": "Chemical", "pos": [71, 108]}, {"entity": "acetylated glucuronide methyl esters", "entity_type": "Chemical", "pos": [129, 165]}], "task": "NER"}
{"text": "Mushroom extracts or isolated compounds may be useful in the search of new potent antimicrobial agents .", "entity": [], "task": "NER"}
{"text": "Herein , it is described the synthesis of protected ( acetylated ) glucuronide derivatives of p - hydroxybenzoic and cinnamic acids , two compounds identified in the medicinal mushroom Ganoderma lucidum .", "entity": [{"entity": "p - hydroxybenzoic and cinnamic acids", "entity_type": "Chemical", "pos": [94, 131]}], "task": "NER"}
{"text": "Their antimicrobial and demelanizing activities were evaluated and compared to the parent acids and G . lucidum extract .", "entity": [], "task": "NER"}
{"text": "p - Hydroxybenzoic and cinnamic acids , as also their protected glucuronide derivatives revealed high antimicrobial ( antibacterial and antifungal ) activity , even better than the one showed by commercial standards .", "entity": [{"entity": "p - Hydroxybenzoic and cinnamic acids", "entity_type": "Chemical", "pos": [0, 37]}], "task": "NER"}
{"text": "Despite the variation in the order of parent acids and the protected glucuronide derivatives , their antimicrobial activity was always higher than the one revealed by the extract .", "entity": [], "task": "NER"}
{"text": "Nevertheless , the extract was the only one with demelanizing activity against Aspergillus niger .", "entity": [], "task": "NER"}
{"text": "The acetylated glucuronide derivatives could be deprotected to obtain glucuronide metabolites , which circulate in the human organism as products of the metabolism of the parent compounds .", "entity": [], "task": "NER"}
{"text": "Synthesis and antiprogestational properties of novel 17 - fluorinated steroids .", "entity": [{"entity": "17 - fluorinated steroids", "entity_type": "Chemical", "pos": [53, 78]}], "task": "NER"}
{"text": "Progesterone receptor ( PR ) plays a key role in reproductive functions , and compounds that inhibit progesterone action ( antiprogestins ) have potential use in the treatment of estrogen - and progesterone - dependent diseases , including uterine leiomyomas and breast cancer .", "entity": [{"entity": "Progesterone", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [101, 113]}, {"entity": "antiprogestins", "entity_type": "Chemical", "pos": [123, 137]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [179, 187]}, {"entity": "progesterone", "entity_type": "Chemical", "pos": [194, 206]}], "task": "NER"}
{"text": "In the present study , we chemically synthesized novel 17 - fluorinated steroids and evaluated the cytotoxicity profiles of these compounds in T47D breast cancer cells compared to the activity of known antiprogestins , including ZK230 211 , RU - 486 , CDB2914 , CDB4124 and ORG33628 .", "entity": [{"entity": "17 - fluorinated steroids", "entity_type": "Chemical", "pos": [55, 80]}, {"entity": "antiprogestins", "entity_type": "Chemical", "pos": [202, 216]}, {"entity": "ZK230 211", "entity_type": "Chemical", "pos": [229, 238]}, {"entity": "RU - 486", "entity_type": "Chemical", "pos": [241, 249]}, {"entity": "CDB2914", "entity_type": "Chemical", "pos": [252, 259]}, {"entity": "CDB4124", "entity_type": "Chemical", "pos": [262, 269]}, {"entity": "ORG33628", "entity_type": "Chemical", "pos": [274, 282]}], "task": "NER"}
{"text": "We analyzed in vitro receptor - binding assays and PR - transactivation assays to establish the antiprogestational activity of these molecules .", "entity": [], "task": "NER"}
{"text": "The representative antiprogestin EC304 was found to inhibit in vitro tumorigenicity in a dose - dependent fashion in T47D cells by a colony formation assay at 1 and 10nM concentrations .", "entity": [{"entity": "EC304", "entity_type": "Chemical", "pos": [33, 38]}], "task": "NER"}
{"text": "The potent in vivo antiprogestational activity of EC304 was also demonstrated in an antinidation assay for the interruption of early pregnancy in rats .", "entity": [{"entity": "EC304", "entity_type": "Chemical", "pos": [50, 55]}], "task": "NER"}
{"text": "The strong antiprogestational activity and absence of antiglucocorticoid activity in EC compounds may demonstrate their utility in the treatment of leiomyoma , endometriosis and breast cancer .", "entity": [], "task": "NER"}
{"text": "Renal accumulation and effects of intraperitoneal injection of extracted microcystins in omnivorous crucian carp ( Carassius auratus ) .", "entity": [], "task": "NER"}
{"text": "An acute toxicological experiment was designed to characterize the sequence of renal ultrastructural changes with accumulated MCs in crucian carp injected intraperitoneally ( i . p . ) with extracted microcystins ( mainly MC - RR and - LR ) at two doses , 50 and 200 mu g MC - LReq . kg ( - 1 ) body weight .", "entity": [], "task": "NER"}
{"text": "Quantitative and qualitative determinations of MCs in the kidney were conducted by HPLC and LC - MS , respectively .", "entity": [], "task": "NER"}
{"text": "MC - RR content in kidney of crucian carp showed a time dose - dependent increase within 48 h post - injection , followed by a sharp decline afterward , while no MC - LR in kidney was detectable throughout the experiment .", "entity": [], "task": "NER"}
{"text": "Ultrastructural changes in the kidney of crucian carp progressed with increasing accumulated MCs and exposure times within 48 h post - injection , whereas renal ultrastructural recovery of crucian carp in the 50 mu g MC - LReq . kg ( - 1 ) dose group was evident at 168 h post - injection .", "entity": [], "task": "NER"}
{"text": "Our ultrastructural observation suggests that the membranous structure is the main action site of MCs in the kidney , among which mitochondria damage in the tubules is clearly an early , and presumably a critically important effect of MCs .", "entity": [], "task": "NER"}
{"text": "The increases in blood urea nitrogen ( BUN ) and creatinine ( CR ) in both dose groups further revealed severe impairment occurred in the kidney of crucian carp .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [23, 27]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [28, 36]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [49, 59]}], "task": "NER"}
{"text": "Cephalic phase insulin secretion is KATP channel - independent .", "entity": [], "task": "NER"}
{"text": "Glucose - induced insulin secretion from pancreatic beta - cells depends critically on activity of ATP - sensitive K + channels ( KATP channel ) .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [99, 102]}, {"entity": "K +", "entity_type": "Chemical", "pos": [115, 118]}], "task": "NER"}
{"text": "We previously generated mice lacking Kir6 . 2 , the pore subunit of the beta - cell KATP channel ( Kir6 . 2 - / - ) , that show almost no insulin secretion in response to glucose in vitro .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [171, 178]}], "task": "NER"}
{"text": "In the present study , we compared insulin secretion by voluntary feeding ( self - motivated , oral nutrient ingestion ) and by forced feeding ( intra - gastric nutrient injection via gavage ) in wild - type ( Kir6 . 2 + / + ) and Kir6 . 2 - / - mice .", "entity": [], "task": "NER"}
{"text": "Under ad libitum feeding or during voluntary feeding of standard chow , blood glucose levels and plasma insulin levels were similar in Kir6 . 2 + / + and Kir6 . 2 - / - mice .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [78, 85]}], "task": "NER"}
{"text": "By voluntary feeding of carbohydrate alone , insulin secretion was induced significantly in Kir6 . 2 - / - mice , but was markedly attenuated compared to that in Kir6 . 2 + / + mice .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [24, 36]}], "task": "NER"}
{"text": "On forced feeding of standard chow or carbohydrate alone , the insulin secretory response was markedly impaired or completely absent in Kir6 . 2 - / - mice .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [38, 50]}], "task": "NER"}
{"text": "Pre - treatment of a muscarine receptor antagonist , atropine methyl nitrate , which does not cross the blood - brain barrier , almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate in Kir6 . 2 - / - mice .", "entity": [{"entity": "atropine", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "methyl nitrate", "entity_type": "Chemical", "pos": [62, 76]}, {"entity": "carbohydrate", "entity_type": "Chemical", "pos": [221, 233]}], "task": "NER"}
{"text": "Substantial glucose - induced insulin secretion was induced in pancreas perfusion study of Kir6 . 2 - / - mice only in the presence of carbamylcholine .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [12, 19]}, {"entity": "carbamylcholine", "entity_type": "Chemical", "pos": [135, 150]}], "task": "NER"}
{"text": "These results suggest that a KATP channel - independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrients in vivo .", "entity": [], "task": "NER"}
{"text": "MAPKAPK2 / 3 Regulate SERCA2a Expression and Fiber Type Composition to Modulate Skeletal Muscle and Cardiomyocyte Function .", "entity": [], "task": "NER"}
{"text": "The MAPK - activated protein kinases 2 and 3 ( MAPKAPK2 / 3 , MK2 / 3 ) represent protein kinases downstream of the p38 mitogen - activated protein kinase ( MAPK ) .", "entity": [], "task": "NER"}
{"text": "Using MK2 / 3 double knockout mice ( MK2 / 3 ( - / - ) ) , we analyzed the role of MK2 / 3 in cross - striated muscle by transcriptome and proteome analyses , and by histology .", "entity": [], "task": "NER"}
{"text": "We demonstrated enhanced expression of the slow oxidative skeletal muscle myofiber gene program , including the PPAR gamma coactivator 1 alpha ( PGC - 1 alpha ) .", "entity": [], "task": "NER"}
{"text": "Using reporter gene and electrophoretic gel mobility shift assays we demonstrated that MK2 catalytic activity directly regulated the promoters of the fast fiber - specific myosin heavy chain IId / x and the slow fiber - specific sarco / endoplasmic reticulum Ca ( 2 + ) - ATPase ( SERCA ) 2 gene .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [259, 269]}], "task": "NER"}
{"text": "Elevated SERCA2a gene expression caused by a decreased transcription factor Egr - 1 to Sp1 ratio was associated with accelerated relaxation and enhanced contractility in MK2 / 3 ( - / - ) cardiomyocytes , concomitant with improved force parameters in MK2 / 3 ( - / - ) soleus muscle .", "entity": [], "task": "NER"}
{"text": "These results link MK2 / 3 to the regulation of calcium dynamics and identify enzymatic activity of MK2 / 3 as a critical factor for modulating cross - striated muscle function by generating a unique muscle phenotype exhibiting both , reduced fatigability and enhanced force in MK2 / 3 ( - / - ) mice .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [48, 55]}], "task": "NER"}
{"text": "Hence , the p38 - MK2 / 3 axis may represent a novel target for the design of therapeutic strategies for diseases related to fiber type changes or impaired SERCA2 function .", "entity": [], "task": "NER"}
{"text": "N - alkylation of highly quaternized chitosan derivatives affects the paracellular permeation enhancement in bronchial epithelia in vitro .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [0, 1]}], "task": "NER"}
{"text": "This study describes the structure - activity relationship for carefully characterized N - alkyl - N - quaternary chitosan derivatives as permeation enhancers for drugs that are mainly absorbed through the paracellular pathway , such as macromolecular drugs and hydrophilic drugs , in a well defined bronchial epithelial cell line .", "entity": [{"entity": "N - alkyl", "entity_type": "Chemical", "pos": [87, 96]}, {"entity": "N", "entity_type": "Chemical", "pos": [99, 100]}], "task": "NER"}
{"text": "The O - methyl free derivatives used in the study were fully trimethylated ( 100 % ) N , N , N - trimethyl chitosan ( TMC ) and N - propyl - ( QuatPropyl ) , N - butyl - ( QuatButyl ) and N - hexyl ( QuatHexyl ) - N , N - dimethyl chitosan , with 85 - 91 % degree of quaternization .", "entity": [{"entity": "O - methyl", "entity_type": "Chemical", "pos": [4, 14]}, {"entity": "N , N , N - trimethyl", "entity_type": "Chemical", "pos": [85, 106]}, {"entity": "N - propyl - ( QuatPropyl )", "entity_type": "Chemical", "pos": [128, 155]}, {"entity": "N - butyl - ( QuatButyl )", "entity_type": "Chemical", "pos": [158, 183]}, {"entity": "N - hexyl ( QuatHexyl ) - N , N - dimethyl", "entity_type": "Chemical", "pos": [188, 230]}], "task": "NER"}
{"text": "The fully trimethylated TMC , from 0 . 25mg / ml , decreased transepithelial electrical resistance ( TER ) in a reversible manner and enhanced the permeation of the macromolecule FITC - dextran 4kDa ( FD4 ) 2 - 5 fold .", "entity": [], "task": "NER"}
{"text": "TMC did not cause any alterations in the tight junction ( TJ ) protein claudin - 4 or in F - actin architecture .", "entity": [], "task": "NER"}
{"text": "QuatHexyl was the most effective polymer to produce enhanced permeation and decreased TER from 0 . 016mg / ml .", "entity": [{"entity": "QuatHexyl", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Nevertheless , this enhanced permeation was accompanied by reduced viability and dissociation of F - actin and claudin - 4 proteins .", "entity": [], "task": "NER"}
{"text": "The structure - activity relationship suggests that more lipophilic derivatives show more permeation enhancement , TJ disassembly , and less viability in the order of hexyl =~ butyl > propyl > methyl and demonstrates that the permeation effect is not only mediated by permanent positive charge but also through by the extent of N - alkylation .", "entity": [{"entity": "hexyl", "entity_type": "Chemical", "pos": [167, 172]}, {"entity": "butyl", "entity_type": "Chemical", "pos": [176, 181]}, {"entity": "propyl", "entity_type": "Chemical", "pos": [184, 190]}, {"entity": "methyl", "entity_type": "Chemical", "pos": [193, 199]}, {"entity": "N", "entity_type": "Chemical", "pos": [328, 329]}], "task": "NER"}
{"text": "These results are relevant to elucidate the structural factors contributing to the permeation enhancement of chitosan derivatives and for potential use in pulmonary applications .", "entity": [], "task": "NER"}
{"text": "Association of PON1 genotype and haplotype with susceptibility to coronary artery disease and clinical outcomes in dual antiplatelet - treated Han Chinese patients .", "entity": [], "task": "NER"}
{"text": "PURPOSE : The aim of this study was to evaluate the association of PON1 genetic variants with the susceptibility to coronary artery disease ( CAD ) and with the clinical endpoints in aspirin and clopidogrel ( dual antiplatelet therapy ) - treated Han Chinese patients with CAD after percutaneous coronary intervention ( PCI ) .", "entity": [{"entity": "aspirin", "entity_type": "Chemical", "pos": [183, 190]}, {"entity": "clopidogrel", "entity_type": "Chemical", "pos": [195, 206]}], "task": "NER"}
{"text": "METHODS : A total of 538 Han Chinese patients undergoing PCI and receiving dual - antiplatelet therapy were sequentially recruited to the study and followed for up to 1 year .", "entity": [], "task": "NER"}
{"text": "Healthy controls ( n = 539 ) were enrolled during the same period .", "entity": [], "task": "NER"}
{"text": "All study participants were genotyped for five genetic variants in PON1 and the cytochrome P450 2C19 * 2 mutation ( CYP2C19 * 2 ) .", "entity": [], "task": "NER"}
{"text": "The effect of genetic variants on disease risk and clinical outcome of major adverse cardiac events ( MACE ) within 1 year or bleeding within 6 months was assessed .", "entity": [], "task": "NER"}
{"text": "RESULTS : CYP2C19 * 2 was associated with a higher risk of MACE ( adjusted P = 0 . 0098 ) , but a lower risk of bleeding events ( adjusted P = 0 . 0016 ) .", "entity": [], "task": "NER"}
{"text": "The PON1 Q192R polymorphism was significantly associated with a lower risk of bleeding events [ odds ratio ( OR ) 0 . 61 , 95 % confidence interval ( CI ) 0 . 43 - 0 . 87 , adjusted P = 0 . 0066 ) .", "entity": [], "task": "NER"}
{"text": "The haplotype bearing the PON1 - 126C allele was associated with a higher risk to CAD ( OR 1 . 48 , 95 % CI 1 . 04 - 2 . 09 , P = 0 . 029 ) and a higher risk of bleeding events ( OR 1 . 68 , 95 % CI 1 . 10 - 2 . 56 , P = 0 . 017 ) compared to the most frequent haplotype .", "entity": [], "task": "NER"}
{"text": "The transcription activity of haplotype p - 162A - 126C - 108C in the PON1 promoter was 2 . 6 - fold higher than that of the most frequent haplotype ( p - 162G - 126G - 108T ) .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Based on these results , we suggest that the haplotype - bearing PON1 - 126C allele contributes to the disease risk and the risk of bleeding events in dual antiplatelet - treated CAD patients after PCI .", "entity": [], "task": "NER"}
{"text": "Structural transitions in mixed ternary noble gas clusters .", "entity": [{"entity": "noble", "entity_type": "Chemical", "pos": [40, 45]}], "task": "NER"}
{"text": "The properties of noble gas systems can be greatly extended by heterogeneous mixtures of elements .", "entity": [{"entity": "noble", "entity_type": "Chemical", "pos": [18, 23]}], "task": "NER"}
{"text": "The geometrical structures and energies of mixed Ar - Kr - Xe clusters were investigated using ternary Lennard - Jones ( TLJ ) potential .", "entity": [{"entity": "Ar", "entity_type": "Chemical", "pos": [49, 51]}, {"entity": "Kr", "entity_type": "Chemical", "pos": [54, 56]}, {"entity": "Xe", "entity_type": "Chemical", "pos": [59, 61]}], "task": "NER"}
{"text": "For the Ar19Kr n Xe19 , Ar19Kr19Xe n , and Ar n Kr19Xe19 ( n = 0 - 17 ) clusters investigated , the results show that only two minimum energy configurations exist , i . e . , polytetrahedron and six - fold pancake .", "entity": [{"entity": "Ar19Kr n Xe19", "entity_type": "Chemical", "pos": [8, 21]}, {"entity": "Ar19Kr19Xe n", "entity_type": "Chemical", "pos": [24, 36]}, {"entity": "Ar n Kr19Xe19", "entity_type": "Chemical", "pos": [43, 56]}], "task": "NER"}
{"text": "The inner core of all these clusters is composed mainly of Ar atoms , and Kr and Xe atoms are distributed on the surface with well mixed pattern for polytetrahedral and segregate pattern for six - fold pancake configurations .", "entity": [{"entity": "Ar", "entity_type": "Chemical", "pos": [59, 61]}, {"entity": "Kr", "entity_type": "Chemical", "pos": [74, 76]}, {"entity": "Xe", "entity_type": "Chemical", "pos": [81, 83]}], "task": "NER"}
{"text": "The relative stability property of Ar - Kr - Xe clusters with a certain composition is discussed .", "entity": [{"entity": "Ar", "entity_type": "Chemical", "pos": [35, 37]}, {"entity": "Kr", "entity_type": "Chemical", "pos": [40, 42]}, {"entity": "Xe", "entity_type": "Chemical", "pos": [45, 47]}], "task": "NER"}
{"text": "Moreover , the role of heterogeneity on the strain was investigated , and reduced strain energies in Ar - Kr - Xe clusters were studied to find possible ways of reducing strain .", "entity": [{"entity": "Ar", "entity_type": "Chemical", "pos": [101, 103]}, {"entity": "Kr", "entity_type": "Chemical", "pos": [106, 108]}, {"entity": "Xe", "entity_type": "Chemical", "pos": [111, 113]}], "task": "NER"}
{"text": "The results showed that the strain energies were affected mainly by Ar - Ar , Ar - Kr , and Xe - Xe bonds .", "entity": [{"entity": "Ar", "entity_type": "Chemical", "pos": [68, 70]}, {"entity": "Ar", "entity_type": "Chemical", "pos": [73, 75]}, {"entity": "Ar", "entity_type": "Chemical", "pos": [78, 80]}, {"entity": "Kr", "entity_type": "Chemical", "pos": [83, 85]}, {"entity": "Xe", "entity_type": "Chemical", "pos": [92, 94]}, {"entity": "Xe", "entity_type": "Chemical", "pos": [97, 99]}], "task": "NER"}
{"text": "Blood - brain barrier structure and function and the challenges for CNS drug delivery .", "entity": [], "task": "NER"}
{"text": "The neurons of the central nervous system ( CNS ) require precise control of their bathing microenvironment for optimal function , and an important element in this control is the blood - brain barrier ( BBB ) .", "entity": [], "task": "NER"}
{"text": "The BBB is formed by the endothelial cells lining the brain microvessels , under the inductive influence of neighbouring cell types within the ' neurovascular unit ' ( NVU ) including astrocytes and pericytes .", "entity": [], "task": "NER"}
{"text": "The endothelium forms the major interface between the blood and the CNS , and by a combination of low passive permeability and presence of specific transport systems , enzymes and receptors regulates molecular and cellular traffic across the barrier layer .", "entity": [], "task": "NER"}
{"text": "A number of methods and models are available for examining BBB permeation in vivo and in vitro , and can give valuable information on the mechanisms by which therapeutic agents and constructs permeate , ways to optimize permeation , and implications for drug discovery , delivery and toxicity .", "entity": [], "task": "NER"}
{"text": "For treating lysosomal storage diseases ( LSDs ) , models can be included that mimic aspects of the disease , including genetically - modified animals , and in vitro models can be used to examine the effects of cells of the NVU on the BBB under pathological conditions .", "entity": [], "task": "NER"}
{"text": "For testing CNS drug delivery , several in vitro models now provide reliable prediction of penetration of drugs including large molecules and artificial constructs with promising potential in treating LSDs .", "entity": [], "task": "NER"}
{"text": "For many of these diseases it is still not clear how best to deliver appropriate drugs to the CNS , and a concerted approach using a variety of models and methods can give critical insights and indicate practical solutions .", "entity": [], "task": "NER"}
{"text": "Region - specific regulation of 5 - HT1B receptors in the rat brain by chronic venlafaxine treatment .", "entity": [{"entity": "venlafaxine", "entity_type": "Chemical", "pos": [79, 90]}], "task": "NER"}
{"text": "RATIONALE : Venlafaxine is a non - selective serotonin and noradrenaline reuptake inhibitor antidepressant drug for which clinical studies have suggested a high level efficacy and a possible early action onset compared to the classical antidepressants .", "entity": [{"entity": "Venlafaxine", "entity_type": "Chemical", "pos": [12, 23]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [45, 54]}, {"entity": "noradrenaline", "entity_type": "Chemical", "pos": [59, 72]}], "task": "NER"}
{"text": "Its therapeutic effects might be due , at least in part , to adaptive changes in serotonergic neurotransmission , through the activation of the different 5 - HT receptor subtypes .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "5 - HT1B receptors are located in the axon terminals of both serotonergic and non - serotonergic neurons , where they act as inhibitory autoreceptors or heteroreceptors , respectively .", "entity": [], "task": "NER"}
{"text": "However , the information about the involvement of this subtype in the mechanism of action of antidepressants is limited and quite controversial .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The aim of this study was to evaluate the effect of venlafaxine ( 10 mg kg ( - 1 ) day ( - 1 ) , p . o . ) after 21 days of treatment on the density of 5 - HT1B receptors and their functionality in rat brain .", "entity": [{"entity": "venlafaxine", "entity_type": "Chemical", "pos": [65, 76]}], "task": "NER"}
{"text": "METHODS : Effects of chronic venlafaxine were evaluated at different levels of 5 - HT1B receptor by using receptor autoradiography , [ ( 35 ) S ] GTP gamma S binding , and the regulation of body temperature induced by selective 5 - HT1B agonist .", "entity": [{"entity": "venlafaxine", "entity_type": "Chemical", "pos": [29, 40]}, {"entity": "[ ( 35 ) S ] GTP gamma S", "entity_type": "Chemical", "pos": [133, 157]}], "task": "NER"}
{"text": "RESULTS : Our results show that venlafaxine induced an increase in sensitivity of 5 - HT1B receptors in hypothalamus both at G - protein level and the control of core temperature without affecting the receptor density .", "entity": [{"entity": "venlafaxine", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "CONCLUSIONS : These results demonstrate that adaptive changes on 5 - HT1B receptors induced by chronic administration of venlafaxine exhibit regional differences suggesting that the hypothalamus might be an important site of drug action .", "entity": [{"entity": "venlafaxine", "entity_type": "Chemical", "pos": [121, 132]}], "task": "NER"}
{"text": "Design , synthesis and spectroscopic characterisation of a focused library based on the polyandrocarpamine natural product scaffold .", "entity": [{"entity": "polyandrocarpamine", "entity_type": "Chemical", "pos": [88, 106]}], "task": "NER"}
{"text": "A focused library based on the marine natural products polyandrocarpamines A ( 1 ) and B ( 2 ) has been designed and synthesised using parallel solution - phase chemistry .", "entity": [{"entity": "polyandrocarpamines A", "entity_type": "Chemical", "pos": [55, 76]}], "task": "NER"}
{"text": "In silico physicochemical property calculations were performed on synthetic candidates in order to optimise the library for drug discovery and chemical biology .", "entity": [], "task": "NER"}
{"text": "A library of ten 2 - aminoimidazolone products ( 3 - 12 ) was prepared by coupling glycocyamidine and a variety of aldehydes using a one - step stereoselective aldol condensation reaction under microwave conditions .", "entity": [{"entity": "2 - aminoimidazolone", "entity_type": "Chemical", "pos": [17, 37]}, {"entity": "glycocyamidine", "entity_type": "Chemical", "pos": [83, 97]}, {"entity": "aldehydes", "entity_type": "Chemical", "pos": [115, 124]}], "task": "NER"}
{"text": "All analogues were characterised by NMR , UV , IR and MS .", "entity": [], "task": "NER"}
{"text": "The library was evaluated for cytotoxicity towards the prostate cancer cell lines , LNCaP , PC - 3 and 22Rv1 .", "entity": [], "task": "NER"}
{"text": "Suppression of Epithelial to Mesenchymal Transitioning ( EMT ) Enhances Ex Vivo Reprogramming of Human Exocrine Pancreatic Tissue towards Functional Insulin Producing beta - Like Cells .", "entity": [], "task": "NER"}
{"text": "Due to the lack of tissue available for islet transplantation , new sources of beta - cells have been sought for the treatment of type 1 diabetes .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine whether the human exocrid fraction from the islet isolation procedure could be reprogrammed to provide additional islet tissue for transplantation .", "entity": [], "task": "NER"}
{"text": "The exocrine enriched cells rapidly dedifferentiated in culture and grew as a mesenchymal monolayer .", "entity": [], "task": "NER"}
{"text": "Genetic lineage tracing confirmed that these mesenchymal cells arose in part through a process of epithelial to mesenchymal transitioning ( EMT ) .", "entity": [], "task": "NER"}
{"text": "A protocol was developed whereby transduction of these mesenchymal cells with adenoviruses containing Pdx1 , Ngn3 , MafA and Pax4 generated a population of cells that were enriched in glucagon - secreting alpha - like cells .", "entity": [], "task": "NER"}
{"text": "Transdifferentiation or reprogramming towards insulin secreting beta - cells was enhanced , however , when using unpassaged cells in combination with inhibition of EMT by inclusion of ROCK and TGF - beta 1 inhibitors .", "entity": [], "task": "NER"}
{"text": "Resultant cells were able to secrete insulin in response to glucose and on transplantation , to normalise blood glucose levels in streptozotocin diabetic NOD / Scid mice .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [60, 67]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [112, 119]}, {"entity": "streptozotocin", "entity_type": "Chemical", "pos": [130, 144]}], "task": "NER"}
{"text": "In conclusion , reprogramming of human exocrine enriched tissue can best be achieved using fresh material under conditions whereby EMT is inhibited .", "entity": [], "task": "NER"}
{"text": ". rather than allowing the culture to expand as a mesenchymal monolayer .", "entity": [], "task": "NER"}
{"text": "Factors Associated With Microalbuminuria in 7 , 549 Children and Adolescents With Type 1 Diabetes in the T1D Exchange Clinic Registry .", "entity": [], "task": "NER"}
{"text": "OBJECTIVETo examine factors associated with clinical microalbuminuria ( MA ) diagnosis in children and adolescents in the T1D Exchange clinic registry . RESEARCH DESIGN AND METHODST1D Exchange participants < 20 years of age with type 1 diabetes >= 1 year and urinary albumin - to - creatinine ratio ( ACR ) measured within the prior 2 years were included in the analysis .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [282, 292]}], "task": "NER"}
{"text": "MA diagnosis required all of the following : 1 ) a clinical diagnosis of sustained MA or macroalbuminuria , 2 ) confirmation of MA diagnosis by either the most recent ACR being >= 30 mg / g or current treatment with an ACE inhibitor ( ACEI ) or angiotensin receptor blocker ( ARB ) , and 3 ) no known cause for nephropathy other than diabetes .", "entity": [], "task": "NER"}
{"text": "Logistic regression was used to assess factors associated with MA . RESULTSMA was present in 329 of 7 , 549 ( 4 . 4 % ) participants , with a higher frequency associated with longer diabetes duration , higher mean glycosylated hemoglobin ( HbA1c ) level , older age , female sex , higher diastolic blood pressure ( BP ) , and lower BMI ( P <= 0 . 01 for each in multivariate analysis ) .", "entity": [], "task": "NER"}
{"text": "Older age was most strongly associated with MA among participants with HbA1c >= 9 . 5 % ( >= 80 mmol / mol ) .", "entity": [], "task": "NER"}
{"text": "MA was uncommon ( < 2 % ) among participants with HbA1c < 7 . 5 % ( < 58 mmol / mol ) .", "entity": [], "task": "NER"}
{"text": "Of those with MA , only 36 % were receiving ACEI / ARB treatment . CONCLUSIONSOur results emphasize the importance of good glycemic and BP control , particularly as diabetes duration increases , in order to reduce the risk of nephropathy .", "entity": [], "task": "NER"}
{"text": "Since age and diabetes duration are important nonmodifiable factors associated with MA , the importance of routine screening is underscored to ensure early diagnosis and timely treatment of MA .", "entity": [], "task": "NER"}
{"text": "Patent indicators : a window to pharmaceutical market success .", "entity": [], "task": "NER"}
{"text": "Pharmaceutical success in the market is the best reward for pharmaceutical investors undergoing the lengthy , costly and risky process of pharmaceutical Research and Development ( R & D ) .", "entity": [], "task": "NER"}
{"text": "Drugs with high market revenues trigger fierce competition between pharmaceutical enterprises , as is demonstrated by the increasing Mergers & Acquisitions ( M & A ) cases focusing on seizing the best - selling products .", "entity": [], "task": "NER"}
{"text": "On the other hand , patents , as the best shield for innovative drugs against generic drugs , become a powerful weapon for pharmaceutical enterprises to win the substantial returns generated by market exclusivity .", "entity": [], "task": "NER"}
{"text": "Patents seem to be directly responsible for the commercial success of new medicines .", "entity": [], "task": "NER"}
{"text": "In this context , it is of great significance to find out the empirical associations between pharmaceutical commercial success and patents .", "entity": [], "task": "NER"}
{"text": "By comprehensively analysing 127 drugs marketed in the USA and their 621 American patents , this article identifies the evidence to link various patent indicators with pharmaceutical sales in actual market .", "entity": [], "task": "NER"}
{"text": "Diversity in Structural Consequences of MexZ Mutations in Pseudomonas aeruginosa .", "entity": [], "task": "NER"}
{"text": "Pseudomonas aeruginosa is the major cause of morbidity and mortality in patients with cystic fibrosis .", "entity": [], "task": "NER"}
{"text": "The high level of intrinsic and acquired antibiotic resistance of P . aeruginosa is attributable to the low permeability of its outer membrane in combination with the expression of several multidrug resistance efflux systems .", "entity": [], "task": "NER"}
{"text": "MexZ , the negative regulator of the MexXY efflux pump , is found to be the most frequently mutated gene in P . aeruginosa isolated from cystic fibrosis patient lungs , confirming its importance in multidrug resistance .", "entity": [], "task": "NER"}
{"text": "Structural consequences of four MexZ mutations , including L25P , G46V , P151L , and S202F , have been explored based on the known structure of MexZ using both molecular modeling and molecular dynamics methods .", "entity": [], "task": "NER"}
{"text": "According to obtained results , G46V mutation , which completely abolishes the ability of MexZ binding to DNA , occurs in a specific evolutionary conserved region of MexZ .", "entity": [], "task": "NER"}
{"text": "In addition , the most fluctuation values occur in DNA - binding domain and Helix4 .", "entity": [], "task": "NER"}
{"text": "The obtained results explore details of diversity in structural consequences of MexZ mutations in P . aeruginosa .", "entity": [], "task": "NER"}
{"text": "Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays .", "entity": [], "task": "NER"}
{"text": "Understanding potential health risks is a significant challenge due to large numbers of diverse chemicals with poorly characterized exposures and mechanisms of toxicities .", "entity": [], "task": "NER"}
{"text": "The present study analyzes 976 chemicals ( including failed pharmaceuticals , alternative plasticizers , food additives , and pesticides ) in Phase I and II of the U . S .", "entity": [], "task": "NER"}
{"text": "EPA ' s ToxCast (TM) project across 331 cell - free enzymatic and ligand - binding high - throughput screening ( HTS ) assays .", "entity": [], "task": "NER"}
{"text": "Half - maximal activity concentrations ( AC50 ) were identified for 729 chemicals in 256 assays ( 7 , 135 chemical - assay pairs ) .", "entity": [], "task": "NER"}
{"text": "Some of the most commonly affected assays were CYPs ( CYP2C9 , CYP2C19 ) , transporters ( mitochondrial TSPO , norepinephrine , dopaminergic ) , and GPCRs ( aminergic ) .", "entity": [{"entity": "norepinephrine", "entity_type": "Chemical", "pos": [111, 125]}], "task": "NER"}
{"text": "Heavy metals , surfactants , and dithiocarbamate fungicides showed promiscuous , but distinctly different patterns of activity whereas many of the pharma compounds showed promiscuous activity across GPCRs .", "entity": [{"entity": "dithiocarbamate", "entity_type": "Chemical", "pos": [33, 48]}], "task": "NER"}
{"text": "Literature analysis confirmed > 50 % of the activities for the most potent chemical - assay pairs ( 56 ) , but also revealed 10 missed interactions .", "entity": [], "task": "NER"}
{"text": "Twenty - two chemicals with known estrogenic activity were correctly identified for the majority ( 77 % ) , missing only the weaker interactions .", "entity": [], "task": "NER"}
{"text": "In many cases , novel findings for previously unreported chemical - target combinations clustered with known chemical - target interactions .", "entity": [], "task": "NER"}
{"text": "Results from this large inventory of chemical - biological interactions can inform read - across methods as well as to link potential targets to molecular initiating events in adverse outcome pathways for diverse toxicities .", "entity": [], "task": "NER"}
{"text": "This abstract does not necessarily reflect U . S .", "entity": [], "task": "NER"}
{"text": "EPA policy .", "entity": [], "task": "NER"}
{"text": "Ultrasensitive Polarized Up - Conversion of Tm ( 3 + ) - Yb ( 3 + ) Doped beta - NaYF4 Single Nanorod .", "entity": [{"entity": "Tm ( 3 + ) - Yb ( 3 + ) Doped beta - NaYF4", "entity_type": "Chemical", "pos": [44, 86]}], "task": "NER"}
{"text": "Up - conversion luminescence in rare earth ions ( REs ) doped nanoparticles has attracted considerable research attention for the promising applications in solid - state lasers , three - dimensional displays , solar cells , biological imaging , and so forth .", "entity": [], "task": "NER"}
{"text": "However , there have been no reports on REs doped nanoparticles to investigate their polarized energy transfer up - conversion , especially for single particle .", "entity": [], "task": "NER"}
{"text": "Herein , the polarized energy transfer up - conversion from REs doped fluoride nanorods is demonstrated in a single particle spectroscopy mode for the first time .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [70, 78]}], "task": "NER"}
{"text": "Unique luminescent phenomena , for example , sharp energy level split and singlet - to - triplet transitions at room temperature , multiple discrete luminescence intensity periodic variation with polarization direction , are observed upon excitation with 980 nm linearly polarized laser .", "entity": [], "task": "NER"}
{"text": "Furthermore , nanorods with the controllable aspect ratio and symmetry are fabricated for analysis of the mechanism of polarization anisotropy .", "entity": [], "task": "NER"}
{"text": "The comparative experiments suggest that intraions transition properties and crystal local symmetry dominate the polarization anisotropy , which is also confirmed by density functional theory calculations .", "entity": [], "task": "NER"}
{"text": "Taking advantage of the REs based up - conversion , potential application in polarized microscopic multi - information transportation is suggested for the polarization anisotropy from REs doped fluoride single nanorod or nanorod array .", "entity": [{"entity": "fluoride", "entity_type": "Chemical", "pos": [194, 202]}], "task": "NER"}
{"text": "Stability of sulforaphane for topical formulation .", "entity": [{"entity": "sulforaphane", "entity_type": "Chemical", "pos": [13, 25]}], "task": "NER"}
{"text": "Abstract Context : Sulforaphane ( SFN ) is a natural compound that has been investigated as a chemopreventive agent .", "entity": [{"entity": "Sulforaphane", "entity_type": "Chemical", "pos": [19, 31]}, {"entity": "SFN", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "SFN has been shown to inhibit the activator - protein - 1 ( AP - 1 ) transcription factor and may be effective for inhibition of ultraviolet ( UV ) induced skin carcinogenesis .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "This study was designed to investigate the stability of SFN as a function of pH , temperature and in various solvents and formulations .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "Materials and methods : Stability was analyzed using high - performance liquid chromatography .", "entity": [], "task": "NER"}
{"text": "A potential lead formulation was identified and evaluated in vivo .", "entity": [], "task": "NER"}
{"text": "Results : SFN was determined to undergo apparent first - order degradation kinetics for the conditions explored .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "It was observed that SFN undergoes base catalyzed degradation .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "Buffer species and solvent type impacts stability as well .", "entity": [], "task": "NER"}
{"text": "SFN was found to be very sensitive to temperature with degradation rate changing by a factor of nearly 3 . 1 for every 10 degrees C change in temperature ( at pH 4 . 0 ) .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "SFN completely degraded after 30 days in a conventional pharmaceutical cream formulation .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Improved stability was observed in organic formulation components .", "entity": [], "task": "NER"}
{"text": "Stability studies were conducted on two nonaqueous topical formulations : a polyethylene glycol ( PEG ) ointment base and an organic oleaginous base .", "entity": [{"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [76, 95]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [98, 101]}], "task": "NER"}
{"text": "Conclusion : Topically applied SFN in the PEG base formulation significantly reduced AP - 1 activation after UV stimulation in the skin of a transgenic mouse model , indicating that SFN in this formulation retains efficacy in vivo .", "entity": [{"entity": "SFN", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "SFN", "entity_type": "Chemical", "pos": [182, 185]}], "task": "NER"}
{"text": "DNA Interactions in Crowded Nanopores .", "entity": [], "task": "NER"}
{"text": "The motion of DNA in crowded environments is a common theme in physics and biology .", "entity": [], "task": "NER"}
{"text": "Examples include gel electrophoresis and the self - interaction of DNA within cells and viral capsids .", "entity": [], "task": "NER"}
{"text": "Here we study the interaction of multiple DNA molecules within a nanopore by tethering the DNA to a bead held in a laser optical trap to produce a \" molecular tug - of - war \" .", "entity": [], "task": "NER"}
{"text": "We measure this tether force as a function of the number of DNA molecules in the pore and show that the force per molecule decreases with the number of molecules .", "entity": [], "task": "NER"}
{"text": "A simple scaling argument based on a mean field theory of the hydrodynamic interactions between multiple DNA strands explains our observations .", "entity": [], "task": "NER"}
{"text": "At high salt concentrations , when the Debye length approaches the size of the counterions , the force per molecule becomes essentially independent of the number of molecules .", "entity": [], "task": "NER"}
{"text": "We attribute this to a sharp decrease in electroosmotic flow which makes the hydrodynamic interactions ineffective .", "entity": [], "task": "NER"}
{"text": "Spontaneous partition of carbon nanotubes in polymer - modified aqueous phases .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [25, 31]}], "task": "NER"}
{"text": "The distribution of nanoparticles in different aqueous environments is a fundamental problem underlying a number of processes , ranging from biomedical applications of nanoparticles to their effects on the environment , health , and safety .", "entity": [], "task": "NER"}
{"text": "Here , we study distribution of carbon nanotubes ( CNTs ) in two immiscible aqueous phases formed by the addition of polyethylene glycol ( PEG ) and dextran .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [32, 38]}, {"entity": "polyethylene glycol", "entity_type": "Chemical", "pos": [117, 136]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [139, 142]}], "task": "NER"}
{"text": "This well - defined model system exhibits a strikingly robust phenomenon : CNTs spontaneously partition between the PEG - and the dextran - rich phases according to nanotube ' s diameter and metallicity .", "entity": [{"entity": "PEG", "entity_type": "Chemical", "pos": [116, 119]}], "task": "NER"}
{"text": "Thermodynamic analysis suggests that this chirality - dependent partition is determined by nanotube ' s intrinsic hydrophobicity and reveals two distinct regimes in hydrophobicity - chirality relation : a small diameter ( < 1 nm ) regime , where curvature effect makes larger diameter tubes more hydrophobic than small diameter ones , and a large diameter ( > 1 . 2 nm ) regime , where nanotube ' s polarizability renders semiconducting tubes more hydrophobic than metallic ones .", "entity": [], "task": "NER"}
{"text": "These findings reveal a general rule governing CNT behaviors in aqueous phase and provide an extremely simple way to achieve spatial separation of CNTs by their electronic structures .", "entity": [], "task": "NER"}
{"text": "Protein kinase inhibitor design by targeting the Asp - Phe - Gly ( DFG ) motif : the role of the DFG motif in the design of epidermal growth factor receptor inhibitors .", "entity": [{"entity": "Asp - Phe - Gly", "entity_type": "Chemical", "pos": [49, 64]}], "task": "NER"}
{"text": "The Asp - Phe - Gly ( DFG ) motif plays an important role in the regulation of kinase activity .", "entity": [{"entity": "Asp - Phe - Gly", "entity_type": "Chemical", "pos": [4, 19]}], "task": "NER"}
{"text": "Structure - based drug design was performed to design compounds able to interact with the DFG motif ; epidermal growth factor receptor ( EGFR ) was selected as an example .", "entity": [], "task": "NER"}
{"text": "Structural insights obtained from the EGFR / 2a complex suggested that an extension from the meta - position on the phenyl group ( ring - 5 ) would improve interactions with the DFG motif .", "entity": [{"entity": "phenyl", "entity_type": "Chemical", "pos": [116, 122]}], "task": "NER"}
{"text": "Indeed , introduction of an N , N - dimethylamino tail resulted in 4b , which showed almost 50 - fold improvement in inhibition compared to 2a .", "entity": [{"entity": "N , N - dimethylamino", "entity_type": "Chemical", "pos": [28, 49]}], "task": "NER"}
{"text": "Structural studies confirmed this N , N - dimethylamino tail moved towards the DFG motif to form a salt bridge with the side chain of Asp831 .", "entity": [{"entity": "N , N - dimethylamino", "entity_type": "Chemical", "pos": [34, 55]}], "task": "NER"}
{"text": "That the interactions with the DFG motif greatly contribute to the potency of 4b is strongly evidenced by synthesizing and testing compounds 2a , 3g and 4f : when the charge interactions are absent , the inhibitory activity decreased significantly .", "entity": [], "task": "NER"}
{"text": "Quantitative analysis of global phosphorylation changes with high - resolution tandem mass spectrometry and stable isotopic labeling .", "entity": [], "task": "NER"}
{"text": "Quantitative measurement of specific protein phosphorylation sites is a primary interest of biologists , as site - specific phosphorylation information provides insights into cell signaling networks and cellular dynamics at a system level .", "entity": [], "task": "NER"}
{"text": "Over the last decade , selective phosphopeptide enrichment methods including IMAC and metal oxides ( TiO2 and ZrO2 ) have been developed and greatly facilitate large scale phosphoproteome analysis of various cells , tissues and living organisms , in combination with modern mass spectrometers featuring high mass accuracy and high mass resolution .", "entity": [{"entity": "metal oxides", "entity_type": "Chemical", "pos": [86, 98]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [101, 105]}, {"entity": "ZrO2", "entity_type": "Chemical", "pos": [110, 114]}], "task": "NER"}
{"text": "Various quantification strategies have been applied to detecting relative changes in expression of proteins , peptides , and specific modifications between samples .", "entity": [], "task": "NER"}
{"text": "The combination of mass spectrometry - based phosphoproteome analysis with quantification strategies provides a straightforward and unbiased method to identify and quantify site - specific phosphorylation .", "entity": [], "task": "NER"}
{"text": "We describe common strategies for mass spectrometric analysis of stable isotope labeled samples , as well as two widely applied phosphopeptide enrichment methods based on IMAC ( NTA - Fe ( 3 + ) ) and metal oxide ( ZrO2 ) .", "entity": [{"entity": "NTA - Fe ( 3 + )", "entity_type": "Chemical", "pos": [178, 194]}, {"entity": "metal oxide", "entity_type": "Chemical", "pos": [201, 212]}, {"entity": "ZrO2", "entity_type": "Chemical", "pos": [215, 219]}], "task": "NER"}
{"text": "Instrumental configurations for on - line LC - tandem mass spectrometric analysis and parameters of conventional bioinformatic analysis of large data sets are also considered for confident identification , localization , and reliable quantification of site - specific phosphorylation .", "entity": [], "task": "NER"}
{"text": "Molecular Mechanisms of the antitumor activity of SB225002 : A novel microtubule inhibitor .", "entity": [{"entity": "SB225002", "entity_type": "Chemical", "pos": [50, 58]}], "task": "NER"}
{"text": "SB225002 ( SB ) is an IL - 8 receptor B ( IL - 8RB ) antagonist that has previously been shown to inhibit IL - 8 - based cancer cell invasion , and to possess in vivo anti - inflammatory and anti - nociceptive effects .", "entity": [{"entity": "SB225002", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The present study presented an evidence for the cell cycle - targeting activity of SB in a panel of p53 - mutant human cancer cell lines of different origin , and investigated the underlying molecular mechanisms .", "entity": [], "task": "NER"}
{"text": "A combination of cell cycle analysis , immunocytometry , immunoblotting , and RNA interference revealed that SB induced a BubR1 - dependent mitotic arrest .", "entity": [], "task": "NER"}
{"text": "Mechanistically , SB was shown to possess a microtubule destabilizing activity evidenced by hyperphosphorylation of Bcl2 and BclxL , suppression of microtubule polymerization and induction of a prometaphase arrest .", "entity": [], "task": "NER"}
{"text": "Molecular docking studies suggested that SB has a good affinity towards vinblastine - binding site on beta - tubulin subunit .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [72, 83]}], "task": "NER"}
{"text": "Of note , SB265610 which is a close structural analogue of SB225002 with a potent IL - 8RB antagonistic activity did not exhibit a similar antimitotic activity .", "entity": [{"entity": "SB265610", "entity_type": "Chemical", "pos": [10, 18]}, {"entity": "SB225002", "entity_type": "Chemical", "pos": [59, 67]}], "task": "NER"}
{"text": "Importantly , in P - glycoprotein overexpressing NCI / Adr - Res cells the antitumor activity of SB was unaffected by multidrug resistance .", "entity": [], "task": "NER"}
{"text": "Interestingly , the mechanisms of SB - induced cell death were cell - line dependent , where in invasive hepatocellular carcinoma HLE cells the significant contribution of BAK - dependent mitochondrial apoptosis was demonstrated .", "entity": [], "task": "NER"}
{"text": "Conversely , SB activated p38 MAPK signaling in colorectal adenocarcinoma cells SW480 , and pharmacologic inhibition of p38 MAPK activity revealed its key role in mediating SB - induced caspase - independent cell death .", "entity": [], "task": "NER"}
{"text": "In summary , the present study introduced SB as a promising antitumor agent which has the potential to exert its activity through dual mechanisms involving microtubules targeting and interference with IL - 8 - drivin cancer progression .", "entity": [], "task": "NER"}
{"text": "Wogonoside displays anti - inflammatory effects through modulating inflammatory mediator expression using RAW264 . 7 cells .", "entity": [{"entity": "Wogonoside", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : The root of Scutellaria baicalensis Georgi , also called Huangqin in China , is an herbal - based nutraceutical which is usually used in Chinese medicated diet ( CMD ) .", "entity": [], "task": "NER"}
{"text": "As an abundant ingredient in Huangqin , wogonoside is a flavonoid glycoside .", "entity": [{"entity": "wogonoside", "entity_type": "Chemical", "pos": [40, 50]}, {"entity": "flavonoid glycoside", "entity_type": "Chemical", "pos": [56, 75]}], "task": "NER"}
{"text": "The present work investigated the anti - inflammatory activities of wogonoside in lipopolysaccharides ( LPS ) - induced RAW264 . 7 cells .", "entity": [{"entity": "wogonoside", "entity_type": "Chemical", "pos": [68, 78]}], "task": "NER"}
{"text": "MATERIALS AND METHODS : RAW264 . 7 cells were used .", "entity": [], "task": "NER"}
{"text": "The inhibition of wogonoside against nitric oxide ( NO ) , prostaglandin E2 ( PGE2 ) , tumor necrosis factor - alpha ( TNF - alpha ) and interleukin - 6 ( IL - 6 ) in LPS - induced RAW264 . 7 cells were measured .", "entity": [{"entity": "wogonoside", "entity_type": "Chemical", "pos": [18, 28]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [37, 49]}, {"entity": "NO", "entity_type": "Chemical", "pos": [52, 54]}, {"entity": "prostaglandin E2", "entity_type": "Chemical", "pos": [59, 75]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [78, 82]}], "task": "NER"}
{"text": "Additionally , the effects of wogonoside on mRNA expression of inducible nitric oxide synthase ( iNOS ) , cyclooxygenase 2 ( COX2 ) , TNF - alpha and IL - 6 were also investigated .", "entity": [{"entity": "wogonoside", "entity_type": "Chemical", "pos": [30, 40]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [73, 85]}], "task": "NER"}
{"text": "RESULTS AND DISCUSSION : Wogonoside not only dose - dependently decreased the production of inflammatory mediators including NO and PGE2 but also inhibited the release of pro - inflammatory cytokines including TNF - alpha and IL - 6 in LPS - induced RAW264 . 7 cells .", "entity": [{"entity": "Wogonoside", "entity_type": "Chemical", "pos": [25, 35]}, {"entity": "NO", "entity_type": "Chemical", "pos": [125, 127]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [132, 136]}], "task": "NER"}
{"text": "Furthermore , wogonoside possessed significantly in vitro inhibitory effects on the gene expression of iNOS , COX2 , TNF - alpha and IL - 6 .", "entity": [{"entity": "wogonoside", "entity_type": "Chemical", "pos": [14, 24]}], "task": "NER"}
{"text": "CONCLUSION : These results suggest that wogonoside may be used as a functional food component for prevention and treatment of inflammation .", "entity": [{"entity": "wogonoside", "entity_type": "Chemical", "pos": [40, 50]}], "task": "NER"}
{"text": "Assuring Safety Without Animal Testing : The Case for the Human Testis In Vitro .", "entity": [], "task": "NER"}
{"text": "From 15 - 17 June 2011 , a dedicated workhop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment .", "entity": [], "task": "NER"}
{"text": "The workshop was sponsored by the Dutch ASAT initiative ( Assuring Safety without Animal Testing ) , which aims at promoting innovative approaches towards toxicological hazard and risk assessment on the basis of human and in vitro data , and replacement of animal studies .", "entity": [], "task": "NER"}
{"text": "Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity , reviewed existing alternative assay models , and brainstormed about future approaches , specifically considering tissue engineering .", "entity": [], "task": "NER"}
{"text": "The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities , as well as different cell compartments in terms of microenvironment and extracellular matrix components .", "entity": [], "task": "NER"}
{"text": "This complexity hampers quick results in the realm of alternative models .", "entity": [], "task": "NER"}
{"text": "Nevertheless , progress has been achieved in recent years , and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro .", "entity": [], "task": "NER"}
{"text": "Although feasible , significant investment is deemed essential to be able to bring new ideas into practice in the laboratory .", "entity": [], "task": "NER"}
{"text": "For the advancement of in vitro testicular toxicity testing , one of the most sensitive end points in regulatory reproductive toxicity testing , such an investment is highly desirable .", "entity": [], "task": "NER"}
{"text": "Relations between stimulation of mesolimbic dopamine and place conditioning in rats produced by cocaine or drugs that are tolerant to dopamine transporter conformational change .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [44, 52]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [96, 103]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [134, 142]}], "task": "NER"}
{"text": "RATIONALE : Dopamine transporter ( DAT ) conformation plays a role in the effectiveness of cocaine - like and other DAT inhibitors .", "entity": [{"entity": "Dopamine", "entity_type": "Chemical", "pos": [12, 20]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [91, 98]}], "task": "NER"}
{"text": "Cocaine - like stimulants are intolerant to DAT conformation changes having decreased potency in cells transfected with DAT constructs that face the cytosol compared to wild - type DAT .", "entity": [{"entity": "Cocaine", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "In contrast , analogs of benztropine ( BZT ) are among compounds that are less affected by DAT conformational change .", "entity": [{"entity": "benztropine", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "BZT", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "METHODS : We compared the displacement of radioligand binding to various mammalian CNS sites , acute stimulation of accumbens shell dopamine levels , and place conditioning in rats among cocaine and four BZT analogs with Cl substitutions on the diphenyl - ether system including two with carboalkoxy substitutions at the 2 - position of the tropane ring .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [132, 140]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [187, 194]}, {"entity": "BZT", "entity_type": "Chemical", "pos": [204, 207]}, {"entity": "Cl", "entity_type": "Chemical", "pos": [221, 223]}, {"entity": "diphenyl - ether", "entity_type": "Chemical", "pos": [245, 261]}, {"entity": "carboalkoxy", "entity_type": "Chemical", "pos": [288, 299]}, {"entity": "tropane", "entity_type": "Chemical", "pos": [341, 348]}], "task": "NER"}
{"text": "RESULTS : Binding assays confirmed high - affinity and selectivity for the DAT with the BZT analogs which also produced significant stimulation of mesolimbic dopamine efflux .", "entity": [{"entity": "BZT", "entity_type": "Chemical", "pos": [88, 91]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [158, 166]}], "task": "NER"}
{"text": "Because BZT analogs produced temporal patterns of extracellular dopamine levels different from those by cocaine ( 3 - 10 mg / kg , i . p . ) , the place conditioning produced by BZT analogs and cocaine was compared at doses and times at which both the increase in dopamine levels and rates of increase were similar to those produced by an effective dose of cocaine .", "entity": [{"entity": "BZT", "entity_type": "Chemical", "pos": [8, 11]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [64, 72]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [104, 111]}, {"entity": "BZT", "entity_type": "Chemical", "pos": [178, 181]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [194, 201]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [264, 272]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [357, 364]}], "task": "NER"}
{"text": "Despite this equilibration , none of the BZT analogs tested produced significant place conditioning .", "entity": [{"entity": "BZT", "entity_type": "Chemical", "pos": [41, 44]}], "task": "NER"}
{"text": "CONCLUSIONS : The present results extend previous findings suggesting that cocaine - like actions are dependent on a binding equilibrium that favors the outward conformational state of the DAT .", "entity": [{"entity": "cocaine", "entity_type": "Chemical", "pos": [75, 82]}], "task": "NER"}
{"text": "In contrast , BZT analogs with reduced dependence on DAT conformation have reduced cocaine - like behavioral effects and may prove useful in development of medications for stimulant abuse .", "entity": [{"entity": "BZT", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "cocaine", "entity_type": "Chemical", "pos": [83, 90]}], "task": "NER"}
{"text": "The von Hippel - Lindau Protein pVHL Inhibits Ribosome Biogenesis and Protein Synthesis .", "entity": [], "task": "NER"}
{"text": "pVHL , product of von Hippel - Lindau ( VHL ) tumor suppressor gene , functions as the substrate recognition component of an E3 - ubiquitin ligase complex that targets hypoxia inducible factor alpha ( HIFalpha ) for ubiquitination and degradation .", "entity": [], "task": "NER"}
{"text": "Besides HIFalpha , pVHL also interacts with other proteins and has multiple functions .", "entity": [], "task": "NER"}
{"text": "Here , we report that pVHL inhibits ribosome biogenesis and protein synthesis .", "entity": [], "task": "NER"}
{"text": "We find that pVHL associates with the 40S ribosomal protein S3 ( RPS3 ) but does not target it for destruction .", "entity": [], "task": "NER"}
{"text": "Rather , the pVHL - RPS3 association interferes with the interaction between RPS3 and RPS2 .", "entity": [], "task": "NER"}
{"text": "Expression of pVHL also leads to nuclear retention of pre - 40S ribosomal subunits , diminishing polysomes and 18S rRNA levels .", "entity": [], "task": "NER"}
{"text": "We also demonstrate that pVHL suppresses both cap - dependent and cap - independent protein synthesis .", "entity": [], "task": "NER"}
{"text": "Our findings unravel a novel function of pVHL and provide insight into the regulation of ribosome biogenesis by the tumor suppressor pVHL .", "entity": [], "task": "NER"}
{"text": "Decreased Permeability Surface Area for Glucose in Obese Women with Postprandial Hyperglycemia : No Effect of Phosphodiesterase - 5 ( PDE - 5 ) Inhibition .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [40, 47]}], "task": "NER"}
{"text": "Insulin - mediated microvascular recruitment is recognized as a potential mechanism contributing to insulin resistance .", "entity": [], "task": "NER"}
{"text": "In this study , we compared a marker of microvascular function , the permeability surface area for glucose ( PSglu ) , and forearm glucose uptake after an OGTT in obese women with impaired glucose metabolism and healthy lean nondiabetic women , with the aim to characterize whether decreased permeability surface area for glucose or decreased glucose uptake may contribute to postprandial hyperglycemia in the obese group .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [99, 106]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [131, 138]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [189, 196]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [322, 329]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [343, 350]}], "task": "NER"}
{"text": "In addition , we evaluated whether the phosphodiesterase - 5 ( PDE - 5 ) inhibitor tadalafil , in a randomized double blind placebo controlled design , might attenuate postprandial glucose levels in obese women .", "entity": [{"entity": "tadalafil", "entity_type": "Chemical", "pos": [83, 92]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [181, 188]}], "task": "NER"}
{"text": "For these purposes , intramuscular microdialysis , blood sampling from arterial and venous blood of the forearm , and measurements of forearm blood flow were performed .", "entity": [], "task": "NER"}
{"text": "The results showed an impaired permeability surface area for glucose ( IAUC PSglu 31 +/- 13 vs . 124 +/- 31 ; p < 0 . 05 ) in obese when compared with lean participants , but no differences in forearm glucose uptake appeared between the groups .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [61, 68]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [201, 208]}], "task": "NER"}
{"text": "Furthermore , a single dose of tadalafil 10 mg showed no improvement of the permeability surface area for glucose , glucose uptake , or circulating glucose levels in obese participants .", "entity": [{"entity": "tadalafil", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [106, 113]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [116, 123]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [148, 155]}], "task": "NER"}
{"text": "In conclusion , the postprandial PSglu response was impaired in obese women showing postprandial hyperglycemia , indicating a compromised microcirculation .", "entity": [], "task": "NER"}
{"text": "However , we were unable to demonstrate any acute effect on either vascular function or glucose uptake of the phosphodiesterase - 5 ( PDE - 5 ) inhibitor tadalafil .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [88, 95]}, {"entity": "tadalafil", "entity_type": "Chemical", "pos": [154, 163]}], "task": "NER"}
{"text": "Dietary Flaxseed Oil Supplementation Mitigates the Effect of Lead on the Enzymes of Carbohydrate Metabolism , Brush Border Membrane , and Oxidative Stress in Rat Kidney Tissues .", "entity": [{"entity": "Carbohydrate", "entity_type": "Chemical", "pos": [84, 96]}], "task": "NER"}
{"text": "Lead is a heavy metal widely distributed in the environment .", "entity": [], "task": "NER"}
{"text": "Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses .", "entity": [], "task": "NER"}
{"text": "Human and animal exposure demonstrates that lead is nephrotoxic .", "entity": [], "task": "NER"}
{"text": "However , attempts to reduce lead - induced nephrotoxicity were not found suitable for clinical use .", "entity": [], "task": "NER"}
{"text": "Recently , flaxseed oil ( FXO ) , a rich source of omega - 3 fatty acids and lignans , has been shown to prevent / reduce the progression of certain types of cardiovascular and renal disorders .", "entity": [{"entity": "omega - 3 fatty acids", "entity_type": "Chemical", "pos": [51, 72]}, {"entity": "lignans", "entity_type": "Chemical", "pos": [77, 84]}], "task": "NER"}
{"text": "In view of this , the present study investigates the protective effect of FXO on lead acetate ( PbAc ) - induced renal damage .", "entity": [{"entity": "lead acetate", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "PbAc", "entity_type": "Chemical", "pos": [96, 100]}], "task": "NER"}
{"text": "Rats were pre - fed normal diet and the diet rich in FXO for 14 days , and then , four doses of lead acetate ( 25 mg / kg body weight ) were administered intraperitoneally while still on diet .", "entity": [{"entity": "lead acetate", "entity_type": "Chemical", "pos": [96, 108]}], "task": "NER"}
{"text": "Various serum parameters , enzymes of carbohydrate metabolism , brush border membrane ( BBM ) , and oxidative stress were analyzed in rat kidney .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [38, 50]}], "task": "NER"}
{"text": "PbAc nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen .", "entity": [{"entity": "PbAc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [57, 67]}, {"entity": "urea", "entity_type": "Chemical", "pos": [78, 82]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "PbAc increased the activities of lactate dehydrogenase and NADP - malic enzyme , whereas it decreased malate and glucose - 6 - phosphate dehydrogenase , glucose - 6 - phosphatase , fructose - 1 , 6 - bisphosphatase , and BBM enzyme activities .", "entity": [{"entity": "PbAc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "lactate", "entity_type": "Chemical", "pos": [33, 40]}, {"entity": "NADP", "entity_type": "Chemical", "pos": [59, 63]}, {"entity": "malate", "entity_type": "Chemical", "pos": [102, 108]}, {"entity": "glucose - 6 - phosphate", "entity_type": "Chemical", "pos": [113, 136]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [153, 160]}, {"entity": "fructose", "entity_type": "Chemical", "pos": [181, 189]}], "task": "NER"}
{"text": "PbAc caused oxidant / antioxidant imbalances as reflected by increased lipid peroxidation and decreased activities of superoxide dismutase , glutathione peroxidase , and catalase .", "entity": [{"entity": "PbAc", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [118, 128]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [141, 152]}], "task": "NER"}
{"text": "In contrast , FXO alone enhanced the enzyme activities of carbohydrate metabolism , BBM , and antioxidant defense system .", "entity": [{"entity": "carbohydrate", "entity_type": "Chemical", "pos": [58, 70]}], "task": "NER"}
{"text": "FXO feeding to PbAc - treated rats markedly enhanced resistance to PbAc - elicited deleterious effects .", "entity": [{"entity": "PbAc", "entity_type": "Chemical", "pos": [15, 19]}, {"entity": "PbAc", "entity_type": "Chemical", "pos": [67, 71]}], "task": "NER"}
{"text": "In conclusion , dietary FXO supplementation ameliorated PbAc - induced specific metabolic alterations and oxidative damage by empowering antioxidant defense mechanism and improving BBM integrity and energy metabolism .", "entity": [{"entity": "PbAc", "entity_type": "Chemical", "pos": [56, 60]}], "task": "NER"}
{"text": "Topological Dangling Bonds with Large Spin Splitting and Enhanced Spin Polarization on the Surfaces of Bi2Se3 .", "entity": [{"entity": "Bi2Se3", "entity_type": "Chemical", "pos": [103, 109]}], "task": "NER"}
{"text": "We investigate the topological surface state properties at various surface cleaves in the topological insulator Bi2Se3 , via first principles calculations and scanning tunneling microscopy / spectroscopy ( STM / STS ) .", "entity": [{"entity": "Bi2Se3", "entity_type": "Chemical", "pos": [112, 118]}], "task": "NER"}
{"text": "While the typical surface termination occurs between two quintuple layers , we report the existence of a surface termination within a single quintuple layer where dangling bonds form with giant spin splitting owing to strong spin - orbit coupling .", "entity": [], "task": "NER"}
{"text": "Unlike Rashba split states in a 2D electron gas , these states are constrained by the band topology of the host insulator with topological properties similar to the typical topological surface state , and thereby offer an alternative candidate for spintronics usage .", "entity": [], "task": "NER"}
{"text": "We name these new states \" topological dangling - bond states \" .", "entity": [], "task": "NER"}
{"text": "The degree of the spin polarization of these states is greatly enhanced .", "entity": [], "task": "NER"}
{"text": "Since dangling bonds are more chemically reactive , the observed topological dangling - bond states provide a new avenue for manipulating band dispersions and spin - textures by adsorbed atoms or molecules .", "entity": [], "task": "NER"}
{"text": "Efficient cell and cell - sheet harvesting based on smart surfaces coated with a multifunctional and self - organizing Elastin - Like Recombinamer .", "entity": [], "task": "NER"}
{"text": "A wide range of smart surfaces with novel properties relevant for biomedical applications have been developed recently .", "entity": [], "task": "NER"}
{"text": "Herein we focus on thermoresponsive surfaces that switch between cell - adherent and non - adherent states , and their applications for cell harvesting .", "entity": [], "task": "NER"}
{"text": "These smart surfaces are obtained by covalently coupling a tailored Elastin - Like Recombinamer onto glass surfaces by means of the well - known and widely applied Click Chemistry methodology .", "entity": [], "task": "NER"}
{"text": "The resulting recombinamer - functionalized surfaces have been characterized by means of water contact angle measurements , XPS and TOF - SIMS .", "entity": [], "task": "NER"}
{"text": "A cell - based analysis of these surfaces with human fibroblasts showed a high degree of adhesion to the surface in its adherent state ( 37 (o) C ) , thus promoting cell viability and proliferation .", "entity": [], "task": "NER"}
{"text": "A temperature decrease triggers reorganization of the recombinamer , thus markedly increasing the number of non - adherent domains and masking the adherent ones .", "entity": [], "task": "NER"}
{"text": "This process allows a specific and efficient temporal control of cell adhesion and cell detachment .", "entity": [], "task": "NER"}
{"text": "After determination of the properties required for a suitable cell - harvesting system , optimization of the process allows single cells or cell sheets from at least two types of cells ( HFF - 1 and ADSCs ) to be rapidly harvested .", "entity": [], "task": "NER"}
{"text": "Aromatic glycosides from the flower buds of Lonicera japonica .", "entity": [{"entity": "Aromatic glycosides", "entity_type": "Chemical", "pos": [0, 19]}], "task": "NER"}
{"text": "Six new glycosides ( 1 - 6 ) have been isolated from the flower buds of Lonicera japonica .", "entity": [], "task": "NER"}
{"text": "Their structures including the absolute configurations were determined by spectroscopic and chemical methods as ( - ) - 2 - hydroxy - 5 - methoxybenzoic acid 2 - O - beta - d - ( 6 - O - benzoyl ) - glucopyranoside ( 1 ) , ( - ) - 4 - hydroxy - 3 , 5 - dimethoxybenzoic acid 4 - O - beta - d - ( 6 - O - benzoyl ) - glucopyranoside ( 2 ) , ( - ) - ( E ) - 3 , 5 - dimethoxyphenylpropenoic acid 4 - O - beta - d - ( 6 - O - benzoyl ) - glucopyranoside ( 3 ) , ( - ) - ( 7S , 8R ) - ( 4 - hydroxyphenylglycerol 9 - O - beta - d - [ 6 - O - ( E ) - 4 - hydroxy - 3 , 5 - dimethoxyphenylpropenoyl ] - glucopyranoside ( 4 ) , ( - ) - ( 7S , 8R ) - ( 4 - hydroxy - 3 - methoxyphenylglycerol 9 - O - beta - d - [ 6 - O - ( E ) - 4 - hydroxy - 3 , 5 - dimethoxyphenylpropenoyl ] - glucopyranoside ( 5 ) , and ( - ) - 4 - hydroxy - 3 - methoxyphenol beta - d - { 6 - O - [ 4 - O - ( 7S , 8R ) - ( 4 - hydroxy - 3 - methoxyphenylglycerol - 8 - yl ) - 3 - methoxybenzoyl ] } - glucopyranoside ( 6 ) , respectively .", "entity": [{"entity": "( - ) - 2 - hydroxy - 5 - methoxybenzoic acid 2 - O - beta - d - ( 6 - O - benzoyl ) - glucopyranoside", "entity_type": "Chemical", "pos": [112, 214]}, {"entity": "( - ) - 4 - hydroxy - 3 , 5 - dimethoxybenzoic acid 4 - O - beta - d - ( 6 - O - benzoyl ) - glucopyranoside", "entity_type": "Chemical", "pos": [223, 331]}, {"entity": "( - ) - ( E ) - 3 , 5 - dimethoxyphenylpropenoic acid 4 - O - beta - d - ( 6 - O - benzoyl ) - glucopyranoside", "entity_type": "Chemical", "pos": [340, 450]}, {"entity": "( - ) - ( 7S , 8R ) - ( 4 - hydroxyphenylglycerol 9 - O - beta - d - [ 6 - O - ( E ) - 4 - hydroxy - 3 , 5 - dimethoxyphenylpropenoyl ] - glucopyranoside", "entity_type": "Chemical", "pos": [459, 612]}, {"entity": "( - ) - ( 7S , 8R ) - ( 4 - hydroxy - 3 - methoxyphenylglycerol 9 - O - beta - d - [ 6 - O - ( E ) - 4 - hydroxy - 3 , 5 - dimethoxyphenylpropenoyl ] - glucopyranoside", "entity_type": "Chemical", "pos": [621, 788]}, {"entity": "( - ) - 4 - hydroxy - 3 - methoxyphenol beta - d - { 6 - O - [ 4 - O - ( 7S , 8R ) - ( 4 - hydroxy - 3 - methoxyphenylglycerol - 8 - yl ) - 3 - methoxybenzoyl ] } - glucopyranoside", "entity_type": "Chemical", "pos": [801, 981]}], "task": "NER"}
{"text": "Sub - nanomolar Detection of Prostate Specific Membrane Antigen in Synthetic Urine by Synergistic , Dual Ligand Phage .", "entity": [], "task": "NER"}
{"text": "The sensitive detection of cancer biomarkers in urine could revolutionize cancer diagnosis and treatment .", "entity": [], "task": "NER"}
{"text": "Such detectors must be inexpensive , easy to interpret , and sensitive .", "entity": [], "task": "NER"}
{"text": "This report describes a bioaffinity matrix of viruses integrated into PEDOT films for electrochemical sensing of prostate specific membrane antigen ( PSMA ) , a prostate cancer biomarker .", "entity": [{"entity": "PEDOT", "entity_type": "Chemical", "pos": [70, 75]}], "task": "NER"}
{"text": "High sensitivity to PSMA resulted from synergistic action by two different ligands to PSMA on the same phage particle .", "entity": [], "task": "NER"}
{"text": "One ligand was chemically synthesized and wrapped around the phage , and the second was genetically encoded .", "entity": [], "task": "NER"}
{"text": "The dual ligands result in a bidentate binder with high copy , dense ligand display for enhanced PSMA detection through a chelate - based , avidity effect .", "entity": [], "task": "NER"}
{"text": "Biosensing with virus - PEDOT films provides a 100 pM limit of detection for PSMA in synthetic urine without requiring enzymatic or other amplification .", "entity": [{"entity": "PEDOT", "entity_type": "Chemical", "pos": [24, 29]}], "task": "NER"}
{"text": "Oxidative damage and genotoxic effect in mice caused by sub - chronic exposure to low - dose volatile organic compounds .", "entity": [], "task": "NER"}
{"text": "Abstract Volatile organic compounds ( VOCs ) are widely used as constituents of household chemicals .", "entity": [], "task": "NER"}
{"text": "Although adverse health effects have been reported , long - term exposure to low - level VOCs mixture has not been studied .", "entity": [], "task": "NER"}
{"text": "Especially , there is a lack of substantial information on the sensitive biomarkers and carcinogenic markers .", "entity": [], "task": "NER"}
{"text": "In the present study , we examined oxidative stress and genotoxic effects of sub - chronic low - dose VOCs mixture ( formaldehyde , benzene , toluene and xylene ) .", "entity": [{"entity": "formaldehyde", "entity_type": "Chemical", "pos": [117, 129]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [132, 139]}, {"entity": "toluene", "entity_type": "Chemical", "pos": [142, 149]}, {"entity": "xylene", "entity_type": "Chemical", "pos": [154, 160]}], "task": "NER"}
{"text": "Male Kunming mice were exposed to 0 ( control ) and three different doses of VOCs mixture ( group 1S , 5S and 10S ) for 90 d ( 2 h / d ) .", "entity": [], "task": "NER"}
{"text": "Group 1S is 0 . 10 , 0 . 11 , 0 . 20 and 0 . 20 mg / m ( 3 ) , group 5S is 0 . 50 , 0 . 55 , 1 . 00 and 1 . 00 mg / m ( 3 ) , group 10S is 1 . 00 , 1 . 10 , 2 . 00 and 2 . 00 mg / m ( 3 ) , which , respectively , corresponded to 1 , 5 and 10 times of indoor air quality standard ( IAQS ) in China .", "entity": [], "task": "NER"}
{"text": "One day following VOCs exposure , oxidative stress markers in lung , 8 - hydroxy - 2 ' - deoxyguanosine in bronchoalveolar lavage fluid and genotoxicity ( DNA damage ) in liver were examined .", "entity": [{"entity": "8 - hydroxy - 2 ' - deoxyguanosine", "entity_type": "Chemical", "pos": [69, 103]}], "task": "NER"}
{"text": "Results showed that exposure to VOCs ( IAQS dose ) resulted in oxidative damages of lung , which were supported by the significant changes on reactive oxygen species , reduced glutathione ( GSH ) , GSH S - transferase , total antioxidative capacity , malondialdehyde , protein carbonyl and nitric oxide ( NO ) .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [151, 157]}, {"entity": "reduced glutathione", "entity_type": "Chemical", "pos": [168, 187]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [190, 193]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [198, 201]}, {"entity": "S", "entity_type": "Chemical", "pos": [202, 203]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [251, 266]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [277, 285]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [290, 302]}, {"entity": "NO", "entity_type": "Chemical", "pos": [305, 307]}], "task": "NER"}
{"text": "Moreover , oxidative stress markers in group 5S and 10S ( except NO ) in lung were affected significantly .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [65, 67]}], "task": "NER"}
{"text": "In addition , VOCs exposure also induced significantly DNA damage in liver .", "entity": [], "task": "NER"}
{"text": "Our study suggested long - term VOCs inhalation at low levels caused oxidative stress and genotoxicity response in mice .", "entity": [], "task": "NER"}
{"text": "Since effects were seen at the current IAQS level , further studies below this level are necessary .", "entity": [], "task": "NER"}
{"text": "Surgical resection of brain metastases - impact on neurological outcome .", "entity": [], "task": "NER"}
{"text": "Brain metastases ( BM ) develop in about 30 % of all cancer patients .", "entity": [], "task": "NER"}
{"text": "Surgery plays an important role in confirming neuropathological diagnosis , relieving mass effects and improving the neurological status .", "entity": [], "task": "NER"}
{"text": "To select patients with the highest benefit from surgical resection , prognostic indices ( RPA , GPA ) have been formulated which are solely focused on survival without considering neurological improvement .", "entity": [], "task": "NER"}
{"text": "In this study we analyzed the impact of surgical resection on the neurological status in addition to overall survival in 206 BM patients .", "entity": [], "task": "NER"}
{"text": "Surgical mortality and morbidity was 0 . 0 % and 10 . 3 % respectively .", "entity": [], "task": "NER"}
{"text": "New neurologic deficits occurred in 6 . 3 % of all patients .", "entity": [], "task": "NER"}
{"text": "The median overall survival was 6 . 3 months .", "entity": [], "task": "NER"}
{"text": "Poor RPA class and short time interval between diagnosis of cancer and the occurrence of BM were independent factors predictive for poor survival .", "entity": [], "task": "NER"}
{"text": "Improvement of neurological performance was achieved in 56 . 8 % of all patients , with the highest improvement rate seen in patients presenting with increased intracranial pressure and hemiparesis .", "entity": [], "task": "NER"}
{"text": "Notably , the neurological benefits were independent from RPA class .", "entity": [], "task": "NER"}
{"text": "In conclusion , surgical resection leads to significant neurological improvement despite poor RPA class and short overall survival .", "entity": [], "task": "NER"}
{"text": "Considering the low mortality and morbidity rates , resection should be considered as a valid option to increase neurological function and quality of life for patients with BM .", "entity": [], "task": "NER"}
{"text": "Molecular sensing : modulating molecular conduction through intermolecular interactions .", "entity": [], "task": "NER"}
{"text": "We observe changes in the molecular conductivity of individual oligophenylene - vinylene ( OPV ) molecules due to interactions with small aromatic molecules .", "entity": [{"entity": "oligophenylene - vinylene", "entity_type": "Chemical", "pos": [63, 88]}, {"entity": "OPV", "entity_type": "Chemical", "pos": [91, 94]}], "task": "NER"}
{"text": "Fluorescence experiments were correlated with scanning tunneling microscopy measurements in order to determine the origin of the observed effect .", "entity": [], "task": "NER"}
{"text": "Both nitrobenzene and 1 , 4 - dinitrobenzene decreased fluorescence intensity and molecular conductivity , while toluene had no effect .", "entity": [{"entity": "nitrobenzene", "entity_type": "Chemical", "pos": [5, 17]}, {"entity": "1 , 4 - dinitrobenzene", "entity_type": "Chemical", "pos": [22, 44]}, {"entity": "toluene", "entity_type": "Chemical", "pos": [113, 120]}], "task": "NER"}
{"text": "The observed changes in the fluorescence and conduction of OPV correlate well with the electron withdrawing ability of the interacting aromatic molecules .", "entity": [{"entity": "OPV", "entity_type": "Chemical", "pos": [59, 62]}], "task": "NER"}
{"text": "These results demonstrate the potential usefulness of OPV as a sensor for aromatic compounds containing electron withdrawing groups .", "entity": [{"entity": "OPV", "entity_type": "Chemical", "pos": [54, 57]}], "task": "NER"}
{"text": "In vitro effect of N - acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites .", "entity": [{"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [19, 37]}, {"entity": "dichlorodiphenyltrichloroethane", "entity_type": "Chemical", "pos": [69, 100]}], "task": "NER"}
{"text": "The organochlorine pesticide , dichlorodiphenyltrichloroethane ( DDT ) , is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo .", "entity": [{"entity": "organochlorine", "entity_type": "Chemical", "pos": [4, 18]}, {"entity": "dichlorodiphenyltrichloroethane", "entity_type": "Chemical", "pos": [31, 62]}, {"entity": "DDT", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "N - Acetylcysteine ( NAC ) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds .", "entity": [{"entity": "N - Acetylcysteine", "entity_type": "Chemical", "pos": [0, 18]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites , dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [47, 50]}, {"entity": "DDT", "entity_type": "Chemical", "pos": [103, 106]}, {"entity": "dichlorodiphenyldichloroethylene", "entity_type": "Chemical", "pos": [138, 170]}, {"entity": "dichlorodiphenyldichloroethane", "entity_type": "Chemical", "pos": [175, 205]}], "task": "NER"}
{"text": "HepG2 cell cultures were used to assess the following parameters of toxicity : cellular viability , intracellular levels of reactive oxygen species ( ROS ) , mitochondrial membrane potential and initiation of apoptosis .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [133, 139]}], "task": "NER"}
{"text": "None of the three test compounds induced ROS generation , yet exposure to any of the three compounds produced mitochondrial hyperpolarization , which was countered by NAC pretreatment .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [167, 170]}], "task": "NER"}
{"text": "All three test compounds also induced apoptotic cell death , which was inhibited by NAC .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [84, 87]}], "task": "NER"}
{"text": "Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure , it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [8, 11]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [68, 82]}, {"entity": "organochlorine", "entity_type": "Chemical", "pos": [148, 162]}], "task": "NER"}
{"text": "As the same outcome may also occur in vivo , results from the present study raise concern about the use of NAC as treatment for DDT - induced hepatotoxicity .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "DDT", "entity_type": "Chemical", "pos": [128, 131]}], "task": "NER"}
{"text": "Improving the default data analysis workflow for large autoimmune biomarker discovery studies with protoarrays .", "entity": [], "task": "NER"}
{"text": "Contemporary protein microarrays like the ProtoArray (R) are used for autoimmune antibody screening studies to discover biomarker panels .", "entity": [], "task": "NER"}
{"text": "For ProtoArray data analysis the software Prospector and a default workflow are suggested by the manufacturer .", "entity": [], "task": "NER"}
{"text": "While analyzing a large data set of a discovery study for diagnostic biomarkers of the Parkinson ' s Disease ( \" ParkCHIP \" ) we have revealed the need for distinct improvements of the suggested workflow concerning raw data acquisition , normalization and pre - selection method availability , batch effects , feature selection , and feature validation .", "entity": [], "task": "NER"}
{"text": "In this work appropriate improvements of the default workflow are proposed and it is shown that completely automatic data acquisition as a batch , a re - implementation of Prospector ' s pre - selection method , multivariate or hybrid feature selection , and validation of the selected protein panel using an independent test set define in combination an improved workflow for large studies .", "entity": [], "task": "NER"}
{"text": "Elucidation of in situ polycyclic aromatic hydrocarbon degradation by functional metaproteomics ( protein - SIP ) .", "entity": [{"entity": "polycyclic aromatic hydrocarbon", "entity_type": "Chemical", "pos": [23, 54]}], "task": "NER"}
{"text": "Current knowledge of the physiology and phylogeny of polycyclic aromatic hydrocarbon ( PAH ) degrading bacteria often relies on laboratory enrichments and isolations .", "entity": [{"entity": "polycyclic aromatic hydrocarbon", "entity_type": "Chemical", "pos": [53, 84]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "In the present study , in situ microcosms consisting of activated carbon pellets ( BACTRAP (R) s ) were loaded with either ( 13 ) C - naphthalene or ( 13 ) C - fluorene and were subsequently exposed in the contaminant source and plume fringe region of an PAH contaminated aquifer .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "( 13 ) C - naphthalene", "entity_type": "Chemical", "pos": [123, 145]}, {"entity": "( 13 ) C - fluorene", "entity_type": "Chemical", "pos": [149, 168]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [255, 258]}], "task": "NER"}
{"text": "Metaproteomic analysis and protein - SIP revealed Burkholderiales , Actinomycetales and Rhizobiales as the most active microorganisms in the groundwater communities .", "entity": [], "task": "NER"}
{"text": "Proteins identified of the naphthalene degradation pathway showed a relative ( 13 ) C isotope abundance of approximately 50 atom % demonstrating that the identified naphthalene degrading bacteria gained at least 80 % of their carbon by PAH degradation .", "entity": [{"entity": "naphthalene", "entity_type": "Chemical", "pos": [27, 38]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [77, 85]}, {"entity": "naphthalene", "entity_type": "Chemical", "pos": [165, 176]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [226, 232]}, {"entity": "PAH", "entity_type": "Chemical", "pos": [236, 239]}], "task": "NER"}
{"text": "Although the microbial community grown on the fluorene - BACTRAPs showed a structure similar to the naphthalene - BACTRAPs , the identification of fluorene degraders and degradation pathways failed in situ .", "entity": [{"entity": "fluorene", "entity_type": "Chemical", "pos": [46, 54]}, {"entity": "naphthalene", "entity_type": "Chemical", "pos": [100, 111]}, {"entity": "fluorene", "entity_type": "Chemical", "pos": [147, 155]}], "task": "NER"}
{"text": "In complementary laboratory microcosms , a clear enrichment in proteins related to Rhodococcus and possible fluorene degradation enzymes was observed .", "entity": [{"entity": "fluorene", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "This result demonstrates the impact of laboratory conditions on microbial community structure and activity of certain species and underlines the need on in situ exploration of microbial community functions .", "entity": [], "task": "NER"}
{"text": "In situ microcosms in combination with protein - SIP may be a significant tool for in situ identification of metabolic key players as well as degradation pathways .", "entity": [], "task": "NER"}
{"text": "Folate - Conjugated PEG on Single Walled Carbon Nanotubes for Targeting Delivery of Doxorubicin to Cancer Cells .", "entity": [{"entity": "Folate", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [20, 23]}, {"entity": "Carbon", "entity_type": "Chemical", "pos": [41, 47]}, {"entity": "Doxorubicin", "entity_type": "Chemical", "pos": [84, 95]}], "task": "NER"}
{"text": "A highly effective drug carrier is constructed by coating folic acid - terminated poly ( ethylene glycol ) ( PEG - FA ) on single walled carbon nanotubes ( SWNTs ) in a facile non - covalent method .", "entity": [{"entity": "folic acid", "entity_type": "Chemical", "pos": [58, 68]}, {"entity": "poly ( ethylene glycol )", "entity_type": "Chemical", "pos": [82, 106]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [109, 112]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [137, 143]}], "task": "NER"}
{"text": "The anti - cancer drug , doxorubicin ( DOX ) , is further loaded on the surface of SWNTs at a very high loading efficiency , 149 . 3 +/- 4 . 1 % .", "entity": [{"entity": "doxorubicin", "entity_type": "Chemical", "pos": [25, 36]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [39, 42]}], "task": "NER"}
{"text": "The drug system ( DOX / PEG - FA / SWNTs ) exhibits excellent stability under neutral pH conditions such as serum , but dramatically releases DOX at reduced pH typical of the tumour environment and intracellular lysosomes and endosomes .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [18, 21]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [24, 27]}, {"entity": "DOX", "entity_type": "Chemical", "pos": [142, 145]}], "task": "NER"}
{"text": "With the help of FA , DOX / PEG - FA / SWNTs tend to selectively attach onto cancer cells and enter the lysosomes or endosomes by clathrin - mediated endocytosis .", "entity": [{"entity": "DOX", "entity_type": "Chemical", "pos": [22, 25]}, {"entity": "PEG", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "This can greatly improve the pharmaceutical efficiency and reduce potential side effects .", "entity": [], "task": "NER"}
{"text": "Physiotherapeutic approach in early and late post - menopausal Brazilian women .", "entity": [], "task": "NER"}
{"text": "Abstract To evaluate changes in joints after physiotherapy in post - menopausal women , specifically to identify clinical responses to the measurements of flexibility , functional capacity and joint pain in early and late post - menopausal women at a multi - disciplinary health education programme .", "entity": [], "task": "NER"}
{"text": "A total of 69 women participated in the Integral Program for the Attention to Climacteric Women at the Department of Gynecology - Federal University of Sao Paulo and were sorted into two groups of early ( n = 32 ) and late ( n = 37 ) post - menopause .", "entity": [], "task": "NER"}
{"text": "The average age of menopause was 47 . 9 +/- 5 . 6 years .", "entity": [], "task": "NER"}
{"text": "The Blatt Kupperman Menopausal Index scores for the early ( baseline = 12 . 8 +/- 6 . 1 ) and late ( baseline = 14 . 1 +/- 7 . 7 ) post - menopausal groups after the programme were 8 . 4 +/- 7 . 1 and 9 . 4 +/- 8 . 1 , respectively .", "entity": [], "task": "NER"}
{"text": "Both groups presented improvements regarding functional capacity ( p < 0 . 01 ) and complaints of pain ( p < 0 . 001 ) after the intervention .", "entity": [], "task": "NER"}
{"text": "The group of early post - menopausal women had better flexibility for hip flexion ( p < 0 . 001 ) , and the late post - menopausal group showed greater improvement in shoulder flexion ( p < 0 . 001 ) , extension ( p < 0 . 001 ) and elbow flexion ( p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "After multi - disciplinary approach , both early and late post - menopausal groups experienced decrease in intensity of climacteric symptoms , reduction in pain intensity and improvement in functional capacity , but the flexibility was different between both the groups .", "entity": [], "task": "NER"}
{"text": "Structural identification of ( 1 --> 6 ) - alpha - D - glucan , a key responsible for the health benefits of longan , and evaluation of anticancer activity .", "entity": [], "task": "NER"}
{"text": "Longan is a delicious subtropical fruit with great health - beneficial effects .", "entity": [], "task": "NER"}
{"text": "It has been utilised for disease prevention and health care since ancient age .", "entity": [], "task": "NER"}
{"text": "To explore the chemicals responsible for the health benefits , water - soluble polysaccharides were extracted from longan flesh in this work .", "entity": [], "task": "NER"}
{"text": "A pure polysaccharide ( LPS1 ) was obtained through column purification .", "entity": [], "task": "NER"}
{"text": "Analysis by gas chromatography showed LPS1 was a homopolysaccharide of glucose with glycosidic linkage of --> 6 ) - D - Glc - ( 1 --> .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [71, 78]}], "task": "NER"}
{"text": "Nuclear magnetic resonance ( NMR ) spectra indicated that the con fi guration of anomeric carbon in glucose residual was alpha - form .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [90, 96]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "The polysaccharide structure was further confirmed to be ( 1 --> 6 ) - alpha - D - glucan by chemcial shift of C6 .", "entity": [], "task": "NER"}
{"text": "The molecular weight of LPS1 was calculated to be 108 kDa , which had 661 glucose residuals .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [74, 81]}], "task": "NER"}
{"text": "Anticancer assay showed that LPS1 had anticancer activity against the growth of HepG2 cells to a certain extent .", "entity": [], "task": "NER"}
{"text": "However , it did not show any cytotoxicity against MCF - 7 breast cancer cells .", "entity": [], "task": "NER"}
{"text": "Hybrid Molecule from O ( 2 ) - ( 2 , 4 - Dinitrophenyl ) diazeniumdiolate and Oleanolic Acid : a GST pi Activated Nitric Oxide Prodrug with Selective Anti - human Hepatocellular Carcinoma Activity and Improved Stability .", "entity": [{"entity": "O ( 2 ) - ( 2 , 4 - Dinitrophenyl ) diazeniumdiolate", "entity_type": "Chemical", "pos": [21, 73]}, {"entity": "Oleanolic Acid", "entity_type": "Chemical", "pos": [78, 92]}, {"entity": "Nitric Oxide", "entity_type": "Chemical", "pos": [114, 126]}], "task": "NER"}
{"text": "A series of hybrids from O ( 2 ) - ( 2 , 4 - dinitrophenyl ) diazeniumdiolate and oleanolic acid ( OA ) were designed , synthesized , and biologically evaluated as novel nitric oxide ( NO ) releasing prodrugs which could be activated by glutathione S - transferase pi ( GST pi ) overexpressed in a number of cancer cells .", "entity": [{"entity": "O ( 2 ) - ( 2 , 4 - dinitrophenyl ) diazeniumdiolate", "entity_type": "Chemical", "pos": [25, 77]}, {"entity": "oleanolic acid", "entity_type": "Chemical", "pos": [82, 96]}, {"entity": "nitric oxide", "entity_type": "Chemical", "pos": [170, 182]}, {"entity": "NO", "entity_type": "Chemical", "pos": [185, 187]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [237, 248]}], "task": "NER"}
{"text": "It was discovered that the most active compound 21 released high levels of NO selectively in HCC cells but not in the normal cells , and exhibited potent antiproliferative activity in vitro as well as remarkable tumor - retarding effects in vivo .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [75, 77]}], "task": "NER"}
{"text": "Compared with the reported GST pi - activated prodrugs JS - K and PABA / NO , 21 exhibited remarkably improved stability in the absence of GST pi .", "entity": [{"entity": "PABA", "entity_type": "Chemical", "pos": [66, 70]}, {"entity": "NO", "entity_type": "Chemical", "pos": [73, 75]}], "task": "NER"}
{"text": "Importantly , the decomposition of 21 occurred in the presence of GST pi , and was much more effective than in GST alpha .", "entity": [], "task": "NER"}
{"text": "Additionally , 21 induced HepG2 cells apoptosis by arresting cell cycle at G2 / M phase , activating both the mitochondria - mediated pathway and the MAPKs pathway , as well as enhancing the intracellular production of ROS .", "entity": [], "task": "NER"}
{"text": "Rationale for the higher reactivity of interfacial sites in methanol decomposition on Au13 / TiO2 ( 110 ) .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "Au13 / TiO2 ( 110 )", "entity_type": "Chemical", "pos": [86, 105]}], "task": "NER"}
{"text": "Interfacial and perimeter sites have been known for their high activity in various reactions on supported gold nanoparticles .", "entity": [], "task": "NER"}
{"text": "We find that the higher activity of interfacial sites in Au13 / TiO2 ( 110 ) towards methanol decomposition originates from charge - transfer - induced Coulomb interaction among the gold , reactant , and reducible TiO2 support , brought about through the formation of an ionic O - Au bond between gold and methoxy in such sites , which turns the participating perimeter gold atom cationic .", "entity": [{"entity": "Au13 / TiO2 ( 110 )", "entity_type": "Chemical", "pos": [57, 76]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [85, 93]}, {"entity": "TiO2", "entity_type": "Chemical", "pos": [214, 218]}, {"entity": "O - Au", "entity_type": "Chemical", "pos": [277, 283]}, {"entity": "methoxy", "entity_type": "Chemical", "pos": [306, 313]}], "task": "NER"}
{"text": "A direct result of such charge - transfer - induced repulsive interaction between cationic gold and positively charged C moiety of methoxy is activation of the positively charged C moiety of methoxy , as manifested by the pronounced elongation of O - C bond length and the tilting of the methoxy axis , which facilitate reaction of methoxy through C - H scission with the bridge oxygen atoms that are readily available from the reducible support .", "entity": [{"entity": "C", "entity_type": "Chemical", "pos": [119, 120]}, {"entity": "methoxy", "entity_type": "Chemical", "pos": [131, 138]}, {"entity": "C", "entity_type": "Chemical", "pos": [179, 180]}, {"entity": "methoxy", "entity_type": "Chemical", "pos": [191, 198]}, {"entity": "O - C", "entity_type": "Chemical", "pos": [247, 252]}, {"entity": "methoxy", "entity_type": "Chemical", "pos": [288, 295]}, {"entity": "methoxy", "entity_type": "Chemical", "pos": [332, 339]}, {"entity": "C - H", "entity_type": "Chemical", "pos": [348, 353]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [379, 385]}], "task": "NER"}
{"text": "More generally , our proposed mechanism for the reactivity of the gold / TiO2 interface should hold for oxidation of organic molecules with the structure of R - O - R ' , where R and R ' are ( saturated ) hydrocarbons .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [73, 77]}, {"entity": "R - O - R '", "entity_type": "Chemical", "pos": [157, 168]}, {"entity": "( saturated ) hydrocarbons", "entity_type": "Chemical", "pos": [191, 217]}], "task": "NER"}
{"text": "Cadmium - Based Quantum Dot Induced Autophagy Formation for Cell Survival via Oxidative Stress .", "entity": [{"entity": "Cadmium", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Quantum dots ( QDs ) are one of most utilized nanomaterials in nanocrystalline semiconductors .", "entity": [], "task": "NER"}
{"text": "QDs emit near - infrared fluorescence and can be applied as probes for detecting vasculature and imaging in biological systems .", "entity": [], "task": "NER"}
{"text": "Since QDs have potential in clinical application , the toxicity of QDs needs to be carefully evaluated .", "entity": [], "task": "NER"}
{"text": "In our present study , we elucidate the cytotoxic mechanisms of QDs using a mouse renal adenocarcinoma ( RAG ) cell line .", "entity": [], "task": "NER"}
{"text": "QDs in RAG cells increased intracellular reactive oxygen species ( ROS ) levels and induced autophagy at 6 h , leading to subsequent apoptosis at 24 h .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [50, 56]}], "task": "NER"}
{"text": "QDs entered the cells and were located within the endoplasmic reticulum ( ER ) , endosome , and lysosome at 6 h and endosome , lysosome , and mitochondria at 24 h .", "entity": [], "task": "NER"}
{"text": "However , QDs only affected mitochondrial function and did not induce ER stress .", "entity": [], "task": "NER"}
{"text": "N - Acetylcysteine , an antioxidant agent , reduced intracellular ROS levels and decreased QD - induced autophagy but enhanced QD - induced cell death .", "entity": [{"entity": "N - Acetylcysteine", "entity_type": "Chemical", "pos": [0, 18]}], "task": "NER"}
{"text": "Moreover , 3 - methylamphetamine ( an autophagy inhibitor ) also reduced the cell viability in QD - treated cells .", "entity": [{"entity": "3 - methylamphetamine", "entity_type": "Chemical", "pos": [11, 32]}], "task": "NER"}
{"text": "These findings suggest that ROS plays an essential role in the regulation of QD - induced autophagy , which subsequently enhances cell survival .", "entity": [], "task": "NER"}
{"text": "Taken together , these results suggest that oxidative stress - induced autophagy is a defense / survival mechanism against the cytotoxicity of QD .", "entity": [], "task": "NER"}
{"text": "MicroRNA - 32 ( miR - 32 ) regulates phosphatase and tensin homologue ( PTEN ) expression and promotes growth , migration , and invasion in colorectal carcinoma cells .", "entity": [], "task": "NER"}
{"text": "BACKGROUND : Colorectal carcinoma ( CRC ) is one of the leading causes of cancer - related mortality worldwide .", "entity": [], "task": "NER"}
{"text": "MicroRNAs ( miRNAs , miRs ) play important roles in carcinogenesis .", "entity": [], "task": "NER"}
{"text": "MiR - 32 has been shown to be upregulated in CRC .", "entity": [], "task": "NER"}
{"text": "In this study , we identified the potential effects of miR - 32 on some important biological properties of CRC cells , and clarified the regulation of PTEN by miR - 32 .", "entity": [], "task": "NER"}
{"text": "METHODS : The effect of miR - 32 on PTEN expression was assessed in CRC cell lines with miR - 32 mimics / inhibitor to increase / decrease miR - 32 expression .", "entity": [], "task": "NER"}
{"text": "Furthermore , the roles of miR - 32 in regulating CRC cells biological properties were analyzed with miR - 32 mimics / inhibitor - transfected cells .", "entity": [], "task": "NER"}
{"text": "The 3 [ prime ] - untranslated region ( 3 [ prime ] - UTR ) of PTEN combined with miR - 32 was verified by dual - luciferase reporter assay .", "entity": [], "task": "NER"}
{"text": "RESULTS : Gain - of - function and loss - of - function studies showed that overexpression of miR - 32 promoted SW480 cell proliferation , migration , and invasion , reduced apoptosis , and resulted in downregulation of PTEN at a posttranscriptional level .", "entity": [], "task": "NER"}
{"text": "However , miR - 32 knock - down inhibited these processes in HCT - 116 cells and enhanced the expression of PTEN protein .", "entity": [], "task": "NER"}
{"text": "In addition , we further identified PTEN as the functional downstream target of miR - 32 by directly targeting the 3 [ prime ] - UTR of PTEN .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Our results demonstrated that miR - 32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN .", "entity": [], "task": "NER"}
{"text": "Structure - - activity relationships and in silico models of P - glycoprotein ( ABCB1 ) inhibitors .", "entity": [], "task": "NER"}
{"text": "The efflux pump p - glycoprotein ( P - gp / ABCB1 ) has received enormous attention in drug ( xenobiotic ) disposition due to its role in modulation of the drug availability and in protection of sensitive organs .", "entity": [], "task": "NER"}
{"text": "P - gp mediated efflux is one of main mechanisms for multidrug resistance in cancer cells .", "entity": [], "task": "NER"}
{"text": "A main approach to reverse the resistance and restore the drug efficacy is to use specific inhibitors of P - gp that suppress the efflux activity .", "entity": [], "task": "NER"}
{"text": "This review summarizes the binding capabilities of known chemical inhibitors based on the analyses of structure - activity relationships , and computational modeling of the inhibitors as well as the binding site of P - gp protein .", "entity": [], "task": "NER"}
{"text": "The molecular models will facilitate the design of lead inhibitors as drug candidates .", "entity": [], "task": "NER"}
{"text": "Also , it helps scientists in early drug discovery phase to synthesize chemical series with better understanding of their P - gp binding liabilities .", "entity": [], "task": "NER"}
{"text": "Nasal dosimetry of inspired naphthalene vapor in the male and female B6C3F1 mouse .", "entity": [{"entity": "naphthalene", "entity_type": "Chemical", "pos": [28, 39]}], "task": "NER"}
{"text": "Naphthalene vapor is a nasal cytotoxicant in the rat and mouse but is a nasal carcinogen in only the rat .", "entity": [{"entity": "Naphthalene", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Inhalation dosimetry is a critical aspect of the inhalation toxicology of inspired vapors and may contribute to the species differences in the nasal response .", "entity": [], "task": "NER"}
{"text": "To define the nasal dosimetry of naphthalene in the B6C3F1 male and female mouse , uptake of naphthalene vapor was measured in the surgically isolated upper respiratory tract ( URT ) at inspiratory flow rates of 25 or 50ml / min .", "entity": [{"entity": "naphthalene", "entity_type": "Chemical", "pos": [33, 44]}, {"entity": "naphthalene", "entity_type": "Chemical", "pos": [93, 104]}], "task": "NER"}
{"text": "Uptake was measured at multiple concentrations ( 0 . 5 , 3 , 10 , 30ppm ) in controls and mice treated with the cytochrome P450 inhibitor 5 - phenyl - 1 - pentyne .", "entity": [{"entity": "5 - phenyl - 1 - pentyne", "entity_type": "Chemical", "pos": [138, 162]}], "task": "NER"}
{"text": "In both sexes , URT uptake efficiency was strongly concentration dependent averaging 90 % at 0 . 5ppm compared to 50 % at 30ppm ( 25ml / min flow rate ) , indicating saturable processes were involved .", "entity": [], "task": "NER"}
{"text": "Both uptake efficiency and the concentration dependence of uptake were significantly diminished by 5 - phenyl - 1 - pentyne indicating inspired naphthalene vapor is extensively metabolized in the mouse nose with saturation of metabolism occurring at the higher concentrations .", "entity": [{"entity": "5 - phenyl - 1 - pentyne", "entity_type": "Chemical", "pos": [99, 123]}, {"entity": "naphthalene", "entity_type": "Chemical", "pos": [144, 155]}], "task": "NER"}
{"text": "A hybrid computational fluid dynamic physiologically based pharmacokinetic model was developed for nasal dosimetry .", "entity": [], "task": "NER"}
{"text": "This model accurately predicted the observed URT uptake efficiencies .", "entity": [], "task": "NER"}
{"text": "Overall , the high URT uptake efficiency of naphthalene in the mouse nose indicates the absence of a tumorigenic response is not attributable to low delivered dose rates in this species .", "entity": [{"entity": "naphthalene", "entity_type": "Chemical", "pos": [44, 55]}], "task": "NER"}
{"text": "Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [32, 42]}], "task": "NER"}
{"text": "Maternal exposure to di ( 2 - ethylhexyl ) phthalate ( DEHP ) decreased the plasma triglyceride in prepartum mice .", "entity": [{"entity": "di ( 2 - ethylhexyl ) phthalate", "entity_type": "Chemical", "pos": [21, 52]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [55, 59]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [83, 95]}], "task": "NER"}
{"text": "To identify the fatty acid ( FA ) species involved and to understand the underlying mechanisms , pregnant Sv / 129 wild - type ( mPPAR alpha ) , peroxisome proliferator - activated receptor alpha - null ( Ppar alpha - null ) and humanized PPAR alpha ( hPPAR alpha ) mice were treated with diets containing 0 % , 0 . 01 % , 0 . 05 % or 0 . 1 % DEHP .", "entity": [{"entity": "fatty acid", "entity_type": "Chemical", "pos": [16, 26]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [343, 347]}], "task": "NER"}
{"text": "Dams were dissected on gestational day 18 together with fetuses , and on postnatal day 2 together with newborns .", "entity": [], "task": "NER"}
{"text": "n - 3 / n - 6 polyunsaturated , saturated , and monounsaturated FAs in maternal plasma and in liver of wild - type offspring , and representative enzymes for FA desaturation and elongation in maternal liver , were measured .", "entity": [{"entity": "n - 3 / n - 6 polyunsaturated , saturated , and monounsaturated FAs", "entity_type": "Chemical", "pos": [0, 67]}], "task": "NER"}
{"text": "The plasma levels of linoleic acid , alpha - linolenic acid , palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara - null and hPPARa mice .", "entity": [{"entity": "linoleic acid", "entity_type": "Chemical", "pos": [21, 34]}, {"entity": "alpha - linolenic acid", "entity_type": "Chemical", "pos": [37, 59]}, {"entity": "palmitic acid", "entity_type": "Chemical", "pos": [62, 75]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [80, 90]}], "task": "NER"}
{"text": "DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPAR alpha mice .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype - independent manner , while it was lower in the livers of fetuses than pups .", "entity": [], "task": "NER"}
{"text": "DEHP exposure slightly increased hepatic arachidonic acid , alpha - linolenic acid , palmitoleic acid and oleic acid in fetuses , but not in pups .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [41, 57]}, {"entity": "alpha - linolenic acid", "entity_type": "Chemical", "pos": [60, 82]}, {"entity": "palmitoleic acid", "entity_type": "Chemical", "pos": [85, 101]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [106, 116]}], "task": "NER"}
{"text": "However , DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice .", "entity": [{"entity": "DEHP", "entity_type": "Chemical", "pos": [10, 14]}], "task": "NER"}
{"text": "Taken together , the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPAR alpha mice than in other genotypes , and DEHP exposure decreased these specific FA concentrations only in mPPAR alpha mice , similarly to triglyceride levels .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [60, 66]}, {"entity": "DEHP", "entity_type": "Chemical", "pos": [145, 149]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [242, 254]}], "task": "NER"}
{"text": "The role of methyl - CpG binding protein 2 in liver fibrosis .", "entity": [{"entity": "methyl", "entity_type": "Chemical", "pos": [12, 18]}, {"entity": "CpG", "entity_type": "Chemical", "pos": [21, 24]}], "task": "NER"}
{"text": "Liver injure is induced by various insults such as alcohol abuse , if insults persistent , may result in the formation of liver fibrosis .", "entity": [{"entity": "alcohol", "entity_type": "Chemical", "pos": [51, 58]}], "task": "NER"}
{"text": "Hepatic stellate cell ( HSC ) activation and transdifferentiation into hepatic myofibroblast , accompanied with potent pro - inflammatory and pro - fibrogenic activities and the down - regulation of anti - inflammatory anti - fibrogenic in gene expression in coordination with epigenetic modifications at the level of the chromatin structure , are pivotal events in liver fibrogenesis .", "entity": [], "task": "NER"}
{"text": "In this review we focus on the role of the methyl - CpG binding protein 2 ( MeCP2 ) transcriptional regulation of different target genes and the interaction MeCP2 with microRNAs ( miRNAs ) during liver fibrosis .", "entity": [{"entity": "methyl", "entity_type": "Chemical", "pos": [43, 49]}, {"entity": "CpG", "entity_type": "Chemical", "pos": [52, 55]}], "task": "NER"}
{"text": "In addition , we address different signaling pathways interacted with MeCP2 regulated HSC activation .", "entity": [], "task": "NER"}
{"text": "Such approaches provide valuable insights into the potential targets of liver fibrosis , and are useful pointers for the development of future therapeutic strategies .", "entity": [], "task": "NER"}
{"text": "Dabigatran for the Prevention of Stroke and Systemic Embolism in Atrial Fibrillation : A NICE Single Technology Appraisal .", "entity": [{"entity": "Dabigatran", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "The National Institute for Health and Clinical Excellence ( NICE ) invited the manufacturer of dabigatran etexilate ( Boehringer Ingelheim Ltd , UK ) to submit evidence for the clinical and cost - effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non - valvular atrial fibrillation ( AF ) as part of the NICE single technology appraisal process .", "entity": [{"entity": "dabigatran etexilate", "entity_type": "Chemical", "pos": [95, 115]}], "task": "NER"}
{"text": "The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group ( ERG ) .", "entity": [], "task": "NER"}
{"text": "This article presents a summary of the manufacturer ' s submission , the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service .", "entity": [{"entity": "dabigatran", "entity_type": "Chemical", "pos": [147, 157]}], "task": "NER"}
{"text": "Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen ( DBG sequential ) , in which patients under 80 years are treated with dabigatran 150 mg twice daily ( DBG150 ) and patients 80 years and over are given dabigatran 110 mg twice daily ( DBG110 ) .", "entity": [{"entity": "Dabigatran", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "dabigatran", "entity_type": "Chemical", "pos": [183, 193]}, {"entity": "dabigatran", "entity_type": "Chemical", "pos": [265, 275]}], "task": "NER"}
{"text": "NICE decisions are bound by the marketing authorisation ; therefore , the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost - effective compared with warfarin or aspirin for patients with non - valvular AF and one or more risk factors .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [202, 210]}, {"entity": "aspirin", "entity_type": "Chemical", "pos": [214, 221]}], "task": "NER"}
{"text": "The RE - LY trial , a large multi - centre non - inferiority randomised clinical trial , was the primary source of clinical evidence .", "entity": [], "task": "NER"}
{"text": "DBG150 was shown to be non - inferior , and subsequently superior to warfarin , for the primary outcome of all stroke / systemic embolism .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "DBG110 was found to be non - inferior to warfarin .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [41, 49]}], "task": "NER"}
{"text": "Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age , where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [229, 237]}], "task": "NER"}
{"text": "This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen .", "entity": [], "task": "NER"}
{"text": "The economic evaluation compared the costs and outcomes of DBG110 , DBG150 and DBG sequential against warfarin , aspirin , and aspirin plus clopidogrel .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [102, 110]}, {"entity": "aspirin", "entity_type": "Chemical", "pos": [113, 120]}, {"entity": "aspirin", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "clopidogrel", "entity_type": "Chemical", "pos": [140, 151]}], "task": "NER"}
{"text": "Across the three dosing regimens , dabigatran was associated with greater costs and better health outcomes than warfarin ; however , DBG150 offered the most benefits and dominated DBG110 and DBG sequential ( i . e . less costly and more effective ) .", "entity": [{"entity": "dabigatran", "entity_type": "Chemical", "pos": [35, 45]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [112, 120]}], "task": "NER"}
{"text": "The cost - effectiveness of DBG150 was less favourable for patients well controlled on warfarin .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [87, 95]}], "task": "NER"}
{"text": "In the first appraisal meeting , the committee issued a ' minded no ' decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer .", "entity": [], "task": "NER"}
{"text": "These additional analyses indicated that the incremental cost - effectiveness ratio ( ICER ) of the DBG sequential regimen compared with warfarin ranged from pound 8 , 388 to pound 18 , 987 per quality - adjusted life year ( QALY ) gained depending on the level of monitoring costs assumed for warfarin .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [137, 145]}, {"entity": "warfarin", "entity_type": "Chemical", "pos": [294, 302]}], "task": "NER"}
{"text": "Patients on warfarin would need to be within therapeutic range 83 - 85 % of the time for the ICER to exceed pound 30 , 000 per additional QALY .", "entity": [{"entity": "warfarin", "entity_type": "Chemical", "pos": [12, 20]}], "task": "NER"}
{"text": "Following consideration of the additional evidence and the responses from a large number of consultees and commentators , the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non - valvular AF with one or more risk factors for ischaemic stroke .", "entity": [{"entity": "dabigatran", "entity_type": "Chemical", "pos": [148, 158]}], "task": "NER"}
{"text": "Asymmetric zinc - catalyzed hydrosilylation of ketones and the effect of carboxylate on the enantioselectivity .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [11, 15]}, {"entity": "ketones", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "carboxylate", "entity_type": "Chemical", "pos": [73, 84]}], "task": "NER"}
{"text": "Several chiral ligands containing ( R , R ) - diaminocyclohexane moieties and pyrrole , furan , or benzene have been synthesized .", "entity": [{"entity": "( R , R ) - diaminocyclohexane", "entity_type": "Chemical", "pos": [34, 64]}, {"entity": "pyrrole", "entity_type": "Chemical", "pos": [78, 85]}, {"entity": "furan", "entity_type": "Chemical", "pos": [88, 93]}, {"entity": "benzene", "entity_type": "Chemical", "pos": [99, 106]}], "task": "NER"}
{"text": "These ligands were tested in enantioselective zinc - catalyzed hydrosilylation reactions ; excellent enantioselectivities were obtained when the ligands containing ( R , R ) - diaminocyclohexane moieties and furan rings were used .", "entity": [{"entity": "zinc", "entity_type": "Chemical", "pos": [46, 50]}, {"entity": "( R , R ) - diaminocyclohexane", "entity_type": "Chemical", "pos": [164, 194]}, {"entity": "furan", "entity_type": "Chemical", "pos": [208, 213]}], "task": "NER"}
{"text": "For comparison , zinc chloride combined with different potassium carboxylate salts and ligands were also tested for catalytic hydrosilylation reactions .", "entity": [{"entity": "zinc chloride", "entity_type": "Chemical", "pos": [17, 30]}, {"entity": "potassium carboxylate", "entity_type": "Chemical", "pos": [55, 76]}], "task": "NER"}
{"text": "Chirality 25 : 275 - 280 , 2013 .", "entity": [], "task": "NER"}
{"text": "Variability in P - Glycoprotein Inhibitory Potency ( IC50 ) Using Various In Vitro Experimental Systems : Implications for Universal Digoxin DDI Risk Assessment Decision Criteria .", "entity": [{"entity": "Digoxin", "entity_type": "Chemical", "pos": [133, 140]}], "task": "NER"}
{"text": "A P - glycoprotein ( P - gp ) IC50 working group was established with twenty - three participating pharmaceutical and contract research laboratories and one academic institution to assess inter - laboratory variability in P - gp IC50 determinations .", "entity": [], "task": "NER"}
{"text": "Each lab followed their in - house protocol to determine in vitro IC50 values for sixteen inhibitors using four different test systems : Caco - 2 ( 11 labs ) , MDCKII - MDR1 ( 6 labs ) and LLC - PK1 - MDR1 ( 4 labs ) cells , and membrane vesicles containing human P - gp ( 5 labs ) .", "entity": [], "task": "NER"}
{"text": "For cell models , various equations to calculate remaining transport activity ( e . g . efflux ratio , unidirectional flux , net secretory flux ) were also evaluated .", "entity": [], "task": "NER"}
{"text": "The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20 - and 24 - fold between lowest and highest IC50 values for sertraline and isradipine , to a maximum of 407 - and 796 - fold for telmisartan and verapamil , respectively .", "entity": [{"entity": "sertraline", "entity_type": "Chemical", "pos": [182, 192]}, {"entity": "isradipine", "entity_type": "Chemical", "pos": [197, 207]}, {"entity": "telmisartan", "entity_type": "Chemical", "pos": [251, 262]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [267, 276]}], "task": "NER"}
{"text": "For telmisartan and verapamil , variability was greatly influenced by data from one laboratory in each case .", "entity": [{"entity": "telmisartan", "entity_type": "Chemical", "pos": [4, 15]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [20, 29]}], "task": "NER"}
{"text": "Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69 - and 159 - fold .", "entity": [{"entity": "telmisartan", "entity_type": "Chemical", "pos": [66, 77]}, {"entity": "verapamil", "entity_type": "Chemical", "pos": [82, 91]}], "task": "NER"}
{"text": "The efflux ratio based - equation generally resulted in several fold lower IC50 values compared to unidirectional or net - secretory flux equations .", "entity": [], "task": "NER"}
{"text": "Statistical analysis indicated that variability in IC50 values was mainly due to inter - laboratory variability , rather than an implicit systematic difference between test systems .", "entity": [], "task": "NER"}
{"text": "Potential reasons for variability are discussed and the simplest , most robust experimental design for P - gp IC50 determination proposed .", "entity": [], "task": "NER"}
{"text": "The impact of these findings on drug - drug interaction risk assessment is discussed in the companion paper and recommendations are provided .", "entity": [], "task": "NER"}
{"text": "Mechanism of Fibrinogen Adsorption at Solid Substrates at lower pH .", "entity": [], "task": "NER"}
{"text": "Adsorption of fibrinogen was theoretically studied using the three dimensional ( 3D ) random sequential adsorption ( RSA ) model .", "entity": [], "task": "NER"}
{"text": "Fibrinogen molecule shape was approximated by the bead model considering the presence of flexible side arms .", "entity": [], "task": "NER"}
{"text": "Various cases were considered inter alia , the side - on adsorption mechanisms and the 3D side - on / end - on simultaneous adsorption mechanism .", "entity": [], "task": "NER"}
{"text": "The latter mechanisms is pertinent to fibrinogen adsorption at lower pH where the entire molecule is positively charged .", "entity": [], "task": "NER"}
{"text": "Extensive calculations enabled one to determine the jamming surface concentration ( coverage ) of molecules adsorbed under the side - on and end - on orientations as well as the total coverage .", "entity": [], "task": "NER"}
{"text": "For the 3D model the maximum surface concentration was 7 . 29x103 mu m - 2 corresponding to the protein coverage of 4 . 12 mg m - 2 ( without considering hydration ) .", "entity": [], "task": "NER"}
{"text": "Additionally , the surface blocking functions for the side - on and the 3D adsorption regimes were determined and analytically approximated for the entire range of coverage by the interpolating polynomials .", "entity": [], "task": "NER"}
{"text": "Using these blocking functions , fibrinogen adsorption kinetics for diffusion controlled transport conditions was evaluated .", "entity": [], "task": "NER"}
{"text": "Comparison of these theoretical results with experimental data was made .", "entity": [], "task": "NER"}
{"text": "It was demonstrated that the 3D model properly reflects the maximum coverage of fibrinogen adsorbed on latex particles determined via the electrokinetic ( electrophoretic mobility ) and AFM measurements .", "entity": [], "task": "NER"}
{"text": "Also , streaming potential measurements of fibrinogen adsorption kinetics on mica were successfully interpreted in terms of the 3D adsorption model .", "entity": [{"entity": "mica", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "The theoretical results derived in this work have implications for basic science providing information on mechanisms of anisotropic protein adsorption .", "entity": [], "task": "NER"}
{"text": "Key words : adsorption of fibrinogen , fibrinogen adsorption at lower pH , irreversible adsorption of fibrinogen , jamming coverage of fibrinogen , kinetics of fibrinogen adsorption , random sequential adsorption modeling of fibrinogen adsorption .", "entity": [], "task": "NER"}
{"text": "Aggregation - Mediated Macromolecular Uptake by a Molecular Transporter .", "entity": [], "task": "NER"}
{"text": "Endocytosis is a key process in cellular delivery of macromolecules by molecular transporters , although the mechanism of internalization remains unclear .", "entity": [], "task": "NER"}
{"text": "Here , we probe the cellular uptake of streptavidin using biotinylated guanidinoneomycin ( biotinGNeo ) , a low molecular weight guanidinium - rich molecular transporter .", "entity": [{"entity": "biotinylated guanidinoneomycin", "entity_type": "Chemical", "pos": [58, 88]}, {"entity": "biotinGNeo", "entity_type": "Chemical", "pos": [91, 101]}, {"entity": "guanidinium", "entity_type": "Chemical", "pos": [129, 140]}], "task": "NER"}
{"text": "Two distinct modes were explored : ( i ) incubation of cells with a preformed tetravalent streptavidin - ( biotinGNeo ) 4 conjugate and ( ii ) preincubation of cells with the biotinGNeo before exposure to streptavidin .", "entity": [{"entity": "biotinGNeo", "entity_type": "Chemical", "pos": [107, 117]}, {"entity": "biotinGNeo", "entity_type": "Chemical", "pos": [175, 185]}], "task": "NER"}
{"text": "A significant enhancement in uptake was observed after preincubation with biotinGNeo .", "entity": [{"entity": "biotinGNeo", "entity_type": "Chemical", "pos": [74, 84]}], "task": "NER"}
{"text": "FRET studies showed that the enhanced uptake was accompanied by extensive aggregation of streptavidin on the cell surface .", "entity": [], "task": "NER"}
{"text": "Because guanidinylated neomycin was previously found to exclusively bind to heparan sulfate , our observations suggest that heparan sulfate proteoglycan aggregation is a pivotal step for endocytic entry into cells by guanidinoglycosides .", "entity": [{"entity": "guanidinylated neomycin", "entity_type": "Chemical", "pos": [8, 31]}, {"entity": "guanidinoglycosides", "entity_type": "Chemical", "pos": [217, 236]}], "task": "NER"}
{"text": "These observations put forward a practical and general pathway for the cellular delivery of diverse macromolecules .", "entity": [], "task": "NER"}
{"text": "Study of Charge - Dependent Transport and Toxicity of Peptide - Functionalized Silver Nanoparticles Using Zebrafish Embryos and Single Nanoparticle Plasmonic Spectroscopy .", "entity": [{"entity": "Silver", "entity_type": "Chemical", "pos": [79, 85]}], "task": "NER"}
{"text": "Nanomaterials possess unusually high surface area - to - volume ratios , and surface - determined physicochemical properties .", "entity": [], "task": "NER"}
{"text": "It is essential to understand their surface - dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications .", "entity": [], "task": "NER"}
{"text": "In this study , we have functionalized the surfaces of silver nanoparticles ( Ag NPs , 11 . 7 +/- 2 . 7 nm in diameters ) with three biocompatible peptides ( CALNNK , CALNNS , CALNNE ) to prepare positively ( Ag - CALNNK NPs + zeta ) , negatively ( Ag - CALNNS NPs - 2 zeta ) , and more negatively charged NPs ( Ag - CALNNE NPs - 4 zeta ) , respectively .", "entity": [{"entity": "silver", "entity_type": "Chemical", "pos": [55, 61]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [78, 80]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [209, 211]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [249, 251]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [312, 314]}], "task": "NER"}
{"text": "Each peptide differs in a single amino acid at its C - terminus , which minimizes the effects of peptide sequences and serves as a model molecule to create positive , neutral and negative charges on the surface of the NPs at pH 4 - 10 .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [33, 43]}, {"entity": "C", "entity_type": "Chemical", "pos": [51, 52]}], "task": "NER"}
{"text": "We have studied their charge - dependent transport into early - developing ( cleavage - stage ) zebrafish embryos and their effects on embryonic development using dark - field optical microscopy and spectroscopy ( DFOMS ) .", "entity": [], "task": "NER"}
{"text": "We found that all three Ag - peptide NPs passively diffused into the embryos via their chorionic pore canals , and stayed inside the embryos throughout their entire development ( 120 h ) , showing charge - independent diffusion modes and charge - dependent diffusion coefficients .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [24, 26]}], "task": "NER"}
{"text": "Notably , the NPs create charge - dependent toxic effects on embryonic development , showing that the Ag - CALNNK NPs + zeta ( positively charged ) are the most biocompatible while the Ag - CALNNE NPs - 4 zeta ( more negatively charged ) are the most toxic .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [102, 104]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [185, 187]}], "task": "NER"}
{"text": "By comparing with our previous studies of the same sized citrated Ag and Au NPs , the Ag - peptide NPs are much more biocompatible than the citrated Ag NPs , and nearly as biocompatible as the Au NPs , showing the dependence of nanotoxicity upon the surface charges , surface functional groups and chemical compositions of the NPs .", "entity": [{"entity": "Ag", "entity_type": "Chemical", "pos": [66, 68]}, {"entity": "Au", "entity_type": "Chemical", "pos": [73, 75]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [86, 88]}, {"entity": "Ag", "entity_type": "Chemical", "pos": [149, 151]}, {"entity": "Au", "entity_type": "Chemical", "pos": [193, 195]}], "task": "NER"}
{"text": "This study also demonstrates powerful applications of single NP plasmonic spectroscopy for quantitative analysis of single NPs in vivo and in tissues , and reveals the possibility of rational design of biocompatible NPs .", "entity": [], "task": "NER"}
{"text": "Small molecule mediated proliferation of primary retinal pigment epithelial cells .", "entity": [{"entity": "retinal", "entity_type": "Chemical", "pos": [49, 56]}], "task": "NER"}
{"text": "Retinal pigment epithelial ( RPE ) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle .", "entity": [{"entity": "Retinal", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "Degeneration of this layer results in vision loss , causing retinal disorders such as age - related macular degeneration .", "entity": [], "task": "NER"}
{"text": "Cell transplant therapies exist to restore vision loss ; however , risks associated with and an inadequate supply of donor cells have limited their therapeutic success .", "entity": [], "task": "NER"}
{"text": "The identification of factors that proliferate RPE cells ex vivo could provide a renewable source of cells for the treatment of such disorders .", "entity": [], "task": "NER"}
{"text": "We show that a small molecule ( WS3 ) can reversibly proliferate primary RPE cells isolated from fetal and adult human donors .", "entity": [], "task": "NER"}
{"text": "Following withdrawal of WS3 , RPE cells differentiate into a functional monolayer , as exhibited by their expression of mature RPE genes and phagocytosis of photoreceptor outer segments .", "entity": [], "task": "NER"}
{"text": "Furthermore , chemically expanded RPE cells preserve vision when transplanted into dystrophic Royal College of Surgeons ( RCS ) rats , a well - established model of retinal degeneration .", "entity": [], "task": "NER"}
{"text": "Two new vinblastine - type N - oxide alkaloids from Catharanthus roseus .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [8, 19]}, {"entity": "N - oxide alkaloids", "entity_type": "Chemical", "pos": [27, 46]}], "task": "NER"}
{"text": "Two new vinblastine - type N - oxide alkaloids , 17 - desacetoxyvinblastine [ Formula : see text ] - oxide ( 1 ) and 20 ' - deoxyvinblastine [ Formula : see text ] - oxide ( 2 ) , were isolated from the leaves of Catharanthus roseus .", "entity": [{"entity": "vinblastine", "entity_type": "Chemical", "pos": [8, 19]}, {"entity": "N - oxide alkaloids", "entity_type": "Chemical", "pos": [27, 46]}, {"entity": "17 - desacetoxyvinblastine", "entity_type": "Chemical", "pos": [49, 75]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [101, 106]}, {"entity": "20 ' - deoxyvinblastine", "entity_type": "Chemical", "pos": [117, 140]}, {"entity": "oxide", "entity_type": "Chemical", "pos": [166, 171]}], "task": "NER"}
{"text": "The structures of 1 and 2 were established by the analysis of their nuclear magnetic resonance and HR - ESI - MS spectroscopic data .", "entity": [], "task": "NER"}
{"text": "All alkaloids were evaluated for their cytotoxic activities against the human hepatocellular carcinoma ( HepG2 ) cell line , human colorectal carcinoma ( Lovo ) cell line and human breast carcinoma ( MCF - 7 ) cell line by the MTT method in vitro , respectively .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [227, 230]}], "task": "NER"}
{"text": "The results showed that cytotoxic activities of alkaloids 1 and 2 exhibited moderate inhibitory activity on the proliferation of three cancer cells .", "entity": [], "task": "NER"}
{"text": "Mechanism - based design of a photo - activatable firefly Luciferase .", "entity": [], "task": "NER"}
{"text": "We developed a photo - activatable firefly luciferase ( fLuc ) whose activation can be controlled by light .", "entity": [], "task": "NER"}
{"text": "A photocaged lysine analogue was site - specifically incorporated into fLuc to replace its key catalytic lysine residue - Lys529 , rendering fLuc inactive until light - triggered removal of the caging group .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [13, 19]}, {"entity": "lysine", "entity_type": "Chemical", "pos": [105, 111]}, {"entity": "Lys529", "entity_type": "Chemical", "pos": [122, 128]}], "task": "NER"}
{"text": "This photo - induced gain - of - luminescence provides a facile approach for assessing the photolysis efficiency of this valuable photosensitive lysine analogue within the context of its carrier protein in vitro and in living cells .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [145, 151]}], "task": "NER"}
{"text": "We further took advantage of the spatial and temporal activation feature of pfLuc for intracellular measurement of labile ATP levels without impairment of a cell ' s physiology .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutS alpha .", "entity": [], "task": "NER"}
{"text": "DNA mismatch repair ( MMR ) ensures replication fidelity by correcting mismatches generated during DNA replication .", "entity": [], "task": "NER"}
{"text": "Although human MMR has been reconstituted in vitro , how MMR occurs in vivo is unknown .", "entity": [], "task": "NER"}
{"text": "Here , we show that an epigenetic histone mark , H3K36me3 , is required in vivo to recruit the mismatch recognition protein hMutS alpha ( hMSH2 - hMSH6 ) onto chromatin through direct interactions with the hMSH6 PWWP domain .", "entity": [], "task": "NER"}
{"text": "The abundance of H3K36me3 in G1 and early S phases ensures that hMutS alpha is enriched on chromatin before mispairs are introduced during DNA replication .", "entity": [], "task": "NER"}
{"text": "Cells lacking the H3K36 trimethyltransferase SETD2 display microsatellite instability ( MSI ) and an elevated spontaneous mutation frequency , characteristic of MMR - deficient cells .", "entity": [], "task": "NER"}
{"text": "This work reveals that a histone mark regulates MMR in human cells and explains the long - standing puzzle of MSI - positive cancer cells that lack detectable mutations in known MMR genes .", "entity": [], "task": "NER"}
{"text": "Antiproliferative activity of 2 , 3 - disubstituted indoles toward apoptosis - resistant cancers cells .", "entity": [{"entity": "2 , 3 - disubstituted indoles", "entity_type": "Chemical", "pos": [30, 59]}], "task": "NER"}
{"text": "Many types of cancer , including glioma , melanoma , NSCLC , among others , are resistant to apoptosis induction and poorly responsive to current therapies with propaptotic agents .", "entity": [], "task": "NER"}
{"text": "We describe a series of 2 , 3 - disubstituted indoles , which display cytostatic rather than cytotoxic effects in cancer cells , and serve as a new chemical scaffold to develop anticancer agents capable of combating apoptosis - resistant cancers associated with dismal prognoses .", "entity": [{"entity": "2 , 3 - disubstituted indoles", "entity_type": "Chemical", "pos": [24, 53]}], "task": "NER"}
{"text": "Synthesis and evaluation of Janus type nucleosides as potential HCV NS5B polymerase inhibitors .", "entity": [{"entity": "Janus type nucleosides", "entity_type": "Chemical", "pos": [28, 50]}], "task": "NER"}
{"text": "The synthesis of new ribo and 2 ' - beta - C - methyl ribo Janus type nucleosides J - AA , J - AG and J - AU is reported along with their ability to block HCV and HIV replication .", "entity": [{"entity": "ribo and 2 ' - beta - C - methyl ribo Janus type nucleosides", "entity_type": "Chemical", "pos": [21, 81]}], "task": "NER"}
{"text": "Their toxicity was also assessed in Huh7 , human lymphocytes , CEM and Vero cells .", "entity": [], "task": "NER"}
{"text": "The Demographic Transition Influences Variance in Fitness and Selection on Height and BMI in Rural Gambia .", "entity": [], "task": "NER"}
{"text": "Recent human history is marked by demographic transitions characterized by declines in mortality and fertility [ 1 ] .", "entity": [], "task": "NER"}
{"text": "By influencing the variance in those fitness components , demographic transitions can affect selection on other traits [ 2 ] .", "entity": [], "task": "NER"}
{"text": "Parallel to changes in selection triggered by demography per se , relationships between fitness and anthropometric traits are also expected to change due to modification of the environment .", "entity": [], "task": "NER"}
{"text": "Here we explore for the first time these two main evolutionary consequences of demographic transitions using a unique data set containing survival , fertility , and anthropometric data for thousands of women in rural Gambia from 1956 - 2010 [ 3 ] .", "entity": [], "task": "NER"}
{"text": "We show how the demographic transition influenced directional selection on height and body mass index ( BMI ) .", "entity": [], "task": "NER"}
{"text": "We observed a change in selection for both traits mediated by variation in fertility : selection initially favored short females with high BMI values but shifted across the demographic transition to favor tall females with low BMI values .", "entity": [], "task": "NER"}
{"text": "We demonstrate that these differences resulted both from changes in fitness variance that shape the strength of selection and from shifts in selective pressures triggered by environmental changes .", "entity": [], "task": "NER"}
{"text": "These results suggest that demographic and environmental trends encountered by current human populations worldwide are likely to modify , but not stop , natural selection in humans .", "entity": [], "task": "NER"}
{"text": "First demonstration that brain CYP2D - mediated opiate metabolic activation alters analgesia in vivo .", "entity": [], "task": "NER"}
{"text": "The response to centrally - acting drugs is highly variable between individuals and does not always correlate with plasma drug levels .", "entity": [], "task": "NER"}
{"text": "Drug - metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations .", "entity": [], "task": "NER"}
{"text": "CYP2D metabolizes codeine to the active morphine metabolite .", "entity": [{"entity": "codeine", "entity_type": "Chemical", "pos": [18, 25]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [40, 48]}], "task": "NER"}
{"text": "We investigate the effect of inhibiting brain , and not liver , CYP2D activity on codeine - induced analgesia .", "entity": [{"entity": "codeine", "entity_type": "Chemical", "pos": [82, 89]}], "task": "NER"}
{"text": "Rats received intracerebroventricular injections of CYP2D inhibitors ( 20 mu g propranolol or 40 mu g propafenone ) or vehicle controls .", "entity": [{"entity": "propranolol", "entity_type": "Chemical", "pos": [79, 90]}, {"entity": "propafenone", "entity_type": "Chemical", "pos": [102, 113]}], "task": "NER"}
{"text": "Compared to vehicle - pretreated rats , inhibitor - pretreated rats had : a ) lower analgesia in the tail - flick test ( p < 0 . 05 ) and lower areas under the analgesia - time curve ( p < 0 . 02 ) within the first hour after 30mg / kg subcutaneous codeine , b ) lower morphine concentrations and morphine to codeine ratios in the brain ( p < 0 . 02 and p < 0 . 05 , respectively ) , but not in plasma ( p > 0 . 6 and p > 0 . 7 , respectively ) , tested at 30min after 30mg / kg subcutaneous codeine , and c ) lower morphine formation from codeine ex vivo by brain membranes ( p < 0 . 04 ) , but not by liver microsomes ( p > 0 . 9 ) .", "entity": [{"entity": "codeine", "entity_type": "Chemical", "pos": [249, 256]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [269, 277]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [297, 305]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [309, 316]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [492, 499]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [516, 524]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [540, 547]}], "task": "NER"}
{"text": "Analgesia trended toward a correlation with brain morphine concentrations ( p = 0 . 07 ) and correlated with brain morphine to codeine ratios ( p < 0 . 005 ) , but not with plasma morphine concentrations ( p > 0 . 8 ) or plasma morphine to codeine ratios ( p > 0 . 8 ) .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [50, 58]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [115, 123]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [127, 134]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [180, 188]}, {"entity": "morphine", "entity_type": "Chemical", "pos": [228, 236]}], "task": "NER"}
{"text": "Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration , and may thereby alter codeine ' s therapeutic efficacy , side - effect profile and abuse liability .", "entity": [{"entity": "morphine", "entity_type": "Chemical", "pos": [52, 60]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [85, 92]}, {"entity": "codeine", "entity_type": "Chemical", "pos": [132, 139]}], "task": "NER"}
{"text": "Brain CYPs are highly variable due to genetics , environmental factors and age , and may therefore contribute to interindividual variation in the response to centrally - acting drugs .", "entity": [], "task": "NER"}
{"text": "Ethnopharmacological and bioactivity guided investigation of five TCM anticancer herbs .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Five herbs , Curcuma longa L .", "entity": [], "task": "NER"}
{"text": "( CL ) , Scutellaria baicalensis Georgi ( SBC ) , Scutellaria barbata D .", "entity": [], "task": "NER"}
{"text": "Don ( SBB ) , Hedyotis diffusa Willd .", "entity": [], "task": "NER"}
{"text": "( HD ) and Solanum nigrum L .", "entity": [], "task": "NER"}
{"text": "( SN ) , are often prescribed in the polyherbal formulas for cancer treatment by traditional Chinese medicine ( TCM ) practitioners .", "entity": [], "task": "NER"}
{"text": "The purpose of the present study was to identify important anticancer herbs used in TCM and carry out bioactivity - directed fractionation and isolation ( BDFI ) using six cancer cell lines as well as peripheral blood mononuclear cells ( PBMCs ) , to identify constituents with anticancer activity but devoid of toxic effects against healthy immune cells .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : Of 243 document anticancer TCM treatments , 199 anticancer TCM herbs were ranked by the number of literature reports for each herb .", "entity": [], "task": "NER"}
{"text": "Five herbs were identified from the top 50 ranked herbs by at least two out of three TCM practitioners as frequently used in the TCM treatment of cancer .", "entity": [], "task": "NER"}
{"text": "BDFI using MTS assay was applied to determine the active anticancer extracts , fractions , and finally discrete compounds .", "entity": [{"entity": "MTS", "entity_type": "Chemical", "pos": [11, 14]}], "task": "NER"}
{"text": "RESULTS : Five herbs were selected for study of their anticancer activities .", "entity": [], "task": "NER"}
{"text": "The extracts of Curcuma longa L . , Scutellaria barbata D .", "entity": [], "task": "NER"}
{"text": "Don , and Hedyotis diffusa showed antiproliferative activity to various extents , extracts of Scutellaria baicalensis Georgi and Solanum nigrum L . showed little anticancer activity .", "entity": [], "task": "NER"}
{"text": "Seven out of the 21 fractions obtained from Hedyotis diffusa showed anticancer activity .", "entity": [], "task": "NER"}
{"text": "One new compound , ethyl 13 ( 2 ) ( S ) - hydroxy - chlorophyllide a ( 1 ) , along with 10 known compounds , i . e . 2 - methyl - 3 - methoxyanthraquinone ( 2 ) , 2 - hydroxymethylanthraquinone ( 3 ) , 2 - hydroxy - 3 - methylanthraquinone ( 4 ) , 2 - hydroxymethy - 1 - hydroxyanthraquinone ( 5 ) , 1 - methoxy - 2 - hydroxyanthraquinone ( 6 ) , 2 - hydroxy - 3 - methyl - 1 - methoxyanthraquinone ( 7 ) , oleanolic acid ( 8 ) , ursolic acid ( 9 ) , stigmasterol ( 10 ) and docosanoic acid ( 11 ) , were isolated and identified .", "entity": [{"entity": "ethyl 13 ( 2 ) ( S ) - hydroxy - chlorophyllide a", "entity_type": "Chemical", "pos": [19, 68]}, {"entity": "2 - methyl - 3 - methoxyanthraquinone", "entity_type": "Chemical", "pos": [117, 154]}, {"entity": "2 - hydroxymethylanthraquinone", "entity_type": "Chemical", "pos": [163, 193]}, {"entity": "2 - hydroxy - 3 - methylanthraquinone", "entity_type": "Chemical", "pos": [202, 239]}, {"entity": "2 - hydroxymethy - 1 - hydroxyanthraquinone", "entity_type": "Chemical", "pos": [248, 291]}, {"entity": "1 - methoxy - 2 - hydroxyanthraquinone", "entity_type": "Chemical", "pos": [300, 338]}, {"entity": "2 - hydroxy - 3 - methyl - 1 - methoxyanthraquinone", "entity_type": "Chemical", "pos": [347, 398]}, {"entity": "oleanolic acid", "entity_type": "Chemical", "pos": [407, 421]}, {"entity": "ursolic acid", "entity_type": "Chemical", "pos": [430, 442]}, {"entity": "stigmasterol", "entity_type": "Chemical", "pos": [451, 463]}, {"entity": "docosanoic acid", "entity_type": "Chemical", "pos": [475, 490]}], "task": "NER"}
{"text": "Compounds 2 - 6 , 8 and 9 dose - dependently inhibited the cell viability of cancer cells within a concentration range of 1 - 200 micro M .", "entity": [], "task": "NER"}
{"text": "Furthermore , compounds 2 , 3 , 5 and 9 showed significantly stronger inhibition of tested cancer cell lines than on that of PBMCs .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : This study identified anticancer herbs , extracts , fractions and eventually compounds from the documented anticancer TCM herbs by using BDFI .", "entity": [], "task": "NER"}
{"text": "It also determined the antiproliferative activity in cancer and healthy immune cells of the isolated compounds from Hedyotis diffusa .", "entity": [], "task": "NER"}
{"text": "The results will be useful in the validation of the clinical application of these herbs and the development of novel anticancer therapeutics .", "entity": [], "task": "NER"}
{"text": "Production of Cyr61 protein is modulated by extracellular acidification and PI3K / Akt signaling in prostate carcinoma PC - 3 cells .", "entity": [], "task": "NER"}
{"text": "High expression of Cyr61 , an extracellular cysteine - rich heparin - binding protein , has been associated with a malignant cell phenotype and poor outcome in prostate cancers .", "entity": [{"entity": "cysteine", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "Although Cyr61 was found by us to be overproduced in androgen - independent PC - 3 cells treated with N - acetylcysteine ( NAC ) , its significance is still unclear .", "entity": [{"entity": "androgen", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "N - acetylcysteine", "entity_type": "Chemical", "pos": [102, 120]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [123, 126]}], "task": "NER"}
{"text": "We therefore aimed to determine how and why Cyr61 protein is overexpressed in NAC - treated cells .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [78, 81]}], "task": "NER"}
{"text": "Here , we found that Cyr61 protein level markedly increased in cells treated with NAC at high cell seeding density .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [82, 85]}], "task": "NER"}
{"text": "Silencing of Cyr61 by siRNA induced enhanced activity of caspase - 3 / 7 , upregulation of the proapototic Bok , BimL and BimS , cleavage of apoptosis hallmarkers such as Bax , PARP and caspase - 3 , and downregulation of antiapoptotic Bcl2 , Bcl - xL and Mcl - 1 proteins .", "entity": [], "task": "NER"}
{"text": "NAC treatment caused a reduction of extracellular medium pH to acidic and an increase in Akt phosphorylation , after which the replacement with NAC - free medium returned them to control levels within 24h .", "entity": [{"entity": "NAC", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "NAC", "entity_type": "Chemical", "pos": [144, 147]}], "task": "NER"}
{"text": "Acid stimulation increased the levels of Cyr61 and p - Akt proteins , whereas it suppressed the induction of proapoptotic and antiapoptotic proteins .", "entity": [], "task": "NER"}
{"text": "Overall , our data indicate that PC - 3 cells overproduce Cyr61 protein via activation of the PI3K / Akt signaling as a part of the survival mechanisms under the conditions causing extracellular acidity and further cytotoxicity .", "entity": [], "task": "NER"}
{"text": "Comparative evaluation of oral and dermal cypermethrin exposure on antioxidant profile in Bubalus bubalis .", "entity": [{"entity": "cypermethrin", "entity_type": "Chemical", "pos": [42, 54]}], "task": "NER"}
{"text": "Cypermethrin , a type II synthetic pyrethroid insecticide , @ 0 . 5mg / kg / day for 14 consecutive weeks produced mild signs of toxicity in buffalo calves .", "entity": [{"entity": "Cypermethrin", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "pyrethroid", "entity_type": "Chemical", "pos": [35, 45]}], "task": "NER"}
{"text": "Significant changes were observed in various antioxidant parameters in blood .", "entity": [], "task": "NER"}
{"text": "There was a marked increase in the extent of lipid peroxidation ( 33 . 9 % ) and enzymic activity of glutathione peroxidase ( 6 . 7 % ) , superoxide dismutase ( 35 . 0 % ) , catalase ( 43 . 7 % ) , glutathione - S - transferase ( 64 . 4 % ) , glutathione reductase ( 36 . 7 % ) and glucose - 6 - phosphate dehydrogenase ( 32 . 1 % ) .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [101, 112]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [138, 148]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [198, 209]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [243, 254]}, {"entity": "glucose - 6 - phosphate", "entity_type": "Chemical", "pos": [282, 305]}], "task": "NER"}
{"text": "A significant decrease in blood glutathione ( 16 . 7 % ) , total antioxidant activity ( 45 . 4 % ) and vitamin E ( 40 . 8 % ) was observed and no significant effect was found on blood selenium levels .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [32, 43]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [103, 112]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [184, 192]}], "task": "NER"}
{"text": "However , the extent of lipid peroxidation ( 42 % ) and the depletion of glutathione ( 28 . 8 % ) was greater after dermal sub - acute toxicity of cypermethrin ( 0 . 25 % ) for 14 consecutive days .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [73, 84]}, {"entity": "cypermethrin", "entity_type": "Chemical", "pos": [147, 159]}], "task": "NER"}
{"text": "Similarly , it was observed that the incline in the enzymic activity of glutathione peroxidase ( 29 . 7 % ) , superoxide dismutase ( 38 . 3 % ) and glutathione reductase ( 38 . 3 % ) was higher in dermally cypermethrin exposed animals .", "entity": [{"entity": "glutathione", "entity_type": "Chemical", "pos": [72, 83]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [110, 120]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [148, 159]}, {"entity": "cypermethrin", "entity_type": "Chemical", "pos": [206, 218]}], "task": "NER"}
{"text": "Thus , the present investigation contemplates that oxidative stress is the important mechanisms involved in cypermethrin - induced toxicity and the oxidative insult produced by dermal route is more severe as compared to oral intoxication .", "entity": [{"entity": "cypermethrin", "entity_type": "Chemical", "pos": [108, 120]}], "task": "NER"}
{"text": "Biological effects induced by BSA - stabilized silica nanoparticles in mammalian cell lines .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [47, 53]}], "task": "NER"}
{"text": "Much of the concerns regarding engineered nanoparticle ( NP ) toxicity are based on knowledge from previous studies on particles in ambient air or occupational situations .", "entity": [], "task": "NER"}
{"text": "E . g . , the effects of exposure to silica dust particles have been studied intensely due to the carcinogenicity of crystalline silica .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [37, 43]}, {"entity": "silica", "entity_type": "Chemical", "pos": [129, 135]}], "task": "NER"}
{"text": "However , the increasing usage of engineered amorphous silica NPs has emphasized the need for further mechanistic insight to predict the consequences of exposure to the amorphous type of silica NPs .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [55, 61]}, {"entity": "silica", "entity_type": "Chemical", "pos": [187, 193]}], "task": "NER"}
{"text": "The present study focused on the in vitro biological effects following exposure to well - dispersed , BSA - stabilized , amorphous silica NPs whereas unmodified silica NPs where included for reasons of comparison .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [131, 137]}, {"entity": "silica", "entity_type": "Chemical", "pos": [161, 167]}], "task": "NER"}
{"text": "The cytotoxicity of the silica NPs was investigated in six different cell lines ( A549 , THP - 1 , CaCo - 2 , ASB - XIV , J - 774A . 1 , and Colon - 26 ) selected to explore the significance of organ and species sensitivity in vitro .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [24, 30]}], "task": "NER"}
{"text": "Viability data demonstrated that macrophages were most sensitive to silica NP and interestingly , murine cell lines were generally found to be more sensitive than comparable human cell lines .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [68, 74]}], "task": "NER"}
{"text": "Further studies were conducted in the human epithelial lung cell line , A549 , to explore the molecular mechanism of silica toxicity .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [117, 123]}], "task": "NER"}
{"text": "Generation of reactive oxygen species , one of the proposed toxicological mechanisms of NPs , was investigated in A549 cells by the dichlorofluorescin ( DCF ) assay to be significantly induced at NP concentrations above 113 mu g / mL .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [23, 29]}, {"entity": "dichlorofluorescin", "entity_type": "Chemical", "pos": [132, 150]}, {"entity": "DCF", "entity_type": "Chemical", "pos": [153, 156]}], "task": "NER"}
{"text": "However , induction of oxidative stress related pathways was not found after silica NP exposure for 24h in gene array studies conducted in A549 cells at a relatively low NP concentration ( EC20 ) .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [77, 83]}], "task": "NER"}
{"text": "Up - regulated genes ( more than 2 - fold ) were primarily related to lipid metabolism and biosynthesis whereas down - regulated genes included several processes such as transcription , cell junction , extra cellular matrix ( ECM ) - receptor interaction and others .", "entity": [], "task": "NER"}
{"text": "Thus , gene expression data proposes that several cellular processes other than oxidative stress could be affected by exposure to silica NPs .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [130, 136]}], "task": "NER"}
{"text": "Anthelmintic activity of Arisaema franchetianum and Arisaema lobatum essential oils against Haemonchus contortus .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Arisaema franchetianum and Arisaema lobatum are two perennial plants native to China .", "entity": [], "task": "NER"}
{"text": "Arisaema franchetianum is universally used to promote the subsidence of induration and swelling , quicken blood and relieve pains , and kill intestinal parasites in humans and animals .", "entity": [], "task": "NER"}
{"text": "Arisaema lobatum is used to treat malaria , intestinal parasites , and snake and insect bites in humans and animals .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine the composition of the essential oils from Arisaema franchetianum and Arisaema lobatum and evaluate the anthelmintic effect against Haemonchus contortus .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : Two oils were investigated by GC and GC - MS .", "entity": [], "task": "NER"}
{"text": "The anthelmintic bioassay tests of Arisaema franchetianum and Arisaema lobatum essential oil , linalool and carvacrol were performed using egg hatch assay ( EHA ) , larval development assay ( LDA ) and larval migration inhibition assay ( LMIA ) .", "entity": [{"entity": "linalool", "entity_type": "Chemical", "pos": [95, 103]}, {"entity": "carvacrol", "entity_type": "Chemical", "pos": [108, 117]}], "task": "NER"}
{"text": "RESULTS : Fifty six components representing 96 . 88 % of the Arisaema franchetianum oil and 64 components representing 96 . 88 % of the Arisaema lobatum oil were identified .", "entity": [], "task": "NER"}
{"text": "Carvacrol and linalool were found to be the major constituents of two oils .", "entity": [{"entity": "Carvacrol", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "linalool", "entity_type": "Chemical", "pos": [14, 22]}], "task": "NER"}
{"text": "In the EHA , greater than 99 % inhibition were observed with Arisaema franchetianum oil at 10mg / mL ( CE50 1 . 63mg / mL ) and Arisaema lobatum oil at 5 and 10mg / mL ( CE50 0 . 48mg / mL ) .", "entity": [], "task": "NER"}
{"text": "In the LDA , both oils induced complete inhibition at 10mg / mL , with the CE50 being 1 . 10mg / mL for Arisaema franchetianum oil and 0 . 73mg / mL for Arisaema lobatum oil .", "entity": [], "task": "NER"}
{"text": "In the LMIA , the Arisaema franchetianum oil and Arisaema lobatum oil at best inhibited 74 . 1 % and 95 . 6 % of larval migration at 10mg / mL , respectively .", "entity": [], "task": "NER"}
{"text": "Carvacrol exhibited similar activity to Arisaema lobatum essential oil and linalool did not show high activity in every assay .", "entity": [{"entity": "Carvacrol", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "linalool", "entity_type": "Chemical", "pos": [75, 83]}], "task": "NER"}
{"text": "CONCLUSIONS : These data show for the first time that the essential oils obtained from Arisaema franchetianum or Arisaema lobatum had promising anthelmintic activity against Haemonchus contortus .", "entity": [], "task": "NER"}
{"text": "Arisaema plant may offer an alternative source for the control of gastrointestinal nematodes of sheep and goats .", "entity": [], "task": "NER"}
{"text": "Sciadopitysin protects osteoblast function via its antioxidant activity in MC3T3 - E1 cells .", "entity": [{"entity": "Sciadopitysin", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Age - related osteoblast dysfunction is the main cause of age - related bone loss in both men and women .", "entity": [], "task": "NER"}
{"text": "In the present study , the effect of sciadopitysin , a type of biflavonoids , on osteoblast function was investigated in osteoblastic MC3T3 - E1 cells .", "entity": [{"entity": "sciadopitysin", "entity_type": "Chemical", "pos": [37, 50]}, {"entity": "biflavonoids", "entity_type": "Chemical", "pos": [63, 75]}], "task": "NER"}
{"text": "Sciadopitysin caused a significant elevation of alkaline phosphatase activity , collagen synthesis , osteocalcin production , mineralization , and glutathione content in the cells ( P < 0 . 05 ) .", "entity": [{"entity": "Sciadopitysin", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [147, 158]}], "task": "NER"}
{"text": "Sciadopitysin also decreased the production of tumor necrosis factor - a ( TNF - alpha ) induced by antimycin A , a mitochondrial electron transport inhibitor .", "entity": [{"entity": "Sciadopitysin", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "antimycin A", "entity_type": "Chemical", "pos": [100, 111]}], "task": "NER"}
{"text": "We investigated the protective effects of sciadopitysin on antimycin A - induced toxicity in osteoblastic MC3T3 - E1 cells .", "entity": [{"entity": "sciadopitysin", "entity_type": "Chemical", "pos": [42, 55]}, {"entity": "antimycin A", "entity_type": "Chemical", "pos": [59, 70]}], "task": "NER"}
{"text": "Exposure of MC3T3 - E1 cells to antimycin A caused a significant reduction in osteoblast dysfunction .", "entity": [{"entity": "antimycin A", "entity_type": "Chemical", "pos": [32, 43]}], "task": "NER"}
{"text": "However , pretreatment with sciadopitysin prior to antimycin A exposure significantly reduced antimycin A - induced cell damage by preventing mitochondrial membrane potential dissipation , adenosine triphosphate ( ATP ) loss , reactive oxygen species ( ROS ) release , and nitrotyrosine increase , suggesting that sciadopitysin may be useful for protecting mitochondria against a burst of oxidative stress .", "entity": [{"entity": "sciadopitysin", "entity_type": "Chemical", "pos": [28, 41]}, {"entity": "antimycin A", "entity_type": "Chemical", "pos": [51, 62]}, {"entity": "antimycin A", "entity_type": "Chemical", "pos": [94, 105]}, {"entity": "adenosine triphosphate", "entity_type": "Chemical", "pos": [189, 211]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [214, 217]}, {"entity": "oxygen", "entity_type": "Chemical", "pos": [236, 242]}, {"entity": "nitrotyrosine", "entity_type": "Chemical", "pos": [273, 286]}, {"entity": "sciadopitysin", "entity_type": "Chemical", "pos": [314, 327]}], "task": "NER"}
{"text": "Moreover , sciadopitysin increased phosphorylation of cAMP - response element - binding protein ( CREB ) inhibited by antimycin A .", "entity": [{"entity": "sciadopitysin", "entity_type": "Chemical", "pos": [11, 24]}, {"entity": "cAMP", "entity_type": "Chemical", "pos": [54, 58]}, {"entity": "antimycin A", "entity_type": "Chemical", "pos": [118, 129]}], "task": "NER"}
{"text": "Our results demonstrate that sciadopitysin may reduce or prevent osteoblasts degeneration .", "entity": [{"entity": "sciadopitysin", "entity_type": "Chemical", "pos": [29, 42]}], "task": "NER"}
{"text": "In vitro binding affinities of a series of flavonoids for mu - opioid receptors .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [43, 53]}], "task": "NER"}
{"text": "Antinociceptive effect of the synthetic flavonoid 3 , 3 - dibromoflavanone in mice .", "entity": [{"entity": "flavonoid", "entity_type": "Chemical", "pos": [40, 49]}, {"entity": "3 , 3 - dibromoflavanone", "entity_type": "Chemical", "pos": [50, 74]}], "task": "NER"}
{"text": "The pharmacotherapy for the treatment of pain is an active area of investigation .", "entity": [], "task": "NER"}
{"text": "There are effective drugs to treat this problem , but there is also a need to find alternative treatments free of undesirable side effects .", "entity": [], "task": "NER"}
{"text": "In the present work the capacity of a series of flavonoids to bind to the mu opioid receptor was evaluated .", "entity": [{"entity": "flavonoids", "entity_type": "Chemical", "pos": [48, 58]}], "task": "NER"}
{"text": "The most active compound , 3 , 3 - dibromoflavanone ( 31 ) , a synthetic flavonoid , presented a significant inhibition of the binding of the selective mu opioid ligand [ ( 3 ) H ] DAMGO , with a Ki of 0 . 846 +/- 0 . 263 mu M .", "entity": [{"entity": "3 , 3 - dibromoflavanone", "entity_type": "Chemical", "pos": [27, 51]}, {"entity": "flavonoid", "entity_type": "Chemical", "pos": [73, 82]}, {"entity": "[ ( 3 ) H ] DAMGO", "entity_type": "Chemical", "pos": [169, 186]}], "task": "NER"}
{"text": "Flavanone 31 was further synthesized using a simple and cheap procedure with good yield .", "entity": [{"entity": "Flavanone", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "Its in vivo effects in mice , after acute treatments , were studied using antinociceptive and behavioral assays .", "entity": [], "task": "NER"}
{"text": "It showed no sedative , anxiolytic , motor incoordination effects or inhibition of the gastrointestinal transit in mice at the doses tested .", "entity": [], "task": "NER"}
{"text": "It evidenced antinociceptive activity on the acetic acid - induced nociception , hot plate and formalin tests ( at 10 mg / kg and 30 mg / kg ) .", "entity": [{"entity": "acetic acid", "entity_type": "Chemical", "pos": [45, 56]}, {"entity": "formalin", "entity_type": "Chemical", "pos": [95, 103]}], "task": "NER"}
{"text": "The results showed that the 5 - HT2 receptor and the adrenoceptors seem unlikely to be involved in its antinociceptive effects .", "entity": [], "task": "NER"}
{"text": "Naltrexone , a nonselective opioid receptors antagonist , totally blocked compound 31 antinociceptive effects on the hot plate test , but naltrindole ( delta opioid antagonist ) and nor - binaltorphimine ( kappa opioid antagonist ) did not .", "entity": [{"entity": "Naltrexone", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "naltrindole", "entity_type": "Chemical", "pos": [138, 149]}, {"entity": "nor - binaltorphimine", "entity_type": "Chemical", "pos": [182, 203]}], "task": "NER"}
{"text": "These findings demonstrated that 3 , 3 - dibromoflavanone ( 31 ) , at doses that did not interfere with the motor performance , exerted clear dose dependent antinociception when assessed in the chemical and thermal models of nociception in mice and it seems that its action is related to the activation of the mu opioid receptor .", "entity": [{"entity": "3 , 3 - dibromoflavanone", "entity_type": "Chemical", "pos": [33, 57]}], "task": "NER"}
{"text": "Trabecular bone adapts to long - term cyclic loading by increasing stiffness and normalization of dynamic morphometric rates .", "entity": [], "task": "NER"}
{"text": "Bone has the ability to adapt to external loading conditions .", "entity": [], "task": "NER"}
{"text": "Especially the beneficial effect of short - term cyclic loading has been investigated in a number of in vivo animal studies .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to assess the long - term effect ( > 10weeks ) of cyclic mechanical loading on the bone microstructure , bone stiffness , and bone remodeling rates .", "entity": [], "task": "NER"}
{"text": "Mice were subjected to cyclic mechanical loading at the sixth caudal vertebra with 8N or 0N ( control ) three times per week for a total period of 14weeks .", "entity": [], "task": "NER"}
{"text": "Structural bone parameters were determined from in vivo micro - computed tomography ( micro - CT ) scans performed at week 0 , 4 , 6 , 8 , 10 , 12 , and 14 .", "entity": [], "task": "NER"}
{"text": "Mechanical parameters were derived from micro - finite element analysis .", "entity": [], "task": "NER"}
{"text": "Dynamic bone morphometry was calculated using registration of serial micro - CT scans .", "entity": [], "task": "NER"}
{"text": "Bone volume fraction and trabecular thickness increased significantly more for the loaded group than for the control group ( p = 0 . 006 and p = 0 . 002 respectively ) .", "entity": [], "task": "NER"}
{"text": "The trabecular bone microstructure adapted to the load of 8N in approximately ten weeks , indicated by the trabecular bone volume fraction , which increased from 16 . 7 % at 0weeks to 21 . 6 % at week 10 and only showed little change afterwards ( bone volume fraction of 21 . 5 % at 14weeks ) .", "entity": [], "task": "NER"}
{"text": "Similarly bone stiffness - at the start of the experiment 649N / mm - reached 846N / mm at 10weeks in the loaded group and was maintained to the end of the experiment ( 850N / mm ) .", "entity": [], "task": "NER"}
{"text": "At 4weeks the bone formation rate was 32 % greater and the bone resorption rate 22 % less for 8N compared to 0N .", "entity": [], "task": "NER"}
{"text": "This difference was significantly reduced as the bone adapted to 8N , with 8N remodeling rates returning to the values of the 0N group at approximately 10weeks .", "entity": [], "task": "NER"}
{"text": "Together these data suggest that once bone has adapted to a new loading state , the remodeling rates reduce gradually while maintaining bone volume fraction and stiffness .", "entity": [], "task": "NER"}
{"text": "The extraction and analysis of cylindrospermopsin from human serum and urine .", "entity": [{"entity": "cylindrospermopsin", "entity_type": "Chemical", "pos": [31, 49]}], "task": "NER"}
{"text": "The naturally derived cyanotoxin , cylindrospermopsin ( CYN ) , has been detected in freshwater systems worldwide and poses a threat to human health .", "entity": [{"entity": "cylindrospermopsin", "entity_type": "Chemical", "pos": [35, 53]}, {"entity": "CYN", "entity_type": "Chemical", "pos": [56, 59]}], "task": "NER"}
{"text": "The methods for the extraction and detection of this toxin in source water are well documented , but methods for CYN determination in exposed individuals have not been investigated .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [113, 116]}], "task": "NER"}
{"text": "In this study , the extraction and detection of CYN from two different matrices , serum and urine , was explored .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "Both serum and urine matrices inherently produce interference with analytical analyses and require extensive clean - up .", "entity": [], "task": "NER"}
{"text": "Methods for extraction of CYN from both matrices were developed and validated using fortified samples .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [26, 29]}], "task": "NER"}
{"text": "Serum extraction included homogenization followed by protein precipitation and solid phase extraction ( SPE ) .", "entity": [], "task": "NER"}
{"text": "Urine samples were processed using filtration , pH manipulation , and SPE .", "entity": [], "task": "NER"}
{"text": "Analyses using a commercially available enzyme - linked immunosorbent assay ( ELISA ) and liquid chromatography coupled with mass spectrometry ( LC / MS / MS ) were assessed .", "entity": [], "task": "NER"}
{"text": "Matrix effects inhibited ELISA ' s use as a quantitative tool for both matrices .", "entity": [], "task": "NER"}
{"text": "LC / MS / MS was determined to be the most effective and reproducible means to detect and quantify CYN .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [99, 102]}], "task": "NER"}
{"text": "The method detection limits determined in this study using LC / MS / MS were 0 . 25 and 0 . 50 ng mL ( - 1 ) for serum and urine , respectively .", "entity": [], "task": "NER"}
{"text": "This method can be used to test individuals exposed to blooms of cyanobacteria producing CYN .", "entity": [{"entity": "CYN", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Developmental toxicity and estrogenic potency of zearalenone in zebrafish ( Danio rerio ) .", "entity": [{"entity": "zearalenone", "entity_type": "Chemical", "pos": [49, 60]}], "task": "NER"}
{"text": "Zearalenone ( ZEA , F2 ) is one of the most common mycotoxins and the only known mycoestrogen .", "entity": [{"entity": "Zearalenone", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "ZEA", "entity_type": "Chemical", "pos": [14, 17]}, {"entity": "mycoestrogen", "entity_type": "Chemical", "pos": [81, 93]}], "task": "NER"}
{"text": "It enters the food and feed chain from contaminated cereals and infiltrates into sewage or natural waters posing potential threat to exposed livestock , wildlife and humans .", "entity": [], "task": "NER"}
{"text": "Therefore evaluation of its biological effects is of international importance .", "entity": [], "task": "NER"}
{"text": "We performed toxicological tests on zebrafish ( Danio rerio ) larvae and adults .", "entity": [], "task": "NER"}
{"text": "Developmental toxicity was assessed by an extended ( 5 days ) fish embryo toxicity test ( FET ) .", "entity": [], "task": "NER"}
{"text": "Effects of early ZEA exposure were concentration - dependent with LC50 and LC10 values of 893 and 335 mu g / L .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [17, 20]}], "task": "NER"}
{"text": "In larvae exposed to 500 mu g / L and above , ZEA induced similar phenotype to has ( heart - and soul ) showing defects in heart and eye development and upward curvature of the body axis .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [46, 49]}], "task": "NER"}
{"text": "From 250 mu g / L at 72hpf the gap in the melanophore streak at the base of the tail fin was missing and the fin fold was abnormal , suggesting disturbance in the development of the adult tail fin primordium .", "entity": [], "task": "NER"}
{"text": "Estrogenic potency was measured on the basis of Vitellogenin ( Vtg ) protein ( adults ) levels and relative abundance of vitellogenin - 1 mRNA ( vtg - 1 ) ( larvae and adults ) .", "entity": [], "task": "NER"}
{"text": "qRT - PCR in larvae proved to be sufficient substitute to adult tests and sensitive enough to detect ZEA in 0 . 1 mu g / L concentrations , that is close to levels observed in wastewaters .", "entity": [{"entity": "ZEA", "entity_type": "Chemical", "pos": [101, 104]}], "task": "NER"}
{"text": "Developmental defects reveal that besides direct estrogenic effects , zearalenone might interact with other ontogenic pathways .", "entity": [{"entity": "zearalenone", "entity_type": "Chemical", "pos": [70, 81]}], "task": "NER"}
{"text": "Controlled electrochemical deposition and transformation of hetero - nanoarchitectured electrodes for energy storage .", "entity": [], "task": "NER"}
{"text": "A review of electrochemically synthesized nanomaterials with different controllable architectures for electrochemical energy storage devices is shown .", "entity": [], "task": "NER"}
{"text": "It is demonstrated that these nano - architectures can be created either by electrodeposition or by the electrochemical transformation of materials .", "entity": [], "task": "NER"}
{"text": "Electrochemical synthesis is presented here as it provides intimate contact between the electrode and current collector and also promotes an electronic pathway for all materials to be connected to the circuit .", "entity": [], "task": "NER"}
{"text": "Although still in their infancy , electrosynthesized nano - architectures show promise to be used in future electrochemical energy storage devices as utilization of this method bypasses the need for bulky conductive additives and electrochemically inactive binders .", "entity": [], "task": "NER"}
{"text": "Furthermore , electrochemical transformations can be used to create additional architectural features or change the chemical make - up of the electrode .", "entity": [], "task": "NER"}
{"text": "This review is meant to show the creativity of current science when it comes to these nano - architectured electrodes .", "entity": [], "task": "NER"}
{"text": "It is organized by technique used for synthesis including hard template , soft template , and template - free synthesis along with electrochemical transformation techniques .", "entity": [], "task": "NER"}
{"text": "Effects of intravenous nicotine on prepulse inhibition in smokers and non - smokers : relationship with familial smoking .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [23, 31]}], "task": "NER"}
{"text": "RATIONALE : The reinforcing properties of nicotine may be , in part , derived from its ability to enhance certain forms of cognitive processing .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "Several animal and human studies have shown that nicotine increases prepulse inhibition ( PPI ) of the startle reflex .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [49, 57]}], "task": "NER"}
{"text": "However , it remains unclear whether these effects are related to smoking susceptibility .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The current study examined the effects of intravenously delivered nicotine on PPI in smokers and non - smokers , as well as its association with a quantitative index of familial smoking .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "METHODS : The sample consisted of 30 non - smokers and 16 smokers , who completed an initial assessment , followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [214, 222]}], "task": "NER"}
{"text": "Separate doses were used in smoker and non - smoker samples .", "entity": [], "task": "NER"}
{"text": "RESULTS : Analyses indicated that both nicotine infusions acutely enhanced PPI among non - smokers , and this enhancement was positively related to the degree of smoking among first and second - degree relatives .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [39, 47]}], "task": "NER"}
{"text": "Smokers also displayed PPI enhancement after receiving the first infusion , but this effect was unrelated to familial smoking .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk .", "entity": [], "task": "NER"}
{"text": "Ventral tegmental area alpha 6 beta 2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [48, 61]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [88, 96]}], "task": "NER"}
{"text": "RATIONALE : Phasic dopamine ( DA ) signaling underlies reward learning .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [19, 27]}], "task": "NER"}
{"text": "Cholinergic and glutamatergic inputs into the ventral tegmental area ( VTA ) are crucial for modulating burst firing activity and subsequent phasic DA release in the nucleus accumbens ( NAc ) , but the specific VTA nicotinic receptor subtypes that regulate phasic DA release have not been identified .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : The goal was to determine the role of VTA N - methyl - D - aspartate receptors ( NMDARs ) and specific subtypes of nicotinic acetylcholine receptors ( nAChRs ) in regulating phasic DA release in the NAc core .", "entity": [{"entity": "N - methyl - D - aspartate", "entity_type": "Chemical", "pos": [54, 80]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [137, 150]}], "task": "NER"}
{"text": "METHODS : Fast - scan cyclic voltammetry in anesthetized rats was combined with intra - VTA micro - infusion to evaluate the ability of glutamatergic and cholinergic drugs to modulate stimulated phasic DA release in the NAc core .", "entity": [], "task": "NER"}
{"text": "RESULTS : VTA NMDAR blockade with AP - 5 decreased , while VTA NMDAR activation with NMDA increased NAc peak phasic DA release .", "entity": [{"entity": "AP - 5", "entity_type": "Chemical", "pos": [34, 40]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [63, 67]}], "task": "NER"}
{"text": "Intra - VTA administration of the nonspecific nAChR antagonist mecamylamine produced a persistent decrease in phasic DA release .", "entity": [{"entity": "mecamylamine", "entity_type": "Chemical", "pos": [63, 75]}], "task": "NER"}
{"text": "Infusion of the alpha 6 - selective antagonist alpha - conotoxin MII ( alpha - ctx MII ) produced a robust , but transient decrease in phasic DA , whereas infusion of selective doses of either the alpha 4 beta 2 - selective antagonist , dihydro - beta - erythroidine , or the alpha 7 antagonist , methyllycaconitine , had no effect .", "entity": [{"entity": "dihydro - beta - erythroidine", "entity_type": "Chemical", "pos": [237, 266]}, {"entity": "methyllycaconitine", "entity_type": "Chemical", "pos": [297, 315]}], "task": "NER"}
{"text": "Co - infusion of AP - 5 and alpha - ctx MII produced a similar phasic DA decrease as either drug alone , with no additive effect .", "entity": [{"entity": "AP - 5", "entity_type": "Chemical", "pos": [17, 23]}], "task": "NER"}
{"text": "CONCLUSIONS : The results suggest that VTA alpha 6 beta 2 nAChRs , but not alpha 4 beta 2 or alpha 7 nAChRs , regulate phasic DA release in the NAc core and that VTA alpha 6 beta 2 nAChRs and NMDA receptors act at a common site or target to regulate NAc phasic DA signaling .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [192, 196]}], "task": "NER"}
{"text": "The Value of Expression of M2 - PK and VEGF in Patients with Advanced Gastric Cancer .", "entity": [], "task": "NER"}
{"text": "Glycolytic pyruvate kinase isoenzyme type M2 ( M2 - PK ) plays a key role in tumor metabolism and energy production .", "entity": [{"entity": "pyruvate", "entity_type": "Chemical", "pos": [11, 19]}], "task": "NER"}
{"text": "Vascular endothelial growth factor ( VEGF ) is critical in regulating angiogenesis which is an essential process required for tumor growth and metastasis .", "entity": [], "task": "NER"}
{"text": "These two genes may function in accordance with tumor development .", "entity": [], "task": "NER"}
{"text": "The purpose of this study was to investigate the relationship between the expression of M2 - PK and VEGF , and their association with clinicopathological features in patients with advanced gastric cancer .", "entity": [], "task": "NER"}
{"text": "Expression of M2 - PK and VEGF were examined in 142 cases of paraffin - embedded tissue blocks from patients with advanced gastric cancer .", "entity": [], "task": "NER"}
{"text": "M2 - PK expression was found to strongly correlate with that of VEGF ( r = 0 . 718 ) .", "entity": [], "task": "NER"}
{"text": "In addition , expression of M2 - PK and VEGF correlates with tumor size ( p = 0 . 0001 , and p = 0 . 0017 , respectively ) , depth of invasion ( p = 0 . 0024 , and p = 0 . 0261 , respectively ) , and lymph node metastasis ( p = 0 . 036 , and p = 0 . 028 , respectively ) .", "entity": [], "task": "NER"}
{"text": "The high expression levels of M2 - PK and VEGF may indicate poor prognosis in patients with advanced gastric cancer .", "entity": [], "task": "NER"}
{"text": "Effects of Soil Trace Elements on Longevity Population in China .", "entity": [], "task": "NER"}
{"text": "Based on background concentrations of elements in soils and the sixth population census data of China , this study discussed the distribution characteristics of soil elements and longevity population at province level in China .", "entity": [], "task": "NER"}
{"text": "Percentages of the aging population are high in Southwest China and the eastern coastal region but low in western and northwestern regions .", "entity": [], "task": "NER"}
{"text": "Provinces in South and Southwest China gain a high level of longevity , while the northern part of China has a low level of longevity .", "entity": [], "task": "NER"}
{"text": "The background concentration of Se in soil has a significant positive correlation with longevity index , while Ba and Ni have a significant negative correlation with longevity indexes .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [32, 34]}, {"entity": "Ba", "entity_type": "Chemical", "pos": [111, 113]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [118, 120]}], "task": "NER"}
{"text": "By regression analysis , longevity index C / 100 , 000 can be expressed as C / 100 , 000 = 1 . 679 - 0 . 205 Ni + 0 . 413 Co + 0 . 006 Se ( with R ( 2 ) = 0 . 402 and p < 0 . 01 ) , C / 65 + can be expressed as C / 65 + = 3 . 425 - 0 . 262 Ni + 0 . 435 Co + 0 . 006 Se ( with R ( 2 ) = 0 . 369 and p < 0 . 01 ) .", "entity": [{"entity": "Ni", "entity_type": "Chemical", "pos": [109, 111]}, {"entity": "Co", "entity_type": "Chemical", "pos": [122, 124]}, {"entity": "Se", "entity_type": "Chemical", "pos": [135, 137]}, {"entity": "Ni", "entity_type": "Chemical", "pos": [240, 242]}, {"entity": "Co", "entity_type": "Chemical", "pos": [253, 255]}, {"entity": "Se", "entity_type": "Chemical", "pos": [266, 268]}], "task": "NER"}
{"text": "Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging : Impact on Renal Drug Dosing .", "entity": [{"entity": "Creatinine", "entity_type": "Chemical", "pos": [50, 60]}], "task": "NER"}
{"text": "OBJECTIVES : To evaluate the performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population .", "entity": [], "task": "NER"}
{"text": "DESIGN : Cross - sectional analysis of data from community - dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1 , 2005 , to December 31 , 2010 .", "entity": [], "task": "NER"}
{"text": "SUBJECTS : A total of 269 men and women with a mean +/- SD age of 81 +/- 6 years , mean serum creatinine concentration ( Scr ) of 1 . 1 +/- 0 . 4 mg / dl , and mean 24 - hour measured creatinine clearance ( mClcr ) of 53 +/- 13 ml / minute .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [94, 104]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [184, 194]}], "task": "NER"}
{"text": "MEASUREMENTS AND MAIN RESULTS : Kidney function was estimated by using the following equations : Cockcroft - Gault ( CG ) , Modification of Diet in Renal Disease ( MDRD ) , and Chronic Kidney Disease Epidemiology Collaboration ( CKD - EPI ) .", "entity": [], "task": "NER"}
{"text": "The performance of each equation was assessed by measuring bias and precision relative to mClcr .", "entity": [], "task": "NER"}
{"text": "Dose calculation errors ( discordance ) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared with the dosages approved by the Food and Drug Administration .", "entity": [], "task": "NER"}
{"text": "The CG equation was the least biased estimate of mClcr .", "entity": [], "task": "NER"}
{"text": "The MDRD and CKD - EPI equations were significantly positively biased compared with CG ( mean +/- SD 34 +/- 20 % and 22 +/- 15 % , respectively , p < 0 . 001 ) and mClcr ( 29 +/- 47 % and 18 +/- 40 % , respectively , p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "Rounding low Scr values ( less than 1 . 0 mg / dl ) up to an arbitrary value of 1 . 0 mg / dl resulted in CG values ( 44 +/- 10 ml / minute ) that were significantly lower than mClcr ( 56 +/- 12 ml / minute , p < 0 . 001 ) and CG ( 56 +/- 15 ml / minute , p < 0 . 001 ) .", "entity": [], "task": "NER"}
{"text": "The MDRD and CKD - EPI equations had median dose discordance rates of 28 . 6 % and 22 . 9 % , respectively .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : The MDRD and CKD - EPI equations significantly overestimated creatinine clearance ( mClcr and CG ) in elderly individuals .", "entity": [{"entity": "creatinine", "entity_type": "Chemical", "pos": [74, 84]}], "task": "NER"}
{"text": "This leads to dose calculation errors for many drugs , particularly in individuals with severe renal impairment .", "entity": [], "task": "NER"}
{"text": "Thus equations estimating glomerular filtration rate should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments .", "entity": [], "task": "NER"}
{"text": "In addition , the common practice of rounding or replacing low Scr values with an arbitrary value of 1 . 0 mg / dl for use in the CG equation should be avoided .", "entity": [], "task": "NER"}
{"text": "Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed .", "entity": [], "task": "NER"}
{"text": "Multiple Site - Selective Insertions of Noncanonical Amino Acids into Sequence - Repetitive Polypeptides .", "entity": [{"entity": "Amino Acids", "entity_type": "Chemical", "pos": [53, 64]}], "task": "NER"}
{"text": "A simple and efficient method is described for the introduction of noncanonical amino acids at multiple , defined sites within recombinant polypeptide sequences .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [80, 91]}], "task": "NER"}
{"text": "Escherichia coli MRA30 , a bacterial host strain with attenuated activity of release factor 1 ( RF1 ) , was assessed for its ability to support incorporation of a diverse range of noncanonical amino acids in response to multiple encoded amber ( TAG ) codons within genes derived from superfolder GFP and an elastin - mimetic protein polymer .", "entity": [{"entity": "amino acids", "entity_type": "Chemical", "pos": [193, 204]}], "task": "NER"}
{"text": "Suppression efficiency and protein yield depended on the identity of the orthogonal aminoacyl - tRNA synthetase / tRNA ( CUA ) pair and the noncanonical amino acid .", "entity": [{"entity": "aminoacyl", "entity_type": "Chemical", "pos": [84, 93]}, {"entity": "amino acid", "entity_type": "Chemical", "pos": [153, 163]}], "task": "NER"}
{"text": "Elastin - mimetic protein polymers were prepared in which noncanonical amino acid derivatives were incorporated at up to 22 specific sites within the polypeptide sequence with high substitution efficiency .", "entity": [{"entity": "amino acid", "entity_type": "Chemical", "pos": [71, 81]}], "task": "NER"}
{"text": "The identities and positions of the variant residues were confirmed by mass spectrometric analysis of the full - length polypeptides and proteolytic cleavage fragments from thermolysin digestion .", "entity": [], "task": "NER"}
{"text": "The data suggest that this multisite suppression approach permits the preparation of protein - based materials in which novel chemical functionalities can be introduced at precisely defined positions within the polypeptide sequence .", "entity": [], "task": "NER"}
{"text": "Studying the effect of antioxidants on cytogenetic manifestations of solvent exposure in paint industry .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : To investigate the antioxidant role in reversing cytogenetic changes caused by solvent exposure in paint industry . Subjects and METHODS : A prospective controlled clinical trial was performed on 39 workers exposed to solvents and 39 workers not exposed to solvents by supplying a mixture of antioxidant vitamins ( A , C , E and selenium ) and the after effects of such regimen were analyzed .", "entity": [{"entity": "vitamins ( A , C , E", "entity_type": "Chemical", "pos": [316, 336]}, {"entity": "selenium", "entity_type": "Chemical", "pos": [341, 349]}], "task": "NER"}
{"text": "Environmental monitoring was carried out for air concentrations of different solvents at workplace .", "entity": [], "task": "NER"}
{"text": "Exposed group was cytogenetically tested before and after giving the mixture of antioxidant vitamins for 1 month duration .", "entity": [], "task": "NER"}
{"text": "RESULTS : Frequency of chromosomal aberrations ( CAs ) and the mean of sister chromatid exchanges ( SCEs ) were statistically significantly higher among exposed workers than among controls .", "entity": [], "task": "NER"}
{"text": "After the supplementation of antioxidants , there was a statistically significant decrease in the frequency of CAs , and 88 % abnormal levels of SCEs were back to normal levels .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : Antioxidant supplementation decreases the frequency of CAs and SCEs among exposed workers .", "entity": [], "task": "NER"}
{"text": "Pirimicarb - based formulation - induced genotoxicity and cytotoxicity in the fresh water fish Cnesterodon decemmaculatus ( Jenyns , 1842 ) ( Pisces , Poeciliidae ) .", "entity": [{"entity": "Pirimicarb", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "We analyzed the aspects of lethality , genotoxicity , and cytotoxicity in the ten spotted live - bearer exposed under laboratory conditions to the pirimicarb - based formulation Patton Flow ( (R) ) ( 50 % active ingredient ( a . i . ) ) .", "entity": [{"entity": "pirimicarb", "entity_type": "Chemical", "pos": [147, 157]}], "task": "NER"}
{"text": "Acute effects were evaluated using different end points for lethality , genotoxicity , and cytotoxicity .", "entity": [], "task": "NER"}
{"text": "Median lethal concentration ( LC50 ) estimation was employed as a bioassay for lethality , whereas micronucleus ( MN ) induction and alterations in erythrocyte / erythroblast frequency were used as end points for genotoxicity and cytotoxicity , respectively .", "entity": [], "task": "NER"}
{"text": "Results demonstrated an LC5096h value of 88 mg / L .", "entity": [], "task": "NER"}
{"text": "Patton Flow ( (R) ) increased the MN frequency in fish erythrocytes after 48 h of exposure at a concentration of 66 mg / L , whereas a concentration range of 22 - 66 mg / L was able to exert the same genotoxic effect at 96 h of treatment .", "entity": [], "task": "NER"}
{"text": "Furthermore , cytotoxicity was also observed by alterations in erythrocyte / erythroblast frequencies within the concentration range of 22 - 66 mg / L , regardless of the exposure time .", "entity": [], "task": "NER"}
{"text": "Our current observations provide evidence that Patton Flow ( (R) ) ( 50 % a . i . ) should be considered a clear lethal , cytotoxic , and genotoxic agent on Cnesterodon decemmaculatus .", "entity": [], "task": "NER"}
{"text": "Thus , repeated applications of this carbamic insecticide can enter the aquatic environment and exert deleterious effects on aquatic organisms other than the evaluated species C . decemmaculatus .", "entity": [{"entity": "carbamic", "entity_type": "Chemical", "pos": [37, 45]}], "task": "NER"}
{"text": "1 , 1 - Diphenyl , 2 - picrylhydrazyl free radical scavenging , bactericidal , fungicidal and leishmanicidal properties of Teucrium stocksianum .", "entity": [{"entity": "1 , 1 - Diphenyl , 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [0, 37]}], "task": "NER"}
{"text": "In the present study , we evaluated the pharmacological and toxicological effects of Teucrium stocksianum .", "entity": [], "task": "NER"}
{"text": "The crude extract of T . stocksianum ( Ts . Cr ) and its subsequent organic fractions : n - hexane ( Ts . Hex ) , chloroform ( Ts . CHCl3 ) and ethyl acetate ( Ts . EtAc ) exhibited 1 , 1 - diphenyl , 2 - picrylhydrazyl free radical scavenging activity with different potencies .", "entity": [{"entity": "n - hexane", "entity_type": "Chemical", "pos": [88, 98]}, {"entity": "Hex", "entity_type": "Chemical", "pos": [106, 109]}, {"entity": "chloroform", "entity_type": "Chemical", "pos": [114, 124]}, {"entity": "CHCl3", "entity_type": "Chemical", "pos": [132, 137]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [144, 157]}, {"entity": "EtAc", "entity_type": "Chemical", "pos": [165, 169]}, {"entity": "1 , 1 - diphenyl , 2 - picrylhydrazyl", "entity_type": "Chemical", "pos": [182, 219]}], "task": "NER"}
{"text": "Ts . EtAc was found to be most potent .", "entity": [{"entity": "EtAc", "entity_type": "Chemical", "pos": [5, 9]}], "task": "NER"}
{"text": "Ts . Cr , Ts . Hex , Ts . CHCl3 and Ts . EtAc showed significant bactericidal activity against Escherichia coli , Staphylococcus aureus , Salmonella typhi , Shigella flexneri and Bacillus subtilis at their extent .", "entity": [{"entity": "Hex", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "CHCl3", "entity_type": "Chemical", "pos": [26, 31]}, {"entity": "EtAc", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Ts . Cr , Ts . Hex , Ts . CHCl3 and Ts . EtAc displayed fungicidal action against Aspergillus niger , Aspergillus flavus , Aspergillus fumigatus and Fusarium solani at various minimum inhibitory concentrations .", "entity": [{"entity": "Hex", "entity_type": "Chemical", "pos": [15, 18]}, {"entity": "CHCl3", "entity_type": "Chemical", "pos": [26, 31]}, {"entity": "EtAc", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Ts . Cr and Ts . EtAc exhibited marked inhibition of Leishmania tropica growth , observed after 48 and 96 hrs of treatment .", "entity": [{"entity": "EtAc", "entity_type": "Chemical", "pos": [17, 21]}], "task": "NER"}
{"text": "These data indicate that the T . stocksianum methanolic extract and its resultant fractions possess antioxidant , antibacterial , antifungal and antileishmanial activities .", "entity": [], "task": "NER"}
{"text": "Thus , the present research unearths the scientific base for T . stocksianum medicinal application as antioxidant and antimicrobial agents .", "entity": [], "task": "NER"}
{"text": "Effect of paraoxonase 1 192 Q / R polymorphism on paraoxonase and acetylcholinesterase enzyme activities in Turkish population exposed to organophosphate .", "entity": [{"entity": "organophosphate", "entity_type": "Chemical", "pos": [138, 153]}], "task": "NER"}
{"text": "Organophosphate ( OP ) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes .", "entity": [{"entity": "Organophosphate", "entity_type": "Chemical", "pos": [0, 15]}], "task": "NER"}
{"text": "Paraoxonase 1 ( PON1 ) enzyme plays an important role in biotransformation of OP compounds , which shows toxic effects via inhibiting the acetylcholinesterase ( AChE ) .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons , and to profile the probability of susceptibility to organophosphorus compounds .", "entity": [{"entity": "organophosphorus", "entity_type": "Chemical", "pos": [162, 178]}, {"entity": "organophosphorus", "entity_type": "Chemical", "pos": [274, 290]}], "task": "NER"}
{"text": "For this purpose , 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied .", "entity": [], "task": "NER"}
{"text": "First , PON1 and AChE enzyme activities were measured .", "entity": [], "task": "NER"}
{"text": "Second , PON1 192 Q / R polymorphism was determined by standard polymerase chain reaction - restriction fragment length polymorphism technique .", "entity": [], "task": "NER"}
{"text": "When the PON1 192 Q / R polymorphism was compared with PON1 enzyme activities , statistically significant association was found in both OP - exposed and control groups ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "PON1 192 R ( + ) ( QR + RR genotypes ) genotype carriers had higher PON1 activities than 192 R ( - ) ( QQ ) genotype carriers .", "entity": [], "task": "NER"}
{"text": "On the other hand , results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP - exposed group ( p < 0 . 05 ) .", "entity": [], "task": "NER"}
{"text": "The mean AChE concentration in the OP - exposed group was determined as 33 . 79 +/- 6 . 84 U / g haemoglobin ( Hb ) for PON1 192 R ( + ) carriers and 30 . 37 +/- 7 . 62 U / g Hb for PON1 192 R ( + ) carriers .", "entity": [], "task": "NER"}
{"text": "As a conclusion , PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level ; 192 R ( + ) > 192 R ( - ) , respectively .", "entity": [], "task": "NER"}
{"text": "Structural Determinants of Agonist Efficacy at the Glutamate Binding Site of NMDA Receptors .", "entity": [{"entity": "Glutamate", "entity_type": "Chemical", "pos": [51, 60]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [77, 81]}], "task": "NER"}
{"text": "NMDA receptors are ligand - gated ion channels assembled from GluN1 and GluN2 subunits .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "We utilized a series of N - hydroxypyrazole - 5 - glycine ( NHP5G ) partial agonists at the GluN2 glutamate binding site as tools to study activation of GluN1 / GluN2A and GluN1 / GluN2D NMDA receptor subtypes .", "entity": [{"entity": "N - hydroxypyrazole - 5 - glycine", "entity_type": "Chemical", "pos": [24, 57]}, {"entity": "NHP5G", "entity_type": "Chemical", "pos": [60, 65]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "NMDA", "entity_type": "Chemical", "pos": [187, 191]}], "task": "NER"}
{"text": "We show using two - electrode voltage - clamp electrophysiology , fast - application patch - clamp , and single channel recordings that propyl - and ethyl - substituted NHP5G agonists have a broad range of agonist efficacies relative to the full agonist glutamate ( < 1 % - 72 % ) .", "entity": [{"entity": "propyl - and ethyl - substituted NHP5G", "entity_type": "Chemical", "pos": [136, 174]}, {"entity": "glutamate", "entity_type": "Chemical", "pos": [254, 263]}], "task": "NER"}
{"text": "Crystal structures of the agonist binding domains ( ABDs ) of GluN2A and GluN2D do not reveal any differences in the overall domain conformation induced by binding of the full agonist glutamate or the partial agonist propyl - NHP5G , which is strikingly different from ABD structures of AMPA and kainate receptors bound to full and partial agonists .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [184, 193]}, {"entity": "propyl - NHP5G", "entity_type": "Chemical", "pos": [217, 231]}, {"entity": "AMPA", "entity_type": "Chemical", "pos": [287, 291]}, {"entity": "kainate", "entity_type": "Chemical", "pos": [296, 303]}], "task": "NER"}
{"text": "Subsequent evaluation of relative NHP5G agonist efficacy at GluN2A - GluN2D chimeric subunits implicates the amino - terminal domain ( ATD ) as a strong determinant of agonist efficacy , suggesting that interdomain interactions between the ABD and the ATD may be a central element in controlling the manner by which agonist binding leads to channel opening .", "entity": [{"entity": "NHP5G", "entity_type": "Chemical", "pos": [34, 39]}, {"entity": "amino", "entity_type": "Chemical", "pos": [109, 114]}], "task": "NER"}
{"text": "We propose that variation in the overall receptor conformation , which is strongly influenced by the nature of interdomain interactions in resting and active states , mediates differences in agonist efficacy and partial agonism at the GluN2 subunits .", "entity": [], "task": "NER"}
{"text": "Microfluidic affinity and ChIP - seq analyses converge on a conserved FOXP2 - binding motif in chimp and human , which enables the detection of evolutionarily novel targets .", "entity": [], "task": "NER"}
{"text": "The transcription factor forkhead box P2 ( FOXP2 ) is believed to be important in the evolution of human speech .", "entity": [], "task": "NER"}
{"text": "A mutation in its DNA - binding domain causes severe speech impairment .", "entity": [], "task": "NER"}
{"text": "Humans have acquired two coding changes relative to the conserved mammalian sequence .", "entity": [], "task": "NER"}
{"text": "Despite intense interest in FOXP2 , it has remained an open question whether the human protein ' s DNA - binding specificity and chromatin localization are conserved .", "entity": [], "task": "NER"}
{"text": "Previous in vitro and ChIP - chip studies have provided conflicting consensus sequences for the FOXP2 - binding site .", "entity": [], "task": "NER"}
{"text": "Using MITOMI 2 . 0 microfluidic affinity assays , we describe the binding site of FOXP2 and its affinity profile in base - specific detail for all substitutions of the strongest binding site .", "entity": [], "task": "NER"}
{"text": "We find that human and chimp FOXP2 have similar binding sites that are distinct from previously suggested consensus binding sites .", "entity": [], "task": "NER"}
{"text": "Additionally , through analysis of FOXP2 ChIP - seq data from cultured neurons , we find strong overrepresentation of a motif that matches our in vitro results and identifies a set of genes with FOXP2 binding sites .", "entity": [], "task": "NER"}
{"text": "The FOXP2 - binding sites tend to be conserved , yet we identified 38 instances of evolutionarily novel sites in humans .", "entity": [], "task": "NER"}
{"text": "Combined , these data present a comprehensive portrait of FOXP2 ' s - binding properties and imply that although its sequence specificity has been conserved , some of its genomic binding sites are newly evolved .", "entity": [], "task": "NER"}
{"text": "Self - Assembly and Near Perfect Macroscopic Alignment of Fluorescent Triangulenium Salt in Spin Cast Thin Films on PTFE .", "entity": [{"entity": "Triangulenium", "entity_type": "Chemical", "pos": [70, 83]}, {"entity": "PTFE", "entity_type": "Chemical", "pos": [116, 120]}], "task": "NER"}
{"text": "Highly fluorescent , discotic trioxatriangulenium dyes were aligned by simple spin casting on substrates with friction transferred PTFE layers .", "entity": [{"entity": "trioxatriangulenium", "entity_type": "Chemical", "pos": [30, 49]}, {"entity": "PTFE", "entity_type": "Chemical", "pos": [131, 135]}], "task": "NER"}
{"text": "The fluorescent crystalline thin films show near perfect macroscopic alignment on centimeter large areas directly from spin casting .", "entity": [], "task": "NER"}
{"text": "Gracing Incidence X - ray Diffraction ( GIXD ) unambiguously allowed to determine a long range order unit cell as well as its orientation with respect to the PTFE fibers .", "entity": [{"entity": "PTFE", "entity_type": "Chemical", "pos": [158, 162]}], "task": "NER"}
{"text": "Further analysis of the X - ray data , in conjunction with polarized absorption spectroscopy , suggest a lamellar packing model with alternating layers of alkyl chains and ionic dyes oriented parallel to the substrate .", "entity": [{"entity": "alkyl", "entity_type": "Chemical", "pos": [155, 160]}], "task": "NER"}
{"text": "This structure results in a highly anisotropic electrostatic potential around the cationic chromophore , causing significant shifts in energy and orientation of the optical transitions .", "entity": [], "task": "NER"}
{"text": "Thus , the optical properties of the material are , to a large extent , controlled by the position of the otherwise inert PF6 - counter ions .", "entity": [], "task": "NER"}
{"text": "The bright fluorescence from the films is also polarized parallel to the PTFE alignment layer .", "entity": [{"entity": "PTFE", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "Doping of the thin films with fluorescent energy acceptor traps shows that efficient exciton migration takes place in the thin films .", "entity": [], "task": "NER"}
{"text": "The excellent exciton transfer capabilities , in conjunction with the perfect alignment , might be of interest in future applications in solar energy harvesting or as thin film sensors .", "entity": [], "task": "NER"}
{"text": "How Selective Are the New Guidelines for Treatment of Subclinical Hypothyroidism for Patients with Thyrotropin Levels At or Below 10 mIU / L ?", "entity": [], "task": "NER"}
{"text": "Background : By consensus , a thyrotropin ( TSH ) level persistently > 10 mIU / L is an indication for the treatment of subclinical hypothyroidism ( SCH ) .", "entity": [], "task": "NER"}
{"text": "Controversy exists regarding patients whose TSH level is elevated but < 10 mIU / L .", "entity": [], "task": "NER"}
{"text": "Recently , the American Thyroid Association ( ATA ) and the American Association of Clinical Endocrinologists ( AACE ) published their position about factors that should be considered in the decision on treating SCH .", "entity": [], "task": "NER"}
{"text": "This study evaluated the frequency of these factors among adult ( non - pregnant ) women with SCH whose TSH levels are <= 10 mIU / L .", "entity": [], "task": "NER"}
{"text": "Methods : The presence of the conditions that should be considered for the treatment of SCH according to ATA and AACE was evaluated in 252 women who were diagnosed with SCH and had TSH levels <= 10 mIU / L .", "entity": [], "task": "NER"}
{"text": "Pregnant women were excluded .", "entity": [], "task": "NER"}
{"text": "Results : Antithyroperoxidase antibodies ( TPOAbs ) were detected in 137 ( 54 . 3 % ) women .", "entity": [], "task": "NER"}
{"text": "A high cardiovascular risk was observed in 43 ( 17 % ) women .", "entity": [], "task": "NER"}
{"text": "Eighty ( 31 . 7 % ) women who were not at high cardiovascular risk presented at least one classical risk factor ( arterial hypertension , elevated level of low - density lipoprotein - cholesterol or low level of high - density lipoprotein - cholesterol , smoking , or first - degree family history of premature coronary artery disease ) .", "entity": [{"entity": "cholesterol", "entity_type": "Chemical", "pos": [184, 195]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [241, 252]}], "task": "NER"}
{"text": "At least one symptom or sign of hypothyroidism that could not be explained by another condition was observed in 180 ( 71 . 4 % ) women .", "entity": [], "task": "NER"}
{"text": "Two hundred thirty - two ( 92 % ) women had positive TPOAbs , or at least one classical cardiovascular risk factor , or at least one symptom or sign of hypothyroidism .", "entity": [], "task": "NER"}
{"text": "Conclusions : According to the new ATA and AACE guidelines , L - T4 therapy would be considered for 92 % of women with SCH and TSH <= 10 mIU / L .", "entity": [{"entity": "L - T4", "entity_type": "Chemical", "pos": [61, 67]}], "task": "NER"}
{"text": "NMDA receptors and memory encoding .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "It is humbling to think that 30 years have passed since the paper by Collingridge , Kehl and McLennan showing that one of Jeff Watkins most interesting compounds , R - 2 - amino - 5 - phosphonopentanoate ( d - AP5 ) , blocked the induction of long - term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission ( Collingridge et al . , 1983 ) .", "entity": [{"entity": "R - 2 - amino - 5 - phosphonopentanoate", "entity_type": "Chemical", "pos": [164, 203]}, {"entity": "d - AP5", "entity_type": "Chemical", "pos": [206, 213]}], "task": "NER"}
{"text": "This dissociation was one of the key triggers for an explosion of interest in glutamate receptors , and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition , of the agonists and antagonists acting on them , and their diverse functions in different networks of the brain and spinal cord .", "entity": [{"entity": "glutamate", "entity_type": "Chemical", "pos": [78, 87]}], "task": "NER"}
{"text": "It can be fairly said that Collingridge et al . ' s ( 1983 ) observation was the stimulus that has led , on the one hand , to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen ; and , on the other , to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits , memory encoding in the hippocampus ( the topic of this article ) , visual cortical plasticity , sensitization in pain , and other functions .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [204, 208]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [356, 363]}], "task": "NER"}
{"text": "In this article , I lay out how my then interest in long - term potentiation ( LTP ) as a model of memory enabled me to recognise the importance of Collingridge et al . ' s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory .", "entity": [], "task": "NER"}
{"text": "This is in some respects a personal story , and I tell it as such .", "entity": [], "task": "NER"}
{"text": "The idea that NMDA receptor activation is essential for memory encoding , though not for storage , took time to develop and to be accepted .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "Along the way , there have been confusions , challenges , and surprises surrounding the idea that activation of NMDA receptors can trigger memory .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [112, 116]}], "task": "NER"}
{"text": "Some of these are described and how they have been addressed and resolved .", "entity": [], "task": "NER"}
{"text": "Last , I touch on some new directions of interest with respect to the functional role of the NMDA receptor in cognition .", "entity": [{"entity": "NMDA", "entity_type": "Chemical", "pos": [93, 97]}], "task": "NER"}
{"text": "Scientific evidence for traditional claim of antiobesity activity of Tecomella undulata bark .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : The bark of Tecomella undulata is traditionally claimed in the treatment of various disease ailments including obesity and cancer .", "entity": [], "task": "NER"}
{"text": "Till now there are no studies about anti obesity activity of Tecomella undulata bark .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : The present study was aimed to establish a scientific evidence for anti obesity efficiency of ethyl acetate extract of Tecomella undulata bark ( EATUB ) .", "entity": [{"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [113, 126]}], "task": "NER"}
{"text": "Further to standardize the active fractions of EATUB using different biomarkers .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : We investigated activity of EATUB fractions ( F1 - F7 ) using 3T3 - L1 fibroblasts .", "entity": [], "task": "NER"}
{"text": "Further , F1 - mediated effects were characterized by determining mRNA and protein levels of SIRT1 , one of the key targets for the treatment of obesity , using semi quantitative RT - PCR ( sqRT - PCR ) and western blot analysis .", "entity": [], "task": "NER"}
{"text": "The consequences of modulation of SIRT1 on mRNA and protein levels of various adipogenesis mediators like PPAR gamma , C / EBP alpha , E2F1 , leptin , adiponectin and LPL were also studied .", "entity": [], "task": "NER"}
{"text": "In - vivo studies were performed using High Fat Diet ( HFD ) obese mice .", "entity": [], "task": "NER"}
{"text": "RESULTS : Our data showed that compared to controls , preadipocytes and adipocytes incubated with F1 exhibited a significant decrease in adipogenesis and lipogenesis .", "entity": [], "task": "NER"}
{"text": "In addition , sqRT - PCR and western blot analysis showed significant increase in SIRT1 and adiponectin levels and decrease in PPAR gamma , C / EBP alpha , E2F1 , leptin and LPL levels in preadipocytes and adipocytes .", "entity": [], "task": "NER"}
{"text": "In - vivo studies of F1 in HFD induced obese mice showed significant improvement in lipid profile and glucose levels .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "The bioactive fraction ( F1 ) was determined to possess 4 . 95 % of ferulic acid .", "entity": [{"entity": "ferulic acid", "entity_type": "Chemical", "pos": [68, 80]}], "task": "NER"}
{"text": "CONCLUSION : Thus , our findings signified the beneficial effects of Tecomella undulata bark in pharmacologic interventions related to obesity and metabolic disorders .", "entity": [], "task": "NER"}
{"text": "Ferulic acid and rutin are being reported and quantified for the first time from the bark of Tecomella undulata .", "entity": [{"entity": "Ferulic acid", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [17, 22]}], "task": "NER"}
{"text": "Cytotoxic effects of amphetamine mixtures in primary hepatocytes are severely aggravated under hyperthermic conditions .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [21, 32]}], "task": "NER"}
{"text": "Amphetamine consumers are often , deliberately or not , polydrug abusers .", "entity": [{"entity": "Amphetamine", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Predicting combination effects based on concentration - response analysis of individual components is a valid strategy for accurate toxicological assessment of mixtures .", "entity": [], "task": "NER"}
{"text": "We previously reported that joint effects of 3 , 4 - methylenedioxymethamphetamine ( MDMA , ecstasy ) and three other often co - ingested amphetamines ( methamphetamine , 4 - methylthyoamphetamine and D - amphetamine ) could be predicted by the concentration addition ( CA ) model in HepG2 cells .", "entity": [{"entity": "3 , 4 - methylenedioxymethamphetamine", "entity_type": "Chemical", "pos": [45, 82]}, {"entity": "MDMA", "entity_type": "Chemical", "pos": [85, 89]}, {"entity": "ecstasy", "entity_type": "Chemical", "pos": [92, 99]}, {"entity": "amphetamines", "entity_type": "Chemical", "pos": [138, 150]}, {"entity": "methamphetamine", "entity_type": "Chemical", "pos": [153, 168]}, {"entity": "4 - methylthyoamphetamine", "entity_type": "Chemical", "pos": [171, 196]}, {"entity": "D - amphetamine", "entity_type": "Chemical", "pos": [201, 216]}], "task": "NER"}
{"text": "We sought to further evaluate the relevance of these findings by extending these studies to a cell model that more closely mimics the in vivo situation .", "entity": [], "task": "NER"}
{"text": "Detailed cytotoxic information of the four individual amphetamines on primary rat hepatocytes was recorded by the MTT assay , at 37 degrees C and 40 . 5 degrees C , simulating the rise in body temperature that could be induced following amphetamine intake .", "entity": [{"entity": "amphetamines", "entity_type": "Chemical", "pos": [54, 66]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [114, 117]}, {"entity": "amphetamine", "entity_type": "Chemical", "pos": [237, 248]}], "task": "NER"}
{"text": "Mixture expectations were calculated using CA and independent action ( IA ) models .", "entity": [], "task": "NER"}
{"text": "At 37 degrees C , concentration - dependent cytotoxicity occurred for the drugs individually and combined .", "entity": [], "task": "NER"}
{"text": "Mixture effects were accurately predicted by the CA model , while the IA model underestimated cytotoxicity .", "entity": [], "task": "NER"}
{"text": "At 40 . 5 degrees C these cytotoxic effects were aggravated .", "entity": [], "task": "NER"}
{"text": "Our findings provide evidence of the increased risks associated with the abuse of amphetamine mixtures , especially during hyperthermia , emphasising the need to increase awareness of misinformed users who believe these drugs are safe .", "entity": [{"entity": "amphetamine", "entity_type": "Chemical", "pos": [82, 93]}], "task": "NER"}
{"text": "Receiver Operating Characteristic Analysis of HLA , CTLA4 , and Insulin Genotypes for Type 1 Diabetes .", "entity": [], "task": "NER"}
{"text": "OBJECTIVEThis study assessed the ability to distinguish between type 1 diabetes - affected individuals and their unaffected relatives using HLA and single nucleotide polymorphism ( SNP ) genotypes . RESEARCH DESIGN AND METHODSEight models , ranging from only the high - risk DR3 / DR4 genotype to all significantly associated HLA genotypes and two SNPs mapping to the cytotoxic T - cell - associated antigen - 4 gene ( CTLA4 ) and insulin ( INS ) genes , were fitted to high - resolution class I and class II HLA genotyping data for patients from the Type 1 Diabetes Genetics Consortium collection .", "entity": [], "task": "NER"}
{"text": "Pairs of affected individuals and their unaffected siblings were divided into a \" discovery \" ( n = 1 , 015 pairs ) and a \" validation \" set ( n = 318 pairs ) .", "entity": [], "task": "NER"}
{"text": "The discriminating performance of various combinations of genetic information was estimated using receiver operating characteristic ( ROC ) curve analysis . RESULTSThe use of only the presence or absence of the high - risk DR3 / DR4 genotype achieved very modest discriminating ability , yielding an area under the curve ( AUC ) of 0 . 62 in the discovery set and 0 . 59 in the validation set .", "entity": [], "task": "NER"}
{"text": "The full model , which included HLA information from the class II loci DPB1 , DRB1 , DQB1 , selected alleles from HLA class I loci A and B , and SNPs from the CTLA4 and INS genes , increased the AUC to 0 . 74 in the discovery set and to 0 . 71 in the validation set .", "entity": [], "task": "NER"}
{"text": "A cost - effective alternative is proposed , using genotype information equivalent to typing four SNPs ( DR3 , DR4 - DQB1 * 03 : 02 , CTLA - 4 , and INS ) , which achieved an AUC of 0 . 72 in the discovery set and 0 . 69 in the validation set . CONCLUSIONSGenotyping data sufficient to tag DR3 , DR4 - DQB1 * 03 : 02 , CTLA4 , and INS was shown to distinguish between subjects with type 1 diabetes and their unaffected siblings adequately to achieve clinically utility to identify children in multiplex families to be considered for early intervention .", "entity": [], "task": "NER"}
{"text": "Cuf2 boosts the transcription of APC / C activator Fzr1 to terminate the meiotic division cycle .", "entity": [], "task": "NER"}
{"text": "The number of nuclear divisions in meiosis is strictly limited to two .", "entity": [], "task": "NER"}
{"text": "Although the precise mechanism remains unknown , this seems to be achieved by adjusting the anaphase - promoting complex / cyclosome ( APC / C ) activity to degrade cyclin .", "entity": [], "task": "NER"}
{"text": "Here , we describe a fission yeast cuf2 mutant that enters into a third nuclear division cycle , represented by ectopic spindle assembly and abnormal chromosome segregation .", "entity": [], "task": "NER"}
{"text": "Cuf2 is a meiotic transcription factor , and its critical target is fzr1 ( + ) / mfr1 ( + ) , which encodes a meiotic APC / C activator .", "entity": [], "task": "NER"}
{"text": "fzr1 Delta also enters a third nuclear division .", "entity": [], "task": "NER"}
{"text": "Thus , Cuf2 ensures termination of the M - phase cycle by boosting Fzr1 expression to generate functional gametes .", "entity": [], "task": "NER"}
{"text": "Intracellular trafficking of solid lipid nanoparticles and their distribution between cells through tunneling nanotubes .", "entity": [], "task": "NER"}
{"text": "The intracellular fate of nanosized drug delivery systems is still not well understood .", "entity": [], "task": "NER"}
{"text": "Various internalization pathways have been discovered , but knowledge of their intracellular trafficking is still incomplete .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to examine the internalization , pathways , and positioning taken by solid lipid nanoparticles ( SLNs ) in cells .", "entity": [], "task": "NER"}
{"text": "SLNs were fluorescence labeled with a newly synthesized fluorescent probe , 14 - DACA .", "entity": [{"entity": "14 - DACA", "entity_type": "Chemical", "pos": [76, 85]}], "task": "NER"}
{"text": "The probe was strongly incorporated into the nanoparticle core under the influence of its long lipophilic chain , enabling superior visualization of SLNs under complex and dynamic intracellular conditions .", "entity": [], "task": "NER"}
{"text": "The intracellular distribution of SLNs was studied qualitatively using a co - localization technique and quantitatively using fluorescence intensity profiles .", "entity": [], "task": "NER"}
{"text": "SLNs were seen inside the cells as distinct bright blue dots that underwent dynamic movement and were finally positioned in the proximity of the nucleus .", "entity": [], "task": "NER"}
{"text": "A few SLNs were shown to be present in mitochondria and between actin filaments , but none in the cell nucleus or lysosomes .", "entity": [], "task": "NER"}
{"text": "SLNs are here reported to be present in tunneling nanotubes ( TNTs ) , which could be a new route of SLN transfer between cells .", "entity": [], "task": "NER"}
{"text": "More TNTs were observed in cells treated with SLNs .", "entity": [], "task": "NER"}
{"text": "The presence of TNTs was additionally confirmed by atomic force microscopy analysis , which indicated that treated cells were more rough than control cells .", "entity": [], "task": "NER"}
{"text": "Detailed investigation of the subcellular localization of SLNs and the evidence for their transfer and distribution via TNTs to the cells , which are not in direct contact with the source of SLNs , are important for understanding the mechanism of targeted drug delivery .", "entity": [], "task": "NER"}
{"text": "Understanding the possible intercellular distribution of SLNs via TNTs can significantly influence approaches to treating organelle - specific diseases .", "entity": [], "task": "NER"}
{"text": "Ubiquitous trisulfur radical anion : fundamentals and applications in materials science , electrochemistry , analytical chemistry and geochemistry .", "entity": [{"entity": "trisulfur", "entity_type": "Chemical", "pos": [11, 20]}], "task": "NER"}
{"text": "The trisulfur radical anion [ S3 ] . ( - ) is well - known from inorganic chemistry textbooks as the blue chromophore in ultramarine blues in which this highly reactive species is trapped in a zeolitic framework .", "entity": [{"entity": "trisulfur", "entity_type": "Chemical", "pos": [4, 13]}, {"entity": "[ S3 ] . ( - )", "entity_type": "Chemical", "pos": [28, 42]}], "task": "NER"}
{"text": "Recent findings have revealed that [ S3 ] . ( - ) has a multi - faceted role in a variety of media , including alkali metal - sulfur batteries , aqueous solutions at high temperatures and pressures , and ionic liquids ; it has also been used to detect trace amounts of water in organic solvents .", "entity": [{"entity": "[ S3 ] . ( - )", "entity_type": "Chemical", "pos": [35, 49]}, {"entity": "sulfur", "entity_type": "Chemical", "pos": [126, 132]}], "task": "NER"}
{"text": "This tutorial review illustrates how various physical techniques are used to identify a reactive species in solution and shows how elucidation of electronic structures can be used to explain spectroscopic and structural properties .", "entity": [], "task": "NER"}
{"text": "Examples of the function of [ S3 ] . ( - ) in materials science , electrochemistry , analytical chemistry and geochemistry are used to illustrate the widespread influence of this fundamentally important triatomic sulfur species .", "entity": [{"entity": "[ S3 ] . ( - )", "entity_type": "Chemical", "pos": [28, 42]}, {"entity": "triatomic sulfur", "entity_type": "Chemical", "pos": [203, 219]}], "task": "NER"}
{"text": "COMPLETE ARTIFICIAL SALIVA ALTERS EXPRESSION OF PROINFLAMMATORY CYTOKINES IN HUMAN DERMAL FIBROBLASTS .", "entity": [], "task": "NER"}
{"text": "Complete artificial saliva ( CAS ) is a saliva substitute often used as a vehicle for test articles , including smokeless tobacco products .", "entity": [], "task": "NER"}
{"text": "In the course of a study employing normal adult human dermal fibroblasts ( HDFa ) as a model in vitro , we discovered that CAS as a vehicle introduced a significant change in the expression of proinflammatory cytokines .", "entity": [], "task": "NER"}
{"text": "To determine the effects of CAS on gene expression , real - time quantitative reverse - transcriptase polymerase chain reaction ( qRT - PCR ) gene array analysis was used .", "entity": [], "task": "NER"}
{"text": "Results indicate that robust changes in the expression of the proinflammatory cytokine interleukin 8 ( IL8 ) and the vascular cell adhesion molecule 1 ( VCAM1 ) occur within 5 hours of exposure to CAS .", "entity": [], "task": "NER"}
{"text": "To determine whether CAS also alters cytokine release into the culture media , cytometric bead array ( CBA ) assays for human inflammatory cytokines were performed .", "entity": [], "task": "NER"}
{"text": "Analysis shows that CAS induced the release of IL8 and interleukin 6 ( IL6 ) .", "entity": [], "task": "NER"}
{"text": "This study focused on determining which components in CAS were responsible for the proinflammatory response in HDFa .", "entity": [], "task": "NER"}
{"text": "The following components were investigated : alpha - amylase , lysozyme , acid phosphatase , and urea .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [97, 101]}], "task": "NER"}
{"text": "Results demonstrated that enzymatically active alpha - amylase induced gene expression for proinflammatory cytokines IL8 , IL6 , tumor necrosis factor - alpha ( TNF alpha ) , and interleukin 1 alpha ( IL1 alpha ) , and for VCAM1 .", "entity": [], "task": "NER"}
{"text": "Therefore , it is important to carefully evaluate the \" vehicle effects \" of CAS and its components in in vitro toxicology research .", "entity": [], "task": "NER"}
{"text": "Simple and Rapid Synthesis of Magnetite / Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route .", "entity": [{"entity": "Magnetite", "entity_type": "Chemical", "pos": [30, 39]}, {"entity": "Hydroxyapatite", "entity_type": "Chemical", "pos": [42, 56]}], "task": "NER"}
{"text": "This paper presents a simple method for the rapid synthesis of magnetite / hydroxyapatite composite particles .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [63, 72]}, {"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [75, 89]}], "task": "NER"}
{"text": "In this method , superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [35, 44]}, {"entity": "ferrous chloride", "entity_type": "Chemical", "pos": [106, 122]}, {"entity": "ferric chloride", "entity_type": "Chemical", "pos": [127, 142]}], "task": "NER"}
{"text": "Immediately following the synthesis , carbonate - substituted ( B - type ) hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles , during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix .", "entity": [{"entity": "carbonate", "entity_type": "Chemical", "pos": [38, 47]}, {"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [75, 89]}, {"entity": "dicalcium phosphate dihydrate", "entity_type": "Chemical", "pos": [149, 178]}, {"entity": "calcium carbonate", "entity_type": "Chemical", "pos": [183, 200]}, {"entity": "magnetite", "entity_type": "Chemical", "pos": [230, 239]}, {"entity": "magnetite", "entity_type": "Chemical", "pos": [273, 282]}, {"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [323, 337]}], "task": "NER"}
{"text": "We observed that the resultant magnetite / hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles , characterized by an absence of large aggregates .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [31, 40]}, {"entity": "hydroxyapatite", "entity_type": "Chemical", "pos": [43, 57]}, {"entity": "magnetite", "entity_type": "Chemical", "pos": [107, 116]}], "task": "NER"}
{"text": "When this material was subjected to an alternating magnetic field , the heat generated increased with increasing magnetite concentration .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [113, 122]}], "task": "NER"}
{"text": "For a magnetite concentration of 30 mass % , a temperature increase greater than 20 K was achieved in less than 50 s .", "entity": [{"entity": "magnetite", "entity_type": "Chemical", "pos": [6, 15]}], "task": "NER"}
{"text": "These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments .", "entity": [], "task": "NER"}
{"text": "A Detailed Experimental and Theoretical Study into the Properties of C60 Dumbbell Junctions .", "entity": [{"entity": "C60", "entity_type": "Chemical", "pos": [69, 72]}], "task": "NER"}
{"text": "A combined experimental and theoretical investigation is carried out into the electrical transport across a fullerene dumbbell one - molecule junction .", "entity": [{"entity": "fullerene", "entity_type": "Chemical", "pos": [108, 117]}], "task": "NER"}
{"text": "The newly designed molecule comprises two C60 s connected to a fluorene backbone via cyclopropyl groups .", "entity": [{"entity": "C60", "entity_type": "Chemical", "pos": [42, 45]}, {"entity": "fluorene", "entity_type": "Chemical", "pos": [63, 71]}, {"entity": "cyclopropyl", "entity_type": "Chemical", "pos": [85, 96]}], "task": "NER"}
{"text": "It is wired between gold electrodes under ambient conditions by pressing the tip of a scanning tunnelling microscope ( STM ) onto one of the C60 groups .", "entity": [{"entity": "C60", "entity_type": "Chemical", "pos": [141, 144]}], "task": "NER"}
{"text": "The STM allows us to identify a single molecule before the junction is formed through imaging , which means unambiguously that only one molecule is wired .", "entity": [], "task": "NER"}
{"text": "Once lifted , the same molecule could be wired many times as it was strongly fixed to the tip , and a high conductance state close to 10 ( - 2 ) G0 is found .", "entity": [], "task": "NER"}
{"text": "The results also suggest that the relative conductance fluctuations are low as a result of the low mobility of the molecule .", "entity": [], "task": "NER"}
{"text": "Theoretical analysis indicates that the molecule is connected directly to one electrode through the central fluorene , and that to bind it to the gold fully it has to be pushed through a layer of adsorbates naturally present in the experiment .", "entity": [{"entity": "fluorene", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "Extracellular Electron Transfer across Bacterial Cell Membranes via a Cytocompatible Redox - Active Polymer .", "entity": [], "task": "NER"}
{"text": "A redox - active phospholipid polymer with a phospholipid - mimicking structure ( 2 - methacryloyloxyethyl phosphorylcholine ; MPC ) was synthesized to construct a biocompatible electron mediator between bacteria and an electrode .", "entity": [{"entity": "2 - methacryloyloxyethyl phosphorylcholine", "entity_type": "Chemical", "pos": [82, 124]}, {"entity": "MPC", "entity_type": "Chemical", "pos": [127, 130]}], "task": "NER"}
{"text": "In this study , a copolymer of MPC and vinylferrocene [ VF ; poly ( MPC - co - VF ) ] ( PMF ) is synthesized .", "entity": [{"entity": "MPC", "entity_type": "Chemical", "pos": [31, 34]}, {"entity": "vinylferrocene", "entity_type": "Chemical", "pos": [39, 53]}, {"entity": "poly ( MPC - co - VF )", "entity_type": "Chemical", "pos": [61, 83]}, {"entity": "PMF", "entity_type": "Chemical", "pos": [88, 91]}], "task": "NER"}
{"text": "When PMF is added to cultures of the bacterial species Escherichia coli ( Gram negative ) and Lactobacillus plantarum ( Gram positive ) , which have different cell wall structures , a catalytic current mediated by PMF is observed .", "entity": [{"entity": "PMF", "entity_type": "Chemical", "pos": [5, 8]}, {"entity": "PMF", "entity_type": "Chemical", "pos": [214, 217]}], "task": "NER"}
{"text": "In addition , growth curves and live / dead assays indicate that PMF does not decrease metabolic activity or cell viability .", "entity": [{"entity": "PMF", "entity_type": "Chemical", "pos": [65, 68]}], "task": "NER"}
{"text": "These results indicate that PMF mediates extracellular electron transfer across bacterial cell membranes without associated cytotoxicity .", "entity": [{"entity": "PMF", "entity_type": "Chemical", "pos": [28, 31]}], "task": "NER"}
{"text": "PICK1 Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [100, 107]}], "task": "NER"}
{"text": "Secretory vesicles in endocrine cells store hormones such as growth hormone ( GH ) and insulin before their release into the bloodstream .", "entity": [], "task": "NER"}
{"text": "The molecular mechanisms governing budding of immature secretory vesicles from the trans - Golgi network ( TGN ) and their subsequent maturation remain unclear .", "entity": [], "task": "NER"}
{"text": "Here , we identify the lipid binding BAR ( Bin / amphiphysin / Rvs ) domain protein PICK1 ( protein interacting with C kinase 1 ) as a key component early in the biogenesis of secretory vesicles in GH - producing cells .", "entity": [], "task": "NER"}
{"text": "Both PICK1 - deficient Drosophila and mice displayed somatic growth retardation .", "entity": [], "task": "NER"}
{"text": "Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides .", "entity": [], "task": "NER"}
{"text": "PICK1 - deficient mice were characterized by decreased body weight and length , increased fat accumulation , impaired GH secretion , and decreased storage of GH in the pituitary .", "entity": [], "task": "NER"}
{"text": "Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number .", "entity": [], "task": "NER"}
{"text": "Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [84, 91]}], "task": "NER"}
{"text": "PICK1 localized in cells to immature secretory vesicles , and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane - sculpting properties in vitro .", "entity": [], "task": "NER"}
{"text": "In mouse pituitary , PICK1 co - localized with the BAR domain protein ICA69 , and PICK1 deficiency abolished ICA69 protein expression .", "entity": [], "task": "NER"}
{"text": "In the Drosophila brain , PICK1 and ICA69 co - immunoprecipitated and showed mutually dependent expression .", "entity": [], "task": "NER"}
{"text": "Finally , both in a Drosophila model of type 2 diabetes and in high - fat - diet - induced obese mice , we observed up - regulation of PICK1 mRNA expression .", "entity": [], "task": "NER"}
{"text": "Our findings suggest that PICK1 , together with ICA69 , is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones .", "entity": [], "task": "NER"}
{"text": "The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1 / ICA69 in maintenance of metabolic homeostasis .", "entity": [], "task": "NER"}
{"text": "X - ray structure analysis of a solid solution of milbemycins A3 and A4 .", "entity": [{"entity": "milbemycins A3 and A4", "entity_type": "Chemical", "pos": [50, 71]}], "task": "NER"}
{"text": "Milbemycins A3 and A4 are pharmaceutically and agriculturally useful macrolides isolated from Streptomyces species .", "entity": [{"entity": "Milbemycins A3 and A4", "entity_type": "Chemical", "pos": [0, 21]}], "task": "NER"}
{"text": "The molecular structures of the title compounds were unambiguously established by a single crystal X - ray analysis of the solid solution of both compounds .", "entity": [], "task": "NER"}
{"text": "The crystals present trigonal system , space group P32 with Z = 3 , unit cell dimensions : a = 12 . 2211 ( 4 ) , c = 17 . 5372 ( 7 ) A ; V = 2268 . 4 ( 1 ) A ( 3 ) , mu = 0 . 082 mm ( - 1 ) ; d = 1 . 183 g cm ( - 3 ) .", "entity": [], "task": "NER"}
{"text": "An interesting system of intramolecular hydrogen bonds and weak intermolecular CH ... O type hydrogen bond was observed in the solid state .", "entity": [{"entity": "hydrogen", "entity_type": "Chemical", "pos": [40, 48]}, {"entity": "CH", "entity_type": "Chemical", "pos": [79, 81]}, {"entity": "O", "entity_type": "Chemical", "pos": [86, 87]}, {"entity": "hydrogen", "entity_type": "Chemical", "pos": [93, 101]}], "task": "NER"}
{"text": "Site - specific and Far - Red Light - Activatable Prodrug of Combretastain A - 4 Using Photo - Unclick Chemistry .", "entity": [{"entity": "Combretastain A - 4", "entity_type": "Chemical", "pos": [61, 80]}], "task": "NER"}
{"text": "Although tissue - penetrable light ( red and NIR ) has a great potential for spatiotemporally controlled release of therapeutic agents , it has been hampered because of the lack of chemistry translating the photonic energy to a cleavage of a chemical bond .", "entity": [], "task": "NER"}
{"text": "Recently , we discovered that an aminoacrylate group could be cleaved to release parent drugs after oxidation by SO , and have called this \" photo - unclick chemistry \" .", "entity": [{"entity": "aminoacrylate", "entity_type": "Chemical", "pos": [33, 46]}], "task": "NER"}
{"text": "We demonstrate its application to far - red light - activated prodrugs .", "entity": [], "task": "NER"}
{"text": "A prodrug of combretastatin A - 4 ( CA4 ) was prepared , CMP - L - CA4 : CMP ( dithiaporphyrin , a photosensitizer ) and L ( aminoacrylate linker ) .", "entity": [{"entity": "combretastatin A - 4", "entity_type": "Chemical", "pos": [13, 33]}, {"entity": "CA4", "entity_type": "Chemical", "pos": [36, 39]}, {"entity": "CMP - L - CA4", "entity_type": "Chemical", "pos": [57, 70]}, {"entity": "CMP", "entity_type": "Chemical", "pos": [73, 76]}, {"entity": "dithiaporphyrin", "entity_type": "Chemical", "pos": [79, 94]}, {"entity": "aminoacrylate", "entity_type": "Chemical", "pos": [125, 138]}], "task": "NER"}
{"text": "Upon irradiation with 690 nm diode laser , the aminoacrylate linker of the prodrug was cleaved rapidly releasing CA4 ( > 80 % in 10 min ) in CDCl3 .", "entity": [{"entity": "aminoacrylate", "entity_type": "Chemical", "pos": [47, 60]}, {"entity": "CA4", "entity_type": "Chemical", "pos": [113, 116]}, {"entity": "CDCl3", "entity_type": "Chemical", "pos": [141, 146]}], "task": "NER"}
{"text": "In the tissue culture , it showed about a 6 - fold increase in its IC50 in MCF - 7 after the irradiation , most likely , because of the released CA4 .", "entity": [{"entity": "CA4", "entity_type": "Chemical", "pos": [145, 148]}], "task": "NER"}
{"text": "Most significantly , CMP - L - CA4 had better antitumor efficacy in vivo than its non - cleavable ( NC ) analog , CMP - NCL - CA4 .", "entity": [{"entity": "CMP - L - CA4", "entity_type": "Chemical", "pos": [21, 34]}, {"entity": "CMP - NCL - CA4", "entity_type": "Chemical", "pos": [114, 129]}], "task": "NER"}
{"text": "This is the first demonstration of the in vivo efficacy of the novel low - energy light - activatable prodrug using the photo - unclick chemistry .", "entity": [], "task": "NER"}
{"text": "\" Strange Kinetics \" in the Temperature Dependence of Methionine Ligand Rebinding Dynamics in Cytochrome c .", "entity": [{"entity": "Methionine", "entity_type": "Chemical", "pos": [54, 64]}], "task": "NER"}
{"text": "Temperature dependence of methionine ligand dissociation and rebinding dynamics in cytochrome c in aqueous solution has been studied using classical molecular dynamics simulation .", "entity": [{"entity": "methionine", "entity_type": "Chemical", "pos": [26, 36]}], "task": "NER"}
{"text": "Results are compared with previous study of rebinding dynamics at 300K in water in order to understand how the change of protein environment and the underlying protein energy landscape influence the dynamics .", "entity": [], "task": "NER"}
{"text": "Rebinding dynamics at 77K , 180K , and 300K exhibits changes in both timescale and mechanism as the protein and solvent undergo a dynamic \" glass transition . \" At each temperature , the rebinding dynamics yields a subset of trajectories that undergo fast rebinding as well as a subset of trajectories that undergo slower rebinding .", "entity": [], "task": "NER"}
{"text": "At 300K in water , both a fast ( 4 . 0 ps ) and slow ( 14 . 6 ps ) rebinding is observed .", "entity": [], "task": "NER"}
{"text": "While fast rebinding occurs from a \" downward \" ( heme pointing ) substate of the methionine , the slow rebinding involves interconversion between an \" upward \" substate , from which rebinding cannot occur , and the downward substate .", "entity": [{"entity": "heme", "entity_type": "Chemical", "pos": [50, 54]}, {"entity": "methionine", "entity_type": "Chemical", "pos": [82, 92]}], "task": "NER"}
{"text": "At lower temperatures ( 77K and 180K ) the upward dissociated substate was not observed due to the high barrier imposed by the \" frozen \" protein structure .", "entity": [], "task": "NER"}
{"text": "However , a slow rebinding phase is observed at both 77K and 180K and is associated with a process of trapping in downward but \" binding forbidden \" substates with subsequent slow dynamical conversion to \" binding competent \" substates from which rebinding is relatively rapid .", "entity": [], "task": "NER"}
{"text": "Distinctive rebinding dynamics at 77K and 180K suggest that different rebinding time scales are predetermined by the protein and solvent structural arrangement prior to photodissociation , which causes either fast rebinding ( about 2ps ) or slow ( > 50ps ) rebinding .", "entity": [], "task": "NER"}
{"text": "Suggestions for future experiments to further probe the role of dynamic heterogeneity in the kinetics of methionine ligand binding in cytochrome c protein are proposed .", "entity": [{"entity": "methionine", "entity_type": "Chemical", "pos": [105, 115]}], "task": "NER"}
{"text": "( De ) Lithiation Mechanism of Li / SeSx ( x = 0 - 7 ) Batteries Determined by In - situ Synchrotron X - ray Diffraction and X - ray Absorption Spectroscopy .", "entity": [{"entity": "Li", "entity_type": "Chemical", "pos": [7, 9]}, {"entity": "SeSx", "entity_type": "Chemical", "pos": [36, 40]}], "task": "NER"}
{"text": "Electrical energy storage for transportation has going beyond the limit of converntional lithium - ion batteries currently .", "entity": [{"entity": "lithium", "entity_type": "Chemical", "pos": [89, 96]}], "task": "NER"}
{"text": "New material or new battery system development is an alternative approach to achieve the goal of new high energy storage system with energy densities five times or more greater .", "entity": [], "task": "NER"}
{"text": "A series of SeSx - carbon ( x = 0 - 7 ) composite materials has been prepared and evaluated as the positive electrodes in secondary lithium cells with ether - based electrolyte .", "entity": [{"entity": "SeSx", "entity_type": "Chemical", "pos": [12, 16]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "lithium", "entity_type": "Chemical", "pos": [132, 139]}, {"entity": "ether", "entity_type": "Chemical", "pos": [151, 156]}], "task": "NER"}
{"text": "In - situ synchrotron high energy X - ray diffraction was utilized to investigate the crystalline phase transition during cell cycling .", "entity": [], "task": "NER"}
{"text": "Complementary , in - situ Se K - edge X - ray absorption near edge structure analysis was used to track the evolution of the Se valence state for both crystalline and non - crystalline phases , including amorphous and electrolyte - dissolved phases in the ( de ) lithiation process .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [26, 28]}, {"entity": "Se", "entity_type": "Chemical", "pos": [125, 127]}], "task": "NER"}
{"text": "On the basis of these reuslts , a mechanism for the ( de ) lithiation process is proposed , where Se is reduced to the polyselenides , Li2Sen ( n >= 4 ) , Li2Se2 , and Li2Se sequentially during the lithiation , and Li2Se is oxidized to Se through Li2Sen ( n >= 4 ) during the delithiation .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [98, 100]}, {"entity": "polyselenides", "entity_type": "Chemical", "pos": [119, 132]}, {"entity": "Li2Sen", "entity_type": "Chemical", "pos": [135, 141]}, {"entity": "Li2Se2", "entity_type": "Chemical", "pos": [155, 161]}, {"entity": "Li2Se", "entity_type": "Chemical", "pos": [168, 173]}, {"entity": "Li2Se", "entity_type": "Chemical", "pos": [215, 220]}, {"entity": "Se", "entity_type": "Chemical", "pos": [236, 238]}, {"entity": "Li2Sen", "entity_type": "Chemical", "pos": [247, 253]}], "task": "NER"}
{"text": "In addition , X - ray photoelectron spectroscopy and electrochemical impedance spectroscopy demonstrated the reversibility of the Li / Se system in ether - based electrolyte and the presence of side products in the carbonate - based electrolytes .", "entity": [{"entity": "Li", "entity_type": "Chemical", "pos": [130, 132]}, {"entity": "Se", "entity_type": "Chemical", "pos": [135, 137]}, {"entity": "ether", "entity_type": "Chemical", "pos": [148, 153]}, {"entity": "carbonate", "entity_type": "Chemical", "pos": [215, 224]}], "task": "NER"}
{"text": "For Li / SeS2 and Li / SeS7 cells , Li2Se and Li2S are the discharged products with the presence of Se only as the crystalline phase in the end of charge .", "entity": [{"entity": "Li", "entity_type": "Chemical", "pos": [4, 6]}, {"entity": "SeS2", "entity_type": "Chemical", "pos": [9, 13]}, {"entity": "Li", "entity_type": "Chemical", "pos": [18, 20]}, {"entity": "SeS7", "entity_type": "Chemical", "pos": [23, 27]}, {"entity": "Li2Se", "entity_type": "Chemical", "pos": [36, 41]}, {"entity": "Li2S", "entity_type": "Chemical", "pos": [46, 50]}, {"entity": "Se", "entity_type": "Chemical", "pos": [100, 102]}], "task": "NER"}
{"text": "The Governing Role of Surface Hydration in Ion Specific Adsorption to Silica - an AFM Based Account of the Hofmeister Universality and its Reversal .", "entity": [{"entity": "Silica", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "AFM measurements of the force acting between silica surfaces in the presence of varied alkali - chloride salts and pH ' s elucidate the origin of the Hofmeister adsorption series and its reversal .", "entity": [{"entity": "silica", "entity_type": "Chemical", "pos": [45, 51]}, {"entity": "alkali - chloride", "entity_type": "Chemical", "pos": [87, 104]}], "task": "NER"}
{"text": "At low pH , electrostatics is shown to be insignificant .", "entity": [], "task": "NER"}
{"text": "The preferential adsorption of Cs + to the silica surface is traced to the weak hydration of neutral silanols and the resulting hydrophobic expulsion of weakly hydrated ions from bulk solution to the interface .", "entity": [{"entity": "Cs +", "entity_type": "Chemical", "pos": [31, 35]}, {"entity": "silica", "entity_type": "Chemical", "pos": [43, 49]}, {"entity": "silanols", "entity_type": "Chemical", "pos": [101, 109]}], "task": "NER"}
{"text": "The same interactions keep the strongly hydrated Li + and Na + in solution .", "entity": [{"entity": "Li +", "entity_type": "Chemical", "pos": [49, 53]}, {"entity": "Na +", "entity_type": "Chemical", "pos": [58, 62]}], "task": "NER"}
{"text": "As pH is increased , a tightly bound hydration layer forms on deprotonating silanols .", "entity": [{"entity": "silanols", "entity_type": "Chemical", "pos": [76, 84]}], "task": "NER"}
{"text": "Cs + is correspondingly expelled from the surface and adsorption of small ions is encouraged .", "entity": [{"entity": "Cs +", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "The deduced role of surface hydration is corroborated by hydration repulsion observed at high pH , surface over - charging at low pH , and data in other oxides .", "entity": [{"entity": "oxides", "entity_type": "Chemical", "pos": [153, 159]}], "task": "NER"}
{"text": "Fungal ABC Transporter - Associated Activity of Isoflavonoids from the Root Extract of Dalea formosa .", "entity": [{"entity": "Isoflavonoids", "entity_type": "Chemical", "pos": [48, 61]}], "task": "NER"}
{"text": "New potential treatments for disseminated fungal infections are needed , especially for infections caused by the commonly drug - resistant pathogens Candida albicans and C . glabrata .", "entity": [], "task": "NER"}
{"text": "These pathogens cause systemic candidiasis , a significant cause of mortality in immune - compromised patients .", "entity": [], "task": "NER"}
{"text": "ABC transporters of the pleiotropic drug resistance subfamily , such as Cdr1p of C . albicans , play an important role in antifungal resistance and are potential bioassay targets for antifungal therapies against drug - resistant pathogens .", "entity": [], "task": "NER"}
{"text": "We observed strong antifungal growth inhibitory activity in the methanol extract of Dalea formosa roots .", "entity": [{"entity": "methanol", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "This extract afforded six new isoflavonoids , sedonans A - F ( 1 - 6 ) , a new but - 2 - enolide , 4 ' - O - methylpuerol A ( 7 ) , and the new pterocarpan ent - sandwicensin ( 8 ) .", "entity": [{"entity": "isoflavonoids", "entity_type": "Chemical", "pos": [30, 43]}, {"entity": "sedonans A - F", "entity_type": "Chemical", "pos": [46, 60]}, {"entity": "but - 2 - enolide", "entity_type": "Chemical", "pos": [79, 96]}, {"entity": "4 ' - O - methylpuerol A", "entity_type": "Chemical", "pos": [99, 123]}, {"entity": "ent - sandwicensin", "entity_type": "Chemical", "pos": [156, 174]}], "task": "NER"}
{"text": "The structures and absolute configurations of these compounds were assigned using spectroscopic and chiroptical techniques .", "entity": [], "task": "NER"}
{"text": "The direct antifungal activity of 1 against C . glabrata ( MIC = 20 mu M ) was higher than that of fluconazole .", "entity": [{"entity": "fluconazole", "entity_type": "Chemical", "pos": [99, 110]}], "task": "NER"}
{"text": "Sedonans A - F and ent - sandwicensin were also active against Saccharomyces cerevisiae strains that express differing ABC transporter - associated resistance mechanisms but differed in their susceptibility to Cdr1p - mediated detoxification .", "entity": [{"entity": "Sedonans A - F", "entity_type": "Chemical", "pos": [0, 14]}, {"entity": "ent - sandwicensin", "entity_type": "Chemical", "pos": [19, 37]}], "task": "NER"}
{"text": "A sedonan A ( 1 ) / ent - sandwicensin ( 8 ) combination exhibited synergistic growth inhibition .", "entity": [{"entity": "sedonan A", "entity_type": "Chemical", "pos": [2, 11]}, {"entity": "ent - sandwicensin", "entity_type": "Chemical", "pos": [20, 38]}], "task": "NER"}
{"text": "The results demonstrate that multiple crude extract compounds are differentially affected by efflux - mediated resistance and are collectively responsible for the observed bioactivity .", "entity": [], "task": "NER"}
{"text": "A Chemometric Approach to Distribution of Selenium in Medicinal Plants Cultivated in Poland .", "entity": [{"entity": "Selenium", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "Abstract The aim of this study was to evaluate the level of selenium ( Se ) in common raw plant materials ( herbs , leaves , flowers , fruits , and roots ) obtained from medicinal plants cultivated in Poland .", "entity": [{"entity": "selenium", "entity_type": "Chemical", "pos": [60, 68]}, {"entity": "Se", "entity_type": "Chemical", "pos": [71, 73]}], "task": "NER"}
{"text": "Furthermore , the relationship between the morphological part of a plant and its species was examined , and the concentration of Se in it was measured .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [129, 131]}], "task": "NER"}
{"text": "Spectrofluorimetric determination of Se in 148 samples of 44 plant species revealed that the majority of the plants contained Se at a level from several to several tens of mu g / kg dry weight ( d . w . ) .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [37, 39]}, {"entity": "Se", "entity_type": "Chemical", "pos": [126, 128]}], "task": "NER"}
{"text": "A relatively high Se concentration , in the order of 50 mu g / kg d . w . , was found in Majoranae herba , Crataegi fructus , and Lini semen .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [18, 20]}], "task": "NER"}
{"text": "An especially high Se level , > 100 mu g / kg d . w . , was found in only three plants - Equiseti herba , Farfarae folium , and Cichorii radix .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [19, 21]}], "task": "NER"}
{"text": "Application of a nonparametric Kruskal - Wallis analysis of variance test indicates that the morphological variable influences the level of Se in the studied groups of raw plant materials .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [140, 142]}], "task": "NER"}
{"text": "The mean concentration of Se in fruits differs significantly from that found in flowers and roots .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [26, 28]}], "task": "NER"}
{"text": "However , there was no statistically significant difference between the Se content in herbs and leaves and its levels in fruits , flowers , and roots .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [72, 74]}], "task": "NER"}
{"text": "Cluster analysis and principal component analysis calculations show that it is possible to relate the Se concentration in plant material to the plant species and botanical family of the medicinal plant in only a few cases .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [102, 104]}], "task": "NER"}
{"text": "Analysis of average Se levels in the plant species showed that the plants belonging to the Apiaceae and Labiatae are more Se - rich than those belonging to Rosaceae botanical families .", "entity": [{"entity": "Se", "entity_type": "Chemical", "pos": [20, 22]}, {"entity": "Se", "entity_type": "Chemical", "pos": [122, 124]}], "task": "NER"}
{"text": "Non - destructive monitoring of creaming of oil - in - water emulsion - based formulations using magnetic resonance imaging .", "entity": [], "task": "NER"}
{"text": "Abstract A non - destructive method for monitoring creaming of emulsion - based formulations is in great demand because it allows us to understand fully their instability mechanisms .", "entity": [], "task": "NER"}
{"text": "This study was aimed at demonstrating the usefulness of magnetic resonance ( MR ) techniques , including MR imaging ( MRI ) and MR spectroscopy ( MRS ) , for evaluating the physicochemical stability of emulsion - based formulations .", "entity": [], "task": "NER"}
{"text": "Emulsions that are applicable as the base of practical skin creams were used as test samples .", "entity": [], "task": "NER"}
{"text": "Substantial creaming was developed by centrifugation , which was then monitored by MRI .", "entity": [], "task": "NER"}
{"text": "The creaming oil droplet layer and aqueous phase were clearly distinguished by quantitative MRI by measuring T1 and the apparent diffusion coefficient .", "entity": [], "task": "NER"}
{"text": "Components in a selected volume in the emulsions could be analyzed using MRS .", "entity": [], "task": "NER"}
{"text": "Then , model emulsions having different hydrophilic - lipophilic balance ( HLB ) values were tested , and the optimal HLB value for a stable dispersion was determined .", "entity": [], "task": "NER"}
{"text": "In addition , the MRI examination enables the detection of creaming occurring in a polyethylene tube , which is commonly used for commercial products , without losing any image quality .", "entity": [{"entity": "polyethylene", "entity_type": "Chemical", "pos": [83, 95]}], "task": "NER"}
{"text": "These findings strongly indicate that MR techniques are powerful tools to evaluate the physicochemical stability of emulsion - based formulations .", "entity": [], "task": "NER"}
{"text": "This study will make a great contribution to the development and quality control of emulsion - based formulations .", "entity": [], "task": "NER"}
{"text": "Spectroscopic Study of the Light - Harvesting CP29 Antenna Complex of Photosystem II - Part I .", "entity": [], "task": "NER"}
{"text": "Recent structural data revealed that the CP29 protein of higher plant Photosystem II ( PSII ) contains 13 chlorophylls ( Chls ) per complex [ Pan et al . , Nat . Struct . Mol . Biol . 2011 , 18 , 309 ] , i . e . , five Chls more than in the predicted CP29 homology - based structure model [ Bassi et al . , Proc . Natl . Acad . Sci . USA 1999 , 96 , 10056 ] .", "entity": [{"entity": "chlorophylls", "entity_type": "Chemical", "pos": [106, 118]}, {"entity": "Chls", "entity_type": "Chemical", "pos": [121, 125]}], "task": "NER"}
{"text": "This lack of consensus presents a constraint on the interpretation of CP29 optical spectra and their underlying electronic structure .", "entity": [], "task": "NER"}
{"text": "To address this problem , we present new low - temperature ( 5 K ) absorption , fluorescence , and hole - burned ( HB ) spectra for CP29 proteins from spinach , which are compared with the previously reported data .", "entity": [], "task": "NER"}
{"text": "We focus on excitation energy transfer ( EET ) and the nature of the lowest - energy state ( s ) .", "entity": [], "task": "NER"}
{"text": "We argue that CP29 proteins previously studied by HB spectroscopy lacked at least one Chl a molecule ( i . e . , a615 or a611 ) , which along with Chl a612 contribute to the lowest energy state in more intact CP29 , and one Chl b ( most likely b607 ) .", "entity": [{"entity": "Chl a", "entity_type": "Chemical", "pos": [86, 91]}, {"entity": "Chl b", "entity_type": "Chemical", "pos": [224, 229]}], "task": "NER"}
{"text": "This is why the low - energy state and fluorescence maxima reported by Pieper et al .", "entity": [], "task": "NER"}
{"text": "[ Photochem . Photobiol . 2000 , 71 , 574 ] were blueshifted by ~ 1 nm , the low - energy state appeared to be highly localized on a single Chl a molecule , and the position of the low - energy state was independent of burning fluence .", "entity": [{"entity": "Chl a", "entity_type": "Chemical", "pos": [140, 145]}], "task": "NER"}
{"text": "In contrast , the position of the nonresonant HB spectrum shifts blue with increasing fluence in intact CP29 , as this state is strongly contributed to by several pigments ( i . e . , a611 , a612 , a615 and a610 ) .", "entity": [], "task": "NER"}
{"text": "Zero - phonon hole widths obtained for the Chl b band at 638 . 5 nm ( 5 K ) revealed two independent Chl b --> Chl a EET times , i . e . , 4 +/- 0 . 5 ps and 0 . 4 +/- 0 . 1 ps .", "entity": [{"entity": "Chl b", "entity_type": "Chemical", "pos": [43, 48]}, {"entity": "Chl b", "entity_type": "Chemical", "pos": [101, 106]}, {"entity": "Chl a", "entity_type": "Chemical", "pos": [111, 116]}], "task": "NER"}
{"text": "The latter value is a factor of two faster than previously observed by HB spectroscopy and very similar to the one observed by Gradinaru et al .", "entity": [], "task": "NER"}
{"text": "[ J . Phys . Chem . B 2000 , 104 , 9330 ] in pump - probe experiments .", "entity": [], "task": "NER"}
{"text": "EET time from 650 nm Chl b --> Chl a and downward EET from Chl ( s ) a state ( s ) at 665 nm occurs in 4 . 9 +/- 0 . 7 ps .", "entity": [{"entity": "Chl b", "entity_type": "Chemical", "pos": [21, 26]}, {"entity": "Chl a", "entity_type": "Chemical", "pos": [31, 36]}], "task": "NER"}
{"text": "These findings provide important constraints for excitonic calculations that are discussed in the accompanying paper ( Part II ) .", "entity": [], "task": "NER"}
{"text": "Group B Streptococcus pilus sortase regulation : a single mutation in the lid region induces pilin protein polymerization in vitro .", "entity": [], "task": "NER"}
{"text": "Gram - positive bacteria build pili on their cell surface via a class C sortase - catalyzed transpeptidation mechanism from pilin protein substrates .", "entity": [], "task": "NER"}
{"text": "Despite the availability of several crystal structures , pilus - related C sortases remain poorly characterized to date , and their mechanisms of transpeptidation and regulation need to be further investigated .", "entity": [], "task": "NER"}
{"text": "The available 3 - dimensional structures of these enzymes reveal a typical sortase fold , except for the presence of a unique feature represented by an N - terminal highly flexible loop known as the \" lid . \" This region interacts with the residues composing the catalytic triad and covers the active site , thus maintaining the enzyme in an autoinhibited state and preventing the accessibility to the substrate .", "entity": [{"entity": "N", "entity_type": "Chemical", "pos": [152, 153]}], "task": "NER"}
{"text": "It is believed that enzyme activation may occur only after lid displacement from the catalytic domain .", "entity": [], "task": "NER"}
{"text": "In this work , we provide the first direct evidence of the regulatory role of the lid , demonstrating that it is possible to obtain in vitro an efficient polymerization of pilin subunits using an active C sortase lid mutant carrying a single residue mutation in the lid region .", "entity": [], "task": "NER"}
{"text": "Moreover , biochemical analyses of this recombinant mutant reveal that the lid confers thermodynamic and proteolytic stability to the enzyme . - Cozzi , R . , Zerbini , F . , Assfalg , M . , D ' Onofrio , M . , Biagini , M . , Martinelli , M . , Nuccitelli , A . , Norais , N . , Telford , J .", "entity": [], "task": "NER"}
{"text": "L . , Maione , D . , Rinaudo , C .", "entity": [], "task": "NER"}
{"text": "D .", "entity": [], "task": "NER"}
{"text": "Anti - allergic actions of rottlerin from Mallotus philippinensis in experimental mast cell - mediated anaphylactic models .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross - linking of the allergen - specific IgE - bound high - affinity IgE receptors , leading to immediate mast cell degranulation .", "entity": [], "task": "NER"}
{"text": "Rottlerin is an active molecule isolated from Mallotus philippinensis , a medicinal plant used in Ayurvedic Medicine System for anti - allergic and anti - helminthic treatments .", "entity": [{"entity": "Rottlerin", "entity_type": "Chemical", "pos": [0, 9]}], "task": "NER"}
{"text": "The present study investigated potential anti - allergic effects of rottlerin in animal models of IgE - dependent anaphylaxis and the anti - allergic mechanisms of action of rottlerin in mast cells .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [68, 77]}, {"entity": "rottlerin", "entity_type": "Chemical", "pos": [174, 183]}], "task": "NER"}
{"text": "Anti - allergic actions of rottlerin were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models , and in anaphylactic contraction of bronchial rings isolated from sensitized guinea pigs .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "Direct mast cell - stabilizing effect of rottlerin was examined in RBL - 2H3 mast cell line .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [41, 50]}], "task": "NER"}
{"text": "Anti - allergic signaling mechanisms of action of rottlerin in mast cells were also examined .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [50, 59]}], "task": "NER"}
{"text": "Rottlerin prevented IgE - mediated cutaneous vascular extravasation , hypothermia , elevation in plasma histamine level and tracheal tissue mast cell degranulation in mice in a dose - dependent manner .", "entity": [{"entity": "Rottlerin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "histamine", "entity_type": "Chemical", "pos": [104, 113]}], "task": "NER"}
{"text": "In addition , rottlerin suppressed ovalbumin - induced guinea pig bronchial smooth muscle contraction .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Furthermore , rottlerin concentration - dependently blocked IgE - mediated immediate release of beta - hexosaminidase from RBL - 2H3 mast cells .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [14, 23]}], "task": "NER"}
{"text": "Rottlerin was found to inhibit IgE - induced PLC gamma 1 and Akt phosphorylation , production of IP3 and rise in cytosolic Ca ( 2 + ) level in mast cells .", "entity": [{"entity": "Rottlerin", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [123, 133]}], "task": "NER"}
{"text": "We report here for the first time that rottlerin possesses anti - allergic activity by blocking IgE - induced mast cell degranulation , providing a foundation for developing rottlerin for the treatment of allergic asthma and other mast cell - mediated allergic disorders .", "entity": [{"entity": "rottlerin", "entity_type": "Chemical", "pos": [39, 48]}, {"entity": "rottlerin", "entity_type": "Chemical", "pos": [174, 183]}], "task": "NER"}
{"text": "Clock Gene Expression in the Liver of Streptozotocin - induced and Spontaneous Type 1 Diabetic Rats .", "entity": [{"entity": "Streptozotocin", "entity_type": "Chemical", "pos": [38, 52]}], "task": "NER"}
{"text": "Several investigations have shown a relation between diabetes and alterations of the liver circadian clock .", "entity": [], "task": "NER"}
{"text": "We investigated the diurnal expression of clock genes and clock - controlled genes ( CCGs ) in 3 - hour intervals for a 24 - h period in the livers of male streptozotocin ( STZ ) - treated rats , male spontaneous type 1 diabetic LEW . 1AR1 - iddm ( Iddm ) rats , and Iddm rats treated for 10 days with insulin .", "entity": [{"entity": "streptozotocin", "entity_type": "Chemical", "pos": [156, 170]}, {"entity": "STZ", "entity_type": "Chemical", "pos": [173, 176]}], "task": "NER"}
{"text": "Hepatic mRNA was extracted , and the relative expression of clock genes ( Per1 , Per2 , Bmal1 , Clock , Cry1 ) , as well as CCGs ( Dbp , E4bp4 , RevErb alpha , Ror alpha , Ppar gamma ) , was analyzed by reverse transcription followed by real - time polymerase chain reaction .", "entity": [], "task": "NER"}
{"text": "Diabetic STZ and Iddm rats , as well as insulin - substituted Iddm rats , exhibited a significant diurnal expression pattern of clock genes as determined by Cosinor analysis ; however , the MESOR ( midline estimating statistic of rhythm ) of Bmal1 , Per2 , and Clock transcript expression was altered in Iddm and insulin - substituted Iddm rats .", "entity": [{"entity": "STZ", "entity_type": "Chemical", "pos": [9, 12]}], "task": "NER"}
{"text": "The hepatic expression of the CCGs Dbp and RevErb alpha revealed a diurnal rhythm in all investigated groups .", "entity": [], "task": "NER"}
{"text": "Insulin administration to Iddm rats normalized the enhanced MESOR in the expression of Dbp , RevErb alpha , and E4bp4 to the levels of normoglycemic controls .", "entity": [], "task": "NER"}
{"text": "Cosinor analysis indicated no diurnal rhythm of Ppar gamma expression in the livers of diabetic STZ or Iddm rats or in those of insulin - substituted Iddm rats .", "entity": [{"entity": "STZ", "entity_type": "Chemical", "pos": [96, 99]}], "task": "NER"}
{"text": "Also , insulin substitution could not reverse the decreased MESOR of Ppar gamma expression in Iddm rats .", "entity": [], "task": "NER"}
{"text": "In consequence of the diabetic disease , changes in the expression of clock genes and CCGs suggest alterations in the hepatic peripheral clock mechanism .", "entity": [], "task": "NER"}
{"text": "Studies on the Himbert Intramolecular Arene / Allene Diels - Alder Cycloaddition .", "entity": [{"entity": "Arene", "entity_type": "Chemical", "pos": [38, 43]}, {"entity": "Allene", "entity_type": "Chemical", "pos": [46, 52]}], "task": "NER"}
{"text": "Mechanistic Studies and Expansion of Scope to All - Carbon Tethers .", "entity": [{"entity": "Carbon", "entity_type": "Chemical", "pos": [52, 58]}], "task": "NER"}
{"text": "The unusual intramolecular arene / allene cycloaddition described 30 years ago by Himbert permits rapid access to strained polycyclic compounds that offer great potential for the synthesis of complex scaffolds .", "entity": [{"entity": "arene", "entity_type": "Chemical", "pos": [27, 32]}, {"entity": "allene", "entity_type": "Chemical", "pos": [35, 41]}], "task": "NER"}
{"text": "To more fully understand the mechanism of this cycloaddition reaction , and to guide efforts to extend its scope to new substrates , quantum mechanical computational methods were employed in concert with laboratory experiments .", "entity": [], "task": "NER"}
{"text": "These studies indicated that the cycloadditions likely proceed via concerted processes ; a stepwise biradical mechanism was shown to be higher in energy in the cases studied .", "entity": [], "task": "NER"}
{"text": "The original Himbert cycloaddition chemistry is also extended from heterocyclic to carbocyclic systems , with computational guidance used to predict thermodynamically favorable cases .", "entity": [], "task": "NER"}
{"text": "Complex polycyclic scaffolds result from the combination of the cycloaddition and subsequent ring - rearrangement metathesis reactions .", "entity": [], "task": "NER"}
{"text": "Reversible Sliding in Networks of Nanowires .", "entity": [], "task": "NER"}
{"text": "This work demonstrates that metal nanowires in a percolating network can reversibly slide across one another .", "entity": [], "task": "NER"}
{"text": "Reversible sliding allows networks of metal nanowires to maintain electrical contact while being stretched to strains greater than the fracture strain for individual nanowires .", "entity": [], "task": "NER"}
{"text": "This phenomenon was demonstrated by using networks of nanowires as compliant electrodes for a dielectric elastomer actuator .", "entity": [], "task": "NER"}
{"text": "Reversible nanowire sliding enabled actuation to a maximum area strain of 200 % , and repetitive cycling of the actuator to an area strain of 25 % over 150 times .", "entity": [], "task": "NER"}
{"text": "During actuation , the transmittance of the network increased 4 . 5 times , from 13 % to 58 % .", "entity": [], "task": "NER"}
{"text": "Compared to carbon - based compliant electrodes , networks of metal nanowires can actuate across a broader range of optical transmittance .", "entity": [{"entity": "carbon", "entity_type": "Chemical", "pos": [12, 18]}], "task": "NER"}
{"text": "The widely tunable transmittance of nanowire - based actuators allows for their use as a light valve .", "entity": [], "task": "NER"}
{"text": "Piezotronic Effect in Solution - Grown p - Type ZnO Nanowires and Films .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [48, 51]}], "task": "NER"}
{"text": "Investigating the piezotronic effect in p - type piezoelectric semiconductor is critical for developing a complete piezotronic theory and designing / fabricating novel piezotronic applications with more complex functionality .", "entity": [], "task": "NER"}
{"text": "Using a low temperature solution method , we were able to produce ultralong ( up to 60 mu m in length ) Sb doped p - type ZnO nanowires on both rigid and flexible substrates .", "entity": [{"entity": "Sb", "entity_type": "Chemical", "pos": [104, 106]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [122, 125]}], "task": "NER"}
{"text": "For the p - type nanowire field effect transistor , the on / off ratio , threshold voltage , mobility , and carrier concentration of 0 . 2 % Sb - doped sample are found to be 10 ( 5 ) , 2 . 1 V , 0 . 82 cm ( 2 ) . V ( - 1 ) . s ( - 1 ) , and 2 . 6 x 10 ( 17 ) cm ( - 3 ) , respectively , and the corresponding values for 1 % Sb doped samples are 10 ( 4 ) , 2 . 0 V , 1 . 24 cm ( 2 ) . V ( - 1 ) . s ( - 1 ) , and 3 . 8 x 10 ( 17 ) cm ( - 3 ) .", "entity": [{"entity": "Sb", "entity_type": "Chemical", "pos": [141, 143]}, {"entity": "Sb", "entity_type": "Chemical", "pos": [325, 327]}], "task": "NER"}
{"text": "We further investigated the universality of piezotronic effect in the as - synthesized Sb - doped p - type ZnO NWs and reported for the first time strain - gated piezotronic transistors as well as piezopotential - driven mechanical energy harvesting based on solution - grown p - type ZnO NWs .", "entity": [{"entity": "Sb", "entity_type": "Chemical", "pos": [87, 89]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [107, 110]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [285, 288]}], "task": "NER"}
{"text": "The results presented here broaden the scope of piezotronics and extend the framework for its potential applications in electronics , optoelectronics , smart MEMS / NEMS , and human - machine interfacing .", "entity": [], "task": "NER"}
{"text": "Topographically - patterned porous membranes in a microfluidic device as an in vitro model of renal reabsorptive barriers .", "entity": [], "task": "NER"}
{"text": "Models of reabsorptive barriers require both a means to provide realistic physiologic cues to and quantify transport across a layer of cells forming the barrier .", "entity": [], "task": "NER"}
{"text": "Here we have topographically - patterned porous membranes with several user - defined pattern types .", "entity": [], "task": "NER"}
{"text": "To demonstrate the utility of the patterned membranes , we selected one type of pattern and applied it to a membrane to serve as a cell culture support in a microfluidic model of a renal reabsorptive barrier .", "entity": [], "task": "NER"}
{"text": "The topographic cues in the model resemble physiological cues found in vivo while the porous structure allows quantification of transport across the cell layer .", "entity": [], "task": "NER"}
{"text": "Sub - micron surface topography generated via hot - embossing onto a track - etched polycarbonate membrane , fully replicated topographical features and preserved porous architecture .", "entity": [{"entity": "polycarbonate", "entity_type": "Chemical", "pos": [84, 97]}], "task": "NER"}
{"text": "Pore size and shape were analyzed with SEM and image analysis to determine the effect of hot embossing on pore morphology .", "entity": [], "task": "NER"}
{"text": "The membrane was assembled into a bilayer microfluidic device and a human kidney proximal tubule epithelial cell line ( HK - 2 ) and primary renal proximal tubule epithelial cells ( RPTEC ) were cultured to confluency on the membrane .", "entity": [], "task": "NER"}
{"text": "Immunofluorescent staining of both cell types revealed protein expression indicative of the formation of a reabsorptive barrier responsive to mechanical stimulation : ZO - 1 ( tight junction ) , paxillin ( focal adhesions ) and acetylated alpha - tubulin ( primary cilia ) .", "entity": [], "task": "NER"}
{"text": "HK - 2 and RPTEC aligned in the direction of ridge / groove topography of the membrane in the device , evidence that the device has mechanical control over cell response .", "entity": [], "task": "NER"}
{"text": "This topographically - patterned porous membrane provides an in vitro platform on which to model reabsorptive barriers with meaningful applications for understanding biological transport phenomenon , underlying disease mechanisms , and drug toxicity .", "entity": [], "task": "NER"}
{"text": "Rapeseed oil - rich diet alters hepatic mitochondrial membrane lipid composition and disrupts bioenergetics .", "entity": [], "task": "NER"}
{"text": "Diet is directly related with physiological alterations occurring at a cell and subcellular level .", "entity": [], "task": "NER"}
{"text": "However , the role of diet manipulation on mitochondrial physiology is still largely unexplored .", "entity": [], "task": "NER"}
{"text": "Aiming at correlating diet with alterations of mitochondrial membrane composition and bioenergetics , Wistar - Han male rats were fed for 11 , 22 and 33 days with a rapeseed oil - based diet and mitochondrial bioenergetics , and membrane composition were compared at each time point with a standard diet group .", "entity": [], "task": "NER"}
{"text": "Considerable differences were noticed in mitochondrial membrane lipid composition , namely in terms of fatty acyl chains and relative proportions of phospholipid classes , the modified diet inducing a decrease in the saturated to unsaturated molar ratio and an increase in the phosphatidylcholine to phosphatidylethanolamine molar ratio .", "entity": [{"entity": "fatty acyl", "entity_type": "Chemical", "pos": [103, 113]}, {"entity": "phosphatidylcholine", "entity_type": "Chemical", "pos": [277, 296]}, {"entity": "phosphatidylethanolamine", "entity_type": "Chemical", "pos": [300, 324]}], "task": "NER"}
{"text": "Mass spectrometry lipid analysis showed significant differences in the major species of cardiolipin , with an apparent increased incorporation of oleic acid as a result of exposure to the modified diet .", "entity": [{"entity": "cardiolipin", "entity_type": "Chemical", "pos": [88, 99]}, {"entity": "oleic acid", "entity_type": "Chemical", "pos": [146, 156]}], "task": "NER"}
{"text": "Rats fed the modified diet during 22 days showed decreased hepatic mitochondrial state 3 respiration and were more susceptible to Ca ( 2 + ) - induced transition pore opening .", "entity": [{"entity": "Ca ( 2 + )", "entity_type": "Chemical", "pos": [130, 140]}], "task": "NER"}
{"text": "Rapeseed oil - enriched diet also appeared to promote a decrease in hydroperoxide production by the respiratory chain , although a simultaneous decrease in vitamin E content was detected .", "entity": [{"entity": "hydroperoxide", "entity_type": "Chemical", "pos": [68, 81]}, {"entity": "vitamin E", "entity_type": "Chemical", "pos": [156, 165]}], "task": "NER"}
{"text": "In conclusion , our data indicate that the rapeseed oil diet causes negative alterations on hepatic mitochondrial bioenergetics , which may result from membrane remodeling .", "entity": [], "task": "NER"}
{"text": "Such alterations may have an impact not only on energy supply to the cell , but also on drug - induced hepatic mitochondrial liabilities .", "entity": [], "task": "NER"}
{"text": "Individual multi - locus heterozygosity is associated with lower morning plasma cortisol concentration .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [80, 88]}], "task": "NER"}
{"text": "OBJECTIVE .", "entity": [], "task": "NER"}
{"text": "STRESS IS IMPLICATED AS A RISK FACTOR FOR NUMEROUS ILLNESSES IN HUMANS , PUTATIVELY IN PART MEDIATED BY BIOLOGICAL RESPONSES TO STRESS , SUCH AS ELEVATED CORTISOL .", "entity": [{"entity": "CORTISOL", "entity_type": "Chemical", "pos": [154, 162]}], "task": "NER"}
{"text": "THE THEORY OF GENETIC HOMEOSTASIS SUGGESTS THAT INDIVIDUAL HETEROZYGOSITY FACILITATES COMPENSATION FOR ENVIRONMENTAL STRESSES .", "entity": [], "task": "NER"}
{"text": "WE HYPOTHESIZED THAT HETEROZYGOSITY AMELIORATES THE BIOLOGICAL RESPONSE TO A GIVEN LEVEL OF PERCEIVED STRESS , REFLECTED IN LOWER PLASMA CORTISOL CONCENTRATIONS . DESIGN .", "entity": [{"entity": "CORTISOL", "entity_type": "Chemical", "pos": [137, 145]}], "task": "NER"}
{"text": "WE EXAMINE THE ROLE OF HETEROZYGOSITY ON THE ASSOCIATION BETWEEN PERCEIVED PSYCHOLOGICAL STRESS AND MORNING CORTISOL CONCENTRATIONS IN 854 INDIVIDUALS FROM THE ISOLATED ISLAND OF VIS , CROATIA . METHODS .", "entity": [{"entity": "CORTISOL", "entity_type": "Chemical", "pos": [108, 116]}], "task": "NER"}
{"text": "CORTISOL WAS MEASURED IN MORNING PLASMA SAMPLES .", "entity": [{"entity": "CORTISOL", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "1184 AUTOSOMAL MICROSATELLITE MARKERS WERE GENOTYPED AND INDIVIDUAL MULTI - LOCUS HETEROZYGOSITY WAS CALCULATED AS THE PROPORTION OF HETEROZYGOUS MARKERS .", "entity": [], "task": "NER"}
{"text": "GENERAL HEALTH QUESTIONNAIRE ( GHQ - 30 ) WAS USED TO ASSESS THE DEGREE OF PSYCHOLOGICAL DISTRESS . RESULTS .", "entity": [], "task": "NER"}
{"text": "MEAN MULTI - LOCUS HETEROZYGOSITY WAS 34 . 850 . 45 % ( RANGE : 31 . 97 - 36 . 22 % ) .", "entity": [], "task": "NER"}
{"text": "Psychological distress ( GHQ Likert score > 31 ) was more prevalent in women ( 37 % versus 18 % in men , p < 0 . 0001 ) , in less educated people ( beta = - 0 . 35 per year in school , p < 0 . 001 ) and in lower socio - economic classes ( beta = - 3 . 59 , p < 0 . 0001 ) .", "entity": [], "task": "NER"}
{"text": "Cortisol was positively associated with psychological distress ( beta = 2 . 20 , p = 0 . 01 ) .", "entity": [{"entity": "Cortisol", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "In a regression model adjusting for age , BMI , education and GHQ - 30 score , multi - locus heterozygosity was independently and inversely associated with morning plasma cortisol ( p = 0 . 005 ) . Conclusion .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [171, 179]}], "task": "NER"}
{"text": "More heterozygous individuals , as measured by microsatellite markers , had lower morning plasma cortisol concentrations for a given level of perceived psychological stress .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [97, 105]}], "task": "NER"}
{"text": "This may be important , as higher cortisol concentrations may increase allostatic load and be associated with higher risk of stress - related illness .", "entity": [{"entity": "cortisol", "entity_type": "Chemical", "pos": [34, 42]}], "task": "NER"}
{"text": "Efficient Light Harvesting with Micropatterned 3D Pyramidal Photoanodes in Dye - Sensitized Solar Cells .", "entity": [], "task": "NER"}
{"text": "3D TiO2 photoanodes in dye - sensitized solar cells ( DSCs ) are fabricated by the soft lithographic technique for efficient light trapping .", "entity": [{"entity": "TiO2", "entity_type": "Chemical", "pos": [3, 7]}], "task": "NER"}
{"text": "An extended strategy to the construction of randomized pyramid structure is developed by the conventional wet - etching of a silicon wafer for low - cost fabrication .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [125, 132]}], "task": "NER"}
{"text": "Moreover , the futher enhancement of light absorption resulting in photocurrent increase is achieved by combining the 3D photoanode with a conventional scattering layer .", "entity": [], "task": "NER"}
{"text": "Buckling - Induced Reversible Symmetry Breaking and Amplification of Chirality Using Supported Cellular Structures .", "entity": [], "task": "NER"}
{"text": "Buckling - induced reversible symmetry breaking and amplification of chirality using macro - and microscale supported cellular structures is described .", "entity": [], "task": "NER"}
{"text": "Guided by extensive theoretical analysis , cellular structures are rationally designed , in which buckling induces a reversible switching between achiral and chiral configurations .", "entity": [], "task": "NER"}
{"text": "Additionally , it is demonstrated that the proposed mechanism can be generalized over a wide range of length scales , geometries , materials , and stimuli .", "entity": [], "task": "NER"}
{"text": "Upgraded Silicon Nanowires by Metal - Assisted Etching of Metallurgical Silicon : A New Route to Nanostructured Solar - Grade Silicon .", "entity": [{"entity": "Silicon", "entity_type": "Chemical", "pos": [9, 16]}, {"entity": "Silicon", "entity_type": "Chemical", "pos": [72, 79]}, {"entity": "Silicon", "entity_type": "Chemical", "pos": [126, 133]}], "task": "NER"}
{"text": "Through metal assisted chemical etching ( MaCE ) , superior purification of dirty Si was observed , from 99 . 74 to 99 . 9884 % for metallurgical Si and from 99 . 999772 to 99 . 999899 % for upgraded metallurgical Si .", "entity": [{"entity": "Si", "entity_type": "Chemical", "pos": [82, 84]}, {"entity": "Si", "entity_type": "Chemical", "pos": [146, 148]}, {"entity": "Si", "entity_type": "Chemical", "pos": [214, 216]}], "task": "NER"}
{"text": "Meanwhile , large area of silicon nanowires ( SiNW ) was fabricated .", "entity": [{"entity": "silicon", "entity_type": "Chemical", "pos": [26, 33]}], "task": "NER"}
{"text": "The purification effect induced ~ 35 % increase in photocurrent for SiNW based photoelectrochemical cell .", "entity": [], "task": "NER"}
{"text": "High - Performance Vertical Organic Transistors .", "entity": [], "task": "NER"}
{"text": "Vertical organic thin - film transistors ( VOTFTs ) are promising devices to overcome the transconductance and cut - off frequency restrictions of horizontal organic thin - film transistors .", "entity": [], "task": "NER"}
{"text": "The basic physical mechanisms of VOTFT operation , however , are not well understood and VOTFTs often require complex patterning techniques using self - assembly processes which impedes a future large - area production .", "entity": [], "task": "NER"}
{"text": "In this contribution , high - performance vertical organic transistors comprising pentacene for p - type operation and C60 for n - type operation are presented .", "entity": [{"entity": "pentacene", "entity_type": "Chemical", "pos": [82, 91]}, {"entity": "C60", "entity_type": "Chemical", "pos": [119, 122]}], "task": "NER"}
{"text": "The static current - voltage behavior as well as the fundamental scaling laws of such transistors are studied , disclosing a remarkable transistor operation with a behavior limited by injection of charge carriers .", "entity": [], "task": "NER"}
{"text": "The transistors are manufactured by photolithography , in contrast to other VOTFT concepts using self - assembled source electrodes .", "entity": [], "task": "NER"}
{"text": "Fluorinated photoresist and solvent compounds allow for photolithographical patterning directly and strongly onto the organic materials , simplifying the fabrication protocol and making VOTFTs a prospective candidate for future high - performance applications of organic transistors .", "entity": [], "task": "NER"}
{"text": "Protective Role of ( RS ) - glucoraphanin Bioactivated with Myrosinase in an Experimental Model of Multiple Sclerosis .", "entity": [{"entity": "( RS ) - glucoraphanin", "entity_type": "Chemical", "pos": [19, 41]}], "task": "NER"}
{"text": "AIM : The discovery of new natural compounds with pharmacological properties is a field of interest widely growing .", "entity": [], "task": "NER"}
{"text": "Recent literature shows that Brassica vegetables ( Cruciferae ) possess therapeutic effects particularly ascribed due to their content in glucosinolates , which upon myrosinase hydrolysis release the corresponding isothiocyanates .", "entity": [{"entity": "glucosinolates", "entity_type": "Chemical", "pos": [138, 152]}, {"entity": "isothiocyanates", "entity_type": "Chemical", "pos": [214, 229]}], "task": "NER"}
{"text": "This study examines the potential neuroprotective and immunomodulatory effects of ( RS ) - glucoraphanin from Tuscan black kale ( Brassica oleracea L . var . acephala sabellica ) bioactivated with myrosinase ( bioactive RS - GRA ) ( 10 mg / kg / day intraperitoneally ) , in an experimental autoimmune encephalomyelitis ( EAE ) , a model of multiple sclerosis .", "entity": [{"entity": "( RS ) - glucoraphanin", "entity_type": "Chemical", "pos": [82, 104]}, {"entity": "RS - GRA", "entity_type": "Chemical", "pos": [220, 228]}], "task": "NER"}
{"text": "METHODS : EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide ( MOG35 - 55 ) in mice .", "entity": [], "task": "NER"}
{"text": "After immunization , mice were observed daily for signs of EAE and weight loss .", "entity": [], "task": "NER"}
{"text": "Clinical score was evaluated using a standardized scoring system .", "entity": [], "task": "NER"}
{"text": "RESULTS : By Western blot analysis of spinal cord tissues , we have demonstrated that treatment with bioactive RS - GRA significantly decreased nuclear factor ( NF ) - kB translocation , pro - inflammatory cytokine production such as interleukin - 1 beta ( IL - 1 beta ) , and apoptosis ( Bax and caspase 3 expression ) .", "entity": [{"entity": "RS - GRA", "entity_type": "Chemical", "pos": [111, 119]}], "task": "NER"}
{"text": "CONCLUSION : Our results clearly demonstrate that bioactive RS - GRA treatment may represent a useful therapeutic perspective in the treatment of this disease .", "entity": [{"entity": "RS - GRA", "entity_type": "Chemical", "pos": [60, 68]}], "task": "NER"}
{"text": "Anti - HIV and NO production inhibition activities of epi - aleuritolic acid derivatives .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [15, 17]}, {"entity": "epi - aleuritolic acid", "entity_type": "Chemical", "pos": [54, 76]}], "task": "NER"}
{"text": "Fifteen epi - aleuritolic acid derivatives were synthesized and evaluated for anti - HIV activity in 293 T cells and NO production inhibition activity .", "entity": [{"entity": "epi - aleuritolic acid", "entity_type": "Chemical", "pos": [8, 30]}, {"entity": "NO", "entity_type": "Chemical", "pos": [117, 119]}], "task": "NER"}
{"text": "Of the derivatives , 1 , 2 , 3 , 4 , 11 , and 13 showed relatively potent anti - HIV activity with EC50 values ranging from 5 . 80 to 13 . 30 mu M .", "entity": [], "task": "NER"}
{"text": "The most potent compound , 3 alpha - 2 ' , 2 ' - dimethylsuccinic acyl epi - aleuritolic acid ( 11 ) , displayed significant anti - HIV activity with an EC50 value of 5 . 80 mu M .", "entity": [{"entity": "3 alpha - 2 ' , 2 ' - dimethylsuccinic acyl epi - aleuritolic acid", "entity_type": "Chemical", "pos": [27, 93]}], "task": "NER"}
{"text": "Compounds 1 , 3 , 4 , and 11 showed NO inhibition activity , with IC50 values ranging from 3 . 40 to 7 . 10 mu M and compound 1 inhibited NO production with an IC50 value of 3 . 40 mu M .", "entity": [{"entity": "NO", "entity_type": "Chemical", "pos": [36, 38]}, {"entity": "NO", "entity_type": "Chemical", "pos": [138, 140]}], "task": "NER"}
{"text": "Phytochemical investigation on Atriplex halimus L . from Sardinia .", "entity": [], "task": "NER"}
{"text": "In this study , we reported the phytochemical composition of the aerial parts of Atriplex halimus L . collected from Sardinia .", "entity": [], "task": "NER"}
{"text": "This species is a halophytic shrub , typical of the Mediterranean Basin .", "entity": [], "task": "NER"}
{"text": "Four new glycosylated flavonoids were isolated and their structures were elucidated on the basis of 1D , 2D NMR and MS spectra as 3 ' , 5 ' - dimethoxymyricetin - 3 - O - beta - d - xylopyranosyl - 7 - O - fucopyranosyl - ( 1 --> 3 ) - beta - d - glucopyranoside ( 1 ) , 3 ' - methoxyquercetin - 7 - O - beta - d - fucopyranosyl - ( 1 --> 3 ) - beta - d - glucopyranosyl - 3 - O - beta - xylopyranosyl - ( 1 --> 4 ) - beta - xylopyranoside ( 2 ) , 3 ' - methoxyquercetin - 7 - O - alpha - l - rhamnopyranosyl - 3 - O - alpha - arabinofuranosyl - ( 1 --> 6 ) - beta - d - glucopyranoside ( 3 ) and 3 ' , 5 ' - dimethoxymyricetin - 7 - O - fucopyranosyl - ( 1 --> 3 ) - beta - d - glucopyranoside ( 4 ) .", "entity": [{"entity": "glycosylated flavonoids", "entity_type": "Chemical", "pos": [9, 32]}, {"entity": "3 ' , 5 ' - dimethoxymyricetin - 3 - O - beta - d - xylopyranosyl - 7 - O - fucopyranosyl - ( 1 --> 3 ) - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [130, 262]}, {"entity": "3 ' - methoxyquercetin - 7 - O - beta - d - fucopyranosyl - ( 1 --> 3 ) - beta - d - glucopyranosyl - 3 - O - beta - xylopyranosyl - ( 1 --> 4 ) - beta - xylopyranoside", "entity_type": "Chemical", "pos": [271, 439]}, {"entity": "3 ' - methoxyquercetin - 7 - O - alpha - l - rhamnopyranosyl - 3 - O - alpha - arabinofuranosyl - ( 1 --> 6 ) - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [448, 586]}, {"entity": "3 ' , 5 ' - dimethoxymyricetin - 7 - O - fucopyranosyl - ( 1 --> 3 ) - beta - d - glucopyranoside", "entity_type": "Chemical", "pos": [597, 694]}], "task": "NER"}
{"text": "LC - MS ( n ) analysis on the extract revealed the presence of other myricetin , quercetin , isorhamnetin glycosides , simple phenolic acids and esters .", "entity": [{"entity": "myricetin", "entity_type": "Chemical", "pos": [69, 78]}, {"entity": "quercetin", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "isorhamnetin glycosides", "entity_type": "Chemical", "pos": [93, 116]}, {"entity": "phenolic acids", "entity_type": "Chemical", "pos": [126, 140]}, {"entity": "esters", "entity_type": "Chemical", "pos": [145, 151]}], "task": "NER"}
{"text": "Indanomycin - related antibiotics from marine Streptomyces antibioticus PTZ0016 .", "entity": [{"entity": "Indanomycin", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Four indanomycin - related antibiotics 2 - 5 were isolated from the cultured broth of marine Streptomyces antibioticus strain PTZ0016 .", "entity": [{"entity": "indanomycin", "entity_type": "Chemical", "pos": [5, 16]}], "task": "NER"}
{"text": "Their structures were characterised as 16 - deethylindanomycin ( 2 ) , iso - 16 - deethylindanomycin ( 3 ) , 16 - deethylindanomycin methyl ester ( 4 ) and iso - 16 - deethylindanomycin methyl ester ( 5 ) on the basis of NMR , HR - ESI - MS and CD evidences .", "entity": [{"entity": "16 - deethylindanomycin", "entity_type": "Chemical", "pos": [39, 62]}, {"entity": "iso - 16 - deethylindanomycin", "entity_type": "Chemical", "pos": [71, 100]}, {"entity": "16 - deethylindanomycin methyl ester", "entity_type": "Chemical", "pos": [109, 145]}, {"entity": "iso - 16 - deethylindanomycin methyl ester", "entity_type": "Chemical", "pos": [156, 198]}], "task": "NER"}
{"text": "Compounds 3 - 5 are new additions to the class of indanomycin antibiotics .", "entity": [{"entity": "indanomycin", "entity_type": "Chemical", "pos": [50, 61]}], "task": "NER"}
{"text": "All isolated compounds showed in vitro activity against Staphylococcus aureus with minimal inhibitory concentration at 4 . 0 - 8 . 0 mu g / ml .", "entity": [], "task": "NER"}
{"text": "Amelioration of palmitate - induced insulin resistance in C2C12 muscle cells by rooibos ( Aspalathus linearis ) .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [16, 25]}], "task": "NER"}
{"text": "Increased levels of free fatty acids ( FFAs ) , specifically saturated free fatty acids such as palmitate are associated with insulin resistance of muscle , fat and liver .", "entity": [{"entity": "free fatty acids", "entity_type": "Chemical", "pos": [20, 36]}, {"entity": "FFAs", "entity_type": "Chemical", "pos": [39, 43]}, {"entity": "saturated free fatty acids", "entity_type": "Chemical", "pos": [61, 87]}, {"entity": "palmitate", "entity_type": "Chemical", "pos": [96, 105]}], "task": "NER"}
{"text": "Skeletal muscle , responsible for up to 80 % of the glucose disposal from the peripheral circulation , is particularly vulnerable to increased levels of saturated FFAs .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [52, 59]}, {"entity": "FFAs", "entity_type": "Chemical", "pos": [163, 167]}], "task": "NER"}
{"text": "Rooibos ( Aspalathus linearis ) and its unique dihydrochalcone C - glucoside , aspalathin , shown to reduce hyperglycemia in diabetic rats , could play a role in preventing or ameliorating the development of insulin resistance .", "entity": [{"entity": "dihydrochalcone C - glucoside", "entity_type": "Chemical", "pos": [47, 76]}, {"entity": "aspalathin", "entity_type": "Chemical", "pos": [79, 89]}], "task": "NER"}
{"text": "This study aims to establish whether rooibos can ameliorate experimentally - induced insulin - resistance in C2C12 skeletal muscle cells .", "entity": [], "task": "NER"}
{"text": "Palmitate - induced insulin resistant C2C12 cells were treated with an aspalathin - enriched green ( unfermented ) rooibos extract ( GRE ) , previously shown for its blood glucose lowering effect in vitro and in vivo or an aqueous extract of fermented rooibos ( FRE ) .", "entity": [{"entity": "Palmitate", "entity_type": "Chemical", "pos": [0, 9]}, {"entity": "aspalathin", "entity_type": "Chemical", "pos": [71, 81]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [172, 179]}], "task": "NER"}
{"text": "Glucose uptake and mitochondrial activity were measured using 2 - deoxy - [ ( 3 ) H ] - d - glucose , MTT and ATP assays , respectively .", "entity": [{"entity": "Glucose", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "2 - deoxy - [ ( 3 ) H ] - d - glucose", "entity_type": "Chemical", "pos": [62, 99]}, {"entity": "MTT", "entity_type": "Chemical", "pos": [102, 105]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [110, 113]}], "task": "NER"}
{"text": "Expression of proteins relevant to glucose metabolism was analysed by Western blot .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [35, 42]}], "task": "NER"}
{"text": "GRE contained higher levels of all compounds , except the enolic phenylpyruvic acid - 2 - O - glucoside and luteolin - 7 - O - glucoside .", "entity": [{"entity": "phenylpyruvic acid - 2 - O - glucoside", "entity_type": "Chemical", "pos": [65, 103]}, {"entity": "luteolin - 7 - O - glucoside", "entity_type": "Chemical", "pos": [108, 136]}], "task": "NER"}
{"text": "Both rooibos extracts increased glucose uptake , mitochondrial activity and ATP production .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [32, 39]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "Compared to FRE , GRE was more effective at increasing glucose uptake and ATP production .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [55, 62]}, {"entity": "ATP", "entity_type": "Chemical", "pos": [74, 77]}], "task": "NER"}
{"text": "At a mechanistic level both extracts down - regulated PKC theta activation , which is associated with palmitate - induced insulin resistance .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [102, 111]}], "task": "NER"}
{"text": "Furthermore , the extracts increased activation of key regulatory proteins ( AKT and AMPK ) involved in insulin - dependent and non - insulin regulated signalling pathways .", "entity": [], "task": "NER"}
{"text": "Protein levels of the glucose transporter ( GLUT4 ) involved in glucose transport via these two pathways were also increased .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [22, 29]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [64, 71]}], "task": "NER"}
{"text": "This in vitro study therefore confirms that rooibos can ameliorate palmitate - induced insulin resistance in C2C12 skeletal muscle cells .", "entity": [{"entity": "palmitate", "entity_type": "Chemical", "pos": [67, 76]}], "task": "NER"}
{"text": "Inhibition of PKC theta activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect .", "entity": [], "task": "NER"}
{"text": "Mikania laevigata : Chemical characterization and selective cytotoxic activity of extracts on tumor cell lines .", "entity": [], "task": "NER"}
{"text": "Cancer is the second major cause of mortality worldwide , losing only to cardiovascular disease .", "entity": [], "task": "NER"}
{"text": "Nowadays , around 50 % of antineoplastic drugs were discovered and isolated by indications of plants in folk medicine .", "entity": [], "task": "NER"}
{"text": "In Brazilian flora there are many species of plants which have great therapeutic importance , highlighting the Mikania laevigata ( Asteraceae ) that has been used for their valuable properties , especially in the respiratory tract .", "entity": [], "task": "NER"}
{"text": "In the present study , the compounds of M . laevigata extracts were characterized by High Resolution Mass Spectrometry ( HRMS ) and Gas Chromatography with Mass analysis ( GC / MS - EI ) .", "entity": [], "task": "NER"}
{"text": "Therefore , the presence of some compounds with promising biological properties as antitumor activity was detected .", "entity": [], "task": "NER"}
{"text": "Coumarin ( 1 , 2 - benzopyrone ) was previously reported as responsible for some biological activities of this plant species .", "entity": [{"entity": "Coumarin", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "1 , 2 - benzopyrone", "entity_type": "Chemical", "pos": [11, 30]}], "task": "NER"}
{"text": "Here , the extracts were evaluated by their cytotoxic activity against tumor ( Hep - 2 , HeLa ) and non tumor ( MRC - 5 ) cell lines , presenting significant inhibitory activity of cell growth in all extracts analyzed , chloroform , ethyl acetate , hexane , ethanol , which is related to its chemical composition .", "entity": [{"entity": "chloroform", "entity_type": "Chemical", "pos": [220, 230]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [233, 246]}, {"entity": "hexane", "entity_type": "Chemical", "pos": [249, 255]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [258, 265]}], "task": "NER"}
{"text": "From the four different extracts here tested , two of them , hexane and ethanol , presented a clear selectivity against both tumor cells lines investigated .", "entity": [{"entity": "hexane", "entity_type": "Chemical", "pos": [61, 67]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [72, 79]}], "task": "NER"}
{"text": "This can be explained by variances and increase of phenolic compounds in the ethanol fraction and an association of molecules with coumarin found in the hexane fraction .", "entity": [{"entity": "phenolic", "entity_type": "Chemical", "pos": [51, 59]}, {"entity": "ethanol", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "coumarin", "entity_type": "Chemical", "pos": [131, 139]}, {"entity": "hexane", "entity_type": "Chemical", "pos": [153, 159]}], "task": "NER"}
{"text": "Rokumi - jio - gan - containing prescriptions regulate oxidative stress through improving dyslipidemia in a subtotal nephrectomized rat model .", "entity": [], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Rokumi - jio - gan - containing prescriptions , traditional medicine , are widely used to treat renal dysfunction in Japan .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : The present study was conducted to examine whether two Rokumi - jio - gan - containing prescriptions ( Hachimi - jio - gan and Bakumi - jio - gan ) have an ameliorative effect on dyslipidemia in nephrectomized rats .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : Each prescription was orally administered to nephrectomized rats at 150mg / kg body weight per day for 10 weeks , and its effect was compared with vehicle - treated nephrectomized rats .", "entity": [], "task": "NER"}
{"text": "RESULTS : Rats given Hachimi - jio - gan and Bakumi - jio - gan showed an improvement of renal functional parameters such as serum urea nitrogen , creatinine , creatinine clearance , and urinary protein .", "entity": [{"entity": "urea", "entity_type": "Chemical", "pos": [131, 135]}, {"entity": "nitrogen", "entity_type": "Chemical", "pos": [136, 144]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [147, 157]}, {"entity": "creatinine", "entity_type": "Chemical", "pos": [160, 170]}], "task": "NER"}
{"text": "The increased triglyceride , total cholesterol , non - esterified fatty acid , high - density lipoprotein cholesterol , and very low - density lipoprotein cholesterol / low - density lipoprotein cholesterol levels in serum , and triglyceride and total cholesterol contents in the kidney of nephrectomized rats were significantly decreased by Hachimi - jio - gan and Bakumi - jio - gan administration .", "entity": [{"entity": "triglyceride", "entity_type": "Chemical", "pos": [14, 26]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [35, 46]}, {"entity": "fatty acid", "entity_type": "Chemical", "pos": [66, 76]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [106, 117]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [155, 166]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [195, 206]}, {"entity": "triglyceride", "entity_type": "Chemical", "pos": [229, 241]}, {"entity": "cholesterol", "entity_type": "Chemical", "pos": [252, 263]}], "task": "NER"}
{"text": "Furthermore , Hachimi - jio - gan acts as a regulator of peroxisome proliferator - activated receptor alpha , sterol regulatory element binding protein ( SREBP ) - 1 , and SREBP - 2 .", "entity": [{"entity": "sterol", "entity_type": "Chemical", "pos": [110, 116]}], "task": "NER"}
{"text": "On the contrary , the increased reactive oxygen species and thiobarbituric acid - reactive substance were decreased , while superoxide dismutase and the reduced glutathione / oxidized glutathione ratio were augmented by Hachimi - jio - gan rather than Bakumi - jio - gan .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [41, 47]}, {"entity": "thiobarbituric acid", "entity_type": "Chemical", "pos": [60, 79]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [124, 134]}, {"entity": "reduced glutathione", "entity_type": "Chemical", "pos": [153, 172]}, {"entity": "oxidized glutathione", "entity_type": "Chemical", "pos": [175, 195]}], "task": "NER"}
{"text": "The improvement of nuclear factor - kappa Bp65 , cyclooxygenase - 2 , inducible nitric oxide synthase , NF - E2 - related factor 2 , and heme oxygenase - 1 was marked in the group administered Bakumi - jio - gan .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [80, 92]}, {"entity": "heme", "entity_type": "Chemical", "pos": [137, 141]}], "task": "NER"}
{"text": "However , oil red O staining showed that the increased lipid deposition in the kidney of nephrectomized rats improved on Hachimi - jio - gan and Bakumi - jio - gan administration .", "entity": [{"entity": "oil red O", "entity_type": "Chemical", "pos": [10, 19]}], "task": "NER"}
{"text": "CONCLUSION : This study provides scientific evidence that two Rokumi - jio - gan - containing prescriptions ( Hachimi - jio - gan and Bakumi - jio - gan ) improves oxidative stress via dyslipidemia in the remnant kidney of nephrectomized rats .", "entity": [], "task": "NER"}
{"text": "Cyperi Rhizoma inhibits the 1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine - induced reduction in nigrostriatal dopaminergenic neurons in estrogen - deprived mice .", "entity": [{"entity": "1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine", "entity_type": "Chemical", "pos": [28, 88]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "ETHNOPHARMACOLOGICAL RELEVANCE : Cyperi Rhizoma has commonly been used for the treatment of gynecological and neuropsychiatric disorders in traditional medicine .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to evaluate the estrogenic properties and neuroprotective effects of Cyperi Rhizoma under estrogen - deprived condition in female mice .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "MATERIALS AND METHODS : To determine the estrogen - like effect of Cyperi Rhizoma extract ( CRE ) , we measured luciferase expression after transfection of a promoter construct containing an estrogen response element ( ERE ) and treatment of CRE .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [41, 49]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [191, 199]}], "task": "NER"}
{"text": "To evaluate the neuroprotective effect of CRE , we measured striatal dopamine , movement ability , tyrosine hydroxylase ( TH ) immunoreactivity , and apoptosis - related protein expression levels after treatment of CRE either with or without 1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine ( MPTP ) in ovariectomized female mice .", "entity": [{"entity": "dopamine", "entity_type": "Chemical", "pos": [69, 77]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [99, 107]}, {"entity": "1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine", "entity_type": "Chemical", "pos": [242, 302]}, {"entity": "MPTP", "entity_type": "Chemical", "pos": [305, 309]}], "task": "NER"}
{"text": "RESULTS : CRE significantly induced the luciferase expression driven by an ERE in PC12 cells , a dopaminergic cell line , in a dose - dependent manner .", "entity": [], "task": "NER"}
{"text": "In mice , MPTP significantly decreased the levels of dopamine in the striatum and behavior performance ; in contrast , both CRE and 17 beta - estradiol benzoate ( EB ) recovered these parameters to normal levels .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [10, 14]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [53, 61]}, {"entity": "17 beta - estradiol benzoate", "entity_type": "Chemical", "pos": [132, 160]}], "task": "NER"}
{"text": "CRE and EB treatment also recovered TH immunopositive fibers and cells , respectively , from MPTP toxicity .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [93, 97]}], "task": "NER"}
{"text": "Additionally , MPTP significantly down - regulated Bcl - 2 expression in the mitochondria of dopaminergic cells in the SN , followed by an increase in Bax expression , cytochrome C translocation to the cytosol , andcleaved - caspase - 3 expression , whereas these were inhibited by CRE or EB treatment .", "entity": [{"entity": "MPTP", "entity_type": "Chemical", "pos": [15, 19]}], "task": "NER"}
{"text": "CONCLUSIONS : These findings provide the first evidence that CRE has estrogen - like and neuroprotective effects on dopaminergic neurons in estrogen - deprived mice treated with MPTP - toxin .", "entity": [{"entity": "estrogen", "entity_type": "Chemical", "pos": [69, 77]}, {"entity": "estrogen", "entity_type": "Chemical", "pos": [140, 148]}, {"entity": "MPTP", "entity_type": "Chemical", "pos": [178, 182]}], "task": "NER"}
{"text": "Antecedents and consequences of drug abuse in rats selectively bred for high and low response to novelty .", "entity": [], "task": "NER"}
{"text": "Human genetic and epidemiological studies provide evidence that only a subset of individuals who experiment with potentially addictive drugs become addicts .", "entity": [], "task": "NER"}
{"text": "What renders some individuals susceptible to addiction remains to be determined , but most would agree that there is no single trait underlying the disorder .", "entity": [], "task": "NER"}
{"text": "However , there is evidence in humans that addiction liability has a genetic component , and that certain personality characteristics related to temperament ( e . g . the sensation - seeking trait ) are associated with individual differences in addiction liability .", "entity": [], "task": "NER"}
{"text": "Consequently , we have used a selective breeding strategy based on locomotor response to a novel environment to generate two lines of rats with distinct behavioral characteristics .", "entity": [], "task": "NER"}
{"text": "We have found that the resulting phenotypes differ on a number of neurobehavioral dimensions relevant to addiction .", "entity": [], "task": "NER"}
{"text": "Relative to bred low - responder ( bLR ) rats , bred high - responder ( bHR ) rats exhibit increased exploratory behavior , are more impulsive , more aggressive , seek stimuli associated with rewards , and show a greater tendency to relapse .", "entity": [], "task": "NER"}
{"text": "We therefore utilize this unique animal model to parse the genetic , neural and environmental factors that contribute to addiction liability .", "entity": [], "task": "NER"}
{"text": "Our work shows that the glucocorticoid receptor ( GR ) , dopaminergic molecules , and members of the fibroblast growth factor family are among the neurotransmitters and neuromodulators that play a role in both the initial susceptibility to addiction as well as the altered neural responses that follow chronic drug exposure .", "entity": [], "task": "NER"}
{"text": "Moreover , our findings suggest that the hippocampus plays a major role in mediating vulnerability to addiction .", "entity": [], "task": "NER"}
{"text": "It is hoped that this work will emphasize the importance of personalized treatment strategies and identify novel therapeutic targets for humans suffering from addictive disorders .", "entity": [], "task": "NER"}
{"text": "Fusidic acid and rifampicin co - loaded PLGA nanofibers for the prevention of orthopedic implant associated infections .", "entity": [{"entity": "Fusidic acid", "entity_type": "Chemical", "pos": [0, 12]}, {"entity": "rifampicin", "entity_type": "Chemical", "pos": [17, 27]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [40, 44]}], "task": "NER"}
{"text": "Implant - associated infections following invasive orthopedic surgery are a major clinical problem , and are one of the primary causes of joint failure following total joint arthroplasty .", "entity": [], "task": "NER"}
{"text": "Current strategies using perioperative antibiotics have been met with little clinical success and have resulted in various systemic toxicities and the promotion of antibiotic resistant microorganisms .", "entity": [], "task": "NER"}
{"text": "Here we report the development of a biodegradable localized delivery system using poly ( D , L - lactic acid - co - glycolic acid ) ( PLGA ) for the combinatorial release of fusidic acid ( FA ) ( or its sodium salt ; SF ) and rifampicin ( RIF ) using electrospinning .", "entity": [{"entity": "poly ( D , L - lactic acid - co - glycolic acid )", "entity_type": "Chemical", "pos": [82, 131]}, {"entity": "PLGA", "entity_type": "Chemical", "pos": [134, 138]}, {"entity": "fusidic acid", "entity_type": "Chemical", "pos": [174, 186]}, {"entity": "sodium", "entity_type": "Chemical", "pos": [203, 209]}, {"entity": "rifampicin", "entity_type": "Chemical", "pos": [226, 236]}, {"entity": "RIF", "entity_type": "Chemical", "pos": [239, 242]}], "task": "NER"}
{"text": "The drug - loaded formulations showed good antibiotic encapsulation ( ~ 75 % - 100 % ) , and a biphasic drug release profile .", "entity": [], "task": "NER"}
{"text": "All dual - loaded formulations showed direct antimicrobial activity in vitro against Staphylococcus epidermidis , and two strains of methicillin - resistant Staphylococcus aureus ( MRSA ) .", "entity": [{"entity": "methicillin", "entity_type": "Chemical", "pos": [133, 144]}], "task": "NER"}
{"text": "Furthermore , lead formulations containing 10 % ( w / w ) FA / SF and 5 % ( w / w ) RIF were able to prevent the adherence of MRSA to a titanium implant in an in vivo rodent model of subcutaneous implant - associated infection .", "entity": [{"entity": "RIF", "entity_type": "Chemical", "pos": [84, 87]}, {"entity": "titanium", "entity_type": "Chemical", "pos": [136, 144]}], "task": "NER"}
{"text": "Immune circuits in asthma .", "entity": [], "task": "NER"}
{"text": "Asthma is an inflammatory disorder of the conducting airways that has traditionally been classified according to severity .", "entity": [], "task": "NER"}
{"text": "While this has been helpful in guiding treatment with drugs that are currently available such as beta 2 - adrenoceptor agonists and corticosteroids , it takes little account of disease heterogeneity and causal pathways .", "entity": [], "task": "NER"}
{"text": "This review draws attention to subphenotypes of asthma involving different mechanisms and moves the focus away from the adaptive immune response more towards innate immune mechanisms .", "entity": [], "task": "NER"}
{"text": "This mandates a new view of the disease in which causal pathways linked to biomarkers are found and treatments targeted to these pathways as described in a more personalised approach to medicine .", "entity": [], "task": "NER"}
{"text": "Synthesis , spectral and antimicrobial evaluation of some novel 1 - methyl - 3 - alkyl - 2 , 6 - diphenylpiperidin - 4 - one oxime carbonates .", "entity": [{"entity": "1 - methyl - 3 - alkyl - 2 , 6 - diphenylpiperidin - 4 - one oxime carbonates", "entity_type": "Chemical", "pos": [64, 141]}], "task": "NER"}
{"text": "Synthesis of some novel biologically active piperidin - 4 - one oxime carbonates from 1 - methyl - 3alkyl - 2 , 6 - diphenylpiperidin - 4 - one oximes and substituted chloroformates was carried out in the presence of potassium carbonate as base and tetrabutylammonium bromide ( TBAB ) as catalyst .", "entity": [{"entity": "piperidin - 4 - one oxime carbonates", "entity_type": "Chemical", "pos": [44, 80]}, {"entity": "1 - methyl - 3alkyl - 2 , 6 - diphenylpiperidin - 4 - one oximes", "entity_type": "Chemical", "pos": [86, 150]}, {"entity": "chloroformates", "entity_type": "Chemical", "pos": [167, 181]}, {"entity": "potassium carbonate", "entity_type": "Chemical", "pos": [217, 236]}, {"entity": "tetrabutylammonium bromide", "entity_type": "Chemical", "pos": [249, 275]}, {"entity": "TBAB", "entity_type": "Chemical", "pos": [278, 282]}], "task": "NER"}
{"text": "The newly synthesized compounds were characterized by IR , ( 1 ) H , ( 13 ) C NMR and LC - mass spectra .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [59, 66]}, {"entity": "( 13 ) C", "entity_type": "Chemical", "pos": [69, 77]}], "task": "NER"}
{"text": "Based on the ( 1 ) H NMR analysis , all the compounds were found to adopt normal chair conformation with equatorial orientation of all the substituents .", "entity": [{"entity": "( 1 ) H", "entity_type": "Chemical", "pos": [13, 20]}], "task": "NER"}
{"text": "For all the synthesized compounds ( 5a - 5l ) antimicrobial activity has been tested against bacterial and fungal strains using Streptomycin and Amphotericin B as standards .", "entity": [{"entity": "Streptomycin", "entity_type": "Chemical", "pos": [128, 140]}, {"entity": "Amphotericin B", "entity_type": "Chemical", "pos": [145, 159]}], "task": "NER"}
{"text": "Synthesis of proline analogues as potent and selective cathepsin S inhibitors .", "entity": [{"entity": "proline", "entity_type": "Chemical", "pos": [13, 20]}], "task": "NER"}
{"text": "Cathepsin S is a potential target of autoimmune disease .", "entity": [], "task": "NER"}
{"text": "A series of proline derived compounds were synthesized and evaluated as cathepsin S inhibitors .", "entity": [{"entity": "proline", "entity_type": "Chemical", "pos": [12, 19]}], "task": "NER"}
{"text": "We discovered potent cathepsin S inhibitors through structure - activity relationship studies of proline analogues .", "entity": [{"entity": "proline", "entity_type": "Chemical", "pos": [97, 104]}], "task": "NER"}
{"text": "In particular , compound 19 - ( S ) showed promising in vitro / vivo pharmacological activities and properties as a selective cathepsin S inhibitor .", "entity": [], "task": "NER"}
{"text": "The preventive effect of uncarboxylated osteocalcin against free fatty acid - induced endothelial apoptosis through the activation of phosphatidylinositol 3 - kinase / Akt signaling pathway : Uncarboxylated osteocalcin and endothelial apoptosis .", "entity": [{"entity": "free fatty acid", "entity_type": "Chemical", "pos": [60, 75]}, {"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [134, 154]}], "task": "NER"}
{"text": "OBJECTIVE : Increasing evidence suggests that osteocalcin ( OC ) , one of the osteoblast - specific proteins , has been associated with atherosclerosis , but results are conflicting .", "entity": [], "task": "NER"}
{"text": "The aim of this study was to elucidate the independent effect of uncarboxylated osteocalcin ( ucOC ) , an active form of osteocalcin which has been suggested to have an insulin sensitizing effect , on vascular endothelial cells .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : We used human aortic endothelial cells and treated them with ucOC .", "entity": [], "task": "NER"}
{"text": "Linoleic acid ( LA ) was used as a representative free fatty acid .", "entity": [{"entity": "Linoleic acid", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "free fatty acid", "entity_type": "Chemical", "pos": [50, 65]}], "task": "NER"}
{"text": "Apoptosis was evaluated using various methods including a terminal deoxyribonucleotide transferase - mediated deoxyuridine triphosphate nick - end labeling analysis kit and Western blotting for cleaved caspase 3 , cleaved poly ( ADP - ribose ) polymerase and Bcl - xL .", "entity": [{"entity": "deoxyribonucleotide", "entity_type": "Chemical", "pos": [67, 86]}, {"entity": "deoxyuridine triphosphate", "entity_type": "Chemical", "pos": [110, 135]}, {"entity": "poly ( ADP - ribose )", "entity_type": "Chemical", "pos": [222, 243]}], "task": "NER"}
{"text": "The phosphorylations of Akt and endothelial nitric oxide synthase ( eNOS ) as well as the level of NO were measured to confirm the effect of ucOC on insulin signaling pathway .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [44, 56]}, {"entity": "NO", "entity_type": "Chemical", "pos": [69, 71]}], "task": "NER"}
{"text": "RESULTS : Pretreatment of ucOC ( 30ng / ml ) prevented LA - induced apoptosis in insulin - stimulated endothelial cells ; effects were abolished by pretreatment with the phosphatidylinositol 3 - kinase ( PI3 - kinase ) inhibitor , wortmannin .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [170, 190]}, {"entity": "wortmannin", "entity_type": "Chemical", "pos": [231, 241]}], "task": "NER"}
{"text": "Treatment of ucOC ( ranged from 0 . 3 to 30ng / ml ) significantly increased the phosphorylation of Akt and eNOS and nitric oxide secretion from endothelial cells in a PI3 - kinase dependent manner .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [117, 129]}], "task": "NER"}
{"text": "CONCLUSIONS : Our study is the first to demonstrate the independent effect of ucOC on vascular endothelial cells .", "entity": [], "task": "NER"}
{"text": "Our results further suggest that ucOC could have beneficial effects on atherosclerosis .", "entity": [], "task": "NER"}
{"text": "Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats .", "entity": [{"entity": "triptolide", "entity_type": "Chemical", "pos": [76, 86]}], "task": "NER"}
{"text": "Triptolide ( TP ) , a major component of TWHF , is widely used to treat rheumatoid arthritis , systemic lupus erythematosus , nephritis and leprosy .", "entity": [{"entity": "Triptolide", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "However , its clinical use is limited by hepatotoxicity .", "entity": [], "task": "NER"}
{"text": "To further elucidate the underlying mechanism of its hepatotoxic effects , hepatic gene expression profiles were analyzed .", "entity": [], "task": "NER"}
{"text": "TP ( 1000 and 300 mu g / kg ) was orally administered to Wistar rats for 14days .", "entity": [], "task": "NER"}
{"text": "Current study indicated that female rats were more sensitive to TP - induced hepatotoxicity than males .", "entity": [], "task": "NER"}
{"text": "Genome - wide microarray analyses identified 3329 differentially expressed genes in liver of female rats .", "entity": [], "task": "NER"}
{"text": "Analyses of these genes identified over - represented functions associated with insulin signaling pathway , glucose metabolism , cell cycle , oxidative stress and apoptosis , which were consistent with the results of significant increase of Caspase - 3 activity and reduction of serum glucose , GSH / GSSG ratio , glucose - 6 - phosphatase and phosphoenolpyruvate carboxykinase activities , liver glycogen .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [108, 115]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [285, 292]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [295, 298]}, {"entity": "GSSG", "entity_type": "Chemical", "pos": [301, 305]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [314, 321]}, {"entity": "phosphoenolpyruvate", "entity_type": "Chemical", "pos": [344, 363]}], "task": "NER"}
{"text": "In addition , it was observed for the first time that glucocorticoids and IGF1 might get involved in TP - induced hepatotoxicity .", "entity": [], "task": "NER"}
{"text": "These data suggest that TP treatment could alter the hepatic redox status , reduce serum glucose and induce hepatocyte apoptosis , consistent with the differential expression of genes involved in insulin signaling pathway , glucose metabolism pathway and cell stress pathway , all of which might contribute to the overall TP - induced hepatotoxicity .", "entity": [{"entity": "glucose", "entity_type": "Chemical", "pos": [89, 96]}, {"entity": "glucose", "entity_type": "Chemical", "pos": [224, 231]}], "task": "NER"}
{"text": "TCDD induces the expression of insulin - like growth factor binding protein 4 in 5L rat hepatoma cells : a cautionary tale of the use of this cell line in studies on dioxin toxicity .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "dioxin", "entity_type": "Chemical", "pos": [166, 172]}], "task": "NER"}
{"text": "Previous quantitative proteomic studies on the actions of 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) in 5L rat hepatoma cells , a cell model frequently used for investigating the mechanisms of TCDD toxicity , had indicated that dioxin exposure reduced the abundance of numerous proteins which are regulated at the level of protein synthesis initiation .", "entity": [{"entity": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin", "entity_type": "Chemical", "pos": [58, 105]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [108, 112]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [207, 211]}, {"entity": "dioxin", "entity_type": "Chemical", "pos": [242, 248]}], "task": "NER"}
{"text": "In the present study , we have analysed the mechanism mediating this inhibition .", "entity": [], "task": "NER"}
{"text": "TCDD treatment of the cells largely prevented the activation of eukaryotic translation initiation factor 4E - binding protein 1 , a regulator of translation initiation and substrate of the mammalian target of rapamycin ( mTOR ) .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [0, 4]}, {"entity": "rapamycin", "entity_type": "Chemical", "pos": [209, 218]}], "task": "NER"}
{"text": "By \" working upwards \" from mTOR , we observed that TCDD inhibited endogenous and IGF - I - induced AKT and ERK activation by interfering with tyrosine phosphorylation of insulin receptor substrate 1 .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [52, 56]}, {"entity": "tyrosine", "entity_type": "Chemical", "pos": [143, 151]}], "task": "NER"}
{"text": "This inhibition was mediated by a TCDD - induced secreted factor which was identified as insulin - like growth factor binding protein 4 ( IGFBP - 4 ) .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [34, 38]}], "task": "NER"}
{"text": "The induction of IGFBP - 4 protein was dependent on a functional aryl hydrocarbon receptor and was preceded by a rapid increase in the level of IGFBP - 4 mRNA indicating that IGFBP - 4 is a previously unknown transcriptional target of TCDD in 5L cells .", "entity": [{"entity": "aryl hydrocarbon", "entity_type": "Chemical", "pos": [65, 81]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [235, 239]}], "task": "NER"}
{"text": "IGFBP - 4 was not induced by TCDD in the parental cell line of 5L cells , Fao , and in various closely related rat hepatoma cell lines as well as in other unrelated cell types .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "Analysis of 5L cell chromosomes by multicolour spectral karyotyping ( SKY ) revealed that the cells carry several hitherto uncharacterised chromosomal translocations .", "entity": [], "task": "NER"}
{"text": "The observations suggest that in 5L cells the Igfbp - 4 gene may have got under the control of a promoter containing dioxin responsive element ( s ) leading to the induction of IGFBP - 4 by TCDD .", "entity": [{"entity": "dioxin", "entity_type": "Chemical", "pos": [117, 123]}, {"entity": "TCDD", "entity_type": "Chemical", "pos": [190, 194]}], "task": "NER"}
{"text": "These findings emphasise a particular caution when interpreting and extrapolating results on the action mechanisms of TCDD obtained in studies using 5L cells as a model system .", "entity": [{"entity": "TCDD", "entity_type": "Chemical", "pos": [118, 122]}], "task": "NER"}
{"text": "Pyrazole derivatives as inhibitors of arachidonic acid - induced platelet aggregation .", "entity": [{"entity": "Pyrazole", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [38, 54]}], "task": "NER"}
{"text": "Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis , most prominently in myocardial infarction and ischemic stroke .", "entity": [], "task": "NER"}
{"text": "Here , we describe the synthesis and structure - activity relationships of potent inhibitors of platelet aggregation based on the 1 , 5 - diarylpyrazol - 3 - carboxamide scaffold .", "entity": [{"entity": "1 , 5 - diarylpyrazol - 3 - carboxamide", "entity_type": "Chemical", "pos": [130, 169]}], "task": "NER"}
{"text": "Analogs from this series demonstrated potent anti - aggregatory activities against arachidonic acid - induced platelet aggregation , as measured by turbidimetric method of Born .", "entity": [{"entity": "arachidonic acid", "entity_type": "Chemical", "pos": [83, 99]}], "task": "NER"}
{"text": "1 , 5 - Diarylpyrazole - 3 - carboxamides obtained with small - basic amines ( 7 , 8 , 50 , 51 , 61 , 62 ) displayed the strongest activity with IC50 values in low nanomolar range ( 5 . 7 - 83 nM ) .", "entity": [{"entity": "1 , 5 - Diarylpyrazole - 3 - carboxamides", "entity_type": "Chemical", "pos": [0, 41]}, {"entity": "amines", "entity_type": "Chemical", "pos": [70, 76]}], "task": "NER"}
{"text": "On the basis of their high potency in cellular environment , these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases .", "entity": [{"entity": "pyrazole", "entity_type": "Chemical", "pos": [83, 91]}], "task": "NER"}
{"text": "A selective antagonist reveals a potential role of G protein - coupled receptor 55 in platelet and endothelial cell function .", "entity": [], "task": "NER"}
{"text": "The G protein coupled receptor 55 ( GPR55 ) is a lysophosphatidylinositol ( LPI ) receptor that is also responsive to certain cannabinoids .", "entity": [{"entity": "lysophosphatidylinositol", "entity_type": "Chemical", "pos": [49, 73]}, {"entity": "LPI", "entity_type": "Chemical", "pos": [76, 79]}], "task": "NER"}
{"text": "Although GPR55 has been implicated in several ( patho ) physiological functions , its role is still enigmatic mainly owing to the lack of selective GPR55 antagonists .", "entity": [], "task": "NER"}
{"text": "Here we show that the compound CID16020046 ( ( 4 - [ 4 - ( 3 - hydroxyphenyl ) - 3 - ( 4 - methylphenyl ) - 6 - oxo - 1H , 4H , 5H , 6H - pyrrolo [ 3 , 4 - c ] pyrazol - 5 - yl ] benzoic acid ) is a selective GPR55 antagonist .", "entity": [{"entity": "CID16020046", "entity_type": "Chemical", "pos": [31, 42]}, {"entity": "( 4 - [ 4 - ( 3 - hydroxyphenyl ) - 3 - ( 4 - methylphenyl ) - 6 - oxo - 1H , 4H , 5H , 6H - pyrrolo [ 3 , 4 - c ] pyrazol - 5 - yl ] benzoic acid", "entity_type": "Chemical", "pos": [45, 191]}], "task": "NER"}
{"text": "In yeast cells expressing human GPR55 , CID16020046 antagonized agonist - induced receptor activation .", "entity": [{"entity": "CID16020046", "entity_type": "Chemical", "pos": [40, 51]}], "task": "NER"}
{"text": "In HEK293 cells stably expressing human GPR55 ( HEK - GPR55 ) , the compound behaved as an antagonist on LPI - mediated Ca2 + release and extracellular signal - regulated kinases ( ERK1 / 2 ) activation , but not in HEK293 cells expressing cannabinoid receptor 1 or 2 ( CB1 or CB2 ) .", "entity": [{"entity": "LPI", "entity_type": "Chemical", "pos": [105, 108]}, {"entity": "Ca2 +", "entity_type": "Chemical", "pos": [120, 125]}], "task": "NER"}
{"text": "CID16020046 concentration - dependently inhibited LPI - induced activation of nuclear factor of activated T - cells ( NFAT ) , nuclear factor kappa of activated B cells ( NF - kappa B ) and serum response element ( SRE ) , translocation of NFAT and NF - kappa B , and GPR55 internalization .", "entity": [{"entity": "CID16020046", "entity_type": "Chemical", "pos": [0, 11]}, {"entity": "LPI", "entity_type": "Chemical", "pos": [50, 53]}], "task": "NER"}
{"text": "It reduced LPI - induced wound healing in primary human lung microvascular endothelial cells ( HMVEC - L ) and reversed LPI - inhibited platelet aggregation , suggesting a novel role for GPR55 in platelet and endothelial cell function .", "entity": [{"entity": "LPI", "entity_type": "Chemical", "pos": [11, 14]}, {"entity": "LPI", "entity_type": "Chemical", "pos": [120, 123]}], "task": "NER"}
{"text": "CID16020046 is therefore a valuable tool to study GPR55 - mediated mechanisms in primary cells and tissues .", "entity": [{"entity": "CID16020046", "entity_type": "Chemical", "pos": [0, 11]}], "task": "NER"}
{"text": "Method for quantitative measurements of the elastic modulus of biological cells in AFM indentation experiments .", "entity": [], "task": "NER"}
{"text": "Here we overview and further develop a quantitative method to measure mechanics of biological cells in indentation experiments , which is based on the use of atomic force microscopy ( AFM ) .", "entity": [], "task": "NER"}
{"text": "We demonstrate how the elastic modulus of the cell body should be measured when the cellular brush is taken into account .", "entity": [], "task": "NER"}
{"text": "The brush is an essential inelastic part of the cell , which surrounds all eukaryotic ( the brush is mostly microvilli and glycocalyx ) and gram - negative prokaryotic cells ( the brush is polysaccharides ) .", "entity": [], "task": "NER"}
{"text": "The other main feature of the described method is the use of a relatively dull AFM probe to stay in the linear stress - strain regime .", "entity": [], "task": "NER"}
{"text": "In particular , we show that the elastic modulus ( aka the Young ' s modulus ) of cells is independent of the indentation depth up to 10 - 20 % deformation for the eukaryotic cells studied here .", "entity": [], "task": "NER"}
{"text": "Besides the elastic modulus , the method presented allows obtaining the parameters of cellular brush , such as the effective length and grafting density of the brush .", "entity": [], "task": "NER"}
{"text": "Although the method is demonstrated on eukaryotic cells , it is directly applicable for all types of cells , and even non - biological soft materials surrounded by either a brush or any field of long - range forces .", "entity": [], "task": "NER"}
{"text": "Prostaglandin E2 acts via bone marrow macrophages to block PTH - stimulated osteoblast differentiation in vitro .", "entity": [{"entity": "Prostaglandin E2", "entity_type": "Chemical", "pos": [0, 16]}], "task": "NER"}
{"text": "Intermittent PTH is the major anabolic therapy for osteoporosis while continuous PTH causes bone loss .", "entity": [], "task": "NER"}
{"text": "PTH acts on the osteoblast ( OB ) lineage to regulate bone resorption and formation .", "entity": [], "task": "NER"}
{"text": "PTH also induces cyclooxygenase - 2 ( COX - 2 ) , producing prostaglandin E2 ( PGE2 ) , that can act on both OBs and osteoclasts ( OCs ) .", "entity": [{"entity": "prostaglandin E2", "entity_type": "Chemical", "pos": [60, 76]}, {"entity": "PGE2", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "Because intermittent PTH is more anabolic in Cox - 2 knockout ( KO ) than wild type ( WT ) mice , we hypothesized COX - 2 might contribute to the effects of continuous PTH by suppressing PTH - stimulated differentiation of mesenchymal stem cells into OBs .", "entity": [], "task": "NER"}
{"text": "We compared effects of continuous PTH on bone marrow stromal cells ( BMSCs ) and primary OBs ( POBs ) from Cox - 2 KO mice , mice with deletion of PGE2 receptors ( Ptger4 and Ptger2 KO mice ) , and WT controls .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [147, 151]}], "task": "NER"}
{"text": "PTH increased OB differentiation in BMSCs only in the absence of COX - 2 expression or activity .", "entity": [], "task": "NER"}
{"text": "In the absence of COX - 2 , PTH stimulated differentiation if added during the first week of culture .", "entity": [], "task": "NER"}
{"text": "In Cox - 2 KO BMSCs , PTH - stimulated differentiation was prevented by adding PGE2 to cultures .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [79, 83]}], "task": "NER"}
{"text": "Co - culture of POBs with M - CSF - expanded bone marrow macrophages ( BMMs ) showed that the inhibition of PTH - stimulated OB differentiation required not only COX - 2 or PGE2 but also BMMs .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [173, 177]}], "task": "NER"}
{"text": "Sufficient PGE2 to mediate the inhibitory effect was made by either WT POBs or WT BMMs .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [11, 15]}], "task": "NER"}
{"text": "The inhibitory effect mediated by COX - 2 / PGE2 was transferred by conditioned media from RANKL - treated BMMs and could be blocked by osteoprotegerin , which interferes with RANKL binding to its receptor on OC lineage cells .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [44, 48]}], "task": "NER"}
{"text": "Deletion of Ptger4 , but not Ptger2 , in BMMs prevented the inhibition of PTH - stimulated OB differentiation .", "entity": [], "task": "NER"}
{"text": "As expected , PGE2 also stimulated OB differentiation , but when given in combination with PTH , the stimulatory effects of both were abrogated .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [14, 18]}], "task": "NER"}
{"text": "These data suggest that PGE2 , acting via EP4R on BMMs committed to the OC lineage , stimulated secretion of a factor or factors that acted to suppress PTH - stimulated OB differentiation .", "entity": [{"entity": "PGE2", "entity_type": "Chemical", "pos": [24, 28]}], "task": "NER"}
{"text": "This suppression of OB differentiation could contribute to the bone loss seen with continuous PTH in vivo .", "entity": [], "task": "NER"}
{"text": "Zno nanoparticle based highly efficient CdS / CdSe quantum dot - sensitized solar cells .", "entity": [{"entity": "Zno", "entity_type": "Chemical", "pos": [0, 3]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [40, 43]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [46, 50]}], "task": "NER"}
{"text": "20 nm ZnO nanoparticles are used to fabricate the mesoporous photoanode of the CdS / CdSe quantum dot - sensitized solar cells by the simple doctor blade method .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [6, 9]}, {"entity": "CdS", "entity_type": "Chemical", "pos": [79, 82]}, {"entity": "CdSe", "entity_type": "Chemical", "pos": [85, 89]}], "task": "NER"}
{"text": "A maximum power conversion efficiency of 4 . 46 % has been achieved , which indicated exciting prospects for ZnO nanoparticle based quantum dot - sensitized solar cells .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [109, 112]}], "task": "NER"}
{"text": "A randomized , double - blind , placebo - controlled crossover study of alpha 4 beta 2 * nicotinic acetylcholine receptor agonist AZD1446 ( TC - 6683 ) in adults with attention - deficit / hyperactivity disorder .", "entity": [{"entity": "acetylcholine", "entity_type": "Chemical", "pos": [99, 112]}, {"entity": "AZD1446", "entity_type": "Chemical", "pos": [130, 137]}, {"entity": "TC - 6683", "entity_type": "Chemical", "pos": [140, 149]}], "task": "NER"}
{"text": "RATIONALE : Stimulation of nicotinic cholinergic systems has been shown to alleviate ADHD symptoms and to improve cognitive performance .", "entity": [], "task": "NER"}
{"text": "AZD1446 is a selective alpha 4 beta 2 * nicotinic acetylcholine receptor agonist with potential effect on the symptoms of ADHD .", "entity": [{"entity": "AZD1446", "entity_type": "Chemical", "pos": [0, 7]}, {"entity": "acetylcholine", "entity_type": "Chemical", "pos": [50, 63]}], "task": "NER"}
{"text": "OBJECTIVES : The purpose of this study is to evaluate the efficacy , safety , and pharmacokinetics of AZD1446 in adults with ADHD treated for 2 weeks .", "entity": [{"entity": "AZD1446", "entity_type": "Chemical", "pos": [102, 109]}], "task": "NER"}
{"text": "METHOD : This was a randomized , double - blind , placebo - controlled crossover trial .", "entity": [], "task": "NER"}
{"text": "Participants were 79 adults with ADHD , grouped according to their use of nicotine - containing products .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [74, 82]}], "task": "NER"}
{"text": "Nicotine non - users received placebo and two of three AZD1446 treatment regimens ( 80 mg tid , 80 mg qd , 10 mg tid ) .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "AZD1446", "entity_type": "Chemical", "pos": [55, 62]}], "task": "NER"}
{"text": "Nicotine users received placebo , AZD1446 80 mg tid and 80 mg qd .", "entity": [{"entity": "Nicotine", "entity_type": "Chemical", "pos": [0, 8]}, {"entity": "AZD1446", "entity_type": "Chemical", "pos": [34, 41]}], "task": "NER"}
{"text": "Efficacy measures included the Conners ' Adult ADHD Rating Scale and cognitive measures of immediate and delayed verbal episodic memory , learning , attention , working memory , executive functioning , and spatial problem solving ( CogState computerized test battery ) .", "entity": [], "task": "NER"}
{"text": "RESULTS : There was no significant effect of AZD1446 on any of the clinical scores irrespective of dose , schedule , or concomitant use of nicotine products .", "entity": [{"entity": "AZD1446", "entity_type": "Chemical", "pos": [45, 52]}, {"entity": "nicotine", "entity_type": "Chemical", "pos": [139, 147]}], "task": "NER"}
{"text": "A statistically significant improvement was seen on the Groton Maze Learning Task , a measure of executive functioning , in nicotine non - users after treatment with AZD1446 80 mg qd .", "entity": [{"entity": "nicotine", "entity_type": "Chemical", "pos": [124, 132]}, {"entity": "AZD1446", "entity_type": "Chemical", "pos": [166, 173]}], "task": "NER"}
{"text": "CONCLUSIONS : AZD1446 was well tolerated , but did not significantly improve ADHD symptoms after 2 weeks of treatment compared to placebo .", "entity": [{"entity": "AZD1446", "entity_type": "Chemical", "pos": [14, 21]}], "task": "NER"}
{"text": "While the present study does not support the therapeutic utility of AZD1446 in ADHD , its potential pro - cognitive effects remain to be explored in other neuropsychiatric disorders .", "entity": [{"entity": "AZD1446", "entity_type": "Chemical", "pos": [68, 75]}], "task": "NER"}
{"text": "Modelling the Cost Effectiveness of Disease - Modifying Treatments for Multiple Sclerosis : Issues to Consider .", "entity": [], "task": "NER"}
{"text": "Several cost - effectiveness models of disease - modifying treatments ( DMTs ) for multiple sclerosis ( MS ) have been developed for different populations and different countries .", "entity": [], "task": "NER"}
{"text": "Vast differences in the approaches and discrepancies in the results give rise to heated discussions and limit the use of these models .", "entity": [], "task": "NER"}
{"text": "Our main objective is to discuss the methodological challenges in modelling the cost effectiveness of treatments for MS .", "entity": [], "task": "NER"}
{"text": "We conducted a review of published models to describe the approaches taken to date , to identify the key parameters that influence the cost effectiveness of DMTs , and to point out major areas of weakness and uncertainty .", "entity": [], "task": "NER"}
{"text": "Thirty - six published models and analyses were identified .", "entity": [], "task": "NER"}
{"text": "The greatest source of uncertainty is the absence of head - to - head randomized clinical trials .", "entity": [], "task": "NER"}
{"text": "Modellers have used various techniques to compensate , including utilizing extension trials .", "entity": [], "task": "NER"}
{"text": "The use of large observational cohorts in recent studies aids in identifying population - based , ' real - world ' treatment effects .", "entity": [], "task": "NER"}
{"text": "Major drivers of results include the time horizon modelled and DMT acquisition costs .", "entity": [], "task": "NER"}
{"text": "Model endpoints must target either policy makers ( using cost - utility analysis ) or clinicians ( conducting cost - effectiveness analyses ) .", "entity": [], "task": "NER"}
{"text": "Lastly , the cost effectiveness of DMTs outside North America and Europe is currently unknown , with the lack of country - specific data as the major limiting factor .", "entity": [], "task": "NER"}
{"text": "We suggest that limited data should not preclude analyses , as models may be built and updated in the future as data become available .", "entity": [], "task": "NER"}
{"text": "Disclosure of modelling methods and assumptions could improve the transferability and applicability of models designed to reflect different healthcare systems .", "entity": [], "task": "NER"}
{"text": "Three Ubiquitination Sites of Organic Anion Transporter - 1 Synergistically Mediate Protein Kinase C - dependent Endocytosis of the Transporter .", "entity": [], "task": "NER"}
{"text": "Organic anion transporter - 1 ( OAT1 ) mediates the body disposition of a diverse array of clinically important drugs , including anti - HIV therapeutics , anti - tumor drugs , antibiotics , anti - hypertensives , and anti - inflammatories .", "entity": [], "task": "NER"}
{"text": "Therefore , understanding the regulation of OAT1 has profound clinical significance .", "entity": [], "task": "NER"}
{"text": "We previously established that OAT1 constitutively internalizes from and recycles back to cell surface , and that activation of protein kinase C ( PKC ) inhibits OAT1 activity by promoting ubiquitination of the transporter , which then leads to an accelerated internalization of the transporter from cell surface to intracellular compartments .", "entity": [], "task": "NER"}
{"text": "In the current study , we demonstrated that PKC isoform PKC - alpha was responsible for OAT1 ubiquitination .", "entity": [], "task": "NER"}
{"text": "To directly address the role of OAT1 ubiquitination , we then generated two OAT1 mutants , each having multiple lysines ( K ) simultaneously mutated to arginine ( R ) .", "entity": [{"entity": "lysines", "entity_type": "Chemical", "pos": [112, 119]}, {"entity": "arginine", "entity_type": "Chemical", "pos": [152, 160]}], "task": "NER"}
{"text": "One mutant K163 / 297 / 303 / 315 / 321R lost sensitivities to PKC - induced inhibition of transport activity , to PKC - induced ubiquitination , and to PKC - induced acceleration of transporter internalization .", "entity": [], "task": "NER"}
{"text": "Further dissecting each lysine within this mutant , we identified Lys297 , Lys303 and Lys315 being the ubiquitin - conjugation sites .", "entity": [{"entity": "lysine", "entity_type": "Chemical", "pos": [24, 30]}, {"entity": "Lys297", "entity_type": "Chemical", "pos": [66, 72]}, {"entity": "Lys303", "entity_type": "Chemical", "pos": [75, 81]}, {"entity": "Lys315", "entity_type": "Chemical", "pos": [86, 92]}], "task": "NER"}
{"text": "Interestingly , mutating any one of the three lysines prevented the ubiquitin - conjugation to the other two lysines , suggesting that Lys297 , Lys303 and Lys315 may form an optimal structure to interact with ubiquitination machineries .", "entity": [{"entity": "lysines", "entity_type": "Chemical", "pos": [46, 53]}, {"entity": "lysines", "entity_type": "Chemical", "pos": [109, 116]}, {"entity": "Lys297", "entity_type": "Chemical", "pos": [135, 141]}, {"entity": "Lys303", "entity_type": "Chemical", "pos": [144, 150]}, {"entity": "Lys315", "entity_type": "Chemical", "pos": [155, 161]}], "task": "NER"}
{"text": "This is the first demonstration that Lys297 , Lys303 and Lys315 play synergistic role in PKC - regulated OAT1 ubiquitination , trafficking and transport activity .", "entity": [{"entity": "Lys297", "entity_type": "Chemical", "pos": [37, 43]}, {"entity": "Lys303", "entity_type": "Chemical", "pos": [46, 52]}, {"entity": "Lys315", "entity_type": "Chemical", "pos": [57, 63]}], "task": "NER"}
{"text": "Progesterone receptor induces bcl - x expression through intragenic binding sites favoring RNA polymerase II elongation .", "entity": [{"entity": "Progesterone", "entity_type": "Chemical", "pos": [0, 12]}], "task": "NER"}
{"text": "Steroid receptors were classically described for regulating transcription by binding to target gene promoters .", "entity": [{"entity": "Steroid", "entity_type": "Chemical", "pos": [0, 7]}], "task": "NER"}
{"text": "However , genome - wide studies reveal that steroid receptors - binding sites are mainly located at intragenic regions .", "entity": [{"entity": "steroid", "entity_type": "Chemical", "pos": [44, 51]}], "task": "NER"}
{"text": "To determine the role of these sites , we examined the effect of progestins on the transcription of the bcl - x gene , where only intragenic progesterone receptor - binding sites ( PRbs ) were identified .", "entity": [{"entity": "progesterone", "entity_type": "Chemical", "pos": [141, 153]}], "task": "NER"}
{"text": "We found that in response to hormone treatment , the PR is recruited to these sites along with two histone acetyltransferases CREB - binding protein ( CBP ) and GCN5 , leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI / SNF complex .", "entity": [], "task": "NER"}
{"text": "Concomitant , a more relaxed chromatin was detected along bcl - x gene mainly in the regions surrounding the intragenic PRbs .", "entity": [], "task": "NER"}
{"text": "PR also mediated the recruitment of the positive elongation factor pTEFb , favoring RNA polymerase II ( Pol II ) elongation activity .", "entity": [], "task": "NER"}
{"text": "Together these events promoted the re - distribution of the active Pol II toward the 3 ' - end of the gene and a decrease in the ratio between proximal and distal transcription .", "entity": [], "task": "NER"}
{"text": "These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone - dependent genes .", "entity": [], "task": "NER"}
{"text": "Seawater - driven magnesium based Janus micromotors for environmental remediation .", "entity": [{"entity": "magnesium", "entity_type": "Chemical", "pos": [18, 27]}], "task": "NER"}
{"text": "We describe the use of seawater as fuel to propel Janus micromotors .", "entity": [], "task": "NER"}
{"text": "The new micromotors consist of biodegradable and environmentally friendly magnesium microparticles and a nickel - gold bilayer patch for magnetic guidance and surface modification .", "entity": [{"entity": "magnesium", "entity_type": "Chemical", "pos": [74, 83]}, {"entity": "nickel", "entity_type": "Chemical", "pos": [105, 111]}], "task": "NER"}
{"text": "Such seawater - driven micromotors , which utilize macrogalvanic corrosion and chloride pitting corrosion processes , eliminate the need for external fuels to offer efficient and prolonged propulsion towards diverse applications in aquatic environments .", "entity": [{"entity": "chloride", "entity_type": "Chemical", "pos": [79, 87]}], "task": "NER"}
{"text": "Electrically driven ultraviolet random lasing from an n - MgZnO / i - ZnO / SiO2 / p - Si asymmetric double heterojunction .", "entity": [{"entity": "MgZnO", "entity_type": "Chemical", "pos": [58, 63]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [70, 73]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [76, 80]}, {"entity": "Si", "entity_type": "Chemical", "pos": [87, 89]}], "task": "NER"}
{"text": "Electrically pumped lasing action has been realized in ZnO from an n - MgZnO / i - ZnO / SiO2 / p - Si asymmetric double heterostructure , an ultralow threshold of 3 . 9 mA was obtained .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [55, 58]}, {"entity": "MgZnO", "entity_type": "Chemical", "pos": [71, 76]}, {"entity": "ZnO", "entity_type": "Chemical", "pos": [83, 86]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [89, 93]}, {"entity": "Si", "entity_type": "Chemical", "pos": [100, 102]}], "task": "NER"}
{"text": "The mechanism of the laser is associated with the in - plane random resonator cavities formed in the ZnO films and the elaborate hollow - shaped SiO2 cladding pattern , which prevent the lateral diffusion of injection current and ultimately lower the threshold current of the laser diode .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [101, 104]}, {"entity": "SiO2", "entity_type": "Chemical", "pos": [145, 149]}], "task": "NER"}
{"text": "In addition , a waveguide mechanism due to different refractive indices of three epilayers enhances the guided optical field on the ZnO side , resulting in an improved light extraction efficiency .", "entity": [{"entity": "ZnO", "entity_type": "Chemical", "pos": [132, 135]}], "task": "NER"}
{"text": "Drug - Induced Macular Edema .", "entity": [], "task": "NER"}
{"text": "Macular edema constitutes a serious pathologic entity of ophthalmology resulting in vision loss with a remarkable impact on the quality of life of patients .", "entity": [], "task": "NER"}
{"text": "It is the final common pathway of various systemic diseases and underlying intraocular conditions , with diabetes mellitus being the most frequent cause .", "entity": [], "task": "NER"}
{"text": "Other causes include venous occlusive disease , intraocular surgery , and inflammatory conditions of the posterior segment of the eye .", "entity": [], "task": "NER"}
{"text": "Macular edema is a recognized side effect of various systemic and local medications and requires special consideration among ophthalmologists and other clinicians .", "entity": [], "task": "NER"}
{"text": "Recently , antidiabetic thiazolidinediones have been implicated in the development of macular edema , and a review of the English literature revealed that other systemically administered drugs like fingolimod , recently approved for relapsing forms of multiple sclerosis , the anticancer agents tamoxifen and the taxanes , as well as niacin and interferons have been reported to cause macular edema .", "entity": [{"entity": "thiazolidinediones", "entity_type": "Chemical", "pos": [24, 42]}, {"entity": "fingolimod", "entity_type": "Chemical", "pos": [198, 208]}, {"entity": "tamoxifen", "entity_type": "Chemical", "pos": [295, 304]}, {"entity": "taxanes", "entity_type": "Chemical", "pos": [313, 320]}, {"entity": "niacin", "entity_type": "Chemical", "pos": [334, 340]}], "task": "NER"}
{"text": "Ophthalmologic pharmaceutical agents , like prostaglandin analogs , epinephrine , timolol , and ophthalmic preparation preservatives have also been reported to cause macular edema as an adverse event .", "entity": [{"entity": "prostaglandin", "entity_type": "Chemical", "pos": [44, 57]}, {"entity": "epinephrine", "entity_type": "Chemical", "pos": [68, 79]}, {"entity": "timolol", "entity_type": "Chemical", "pos": [82, 89]}], "task": "NER"}
{"text": "The purpose of this article is to provide a short , balanced overview of the available evidence in this regard .", "entity": [], "task": "NER"}
{"text": "The available data and the possible pathophysiologic mechanisms leading to the development of macular edema are discussed .", "entity": [], "task": "NER"}
{"text": "Possible therapeutic strategies for drug - induced macular edema are also proposed .", "entity": [], "task": "NER"}
{"text": "A Highly Crystalline Manganese - Doped Iron Oxide Nanocontainer with Predesigned Void Volume and Shape for Theranostic Applications .", "entity": [{"entity": "Manganese - Doped Iron Oxide", "entity_type": "Chemical", "pos": [21, 49]}], "task": "NER"}
{"text": "Hollow Mn - doped iron oxide nanocontainers , formed by a novel one - pot synthetic process , fulfill the dual requirements of delivering an effective dose of an anticancer drug to tumor tissue and enabling image - contrast monitoring of the nanocontainer fate through T2 - weighted magnetic resonance imaging , thereby determining the optimal balance between diagnostic and therapeutic moieties in an all - in - one theranostic nanoplatform .", "entity": [{"entity": "Mn - doped iron oxide", "entity_type": "Chemical", "pos": [7, 28]}], "task": "NER"}
{"text": "Oxygen - functionalized few - layer graphene sheets as active catalysts for oxidative dehydrogenation reactions .", "entity": [{"entity": "Oxygen", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "graphene", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Invited for this month ' s cover is the group from the Center for Nanophase Materials Sciences ( CNMS ) at the Oak Ridge National Laboratory .", "entity": [], "task": "NER"}
{"text": "The illustration is of the catalytic activity of the reported oxygen - functionalized few - layer graphenes , whereas the micrograph background image is of the same graphenes recorded by the authors using a new helium - ion microscope at the CNMS .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [62, 68]}, {"entity": "graphenes", "entity_type": "Chemical", "pos": [98, 107]}, {"entity": "graphenes", "entity_type": "Chemical", "pos": [165, 174]}, {"entity": "helium", "entity_type": "Chemical", "pos": [211, 217]}], "task": "NER"}
{"text": "Read the full text of the article at 10 . 1002 / cssc . 201200756 .", "entity": [], "task": "NER"}
{"text": "NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS INDUCE A MITOPHAGY - ASSOCIATED ENDOTHELIAL DYSFUNCTION THAT IS REVERSED BY COENZYME Q10 CO - TREATMENT .", "entity": [{"entity": "NUCLEOSIDE", "entity_type": "Chemical", "pos": [0, 10]}, {"entity": "COENZYME Q10", "entity_type": "Chemical", "pos": [120, 132]}], "task": "NER"}
{"text": "Cardiovascular complications have been documented in HIV - 1 infected populations , and antiretroviral therapy may play a role .", "entity": [], "task": "NER"}
{"text": "Nucleoside reverse transcriptase inhibitors ( NRTI ) are antiretrovirals known to induce mitochondrial damage in endothelial cells , culminating in endothelial dysfunction , an initiating event in atherogenesis .", "entity": [{"entity": "Nucleoside", "entity_type": "Chemical", "pos": [0, 10]}], "task": "NER"}
{"text": "Though the mechanism for NRTI - induced endothelial toxicity is not yet clear , our prior work suggested that a mitochondrial oxidative stress may be involved .", "entity": [], "task": "NER"}
{"text": "To further delineate the mechanism of toxicity , endothelial cells were treated with NRTI of varying subclasses , and the level of reactive oxygen species ( ROS ) and mitochondrial function were assessed .", "entity": [{"entity": "oxygen", "entity_type": "Chemical", "pos": [140, 146]}], "task": "NER"}
{"text": "To test whether rescue of mitochondrial electron transport attenuated NRTI - induced endothelial dysfunction , in some cases , cells were co - treated with the electron transport cofactor coenzyme Q10 ( Q10 ) .", "entity": [{"entity": "coenzyme Q10", "entity_type": "Chemical", "pos": [188, 200]}, {"entity": "Q10", "entity_type": "Chemical", "pos": [203, 206]}], "task": "NER"}
{"text": "At 4 - 6h , NRTI increased levels of ROS but decreased the activities of electron transport chain complexes I - IV , levels of ATP and the NAD / NADH ratio .", "entity": [{"entity": "ATP", "entity_type": "Chemical", "pos": [127, 130]}, {"entity": "NAD", "entity_type": "Chemical", "pos": [139, 142]}, {"entity": "NADH", "entity_type": "Chemical", "pos": [145, 149]}], "task": "NER"}
{"text": "Moreover , nitric oxide levels were decreased , while endothelin - 1 release was increased .", "entity": [{"entity": "nitric oxide", "entity_type": "Chemical", "pos": [11, 23]}], "task": "NER"}
{"text": "Q10 abolished NRTI - induced mitochondria injury and effects on endothelial agonist production .", "entity": [{"entity": "Q10", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "Interestingly , in cells treated with NRTI only , markers for mitochondrial toxicity returned to baseline levels by 18 - 24h , suggesting a compensatory mechanism for clearing damaged mitochondria .", "entity": [], "task": "NER"}
{"text": "Using confocal microscopy , with confirmation utilizing the autophagy and mitophagy markers LC - 3 and NIX , respectively , we observed autophagy of mitochondria at 8 - 10 h after treatment .", "entity": [], "task": "NER"}
{"text": "Q10 prevented NRTI - mediated increase in LC - 3 .", "entity": [{"entity": "Q10", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "These findings suggest that NRTI - induced mitophagy may be involved in NRTI - induced endothelial dysfunction and that this damage likely results from oxidant injury .", "entity": [], "task": "NER"}
{"text": "Further , Q10 supplementation could potentially prevent NRTI - induced endothelial dysfunction .", "entity": [{"entity": "Q10", "entity_type": "Chemical", "pos": [10, 13]}], "task": "NER"}
{"text": "X - ray structure analysis and characterization of AFUEI , an elastase inhibitor from Aspergillus fumigatus .", "entity": [], "task": "NER"}
{"text": "Elastase from Aspergillus sp .", "entity": [], "task": "NER"}
{"text": "is an important factor for aspergillosis .", "entity": [], "task": "NER"}
{"text": "AFUEI is an inhibitor of the elastase derived from Aspergillus fumigatus .", "entity": [], "task": "NER"}
{"text": "AFUEI is a member of the I78 inhibitor family , and has a high inhibitory activity against elastases of Aspergillus fumigatus and Aspergillus flavus , human neutrophil elastase and bovine chymotrypsin , but does not inhibit bovine trypsin .", "entity": [], "task": "NER"}
{"text": "Here we report the crystal structure of AFUEI in two crystal forms .", "entity": [], "task": "NER"}
{"text": "AFUEI is a wedge - shaped protein composed of an extended loop and a scaffold protein core .", "entity": [], "task": "NER"}
{"text": "The structure of AFUEI shows remarkable similarity to serine protease inhibitors of the potato inhibitor I family , although they are classified into different inhibitor families .", "entity": [{"entity": "serine", "entity_type": "Chemical", "pos": [54, 60]}], "task": "NER"}
{"text": "A structural comparison with the potato I family inhibitors suggests that the extended loop of AFUEI corresponds to the binding loop of the potato inhibitor I family and AFUEI inhibits its cognate proteases through the same mechanism as the Potato I family inhibitors .", "entity": [], "task": "NER"}
{"text": "Copolymerization of 2 - methylene - 1 , 3 - dioxepane and glycidyl methacrylate , a well - defined and efficient process for achieving functionalized polyesters for covalent binding of bioactive molecules .", "entity": [{"entity": "2 - methylene - 1 , 3 - dioxepane", "entity_type": "Chemical", "pos": [20, 53]}, {"entity": "glycidyl methacrylate", "entity_type": "Chemical", "pos": [58, 79]}, {"entity": "polyesters", "entity_type": "Chemical", "pos": [150, 160]}], "task": "NER"}
{"text": "The understanding of cell - material interactions is important for creating personalized implants for tissue engineering .", "entity": [], "task": "NER"}
{"text": "This has resulted in an interest in developing polymers with functional groups with the possibility of controlling the macromolecular surface .", "entity": [], "task": "NER"}
{"text": "We have in a one - pot reaction synthesized a series of amorphous and degradable polyester - based copolymers with active functional groups by copolymerization of 2 - methylene - 1 , 3 - dioxepane and glycidyl methacrylate .", "entity": [{"entity": "polyester", "entity_type": "Chemical", "pos": [81, 90]}, {"entity": "2 - methylene - 1 , 3 - dioxepane", "entity_type": "Chemical", "pos": [163, 196]}, {"entity": "glycidyl methacrylate", "entity_type": "Chemical", "pos": [201, 222]}], "task": "NER"}
{"text": "The properties of the final polymers were varied by varying the feed ratios of the monomers and it was seen that it was possible to control the amount of active functional groups .", "entity": [], "task": "NER"}
{"text": "The resulting epoxy - functionalized polyester was further modified by covalent immobilization of heparin .", "entity": [{"entity": "epoxy - functionalized polyester", "entity_type": "Chemical", "pos": [14, 46]}], "task": "NER"}
{"text": "The heparinization was done in order , in a future aspect , to enhance the osteogenic differentiation of mesenchymal stem cells .", "entity": [], "task": "NER"}
{"text": "Heparin binds directly with the growth factor bone morphogenetic protein - 2 and helps to retain its activity .", "entity": [], "task": "NER"}
{"text": "The molecular structure of the copolymers was characterized by nuclear magnetic resonance , size exclusion chromatography , and fourier transform infrared spectroscopy .", "entity": [], "task": "NER"}
{"text": "Differential scanning calorimetry and tensile testing showed that the monomer feed ratio had a great influence on the properties of the final polymer and that it thus was possible to control the mechanical properties to suit an intended application .", "entity": [], "task": "NER"}
{"text": "The presence of heparin was verified by toluidine blue staining and all the films tested showed positive signals for heparin .", "entity": [{"entity": "toluidine blue", "entity_type": "Chemical", "pos": [40, 54]}], "task": "NER"}
{"text": "Influence of histidine incorporation on buffer capacity and gene transfection efficiency of HPMA - co - oligolysine brush polymers .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [13, 22]}, {"entity": "HPMA", "entity_type": "Chemical", "pos": [92, 96]}], "task": "NER"}
{"text": "One of the major intracellular barriers to non - viral gene delivery is efficient endosomal escape .", "entity": [], "task": "NER"}
{"text": "The incorporation of histidine residues into polymeric constructs has been found to increase endosomal escape via the proton sponge effect .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [21, 30]}], "task": "NER"}
{"text": "Statistical and diblock copolymers of N - ( 2 - hydroxypropyl ) methacrylamide ( HPMA ) , oligolysine , and oligohistidine were synthesized via reversible - addition fragmentation chain transfer ( RAFT ) polymerization , and tested for in vitro transfection efficiency , buffering ability , and polyplex uptake mechanism via the use of chemical endocytic inhibitors .", "entity": [{"entity": "N - ( 2 - hydroxypropyl ) methacrylamide", "entity_type": "Chemical", "pos": [38, 78]}, {"entity": "HPMA", "entity_type": "Chemical", "pos": [81, 85]}], "task": "NER"}
{"text": "Interestingly , histidine - containing statistical and diblock polymers exhibited increased buffer capacity in different endosomal pH ranges .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [16, 25]}], "task": "NER"}
{"text": "Statistical copolymers transfected better than block copolymers that contained similar amounts of histidine .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [98, 107]}], "task": "NER"}
{"text": "In addition , only the polymer containing the highest incorporation of oligohistidine residues led to increases in transfection efficiency over the HPMA - oligolysine base polymer .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [148, 152]}], "task": "NER"}
{"text": "Thus , for these polymer architectures , high histidine incorporation may be required for efficient endosomal escape .", "entity": [{"entity": "histidine", "entity_type": "Chemical", "pos": [46, 55]}], "task": "NER"}
{"text": "Furthermore , uptake studies indicate that non - acidified caveolae - mediated endocytosis may be the primary route of transfection for these copolymers , suggesting that alternative approaches for increasing endosomal escape may be beneficial for enhancing transfection efficiency with these HPMA - oligolysine copolymers .", "entity": [{"entity": "HPMA", "entity_type": "Chemical", "pos": [293, 297]}], "task": "NER"}
{"text": "Surface - sensitive two - dimensional magneto - fingerprint in mesoscopic Bi2Se3 channels .", "entity": [{"entity": "Bi2Se3", "entity_type": "Chemical", "pos": [74, 80]}], "task": "NER"}
{"text": "Periodic Aharonov - Bohm and Altshuler - Aronov - Spivak oscillations have traditionally been observed in lateral transport through patterned mesoscopic loops of diffusive conductors .", "entity": [], "task": "NER"}
{"text": "However , our studies of perpendicular - to - plane magnetotransport in straight - channel , diffusive devices of epitaxial Bi2Se3 surprisingly reveal signatures of Aharonov - Bohm orbits - - periodic conductance fluctuation magneto - fingerprints - - even though the devices are not explicitly patterned into loops .", "entity": [{"entity": "Bi2Se3", "entity_type": "Chemical", "pos": [124, 130]}], "task": "NER"}
{"text": "We show that the length scale of these orbits corresponds to the typical perimeter of triangular terraces found on the surface of these thin film devices , strongly suggesting that the periodic magneto - fingerprint arises from coherent scattering of electron waves from the step - edges .", "entity": [], "task": "NER"}
{"text": "Our interpretation is bolstered by control measurements in devices without such surface morphology which only show a conventional , aperiodic magneto - fingerprint .", "entity": [], "task": "NER"}
{"text": "These results show that lithographically patterned Bi2Se3 devices provide a novel class of mesoscopic physical systems for systematic studies of coherent surface sensitive transport .", "entity": [{"entity": "Bi2Se3", "entity_type": "Chemical", "pos": [51, 57]}], "task": "NER"}
{"text": "Simulations of droplet coalescence in simple shear flow .", "entity": [], "task": "NER"}
{"text": "Simulating droplet coalescence is challenging because small - scale ( tens of nanometers ) phenomena determine the behaviour of much larger ( micron - to millimetre - scale ) droplets .", "entity": [], "task": "NER"}
{"text": "In general , liquid droplets colliding in a liquid medium coalesce when the capillary number is less than a critical value .", "entity": [], "task": "NER"}
{"text": "We present simulations of droplet collisions and coalescence in simple shear flow using the free - energy binary - liquid lattice Boltzmann method .", "entity": [], "task": "NER"}
{"text": "In previous simulations of low - speed collisions , droplets coalesced at unrealistically high capillary numbers .", "entity": [], "task": "NER"}
{"text": "Simulations of non - coalescing droplets have not been reported , and therefore the critical capillary number for simulated collisions was unknown .", "entity": [], "task": "NER"}
{"text": "By simulating droplets with radii up to 100 lattice nodes , we determine the critical capillary number for coalescence and quantify the effects of several numerical and geometric parameters .", "entity": [], "task": "NER"}
{"text": "The simulations were performed with a well - resolved interface , a Reynolds number of one , and capillary numbers from 0 . 01 to 0 . 2 .", "entity": [], "task": "NER"}
{"text": "The ratio of the droplet radius and interface thickness has the greatest effect on the critical capillary number .", "entity": [], "task": "NER"}
{"text": "As in experiments , the critical capillary number decreases with increasing droplet size .", "entity": [], "task": "NER"}
{"text": "A second numerical parameter , the interface diffusivity ( Peclet number ) also influences the conditions for coalescence : coalescence occurs at higher capillary numbers with lower Peclet numbers ( higher diffusivity ) .", "entity": [], "task": "NER"}
{"text": "The effects of the vertical offset between the droplets and the confinement of the droplets were also studied .", "entity": [], "task": "NER"}
{"text": "Physically reasonable results were obtained and provide insight into the conditions for coalescence .", "entity": [], "task": "NER"}
{"text": "Simulations that match the conditions of experiments reported in the literature remain computationally impractical .", "entity": [], "task": "NER"}
{"text": "However , the scale of the simulations is now sufficiently large that a comparison with experiments involving smaller droplets ( ~ 10 mu m ) and lower viscosities ( 10 ( - 6 ) m ( 2 ) / s , the viscosity of water ) may be possible .", "entity": [], "task": "NER"}
{"text": "Experiments at these conditions are therefore needed to determine the interface thickness and Peclet number that should be used for predictive simulations of coalescence phenomena .", "entity": [], "task": "NER"}
{"text": "Carbonic anhydrase inhibitors .", "entity": [], "task": "NER"}
{"text": "Benzenesulfonamides incorporating cyanoacrylamide moieties strongly inhibit Saccharomyces cerevisiae beta - carbonic anhydrase .", "entity": [{"entity": "Benzenesulfonamides", "entity_type": "Chemical", "pos": [0, 19]}, {"entity": "cyanoacrylamide", "entity_type": "Chemical", "pos": [34, 49]}], "task": "NER"}
{"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties ( tyrphostine analogs ) were assayed as inhibitors of the beta - carbonic anhydrase ( CA , EC 4 . 2 . 1 . 1 ) from Saccharomyces cerevisiae , ScCA .", "entity": [{"entity": "benzenesulfonamides", "entity_type": "Chemical", "pos": [12, 31]}, {"entity": "cyanoacrylamide", "entity_type": "Chemical", "pos": [46, 61]}, {"entity": "tyrphostine", "entity_type": "Chemical", "pos": [73, 84]}], "task": "NER"}
{"text": "Some of these compounds were low nanomolar or subnanomolar ScCA inhibitors and showed selectivity ratios in the range of 4 . 91 - 69 . 86 for inhibiting the yeast enzyme over the offtarget human ( h ) isoforms hCA I and of 6 . 46 - 13 . 52 for inhibiting ScCA over hCA II .", "entity": [], "task": "NER"}
{"text": "The model organism S . cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged .", "entity": [{"entity": "azole", "entity_type": "Chemical", "pos": [160, 165]}], "task": "NER"}
{"text": "Indeed , some of these sulfonamides inhibited the growth of the yeast with CC50 - s in the range of 0 . 73 - 6 . 54 mu M .", "entity": [{"entity": "sulfonamides", "entity_type": "Chemical", "pos": [23, 35]}], "task": "NER"}
{"text": "Apoptosis inducing activity of benzophenanthridine - type alkaloids and 2 - arylbenzofuran neolignans in HCT116 colon carcinoma cells .", "entity": [{"entity": "benzophenanthridine - type alkaloids", "entity_type": "Chemical", "pos": [31, 67]}, {"entity": "2 - arylbenzofuran neolignans", "entity_type": "Chemical", "pos": [72, 101]}], "task": "NER"}
{"text": "Thirteen compounds belonging to different classes of alkaloids ( 1 - 9 ) and lignans ( 10 - 13 ) , isolated from the methanol extract of roots of the African medicinal plant Zanthoxylum capense , were assayed for their ability as apoptosis inducers in HCT116 colon carcinoma cells .", "entity": [{"entity": "lignans", "entity_type": "Chemical", "pos": [77, 84]}, {"entity": "methanol", "entity_type": "Chemical", "pos": [117, 125]}], "task": "NER"}
{"text": "The cytotoxicity of these compounds was evaluated in HCT116 colon carcinoma cells by the MTS assay .", "entity": [{"entity": "MTS", "entity_type": "Chemical", "pos": [89, 92]}], "task": "NER"}
{"text": "Out of the tested compounds , three benzophenanthridine alkaloids ( 1 , 4 , and 7 ) , a dibenzyl butyrolactone lignan ( 10 ) , and two 2 - arylbenzofuran neolignans ( 12 and 13 ) displayed significant cytotoxicity to HCT116 cells , confirmed by the Guava ViaCount viability assay .", "entity": [{"entity": "benzophenanthridine alkaloids", "entity_type": "Chemical", "pos": [36, 65]}, {"entity": "dibenzyl butyrolactone lignan", "entity_type": "Chemical", "pos": [88, 117]}, {"entity": "2 - arylbenzofuran neolignans", "entity_type": "Chemical", "pos": [135, 164]}], "task": "NER"}
{"text": "The selected compounds ( 1 , 4 , 7 , 10 , 12 , and 13 ) were further tested for apoptosis induction activity in HCT116 cells , by evaluation of nuclear morphology following Hoechst staining , and by caspase - 3 like activity assays .", "entity": [], "task": "NER"}
{"text": "Morphologic evaluation of HCT116 nuclei following Hoechst staining and fluorescence microscopy revealed that compounds 1 , 4 , 7 , 10 , 12 , and 13 induced apoptosis in HCT116 colon carcinoma cells , producing similar , or higher , apoptosis levels when compared with 5 - fluorouracil ( 5 - FU ) , the cornerstone cytotoxic used in colon cancer treatment for several decades .", "entity": [{"entity": "5 - fluorouracil", "entity_type": "Chemical", "pos": [268, 284]}, {"entity": "5 - FU", "entity_type": "Chemical", "pos": [287, 293]}], "task": "NER"}
{"text": "In fact , HCT116 cells developed morphological changes characteristic of apoptosis , including chromatin condensation , nuclear fragmentation and formation of apoptotic bodies .", "entity": [], "task": "NER"}
{"text": "Importantly , compounds 4 and 13 at 20 mu M were the most promising in this study , inducing respectively ~ 11 - and 7 - fold increases in apoptotic cells as compared to vehicle control , whereas 5 - FU increased apoptosis by ~ 2 - fold .", "entity": [{"entity": "5 - FU", "entity_type": "Chemical", "pos": [196, 202]}], "task": "NER"}
{"text": "Apoptosis induction for compounds 4 and 13 was further confirmed by caspase - 3 - like activity assays , which showed respectively ~ 2 - and 1 . 5 - fold increases in caspase - 3 - like activity compared to vehicle control .", "entity": [], "task": "NER"}
{"text": "These results suggested that specific benzophenanthridine alkaloids and 2 - arylbenzofuran neolignans isolated from Zanthoxylum capense show strong anticancer activity in HCT116 colon carcinoma cells .", "entity": [{"entity": "benzophenanthridine alkaloids", "entity_type": "Chemical", "pos": [38, 67]}, {"entity": "2 - arylbenzofuran neolignans", "entity_type": "Chemical", "pos": [72, 101]}], "task": "NER"}
{"text": "Nordihydroguaiaretic acid induces Nrf2 nuclear translocation in vivo and attenuates renal damage and apoptosis in the ischemia and reperfusion model .", "entity": [{"entity": "Nordihydroguaiaretic acid", "entity_type": "Chemical", "pos": [0, 25]}], "task": "NER"}
{"text": "It has been shown that the pretreatment with nordihydroguaiaretic acid ( NDGA ) , a lignan with direct and indirect antioxidant properties , protects against the ischemia - reperfusion ( I / R ) - induced renal oxidant damage .", "entity": [{"entity": "nordihydroguaiaretic acid", "entity_type": "Chemical", "pos": [45, 70]}, {"entity": "NDGA", "entity_type": "Chemical", "pos": [73, 77]}], "task": "NER"}
{"text": "Although it has been shown that NDGA induces Nrf2 nuclear translocation in renal epithelial LLC - PK1 cells in culture , it is unknown if NDGA may induce Nrf2 translocation in vivo .", "entity": [{"entity": "NDGA", "entity_type": "Chemical", "pos": [32, 36]}, {"entity": "NDGA", "entity_type": "Chemical", "pos": [138, 142]}], "task": "NER"}
{"text": "In this work was explored if NDGA is able to induce in vivo Nrf2 nuclear translocation in kidneys of rats submitted to uni - nephrectomy ( U - NX ) or I / R injury .", "entity": [{"entity": "NDGA", "entity_type": "Chemical", "pos": [29, 33]}], "task": "NER"}
{"text": "Four groups of male Wistar rats were used : U - NX , NDGA , I / R , and I / R + NDGA .", "entity": [{"entity": "NDGA", "entity_type": "Chemical", "pos": [53, 57]}, {"entity": "NDGA", "entity_type": "Chemical", "pos": [80, 84]}], "task": "NER"}
{"text": "NDGA was injected i . p .", "entity": [{"entity": "NDGA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "( 10mg / kg / day ) starting 48h before I / R .", "entity": [], "task": "NER"}
{"text": "Kidney samples were obtained at 3h of reperfusion after to measure Nrf2 translocation .", "entity": [], "task": "NER"}
{"text": "Additional groups of rats were studied at 24h of reperfusion to measure histological damage and apoptosis .", "entity": [], "task": "NER"}
{"text": "NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U - NX and I / R injury and to protect against renal histological damage and apoptosis .", "entity": [{"entity": "NDGA", "entity_type": "Chemical", "pos": [0, 4]}], "task": "NER"}
{"text": "It is concluded that the pretreatment of NDGA is able to induce in vivo nuclear Nrf2 translocation in kidney of rats suggesting that this may be involved in the renoprotection against I / R .", "entity": [{"entity": "NDGA", "entity_type": "Chemical", "pos": [41, 45]}], "task": "NER"}
{"text": "Cytokine targets in airway inflammation .", "entity": [], "task": "NER"}
{"text": "Asthma is an inflammatory disease of the airway wall that leads to bronchial hyper - reactivity and airway obstruction , caused by inflammation , mucus hyper - production and airway wall remodelling .", "entity": [], "task": "NER"}
{"text": "Central to pathogenesis , Th2 and Th17 lymphocytes of the adaptive immune system control many aspects of the disease by producing cytokines such as IL - 4 , IL - 5 , IL - 13 , and IL - 17 .", "entity": [], "task": "NER"}
{"text": "In addition , many cells of the innate immune system such as mast cells , basophils , neutrophils , eosinophils , dendritic cells ( DCs ) , and innate lymphoid cells ( ILCs ) play an important role in the initiation or maintenance of disease .", "entity": [], "task": "NER"}
{"text": "Epithelial cells are ever more implicated in disease pathogenesis , as they are able to sense exposure to pathogens via pattern recognition receptors ( PRRs ) and can activate DCs .", "entity": [], "task": "NER"}
{"text": "This review article will deal with the role of cytokines that are considered essential controllers of the inflammatory , immune and regenerative response to allergens , viruses and environmental pollutants .", "entity": [], "task": "NER"}
{"text": "Emerging Th2 cytokines such as thymic stromal lymphopoietin , GM - CSF , IL - 1 , IL - 33 , IL - 25 mediate the crosstalk between epithelial cells , DCs , and ILCs .", "entity": [], "task": "NER"}
{"text": "Understanding the crosstalk between structural cells , innate and adaptive immune cells that is mediated by cytokines provides important mechanistic insights into how asthma develops and perpetuates itself .", "entity": [], "task": "NER"}
{"text": "It could also provide the framework on which we will select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease .", "entity": [], "task": "NER"}
{"text": "Pharmacokinetic study of four flavones of Glycyrrhiza in rat plasma using HPLC - MS .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "AIM OF THE STUDY : This study aimed to develop a specific HPLC - MS method for simultaneous quantification of four flavones of Glycyrrhiza in rat plasma after oral administration and to describe the pharmacokinetics of four flavones in rat plasma .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [115, 123]}, {"entity": "flavones", "entity_type": "Chemical", "pos": [224, 232]}], "task": "NER"}
{"text": "MATERIALS AND METHODS : A simple , sensitive and selective method for simultaneous determination of four flavones of Glycyrrhiza in rat plasma , i . e . , liquiritin , isoliquiritin , liquiritigenin , isoliquiritigenin , by high performance liquid chromato - graphy - tandem mass spectrometry ( HPLC - MS ) with negative electrospray ionization mode , was developed and validated .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [105, 113]}, {"entity": "liquiritin", "entity_type": "Chemical", "pos": [155, 165]}, {"entity": "isoliquiritin", "entity_type": "Chemical", "pos": [168, 181]}, {"entity": "liquiritigenin", "entity_type": "Chemical", "pos": [184, 198]}, {"entity": "isoliquiritigenin", "entity_type": "Chemical", "pos": [201, 218]}], "task": "NER"}
{"text": "The method was applied to investigate the pharmacokinetics of four flavones in rat plasma after oral administration of Glycyrrhiza flavones .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [67, 75]}, {"entity": "flavones", "entity_type": "Chemical", "pos": [131, 139]}], "task": "NER"}
{"text": "Chromatographic separation was accomplished on an Agilent TC - C18 column ( 4 . 6mm x 250mm , 5 mu m ) , with gradient elution by using a mixture of methanoic acid ( A ) and acetonitrile ( B ) as the mobile phase at a flow rate of 0 . 8mL / min .", "entity": [{"entity": "methanoic acid", "entity_type": "Chemical", "pos": [149, 163]}, {"entity": "acetonitrile", "entity_type": "Chemical", "pos": [174, 186]}], "task": "NER"}
{"text": "RESULTS : The calibration curves for four flavones had good linearity in the measured range with higher than 0 . 997 .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "Relative standard deviations ( RSDs ) of the intra - and inter - day precision at different levels were all less than 4 . 8 % .", "entity": [], "task": "NER"}
{"text": "The pharmacokinetic profile of four flavones in rat plasma was fitted with a two - compartment model detected by a simple , rapid and accurate HPLC - MS method .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [36, 44]}], "task": "NER"}
{"text": "Time ( h ) to reach peak concentration ( mu g / mL ) of liquiritin ( 2 . 69 +/- 0 . 04 ) , isoliquiritin ( 10 . 16 +/- 0 . 02 ) , liquiritigenin ( 2 . 83 +/- 0 . 02 ) , isoliquiritigenin ( 0 . 28 +/- 0 . 01 ) were 2 . 02 +/- 0 . 23 , 1 . 97 +/- 0 . 20 , 0 . 48 +/- 0 . 02 , 1 . 93 +/- 0 . 36 , respectively .", "entity": [{"entity": "liquiritin", "entity_type": "Chemical", "pos": [56, 66]}, {"entity": "isoliquiritin", "entity_type": "Chemical", "pos": [91, 104]}, {"entity": "liquiritigenin", "entity_type": "Chemical", "pos": [130, 144]}, {"entity": "isoliquiritigenin", "entity_type": "Chemical", "pos": [169, 186]}], "task": "NER"}
{"text": "The distribution and elimination half - life ( h ) and area under the concentration - time curve ( mu g / mL * h ) from t = 0 to last time of liquiritin , isoliquiritin , liquiritigenin , isoliquiritigenin were 1 . 02 +/- 0 . 48 / 2 . 27 +/- 0 . 53 / 16 . 97 +/- 0 . 43 , 2 . 04 +/- 1 . 01 / 2 . 38 +/- 0 . 80 / 69 . 20 +/- 5 . 24 , 0 . 35 +/- 0 . 10 / 4 . 26 +/- 0 . 16 / 14 . 83 +/- 0 . 11 , 1 . 18 +/- 0 . 32 / 3 . 04 , +/- 0 . 22 / 2 . 10 +/- 0 . 09 , respectively .", "entity": [{"entity": "liquiritin", "entity_type": "Chemical", "pos": [142, 152]}, {"entity": "isoliquiritin", "entity_type": "Chemical", "pos": [155, 168]}, {"entity": "liquiritigenin", "entity_type": "Chemical", "pos": [171, 185]}, {"entity": "isoliquiritigenin", "entity_type": "Chemical", "pos": [188, 205]}], "task": "NER"}
{"text": "Isoliquiritin presented the phenomenon of double peaks and the others appeared together in a single and plateau absorption phase .", "entity": [{"entity": "Isoliquiritin", "entity_type": "Chemical", "pos": [0, 13]}], "task": "NER"}
{"text": "Isoliquiritigenin had the lowest oral bioavailability because of Cmax and AUC0 - infinity .", "entity": [{"entity": "Isoliquiritigenin", "entity_type": "Chemical", "pos": [0, 17]}], "task": "NER"}
{"text": "Liquiritigenin had the fastest absorption and distribution rate and the lowest elimination rate according to Tmax , t1 / 2 alpha , t1 / 2 beta .", "entity": [{"entity": "Liquiritigenin", "entity_type": "Chemical", "pos": [0, 14]}], "task": "NER"}
{"text": "CONCLUSIONS : This paper first reported on identification and determination of four flavones of Glycyrrhiza in rat plasma and their respective pharmacokinetic characteristics .", "entity": [{"entity": "flavones", "entity_type": "Chemical", "pos": [84, 92]}], "task": "NER"}
{"text": "The results provided a meaningful basis for better understanding the absorption mechanism of Glycyrrhiza and evaluating the clinical application of this medicine .", "entity": [], "task": "NER"}
{"text": "Herbalists and wild medicinal plants in M ' Sila ( North Algeria ) : An ethnopharmacology survey .", "entity": [], "task": "NER"}
{"text": "AIM OF THE STUDY : The main aim of this study was to identify , catalogue and document the large number of wild medicinal plants used in the M ' Sila region ( northern Algeria ) for the treatment of several human pathologies .", "entity": [], "task": "NER"}
{"text": "Another more ambitious aim is to contribute to overcoming the limits of an orally transmitted pharmacopoeia , attempting to exploit the large ethnopharmacology patrimony of the region for further pharmacological purposes .", "entity": [], "task": "NER"}
{"text": "MATERIALS AND METHODS : Our field study was carried out over a period of three years ( 2008 - 2010 ) .", "entity": [], "task": "NER"}
{"text": "During this period , herbalists were interviewed using semi - structured questionnaires investigating the herbalist as a holder of information ( gender , age and educational level ) and about wild medicinal plants ( local name , uses and part used ) .", "entity": [], "task": "NER"}
{"text": "In addition , the relative importance value of the species was determined and informant consensus factor ( ICF ) was calculated for the medicinal plants included in the study .", "entity": [], "task": "NER"}
{"text": "RESULTS : A total of 83 herbalists were interviewed , men dominate the practice of traditional medicine in the region .", "entity": [], "task": "NER"}
{"text": "About 41 % of them are between 31 - 40 years , and about a third ( 34 % ) is illiterate .", "entity": [], "task": "NER"}
{"text": "The traditional herbal knowledge is passed from generation to generation in the verbal form , being almost totally absent a writing tradition .", "entity": [], "task": "NER"}
{"text": "The interviewed herbalists identified and recorded 58 plants species and 50 genera belonging to 27 plant families .", "entity": [], "task": "NER"}
{"text": "Lamiaceae and Asteraceae were the most represented plant families .", "entity": [], "task": "NER"}
{"text": "The aerial parts were the most commonly used plant part , while infusion and decoction were the most common method of traditional drug preparation .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : The survey provides a veritable source of information on the herbalists and wild medicinal plants .", "entity": [], "task": "NER"}
{"text": "Plants which are used in different parts of the world for the treatment of similar diseases may be deemed to be effective in pharmacological terms .", "entity": [], "task": "NER"}
{"text": "These medicinal plants may be incorporated into the healthcare delivery system of the country .", "entity": [], "task": "NER"}
{"text": "Epidemiology of Paget ' s disease of Bone : A systematic review and meta - analysis of secular changes .", "entity": [], "task": "NER"}
{"text": "CONTEXT : Several studies have suggested that the prevalence and severity of PDB have fallen in recent years .", "entity": [], "task": "NER"}
{"text": "The magnitude of this trend and its globalization have not been well established .", "entity": [], "task": "NER"}
{"text": "OBJECTIVE : To estimate the pooled magnitude of the changes in the prevalence of PDB .", "entity": [], "task": "NER"}
{"text": "As a secondary objective , to make up a world atlas of PDB prevalence .", "entity": [], "task": "NER"}
{"text": "METHODS : Systematic review of English and non - English articles using MEDLINE ( 1946 to 2013 ) and EMBASE ( 1980 to 2013 ) .", "entity": [], "task": "NER"}
{"text": "Search terms included epidemiology , incidence , prevalence , cohort studies , osteitis deformans or Paget disease of bone .", "entity": [], "task": "NER"}
{"text": "Studies with incidence and / or prevalence rate for PDB were included .", "entity": [], "task": "NER"}
{"text": "Two authors independently extracted the data using predefined data fields and quality assessment .", "entity": [], "task": "NER"}
{"text": "A pooled analyses based on random - effects models was carried out for secular trends .", "entity": [], "task": "NER"}
{"text": "RESULTS : Twenty - eight articles documented the prevalence of PDB ; four articles the incidence and two articles the rate of new referrals .", "entity": [], "task": "NER"}
{"text": "The prevalence of PDB varied greatly between the different countries , from 0 . 00028 % in Japan to 5 . 4 % in UK .", "entity": [], "task": "NER"}
{"text": "There were available data on changes in prevalence from two different surveys over two different time frames in Europe and New Zealand .", "entity": [], "task": "NER"}
{"text": "In all but one city ( Turin ) , a drop in the prevalence of PDB was recorded ( pooled OR 0 . 64 : 95 % CI : 0 . 45 - 0 . 91 ) .", "entity": [], "task": "NER"}
{"text": "CONCLUSION : The incidence and prevalence rates of PDB vary widely between populations but both have decreased in most regions over recent years .", "entity": [], "task": "NER"}
{"text": "The changes are heterogeneous however and within countries , the largest changes have been in areas that previously had a high prevalence .", "entity": [], "task": "NER"}
{"text": "The reasons for these changes remain unclear at present but are likely to be due to an interaction between genetic factors and environmental triggers which may differ in different regions .", "entity": [], "task": "NER"}
{"text": "Diminished response to in vivo mechanical loading in trabecular and not cortical bone in adulthood of female C57Bl / 6 mice coincides with a reduction in deformation to load .", "entity": [], "task": "NER"}
{"text": "Bone loss occurs during adulthood in both women and men and affects trabecular bone more than cortical bone .", "entity": [], "task": "NER"}
{"text": "The mechanism responsible for trabecular bone loss during adulthood remains unexplained , but may be due at least in part to a reduced mechanoresponsiveness .", "entity": [], "task": "NER"}
{"text": "We hypothesized that trabecular and cortical bone would respond anabolically to loading and that the bone response to mechanical loading would be reduced and the onset delayed in adult compared to postpubescent mice .", "entity": [], "task": "NER"}
{"text": "We evaluated the longitudinal adaptive response of trabecular and cortical bone in postpubescent , young ( 10 week old ) and adult ( 26 week old ) female C57Bl / 6J mice to axial tibial compression using in vivo microCT ( day 0 , 5 , 10 , and 15 ) and dynamic histomorphometry ( day 15 ) .", "entity": [], "task": "NER"}
{"text": "Loading elicited an anabolic response in both trabecular and cortical bone in young and adult mice .", "entity": [], "task": "NER"}
{"text": "As hypothesized , trabecular bone in adult mice exhibited a reduced and delayed response to loading compared to the young mice , apparent in trabecular bone volume fraction and architecture after 10 days .", "entity": [], "task": "NER"}
{"text": "No difference in mechanoresponsiveness of the cortical bone was observed between young and adult mice .", "entity": [], "task": "NER"}
{"text": "Finite element analysis showed that load - induced strain was reduced with age .", "entity": [], "task": "NER"}
{"text": "Our results suggest that trabecular bone loss that occurs in adulthood may in part be due to a reduced mechanoresponsiveness in this tissue and / or a reduction in the induced tissue deformation which occurs during habitual loading .", "entity": [], "task": "NER"}
{"text": "Therapeutic approaches that address the mechanoresponsiveness of the bone tissue may be a promising and alternate strategy to maintain trabecular bone mass during aging .", "entity": [], "task": "NER"}
{"text": "Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays .", "entity": [{"entity": "nitrile", "entity_type": "Chemical", "pos": [30, 37]}], "task": "NER"}
{"text": "Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family .", "entity": [{"entity": "nitrile", "entity_type": "Chemical", "pos": [93, 100]}], "task": "NER"}
{"text": "These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles .", "entity": [{"entity": "nitriles", "entity_type": "Chemical", "pos": [6, 14]}, {"entity": "nitriles", "entity_type": "Chemical", "pos": [141, 149]}], "task": "NER"}
{"text": "The 8 nitriles were assessed for genotoxicity using an Ames test , in - vitro chromosome aberration test or in - vitro micronucleus test .", "entity": [{"entity": "nitriles", "entity_type": "Chemical", "pos": [6, 14]}], "task": "NER"}
{"text": "The positive results observed in the in - vitro tests were further investigated using an in - vivo micronucleus test .", "entity": [], "task": "NER"}
{"text": "The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic .", "entity": [{"entity": "nitriles", "entity_type": "Chemical", "pos": [65, 73]}], "task": "NER"}
{"text": "Dodecanitrile and 2 , 2 , 3 - trimethylcyclopent - 3 - enylacetonitrile were negative in the in - vitro chromosome aberration test and in - vitro micronucleus test , respectively .", "entity": [{"entity": "Dodecanitrile", "entity_type": "Chemical", "pos": [0, 13]}, {"entity": "2 , 2 , 3 - trimethylcyclopent - 3 - enylacetonitrile", "entity_type": "Chemical", "pos": [18, 71]}], "task": "NER"}
{"text": "While citronellyl nitrile , 3 - methyl - 5 - phenylpentanenitrile , cinnamyl nitrile , and 3 - methyl - 5 - phenylpent - 2 - enenitrile revealed positive results in the in - vitro tests , but confirmatory in - vivo tests determined these nitriles to be negative in the in - vivo micronucleus assay .", "entity": [{"entity": "citronellyl nitrile", "entity_type": "Chemical", "pos": [6, 25]}, {"entity": "3 - methyl - 5 - phenylpentanenitrile", "entity_type": "Chemical", "pos": [28, 65]}, {"entity": "cinnamyl nitrile", "entity_type": "Chemical", "pos": [68, 84]}, {"entity": "3 - methyl - 5 - phenylpent - 2 - enenitrile", "entity_type": "Chemical", "pos": [91, 135]}, {"entity": "nitriles", "entity_type": "Chemical", "pos": [238, 246]}], "task": "NER"}
{"text": "The remaining two nitriles ( benzonitrile and alpha - cyclohexylidene benzeneacetonitrile ) were negative in the in - vivo micronucleus test .", "entity": [{"entity": "nitriles", "entity_type": "Chemical", "pos": [18, 26]}, {"entity": "benzonitrile", "entity_type": "Chemical", "pos": [29, 41]}, {"entity": "alpha - cyclohexylidene benzeneacetonitrile", "entity_type": "Chemical", "pos": [46, 89]}], "task": "NER"}
{"text": "This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients .", "entity": [{"entity": "nitriles", "entity_type": "Chemical", "pos": [64, 72]}], "task": "NER"}
{"text": "Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats .", "entity": [{"entity": "Hydroxytyrosyl alkyl ether", "entity_type": "Chemical", "pos": [0, 26]}], "task": "NER"}
{"text": "The low lipophilicity of hydroxytyrosol ( HT ) has motivated efforts to synthesize homologous series with better lipid solubility , such as the ethers , which are more lipophilic than HT .", "entity": [{"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [25, 39]}, {"entity": "ethers", "entity_type": "Chemical", "pos": [144, 150]}], "task": "NER"}
{"text": "Because HT inhibits platelet aggregation , the aim of the study was to assess the possible anti - platelet effect of five HT ether derivatives ( ethyl , butyl , hexyl , octyl and dodecyl ) after oral administration to rats .", "entity": [{"entity": "ether", "entity_type": "Chemical", "pos": [125, 130]}, {"entity": "ethyl", "entity_type": "Chemical", "pos": [145, 150]}, {"entity": "butyl", "entity_type": "Chemical", "pos": [153, 158]}, {"entity": "hexyl", "entity_type": "Chemical", "pos": [161, 166]}, {"entity": "octyl", "entity_type": "Chemical", "pos": [169, 174]}, {"entity": "dodecyl", "entity_type": "Chemical", "pos": [179, 186]}], "task": "NER"}
{"text": "Whole blood collagen - induced platelet aggregation and calcium - induced thromboxane B2 ( TxB2 ) , aortic 6 - keto - prostaglandin F1 alpha ( 6 - keto - PGF1 alpha ) and nitrites + nitrates , plasma concentration of lipid peroxides ( TBARS ) and red blood cell content of reduced glutathione ( GSH ) were measured .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [56, 63]}, {"entity": "thromboxane B2", "entity_type": "Chemical", "pos": [74, 88]}, {"entity": "TxB2", "entity_type": "Chemical", "pos": [91, 95]}, {"entity": "6 - keto - prostaglandin F1 alpha", "entity_type": "Chemical", "pos": [107, 140]}, {"entity": "6 - keto - PGF1 alpha", "entity_type": "Chemical", "pos": [143, 164]}, {"entity": "nitrites", "entity_type": "Chemical", "pos": [171, 179]}, {"entity": "nitrates", "entity_type": "Chemical", "pos": [182, 190]}, {"entity": "peroxides", "entity_type": "Chemical", "pos": [223, 232]}, {"entity": "reduced glutathione", "entity_type": "Chemical", "pos": [273, 292]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [295, 298]}], "task": "NER"}
{"text": "The administration of 20 mg / kg / day inhibited platelet aggregation , TxB2 and TBARS in a non - linear manner related to the length of the carbon chain , with a cut - off effect in the hexyl derivative .", "entity": [{"entity": "TxB2", "entity_type": "Chemical", "pos": [72, 76]}, {"entity": "carbon", "entity_type": "Chemical", "pos": [141, 147]}, {"entity": "hexyl", "entity_type": "Chemical", "pos": [187, 192]}], "task": "NER"}
{"text": "Aortic nitrite and red blood cell GSH production were also increased .", "entity": [{"entity": "nitrite", "entity_type": "Chemical", "pos": [7, 14]}, {"entity": "GSH", "entity_type": "Chemical", "pos": [34, 37]}], "task": "NER"}
{"text": "The aortic production of 6 - keto - PGF1 alpha was unaltered except in the group treated with the dodecyl derivative .", "entity": [{"entity": "6 - keto - PGF1 alpha", "entity_type": "Chemical", "pos": [25, 46]}, {"entity": "dodecyl", "entity_type": "Chemical", "pos": [98, 105]}], "task": "NER"}
{"text": "The administration of 50 mg / kg / day showed a similar pharmacodynamic profile but without the non - linear effect .", "entity": [], "task": "NER"}
{"text": "In conclusion , HT ethers , especially the hexyl derivative , are a potential alternative to hydroxytyrosol , and their effect merits additional research to determine their role in the prophylaxis of vascular disease .", "entity": [{"entity": "ethers", "entity_type": "Chemical", "pos": [19, 25]}, {"entity": "hexyl", "entity_type": "Chemical", "pos": [43, 48]}, {"entity": "hydroxytyrosol", "entity_type": "Chemical", "pos": [93, 107]}], "task": "NER"}
{"text": "Medicines Combinations Options and Regulatory Hurdles .", "entity": [], "task": "NER"}
{"text": "The number of fixed dose combinations ( FDC ) on the market is increasing .", "entity": [], "task": "NER"}
{"text": "However , both regulatory guidelines and the evidence for better effectiveness of fixed dose combinations are not established yet .", "entity": [], "task": "NER"}
{"text": "These aspects were the topic for a recent EUFEPS workshop in Copenhagen .", "entity": [], "task": "NER"}
{"text": "The discussion confirms the presence of hurdles and recommendations to further progress and alleviate the problems .", "entity": [], "task": "NER"}
{"text": "The general conclusion was : Refinement of general systems pharmacology tools for identification of key molecular targets in disease development ; Precompetitive methodologies and technologies designed for ( co - ) development of FDCs ; Simulation and modeling algorithms applied on pharmacodynamics ( synergy ) , pharmacokinetics and safety ; New formulations of FDCs of solid , liquid or inhalation forms ; Prospective clinical studies for measuring the efficacy and effectiveness of use of drug - drug combinations in elderly .", "entity": [], "task": "NER"}
{"text": "Cyclooxygenase activity contributes to the monoaminergic damage caused by serial exposure to stress and methamphetamine .", "entity": [{"entity": "methamphetamine", "entity_type": "Chemical", "pos": [104, 119]}], "task": "NER"}
{"text": "Methamphetamine ( Meth ) is a widely abused psychostimulant that causes long - term dopamine ( DA ) and serotonin ( 5 - HT ) depletions .", "entity": [{"entity": "Methamphetamine", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [18, 22]}, {"entity": "dopamine", "entity_type": "Chemical", "pos": [84, 92]}, {"entity": "serotonin", "entity_type": "Chemical", "pos": [104, 113]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [116, 122]}], "task": "NER"}
{"text": "Stress and Meth abuse are comorbid events in society and stress exacerbates Meth - induced monoaminergic terminal damage .", "entity": [{"entity": "Meth", "entity_type": "Chemical", "pos": [11, 15]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [76, 80]}], "task": "NER"}
{"text": "Stress is also known to produce neuroinflammation .", "entity": [], "task": "NER"}
{"text": "This study examined the role of the neuroinflammatory mediator , cyclooxygenase ( COX ) , in the depletions of monoamines caused by serial exposure to chronic unpredictable stress ( CUS ) and Meth .", "entity": [{"entity": "monoamines", "entity_type": "Chemical", "pos": [111, 121]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [192, 196]}], "task": "NER"}
{"text": "CUS produced an increase in COX - 2 protein expression and enhanced Meth - induced monoaminergic depletions in the striatum and hippocampus .", "entity": [{"entity": "Meth", "entity_type": "Chemical", "pos": [68, 72]}], "task": "NER"}
{"text": "The enhanced DA and 5 - HT depletions in the striatum , but not the hippocampus , were prevented by pretreatment with COX inhibitor , ketoprofen , during stress or during Meth ; however , ketoprofen did not attenuate the monoaminergic damage caused by Meth alone .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [20, 26]}, {"entity": "ketoprofen", "entity_type": "Chemical", "pos": [134, 144]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [171, 175]}, {"entity": "ketoprofen", "entity_type": "Chemical", "pos": [188, 198]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [252, 256]}], "task": "NER"}
{"text": "The COX - dependent enhancement by stress of Meth - induced monoaminergic depletions was independent of hyperthermia , as ketoprofen did not attenuate Meth - induced hyperthermia .", "entity": [{"entity": "Meth", "entity_type": "Chemical", "pos": [45, 49]}, {"entity": "ketoprofen", "entity_type": "Chemical", "pos": [122, 132]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [151, 155]}], "task": "NER"}
{"text": "In addition , the EP1 receptor antagonist , SC - 51089 , did not attenuate DA or 5 - HT depletions caused by stress and Meth .", "entity": [{"entity": "SC - 51089", "entity_type": "Chemical", "pos": [44, 54]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [81, 87]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [120, 124]}], "task": "NER"}
{"text": "These findings illustrate that COX activity , but not activation of the EP1 receptor , is responsible for the potentiation of Meth - induced damage to striatal monoamine terminals by stress and suggests the use of anti - inflammatory drugs for mitigating the neurotoxic effects associated with the combination of stress and Meth .", "entity": [{"entity": "Meth", "entity_type": "Chemical", "pos": [126, 130]}, {"entity": "monoamine", "entity_type": "Chemical", "pos": [160, 169]}, {"entity": "Meth", "entity_type": "Chemical", "pos": [324, 328]}], "task": "NER"}
{"text": "Upregulation of the dorsal raphe nucleus - prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar - Kyoto rats .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [61, 70]}, {"entity": "escitalopram", "entity_type": "Chemical", "pos": [104, 116]}], "task": "NER"}
{"text": "Wistar - Kyoto ( WKY ) rats are sensitive to chronic stressors and exhibit depression - like behavior .", "entity": [], "task": "NER"}
{"text": "Dorsal raphe nucleus ( DRN ) serotonin ( 5 - HT ) neurons projecting to the prefrontal cortex ( PFC ) comprise the important neurocircuitry underlying the pathophysiology of depression .", "entity": [{"entity": "serotonin", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [41, 47]}], "task": "NER"}
{"text": "To evaluate the DRN - PFC 5 - HT system in WKY rats , we examined the effects of escitalopram ( ESCIT ) on the extracellular 5 - HT level in comparison with Wistar rats using dual - probe microdialysis .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [26, 32]}, {"entity": "escitalopram", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "ESCIT", "entity_type": "Chemical", "pos": [96, 101]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [125, 131]}], "task": "NER"}
{"text": "The basal levels of 5 - HT in the DRN , but not in the PFC , in WKY rats was reduced as low as 30 % of Wistar rats .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [20, 26]}], "task": "NER"}
{"text": "Responses of 5 - HT in the DRN and PFC to ESCIT administered systemically and locally were attenuated in WKY rats .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [13, 19]}, {"entity": "ESCIT", "entity_type": "Chemical", "pos": [42, 47]}], "task": "NER"}
{"text": "Feedback inhibition of DRN 5 - HT release induced by ESCIT into the PFC was also attenuated in WKY rats .", "entity": [{"entity": "5 - HT", "entity_type": "Chemical", "pos": [27, 33]}, {"entity": "ESCIT", "entity_type": "Chemical", "pos": [53, 58]}], "task": "NER"}
{"text": "Chronic ESCIT induced upregulation of the DRN - PFC 5 - HT system in WKY rats , with increases in basal 5 - HT in the DRN , responsiveness to ESCIT in the DRN and PFC , and feedback inhibition , whereas downregulation of these effects was induced in Wistar rats .", "entity": [{"entity": "ESCIT", "entity_type": "Chemical", "pos": [8, 13]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [52, 58]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [104, 110]}, {"entity": "ESCIT", "entity_type": "Chemical", "pos": [142, 147]}], "task": "NER"}
{"text": "Thus , the WKY rat is an animal model of depression with low activity of the DRN - PFC 5HT system .", "entity": [{"entity": "5HT", "entity_type": "Chemical", "pos": [87, 90]}], "task": "NER"}
{"text": "The finding that chronic ESCIT upregulates the 5 - HT system in hyposerotonergic WKY rats may contribute to improved understanding of mechanisms of action of antidepressants , especially in depression with 5 - HT deficiency .", "entity": [{"entity": "ESCIT", "entity_type": "Chemical", "pos": [25, 30]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [47, 53]}, {"entity": "5 - HT", "entity_type": "Chemical", "pos": [206, 212]}], "task": "NER"}
{"text": "Bioconcentration of chromium in edible mushrooms : influence of environmental and genetic factors .", "entity": [{"entity": "chromium", "entity_type": "Chemical", "pos": [20, 28]}], "task": "NER"}
{"text": "Chromium concentrations were determined in 167 samples of wild edible mushrooms , collected from three different sites ( urban , traffic and pastureland areas ) in Lugo ( NW Spain ) .", "entity": [{"entity": "Chromium", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "The hymenophore ( H ) and the rest of the fruiting body ( RFB ) were analysed separately .", "entity": [], "task": "NER"}
{"text": "The analyses were performed using inductively coupled plasma optical emission spectrometry ( ICP - OES ) .", "entity": [], "task": "NER"}
{"text": "The highest mean chromium levels ( mg / kg dry weight ) of 3 . 5 and 8 . 0 , 4 . 5 and 6 . 2 , and 6 . 2 and 4 . 3 were found in Lycoperdon utriforme , Coprinus comatus and Agaricus campestris in H and RFB , respectively .", "entity": [{"entity": "chromium", "entity_type": "Chemical", "pos": [17, 25]}], "task": "NER"}
{"text": "The highest concentrations of chromium were observed in terrestrial saprophytic species in relation to mycorrhizal species .", "entity": [{"entity": "chromium", "entity_type": "Chemical", "pos": [30, 38]}], "task": "NER"}
{"text": "With respect to the underlying substrates , chromium concentration was lowest in the pastureland area ( 24 . 6 mg / kg dw ) .", "entity": [{"entity": "chromium", "entity_type": "Chemical", "pos": [44, 52]}], "task": "NER"}
{"text": "All mushroom species were bioexclusors of chromium ( BCF < 1 ) with statistically significant differences ( p < 0 . 001 ) .", "entity": [{"entity": "chromium", "entity_type": "Chemical", "pos": [42, 50]}], "task": "NER"}
{"text": "The consumption of mushrooms harvested from the areas investigated poses no toxicological risk to human health due to chromium .", "entity": [{"entity": "chromium", "entity_type": "Chemical", "pos": [118, 126]}], "task": "NER"}
{"text": "Synthetic pathway to 22 , 23 - dioxocholestanic chain derivatives and their usefulness for obtaining brassinosteroid analogues .", "entity": [{"entity": "22 , 23 - dioxocholestanic", "entity_type": "Chemical", "pos": [21, 47]}, {"entity": "brassinosteroid", "entity_type": "Chemical", "pos": [101, 116]}], "task": "NER"}
{"text": "Recognizing the functionality of the pentacyclic steroidal derivative 7a as important synthon to obtain new brassinosteroid analogs , we have accomplished the derivatization of hecogenin , a sapogenin from the 25R serie containing a carbonyl group at C - 12 , to a 22 , 23 - dioxocholestanic chain derivative .", "entity": [{"entity": "pentacyclic steroidal", "entity_type": "Chemical", "pos": [37, 58]}, {"entity": "brassinosteroid", "entity_type": "Chemical", "pos": [108, 123]}, {"entity": "hecogenin", "entity_type": "Chemical", "pos": [177, 186]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [233, 241]}, {"entity": "22 , 23 - dioxocholestanic", "entity_type": "Chemical", "pos": [265, 291]}], "task": "NER"}
{"text": "Starting from hecogenin acetate ( 5a ) or hecogenin tosylate ( 5b ) , we obtained two pentacyclic derivatives ( 7a and 7b ) which were subjected to an oxidation reaction on the double bond at C - 12 ( 23 ) to obtain a 22 , 23 - dioxocholestanic chain , with the regeneration of the carbonyl group at C - 12 .", "entity": [{"entity": "hecogenin acetate", "entity_type": "Chemical", "pos": [14, 31]}, {"entity": "hecogenin tosylate", "entity_type": "Chemical", "pos": [42, 60]}, {"entity": "22 , 23 - dioxocholestanic", "entity_type": "Chemical", "pos": [218, 244]}, {"entity": "carbonyl", "entity_type": "Chemical", "pos": [282, 290]}], "task": "NER"}
{"text": "Reduction of the carbonyl groups lead to the 20 - epi - 12 , 23 - dihydroxy - 22 - oxo system 11a - b .", "entity": [{"entity": "carbonyl", "entity_type": "Chemical", "pos": [17, 25]}, {"entity": "20 - epi - 12 , 23 - dihydroxy - 22 - oxo", "entity_type": "Chemical", "pos": [45, 86]}], "task": "NER"}
{"text": "The absolute configuration of compound 11a was established by X - ray diffraction analysis .", "entity": [], "task": "NER"}
{"text": "Evolution of Manduca sexta hornworms and relatives : Biogeographical analysis reveals an ancestral center of diversification in Central America .", "entity": [], "task": "NER"}
{"text": "The hawkmoth genus Manduca is a diverse group of very large , conspicuous moths that has served as an important model across many biological disciplines .", "entity": [], "task": "NER"}
{"text": "Two species in particular , the tobacco hornworm ( Manduca sexta ) and the tomato hornworm ( Manduca quinquemaculatus ) have been researched extensively .", "entity": [], "task": "NER"}
{"text": "Studies across biological fields have referred to these two species as being closely related or even sister species , but the extent to which these two model organisms are related remains largely unknown .", "entity": [], "task": "NER"}
{"text": "We conducted a comprehensive multi - gene phylogenetic analysis of Manduca , based on both an ML and Bayesian framework , which resulted in a monophyletic Manduca but only when two other genera , Dolba and Euryglottis are included .", "entity": [], "task": "NER"}
{"text": "We tentatively conclude that the sister group to Manduca sexta comprises the Caribbean M . afflicta and M . johanni , and the sister lineage to this clade includes M . quinquemaculatus and the Hawaiian M . blackburni .", "entity": [], "task": "NER"}
{"text": "Thus , M . sexta and M . quinquemaculatus are closely related , but are not sister species .", "entity": [], "task": "NER"}
{"text": "Biogeographical analyses reveal an ancestral center of diversification in Central America , and Manduca appears to have subsequently colonized North and South America .", "entity": [], "task": "NER"}
{"text": "Our phylogeny provides an important foundation for comparative studies of two model organisms and their relatives .", "entity": [], "task": "NER"}
{"text": "Designing , structural elucidation , comparison of DNA binding , cleavage , radical scavenging activity and anticancer activity of copper ( I ) complex with 5 - dimethyl - 2 - phenyl - 4 - [ ( pyridin - 2 - ylmethylene ) - amino ] - 1 , 2 - dihydro - pyrazol - 3 - one Schiff base ligand .", "entity": [{"entity": "copper ( I )", "entity_type": "Chemical", "pos": [131, 143]}, {"entity": "5 - dimethyl - 2 - phenyl - 4 - [ ( pyridin - 2 - ylmethylene ) - amino ] - 1 , 2 - dihydro - pyrazol - 3 - one", "entity_type": "Chemical", "pos": [157, 268]}, {"entity": "Schiff base", "entity_type": "Chemical", "pos": [269, 280]}], "task": "NER"}
{"text": "A novel copper ( I ) Schiff base complex has been synthesized and fully characterized by spectral , analytical and structural modes .", "entity": [{"entity": "copper ( I ) Schiff base", "entity_type": "Chemical", "pos": [8, 32]}], "task": "NER"}
{"text": "Single crystal X - ray diffraction studies revealed that the copper ( I ) complex [ CuCl ( PPh3 ) L ] has a distorted tetrahedral geometry around the central copper ( I ) ion .", "entity": [{"entity": "copper ( I )", "entity_type": "Chemical", "pos": [61, 73]}, {"entity": "[ CuCl ( PPh3 ) L ]", "entity_type": "Chemical", "pos": [82, 101]}, {"entity": "copper ( I )", "entity_type": "Chemical", "pos": [158, 170]}], "task": "NER"}
{"text": "The interaction of the ligand and the complex with CT - DNA has been explored by absorption titration method which revealed that the compounds could interact with CT - DNA through intercalation .", "entity": [], "task": "NER"}
{"text": "A gel electrophoresis assay demonstrated the ability of the complex to cleave the pBR322 DNA .", "entity": [], "task": "NER"}
{"text": "The antioxidative properties showed that the copper ( I ) complex has a strong radical - scavenging potency than ligands .", "entity": [{"entity": "copper ( I )", "entity_type": "Chemical", "pos": [45, 57]}], "task": "NER"}
{"text": "Further the cytotoxic effect of the compounds examined on cancerous cell lines showed that the complex exhibited substantial anticancer activity .", "entity": [], "task": "NER"}
{"text": "Synthesis and biological evaluation of novel phosphatidylinositol 3 - kinase inhibitors : Solubilized 4 - substituted benzimidazole analogs of 2 - ( difluoromethyl ) - 1 - [ 4 , 6 - di ( 4 - morpholinyl ) - 1 , 3 , 5 - triazin - 2 - yl ] - 1H - benzimidazole ( ZSTK474 ) .", "entity": [{"entity": "phosphatidylinositol", "entity_type": "Chemical", "pos": [45, 65]}, {"entity": "4 - substituted benzimidazole", "entity_type": "Chemical", "pos": [102, 131]}, {"entity": "2 - ( difluoromethyl ) - 1 - [ 4 , 6 - di ( 4 - morpholinyl ) - 1 , 3 , 5 - triazin - 2 - yl ] - 1H - benzimidazole", "entity_type": "Chemical", "pos": [143, 258]}, {"entity": "ZSTK474", "entity_type": "Chemical", "pos": [261, 268]}], "task": "NER"}
{"text": "A range of 4 - substituted derivatives of the pan class I PI 3 - kinase inhibitor 2 - ( difluoromethyl ) - 1 - [ 4 , 6 - di - ( 4 - morpholinyl ) - 1 , 3 , 5 - triazin - 2 - yl ] - 1H - benzimidazole ( ZSTK474 ) were prepared in a search for more soluble analogs .", "entity": [{"entity": "2 - ( difluoromethyl ) - 1 - [ 4 , 6 - di - ( 4 - morpholinyl ) - 1 , 3 , 5 - triazin - 2 - yl ] - 1H - benzimidazole", "entity_type": "Chemical", "pos": [82, 199]}, {"entity": "ZSTK474", "entity_type": "Chemical", "pos": [202, 209]}], "task": "NER"}
{"text": "4 - Aminoalkoxy substituents provided the most potent derivatives , with the 4 - O ( CH2 ) 3NMe2 analog ( compound 14 ) being identified as displaying the best overall activity in combination with good aqueous solubility ( 25 mg / mL for the hydrochloride salt ) .", "entity": [{"entity": "4 - Aminoalkoxy", "entity_type": "Chemical", "pos": [0, 15]}, {"entity": "4 - O ( CH2 ) 3NMe2", "entity_type": "Chemical", "pos": [77, 96]}, {"entity": "hydrochloride", "entity_type": "Chemical", "pos": [242, 255]}], "task": "NER"}
{"text": "This compound was tested in a U87MG xenograft model , but displayed less potency than ZSTK474 as a result of an unfavorable pharmacokinetic profile .", "entity": [{"entity": "ZSTK474", "entity_type": "Chemical", "pos": [86, 93]}], "task": "NER"}
{"text": "Nitroimidazolyl hydrazones are better amoebicides than their cyclized 1 , 3 , 4 - oxadiazoline analogues : In vitro studies and Lipophilic efficiency analysis .", "entity": [{"entity": "Nitroimidazolyl hydrazones", "entity_type": "Chemical", "pos": [0, 26]}, {"entity": "1 , 3 , 4 - oxadiazoline", "entity_type": "Chemical", "pos": [70, 94]}], "task": "NER"}
{"text": "Two series of compounds with hydrazone derivatives ( HZ1 - HZl2 , series 1 ) and oxadiazoline derivatives ( OZ1 - OZ12 , series 2 ) of the 2 - methyl - 5 - nitro - 1H - imidazole scaffold were designed and synthesized .", "entity": [{"entity": "hydrazone", "entity_type": "Chemical", "pos": [29, 38]}, {"entity": "oxadiazoline", "entity_type": "Chemical", "pos": [81, 93]}, {"entity": "2 - methyl - 5 - nitro - 1H - imidazole", "entity_type": "Chemical", "pos": [139, 178]}], "task": "NER"}
{"text": "Physicochemical properties and Lipophilic efficiency ( LipE ) analysis predicted higher intrinsic quality of the acylhydrazone derivatives ( series 1 ) than their corresponding oxadiazoline analogues ( series 2 ) .", "entity": [{"entity": "acylhydrazone", "entity_type": "Chemical", "pos": [113, 126]}, {"entity": "oxadiazoline", "entity_type": "Chemical", "pos": [177, 189]}], "task": "NER"}
{"text": "In vitro antiamoebic results supported the above findings and validated that the acylhydrazone derivatives ( HZ1 - HZl2 ) show better activity than the oxadiazoline derivatives ( OZ1 - OZ12 ) .", "entity": [{"entity": "acylhydrazone", "entity_type": "Chemical", "pos": [81, 94]}, {"entity": "oxadiazoline", "entity_type": "Chemical", "pos": [152, 164]}], "task": "NER"}
{"text": "MTT assay , using HepG2 cell line , revealed noncytotoxic nature of the compounds .", "entity": [{"entity": "MTT", "entity_type": "Chemical", "pos": [0, 3]}], "task": "NER"}
{"text": "The most promising results were observed for compounds HZ5 ( IC50 = 0 . 96 mu M ) and HZ9 ( IC50 = 0 . 81 mu M ) both in silico and in vitro .", "entity": [], "task": "NER"}
{"text": "Analysis of the Lipophilic efficiency ( LipE ) of the compounds provided new insight for the design of potent and selective amoebicides .", "entity": [], "task": "NER"}
{"text": "Enmein - type diterpenoid analogs from natural kaurene - type oridonin : Synthesis and their antitumor biological evaluation .", "entity": [{"entity": "Enmein", "entity_type": "Chemical", "pos": [0, 6]}, {"entity": "diterpenoid", "entity_type": "Chemical", "pos": [14, 25]}, {"entity": "kaurene", "entity_type": "Chemical", "pos": [47, 54]}, {"entity": "oridonin", "entity_type": "Chemical", "pos": [62, 70]}], "task": "NER"}
{"text": "A series of enmein - type diterpenoid analogs ( 11 - 20 ) derived from natural kaurene - type diterpenoid oridonin were synthesized and biologically evaluated .", "entity": [{"entity": "enmein", "entity_type": "Chemical", "pos": [12, 18]}, {"entity": "diterpenoid", "entity_type": "Chemical", "pos": [26, 37]}, {"entity": "kaurene", "entity_type": "Chemical", "pos": [79, 86]}, {"entity": "oridonin", "entity_type": "Chemical", "pos": [106, 114]}], "task": "NER"}
{"text": "All target compounds showed improved anti - proliferative activities against four human cancer cell lines compared with natural oridonin and parent compound 10 .", "entity": [{"entity": "oridonin", "entity_type": "Chemical", "pos": [128, 136]}], "task": "NER"}
{"text": "Some compounds were more potent than positive control Taxol .", "entity": [{"entity": "Taxol", "entity_type": "Chemical", "pos": [54, 59]}], "task": "NER"}
{"text": "Furthermore , mechanistic investigation showed that the representative compound 17 affected cell cycle and induced apoptosis at low micro - molar level in human hepatoma Bel - 7402 cells , via an oxidative stress triggered mitochondria - related caspase - dependent pathway .", "entity": [], "task": "NER"}
{"text": "Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability .", "entity": [], "task": "NER"}
{"text": "Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity .", "entity": [], "task": "NER"}
{"text": "The tumor suppressor protein ASPP ( Apoptosis - Stimulating Proteins of p53 ) 2 has been implicated in control of cell adhesion and polarity through its effect on the PAR complex .", "entity": [], "task": "NER"}
{"text": "Here we demonstrate that under hypoxic conditions , the ubiquitin ligase Siah ( seven in absentia homolog ) 2 controls ASPP2 availability , with concomitant effect on epithelial cell polarity .", "entity": [], "task": "NER"}
{"text": "LC - MS / MS analysis identified ASPP2 and ASPP1 as Siah2 - interacting proteins .", "entity": [], "task": "NER"}
{"text": "Biochemical analysis confirmed this interaction and mapped degron motifs within ASPP2 , which are required for Siah2 - mediated ubiquitination and proteasomal - dependent degradation .", "entity": [], "task": "NER"}
{"text": "Inhibition of Siah2 expression increases ASPP2 levels and enhances ASPP2 - dependent maintenance of tight junction ( TJ ) integrity , and polarized architecture in three dimensional ( 3D ) organotypic culture .", "entity": [], "task": "NER"}
{"text": "Conversely , increase of Siah2 expression under hypoxia decreases ASPP2 levels and the formation of apical polarity in 3D culture .", "entity": [], "task": "NER"}
{"text": "In all , our studies demonstrate the role of Siah2 in regulation of TJ integrity and cell polarity under hypoxia , through its regulation of ASPP2 stability . Oncogene advance online publication , 6 May 2013 ; doi : 10 . 1038 / onc . 2013 . 149 .", "entity": [], "task": "NER"}
{"text": "The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample .", "entity": [{"entity": "oxytocin", "entity_type": "Chemical", "pos": [25, 33]}], "task": "NER"}
{"text": "RATIONALE : To improve outcomes for patients undergoing extinction - based therapies ( e . g . , exposure therapy ) for anxiety disorders such as post - traumatic stress disorder ( PTSD ) , there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall .", "entity": [], "task": "NER"}
{"text": "Oxytocin ( OT ) is a mammalian neuropeptide that modulates activation of fear extinction - based neural circuits and fear responses .", "entity": [{"entity": "Oxytocin", "entity_type": "Chemical", "pos": [0, 8]}], "task": "NER"}
{"text": "Little is known , however , about the effects of OT treatment on conditioned fear responding and extinction in humans .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The purpose of the present study was to assess the effects of OT in a fear - potentiated startle task of fear conditioning and extinction .", "entity": [], "task": "NER"}
{"text": "METHODS : A double - blind , placebo - controlled study of 44 healthy human participants was conducted .", "entity": [], "task": "NER"}
{"text": "Participants underwent a conditioned fear acquisition procedure , after which they were randomized to treatment group and delivered OT ( 24 IU ) or placebo via intranasal ( IN ) spray .", "entity": [], "task": "NER"}
{"text": "Forty - five minutes after treatment , participants underwent extinction training .", "entity": [], "task": "NER"}
{"text": "Twenty - four hours later , subjects were tested for extinction recall .", "entity": [], "task": "NER"}
{"text": "RESULTS : Relative to placebo , the OT group showed increased fear - potentiated startle responding during the earliest stage of extinction training relative to placebo ; however , all treatment groups showed the same level of reduced responding by the end of extinction training .", "entity": [], "task": "NER"}
{"text": "Twenty - four hours later , the OT group showed significantly higher recall of extinction relative to placebo .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans .", "entity": [], "task": "NER"}
{"text": "These results support further study of OT as a potential adjunctive treatment for extinction - based therapies in fear - related disorders .", "entity": [], "task": "NER"}
{"text": "Greater risk sensitivity of dorsolateral prefrontal cortex in young smokers than in nonsmokers .", "entity": [], "task": "NER"}
{"text": "RATIONALE : Despite a national reduction in the prevalence of cigarette smoking , ~ 19 % of the adult US population persists in this behavior , with the highest prevalence among 18 - 25 - year - olds .", "entity": [], "task": "NER"}
{"text": "Given that the choice to smoke imposes a known health risk , clarification of brain function related to decision - making , particularly involving risk - taking , in smokers may inform prevention and smoking cessation strategies .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : This study aimed to compare brain function related to decision - making in young smokers and nonsmokers .", "entity": [], "task": "NER"}
{"text": "METHODS : The Balloon Analogue Risk Task ( BART ) is a computerized risky decision - making task in which participants pump virtual balloons , each pump associated with an incremental increase in potential payoff on a given trial but also with greater risk of balloon explosion and loss of payoff .", "entity": [], "task": "NER"}
{"text": "We used this task to compare brain activation associated with risky decision - making in smokers ( n = 18 ) and nonsmokers ( n = 25 ) , while they performed the BART during functional magnetic resonance imaging ( fMRI ) .", "entity": [], "task": "NER"}
{"text": "The participants were young men and women , 17 - 21 years of age .", "entity": [], "task": "NER"}
{"text": "RESULTS : Risk level ( number of pumps ) modulated brain activation in the right dorsolateral and ventrolateral prefrontal cortices more in smokers than in nonsmokers , and smoking severity ( Heaviness of Smoking Index ) was positively related to this modulation in an adjacent frontal region .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Given evidence for involvement of the right dorsolateral and ventrolateral prefrontal cortices in inhibitory control , these findings suggest that young smokers have a different contribution of prefrontal cortical substrates to risky decision - making than nonsmokers .", "entity": [], "task": "NER"}
{"text": "Future studies are warranted to determine whether the observed neurobiological differences precede or result from smoking .", "entity": [], "task": "NER"}
{"text": "Measuring nanoparticle flow with the image structure function .", "entity": [], "task": "NER"}
{"text": "We present a technique to measure the velocity and flow profiles of a nanofluid in a microfluidic channel .", "entity": [], "task": "NER"}
{"text": "Importantly , we extract the flow velocity from a series of standard brightfield images without employing particle tracking or laser - enhanced methods .", "entity": [], "task": "NER"}
{"text": "Our analysis retrieves the flow information from the image structure function of sub - diffraction limited nanoparticles in suspension .", "entity": [], "task": "NER"}
{"text": "We are able to spatially resolve the flow velocity and map out the parabolic flow profile across the width of a microfluidic channel .", "entity": [], "task": "NER"}
{"text": "Role of quercetin in cadmium - induced oxidative stress , neuronal damage , and apoptosis in rats .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [8, 17]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [21, 28]}], "task": "NER"}
{"text": "The present study was carried out to evaluate the neuroprotective effect of quercetin ( QE ) in protecting the cadmium ( Cd ) - induced neuronal injury in frontal cortex of rats .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [76, 85]}, {"entity": "cadmium", "entity_type": "Chemical", "pos": [111, 118]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [121, 123]}], "task": "NER"}
{"text": "A total of 30 adult male Sprague - Dawley rats were randomly divided into three groups of 10 animals each : control , Cd treated and Cd treated with QE .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [118, 120]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [133, 135]}], "task": "NER"}
{"text": "The Cd - treated group was injected subcutaneously with cadmium chloride ( CdCl2 ) dissolved in saline at a dose of 2 ml / kg / day for 30 days , resulting in a dosage of 1 mg / kg Cd .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [4, 6]}, {"entity": "cadmium chloride", "entity_type": "Chemical", "pos": [56, 72]}, {"entity": "CdCl2", "entity_type": "Chemical", "pos": [75, 80]}, {"entity": "Cd", "entity_type": "Chemical", "pos": [181, 183]}], "task": "NER"}
{"text": "The rats in QE - treated groups were given QE ( 15 mg / kg body weight ) once a day intraperitoneally starting 2 days prior to Cd injection , during the study period .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [127, 129]}], "task": "NER"}
{"text": "Rats were sacrificed at the end of the study and the frontal cortex tissues were removed for biochemical and histopathological investigation .", "entity": [], "task": "NER"}
{"text": "To date , there is no available information on the effect of QE on neuronal injury after Cd exposure .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [89, 91]}], "task": "NER"}
{"text": "Rats intoxicated with Cd for 30 days , significantly increased tissue malondialdehyde ( MDA ) levels and significantly decreased enzymatic antioxidants superoxide dismutase , glutathione peroxidase and catalase in the frontal cortex tissue .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [22, 24]}, {"entity": "malondialdehyde", "entity_type": "Chemical", "pos": [70, 85]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [88, 91]}, {"entity": "superoxide", "entity_type": "Chemical", "pos": [152, 162]}, {"entity": "glutathione", "entity_type": "Chemical", "pos": [175, 186]}], "task": "NER"}
{"text": "Administration of QE with Cd significantly diminished the levels of MDA and significantly elevated the levels of enzymatic antioxidants in the frontal cortex tissue .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [26, 28]}, {"entity": "MDA", "entity_type": "Chemical", "pos": [68, 71]}], "task": "NER"}
{"text": "The histopathological studies in the brain of rats also supported that QE markedly reduced the Cd - induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [95, 97]}], "task": "NER"}
{"text": "The caspase - 3 immunopositivity was increased in degenerating neurons of the Cd group .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [78, 80]}], "task": "NER"}
{"text": "Treatment with QE markedly reduced the immunoreactivity of degenerating neurons .", "entity": [], "task": "NER"}
{"text": "In conclusion , the results of the current study suggest that QE may be beneficial in combating the Cd - induced neurotoxicity in the brain of rats .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [100, 102]}], "task": "NER"}
{"text": "We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment for neurodegeneration after Cd exposure in rats .", "entity": [{"entity": "Cd", "entity_type": "Chemical", "pos": [149, 151]}], "task": "NER"}
{"text": "Differential regulation of Arabidopsis plastid gene expression and RNA editing in non - photosynthetic tissues .", "entity": [], "task": "NER"}
{"text": "RNA editing is one of the post - transcriptional processes that commonly occur in plant plastids and mitochondria .", "entity": [], "task": "NER"}
{"text": "In Arabidopsis , 34 C - to - U RNA editing events , affecting transcripts of 18 plastid genes , have been identified .", "entity": [], "task": "NER"}
{"text": "Here , we examined the editing and expression of these transcripts in different organs , and in green and non - green seedlings ( etiolated , cia5 - 2 , ispF and ispG albino mutants , lincomycin - , and norflurazon - treated ) .", "entity": [{"entity": "lincomycin", "entity_type": "Chemical", "pos": [184, 194]}, {"entity": "norflurazon", "entity_type": "Chemical", "pos": [203, 214]}], "task": "NER"}
{"text": "The editing efficiency of Arabidopsis plastid transcripts varies from site to site , and may be specifically regulated in different tissues .", "entity": [], "task": "NER"}
{"text": "Steady state levels of plastid transcripts are low or undetectable in etiolated seedlings , but most editing sites are edited with efficiencies similar to those observed in green seedlings .", "entity": [], "task": "NER"}
{"text": "By contrast , the editing of some sites is completely lost or significantly reduced in other non - green tissues ; for instance , the editing of ndhB - 149 , ndhB - 1255 , and ndhD - 2 is completely lost in roots and in lincomycin - treated seedlings .", "entity": [{"entity": "lincomycin", "entity_type": "Chemical", "pos": [220, 230]}], "task": "NER"}
{"text": "The editing of ndhD - 2 is also completely lost in albino mutants and norflurazon - treated seedlings .", "entity": [{"entity": "norflurazon", "entity_type": "Chemical", "pos": [70, 81]}], "task": "NER"}
{"text": "However , matK - 640 is completely edited , and accD - 794 , atpF - 92 , psbE - 214 , psbF - 77 , psbZ - 50 , and rps14 - 50 are completely or highly edited in both green and non - green tissues .", "entity": [], "task": "NER"}
{"text": "In addition , the expression of nucleus - encoded RNA polymerase dependent transcripts is specifically induced by lincomycin , and the splicing of ndhB transcripts is significantly reduced in the albino mutants and inhibitor - treated seedlings .", "entity": [{"entity": "lincomycin", "entity_type": "Chemical", "pos": [114, 124]}], "task": "NER"}
{"text": "Our results indicate that plastid gene expression , and the splicing and editing of plastid transcripts are specifically and differentially regulated in various types of non - green tissues .", "entity": [], "task": "NER"}
{"text": "Analysis of the inhibitory activity of Abeliophyllum distichum leaf constituents against aldose reductase by using high - speed counter current chromatography .", "entity": [{"entity": "aldose", "entity_type": "Chemical", "pos": [89, 95]}], "task": "NER"}
{"text": "We isolated five phenolic glycosides ( acteoside , eutigoside B , isoacteoside , rutin and cornoside ) from Abeliophyllum distichum leaves by high - speed counter current chromatography ( HSCCC ) using a solvent system of ethyl acetate : n - butanol : water ( 8 : 0 . 7 : 5 ) .", "entity": [{"entity": "phenolic glycosides", "entity_type": "Chemical", "pos": [17, 36]}, {"entity": "acteoside", "entity_type": "Chemical", "pos": [39, 48]}, {"entity": "eutigoside B", "entity_type": "Chemical", "pos": [51, 63]}, {"entity": "isoacteoside", "entity_type": "Chemical", "pos": [66, 78]}, {"entity": "rutin", "entity_type": "Chemical", "pos": [81, 86]}, {"entity": "cornoside", "entity_type": "Chemical", "pos": [91, 100]}, {"entity": "ethyl acetate", "entity_type": "Chemical", "pos": [222, 235]}, {"entity": "n - butanol", "entity_type": "Chemical", "pos": [238, 249]}], "task": "NER"}
{"text": "We determined the purity of the 5 compounds by high - performance liquid chromatography , and confirmed their chemical structures by using nuclear magnetic resonance data .", "entity": [], "task": "NER"}
{"text": "We examined the inhibitory effect of these compounds on rat lens aldose reductase .", "entity": [{"entity": "aldose", "entity_type": "Chemical", "pos": [65, 71]}], "task": "NER"}
{"text": "Among these compounds , acteoside ( 1 ) showed the most potent inhibitory effect , with an IC50 value of 1 . 39 mu M .", "entity": [{"entity": "acteoside", "entity_type": "Chemical", "pos": [24, 33]}], "task": "NER"}
{"text": "The inhibitory effect of 1 was 5 . 0 times greater than that of quercetin ( 7 . 05 mu M ) , which was used as a positive control .", "entity": [{"entity": "quercetin", "entity_type": "Chemical", "pos": [64, 73]}], "task": "NER"}
{"text": "These results suggest that acteoside may be a promising agent for the prevention or treatment of diabetic complications .", "entity": [{"entity": "acteoside", "entity_type": "Chemical", "pos": [27, 36]}], "task": "NER"}
{"text": "Moreover , HSCCC is a promising method for the isolation and purification of biologically active compounds from natural products .", "entity": [], "task": "NER"}
{"text": "Understanding the Cost - Effectiveness of Influenza Vaccination in Children : Methodological Choices and Seasonal Variability .", "entity": [], "task": "NER"}
{"text": "BACKGROUND : The universal vaccination of children for influenza has recently been recommended in the UK and is being considered in other developed countries .", "entity": [], "task": "NER"}
{"text": "OBJECTIVES : The aim of this study was to explore the potential costs and benefits of childhood influenza vaccination to gain a better understanding of the key drivers of cost - effectiveness .", "entity": [], "task": "NER"}
{"text": "METHODS : As our case study we examined the cost - effectiveness of vaccination in Australian schoolchildren using an age - stratified Susceptible Exposed Infectious Recovered model .", "entity": [], "task": "NER"}
{"text": "RESULTS : The results of this study highlight the critical role that methodological choices play in determining the cost - effectiveness of influenza vaccination .", "entity": [], "task": "NER"}
{"text": "These choices include decisions about the structure of the model ( including / excluding herd immunity ) and what costs and benefits to include in the analysis .", "entity": [], "task": "NER"}
{"text": "In scenarios where herd protection was included we estimated that the program was likely to be cost - effective .", "entity": [], "task": "NER"}
{"text": "The study also illustrates the importance of the inherent seasonal variability of influenza , which can produce counter - intuitive results , with low transmission seasons being easier to control by vaccination but resulting in fewer benefits .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS : Universal childhood influenza vaccination is likely to be cost - effective if a substantial herd protection effect can be achieved by the program .", "entity": [], "task": "NER"}
{"text": "However , it is important that decision makers understand the role of seasonal variability and the impact of alternative methodological choices in economic evaluations of influenza vaccination .", "entity": [], "task": "NER"}
{"text": "The bacterial translocon SecYEG opens upon ribosome binding .", "entity": [], "task": "NER"}
{"text": "In cotranslational translocation , the ribosome funnel and the channel of the protein translocation complex SecYEG are aligned .", "entity": [], "task": "NER"}
{"text": "For the nascent chain to enter the channel immediately after synthesis , a yet unidentified signal triggers displacement of the SecYEG sealing plug from the pore .", "entity": [], "task": "NER"}
{"text": "Here we show that ribosome binding to the resting SecYEG channel triggers this conformational transition .", "entity": [], "task": "NER"}
{"text": "The purified and reconstituted SecYEG channel opens to form a large ion - conducting channel which has the conductivity of the plug deletion mutant .", "entity": [], "task": "NER"}
{"text": "The number of ion conducting channels inserted into the planar bilayer per fusion event roughly equals the number of SecYEG channels counted by fluorescence correlation spectroscopy in a single proteoliposome .", "entity": [], "task": "NER"}
{"text": "Thus , the open probability of the channel must be close to unity .", "entity": [], "task": "NER"}
{"text": "To prevent the otherwise lethal proton leak , a closed post - translational conformation of the SecYEG complex bound to a ribosome must exist .", "entity": [], "task": "NER"}
{"text": "Gain - of - function mutations in transient receptor potential C6 ( TRPC6 ) activate extracellular - signal - regulated kinases Erk1 / 2 .", "entity": [], "task": "NER"}
{"text": "Gain - of - function mutations in the canonical transient receptor potential 6 ( TRPC6 ) gene are a cause of autosomal dominant focal segmental glomerulosclerosis ( FSGS4 ) .", "entity": [], "task": "NER"}
{"text": "The mechanisms whereby abnormal TRPC6 activity results in proteinuria remain unknown .", "entity": [], "task": "NER"}
{"text": "The Erk1 / 2 MAP kinases are activated in glomeruli and podocytes in several proteinuric disease models .", "entity": [], "task": "NER"}
{"text": "We therefore examined whether FSGS - associated mutations in TRPC6 result in activation of these kinases .", "entity": [], "task": "NER"}
{"text": "In 293T cells and cultured podocytes , overexpression of gain - of - function TRPC6 mutants resulted in increased Erk1 / 2 phosphorylation , an effect dependent upon channel function .", "entity": [], "task": "NER"}
{"text": "Pharmacologic inhibitor studies implicated several signaling mediators , including calmodulin and calcineurin , supporting the importance of TRPC6 - mediated calcium influx in this process .", "entity": [{"entity": "calcium", "entity_type": "Chemical", "pos": [158, 165]}], "task": "NER"}
{"text": "Through media transfer experiments , we uncovered two distinct mechanisms for Erk activation by mutant TRPC6 , a cell autonomous , EGFR - independent mechanism and a cell non - autonomous mechanism involving metalloprotease - mediated release of a presumed EGFR ligand .", "entity": [], "task": "NER"}
{"text": "The inhibitors KN - 92 and H89 were able to block both pathways in mutant TRPC6 expressing cells , as well as the prolonged elevation of intracellular calcium levels upon carbachol stimulation seen in these cells .", "entity": [{"entity": "KN - 92", "entity_type": "Chemical", "pos": [15, 22]}, {"entity": "H89", "entity_type": "Chemical", "pos": [27, 30]}, {"entity": "calcium", "entity_type": "Chemical", "pos": [151, 158]}, {"entity": "carbachol", "entity_type": "Chemical", "pos": [171, 180]}], "task": "NER"}
{"text": "However , these effects appear independent of their effects on CaMKII and PKA , respectively .", "entity": [], "task": "NER"}
{"text": "Phosphorylation of T70 , S282 and Y31 / Y285 were not necessary for Erk activation by mutant TRPC6 , though a phosphomimetic TRPC6 S282E mutant was capable of Erk activation .", "entity": [], "task": "NER"}
{"text": "Taken together , these results identify two pathways downstream of mutant TRPC6 leading to Erk activation that may play a role in the development of FSGS .", "entity": [], "task": "NER"}